Interferon-free treatment for patients with chronic hepatitis C and autoimmune liver disease: higher SVR rates with special precautions for deterioration of autoimmune hepatitis.

PubMed

Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Nakamoto, Shingo; Takahashi, Koji; Wu, Shuang; Sasaki, Reina; Haga, Yuki; Ogasawara, Sadahisa; Saito, Tomoko; Kobayashi, Kazufumi; Kiyono, Soichiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Chiba, Tetsuhiro; Maruyama, Hitoshi; Imazeki, Fumio; Moriyama, Mitsuhiko; Kato, Naoya

2018-02-20

Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR. Three patients took prednisolone (PSL) at baseline, and 3 did not take PSL during interferon-free treatment. In one HCV patient with AIH and cirrhosis, PSL were not administered at baseline, but she needed to take 40 mg/day PSL at week 8 for liver dysfunction. She also complained back pain and was diagnosed with vasospastic angina by coronary angiography at week 11. However, she completed interferon-free treatment. All 5 HCV patients with primary biliary cholangitis (PBC) completed treatment and achieved SVR. Three of these HCV patients with PBC were treated with UDCA during interferon-free treatment. Interferon-free regimens could result in higher SVR rates in HCV patients with autoimmune liver diseases. As interferon-free treatment for HCV may have an effect on hepatic immunity and activity of the autoimmune liver diseases, careful attention should be paid to unexpected adverse events in their treatments. Total 12 patients with HCV and autoimmune liver diseases [7 AIH and PBC], who were treated with interferon-free regimens, were retrospectively analyzed.

Sensitization to autoimmune hepatitis in group VIA calcium-independent phospholipase A2-null mice led to duodenal villous atrophy with apoptosis, goblet cell hyperplasia and leaked bile acids.

PubMed

Jiao, Li; Gan-Schreier, Hongying; Tuma-Kellner, Sabine; Stremmel, Wolfgang; Chamulitrat, Walee

2015-08-01

Chronic bowel disease can co-exist with severe autoimmune hepatitis (AIH) in an absence of primary sclerosing cholangitis. Genetic background may contribute to this overlap syndrome. We previously have shown that the deficiency of iPLA2β causes an accumulation of hepatocyte apoptosis, and renders susceptibility for acute liver injury. We here tested whether AIH induction in iPLA2β-null mice could result in intestinal injury, and whether bile acid metabolism was altered. Control wild-type (WT) and female iPLA2β-null (iPLA2β(-/-)) mice were intravenously injected with 10mg/kg concanavalinA (ConA) or saline for 24h. ConA treatment of iPLA2β(-/-) mice caused massive liver injury with increased liver enzymes, fibrosis, and necrosis. While not affecting WT mice, ConA treatment of iPLA2β(-/-) mice caused severe duodenal villous atrophy concomitant with increased apoptosis, cell proliferation, globlet cell hyperplasia, and endotoxin leakage into portal vein indicating a disruption of intestinal barrier. With the greater extent than in WT mice, ConA treatment of iPLA2β(-/-) mice increased jejunal expression of innate response cytokines CD14, TNF-α, IL-6, and SOCS3 as well as chemokines CCL2 and the CCL3 receptor CCR5. iPLA2β deficiency in response to ConA-induced AIH caused a significant decrease in hepatic and biliary bile acids, and this was associated with suppression of hepatic Cyp7A1, Ntcp and ABCB11/Bsep and upregulation of intestinal FXR/FGF15 mRNA expression. The suppression of hepatic Ntcp expression together with the loss of intestinal barrier could account for the observed bile acid leakage into peripheral blood. Thus, enteropathy may result from acute AIH in a susceptible host such as iPLA2β deficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

Interferon-free treatment for patients with chronic hepatitis C and autoimmune liver disease: higher SVR rates with special precautions for deterioration of autoimmune hepatitis

PubMed Central

Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Nakamoto, Shingo; Takahashi, Koji; Wu, Shuang; Sasaki, Reina; Haga, Yuki; Ogasawara, Sadahisa; Saito, Tomoko; Kobayashi, Kazufumi; Kiyono, Soichiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Chiba, Tetsuhiro; Maruyama, Hitoshi; Imazeki, Fumio; Moriyama, Mitsuhiko; Kato, Naoya

2018-01-01

Background Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. Results All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR. Three patients took prednisolone (PSL) at baseline, and 3 did not take PSL during interferon-free treatment. In one HCV patient with AIH and cirrhosis, PSL were not administered at baseline, but she needed to take 40 mg/day PSL at week 8 for liver dysfunction. She also complained back pain and was diagnosed with vasospastic angina by coronary angiography at week 11. However, she completed interferon-free treatment. All 5 HCV patients with primary biliary cholangitis (PBC) completed treatment and achieved SVR. Three of these HCV patients with PBC were treated with UDCA during interferon-free treatment. Conclusions Interferon-free regimens could result in higher SVR rates in HCV patients with autoimmune liver diseases. As interferon-free treatment for HCV may have an effect on hepatic immunity and activity of the autoimmune liver diseases, careful attention should be paid to unexpected adverse events in their treatments. Methods Total 12 patients with HCV and autoimmune liver diseases [7 AIH and PBC], who were treated with interferon-free regimens, were retrospectively analyzed. PMID:29545925

Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood.

PubMed

Maggiore, G; Riva, S; Sciveres, M

2009-03-01

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct infiltration and destruction) and/or lesions suggesting chronic cholangitis as well (bile duct paucity and/or proliferation, periductal sclerosis). Small bile ducts damage may be associated, at onset or in the following years, with lesions of larger bile ducts with duct wall irregularities, strictures, dilations, and beading resulting in the characteristic ''bead-on-a-string'' appearance. The ''small duct'' (autoimmune) sclerosing cholangitis is also called autoimmune cholangitis. PSC is strictly associated to a particular form of inflammatory bowel disease (IBD) which shows features not typical of ulcerative colitis neither of Crohn's disease. Symptoms related to IBD often are present at onset (abdominal pain, weight loss, bloody stools) but the liver disease is frequently asymptomatic and it may be discovered fortuitously. Treatment of PSC is particularly challenging. In case of ''small duct'' SC or in case of evidence active inflammation on liver biopsy, immunosuppressive treatment is probably useful while in case of large bile ducts non inflammatory sclerosis, immunosuppression is probably uneffective. Ursodeoxycholic acid, however, may leads to an improvement of liver biochemistry even if there's no evidence that it may alter the course of disease. Thus, liver transplantation, is often necessary in the long term follow-up, even with a risk of disease recurrence. In adjunction to these two main disorders, many patients show an''overlap'' disease with features of both AIH and PSC. In such disorders the immune-mediated damage concerns both the hepatocyte and the cholangiocyte with a continuous clinical spectrum from AIH with minimal bile ducts lesions and PSC with portal inflammation and active inflammatory liver damage.

Characteristics and outcome of autoimmune liver disease in Asian children.

PubMed

Lee, Way S; Lum, Su H; Lim, Chooi B; Chong, Sze Y; Khoh, Kim M; Ng, Ruey T; Teo, Kai M; Boey, Christopher C M; Pailoor, Jayalakshmi

2015-04-01

Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population. Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia. At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012]. Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.

Evaluation of a computer-aided detection algorithm for timely diagnosis of small acute intracranial hemorrhage on computed tomography in a critical care environment

NASA Astrophysics Data System (ADS)

Lee, Joon K.; Chan, Tao; Liu, Brent J.; Huang, H. K.

2009-02-01

Detection of acute intracranial hemorrhage (AIH) is a primary task in the interpretation of computed tomography (CT) brain scans of patients suffering from acute neurological disturbances or after head trauma. Interpretation can be difficult especially when the lesion is inconspicuous or the reader is inexperienced. We have previously developed a computeraided detection (CAD) algorithm to detect small AIH. One hundred and thirty five small AIH CT studies from the Los Angeles County (LAC) + USC Hospital were identified and matched by age and sex with one hundred and thirty five normal studies. These cases were then processed using our AIH CAD system to evaluate the efficacy and constraints of the algorithm.

Epstein-Barr Virus as a Trigger of Autoimmune Liver Diseases

PubMed Central

Rigopoulou, Eirini I.; Smyk, Daniel S.; Matthews, Claire E.; Billinis, Charalambos; Burroughs, Andrew K.; Lenzi, Marco; Bogdanos, Dimitrios P.

2012-01-01

The pathogenesis of autoimmune diseases includes a combination of genetic factors and environmental exposures including infectious agents. Infectious triggers are commonly indicated as being involved in the induction of autoimmune disease, with Epstein-Barr virus (EBV) being implicated in several autoimmune disorders. EBV is appealing in the pathogenesis of autoimmune disease, due to its high prevalence worldwide, its persistency throughout life in the host's B lymphocytes, and its ability to alter the host's immune response and to inhibit apoptosis. However, the evidence in support of EBV in the pathogenesis varies among diseases. Autoimmune liver diseases (AiLDs), including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), have a potential causative link with EBV. The data surrounding EBV and AiLD are scarce. The lack of evidence surrounding EBV in AiLD may also be reflective of the rarity of these conditions. EBV infection has also been linked to other autoimmune conditions, which are often found to be concomitant with AiLD. This paper will critically examine the literature surrounding the link between EBV infection and AiLD development. The current evidence is far from being conclusive of the theory of a link between EBV and AiLD. PMID:22693505

Clinical significance of autoantibodies in autoimmune hepatitis.

PubMed

Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

2013-10-01

The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protocol of a prospective study for the combination treatment of Shu-Gan-jian-Pi decoction and steroid standard therapy in autoimmune hepatitis patients.

PubMed

Chi, Xiao-Ling; Xiao, Huan-Ming; Xie, Yu-Bao; Cai, Gao-Shu; Jiang, Jun-Min; Tian, Guang-Jun; Shi, Mei-Jie; Wu, Shu-Duo; Zhao, Peng-Tao; Chen, Hui-Jun

2016-12-07

Prednisone plus azathioprine is considered the mainstay of therapy in the current recommendations for autoimmune hepatitis (AIH). However, it does not provide good benefits for AIH patients because of its serious side effects. Therefore, more and more AIH patients prefer to seek for traditional Chinese medicine (TCM) to manage their symptoms and reduce the side effects of steroids in China. Shu-Gan-Jian-Pi Decoction is a popular used Chinese herbal formula in Guangdong province of China, which has demonstrated the effect of improving efficacy and reducing side effects of corticosteroids in AIH patients. The aim of this study is to evaluate the effects of Shu-Gan-Jian-Pi Decoction combined with steroid in AIH patients. So, this study aims to explore whether the combination treatment of Shu-Gan-Jian-Pi Decoction and steroid standard therapy could improve the clinical management of AIH. A prospective non-randomized study on AIH will be conducted between October 2015 and June 2017 in Guangdong Provincial hospital of Chinese medicine. Eligible AIH patients will be classified as the case group (n = 66) and the control group (n = 66) based on the interventions. Patients taking Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine will be in the case group and those taking prednisone and azathioprine will be in the control group. The whole study will last 48 weeks, including a 24-week observation period and a 24-week follow-up period. The primary outcome was complete response to therapy, defined as complete biochemical remission at the patient's last visit of observation period and the absence of predefined steroid-specific side effects throughout treatment. This trial will evaluate the efficacy and safety of Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine on AIH patients. The achievement of this trial will provide evidence-based data for Shu-Gan-Jian-Pi Decoction, which could provide good benefits for AIH patients. Chinese Clinical Trial Registry: ChiCTR-OOC-15006155 . Registration date: 28 March 2015.

Natural History and Treatment Outcomes of Severe Autoimmune Hepatitis.

PubMed

Sonthalia, Nikhil; Rathi, Pravin M; Jain, Samit S; Surude, Ravindra G; Mohite, Ashok R; Pawar, Sunil V; Contractor, Qais

2017-07-01

The aim of this study was to analyze the natural history and treatment outcomes of autoimmune hepatitis (AIH) variants presenting with severe-AIH. Severe acute presentation is an uncommon manifestation of AIH, and it remains poorly characterized. We included 101 patients with AIH from January 2011 to December 2015. Patients were classified as seropositive-AIH and seronegative-AIH. Patients with acute liver failure, acute-on-chronic liver failure, and severe acute hepatitis were defined as severe-AIH patients. Patient characteristics and treatment outcomes with follow-up until 12 months were analyzed between the different groups. Out of 101 cases, 24 (23.76%) had severe AIH. Of them 9 (37.5%) had severe acute hepatitis, 3 (12.5%) had acute liver failure, and 12 (50%) had acute-on-chronic liver failure. Seronegative-AIH patients presented with severe-AIH significantly more frequently compared with seropositive-AIH patients (50% vs. 20.27%, P=0.022). Severe-AIH had 50% complete responders, 25% partial responders, and 25% treatment failures. Jaundice (88.88% vs. 68.7%, P=0.048), encephalopathy (55.55% vs. 6.66%, P=0.014), and higher international normalized ratio values (2.17±0.60 vs. 1.82±0.14, P=0.038) were factors associated with nonresponse rather than the presence or absence of autoantibodies in severe-AIH. The hazard ratio for predicting remission in the non-severe AIH group as compared with the severe-AIH group was 1.502, which was statistically not significant (95% CI, 0.799-2.827; P=0.205). Approximately 24% of patients with AIH have severe-AIH. Conventional autoantibodies are often absent in severe-AIH; however, it does not alter the outcome. Immunosuppressants should be given expediently in patients with severe-AIH.

[Autoimmune hepatitis in children and adolescents: clinical study, diagnosis and therapeutic response].

PubMed

Ferreira, Alexandre R; Roquete, Mariza L V; Penna, Francisco J; Toppa, Nivaldo H

2002-01-01

The aim of this study was to evaluate the clinical, laboratory and histopathological characteristics and the response to immunosuppression in children and adolescents with autoimmune hepatitis (AIH). The present research is a descriptive study consisting of 39 children and adolescents with AIH who receive care at the Department of Pediatric Gastroenterology of Hospital das Clínicas (UFMG) from 1986 to 1998. Children's age ranged from 1.6 to 17 years (mean 8.7 +/- 3.49), most of them were females (87.2%). There were three types of clinical presentations: chronic (53.9%), acute (41%), and serious hepatic failure (5.1%). The most relevant laboratory parameters were the aminotransferases and gamma-globulin increase. Antinuclear antibodies were positive in 66.7% of the patients, while smooth muscle antibodies were positive in 52.8% and anti-LKM1 in 3% of the patients. In the histopathology the most important findings were the piecemeal necrosis (93.7%), moderate to severe portal inflammation (78.1%), definitive or incomplete cirrhosis (76.9%), absence of lesion of biliary ducts (93.7%) and presence of rosettes (90.6%). During the treatment, 77.8% obtained complete resolution, associated to side effects in 27.8% of them. Seven patients died (17.9%). During the treatment there was significant z score reduction (p<0.05) for height/age. After carrying out this study, we observed that the typical characteristics of AIH were: female sex, several clinical presentations, increased aminotransferase, and hypergammaglobulinemia. Histopathology showed a predominance of incipient and/or definitive cirrhosis associated with moderate to severe portal inflammation and piecemeal necrosis. Treatment using corticosteroids and azathioprine, turned out to be effective. However, the reduction in the height/age z score probably represents an adverse effect of corticoid treatment.

Improving the Explosive Performance of Aluminum Nanoparticles with Aluminum Iodate Hexahydrate (AIH).

PubMed

Gottfried, Jennifer L; Smith, Dylan K; Wu, Chi-Chin; Pantoya, Michelle L

2018-05-23

A new synthesis approach for aluminum particles enables an aluminum core to be passivated by an oxidizing salt: aluminum iodate hexahydrate (AIH). Transmission electron microscopy (TEM) images show that AIH replaces the Al 2 O 3 passivation layer on Al particles that limits Al oxidation. The new core-shell particle reactivity was characterized using laser-induced air shock from energetic materials (LASEM) and results for two different Al-AIH core-shell samples that vary in the AIH concentration demonstrate their potential use for explosive enhancement on both fast (detonation velocity) and slow (blast effects) timescales. Estimates of the detonation velocity for TNT-AIH composites suggest an enhancement of up to 30% may be achievable over pure TNT detonation velocities. Replacement of Al 2 O 3 with AIH allows Al to react on similar timescales as detonation waves. The AIH mixtures tested here have relatively low concentrations of AIH (15 wt. % and 6 wt. %) compared to previously reported samples (57.8 wt. %) and still increase TNT performance by up to 30%. Further optimization of AIH synthesis could result in additional increases in explosive performance.

Autoantibody Profiling in a Cohort of Pediatric and Adult Patients With Autoimmune Hepatitis.

PubMed

Villalta, Danilo; Girolami, Elia; Alessio, Maria Grazia; Sorrentino, Maria Concetta; Tampoia, Marilina; Brusca, Ignazio; Daves, Massimo; Porcelli, Brunetta; Barberio, Giuseppina; Conte, Mariaelisabetta; Pantarotto, Lisa; Bizzaro, Nicola

2016-01-01

Autoimmune hepatitis (AIH) is a rare condition characterized by the presence of autoantibodies distinctive of type 1 AIH (AIH-1) and type 2 AIH (AIH-2). The aim of this study was to evaluate the autoantibody profile in a cohort of pediatric and adult AIH patients, using both indirect immunofluorescence (IIF) and a new multiplexed line-blot assay. Sera from 63 pediatric and 53 adult AIH patients were tested for antinuclear (ANA), antismooth muscle (SMA), anti-liver kidney microsome 1 (anti-LKM1), anti-liver cytosol 1 (anti-LC1) autoantibodies using IIF methods; for anti-LKM1, anti-LC1, and soluble liver antigen/liver-pancreas (anti-SLA/LP) autoantibodies using the line-blot; for anti-F-actin autoantibodies using IIF both on VSM47 cell-line and on rat intestinal epithelial cells. AIH-1 was the most common type of AIH in the adult cohort (73.6%), while AIH-2 was the most common AIH in the pediatric cohort (61.9%). Both in adult and pediatric AIH-2 anti-LKM1 were the prevalent autoantibodies. In pediatric AIH-2 anti-LC1 autoantibodies were more frequent than in adult AIH-2 (59 vs. 28.6%), and in 35.9% of cases they were present alone. In 17 patients anti-LC1 autoantibodies were detected only with the line-blot assay. The levels of anti-LKM1 and of anti-LC1 were not different between adult and pediatric AIH, and the overall agreement between the results obtained with the two IIF methods for F-actin detection was 98.8% (CI 95%: 94.4-99.7%). The line-blot assay showed a higher sensitivity than IIF for anti-LC1 detection. Anti-LKM1 and anti-LC1 autoantibody levels are not different in adults and children. An almost perfect agreement between the two IIF methods for anti-F-actin detection has been observed. © 2014 Wiley Periodicals, Inc.

Autoimmune hepatitis in children: progression of 20 cases in northern Mexico.

PubMed

Nares-Cisneros, J; Jaramillo-Rodríguez, Y

2014-01-01

Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver with nonspecific clinical manifestations that causes greater liver damage in children than in adults. To analyze the clinical progression, biochemical profiles, histopathologic changes, and treatment response in 20 children with AIH. A retrospective study was carried out on the variables associated with clinical progression, diagnosis, and treatment response in children seen at the the Unidad Médica de Alta Especialidad (UMAE) No. 71 IMSS in Torreón, Coahuila, Mexico, from 1992 to 2012. Twenty patients were analyzed, 75% with type 1 AIH (AIH-1) and 25% with type 2 AIH (AIH-2). Girls predominated with a 3:1 ratio of girls to boys. The mean age was 10.07 ± 6.53 years for the AIH-1 cases and 6.75 ± 3.77 years for the AIH-2 cases. There was an association with immunologic diseases in 40% of the patients. The patients in the AIH-2 group had greater biochemical profile alterations and IgA deficiency. Anti-nuclear antibody and anti-smooth muscle antibody were positive in 100% of the patients with AIH-1, and anti-liver kidney microsomal type 1 antibody was positive in 100% of the AIH-2 patients. Liver biopsy revealed interface hepatitis in both groups. The AIH-2 group responded more quickly to treatment, but had a higher recurrence rate. Autoimmune hepatitis in the pediatric patient should be suspected in order to make an early diagnosis and thereby establish opportune treatment. Determining the type of AIH is necessary for making adequate diagnosis and for achieving a better outcome in relation to recurrence and complication rates. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Outcomes in children who underwent transplantation for autoimmune hepatitis.

PubMed

Martin, Steven R; Alvarez, Fernando; Anand, Ravinder; Song, Changhong; Yin, Wanrong

2011-04-01

The outcomes of 113 children with autoimmune hepatitis (AIH), registered with Studies of Pediatric Liver Transplantation and who underwent transplantation between 1995 and 2006, were compared with those who underwent transplantation for other diagnoses (non-AIH). A total of 4.9% of liver transplants were for AIH; 81% of these patients had AIH type 1 and most underwent transplantation for complications of chronic disease (60%), the majority in females (72%). Transplantation for fulminant AIH was more common in males (52.5% versus 47.5% chronic; P = 0.042). Patients with AIH differed from non-AIH patients by: age (13.0 ± 0.4 versus 4.6 ± 0.1 years; P < 0.0001), sex (64.6% female versus 52.9%; P = 0.016), ethnicity (48.7% white versus 58.2%; P < 0.0001), initial immunosuppression (tacrolimus-based: 72.6% versus 62.6%; P = 0.045; mycophenolate mofetil use: 31.0% versus 21.6%; P = 0.02), and immunosuppression at 2 years after transplant (monotherapy: 51.9% versus 17.3%; P < 0.0001). Late (>3 months), but not steroid-resistant or chronic, rejection was more common in AIH (log-rank P = 0.0015). The 5-year posttransplant survival for AIH was 86% (95% confidence interval: 73-93). Patient and graft survival, infectious and metabolic complications, and retransplantation rates did not differ between AIH and non-AIH groups. In conclusion, the higher risk for late acute rejection and greater degree of immunosuppression does not compromise outcomes of liver transplantation for AIH. Children who undergo transplantation for AIH in North America are typically female adolescents with complications of chronic AIH type 1 and include more children of African American or Latino American origin compared to the overall liver transplant population. These observations may inform detection, treatment, and surveillance strategies designed to reduce the progression of autoimmune hepatitis and subsequently, the need for transplantation. Copyright © 2010 American Association for the Study of Liver Diseases.

Severe acute intermittent hypoxia elicits phrenic long-term facilitation by a novel adenosine-dependent mechanism

PubMed Central

Nichols, Nicole L.; Dale, Erica A.

2012-01-01

Acute intermittent hypoxia [AIH; 3, 5-min episodes; 35–45 mmHg arterial Po2 (PaO2)] elicits serotonin-dependent phrenic long-term facilitation (pLTF), a form of phrenic motor facilitation (pMF) initiated by Gq protein-coupled metabotropic 5-HT2 receptors. An alternate pathway to pMF is induced by Gs protein-coupled metabotropic receptors, including adenosine A2A receptors. AIH-induced pLTF is dominated by the serotonin-dependent pathway and is actually restrained via inhibition from the adenosine-dependent pathway. Here, we hypothesized that severe AIH shifts pLTF from a serotonin-dependent to an adenosine-dependent form of pMF. pLTF induced by severe (25–30 mmHg PaO2) and moderate (45–55 mmHg PaO2) AIH were compared in anesthetized rats, with and without intrathecal (C4) spinal A2A (MSX-3, 130 ng/kg, 12 μl) or 5-HT receptor antagonist (methysergide, 300 μg/kg, 15 μl) injections. During severe, but not moderate AIH, progressive augmentation of the phrenic response during hypoxic episodes was observed. Severe AIH (78% ± 8% 90 min post-AIH, n = 6) elicited greater pLTF vs. moderate AIH (41% ± 12%, n = 8; P < 0.05). MSX-3 (28% ± 6%; n = 6; P < 0.05) attenuated pLTF following severe AIH, but enhanced pLTF following moderate AIH (86% ± 26%; n = 8; P < 0.05). Methysergide abolished pLTF after moderate AIH (12% ± 5%; n = 6; P = 0.035), but had no effect after severe AIH (66 ± 13%; n = 5; P > 0.05). Thus severe AIH shifts pLTF from a serotonin-dependent to an adenosine-dependent mechanism; the adenosinergic pathway inhibits the serotonergic pathway following moderate AIH. Here we demonstrate a novel adenosine-dependent pathway to pLTF following severe AIH. Shifts in the mechanisms of respiratory plasticity provide the ventilatory control system greater flexibility as challenges that differ in severity are confronted. PMID:22403346

Repetitive acute intermittent hypoxia increases expression of proteins associated with plasticity in the phrenic motor nucleus

PubMed Central

Satriotomo, Irawan; Dale, Erica A.; Dahlberg, Jenny M.; Mitchell, Gordon S.

2015-01-01

Acute intermittent hypoxia (AIH) initiates plasticity in respiratory motor control, including phrenic long term facilitation (pLTF). Since pLTF is enhanced by preconditioning with repetitive exposure to AIH (rAIH), we hypothesized that a rAIH protocol consisting of 3 AIH exposures per week for 10 weeks (3×wAIH; AIH: 10, 5-min episodes of 10.5% O2; 5-min normoxic intervals) would enhance expression of molecules that play key roles in pLTF within the phrenic motor nucleus. Immunohistochemical analyses revealed that 3×wAIH for 10 weeks increased serotonin terminal density in the C4 phrenic motor nucleus and serotonin 2A (5-HT2A) receptor expression in presumptive phrenic motor neurons. Immunoreactive brain derived neurotrophic factor (BDNF) and its high affinity receptor (TrkB) also increased following 3×wAIH. 3×wAIH also increased expression of another hypoxia-sensitive growth factor known to elicit phrenic motor facilitation, vascular endothelial growth factor (VEGF), and its receptor (VEGFR-2). Kinases “downstream” from TrkB and VEGFR-2 were up-regulated in or near presumptive phrenic motor neurons, including phosphorylated extracellular-signal regulated kinase (p-ERK) and protein kinase B (p-AKT). Thus, 3×wAIH up-regulates neurochemicals known to be associated with phrenic motor plasticity. Since 3×wAIH upregulates pro-plasticity molecules without evidence for CNS pathology, it may be a useful therapeutic tool in treating disorders that cause respiratory insufficiency, such as spinal injury or motor neuron disease. PMID:22704858

Association of a single nucleotide polymorphism in TNIP1 with type-1 autoimmune hepatitis in the Japanese population.

PubMed

Oka, Shomi; Higuchi, Takashi; Furukawa, Hiroshi; Nakamura, Minoru; Komori, Atsumasa; Abiru, Seigo; Nagaoka, Shinya; Hashimoto, Satoru; Naganuma, Atsushi; Naeshiro, Noriaki; Yoshizawa, Kaname; Shimada, Masaaki; Nishimura, Hideo; Tomizawa, Minoru; Kikuchi, Masahiro; Makita, Fujio; Yamashita, Haruhiro; Ario, Keisuke; Yatsuhashi, Hiroshi; Tohma, Shigeto; Kawasaki, Aya; Tsuchiya, Naoyuki; Migita, Kiyoshi

2018-06-01

Several studies reported that autoimmune diseases share a number of susceptibility genes. Of these genes, a SNP rs7708392 in TNIP1 was reported to be associated with systemic lupus erythematosus (SLE). Autoimmune hepatitis (AIH), a rare chronic progressive liver disease, shares some clinical features with SLE. Therefore, we investigated whether the SNP is associated with Japanese AIH. An association study of rs7708392 was conducted in 343 Japanese AIH patients and 828 controls. We found that rs7708392 is associated with AIH (P = 0.0236, odds ratio (OR) 1.26, 95% confidence interval (CI): 1.03-1.54), under the allele model for C allele. Significant differences of clinical characteristics of the AIH patients with or without G allele of rs7708392 were not detected. Of interest, the association was stronger in AIH without HLA-DRB1*04:05 allele (P = 0.0063, Q = 0.0127, OR 1.48, 95% CI: 1.12-1.96), though the association was not detected in AIH with DRB1*04:05. The C allele of rs7708392 was associated with AIH, especially AIH without DRB1*04:05, an already established risk factor.

Detection of anti-lactoferrin antibodies and anti-myeloperoxidase antibodies in autoimmune hepatitis: a retrospective study.

PubMed

Tan, Liming; Zhang, Yuhong; Peng, Weihua; Chen, Juanjuan; Li, Hua; Ming, Feng

2014-01-01

Anti-lactoferrin antibodies (ALA) and anti-myeloperoxidase antibodies (AMPA) are specific serological markers for autoimmune hepatitis (AIH). The project aimed to detect ALA and AMPA and explore their clinical significances in AIH patients. 59 AIH patients, 217 non AIH patients, and 50 healthy controls were enrolled in this study. ALA and AMPA were detected by ELISA. Antineutropil cytoplasmic antibodies (ANCA) and anti-smooth muscle antibodies (ASMA) were examined by indirect immunofluorescence. Antimitochondrial antibody M2 subtype (AMA-M2), anti-liver kidney microsomal antibody Type 1 (LKM1), anti-liver cytosol antibody Type 1 (LC1), and anti-soluble liver antigen/liver-pancreas antibodies (SLA/LP) were tested by immunoblot. The positivity for ALA was 18.6% in AIH group, only one patient in non-AIH group was positive for ALA; the positivity for AMPA was 59.3% in AIH group, with significant differences (P < 0.01) compared with other groups. The specificities for ALA and AMPA were 99.63% and 97.75%; the sensitivities were 18.64% and 59.32%; and the accuracy rates were 84.97% and 90.80%, respectively. A certain correlation was observed between ALA and SLA/LP, AMPA and ANCA, ASMA in AIH group. ALA and AMPA were associated with AIH, and had high clinical diagnostic value. Co-detection with other relative autoantibodies could play an important role in differential diagnosis of AIH.

Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

PubMed Central

Streeter, Kristi A.; Sunshine, Michael D.; Patel, Shreya; Gonzalez-Rothi, Elisa J.; Reier, Paul J.

2017-01-01

Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most midcervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multielectrode array was used to record C4/5 spinal discharge before [baseline (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O2, H1–H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared with BL (19%; p < 0.0001). Another subset had a similar response following each episode (40%) compared with BL (19%; p < 0.0001). In the latter group, connectivity remained elevated 15 min post-AIH (30%; p = 0.0002). Inhibitory C-IN connectivity increased during H1–H3 (4.5%; p = 0.0160), but was reduced 15 min post-AIH (0.5%; p = 0.0439). Spike-triggered averaging indicated that a subset of C-INs is synaptically coupled to phrenic motoneurons and excitatory inputs to these “pre-phrenic” cells increased during AIH. We conclude that AIH alters connectivity of the midcervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network. SIGNIFICANCE STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH. PMID:28751456

Amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene in gallbladder bile from patients with primary biliary cirrhosis.

PubMed

Hiramatsu, K; Harada, K; Tsuneyama, K; Sasaki, M; Fujita, S; Hashimoto, T; Kaneko, S; Kobayashi, K; Nakanuma, Y

2000-07-01

The etiopathogenesis of bile duct lesion in primary biliary cirrhosis is unknown, though the participation of bacteria and/or their components and products is suspected. In this study, we tried to detect and identify bacteria in the bile of patients with primary biliary cirrhosis by polymerase chain reaction using universal bacterial primers of the 16S ribosomal RNA gene. Gallbladder bile samples from 15 patients with primary biliary cirrhosis, 5 with primary sclerosing cholangitis, 5 with hepatitis C virus-related liver cirrhosis, 11 with cholecystolithiasis, and from 12 normal adult gallbladders were used. In addition to the culture study, partial bacterial 16S ribosomal RNA gene was amplified by polymerase chain reaction (PCR) taking advantage of universal primers that can amplify the gene of almost all bacterial species, and the amplicons were cloned and sequenced. Sequence homology with specific bacterial species was analyzed by database research. Bacterial contamination at every step of the bile sampling, DNA extraction and PCR study was avoided. Furthermore, to confirm whether bacterial DNA is detectable in liver explants, the same analysis was performed using 10 liver explants of patients with primary biliary cirrhosis. In primary biliary cirrhosis, 75% (p<0.0001) of 100 clones were identified as so-called gram-positive cocci while these cocci were positive in only 5% in cholecystolithiasis (p<0.0001). In cholecystolithiasis gram-negative rods were predominant instead. One bacterial species detected in a normal adult was not related to those detected in primary biliary cirrhosis and cholecystolithiasis patients. No bacterial DNA was detected by PCR amplification in 10 liver explants of patients with primary biliary cirrhosis. The present results raise several possible roles of gram-positive bacteria in bile in the etiopathogenesis of primary biliary cirrhosis. However, these results could also reflect an epiphenomenon due to decreased bile flow in the patients with primary biliary cirrhosis at an advanced stage.

Anti-soluble liver antigen/liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis.

PubMed

Vitozzi, Susana; Djilali-Saiah, Idriss; Lapierre, Pascal; Alvarez, Fernando

2002-12-01

Antibodies against soluble liver antigen/liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immunoassay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with liver and non-liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 +/- 339) than in type 1 AIH (1:600 +/- 71; p < 0.0001) and closely associated with higher titers of anti-liver kidney microsome type 1 (LKM1) and anti-liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.

Autoimmune hepatitis.

PubMed

Vergani, D; Mieli-Vergani, G

2004-06-01

Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

[Role of hepatitis A and E viruses in the development of autoimmune diseases].

PubMed

Iakimchuk, K S; Malinnikova, E Iu; Poleshchuk, V F; Mikhaĭlov, M I

2011-01-01

The mechanisms of development of autoimmune diseases may be associated with a complex of genetic, immune, hormonal, and infectious factors. Autoimmune diseases include a wide range of systemic and organ-specific diseases, including autoimmune hepatitis (AIH). It is currently assumed that the pathogenesis of AIH is due to compromised immune regulation in the presence of an exogenous triggering factor. Exogenous factors, such as viruses, may be triggers of AIH. There may be different ways of initiating an autoimmune response by viruses, which includes nonspecific T-lymphocyte activation and molecular mimicry. There is much evidence supporting the initiating role of hepatitis viruses in the development of AIH and other autoimmune diseases. The development of AIH symptoms during hepatitis A and E virus infections has been described elsewhere. The creation of animal models of viral hepatitis is required to confirm the hypothesis that the viruses trigger the development of AIH and other autoimmune manifestations.

HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis.

PubMed

Djilali-Saiah, Idriss; Fakhfakh, Amin; Louafi, Hamida; Caillat-Zucman, Sophie; Debray, Dominique; Alvarez, Fernando

2006-12-01

Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P < 0.0001) among patients with both anti-LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P < 0.0001) with anti-LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.

Acute intermittent hypoxia and rehabilitative training following cervical spinal injury alters neuronal hypoxia- and plasticity-associated protein expression.

PubMed

Hassan, Atiq; Arnold, Breanna M; Caine, Sally; Toosi, Behzad M; Verge, Valerie M K; Muir, Gillian D

2018-01-01

One of the most promising approaches to improve recovery after spinal cord injury (SCI) is the augmentation of spontaneously occurring plasticity in uninjured neural pathways. Acute intermittent hypoxia (AIH, brief exposures to reduced O2 levels alternating with normal O2 levels) initiates plasticity in respiratory systems and has been shown to improve recovery in respiratory and non-respiratory spinal systems after SCI in experimental animals and humans. Although the mechanism by which AIH elicits its effects after SCI are not well understood, AIH is known to alter protein expression in spinal neurons in uninjured animals. Here, we examine hypoxia- and plasticity-related protein expression using immunofluorescence in spinal neurons in SCI rats that were treated with AIH combined with motor training, a protocol which has been demonstrated to improve recovery of forelimb function in this lesion model. Specifically, we assessed protein expression in spinal neurons from animals with incomplete cervical SCI which were exposed to AIH treatment + motor training either for 1 or 7 days. AIH treatment consisted of 10 episodes of AIH: (5 min 11% O2: 5 min 21% O2) for 7 days beginning at 4 weeks post-SCI. Both 1 or 7 days of AIH treatment + motor training resulted in significantly increased expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) relative to normoxia-treated controls, in neurons both proximal (cervical) and remote (lumbar) to the SCI. All other markers examined were significantly elevated in the 7 day AIH + motor training group only, at both cervical and lumbar levels. These markers included vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and phosphorylated and nonphosphorylated forms of the BDNF receptor tropomyosin-related kinase B (TrkB). In summary, AIH induces plasticity at the cellular level after SCI by altering the expression of major plasticity- and hypoxia-related proteins at spinal regions proximal and remote to the SCI. These changes occur under the same AIH protocol which resulted in recovery of limb function in this animal model. Thus AIH, which induces plasticity in spinal circuitry, could also be an effective therapy to restore motor function after nervous system injury.

Histological Changes in Autoimmune Hepatitis with Graves' Disease: A Child Case Report.

PubMed

Yamada, Mamiko; Shibata, Hironori; Masugi, Yohei; Ishi, Tomohiro; Kameyama, Kaori; Ebinuma, Hirotoshi; Hasegawa, Tomonobu

2017-08-15

We herein report a child case of autoimmune hepatitis (AIH) accompanied with Graves' disease. Elevated aminotransferase levels were found in a 12-year-old Japanese girl with Graves' disease. In her first liver biopsy, necrosis and inflammation was limited to the centrilobular area, while the second biopsy showed different findings. Namely, portal injury newly appeared, including interface hepatitis, which represents the histological characteristics of AIH. As the histological findings at the onset of AIH do not always show typical findings, a re-biopsy is considered to be important in individuals suspected to have AIH. AIH should be included in the differential diagnosis of liver dysfunction in Graves' disease, even in children.

A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation

PubMed Central

Yuksel, Muhammed; Wang, Yipeng; Tai, Ningwen; Peng, Jian; Guo, Junhua; Beland, Kathie; Lapierre, Pascal; David, Chella; Alvarez, Fernando; Colle, Isabelle; Yan, Huiping; Mieli-Vergani, Giorgina; Vergani, Diego; Ma, Yun; Wen, Li

2016-01-01

Background Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease, characterized by interface hepatitis, the presence of circulating autoantibodies and hyper-gammaglobulinemia. There are two types of AIH, type-1 (AIH-1) and type-2 (AIH-2) characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or anti-nuclear (SMA/ANA) autoantibodies whereas patients with AIH-2 have anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. Cytochrome P4502D6 (CYP2D6) is the antigenic target of anti-LKM1 and formiminotransferase cyclodeaminase (FTCD) is the antigenic target of anti-LC1. It is known that AIH, both type-1 and type-2, is strongly linked to the Human Leukocyte Antigen (HLA) alleles -DR3, -DR4 and -DR7. However, the direct evidence of the association of HLA with AIH is lacking. Methods We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the non-obese diabetic (NOD) background (HLA-DR3 NOD) by immunization of HLA-DR3− and HLA-DR3+ NOD mice with a DNA plasmid, coding for human CYP2D6/FTCD fusion protein. Results Immunization with CYP2D6/FTCD leads to a sustained elevation of alanine aminotransferase (ALT), development of ANA and anti-LKM1/anti-LC1 autoantibodies, chronic immune cell infiltration and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced Th1 immune response and paucity of the frequency of regulatory T-cell (Treg) in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria. Conclusion Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo. PMID:26185095

Autoimmune paediatric liver disease

PubMed Central

Mieli-Vergani, Giorgina; Vergani, Diego

2008-01-01

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy. PMID:18528933

rs10499194 polymorphism in the tumor necrosis factor-α inducible protein 3 (TNFAIP3) gene is associated with type-1 autoimmune hepatitis risk in Chinese Han population

PubMed Central

Lin, Liming; Liu, Honglong

2017-01-01

Previous studies have found that the polymorphisms of tumor necrosis factor-α induced protein 3 (TNFAIP3) were associated with several autoimmune diseases. However, the role of TNFAIP3 polymorphisms in type-1 autoimmune hepatitis (AIH-1) remained unclear. The present study aimed to clarify the association of TNFAIP3 polymorphisms with AIH-1 risk in a Chinese Han population. The TaqMan SNP genotyping assay was used to determine the distribution of TNFAIP3 polymorphisms in 432 AIH-1 patients and 500 healthy controls. The association of TNFAIP3 polymorphisms and clinical characteristic was further evaluated. Five TNFAIP3 polymorphisms (rs2230926, rs5029939, rs10499194, rs6920220, rs582757) were analyzed in the present study. No significant association could be observed between rs2230926, rs5029939, rs6920220, rs582757 and the susceptibility to AIH-1 in Chinese Han population. Compared with wild-type genotype CC at rs10499194, individuals carrying CT genotype had a significantly increased risk for developing AIH-1 (OR = 2.32, 95%CI 1.44–3.74). Under a dominant model, CT/TT carriers have a 140% increased risk of AIH-1 than CC carriers (OR = 2.40, 95%CI 1.50–3.87). The rs10499194 T allele was also found to be significantly associated with AIH-1 risk (OR = 2.41, 95%CI 1.51–3.82). In addition, higher serum ALT, AST levels and more common cirrhosis were observed in AIH-1 patients with T allele (CT/TT) than those with CC genotype. In conclusion, TNFAIP3 rs10499194 T allele and CT genotype were associated with an increased risk for AIH-1, suggesting rs10499194 polymorphism as a candidate of susceptibility locus to AIH-1. PMID:28448618

Autoimmune paediatric liver disease.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2008-06-07

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy.

A genomewide DNA microsatellite association study of Japanese patients with autoimmune hepatitis type 1.

PubMed

Yokosawa, Shuichi; Yoshizawa, Kaname; Ota, Masao; Katsuyama, Yoshihiko; Kawa, Shigeyuki; Ichijo, Tetsuya; Umemura, Takeji; Tanaka, Eiji; Kiyosawa, Kendo

2007-02-01

Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA class II genes. We previously searched the whole HLA region for AIH susceptibility genes using microsatellite markers and found only HLA-DR/DQ to be a candidate region for this suspected multifactorial disease. As such, the aim of this study was to broaden our search and screen the whole genome for additional genes that might contribute to type 1 AIH susceptibility. Eighty-one patients with type 1 AIH (15 men, 66 women, average age 55.9) and 80 healthy sex- and age-matched Japanese controls were enrolled in this study. We performed a case-control association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. Two markers, one on chromosome 11 (D11S902, Pc = 0.013) and one on chromosome 18 (D18S464, Pc = 0.008), were revealed to have statistically significant associations with AIH. An additional 7 markers (D2S367, D6S309, D9S273, D11S1320, D16S423, D17S938, and D18S68) were also found to be candidate susceptibility regions. In addition, our results showed there were 17 regions that may contain genes of resistance to AIH. No specific markers were detected in HLA-DR4-negative patients, and no differences were seen in the clinical courses of patients (severe versus mild to moderate). This first genomewide scan of Japanese AIH patients revealed at least 26 candidate AIH susceptibility or resistance regions other than HLA class II loci. These results also suggested that the products of several genes interact to determine heritable susceptibility to AIH.

Ulcerative colitis associated with primary biliary cirrhosis.

PubMed

Koulentaki, M; Koutroubakis, I E; Petinaki, E; Tzardi, M; Oekonomaki, H; Mouzas, I; Kouroumalis, E A

1999-10-01

Primary biliary cirrhosis and ulcerative colitis are two diseases with many features of autoimmunity. Thirteen cases of coexistence of the two diseases have been reported in the literature so far. Patients are usually younger and more often males than the ordinary primary biliary cirrhosis patient, while the colitis is mild and easily controllable. In a homogeneous population of 550,000 inhabitants of the island of Crete, 412 cases of ulcerative colitis and 82 individuals with primary biliary cirrhosis or autoimmune cholangitis have been identified. In two cases, coexistence of the two diseases was found. Immunological screening for AMA positivity in 150 ulcerative colitis sera disclosed no further cases. Prevalence of primary biliary cirrhosis in ulcerative colitis patients seems at least 30 times higher than in the general population in our area. A possible immunological link between the two diseases is discussed.

Autoimmune hepatitis in children.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2002-08-01

AIH, ASC, and de novo AIH after liver transplantation are childhood liver diseases of an autoimmune nature. The mode of presentation of AIH in childhood is variable, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. Although corticosteroids are effective in all types of childhood AIH, patients with LKM1 have a higher frequency of acute hepatic failure and relapse after corticosteroid withdrawal than do patients with ANA/SMA. ASC occurs commonly in the absence of inflammatory bowel disease, requires cholangiography for diagnosis, and improves during corticosteroid therapy. The development of AIH de novo in children who undergo liver transplantation for nonautoimmune liver disease may reflect interference with the maturation of T cells by immunosuppressive drugs.

Autoimmune hepatitis in children: what is different from adult AIH?

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. Copyright Thieme Medical Publishers.

Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis.

PubMed

Bektas, Mehmet; Seven, Gulseren; Idilman, Ramazan; Yakut, Mustafa; Doğanay, Beyza; Kabacam, Gökhan; Ustun, Yusuf; Korkut, Esin; Kalkan, Çağdaş; Sahin, Günay; Cetinkaya, Hulya; Bozkaya, Hakan; Yurdaydin, Cihan; Bahar, Kadir; Cinar, Kubilay; Soykan, Irfan

2014-03-01

Primary biliary cirrhosis is associated with other autoimmune diseases including Sjögren's syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögren's syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis. The study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed. Manometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mmHg): (24 vs 20, p=0.033); median esophageal contraction amplitude (mmHg): (71 vs 56, p=0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p<0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p=0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p=0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient). Esophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Autoantibodies and their antigens in autoimmune hepatitis.

PubMed

Bogdanos, Dimitrios P; Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoantibody detection assists in the diagnosis and allows differentiation of autoimmune hepatitis (AIH) type 1 (AIH-1), characterized by antinuclear antibody (ANA) and/or smooth muscle antibody (SMA), and type 2 (AIH-2), distinguished by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) and/or antibodies to liver cytosol type 1 (anti-LC1). Detection of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-soluble liver antigen (SLA) antibodies can act as an additional pointer toward the diagnosis of AIH, particularly in the absence of the conventional autoantibodies. Routine autoantibody testing by indirect immunofluorescence has been recently complemented by molecular assays based on purified or recombinant antigens. Although the AIH-1-specific ANA and SMA targets need better definition, those of anti-LKM1 and anti-LC1 in AIH-2 have been clearly identified; the fine specificity of antibody reactivity and its clinical relevance to disease pathogenesis are the focus of ongoing investigation. This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient. Copyright Thieme Medical Publishers.

[Antibodies and physiopathogeny of autoimmune hepatitis].

PubMed

García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo

2003-01-01

Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.

Daily intermittent hypoxia enhances walking after chronic spinal cord injury

PubMed Central

Hayes, Heather B.; Jayaraman, Arun; Herrmann, Megan; Mitchell, Gordon S.; Rymer, William Z.

2014-01-01

Objectives: To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI). Methods: Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349). Results: dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1–6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9–6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5–171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1–173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3–134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6–173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3–206.6 m, p < 0.001). Conclusions: dAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI. Classification of evidence: This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI. PMID:24285617

Incidence and Characteristics of Autoimmune Hepatitis.

PubMed

Jiménez-Rivera, Carolina; Ling, Simon C; Ahmed, Najma; Yap, Jason; Aglipay, Mary; Barrowman, Nick; Graitson, Samantha; Critch, Jeff; Rashid, Mohsin; Ng, Vicky L; Roberts, Eve A; Brill, Herbert; Dowhaniuk, Jenna K; Bruce, Garth; Bax, Kevin; Deneau, Mark; Guttman, Orlee R; Schreiber, Richard A; Martin, Steven; Alvarez, Fernando

2015-11-01

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease of unknown etiology, with limited population-based estimates of pediatric incidence. We reported the incidence of pediatric AIH in Canada and described its clinical characteristics. We conducted a retrospective cohort study of patients aged <18 years diagnosed with AIH between 2000-2009 at all pediatric centers in Canada. A total of 159 children with AIH (60.3% female, 13.2% type 2 AIH) were identified. Annual incidence was 0.23 per 100000 children. Median age at presentation for type 1 was 12 years (interquartile range: 11-14) versus 10 years for type 2 (interquartile range: 4.5-13) (P = .03). Fatigue (58%), jaundice (54%), and abdominal pain (49%) were the most common presenting symptoms. Serum albumin (33 vs 38 g/L; P = .03) and platelet count (187 000 vs 249 000; P <.001) were significantly lower and the international normalized ratio (1.4 vs 1.2; P <.001) was higher in cirrhotic versus noncirrhotic patients. Initial treatment included corticosteroids (80%), azathioprine (32%), and/or cyclosporine (13%). Response to treatment at 1 year was complete in 90%, and partial in 3%. 3% of patients had no response, and 3% responded and later relapsed. Nine patients underwent liver transplantation, and 4 patients died at a mean follow-up of 4 years. AIH is uncommon in children and adolescents in Canada. Type 1 AIH was diagnosed 5.5 times more frequently than type 2 AIH. Most patients respond well to conventional therapy, diminishing the need for liver transplantation. Copyright © 2015 by the American Academy of Pediatrics.

Intermittent hypoxia and neurorehabilitation

PubMed Central

Gonzalez-Rothi, Elisa J.; Lee, Kun-Ze; Dale, Erica A.; Reier, Paul J.; Mitchell, Gordon S.

2015-01-01

In recent years, it has become clear that brief, repeated presentations of hypoxia [i.e., acute intermittent hypoxia (AIH)] can boost the efficacy of more traditional therapeutic strategies in certain cases of neurologic dysfunction. This hypothesis derives from a series of studies in animal models and human subjects performed over the past 35 yr. In 1980, Millhorn et al. (Millhorn DE, Eldridge FL, Waldrop TG. Respir Physiol 41: 87-103, 1980) showed that electrical stimulation of carotid chemoafferent neurons produced a persistent, serotonin-dependent increase in phrenic motor output that outlasts the stimulus for more than 90 min (i.e., a “respiratory memory”). AIH elicits similar phrenic “long-term facilitation” (LTF) by a mechanism that requires cervical spinal serotonin receptor activation and de novo protein synthesis. From 2003 to present, a series of studies demonstrated that AIH can induce neuroplasticity in the injured spinal cord, causing functional recovery of breathing capacity after cervical spinal injury. Subsequently, it was demonstrated that repeated AIH (rAIH) can induce recovery of limb function, and the functional benefits of rAIH are greatest when paired with task-specific training. Since uncontrolled and/or prolonged intermittent hypoxia can elicit pathophysiology, a challenge of intermittent hypoxia research is to ensure that therapeutic protocols are well below the threshold for pathogenesis. This is possible since many low dose rAIH protocols have induced functional benefits without evidence of pathology. We propose that carefully controlled rAIH is a safe and noninvasive modality that can be paired with other neurorehabilitative strategies including traditional activity-based physical therapy or cell-based therapies such as intraspinal transplantation of neural progenitors. PMID:25997947

Uveitis in patients with autoimmune hepatitis.

PubMed

Lim, Lyndell L; Scarborough, John D; Thorne, Jennifer E; Graham, Elizabeth; Kempen, John H; Mackensen, Friederike; Nguyen, Quan Dong; Prabriputaloong, Tisha; Read, Russell W; Suhler, Eric B; Schwartz, Jonathan M; Smith, Justine R

2009-02-01

To report seven cases of uveitis occurring in patients with autoimmune hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic feature of AIH. Multicenter, retrospective, observational case series of patients with AIH and uveitis. One index case was identified at Oregon Health & Science University. Further cases were identified by a web-based survey of members of the American Uveitis Society, the International Uveitis Study Group, the Proctor Foundation mailing list server, and the First SUN International Workshop. Respondents were asked to provide clinical information about uveitis phenotype, AIH features, and treatment. Clinical information was obtained for seven individuals (four females and three males; age range, seven to 67 years) who suffered from AIH and uveitis. Average duration of follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location. Every patient had complications arising from his or her uveitis, including cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To treat the uveitis and/or AIH, the majority of patients required oral prednisone and all seven patients were treated with systemic immunosuppression. Despite the small size of this study, our findings suggest an association between AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight-threatening complications, necessitating systemic immunosuppression in some individuals.

Coexistence of primary biliary cirrhosis and myasthenia gravis: a case study.

PubMed

Horigome, H; Nomura, T; Saso, K; Joh, T; Ohara, H; Akita, S; Sobue, S; Mizuno, Y; Kato, Y; Itoh, M

2000-01-01

We present a case that suggests a relationship between primary biliary cirrhosis and myasthenia gravis. A 43-year-old Japanese woman was admitted to the Nagoya City University Medical School, First Department of Internal Medicine with abnormal liver function in August 1991. She had had ptosis of the right eye since 1990. She had not been treated for liver disease. Ptosis of the right eye and hepatomegaly were present. Serum laboratory examinations revealed elevated biliary enzymes and IgM levels; tests were positive for antimitochondrial antibody and antiacetylcholine antibody. Liver histology revealed chronic non-suppurative destructive cholangitis and led to a diagnosis of primary biliary cirrhosis. The tensilon test was positive. Electromyography with repetitive motor nerve stimulation revealed a neuromuscular junction defect; i.e., the primary characteristic of myasthenia gravis. The patient was diagnosed with myasthenia gravis. Although the development of myasthenia gravis has previously been reported in patients with primary biliary cirrhosis during D-penicillamine administration, this is a very rare case of the coexistence of both diseases before such treatment.

Primary Biliary Cholangitis (Primary Biliary Cirrhosis)

MedlinePlus

... Process Research Training & Career Development Funded Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive ...

Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

PubMed Central

Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

2015-01-01

Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

Liver biopsy

MedlinePlus

... Primary biliary cirrhosis Primary biliary cholangitis Pyogenic liver abscess Reye syndrome Sclerosing cholangitis Wilson disease Risks Risks may include: Collapsed lung Complications from the sedation Injury to the gallbladder ...

Multi-site evaluation of a computer aided detection (CAD) algorithm for small acute intra-cranial hemorrhage and development of a stand-alone CAD system ready for deployment in a clinical environment

NASA Astrophysics Data System (ADS)

Deshpande, Ruchi R.; Fernandez, James; Lee, Joon K.; Chan, Tao; Liu, Brent J.; Huang, H. K.

2010-03-01

Timely detection of Acute Intra-cranial Hemorrhage (AIH) in an emergency environment is essential for the triage of patients suffering from Traumatic Brain Injury. Moreover, the small size of lesions and lack of experience on the reader's part could lead to difficulties in the detection of AIH. A CT based CAD algorithm for the detection of AIH has been developed in order to improve upon the current standard of identification and treatment of AIH. A retrospective analysis of the algorithm has already been carried out with 135 AIH CT studies with 135 matched normal head CT studies from the Los Angeles County General Hospital/ University of Southern California Hospital System (LAC/USC). In the next step, AIH studies have been collected from Walter Reed Army Medical Center, and are currently being processed using the AIH CAD system as part of implementing a multi-site assessment and evaluation of the performance of the algorithm. The sensitivity and specificity numbers from the Walter Reed study will be compared with the numbers from the LAC/USC study to determine if there are differences in the presentation and detection due to the difference in the nature of trauma between the two sites. Simultaneously, a stand-alone system with a user friendly GUI has been developed to facilitate implementation in a clinical setting.

Amelogenesis imperfecta: therapeutic strategy from primary to permanent dentition across case reports.

PubMed

Toupenay, Steve; Fournier, Benjamin Philippe; Manière, Marie-Cécile; Ifi-Naulin, Chantal; Berdal, Ariane; de La Dure-Molla, Muriel

2018-06-15

Hereditary enamel defect diseases are regrouped under the name "Amelogenesis Imperfecta" (AIH). Both dentitions are affected. Clinical expression is heterogeneous and varies between patients. Mutations responsible for this multigene disease may alter various genes and the inheritance can be either autosomal dominant or recessive, or X-linked. Until now, no therapeutic consensus has emerged for this rare disease. The purpose of this article was to report treatments of AIH patients from childhood to early adulthood. Treatment of three patients of 3, 8 16 years old are described. Each therapeutic option was discussed according to patients' age and type of enamel alteration. Paediatric crowns and resin based bonding must be preferred in primary teeth. In permanent teeth, non-invasive or minimally invasive dentistry should be the first choice in order to follow a therapeutic gradient from the less invasive options to prosthodontic treatments. Functional and aesthetic issues require patients to be treated; this clinical care should be provided as early as possible to enable a harmonious growth of the maxillofacial complex and to prevent pain.

Pigment gallstone pathogenesis: slime production by biliary bacteria is more important than beta-glucuronidase production.

PubMed

Stewart, L; Ponce, R; Oesterle, A L; Griffiss, J M; Way, L W

2000-01-01

Pigment stones are thought to form as a result of deconjugation of bilirubin by bacterial beta-glucuronidase, which results in precipitation of calcium bilirubinate. Calcium bilirubinate is then aggregated into stones by an anionic glycoprotein. Slime (glycocalyx), an anionic glycoprotein produced by bacteria causing foreign body infections, has been implicated in the formation of the precipitate that blocks biliary stents. We previously showed that bacteria are present within the pigment portions of gallstones and postulated a bacterial role in pigment stone formation through beta-glucuronidase or slime production. Ninety-one biliary bacterial isolates from 61 patients and 12 control stool organisms were tested for their production of beta-glucuronidase and slime. The average slime production was 42 for biliary bacteria and 2.5 for stool bacteria (P <0.001). Overall, 73% of biliary bacteria and 8% of stool bacteria produced slime (optical density >3). In contrast, only 38% of biliary bacteria produced beta-glucuronidase. Eighty-two percent of all patients, 90% of patients with common bile duct (CBD) stones, 100% of patients with primary CBD stones, and 93% of patients with biliary tubes had one or more bacterial species in their stones that produced slime. By comparison, only 47% of all patients, 60% of patients with CBD stones, 62% of patients with primary CBD stones, and 50% of patients with biliary tubes had one or more bacteria that produced beta-glucuronidase. Most biliary bacteria produced slime, and slime production correlated better than beta-glucuronidase production did with stone formation and the presence of biliary tubes or stents. Patients with primary CBD stones and biliary tubes had the highest incidence of slime production. These findings suggest that bacterial slime is important in gallstone formation and the blockage of biliary tubes.

GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

PubMed Central

Davies, M H; Elias, E; Acharya, S; Cotton, W; Faulder, G C; Fryer, A A; Strange, R C

1993-01-01

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype. Images Figure 1 Figure 2 PMID:8491405

Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis.

PubMed

Couto, Claudia A; Bittencourt, Paulo L; Porta, Gilda; Abrantes-Lemos, Clarice P; Carrilho, Flair J; Guardia, Bianca D; Cançado, Eduardo L R

2014-02-01

Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. © 2013 by the American Association for the Study of Liver Diseases.

Overlapping but distinct specificities of anti-liver-kidney microsome antibodies in autoimmune hepatitis type II and hepatitis C revealed by recombinant native CYP2D6 and novel peptide epitopes

PubMed Central

Klein, R; Zanger, U M; Berg, T; Hopf, U; Berg, P A

1999-01-01

Anti-liver-kidney microsome antibodies (anti-LKM) occur in autoimmune hepatitis (AIH) type II and in a subset of patients with hepatitis C. Anti-LKM1 in AIH are directed against cytochrome P4502D6 (CYP2D6), but conflicting data exist concerning the specificity of anti-LKM in hepatitis C. The aim of this study was to evaluate binding specificities of anti-LKM antibodies in both diseases using novel test antigens as well as their inhibitory capacity on CYP2D6 enzyme activity. Sera from 22 patients with AIH type II and 17 patients with hepatitis C being anti-LKM-positive in the immunofluorescence test were investigated for binding to native recombinant CYP2D6 and liver microsomes by ELISA and immunoblotting, and to synthetic peptides covering the region 254–339 (254–273, 257–269, 270–294, 291–310, 307–324, 321–339, 373–389) as well as the novel peptide 196–218 by ELISA. Furthermore, all sera were tested for inhibition of CYP2D6-dependent bufuralol 1′-hydroxylase activity. Twenty of the 22 AIH type II sera (91%) and nine of the 17 hepatitis C sera (53%) were positive for CYP2D6 by ELISA and/or immunoblotting. The previously described major peptide epitope comprising CYP2D6 amino acids 257–269 was recognized by 16 of the 22 AIH sera but by only one hepatitis C serum. A further epitope, 196–218, could be defined for the first time as another immunodominant epitope for AIH because it was recognized by 15 of the 22 AIH (68%) but only three of the 17 hepatitis C sera (18%). With the exception of the peptide 254–273, the other peptides showed no significant reactivity. Analysing the inhibitory properties of anti-LKM antibodies it emerged that 95% of AIH sera and 88% of hepatitis C sera inhibited enzyme function. These data indicate that anti-LKM antibodies in AIH and hepatitis C react with CYP2D6, as shown by their inhibitory activity, and that besides the known epitope 257–269 a further immunodominant epitope exists on CYP2D6 which is recognized by sera from patients with AIH II but hardly by sera from patients with hepatitis C. PMID:10540193

ABO blood groups, Rhesus negativity, and primary biliary cirrhosis

PubMed Central

Hamlyn, A. N.; Morris, J. S.; Sherlock, S.

1974-01-01

The distribution of blood groups and Rhesus negativity in 91 British patients with primary biliary cirrhosis was compared with a sample of registered blood donors. There were no significant differences from the expected proportions calculated from the control groups. Although the number of cases studied is small the analysis does not confirm previous reports of an excess of A group in the disease. If a genetic basis exists for primary biliary cirrhosis alternative markers must be found. PMID:4211827

Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis.

PubMed

Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan

2017-09-01

Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

Muscle weakness in a girl with autoimmune hepatitis and Graves' disease.

PubMed

Sarkhy, Ahmed; Persad, Rabindranath; Tarnopolsky, Mark

2009-02-01

Autoimmune hepatitis (AIH) is a chronic hepatic autoimmune disease of unknown etiology associated with inflammatory changes and autoantibodies. The combination of AIH, Grave's disease, and myasthenia gravis (MG) is rare, with only one other case reported. We report a pediatric patient with AIH type 2 and Grave's disease who developed MG whilst on a treatment with corticosteroids. A 13-year-old girl, diagnosed with thyrotoxicosis, was identified as having AIH type 2. During the course of her therapy, she developed muscle weakness. Investigations revealed increased anti-acetylcholine receptor (AChR) antibodies and her electromyography (EMG) was characteristic for MG. Her course is described here. This case highlights the importance of investigating muscle weakness in severely ill hospitalized patients.

A comparative evaluation of early stent occlusion among biliary conventional versus wing stents.

PubMed

Khashab, Mouen A; Hutfless, Susan; Kim, Katherine; Lennon, Anne Marie; Canto, Marcia I; Jagannath, Sanjay B; Okolo, Patrick I; Shin, Eun Ji; Singh, Vikesh K

2012-06-01

Conventional plastic stents with a lumen typically have limited patency. The lumenless wing stent was engineered to overcome this problem. The objective of this study was to compare the incidence of early stent occlusion (symptomatic occlusion/cholangitis necessitating re-insertion within 90 days) for wing stents and conventional plastic stents. Patients with biliary pathology treated with plastic biliary stenting during the period 2003-2009 comprised the study cohort. Patients who had at least one biliary wing stent placed comprised the wing stent group, whereas patients who underwent only conventional stent plastic placement comprised the conventional stent group. Patients were stratified by indication: benign biliary strictures (group 1), malignant biliary strictures (group 2), or benign biliary non-stricture pathology (group 3). The association of stent type with the occurrence of primary outcome by indication was analyzed by use of multivariable logistic regression. Three-hundred and forty-six patients underwent 612 ERCP procedures with placement of plastic biliary stent(s). On multivariate analysis, early stent occlusion did not differ between the wing and conventional groups in groups 1, 2, and 3. Among patients who achieved primary outcome in group 2, significantly fewer patients in the wing group had cholangitis (6.7% vs. 39.1%, P = 0.03). Among patients who achieved primary outcome in group 3, significantly fewer patients in the wing group had cholangitis (10% vs. 50%, P = 0.03). Early stent occlusion was similar for wing stents and conventional plastic stents. Wing stents, however, were associated with a lower incidence of cholangitis in patients with malignant biliary obstruction and benign non-stricturing biliary pathology.

Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease.

PubMed Central

Epstein, O; Dick, R; Sherlock, S

1981-01-01

The association of finger clubbing and periostitis has been reported in primary biliary cirrhosis and, more rarely, in other forms of chronic liver disease. The prevalence of periostitis and its relationship to finger clubbing is unknown. In this prospective study, we have determined the prevalence of periostitis and finger clubbing in 74 patients with primary biliary cirrhosis and 54 with other forms of chronic liver disease. Clubbing was present in 24% of patients with primary biliary cirrhosis, 29% with HBsAg negative chronic active hepatitis, and 23% in the group of miscellaneous liver diseases. Symmetrical periostitis affecting the tibiae and fibulae occurred in 35% of patients with primary biliary cirrhosis, 29% with chronic, active hepatitis and 40% of patients in the miscellaneous group. The distal radii and ulnae were affected in only eight patients (6%). In primary biliary cirrhosis, the presence of finger clubbing was strongly associated with periostitis (P less than 0.01), but this association was uncommon in other forms of chronic liver disease. In all forms of chronic liver disease periostitis commonly occurs in the absence of finger clubbing. Marked tenderness over the distal leg bones is a reliable sign of underlying periostitis, but this sign is present in only a third of affected patients. This study indicates that periostitis affecting the lower leg bones is common in patients with chronic liver disease, and its presence should be sought whether or not the patient has finger clubbing. Images Fig. 2 PMID:7227854

Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling.

PubMed

Kido, Masahiro; Watanabe, Norihiko; Okazaki, Taku; Akamatsu, Takuji; Tanaka, Junya; Saga, Kazuyuki; Nishio, Akiyoshi; Honjo, Tasuku; Chiba, Tsutomu

2008-10-01

Because of the lack of animal models developing spontaneous autoimmune hepatitis (AIH), the molecular mechanisms involved in the development of AIH are still unclear. This study aims to examine the regulatory roles of naturally arising CD4(+)CD25(+) regulatory T (Treg) cells and programmed cell death 1 (PD-1)-mediated signaling in the development of AIH. To induce a concurrent loss of Treg cells and PD-1-mediated signaling, neonatal thymectomy (NTx), which severely reduces the number of Treg cells, was performed on PD-1(-/-) mice. After the NTx, we performed histologic examination, assessed autoantibody production and infiltrating cells in the liver, and conducted adoptive transfer experiments. In contrast to NTx mice and PD-1(-/-) mice, NTx-PD-1(-/-) mice produced antinuclear antibodies and developed fatal hepatitis characterized by a CD4(+) and CD8(+) T-cell infiltration invading the parenchyma with massive lobular necrosis. Induction of AIH in NTx-PD-1(-/-) mice was suppressed by transfer of Treg cells, even derived from PD-1(-/-) mice. Transfer of total but not CD4(+) T-cell-depleted splenocytes from NTx-PD-1(-/-) mice into RAG2(-/-) mice induced the development of severe hepatitis. In contrast, the transfer of CD8(+) T-cell-depleted splenocytes triggered only mononuclear infiltrates without massive necrosis of the parenchyma. NTx-PD-1(-/-) mice are the first mouse model of spontaneous fatal AIH. The concurrent loss of Treg cells and PD-1-mediated signaling can induce the development of fatal AIH. Autoreactive CD4(+) T cells are essential for induction of AIH, whereas CD8(+) T cells play an important role in progression to fatal hepatic damage.

Diagnosis and Management of Paediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego; Baumann, Ulrich; Czubkowski, Piotr; Debray, Dominique; Dezsofi, Antal; Fischler, Björn; Gupte, Girish; Hierro, Loreto; Indolfi, Giuseppe; Jahnel, Jörg; Smets, Françoise; Verkade, Henkjan J; Hadzic, Nedim

2017-11-03

Paediatric autoimmune liver disease is characterised by inflammatory liver histology, circulating autoantibodies and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. Two types of paediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (anti-LKM-1/anti-LC-1; AIH-2).Pertinent issues addressing the diagnosis, treatment and long term follow up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate and Mendeley databases over the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Itai, Y.; Araki, T.; Furui, S.

Fifteen patients with primary intrahepatic biliary malignancy (cholangiocarcinoma in 13, biliary cystadenocarcinoma in two) were examined by computed tomography (CT). The CT features were classified into three types: (A) a well-defined round cystic mass with internal papillary projections, (B) a localized intrahepatic biliary dilatation without a definite mass lesion, and (C) miscellaneous low-density masses. Intraphepatic biliary dilatation was noted in all cases of Types A and B and half of those of Type C; dilatation of extrahepatic bile ducts occurred in 4/4, 1/3, and 0/8, respectively. CT patterns, such as a well-defined round cystic mass with papillary projections or dilatationmore » of intra- and extrahepatic ducts, give important clues leading to a correct diagnosis of primary intrahepatic biliary malignancy.« less

One-stage percutaneous triple procedure for treatment of endoscopically unmanageable patients with malignant biliary obstruction and marked ascites.

PubMed

Seif, Hany M A; Zidan, Mohammed; Helmy, Ahmed

2013-12-01

To assess the feasibility, safety and efficacy of one-stage percutaneous triple procedure including; ascites drainage, primary metallic biliary stenting, and tract embolisation with N-butyl 2-cyanoacrylate (NBCA), in treatment of patients with malignant biliary obstruction and marked ascites. This study involved 25 patients with malignant biliary obstruction and marked ascites (age range, 46-78y; mean age±SD, 65y±5) for whom endoscopic treatment failed or was unsuitable. Ascites drainage, percutaneous primary metallic biliary stenting, and tract embolisation with lipiodol/NBCA mixture were performed in a one-stage procedure. The mean±SD follow up period was 26±2weeks. The technical and clinical success rates were 96% and 88% respectively. No procedure related deaths or major complications were observed. The reported minor complications included; moderate pain and vomiting during and after balloon dilation, postprocedural cholangitis, and bile leakage in 44%, 16%, and 8% of the patients respectively. Primary stent patency was achieved in 96%. The 30-days mortality was 8%. The stent obstruction occurred in 3 (13%) of the 23 patients who survived more than 30-days. Percutaneous drainage of ascites followed immediately by primary biliary stenting, together with tract embolisation with NBCA is technically feasible, safe, and effective alternative palliative treatment for endoscopically unmanageable patients with malignant biliary obstruction and marked ascites. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

Plastic biliary stents for benign biliary diseases.

PubMed

Perri, Vincenzo; Familiari, Pietro; Tringali, Andrea; Boskoski, Ivo; Costamagna, Guido

2011-07-01

Biliary plastic stenting plays a key role in the endoscopic management of benign biliary diseases. Complications following surgery of the biliary tract and liver transplantation are amenable to endoscopic treatment by plastic stenting. Insertion of an increasing number of plastic stents is currently the method of choice to treat postoperative biliary strictures. Benign biliary strictures secondary to chronic pancreatitis or primary sclerosing cholangitis may benefit from plastic stenting in select cases. There is a role for plastic stent placement in nonoperative candidates with acute cholecystitis and in patients with irretrievable bile duct stones. Copyright © 2011 Elsevier Inc. All rights reserved.

Risk factors and outcome in patients with primary sclerosing cholangitis with persistent biliary candidiasis.

PubMed

Rupp, Christian; Bode, Konrad Alexander; Chahoud, Fadi; Wannhoff, Andreas; Friedrich, Kilian; Weiss, Karl-Heinz; Sauer, Peter; Stremmel, Wolfgang; Gotthardt, Daniel Nils

2014-10-23

Candidiasis is commonly observed in patients with primary sclerosing cholangitis (PSC), but the clinical risk factors associated with its presence have not been fully investigated. In this study, we aimed to analyse the incidence, risk factors, and transplantation-free survival in primary sclerosing cholangitis (PSC) patients with persistent biliary candidiasis. We retrospectively analysed patients diagnosed with PSC who were admitted to our department during 2002 to 2012. One-hundred fifty patients whose bile cultures were tested for fungal species were selected, and their clinical and laboratory parameters were investigated. The results of endoscopic retrograde cholangiography (ERC) and bile cultures were analysed using chart reviews. The cases of biliary candidiasis were sub-classified as transient or persistent. Thirty out of 150 (20.0%) patients had biliary candidiasis. Although all patients demonstrated comparable baseline characteristics, those with biliary candidiasis showed significantly reduced transplantation-free survival (p < 0.0001) along with a markedly elevated frequency of cholangiocarcinoma (CCA) (p = 0.04). The patients were further sub-classified according to the transient (15/30) or persistent (15/30) nature of their biliary candidiasis. A subgroup analysis showed reduced survival with a greater necessity for orthotopic liver transplantation (OLT) only in patients with persistence of Candida (p = 0.007). The survival in the patients with transient biliary candidiasis was comparable to that in candidiasis-free patients. In a multivariate regression analysis that included Mayo risk score (MRS), sex, age, dominant stenosis, inflammatory bowel disease, autoimmune hepatitis overlap syndrome, and number of times ERC was performed, biliary candidiasis was an independent risk factor for reduced survival (p = 0.008). Risk factors associated with acquisition of biliary candidiasis were age at PSC diagnosis and number of ERCs. The persistence of biliary candidiasis is associated with markedly reduced transplantation-free survival in PSC patients. By contrast, actuarial survival in patients with transient biliary candidiasis approaches that for patients without any evidence of biliary candidiasis. Further studies on the treatment of persistent biliary candidiasis in patients with PSC are warranted.

Utility of common bile duct measurement in ED point of care ultrasound: A prospective study.

PubMed

Lahham, Shadi; Becker, Brent A; Gari, Abdulatif; Bunch, Steven; Alvarado, Maili; Anderson, Craig L; Viquez, Eric; Spann, Sophia C; Fox, John C

2018-06-01

Measurement of the common bile duct (CBD) is considered a fundamental component of biliary point-of-care ultrasound (POCUS), but can be technically challenging. The primary objective of this study was to determine whether CBD diameter contributes to the diagnosis of complicated biliary pathology in emergency department (ED) patients with normal laboratory values and no abnormal biliary POCUS findings aside from cholelithiasis. We performed a prospective, observational study of adult ED patients undergoing POCUS of the right upper quadrant (RUQ) and serum laboratory studies for suspected biliary pathology. The primary outcome was complicated biliary pathology occurring in the setting of normal laboratory values and a POCUS demonstrating the absence of gallbladder wall thickening (GWT), pericholecystic fluid (PCF) and sonographic Murphy's sign (SMS). The association between CBD dilation and complicated biliary pathology was assessed using logistic regression to control for other factors, including laboratory findings, cholelithiasis and other sonographic abnormalities. A total of 158 patients were included in the study. 76 (48.1%) received non-biliary diagnoses and 82 (51.9%) were diagnosed with biliary pathology. Complicated biliary pathology was diagnosed in 39 patients. Sensitivity of CBD dilation for complicated biliary pathology was 23.7% and specificity was 77.9%. Of patients diagnosed with biliary pathology, none had isolated CBD dilatation. In the absence of abnormal laboratory values and GWT, PCF or SMS on POCUS, obtaining a CBD measurement is unlikely to contribute to the evaluation of this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

PubMed

Miao, Yi-Feng; Wu, Hui; Yang, Shao-Feng; Dai, Jiong; Qiu, Yong-Ming; Tao, Zhen-Yi; Zhang, Xiao-Hua

2015-01-01

Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

Spontaneously removed biliary stent drainage versus T-tube drainage after laparoscopic common bile duct exploration.

PubMed

Xu, Yakun; Dong, Chengyong; Ma, Kexin; Long, Fei; Jiang, Keqiu; Shao, Ping; Liang, Rui; Wang, Liming

2016-09-01

Several studies have shown the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) as a minimally invasive treatment options for choledocholithiasis. Use of T-tube or biliary stent drainage tube placement after laparoscopic choledochotomy for common bile duct (CBD) stones is still under debate. This study tried to confirm the safety of spontaneously removable biliary stent in the distal CBD after LCBDE to allow choledochus primary closure. A total of 47 patients with choledocholithiasis underwent LCBDE with primary closure and internal drainage using a spontaneously removable biliary stent drainage tube (stent group, N = 22) or T-tube (T-tube group, N = 25). Operative parameters and outcomes are compared. Surgical time, intraoperative blood loss, length of hospital stay, drainage tube removal time, postoperative intestinal function recovery, and cost of treatment were all significantly lower in the stent group as compared to that in the T-tube group (P < 0.05 for all). Otherwise, Bile leakage between the two groups had no significant difference (P > 0.05). The biliary stent drainage tube was excreted spontaneously 4 to 14 days after surgery with the exception of one case, where endoscopic removal of biliary tube was required due to failure of its spontaneous discharge. LCBDE with primary closure and use of spontaneously removable biliary stent drainage showed advantage over the use of traditional T-tube drainage in patients with choledocholithiasis.

Detection of anti-liver cytosol antibody type 1 (anti-LC1) by immunodiffusion, counterimmunoelectrophoresis and immunoblotting: comparison of different techniques.

PubMed

Muratori, L; Cataleta, M; Muratori, P; Manotti, P; Lenzi, M; Cassani, F; Bianchi, F B

1995-12-01

Liver cytosol specific antibody type 1 (anti-LC1) was first described in a proportion of patients with liver/kidney microsomal antibody type 1 (anti-LKM1)-positive autoimmune hepatitis (AIH) and is routinely evaluated by immunodiffusion (ID). Using human liver cytosol as the source of antigen, we have used ID, counterimmunoelectrophoresis (CIE) and immunoblotting (IB), to test sera from 167 patients with documented chronic liver diseases of different etiology. 15 patients had antinuclear antibody (ANA) and/or smooth muscle antibody (SMA)-positive AIH, 13 had anti-LKM1-positive AIH, four had ANA/SMA/anti-LKM1-negative AIH, 76 had anti-LKM1-positive hepatitis C (recently renamed unclassified chronic hepatitis-UCH), 40 had chronic hepatitis C, 15 had chronic hepatitis B, and 4 had chronic hepatitis D. A precipitin line of identity with an anti-LC1 reference serum was detected both by ID and CIE in 16 patients: six with anti-LKM1-positive 'definite' AIH, four with ANA/SMA/anti-LKM1-negative 'definite' AIH, and six with anti-LKM1-positive UCH. By IB, 14 out of the 16 anti-LC1-positive sera (87.5%) reacted with a 58 kDa human liver cytosolic polypeptide, whereas three out of 16 (19%) recognised an additional 60 kDa band. Compared to ID, CIE is more economical in terms of both time and reagents and provides more clear-cut results. The 58 kDa reactivity by IB was detectable in nearly all CIE/ID anti-LC1-positive patients, was not found among CIE/ID anti-LC1-negative patients. In conclusion, CIE is the ideal screening test for the detection of anti-LC1, an autoantibody that can be regarded as an additional serological marker of AIH and is especially useful in ANA/SMA/anti-LKM1 negative cases.

Autoimmune liver disease in children.

PubMed

Mieli-Vergani, G; Vergani, D

2003-03-01

Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

Novel Immunotherapies for Autoimmune Hepatitis

PubMed Central

Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

2017-01-01

Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

A computer-aided detection (CAD) system with a 3D algorithm for small acute intracranial hemorrhage

NASA Astrophysics Data System (ADS)

Wang, Ximing; Fernandez, James; Deshpande, Ruchi; Lee, Joon K.; Chan, Tao; Liu, Brent

2012-02-01

Acute Intracranial hemorrhage (AIH) requires urgent diagnosis in the emergency setting to mitigate eventual sequelae. However, experienced radiologists may not always be available to make a timely diagnosis. This is especially true for small AIH, defined as lesion smaller than 10 mm in size. A computer-aided detection (CAD) system for the detection of small AIH would facilitate timely diagnosis. A previously developed 2D algorithm shows high false positive rates in the evaluation based on LAC/USC cases, due to the limitation of setting up correct coordinate system for the knowledge-based classification system. To achieve a higher sensitivity and specificity, a new 3D algorithm is developed. The algorithm utilizes a top-hat transformation and dynamic threshold map to detect small AIH lesions. Several key structures of brain are detected and are used to set up a 3D anatomical coordinate system. A rule-based classification of the lesion detected is applied based on the anatomical coordinate system. For convenient evaluation in clinical environment, the CAD module is integrated with a stand-alone system. The CAD is evaluated by small AIH cases and matched normal collected in LAC/USC. The result of 3D CAD and the previous 2D CAD has been compared.

Efficacy of fibrin-sealants in reducing biliary leakage following laparoscopic common bile duct exploration.

PubMed

Parra-Membrives, Pablo; Martínez-Baena, Darío; Lorente-Herce, José Manuel; Martín-Balbuena, Ramón

2018-05-21

In spite of the acquired experience with laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis management, there is still a risk of biliary leakage of 5% to 15% following choledochotomy closure. We evaluate the usefulness of fibrin-collagen sealants to reduce the incidence of biliary fistula after laparoscopic choledochorrhaphy. We report a retrospective analysis of 96 patients undergoing LCBDE from March 2009 to March 2017, whose closure of the bile duct was completed by antegrade stenting and choledochorraphy or by performing a primary suture. The study population was divided into two groups according to whether they received a collagen-fibrin sealant covering the choledochorrhaphy or not, analyzing the incidence of postoperative biliary fistula in each group. Thirty-nine patients (41%) received a fibrin-collagen sponge while the bile duct closure was not covered in the remaining 57 patients (59%). The incidence of biliary fistula was 7.7% (3 patients) in the first group and 14% (8 patients) in the second group (P=.338). In patients who underwent primary choledochorraphy, the fibrin-collagen sealant reduced the incidence of biliary leakage significantly (4.5% vs. 33%, P=.020), which was a protective factor with an odds ratio of 10.5. Fibrin-collagen sealants may decrease the incidence of biliary fistula in patients who have undergone primary bile duct closure following LCBDE. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells.

PubMed

Falkowski, Olga; An, Hee Jung; Ianus, I Andreea; Chiriboga, Luis; Yee, Herman; West, A Brian; Theise, Neil D

2003-09-01

In massive hepatic necrosis, hepatic stem cells constitute a canal of Hering derived, cytokeratin 19 (CK19) positive 'ductular reaction' (DR). Whether DRs in cirrhosis are activated stem cells (so called 'buds') or biliary metaplasia of cholestatic, injured hepatocytes is still debated. We investigate derivation of intraseptal hepatocytes (ISHs) from DRs and from the biliary tree in cirrhosis. Explants of hepatitis B and C, alcohol, primary biliary cirrhosis and primary sclerosing cholangitis-related cirrhosis were examined. ISHs were quantified and their associations with DRs and cholestasis recorded. 3D-reconstruction of ISHs and nearby bile ducts was performed in blocks from hepatitis C and primary sclerosing cholangitis cirrhosis. Seven hundred seventy five/830 (94%) ISHs were associated with CK19 positive DRs. ISHs without ductular reactions were more likely to show cholestatic features (P<0.0001). In 3D, ISHs were seen to bud directly from the biliary tree. In summary: ISHs: (1) are usually associated with stem cell-like DRs; (2) are rarely cholestatic, leaving the associated DRs unexplained; and (3) are linked to the biliary tree in 3D. Dynamic proliferation rates in hepatitis C over time suggest that hepatocyte replication diminishes in late stages, with an associated activation of the biliary stem cell compartment. We therefore suggest that the biliary tree, from at least its smaller branches up to the canals of Hering, are composed of or at least harbor facultative hepatic stem cells, and that ISH largely represent 'buds' of newly formed hepatocytes.

Biliary reconstruction in liver transplant patients with primary sclerosing cholangitis, duct-to-duct or Roux-en-Y?

PubMed

Shamsaeefar, Alireza; Shafiee, Mohammad; Nikeghbalian, Saman; Kazemi, Kourosh; Mansorian, Mohsenreza; Motazedian, Nasrin; Afshinnia, Farsad; Geramizadeh, Bita; Malekhosseini, Seyed Ali

2017-06-01

Roux-en-Y choledochojejunostomy and duct-to-duct (D-D) anastomosis are biliary reconstruction methods for liver transplantation. However, there is a controversy over which method produces better results. We have compared the outcome of D-D anastomosis vs. Roux-en-Y hepaticojejunostomy in patients with primary sclerosing cholangitis who had undergone liver transplant in Shiraz Organ Transplant Center. The medical records of 405 patients with primary sclerosing cholangitis (PSC) who had undergone liver transplant from 1996 to 2015 were reviewed. Patients were divided into two groups: Roux-en-Y group and D-D group. Morbidity, disease recurrence, and graft and patient survival rates were compared between the two groups. Total of 143 patients underwent a D-D biliary reconstruction, and 260 patients had a Roux-en-Y loop. Biliary complication involved 4.2% of patients from the D-D group, and 3.9% from the Roux-en-Y group (P=. 863). Actuarial 1-, 3-, and 5-year patient survival for D-D and Roux-en-Y group was 92%, 85%, and 74%; and 87%, 83%, and 79%, respectively (P=.384). The corresponding 1-, 3-, and 5-year probability of biliary complication was 97%, 95%, and 92%; and 98%, 97%, and 94%, respectively (P=.61). Duct-to-duct biliary reconstruction in liver transplantation for selected patients with PSC is a good alternative instead of Roux-en-Y biliary reconstruction. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC)

PubMed Central

Mattner, Jochen

2016-01-01

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host. Consistent with the close association of PSC and inflammatory bowel disease (IBD), the polyclonal hyper IgM response in PBC and (auto-)antibodies which cross-react to microbial antigens in both diseases, an expansion of individual microbes leads to shifts in the composition of the intestinal or biliary microbiota and a subsequent altered integrity of epithelial layers, promoting microbial translocation. These changes have been implicated in the pathogenesis of both devastating disorders. Thus, we will discuss here these recent findings in the context of novel and alternative therapeutic options. PMID:27834858

Identifying opportunities to improve management of autoimmune hepatitis: evaluation of drug adherence and psychosocial factors.

PubMed

Sockalingam, Sanjeev; Blank, Diana; Abdelhamid, Nour; Abbey, Susan E; Hirschfield, Gideon M

2012-12-01

Recognizing the importance of adherence to therapy in autoimmune hepatitis (AIH) is critical for patient care and avoidance of unnecessary intervention. The influence of psychosocial factors on treatment adherence needs better understanding and prominence. We sought to determine the association between anxiety, depressive symptoms, and avoidant relationship style on self-reported immunosuppressant medication adherence and treatment response in patients with AIH. Fifty two patients with AIH were assessed using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Experiences in Close Relationship Scale (ECR) and a visual analogue scale to measure self-reported adherence. Laboratory markers of adherence and immunosuppressant treatment response were recorded. Chi-square Fisher's exact or Wilcox rank sum tests were used for comparison between groups. Treatment responders compared to non-responders were older (p=0.035), had normal or mild score ranges for anxiety and depression (p=0.025) and were significantly more likely to report >80% treatment adherence (p=0.007). Non-responders had higher anxiety symptoms (p=0.025), and significantly higher ECR-avoidance scores (p=0.023), suggestive of a tendency towards a more avoidant relationship style. We formally document that patients with AIH who have higher depressive and anxiety symptoms and avoidant relationship styles are more likely to be non-adherent to AIH therapy. We reiterate the need for early recognition and treatment of anxiety and depression in patients with AIH, stress the need for treatment adherence and highlight the need for formal evaluation of these factors in trials of therapy targeting apparent treatment non-responders. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens.

PubMed

Lapierre, Pascal; Djilali-Saiah, Idriss; Vitozzi, Susana; Alvarez, Fernando

2004-04-01

Autoimmune hepatitis (AIH) is characterized by an immune-mediated injury of the hepatic parenchyma of unknown pathogenesis. Type 2 AIH is identified by the presence of anti-liver-kidney microsomes type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) autoantibodies. The current study shows that a murine model of AIH can be generated by DNA immunization against type 2 AIH self-antigens (P450 2D6 and formiminotransferase-cyclodeaminase). A pCMV plasmid containing the N-terminal region of mouse CTLA-4 and the antigenic region of human CYP2D6 (672-1,377 bp) and human formiminotransferase cyclodeaminase (FTCD; 1,232-1,668 bp) was used for DNA immunization of C57BL/6 female mice. Immunized mice showed elevated levels of alanine aminotransferase (ALT), with peaks at 4 and 7 months postinjection. Periportal, portal, and intralobular liver inflammatory infiltrates were observed at histology. Mainly CD4+ lymphocytes, but also CD8+ and B lymphocytes, were found in the liver. Cytotoxic-specific T cells were found in both the liver and spleen of these animals. Mice developed anti-LKM1 and anti-LC1 antibodies of immunoglobulin G2 (IgG2) subclass, against specific mouse autoantigens. The ALT levels correlated with both the presence of anti-LKM1/anti-LC1 antibodies and the presence of liver necroinflammation. In conclusion, in mice, DNA immunization against human autoantigens breaks tolerance and induces an autoimmune liver disease. Molecular mimicry between foreign and self-antigens explains the liver injury. This model of AIH resembles human type 2 AIH and will be helpful for the study of its pathogenesis.

Population-based prevalence, incidence, and disease burden of autoimmune hepatitis in South Korea

PubMed Central

Ki, Moran; Kim, Kyung-Ah; Jang, Eun Sun; Jeong, Sook-Hyang

2017-01-01

Background and aim Little is known about population-based epidemiology and disease burden of autoimmune hepatitis (AIH). The aim of this study was to investigate the prevalence, incidence, comorbidity and direct medical cost of AIH in South Korea. Methods The data was from the nationwide, population-based National Health Insurance Service claims database and the Rare Intractable Disease registration program. Age and gender-specific prevalence rates were calculated, and data on comorbidity, diagnostic tests, prescribed drugs, and medical costs were retrieved for patients registered under the disease code K75.4 (AIH) from 2009 to 2013. Results A total of 4,085 patients with AIH were identified between 2009 and 2013 with a female-to-male ratio of 6.4. The age-adjusted prevalence rate was 4.82/100,000 persons and gender adjusted prevalence rates were 8.35 in females and 1.30 in males. The age-adjusted calculated incidence rate was 1.07/100,000 persons (gender-adjusted 1.83 in females and 0.31 in males). Ascites, variceal bleeding, and hepatocellular carcinoma were found in 1.4%, 1.3%, and 2.2% of the patients, respectively. Forty-six patients (1.1%) underwent liver transplantation during the study period. Case-fatality was 2.18%. Corticosteroid and azathioprine were prescribed in 44.1% and 38.0% of prevalent patients with AIH in 2013, respectively. The nationwide total direct medical cost was less than 4.0 million USD, and the average cost for each patient was 1,174 USD in 2013. Conclusion This is the first report on the nationwide epidemiology of AIH in Korea, and it showed a lower prevalence than that of Western countries with considerable disease burden. PMID:28771543

A prospective, randomized study of the patency period of the plastic antireflux biliary stent: an interim analysis.

PubMed

Leong, Quan Wai; Shen, Mira L; Au, Kim W; Luo, Derek; Lau, James Y; Wu, Justin C; Chan, Francis K; Sung, Joseph J

2016-02-01

There is as yet no ideal design of a plastic biliary stent with the longest patency period. To study the safety and effective patency period of a new plastic antireflux biliary stent in the clinical setting. We conducted a prospective, randomized trial to compare the patency of 2 similar plastic biliary stents, one of which has an antiduodenobiliary reflux property. The study was conducted at 2 separate tertiary centers in 2 countries. Patients with inoperable distal malignant biliary obstruction were recruited. One of the 2 types of plastic stents under study was randomly chosen and inserted in the common bile duct of the study subjects. The subjects were followed until the end of study or occlusion occurrence. Our primary endpoint was the time to stent occlusion in days, with stent-related adverse events and all-cause mortality the secondary endpoints. A total of 16 subjects were recruited for the study; 7 were allocated to group A (ordinary Tannenbaum stent) and 9 to group B (antireflux biliary stent). Five of 7 subjects (71%) in group B had stent occlusion within 8 days, and the primary end point was reached in all 7 subjects within 30 days, whereas the primary endpoint was not reached within 30 days in any of the subjects in group A. Our data showed a significantly shorter stent patency period in group B compared with group A (P < .003). Small sample size. Routine use of antireflux plastic biliary stents in the palliative management of malignant biliary obstructions cannot be recommended at present. (Clinical trial registration number: NCT01142921.). Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Primary biliary cirrhosis: an epidemiological study.

PubMed Central

Triger, D R

1980-01-01

A three-year study (1977-9) of primary biliary cirrhosis in the city of Sheffield disclosed 34 cases, a point prevalence of 54 per million population. Closer inspection showed an apparent clustering of cases, and the prevalence in relation to one water reservoir appeared to be more than ten times that of the other reservoirs. Nevertheless, analyses of the water showed no significant relevant differences between the reservoir serving areas with a high prevalence of cirrhosis and other reservoirs. Despite the inconclusive results of the water analyses, these findings do suggest that an environmental agent may be a cause of primary biliary cirrhosis and that further epidemiological studies may help to elucidate the cause. PMID:7427444

Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

PubMed Central

Béland, Kathie; Lapierre, Pascal; Alvarez, Fernando

2009-01-01

The pathogenesis of autoimmune hepatitis (AIH) is complex. However, it is believed that a susceptible individual, owing to his genetic background, sex and age, can develop the disease following exposure to an environmental trigger. Autoimmune hepatitis does not follow a Mendelian pattern of inheritance; hence no single causative genetic locus has been identified. However, several genes, inside and outside the HLA locus, have been linked to an increased susceptibility to AIH. Epidemiological evidence also suggests that the sex and age of the patient plays a role in AIH pathogenesis as the disease onset occurs mainly in the two first decades of life and a higher disease incidence is observed in females. No environmental trigger has been identified, but several have been proposed, mainly viruses and xenobiotics. This article aims at reviewing the current knowledge on susceptibility factors leading to AIH and putative triggers, emphasizing fundamental mechanisms responsible for the break of liver immunological tolerance. PMID:19266593

Chlorella viruses contain genes encoding a complete polyamine biosynthetic pathway

PubMed Central

Baumann, Sascha; Sander, Adrianne; Gurnon, James R.; Yanai-Balser, Giane; VanEtten, James L.; Piotrowski, Markus

2007-01-01

Two genes encoding the putative polyamine biosynthetic enzymes agmatine iminohydrolase (AIH) and N-carbamoylputrescine amidohydrolase (CPA) were cloned from the chloroviruses PBCV-1, NY-2A and MT325. They were expressed in Escherichia coli to form C-terminal (His)6-tagged proteins and the recombinant proteins were purified by Ni2+- binding affinity chromatography. The biochemical properties of the two enzymes are similar to AIH and CPA enzymes from Arabidopsis thaliana and Pseudomonas aeruginosa. Together with the previously known virus genes encoding ornithine/arginine decarboxlyase (ODC/ADC) and homospermidine synthase, the chloroviruses have genes that encode a complete set of functional enzymes that synthesize the rare polyamine homospermidine from arginine via agmatine, N-carbamoylputrescine and putrescine. The PBCV-1 aih and cpa genes are expressed early during virus infection together with the odc/adc gene, suggesting that biosynthesis of putrescine is important in early stages of viral replication. The aih and cpa genes are widespread in the chlorella viruses. PMID:17101165

13C-methacetin and 13C-galactose breath tests can assess restricted liver function even in early stages of primary biliary cirrhosis.

PubMed

Holtmeier, Julia; Leuschner, Maria; Schneider, Arne; Leuschner, Ulrich; Caspary, Wolfgang F; Braden, Barbara

2006-11-01

The 13C-methacetin breath test quantitatively evaluates cytochrome P450-dependent liver function. The 13C-galactose breath test non-invasively measures the galactose oxidation capacity of the liver. The aim of this study was to find out whether these breath tests are sensitive parameters also in non-cirrhotic patients with primary biliary cirrhosis. Nineteen patients with early-stage primary biliary cirrhosis (no cirrhotic alterations in the liver biopsy, Ludwig stage I-III) and 20 healthy controls underwent the 13C-methacetin and 13C-galactose breath tests. Patients with primary biliary cirrhosis metabolized less 13C-methacetin than controls (cumulative recovery within 30 min 7.5+/-2.4% versus 14.0+/-2.6%; p < 0.001). When a cut-off > 9.8% was used for the cumulative recovery after 30 min, the methacetin breath test reached 84.2% sensitivity and 95.0 specificity. In the 13C-galactose breath test, the percentage recovery at 60 min in patients was 3.1+/-1.3%/h, and 6.3+/-1.1%/h in controls (p < 0.001). Using a cut-off > 4.7%/h, the galactose breath test reached 89.5% sensitivity and 95.0 specificity. In non-cirrhotic, early-stage, primary biliary cirrhosis the 13C-methacetin breath test and the 13C-galactose breath test reliably indicate decreased liver function. The 13C-galactose breath test can also predict the histological score.

Current Status of Biliary Metal Stents

PubMed Central

Nam, Hyeong Seok; Kang, Dae Hwan

2016-01-01

Many advances have been achieved in biliary stenting over the past 30 years. Endoscopic stent placement has become the primary management therapy to relieve obstruction in patients with benign or malignant biliary tract diseases. Compared with plastic stents, a self-expandable metallic stent (SEMS) has been used for management in patients with malignant strictures because of a larger lumen and longer stent patency. Recently, SEMS has been used for various benign biliary strictures and leaks. In this article, we briefly review the characteristics of SEMS as well as complications of stent placement. We review the current guidelines for managing malignant and benign biliary obstructions. Recent developments in biliary stenting are also discussed. PMID:26911896

Cyclosporine induced biochemical remission in childhood autoimmune hepatitis.

PubMed

Franulović, Orjena Zaja; Rajacić, Nada; Lesar, Tatjana; Kuna, Andrea Tesija; Morić, Bernardica Valent

2012-09-01

The conventional treatment of autoimmune hepatitis (AIH) in children, which includes prednisone alone or in combination with azathioprine, induces remission in most cases but is often associated with poorly tolerated side effects. To avoid the adverse effects, Alvarez et al. introduced an alternative treatment regimen, using cyclosporine A (CyA) as primary immunosuppression. We carried out a retrospective study to evaluate the efficacy and tolerance of CyA treatment in children and adolescents with AIH treated in our center. During 2000-2010 period, nine children (6 female) aged 5-17.5 years, were diagnosed with AIH according to established international criteria. Following the suggested protocol, CyA was administered orally and when the transaminases tended to normalise, dose was adjusted to lover serum levels. Conversion to low dose of prednisone and azathioprine was started after 6 months, with gradual tapering and discontinuation of CyA. All nine patient had elevated transaminases and gammaglobulin levels, with proven histological changes typical for AIH in 8 patients that underwent liver biopsy (in one patient biopsy was contraindicated due to the prolonged prothrombin time). Serum ANA/SMA autoantibodies were positive in all but one patient, who had positive anti-LKM1. Complete or near complete and persistent normalisation of transaminase activity was observed in 8/9 patients within first 6 to 12 months. In one patient with partial response, an overlap syndrome was established. After ursodeoxycholic acid was added complete remission was observed. All patients had excellent clinical course and histological improvement. During the long-term follow-up (1.5-9 yrs; median 4.5 yrs), biochemical relapse occured in one patient after discontinuation of maintenance corticosteroid dose. Despite registered improvement, none of the patients fulfilled the criteria for therapy discontinuation, so all of them are still receiving maintenance doses of prednisone or azathioprine. The applied protocol allowed for the control of the liver inflammatory disease in all of our patients and protected them from the side effects related to steroid treatment. Side effects of CyA were minimal and were well tolerated.

Expression and cytokine regulation of immune recognition elements by normal human biliary epithelial and established liver cell lines in vitro.

PubMed

Cruickshank, S M; Southgate, J; Selby, P J; Trejdosiewicz, L K

1998-10-01

Biliary epithelial cells are targets of immune-mediated attack in conditions such as primary biliary cirrhosis and allograft rejection. This has been attributed to the ability of biliary epithelial cells to express ligands for T cell receptors. We aimed to investigate the expression of immune recognition elements and the effects of pro-inflammatory and anti-inflammatory cytokines on cell surface phenotypes of normal human biliary epithelial cells and established human liver-derived (PLC/PRF/5, HepG2, Hep3B and CC-SW) lines. Cells were cultured in the presence or absence of cytokines for 72 h, and expression of cell surface molecules was assessed by flow cytometry and immunofluorescence. All cell lines expressed MHC class I, ICAM-1 (CD54), LFA-3 (CD58) and EGF receptor, and all but Hep3B expressed Fas/Apo-1 (CD95). Unlike hepatocyte-derived cell lines, biliary epithelial cells and CC-SW expressed CD40 and CD44. As expected, IFNgamma and TNFalpha upregulated expression of ICAM-1, MHC class I and MHC class II, particularly in biliary epithelial cells. TGFbeta downregulated these molecules and downregulated CD95 on biliary epithelial cells, but upregulated LFA-3. The Th2 cytokines had little effect, although IL-4 upregulated CD95 expression on biliary epithelial cells. IFNgamma upregulated CD40 expression on biliary epithelial cells, CC-SW and HepG2. These findings imply that biliary epithelial cells may be capable of interacting with activated T lymphocytes via CD40 and LFA-3, which are thought to be important T cell accessory ligands for T cell activation in a B7-independent manner. Sensitivity to pro-inflammatory cytokines and expression of CD95 may explain why biliary epithelial cells are primary targets for autoimmune attack.

Future developments in biliary stenting

PubMed Central

Hair, Clark D; Sejpal, Divyesh V

2013-01-01

Biliary stenting has evolved dramatically over the past 30 years. Advancements in stent design have led to prolonged patency and improved efficacy. However, biliary stenting is still affected by occlusion, migration, anatomical difficulties, and the need for repeat procedures. Multiple novel plastic biliary stent designs have recently been introduced with the primary goals of reduced migration and improved ease of placement. Self-expandable bioabsorbable stents are currently being investigated in animal models. Although not US Food and Drug Administration approved for benign disease, fully covered self-expandable metal stents are increasingly being used in a variety of benign biliary conditions. In malignant disease, developments are being made to improve ease of placement and stent patency for both hilar and distal biliary strictures. The purpose of this review is to describe recent developments and future directions of biliary stenting. PMID:23837001

Toll-Like Receptors in Secondary Obstructive Cholangiopathy

PubMed Central

Miranda-Díaz, A. G.; Alonso-Martínez, H.; Hernández-Ojeda, J.; Arias-Carvajal, O.; Rodríguez-Carrizalez, A. D.; Román-Pintos, L. M.

2011-01-01

Secondary obstructive cholangiopathy is characterized by intra- or extrahepatic bile tract obstruction. Liver inflammation and structural alterations develop due to progressive bile stagnation. Most frequent etiologies are biliary atresia in children, and hepatolithiasis, postcholecystectomy bile duct injury, and biliary primary cirrhosis in adults, which causes chronic biliary cholangitis. Bile ectasia predisposes to multiple pathogens: viral infections in biliary atresia; Gram-positive and/or Gram-negative bacteria cholangitis found in hepatolithiasis and postcholecystectomy bile duct injury. Transmembrane toll-like receptors (TLRs) are activated by virus, bacteria, fungi, and parasite stimuli. Even though TLR-2 and TLR-4 are the most studied receptors related to liver infectious diseases, other TLRs play an important role in response to microorganism damage. Acquired immune response is not vertically transmitted and reflects the infectious diseases history of individuals; in contrast, innate immunity is based on antigen recognition by specific receptors designated as pattern recognition receptors and is transmitted vertically through the germ cells. Understanding the mechanisms for bile duct inflammation is essential for the future development of therapeutic alternatives in order to avoid immune-mediated destruction on secondary obstructive cholangiopathy. The role of TLRs in biliary atresia, hepatolithiasis, bile duct injury, and primary biliary cirrhosis is described in this paper. PMID:22114589

Primary closure versus T-tube drainage in laparoscopic common bile duct exploration: a meta-analysis of randomized clinical trials.

PubMed

Wu, Xiangsong; Yang, Yong; Dong, Ping; Gu, Jun; Lu, Jianhua; Li, Maolan; Mu, Jiasheng; Wu, Wenguang; Yang, Jiahua; Zhang, Lin; Ding, Qichen; Liu, Yingbin

2012-08-01

To compare the safety and effectiveness of primary closure with those of T-tube drainage in laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis. A comprehensive search was performed in the PubMed, EmBase, and Cochrane Library databases. Only randomized controlled trials comparing primary closure with T-tube drainage in LCBDE were considered eligible for this meta-analysis. The analyzed outcome variables included postoperative mortality, overall morbidity, biliary complication rate, biliary leak rate, reoperation, operating time, postoperative hospital stay, time to abdominal drain removal, and retained stone. All calculations and statistical tests were performed using ReviewerManager 5.1.2 software. A total of 295 patients (148 patients with primary closure and 147 patients with T-tube drainage) from three trials were identified and analyzed. No deaths occurred in any of the trials. Primary closure showed significantly better results in terms of morbidity (risk ratio (RR), 0.51; 95% confidence interval (CI), 0.30 to 0.88), biliary complication without a combination of retained stone (RR, 0.44; 95% CI, 0.20 to 0.97), reoperation (RR, 0.16; 95% CI, 0.03 to 0.87), operating time (mean difference (MD), -20.72; 95% CI, -29.59 to -11.85), postoperative hospital stay (MD, -3.24; 95% CI, -3.96 to -2.52), and time to abdominal drainage removal (MD, -0.45; 95% CI, -0.86 to -0.04). Statistically significant differences were not found between the two methods in terms of biliary leak, biliary complication, and retained stones. The current meta-analysis indicates that primary closure of the common bile duct is safer and more effective than T-tube drainage for LCBDE. Therefore, we do not recommend routine performance of T-tube drainage in LCBDE.

5'- Adenosine monophosphate induced hypothermia reduces early stage myocardial ischemia/reperfusion injury in a mouse model.

PubMed

Tao, Zhenyin; Zhao, Zhaoyang; Lee, Cheng Chi

2011-08-15

Early intervention using hypothermia treatment has been shown to reduce early inflammation, apoptosis and infarct size in animal models of cardiac ischemia/reperfusion. We have shown that 5'-adenosine monophosphate (5'-AMP) can induce a reversible deep hypothermia in mammals. We hypothesize that 5'-AMP-induced hypothermia (AIH) may reduce ischemic/reperfusion damage following myocardial infarct. C57BL/6J male mice were subjected to myocardial ischemia by ligating the left anterior descending coronary artery (LAD) followed by reperfusion. Compared to euthermic controls, mice given AIH treatment exhibited significant inhibition of neutrophil infiltration and a reduction in matrix metallopeptidase 9 (MMP-9) expressions in the infarcted myocardium. A decrease in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei in the left ventricle myocardium were also observed. The overall infarct size of the heart was significantly smaller in AIH treated mice. Myocardial ischemia in mice given 5'-AMP without hypothermia had similar ischemia/reperfusion injuries as the euthermic control. Thus, the AIH cardio-protective effects were primarily hypothermia based.

Adenosine 5'-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats.

PubMed

Wang, Yunlong; Zhang, Aihua; Lu, Shulai; Pan, Xinting; Jia, Dongmei; Yu, Wenjuan; Jiang, Yanxia; Li, Xinde; Wang, Xuefeng; Zhang, Jidong; Hou, Lin; Sun, Yunbo

2014-11-01

Many studies have shown that LPS mainly activates four signal transduction pathways to induce inflammation, namely the p38, ERK1/2, JNK and IKK/NF-κB pathways. Studies have demonstrated that 5'-AMP-induced hypothermia (AIH) exhibits high anti-inflammatory capabilities. In this study, we explore that how AIH inhibits the inflammatory response. Wistar rats were divided into five groups: a control group, an LPS group, a 5'-AMP pre-treatment group, a 5'-AMP post-treatment group and a 5'-AMP group. For each group, plasma and lung were collected from the rats at 6h and 12h after LPS injection. ELISA assays were used to detect plasma levels of CD14, CRP and MCP-1. Inflammatory pathway activation and TLR4 expression were assayed separately by Western blot analysis and immunohistochemistry. Our results showed that rats treated with AIH either before or after an LPS-challenge had a significant decrease in plasma levels of CD14, CRP and TLR4 compared with rats that received LPS only. Western blot analysis showed that AIH inhibited the activation of extracellular signal-regulated kinases (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) and NF-κB in inflammatory rats. Our study concluded that AIH attenuated LPS-induced inflammation mainly by inhibiting activation on the ERK1/2, p38, JNK and NF-κB signaling pathways. Copyright © 2014 Elsevier B.V. All rights reserved.

Cytochrome P4502D6(193-212): a new immunodominant epitope and target of virus/self cross-reactivity in liver kidney microsomal autoantibody type 1-positive liver disease.

PubMed

Kerkar, Nanda; Choudhuri, Kaushik; Ma, Yun; Mahmoud, Ayman; Bogdanos, Dimitrios P; Muratori, Luigi; Bianchi, Francesco; Williams, Roger; Mieli-Vergani, Giorgina; Vergani, Diego

2003-02-01

Cytochrome P4502D6 (CYP2D6), target of liver kidney microsomal autoantibody type 1 (LKM1), characterizes autoimmune hepatitis type 2 (AIH2) but is also found in patients with chronic hepatitis C virus (HCV) infection. To provide a complete linear epitope B cell map of CYP2D6, we tested peptides spanning the entire sequence of CYP2D6. In addition to confirming previously described antigenic sites, we identified four new epitopes (193-212, 238-257, 268-287, and 478-497). CYP2D6(193-212) is immunodominant and was the target of 12 of 13 (93%) patients with AIH2 and 5 of 10 (50%) HCV/LKM1-positive patients. Because LKM1 is present in both AIH2 and a viral infection, we tested whether Abs to CYP2D6(193-212) arise through cross-reactive immunity between virus and self. We identified a hexameric sequence "RLLDLA" sharing 5 of 6 aa with "RLLDLS" of HCV(2985-2990) and all 6 aa with CMV(130-135). Of 17 CYP2D6(193-212)-reactive sera, 11 (7 AIH and 4 HCV) reacted by ELISA with the HCV homologue, 8 (5 AIH and 3 HCV) with the CMV homologue, and 8 (5 AIH and 3 HCV) showed double reactivity. Autoantibody binding to CYP2D6(193-212) was inhibited by preincubation with HCV(2977-2996) or CMV(121-140). Recombinant HCV-nonstructural protein 5 and CMV-UL98 proteins also inhibited Ab binding to CYP2D6(193-212). Affinity-purified CYP2D6(193-212)-specific Ab inhibited the metabolic activity of CYP2D6. The demonstrated similarity and cross-reactivity between CYP2D6(193-212) and two unrelated viruses suggests that multiple exposure to viruses mimicking self may represent an important pathway to the development of autoimmunity.

De novo autoimmune hepatitis after liver transplantation.

PubMed

Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

2007-10-01

The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin inhibitors supports the view held by most specialists in autoimmune hepatitis that these drugs, even though effective in acute disease, are not helpful in the long-term management of autoimmune liver diseases.

Establishment of a novel radioligand assay using eukaryotically expressed cytochrome P4502D6 for the measurement of liver kidney microsomal type 1 antibody in patients with autoimmune hepatitis and hepatitis C virus infection.

PubMed

Ma, Y; Gregorio, G; Gäken, J; Muratori, L; Bianchi, F B; Mieli-Vergani, G; Vergani, D

1997-06-01

Liver kidney microsomal type 1 antibody (LKM1) is the diagnostic marker of autoimmune hepatitis (AIH) type 2 and is also found in patients with hepatitis C virus (HCV) infection. Cytochrome P4502D6 (CYP2D6) is the documented target antigen of LKM1 in AIH, but not in HCV infection. To compare the reactivity in the two conditions, we established a radioligand assay using eukaryotically expressed CYP2D6 as target. A 1.2-kb human CYP2D6 cDNA was isolated from a human liver cDNA library and subcloned into an in vitro transcription vector pSP64 Poly(A). Recombinant CYP2D6 was then produced by in vitro transcription/translation, metabolically labelled with 35S methionine and used in the immunoprecipitation assay. Antibodies that bound radiolabelled CYP2D6 were immunoprecipitated and their levels assessed as cpm. Sera from 50 LKM1-positive patients (26 with AIH; 24 with HCV infection), 128 LKM1-negative patients and 57 normal controls were tested. Reactivity to 35S labelled CYP2D6 was observed in all LKM1-positive sera from patients with AIH and HCV infection, but in none of the controls. The cpm in both conditions were significantly higher than in normal controls (p<0.0001), and were correlated with the immunofluorescence titres of LKM1 (r 0.87, p<0.001 and r=0.64, p<0.001 for AIH and HCV infection, respectively). Reactivity to 35S labelled CYP2D6 was inhibited by addition of an excess of eukaryotically expressed CYP2D6. CYP2D6 is a major target antigen of both AIH and HCV infection. The novel radioligand assay is highly sensitive and specific.

The induction of autoimmune hepatitis in the human leucocyte antigen‐DR4 non‐obese diabetic mice autoimmune hepatitis mouse model

PubMed Central

Yuksel, M.; Xiao, X.; Tai, N.; Vijay, G. M.; Gülden, E.; Beland, K.; Lapierre, P.; Alvarez, F.; Hu, Z.; Colle, I.; Ma, Y.

2016-01-01

Summary Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti‐smooth muscle actin and/or anti‐nuclear, anti‐liver kidney microsomal type 1 (anti‐LKM1) and anti‐liver cytosol type 1 (anti‐LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)‐DR3, ‐DR7 and ‐DR13. HLA‐DR4 has the second strongest association with adult AIH, after HLA‐DR3. We investigated the role of HLA‐DR4 in the development of AIH by immunization of HLA‐DR4 (DR4) transgenic non‐obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti‐LKM1/anti‐LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs), which had decreased programmed death (PD)‐1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild‐type (WT) NOD mice. Our results demonstrate that HLA‐DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD‐1 expression may result in spontaneous activation of key immune cell subsets, such as antigen‐presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage. PMID:27414259

The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

PubMed

Yuksel, M; Xiao, X; Tai, N; Vijay, G M; Gülden, E; Beland, K; Lapierre, P; Alvarez, F; Hu, Z; Colle, I; Ma, Y; Wen, L

2016-11-01

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (T regs ), which had decreased programmed death (PD)-1 expression. Splenic T regs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8 + T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of T regs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8 + T effectors, facilitating the induction of AIH and persistent liver damage. © 2016 British Society for Immunology.

Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis.

PubMed

Nishioka, M; Morshed, S A; Parveen, S; Kono, K; Matsuoka, H; Manns, M P

1997-12-01

Auto-antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched-chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti-LKM1 was also measured by indirect immunofluorescent test. Anti-P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH-C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non-B non-C (NBNC) and AIH were seronegative for anti-LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH-B. Anti-BCKD-E2 but not anti-PDH-E2 was found in four patients (2.5%), one with AIH, two with CH-C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti-SLA and anti-BCKD-E2. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 are uncommon in adult CH-C, CH-B, CH-NBNC and AIH patients in Japan. Some of these patients positive for auto-antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto-antibodies.

Evaluation of transient elastography in assessing liver fibrosis in patients with autoimmune hepatitis.

PubMed

Xu, Qinyu; Sheng, Li; Bao, Han; Chen, Xiaoyu; Guo, Canjie; Li, Hai; Ma, Xiong; Qiu, Dekai; Hua, Jing

2017-03-01

Transient elastography (TE) can reliably stage liver fibrosis via liver stiffness measurement (LSM) in chronic liver disease. However, the accuracy of TE for assessment of liver fibrosis in patients with autoimmune hepatitis (AIH) is still limited. We evaluate TE in staging liver fibrosis in AIH patients and compare with other noninvasive diagnostic tools. A total of 100 patients with biopsy-proven AIH were included. The correlation between LSM and fibrosis stage was analyzed using Spearman correlation test. The optimal cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. The diagnostic accuracy of LSM for severe fibrosis was compared with those of serum biochemical scores. Median LSM in AIH patients was higher than that of healthy controls (11.2 ± 8.2 kPa vs 4.3 ± 1.4 kPa, P < 0.01). LSM had significant correlation with fibrosis (r = 0.752, P < 0.01) and increased progressively with increasing fibrosis stages in AIH patients. AUROC values of LSM for stages F ≥ 2, F ≥ 3, and F4 were 0.878 (95%CI: 0.789-0.967), 0.883 (0.820-0.946), and 0.914 (0.852-0.976), respectively. The optimal cut-off values of LSM for fibrosis stages F ≥ 2, F ≥ 3, and F4 were 6.45, 8.75, and 12.50 kPa, respectively. LSM was superior to APRI score and FIB-4 score in detecting severe fibrosis (F ≥ 3). Serum ALT levels had minor effect on LSM values. Transient elastography is an accurate and reliable noninvasive tool in assessing liver fibrosis in AIH. Hepatic inflammatory activity had no significant effect on LSM determination. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

TLR2/4 ligand-amplified liver inflammation promotes initiation of autoimmune hepatitis due to sustained IL-6/IL-12/IL-4/IL-25 expression.

PubMed

Chi, Gang; Feng, Xin-Xia; Ru, Ying-Xia; Xiong, Ting; Gao, Yuan; Wang, Han; Luo, Zhen-Long; Mo, Ran; Guo, Fang; He, Yong-Pei; Zhang, Gui-Mei; Tian, De-An; Feng, Zuo-Hua

2018-05-21

Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl 4 ) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4. The amplified inflammation resulted in the increase of multiple cytokines and chemokines in the liver. Among them, the sustained increase of IL-6/IL-12 resulted in the activation of STAT3 and STAT4 in hepatic CD4 + CD25 + Treg cells, thus suppressing Foxp3 gene expression to reduce the suppressive function of Treg cells in the liver, but not those in the spleen. The increase of IL-12 and the impairment of Treg function promoted Th1 response in presence of self-mimicking antigen (human CYP2D6). Intriguingly, the amplified inflammation resulted in the increase of IL-4 and IL-25 in the liver. The moderate increase of IL-4 was sufficient for cooperating with IL-25 to initiate Th2 response, but inefficient in suppressing Th1 response, favoring the initiation of autoimmune response. Consequently, either adenovirus/CYP2D6 or CCl 4 /CYP2D6 could induce the autoimmune response and AIH in the mice, leading to hepatic fibrosis. The findings in this study suggest that the amplified non-AIH inflammation in the liver could be a driving force for the initiation of autoimmune response and AIH. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey.

PubMed

Joshita, Satoru; Yoshizawa, Kaname; Umemura, Takeji; Ohira, Hiromasa; Takahashi, Atsushi; Harada, Kenichi; Hiep, Nguyen Canh; Tsuneyama, Koichi; Kage, Masayoshi; Nakano, Masayuki; Kang, Jong-Hon; Koike, Kazuhiko; Zeniya, Mikio; Yasunaka, Tetsuya; Takaki, Akinobu; Torimura, Takuji; Abe, Masanori; Yokosuka, Osamu; Tanaka, Atsushi; Takikawa, Hajime

2018-02-23

Autoimmune hepatitis (AIH) is characterized by progressive inflammation and necrosis of hepatocytes and eventually leads to a variety of phenotypes, including acute liver dysfunction, chronic progressive liver disease, and fulminant hepatic failure. Although the precise mechanisms of AIH are unknown, environmental factors may trigger disease onset in genetically predisposed individuals. Patients with the recently established entity of AIH with acute presentation often display atypical clinical features that mimic those of acute hepatitis forms even though AIH is categorized as a chronic liver disease. The aim of this study was to identify the precise clinical features of AIH with acute presentation. Eighty-six AIH patients with acute presentation were retrospectively enrolled from facilities across Japan and analyzed for clinical features, histopathological findings, and disease outcomes. Seventy-five patients were female and 11 were male. Patient age ranged from adolescent to over 80 years old, with a median age of 55 years. Median alanine transaminase (ALT) was 776 U/L and median immunoglobulin G (IgG) was 1671 mg/dL. There were no significant differences between genders in terms of ALT (P = 0.27) or IgG (P = 0.51). The number of patients without and with histopathological fibrosis was 29 and 57, respectively. The patients with fibrosis were significantly older than those without (P = 0.015), but no other differences in clinical or histopathological findings were observed. Moreover, antinuclear antibody (ANA)-positive (defined as × 40, N = 63) and -negative (N = 23) patients showed no significant differences in clinical or histopathological findings or disease outcomes. Twenty-five patients experienced disease relapse and two patients died during the study period. ALP ≥ 500 U/L [odds ratio (OR) 3.20; 95% confidence interval (CI) 1.12-9.10; P < 0.030] and GGT ≥ 200 U/L (OR 2.98; 95% CI 1.01-8.77; P = 0.047) were identified as independent risk factors of disease relapse. AIH with acute presentation is a newly recognized disease entity for which diagnostic hallmarks, such as ALT, fibrosis, and ANA, are needed. Further investigation is also required on the mechanisms of this disorder. Clinicians should be mindful of disease relapse during patient care.

Adenosine-dependent phrenic motor facilitation is inflammation resistant

PubMed Central

Agosto-Marlin, Ibis M.; Nichols, Nicole L.

2016-01-01

Phrenic motor facilitation (pMF), a form of respiratory plasticity, can be elicited by acute intermittent hypoxia (i.e., phrenic long-term facilitation, pLTF) or direct application of drugs to the cervical spinal cord. Moderate acute intermittent hypoxia (mAIH; 3 × 5-min episodes of 35–50 mmHg arterial Po2, 5-min normoxic intervals) induces pLTF by a serotonin-dependent mechanism; mAIH-induced pLTF is abolished by mild systemic inflammation induced by a low dose of lipopolysaccharide (LPS; 100 μg/kg ip). In contrast, severe acute intermittent hypoxia (sAIH; 3 × 5-min episodes of 25–30 mmHg arterial Po2, 5-min normoxic intervals) elicits pLTF by a distinct, adenosine-dependent mechanism. Since it is not known if systemic LPS blocks the mechanism giving rise to sAIH-induced pLTF, we tested the hypothesis that sAIH-induced pLTF and adenosine 2A (A2A) receptor-induced pMF are insensitive to mild systemic inflammation elicited by the same low dose of LPS. In agreement with our hypothesis, neither sAIH-induced pLTF nor cervical intrathecal A2A receptor agonist (CGS-21680; 200 μM, 10 μl × 3)-induced pMF were affected 24 h post-LPS. Pretreatment with intrathecal A2A receptor antagonist injections (MSX-3; 10 μM, 12 μl) blocked sAIH-induced pLTF 24 h post LPS, confirming that pLTF was adenosine dependent. Our results give insights concerning the differential impact of systemic inflammation and the functional significance of multiple cascades capable of giving rise to phrenic motor plasticity. The relative resistance of adenosine-dependent pMF to inflammation suggests that it provides a “backup” system in animals lacking serotonin-dependent pMF due to ongoing inflammation associated with systemic infections and/or neural injury. NEW & NOTEWORTHY This study gives novel insights concerning how a mild systemic inflammation impacts phrenic motor plasticity (pMF), particularly adenosine-dependent pMF. We suggest that since this adenosine-dependent pathway is insensitive to systemic inflammation, it represents an alternative or “backup” mechanism of pMF when other mechanisms are suppressed. PMID:27927784

En Bloc Hilar Dissection of the Right Hepatic Artery in Continuity with the Bile Duct: a Technique to Reduce Biliary Complications After Adult Living-Donor Liver Transplantation.

PubMed

Abu-Gazala, Samir; Olthoff, Kim M; Goldberg, David S; Shaked, Abraham; Abt, Peter L

2016-04-01

Techniques that preserve the right hepatic artery and the common bile duct in continuity during the dissection may be associated with lower rates of biliary complications in living-donor liver transplants. This study sought to determine whether en bloc hilar dissections were associated with fewer biliary complications in living-donor liver transplants. This was a retrospective review of 41 adult LDLTs performed in a single, liver transplant center between February 2007 and September 2014. The primary outcome of interest was the occurrence of at least one of the following biliary complications: anastomotic leak, stricture, or biloma. The primary predictor of interest was the hilar dissection technique: conventional hilar dissection vs. en bloc hilar dissection. A total of 41 LDLTs were identified, 24 had a conventional, and 17 an en bloc hilar biliary dissection. The occurrence of any biliary complication was significantly more common in the conventional hilar dissection group compared to the en bloc hilar dissection group (66.7 vs. 35.3%, respectively, p = 0.047). In particularly, anastomotic strictures were significantly more common in the conventional hilar dissection group compared to the en bloc hilar dissection group (54.2 vs. 23.5%., respectively, p = 0.049). En bloc hilar dissection technique may decrease biliary complication rates in living donor liver transplants.

Percutaneous biliary drainage using open cell stents for malignant biliary hilar obstruction.

PubMed

Ahn, Sun Jun; Bae, Jae Ik; Han, Tae Sun; Won, Je Hwan; Kim, Ji Dae; Kwack, Kyu-Sung; Lee, Jae Hee; Kim, Young Chul

2012-01-01

To evaluate the feasibility, safety and the effectiveness of the complex assembly of open cell nitinol stents for biliary hilar malignancy. During the 10 month period between January and October 2007, 26 consecutive patients with malignant biliary hilar obstruction underwent percutaneous insertion of open cell design nitinol stents. Four types of stent placement methods were used according to the patients' ductal anatomy of the hilum. We evaluated the technical feasibility of stent placement, complications, patient survival, and the duration of stent patency. Bilobar biliary stent placement was conducted in 26 patients with malignant biliary obstruction-T (n = 9), Y (n = 7), crisscross (n = 6) and multiple intersecting types (n = 4). Primary technical success was obtained in 24 of 26 (93%) patients. The crushing of the 1st stent during insertion of the 2nd stent occurred in two cases. Major complications occurred in 2 of 26 patients (7.7%). One case of active bleeding from hepatic segmental artery and one case of sepsis after procedure occurred. Clinical success was achieved in 21 of 24 (87.5%) patients, who were followed for a mean of 141.5 days (range 25-354 days). The mean primary stent patency period was 191.8 days and the mean patient survival period was 299 days. Applying an open cell stent in the biliary system is feasible, and can be effective, especially in multiple intersecting stent insertions in the hepatic hilum.

Covered biliary stents with proximal bare stent extension for the palliation of malignant biliary disease: can we reduce tumour overgrowth rate?

PubMed

Krokidis, Miltiadis; Hatzidakis, Adam

2017-08-01

Covered biliary stents have shown significant effectiveness in the palliative management of patients with malignant biliary disease due to prevention of tumour ingrowth. However, stent dysfunction may still occur due to growth of tumour at the borders of the covered stent (tumour overgrowth). The aim of this study is to assess the effectiveness of a bare extension in the prevention of tumour overgrowth when covered stents are used in the palliative treatment of malignant biliary strictures. This is a prospective, single arm, cohort study. Twenty-two patients with inoperable malignant biliary strictures in the distal common bile duct (Bismuth I-II) and life expectancy more than 6 months were included in the study. The combination of a fully covered biliary stent and a bare proximal and distal extension was used in all cases. All patients were followed-up until death. Primary patency, survival, complication rates and dysfunction cause were assessed. Mean survival was 263.7 days (median 255, SD: 77.6). Mean patency was 240 days (median: 237, SD: 87). The primary patency rate at 3, 6 and 12 months was 90%, 86% and 86% respectively. Tumour inor overgrowth did not occur in any of the patients. Dysfunction due to sludge formation occurred in three cases; all three were treated with bilioplasty. The combined use of a covered biliary stent and a bare extension appears to be a very effective tool in the palliation of malignant biliary disease, offering long-term patency for patients with inoperable malignant distal common bile duct strictures and increasing the quality of life of such patients.

Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health.

PubMed

Dilger, Karin; Hohenester, Simon; Winkler-Budenhofer, Ursula; Bastiaansen, Barbara A J; Schaap, Frank G; Rust, Christian; Beuers, Ulrich

2012-07-01

Ursodeoxycholic acid (UDCA) exerts anticholestatic, antifibrotic and antiproliferative effects in primary biliary cirrhosis (PBC) via mechanisms not yet fully understood. Its adequate biliary enrichment is considered mandatory for therapeutic efficacy. However, precise determination of biliary enrichment of UDCA is not possible in clinical practice. Therefore, we investigated (i) the relationship between biliary enrichment and plasma pharmacokinetics of UDCA, (ii) the effect of UDCA on plasma and biliary bile acid composition and conjugation patterns, and (iii) on the intestinal detoxification machinery in patients with PBC and healthy controls. In 11 PBC patients and 11 matched healthy subjects, cystic bile and duodenal tissue were collected before and after 3 weeks of administration of UDCA (15 mg/kg/day). Extensive pharmacokinetic profiling of bile acids was performed. The effect of UDCA on the intestinal detoxification machinery was studied by quantitative PCR and Western blotting. The relative fraction of UDCA and its conjugates in plasma at trough level[x] correlated with their biliary enrichment[y] (r=0.73, p=0.0001, y=3.65+0.49x). Taurine conjugates of the major hydrophobic bile acid, chenodeoxycholic acid, were more prominent in bile of PBC patients than in that of healthy controls. Biliary bile acid conjugation patterns normalized after treatment with UDCA. UDCA induced duodenal expression of key export pumps, BCRP and P-glycoprotein. Biliary and trough plasma enrichment of UDCA are closely correlated in PBC and health. Taurine conjugation may represent an adaptive mechanism in PBC against chenodeoxycholic acid-mediated bile duct damage. UDCA may stabilize small intestinal detoxification by upregulation of efflux pumps. Copyright © 2012. Published by Elsevier B.V.

Grave's Disease and Primary Biliary Cirrhosis-An Unusual and Challenging Association.

PubMed

Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

2014-03-01

Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial.

Grave's Disease and Primary Biliary Cirrhosis—An Unusual and Challenging Association

PubMed Central

Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

2013-01-01

Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial. PMID:25755537

A 4-year treatment with clodronate plus calcium and vitamin D supplements does not improve bone mass in primary biliary cirrhosis.

PubMed

Floreani, A; Carderi, I; Ferrara, F; Rizzotto, E R; Luisetto, G; Camozzi, V; Baldo, V

2007-06-01

International guidelines for managing osteoporosis in cirrhosis or severe cholestasis indicate a <-2.5 t-score as a cut-off for medical treatment, while no treatment is recommended in the case of osteopenia (t-scores ranging from -1.0 to -2.5). We conducted a prospective study in primary biliary cirrhosis with a view to optimizing the rationale for the medical treatment of bone loss. All naïve post-menopausal women with primary biliary cirrhosis were enrolled in the study. Bone metabolism was evaluated by measuring 25-hydroxy-vitamin D, parathyroid hormone, osteocalcin. Bone mineral density was assessed at the lumbar spine by dual-photon X-ray absorptiometry at the baseline and every 2 years for up to 4 years. Patients with either osteopenia or osteoporosis received the following treatment: oral calcium carbonate (1000 mg/day)+vitamin D3 (880 IU/day)+i.m. disodium clodronate 100mg every 10 days for 4 years. Ninety-six patients completed the study: 30 had a normal bone mineral density (group 1), 37 had osteopenia (group 2), 29 had osteoporosis (group 3). No significant differences in biochemical parameters of bone metabolism were observed between the three groups. A total of 288 bone mineral density measurements were taken. Linear regression analysis failed to reveal significant changes in t-score over the follow-up in all groups. A 4-year treatment with clodronate+calcium/vitamin D3 supplements does not significantly improve osteoporosis or osteopenia in primary biliary cirrhosis women in menopause, but prevents the natural bone loss in these patients. Extensive international trials are warranted to optimize the prevention and treatment of bone loss in primary biliary cirrhosis.

Linking human beta retrovirus infection with primary biliary cirrhosis.

PubMed

Mason, A L; Zhang, G

2010-01-01

Several environmental agents have been linked with primary biliary cirrhosis (PBC) that include bacteria, xenobiotics and viruses. A human beta retrovirus (HBRV) related to mouse mammary tumor virus has been cloned and characterized from patients with PBC. This agent can be detected in the majority of patients' perihepatic lymph nodes by immunochemistry and RT-PCR. The HBRV has recently been isolated in culture and integration sites have been identified in the genome of patients to provide convincing evidence of beta retrovirus infection in patients. Three lines of evidence support a role for the virus in PBC. First, the beta retrovirus is linked with aberrant expression of mitochondrial protein(s) on the biliary epithelium cell (BEC) surface, a disease specific phenotype. Second, the related agent, mouse mammary tumor virus has been linked with autoimmune biliary disease in the NOD.c3c4 mouse model for PBC. In this mouse model, the virus is localized to diseased biliary epithelium that also display aberrant expression of the mitochondrial autoantigens. In translational studies, both patients with PBC and NOD.c3c4 mice demonstrate significant improvement in biliary disease with combination antiviral therapy. An overview of the biological relevance of the beta retrovirus infection in PBC will be discussed in this review. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Mapping of the locus for autosomal dominant amelogenesis imperfecta (AIH2) to a 4-Mb YAC contig on chromosome 4q11-q21

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaerrman, C.; Holmgren, G.; Forsman, K.

1997-01-15

Amelogenesis imperfecta (Al) is a clinically and genetically heterogeneous group of inherited enamel defects. We recently mapped a locus for autosomal dominant local hypoplastic amelogenesis imperfecta (AIH2) to the long arm of chromosome 4. The disease gene was localized to a 17.6-cM region between the markers D4S392 and D4S395. The albumin gene (ALB), located in the same interval, was a candidate gene for autosomal dominant AI (ADAI) since albumin has a potential role in enamel maturation. Here we describe refined mapping of the AIH2 locus and the construction of marker maps by radiation hybrid mapping and yeast artificial chromosome (YAC)-basedmore » sequence tagged site-content mapping. A radiation hybrid map consisting of 11 microsatellite markers in the 5-cM interval between D4S409 and D4S1558 was constructed. Recombinant haplotypes in six Swedish ADAI families suggest that the disease gene is located in the interval between D4S2421 and ALB. ALB is therefore not likely to be the disease-causing gene. Affected members in all six families share the same allele haplotypes, indicating a common ancestral mutation in all families. The AIH2 critical region is less than 4 cM and spans a physical distance of approximately 4 Mb as judged from radiation hybrid maps. A YAC contig over the AIH2 critical region including several potential candidate genes was constructed. 35 refs., 4 figs., 1 tab.« less

Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis.

PubMed

Danielsson Borssén, Åsa; Marschall, Hanns-Ulrich; Bergquist, Annika; Rorsman, Fredrik; Weiland, Ola; Kechagias, Stergios; Nyhlin, Nils; Verbaan, Hans; Nilsson, Emma; Werner, Mårten

2017-09-01

Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce. Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort. Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Västerbotten in Northern Sweden. AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p < .001) and died younger than women (p = .002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p < .001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years. Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amygdalos, Michael A.; Haskal, Ziv J.; Cope, Constantin

Two patients with pancreatic malignancies presented with biliary obstruction which could not be treated from an endoscopic approach. Standard transhepatic biliary drainage was relatively contraindicated because of moderate ascites and coagulopathy related to underlying liver disease. In one patient, a transjugular, transvenous approach was used to deliver a Wallstent endoprosthesis across the distal common bile duct obstruction in a single step procedure. In the second case, a previously placed biliary Wallstent was revised with an additional stent from a similar approach. Transjugular biliary catheterization offers a valuable alternative approach for primary stent placement or revision in patients with contraindication tomore » standard transhepatic drainage.« less

Role of stents and laser therapy in biliary strictures

NASA Astrophysics Data System (ADS)

Chennupati, Raja S.; Trowers, Eugene A.

2001-05-01

The most frequent primary cancers causing malignant obstructive jaundice were pancreatic cancer (57%), hilar biliary cancer (19% including metastatic disease), nonhilar biliary cancer (14%) and papillary cancer (10%). Endoscopic stenting has widely replaced palliative surgery for malignant biliary obstruction because of its lower risk and cost. Self-expandable metal stents are the preferred mode of palliation for hilar malignancies. Plastic stents have a major role in benign biliary strictures. Major complications and disadvantages associated with metallic stents include high cost, cholangitis. malposition, migration, unextractability, and breakage of the stents, pancreatitis and stent dysfunction. Dysfunction due to tumor ingrowth can be relieved by thermal methods (argon plasma coagulator therapy). We present a concise review of the efficacy of metallic stents for palliation of malignant strictures.

Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma.

PubMed

Nguyen Canh, Hiep; Harada, Kenichi

2016-12-01

Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.

Sustained Hypoxia Elicits Competing Spinal Mechanisms of Phrenic Motor Facilitation

PubMed Central

Devinney, Michael J.; Nichols, Nicole L.

2016-01-01

Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal motor plasticity. Competing mechanisms give rise to phrenic motor facilitation (pMF; a general term including pLTF) depending on the severity of hypoxia within episodes. In contrast, moderate acute sustained hypoxia (mASH) does not elicit pMF. By varying the severity of ASH and targeting competing mechanisms of pMF, we sought to illustrate why moderate AIH (mAIH) elicits pMF but mASH does not. Although mAIH elicits serotonin-dependent pLTF, mASH does not; thus, mAIH-induced pLTF is pattern sensitive. In contrast, severe AIH (sAIH) elicits pLTF through adenosine-dependent mechanisms, likely from greater extracellular adenosine accumulation. Because serotonin- and adenosine-dependent pMF interact via cross talk inhibition, we hypothesized that pMF is obscured because the competing mechanisms of pMF are balanced and offsetting during mASH. Here, we demonstrate the following: (1) blocking spinal A2A receptors with MSX-3 reveals mASH-induced pMF; and (2) sASH elicits A2A-dependent pMF. In anesthetized rats pretreated with intrathecal A2A receptor antagonist injections before mASH (PaO2 = 40–54 mmHg) or sASH (PaO2 = 25–36 mmHg), (1) mASH induced a serotonin-dependent pMF and (2) sASH induced an adenosine-dependent pMF, which was enhanced by spinal serotonin receptor inhibition. Thus, competing adenosine- and serotonin-dependent mechanisms contribute differentially to pMF depending on the pattern/severity of hypoxia. Understanding interactions between these mechanisms has clinical relevance as we develop therapies to treat severe neuromuscular disorders that compromise somatic motor behaviors, including breathing. Moreover, these results demonstrate how competing mechanisms of plasticity can give rise to pattern sensitivity in pLTF. SIGNIFICANCE STATEMENT Intermittent hypoxia elicits pattern-sensitive spinal plasticity and improves motor function after spinal injury or during neuromuscular disease. Specific mechanisms of pattern sensitivity in this form of plasticity are unknown. We provide evidence that competing mechanisms of phrenic motor facilitation mediated by adenosine 2A and serotonin 2 receptors are differentially expressed, depending on the pattern/severity of hypoxia. Understanding how these distinct mechanisms interact during hypoxic exposures differing in severity and duration will help explain interesting properties of plasticity, such as pattern sensitivity, and may help optimize therapies to restore motor function in patients with neuromuscular disorders that compromise movement. PMID:27466333

Molecular genetics and targeted therapeutics in biliary tract carcinoma.

PubMed

Marks, Eric I; Yee, Nelson S

2016-01-28

The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.

Adenosine 2A Receptor Inhibition Enhances Intermittent Hypoxia-Induced Diaphragm but Not Intercostal Long-Term Facilitation

PubMed Central

Navarrete-Opazo, Angela A.; Vinit, Stéphane

2014-01-01

Abstract Acute intermittent hypoxia (AIH) elicits diaphragm (Dia) and second external intercostal (T2 EIC) long-term facilitation (LTF) in normal unanesthetized rats. Although AIH-induced phrenic LTF is serotonin dependent, adenosine constrained in anesthetized rats, this has not been tested in unanesthetized animals. Cervical (C2) spinal hemisection (C2HS) abolishes phrenic LTF because of loss of serotonergic inputs 2 weeks post-injury, but LTF returns 8 weeks post-injury. We tested three hypotheses in unanesthetized rats: (1) systemic adenosine 2aA (A2A) receptor inhibition with intraperitoneal (IP) KW6002 enhances Dia and T2 EIC LTF in normal rats; (2) Dia and T2 EIC LTF are expressed after chronic (8 weeks), but not acute (1 week) C2HS; and (3) KW6002 enhances Dia and T2 EIC LTF after chronic (not acute) C2HS. Electromyography radiotelemetry was used to record Dia and T2 EIC activity during normoxia (21% O2), before and after AIH (10, 5-min 10.5% O2, 5-min intervals). In normal rats, KW6002 enhanced DiaLTF versus AIH alone (33.1±4.6% vs. 22.1±6.4% baseline, respectively; p<0.001), but had no effect on T2 EIC LTF (p>0.05). Although Dia and T2 EIC LTF were not observed 2 weeks post-C2HS, LTF was observed in contralateral (uninjured) Dia and T2 EIC 8 weeks post-C2HS (18.7±2.7% and 34.9±4.9% baseline, respectively; p<0.05), with variable ipsilateral expression. KW6002 had no significant effects on contralateral Dia (p=0.447) or T2 EIC LTF (p=0.796). We conclude that moderate AIH induces Dia and T2 EIC LTF after chronic, but not acute cervical spinal injuries. A single A2A receptor antagonist dose enhances AIH-induced Dia LTF in normal rats, but this effect is not significant in chronic (8 weeks) C2HS unanesthetized rats. PMID:25003645

Comparison of outcomes among secondary covered metallic, uncovered metallic, and plastic biliary stents in treating occluded primary metallic stents in malignant distal biliary obstruction.

PubMed

Cho, Jae Hee; Jeon, Tae Joo; Park, Jeong Youp; Kim, Hee Man; Kim, Yoon Jae; Park, Seung Woo; Chung, Jae Bock; Song, Si Young; Bang, Seungmin

2011-02-01

The self-expandable metallic stent (SEMS) has been widely used for unresectable malignant biliary obstruction but eventually becomes occluded by tumor ingrowth/overgrowth and sludge. Therefore, we aimed to determine the therapeutic effectiveness of secondary stents and to find differences according to various combinations of the first and second stents for the management of occluded SEMSs in patients with malignant distal biliary obstruction. Between 1999 and November 2008, 77 patients with malignant biliary obstruction underwent secondary biliary stent placement as "stent-in-stent" at three university hospitals in Korea (40 covered, 26 uncovered, and 11 plastic stents). The membrane of the covered SEMS was regarded as the barrier against tumor ingrowth. We categorized the patients into three groups based on whether the covered SEMS was either the first or the second stent: membrane-SEMS (18 covered-covered; 9 covered-uncovered; 22 uncovered-covered SEMS), bare-SEMS (17 uncovered-uncovered SEMS), and plastic stent (3 covered-plastic; 8 uncovered-plastic). The median patency of second stents was 138, 109, and 88 days (covered, uncovered, and plastic stents). The second covered SEMSs had a significantly longer patency than plastic stents (p=0.047). In a multivariate analysis including membrane-SEMS, bare-SEMS, and plastic stent groups, the bare-SEMS had a worse cumulative stent patency (HR=2.04, CI=1.08-3.86) and survival time (HR=2.37, CI=1.25-4.49) than the membrane-SEMS. Patients with ampulla of Vater cancer had better stent patency (HR=0.27, CI=0.08-0.98) and survival (HR=0.17, CI=0.04-0.77) than those with other pancreatobiliary malignancies. In addition, antitumor treatment prolonged survival time (HR=0.50, CI=0.26-0.99). The placement of additional biliary stents using the "stent-in-stent" method is an effective treatment for an occluded metallic primary stent. In addition, double biliary SEMS placement using at least one covered SEMS (in the primary and/or secondary procedure) might provide longer cumulative stent patency and survival than using uncovered SEMSs in both procedures.

Key residues of a major cytochrome P4502D6 epitope are located on the surface of the molecule.

PubMed

Ma, Yun; Thomas, Mark G; Okamoto, Manabu; Bogdanos, Dimitrios P; Nagl, Sylvia; Kerkar, Nanda; Lopes, Agnel R; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B; Mieli-Vergani, Giorgina; Vergani, Diego

2002-07-01

Eukaryotically expressed CYP2D6 is the universal target of liver kidney microsomal Ab type 1 (LKM1) in both type 2 autoimmune hepatitis (AIH) and chronic hepatitis C virus (HCV) infection. In contrast, reactivity to prokaryotically expressed CYP2D6 protein and synthetic peptides is significantly lower in HCV infection than in AIH. The aim of the present study was to characterize LKM1 reactivity against a panel of eukaryotically expressed CYP2D6 constructs in the two conditions. LKM1-positive sera obtained from 16 patients with AIH and 16 with HCV infection were used as probes to perform a complete epitope mapping of CYP2D6. Reactivity to the full-length protein and 16 constructs thereof was determined by radioligand assay. We found that antigenicity is confined to the portion of the molecule C-terminal of aa 193, no reactivity being detectable against the aa sequence 1-193. Reactivity increases stepwise toward the C-terminal in both AIH and HCV, but the frequency of reactivity in the two conditions differs significantly between aa 267-337. To further characterize this region, we introduced a five and a three amino acid swap mutation selected from the homologous regions of CYP2C9 and HCV. This maneuver resulted in a substantial loss of LKM1 binding in both conditions, suggesting that this region contains a major epitope. Molecular modeling revealed that CYP2D6(316-327) is exposed on the surface of the protein, and may represent a key target for the autoantibody. These findings provide an initial characterization of the antigenic constitution of the target of LKM1 in AIH and HCV infection.

Difference in clinical presentation, immunology profile and treatment response of type 1 autoimmune hepatitis between United Kingdom and Singapore patients.

PubMed

Than, Nwe Ni; Ching, Doreen Koay Siew; Hodson, James; McDowell, Patrick; Mann, Jake; Gupta, Ravi; Salazar, Ennaliza; Ngu, Jing Hieng; Oo, Ye Htun

2016-07-01

Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology. Increasing incidence of AIH in Asian patients has been reported. However, the phenotypic difference of Asian patients in Europe and Asia has still not been explored. To evaluate the clinical presentation, biochemical and immunological profiles, treatment response and survival outcome of type 1 AIH from two tertiary liver transplant centres (United Kingdom and Singapore). Patients who fulfilled the simplified diagnostic scoring criteria of AIH were included in the study. Patients with overlap syndrome were excluded. Totals of 40 Asian patients and 159 Caucasian patients from the University Hospital of Birmingham National Health Service Foundation Trust, UK, were compared with 57 Asian patients from Singapore General Hospital, Singapore. Asian patients from Singapore present significantly much later (median 55 vs. 32 years, p < 0.001), had higher MELD (p < 0.001) with lower albumin (p < 0.001) and higher bilirubin (p < 0.001) and lower ASMA positivity (p < 0.001) at diagnosis compared to UK Asian. Jaundice at presentation was much higher in Singapore Asian patients compared to UK Asian (53 vs. 30 %) but cirrhosis at diagnosis was more common in UK patients. Associated autoimmune conditions were less commonly seen in Singapore Asians. Comparing between UK cohorts, Asian patients present at younger age and have higher IgG level compared to Caucasian. Overall, 5-year transplant-free survival in all three cohorts was similar (p = 0.846). We demonstrate that AIH patients from Singapore present at older age with jaundice and have a low positivity of SMA. Despite these differences, transplant-free survival is similar in the two groups.

Urethane inhibits genioglossal long-term facilitation in un-paralyzed anesthetized rats.

PubMed

Cao, Ying; Ling, Liming

2010-06-25

For approximately 3 decades, urethane has been (partially or solely) used as a successful anesthetic in numerous respiratory long-term facilitation (LTF) studies, which were performed on anesthetized, paralyzed, vagotomized and artificially ventilated animals of several different species. However, things become complicated when LTF of muscle activity is studied in un-paralyzed animals. For example, a commonly used acute intermittent hypoxia (AIH) protocol failed to induce muscle LTF in anesthetized, spontaneously breathing rats. But muscle LTF could be induced when hypoxic episode number was increased and/or anesthetics other than urethane were used. In these studies however, neither anesthetic nor paralysis was mentioned as a potential factor influencing AIH-induced muscle LTF. This study tested whether urethane inhibits AIH-induced genioglossal LTF (gLTF) in un-paralyzed ventilated rats, and if so, determined whether reducing urethane dose reverses this inhibition. Three groups of adult male Sprague-Dawley rats were anesthetized (Group 1: approximately 1.6 g kg(-1) urethane; Group 2: 50 mg kg(-1) alpha-chloralose +0.9-1.2 g kg(-1) urethane; Group 3: 0.9 g kg(-1) urethane +200-400 microg kg(-1) min(-1) alphaxalone), vagotomized and mechanically ventilated. Integrated genioglossus activity was measured before, during and after AIH (5 episodes of 3-min isocapnic 12% O(2), separated by 3-min hyperoxic intervals). The AIH-induced gLTF was absent in Group 1 rats (success rate was only approximately 1/7), but was present in Group 2 (in 10/12 rats) and Group 3 (in 11/11 rats) rats. The genioglossal response to hypoxia was not significantly different among the 3 groups. Collectively, these data suggest that urethane dose-dependently inhibits gLTF in un-paralyzed anesthetized rats. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Risk Factors for Hepatic Morbidity Following Nonoperative Management: Multicenter Study

DTIC Science & Technology

2006-05-01

with a primary bile duct leak at ERCP. The last patient underwent laparotomy for a biliary -venous fistula that failed to resolve by ERCP and stenting ...the patient with a biliary -venous fistula underwent laparotomy and ERCP with stenting to manage this complication and then later, IR drainage of a...peritonitis,17 and stenting rather than sphincter- otomy is felt to expedite healing of biliary leaks.18 Al- though we had relatively few bile duct

Concurrent Autoimmune Hepatitis and Grave's Disease in Hepatitis C during Pegylated Interferon α-2a and Ribavirin Therapy

PubMed Central

Trikudanathan, Guru V.; Ahmad, Imad; Israel, Jonathan L

2011-01-01

Classical interferon-α has been shown to be associated with the development of a variety of autoimmune disorders. A 34-year-old white woman with chronic hepatitis C virus infection who was treated with pegylated interferon α-2a and ribavirin, developed Grave's disease and autoimmune hepatitis (AIH) at 32 and 44 weeks, respectively, following initiation of the therapy. The diagnosis of AIH was made based on the new development of anti-smooth muscle antibodies, anti-mitochondrial antibodies, and liver biopsy findings. It was confirmed by positive response to steroid challenge and was assessed according to the international AIH scoring system. Based on the previous case reports, we review the existing literature. Clinicians should be aware of the possibility of multiple autoimmune disorders during interferon-based therapy for chronic hepatitis. PMID:21912063

Concurrent autoimmune hepatitis and grave's disease in hepatitis C during pegylated interferon α-2a and ribavirin therapy.

PubMed

Trikudanathan, Guru V; Ahmad, Imad; Israel, Jonathan L

2011-01-01

Classical interferon-α has been shown to be associated with the development of a variety of autoimmune disorders. A 34-year-old white woman with chronic hepatitis C virus infection who was treated with pegylated interferon α-2a and ribavirin, developed Grave's disease and autoimmune hepatitis (AIH) at 32 and 44 weeks, respectively, following initiation of the therapy. The diagnosis of AIH was made based on the new development of anti-smooth muscle antibodies, anti-mitochondrial antibodies, and liver biopsy findings. It was confirmed by positive response to steroid challenge and was assessed according to the international AIH scoring system. Based on the previous case reports, we review the existing literature. Clinicians should be aware of the possibility of multiple autoimmune disorders during interferon-based therapy for chronic hepatitis.

Possible autoimmune hepatitis induced after chronic active Epstein-Barr virus infection.

PubMed

Wada, Yoshiko; Sato, Chikako; Tomita, Kyoko; Ishii-Aso, Rika; Haga, Hiroaki; Okumoto, Kazuo; Nishise, Yuko; Watanabe, Hisayoshi; Saito, Takafumi; Ueno, Yoshiyuki

2014-02-01

Chronic active Epstein-Barr virus infection (CAEBV) can be manifested in a variety of systemic conditions, including interstitial pneumonia, malignant lymphoma, and coronary aneurysm. Sometimes it may be associated with hepatic failure, although the mechanism underlying CAEBV-related hepatotoxicity remains unclear. We encountered a case of autoimmune hepatitis (AIH) associated with CAEBV. A 61-year-old male was referred to our hospital because of abnormal liver enzyme levels after initial diagnosis of CAEBV had been made by laboratory tests and liver biopsy. On admission, positivity for anti-nuclear antibody was evident, and examination of the liver biopsy specimen showed findings compatible with AIH. Steroid administration was initiated, and the liver function parameters subsequently improved. Although phenotypic changes in liver biopsy specimens are rare in this condition, the present case could provide clues to the possible pathogenesis of AIH.

Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

DTIC Science & Technology

2015-10-01

compensation in unanesthetized rats. 15. SUBJECT TERMS Spinal Injury, Treatment , Intermittent hypoxia, rats, spontaneous recovery, induced recovery, rAIH, PKC...After immunofluoresence for KCC1/NKCC2, confocal z-stacks of cholera - toxin back-labeled phrenic motor neurons were made ipsilateral and contralateral...enhanced excitatory neurotransmission) also did not pan out, we suspect that the timing of rAIH treatment in our studies was not optimal. Indeed

Non-alcoholic fatty liver disease (NAFLD) potentiates autoimmune hepatitis in the CYP2D6 mouse model.

PubMed

Müller, Peter; Messmer, Marie; Bayer, Monika; Pfeilschifter, Josef M; Hintermann, Edith; Christen, Urs

2016-05-01

Non-alcoholic fatty liver disease (NAFLD) and its more severe development non-alcoholic steatohepatitis (NASH) are increasing worldwide. In particular NASH, which is characterized by an active hepatic inflammation, has often severe consequences including progressive fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Here we investigated how metabolic liver injury is influencing the pathogenesis of autoimmune hepatitis (AIH). We used the CYP2D6 mouse model in which wild type C57BL/6 mice are infected with an Adenovirus expressing the major liver autoantigen cytochrome P450 2D6 (CYP2D6). Such mice display several features of human AIH, including interface hepatitis, formation of LKM-1 antibodies and CYP2D6-specific T cells, as well as hepatic fibrosis. NAFLD was induced with a high-fat diet (HFD). We found that pre-existing NAFLD potentiates the severity of AIH. Mice fed for 12 weeks with a HFD displayed increased cellular infiltration of the liver, enhanced hepatic fibrosis and elevated numbers of liver autoantigen-specific T cells. Our data suggest that a pre-existing metabolic liver injury constitutes an additional risk for the severity of an autoimmune condition of the liver, such as AIH. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis exacerbation in a patient with systemic lupus erythematosus.

PubMed

Yamashita, H; Shimizu, A; Tsuchiya, H; Takahashi, Y; Kaneko, H; Kano, T; Mimori, A

2014-07-01

Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms. We report a very rare case with autoimmune hepatitis (AIH) complicated by CAEBV. A 50-year-old woman with systemic lupus erythematosus (SLE) complicated by AIH began to suffer from acute respiratory failure and her clinical symptoms improved rapidly in response to steroid treatment. However, during the gradual tapering of the steroid dose, a steady increase of the serum hepatobiliary enzyme levels subsequently was observed and the patient began to have continuous fever. Moreover, upper gastrointestinal endoscopy revealed multiple intractable gastric ulcers. When EBER-ISH was performed on liver biopsy and gastric mucosal biopsy specimens, EBER-positive lymphocytes were observed. When peripheral blood was examined, 2.1 × 10(6) copies/µg of EBV-DNA were observed in the CD4-positive T cells, confirming the diagnosis of CAEBV. A cooling therapy was started by steroid and cyclosporine. Thereafter, despite the start of CHOP therapy, she developed a malignant lymphoma (PTCL-NOS) and died of hepatic failure. When treatment-resistant AIH patients are encountered, not only AIH exacerbation but also CAEBV should be considered in the differential diagnosis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Primary Biliary Cholangitis: advances in management and treatment of the disease.

PubMed

Invernizzi, Pietro; Floreani, Annarosa; Carbone, Marco; Marzioni, Marco; Craxi, Antonio; Muratori, Luigi; Vespasiani Gentilucci, Umberto; Gardini, Ivan; Gasbarrini, Antonio; Kruger, Paola; Mennini, Francesco Saverio; Ronco, Virginia; Lanati, Elena; Canonico, Pier Luigi; Alvaro, Domenico

2017-08-01

Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer. Ursodeoxycholic acid is the only treatment available today, but even if effective in counteracting the disease progression for the majority of patients, in approximately 40% is not able to decrease effectively the alkaline phosphatase, a surrogate marker of disease activity. Recently, obeticholic acid received the European Medicines Agency conditional approval, as add on treatment in patients non responders or intolerant to ursodeoxycholic acid. The present paper illustrates the opinion of a working group, composed by clinical pharmacologists, gastroenterologists/hepatologists with specific expertise on Primary Biliary Cholangitis and patient associations, on the state of the art and future perspectives of the disease management. The agreement on the document was reached through an Expert Meeting. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Molecular genetics and targeted therapeutics in biliary tract carcinoma

PubMed Central

Marks, Eric I; Yee, Nelson S

2016-01-01

The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract. PMID:26819503

The Role of an Online Community for People With a Rare Disease: Content Analysis of Messages Posted on a Primary Biliary Cirrhosis Mailinglist

PubMed Central

Sogolow, Ellen D; Sharim, Rebecca R

2005-01-01

Background This study focuses on the role of an Internet-based group for people who have an autoimmune liver disease, primary biliary cirrhosis. Primary biliary cirrhosis is a relatively rare disease, affects primarily women in their 40's and older, and is not well understood. The PBCers Organization (PBC stands for primary biliary cirrhosis) provides electronic mailinglists (listservs) and informational resources for those with primary biliary cirrhosis. Objectives (1) to identify the issues of greatest importance to those posting to the listserv, specifically the relative importance of biomedical, socioemotional, and organizational/systems messages; (2) to compare frequency and content of posts by people at different stages of disease; (3) to identify how people with primary biliary cirrhosis represent the psychosocial challenges and dilemmas (role and identity change, uncertainty, and stigma) identified in the social-scientific literature as key elements of the experience of chronic disease. Methods The paper is based on content analysis of messages posted during two months to the Daily Digest listserv for people who have primary biliary cirrhosis. To analyze the posts, we developed a coding system with three major categories--biomedical, socioemotional, and systems/organizations--and 12 codes in each category. Results A total of 275 people posted 710 messages. Of the 250 people for whom information on gender was available, 239 (95.6%) were women and 11 (4.4%) were men. Analysis of 710 messages posted to the listserv revealed a predominance of requests for and reports of biomedical information, such as health care providers (32.7%), medications (30.9%), tests and procedures (25.8%), and symptoms (25.7%), combined with very frequent expressions of emotional support. The most frequent single topics were peer support (included in 40.6% of all posts) and positive emotions (25.3%). Posters who reported fewer years since diagnosis were more likely to be seeking biomedical information than those who were further in time from their diagnosis (r= -.241, P<.001, n=313). Those in later stages posted an average of 3.87 messages, compared to an average of 2.64 for people in earlier stages (t= 1.786, P=.08, n=90), which is different from what we expected. No relation between years since diagnosis or age and number of messages was found. Contrary to our expectations, the topics reflecting issues of role change/identity (2.9%), stigma (0.7%), and thoughts about the future (3.9%), all identified in social-scientific literature as key concerns for people with chronic illness, appeared infrequently in this set of messages. Conclusions Messages exchanged on this particular mailing list have a biomedical, rather than socioemotional or organizational, emphasis. The Internet offers a highly valued opportunity for those with rare diseases to connect with, learn from, and provide support to others having similar experiences. Research that compares those with primary biliary cirrhosis, who are involved in an Internet support group and those who are not, would be an important next step to better understanding the role of the Internet among patients with chronic liver disease and the implications of it in the course of their illness. PMID:15829472

The unfinished business of primary biliary cirrhosis.

PubMed

Selmi, Carlo; Zuin, Massimo; Gershwin, M Eric

2008-09-01

In nearly every multifactorial human disease, there are three periods that characterize our understanding and definition. First, there is a period in which there is rapid accumulation of descriptive data. Second, there is a longer and slower period as information is obtained that redefines and expands basic and clinical knowledge that lacks the final and important area of understanding aetiology and therapeutic intervention. Third, which is much less common for most diseases, is the vigorous definition of pathobiology and treatment. These phases are well illustrated by our current understanding of primary biliary cirrhosis (PBC). The term PBC was first used nearly 60 years ago and for the first 40 or so years, the primary research efforts were directed at clinical definitions and pathology. Subsequently, with the advent of molecular biology, there began a rigorous dissection of the immune response and, in particular, a better understanding of anti-mitochondrial antibodies. These efforts have greatly helped in our understanding of not only the effector mechanisms of disease, but also the uniqueness of the primary target tissue, biliary epithelium. However, this research has still not led to successful translation for specific therapy.

Liver alkaline phosphatase: a missing link between choleresis and biliary inflammation.

PubMed

Poupon, Raoul

2015-06-01

Several lines of evidence show that serum alkaline phosphatase (AP) is not only a signpost of cholestasis but also a surrogate marker of the severity of primary biliary cirrhosis and primary sclerosing cholangitis. In the present opinion article, we review and discuss the putative role of liver AP in health and in cholestatic diseases. In inflammatory cholestatic conditions, loss of activity of liver AP (resulting from its relocation from canaliculi and the acidic milieu) might promote hyper-adenosine triphosphate-bilia, lipopolysaccharide overload, and subsequent exacerbation and perpetuation of inflammation. Drugs that can restore the polarity of hepatocytes and canalicular export of bile acids or act as bile alkalinity modifiers are predicted to exert anti-inflammatory effects and to benefit both primary biliary cirrhosis and primary sclerosing cholangitis. Oral administration of intestinal AP could be a valid therapeutic intervention that deserves further study under experimental conditions as well as in human diseases. Overall, the key role of the liver microenvironment that might shape the different facets of the inflammatory processes in fibrosing cholangiopathies is highlighted. © 2015 by the American Association for the Study of Liver Diseases.

Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: consider primary biliary cholangitis not always primary sclerosing cholangitis.

PubMed

Polychronopoulou, Erietta; Lygoura, Vasiliki; Gatselis, Nikolaos K; Dalekos, George N

2017-09-25

Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)-the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Temporary placement of retrievable fully covered metallic stents versus percutaneous balloon dilation in the treatment of benign biliary strictures.

PubMed

Kim, Jin Hyoung; Gwon, Dong Il; Ko, Gi-Young; Sung, Kyu-Bo; Lee, Sung Koo; Yoon, Hyun-Ki; Shin, Ji Hoon; Song, Ho-Young

2011-06-01

To compare retrospectively percutaneous transhepatic primary placement of a retrievable self-expanding metallic stent with percutaneous balloon dilation for the treatment of benign biliary strictures. From 2005-2009, 66 patients with benign biliary strictures in whom an endoscopic approach failed or in whom such an approach was inaccessible were evaluated. Of 66 patients, 31 underwent balloon dilation, and 35 underwent temporary metallic stent placement. The etiologies of the benign strictures were anastomotic stricture after surgery (n = 54), stricture secondary to intraoperative injury (n = 9), inflammatory stricture (n = 2), and stricture secondary to trauma (n = 1). The primary patency rates were significantly better in the stent group (87% at 3 years) than in the balloon group (44% at 3 years; P = .022). The indwelling period of percutaneous transhepatic biliary drainage (PTBD) catheters after the initial procedure was able to be significantly reduced in the stent group (median 2.5 months) compared with the balloon group (median 4.5 months; P = .001). Significant bleeding (associated with PTBD) occurred in one patient in the balloon group. In the stent group, stent migration occurred in two patients, and one patient underwent surgery for stent removal after failure of removal under fluoroscopic guidance. Percutaneous primary placement of a retrievable self-expanding metallic stent showed superior intermediate-term results compared with percutaneous balloon dilation for the treatment of benign biliary strictures. In addition, the indwelling period of PTBD catheters can be significantly reduced using temporary stent placement. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial).

PubMed

van der Gaag, Niels A; de Castro, Steve M M; Rauws, Erik A J; Bruno, Marco J; van Eijck, Casper H J; Kuipers, Ernst J; Gerritsen, Josephus J G M; Rutten, Jan-Paul; Greve, Jan Willem; Hesselink, Erik J; Klinkenbijl, Jean H G; Rinkes, Inne H M Borel; Boerma, Djamila; Bonsing, Bert A; van Laarhoven, Cees J; Kubben, Frank J G M; van der Harst, Erwin; Sosef, Meindert N; Bosscha, Koop; de Hingh, Ignace H J T; Th de Wit, Laurens; van Delden, Otto M; Busch, Olivier R C; van Gulik, Thomas M; Bossuyt, Patrick M M; Gouma, Dirk J

2007-03-12

Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor.

Medical treatment of primary biliary cirrhosis and primary sclerosing cholangitis.

PubMed

Holtmeier, J; Leuschner, U

2001-01-01

Treatment of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) with ursodeoxycholic acid (UDCA) has been in common use since 1985. In PBC, treatment with UDCA improves laboratory data, liver histology, enables a longer transplantation-free interval and prolongs disease survival. Because UDCA is unable to cure the disease newer drugs or combination therapies are still needed. Studies with UDCA and immunosuppressants such as prednisone, budesonide and azathioprine have shown that in selected patients combination therapy may be superior to UDCA monotherapy. PSC is treated successfully with UDCA and endoscopic dilatation of the bile duct strictures. Treatment of extrahepatic manifestations of cholestatic liver disease such as pruritus, fatigue, osteoporosis and steatorrhea can be problematic and time-consuming. Copyright 2001 S. Karger AG, Basel

[Long-Term Multidisciplinary Therapy for Multiple Liver Metastases from Colorectal Cancer with Biliary Drainage for Occlusive Jaundice--A Case Report].

PubMed

Okamura, Shu; Mikami, Koji; Murata, Kohei; Nushijima, Yoichirou; Okada, Kazuyuki; Yanagisawa, Tetsu; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

2015-11-01

Here, we report the case of a 43-year-old man who was diagnosed with sigmoid colon cancer with synchronous multiple liver metastases following resection of a primary lesion. Subsequent mFOLFOX+BV therapy elicited a marked response in the liver metastases, which led to the patient undergoing hepatic (S7) radiofrequency ablation (RFA), hepatic resection (lateral segmentectomy and partial [S5] resection), and cholecystectomy. Six months later, transluminal RFA was repeated because liver (S7) metastasis recurred, and 8 courses of XELOX plus BV therapy were administered. As obstructive jaundice due to recurrence of the liver metastases developed after a 6 months hiatus in chemotherapy, we endoscopically inserted a biliary stent. Despite reducing IRIS plus BV therapy, obstructive jaundice developed again, and 3 intrahepatic biliary stents were inserted with percutaneous transhepatic biliary drainage. To date, the patient has been alive for 4 years since the initial resection of the primary lesion after undergoing consecutive systemic chemotherapy with different regimens. Some studies have shown that in cases of obstructive jaundice caused by advanced gastrointestinal cancer, longer survival could be expected by reducing the severity of jaundice, suggesting that resuming chemotherapy as well as improving the severity of jaundice could contribute to better outcomes. The patient in the present case was successfully treated twice with biliary drainage for occlusive jaundice and chemotherapy, suggesting that a combination of multidisciplinary therapy and adequate local therapy such as biliary drainage could be important for the treatment of metastatic liver cancer.

The use of silastic transhepatic stents in benign and malignant biliary strictures.

PubMed Central

Cameron, J L; Gayler, B W; Zuidema, G D

1978-01-01

Between 1969 and 1978, 45 patients with biliary strictures have been managed surgically utilizing silastic transhepatic stents. In 25 patients the strictures were benign. After resection or dilatation of the benign stricture, an hepaticojejunostomy was performed to a Roux-en-Y loop. The anastomosis was stented with a large bore silastic tube with multiple side holes passed through the biliary tree, out the anterior surface of the liver, and then out through the abdominal wall. There was one hospital death. Most stents were left in place for one year. Of the 15 patients with long-term follow-up, all have had excellent results. In 20 patients the strictures were malignant and involved the common hepatic duct in 10 patients or its bifuraction in 10 patients. In 14 patients the tumor was thought to be primary in the biliary tree, and in six patients the tumor was felt to represent a metastasis or direct extension from another site. In three patients the tumors were resected, and in the remaining they were dilated or bypassed. After positioning a silastic transhepatic stent, a hepaticojejunostomy was carried out. There were two hospital deaths. Serum bilirubin on admission average 17.1 mg%, and after decompression 1.8 mg%. Five patients have survived over one year, and two over two years. Postoperative radiotherapy and a primary biliary tumor favored longer survival. Images Fig. 1. Fig. 2. Fig. 4. PMID:697437

A real-world observational cohort of patients with primary biliary cholangitis: TARGET-primary biliary cholangitis study design and rationale.

PubMed

Levy, Cynthia; Bowlus, Christopher L; Carey, Elizabeth; Crawford, Julie M; Deane, Karen; Mayo, Marlyn J; Kim, W Ray; Fried, Michael W

2018-05-01

Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first-line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S. Food and Drug Administration approved obeticholic acid to be used in certain patients with PBC. Off-label therapies are also used, and several other therapies are currently under evaluation. Real-world effectiveness of newly approved and off-label therapies remains unknown. TARGET-PBC is a 5-year, longitudinal, observational study of patients with PBC that will evaluate the effectiveness of clinical practice interventions and provide practical information unobtainable in registration trials. Enrollment will take place at both academic and community sites. In addition to consenting to medical records review, participants will be asked to provide an annual blood sample and complete patient reported outcome surveys at predetermined intervals. Any available liver biopsies will be digitally preserved. Conclusion: Key study outcomes will be the evaluation of the safety and effectiveness of PBC interventions and the assessment of disease progression under real-world conditions. ( Hepatology Communications 2018;2:484-491).

Endoscopic management of malignant biliary obstruction by means of covered metallic stents: primary stent placement vs. re-intervention.

PubMed

Kida, M; Miyazawa, S; Iwai, T; Ikeda, H; Takezawa, M; Kikuchi, H; Watanabe, M; Imaizumi, H; Koizumi, W

2011-12-01

Recent progress in chemotherapy has prolonged the survival of patients with malignant biliary strictures, leading to increased rates of stent occlusion. Occlusion of covered metallic stents now occurs in about half of all patients with malignant biliary strictures. The removal of metallic stents followed by placement of a second stent has been attempted, but outcomes remain controversial. The aim of the current study was to evaluate the effectiveness and safety of the primary placement and secondary placement (re-intervention) of covered metallic stents and to assess the feasibility and safety of stent removal. The study included 186 patients with unresectable malignant biliary strictures who underwent primary stent placement between October 2001 and March 2010.  Covered biliary self-expandable metal stents (SEMSs) were removed in 39 of these patients, and 36 underwent re-intervention. The patency times, occlusion rates of the first stent and re-intervention, success rates of stent removal, and complications were investigated. Covered SEMSs were placed in 186 patients. The median patency time of the first stent was 352 days. Stent occlusion occurred in 48.9 % of the patients and was mainly caused by debris or food residue (37 %), dislocation (19 %), and migration with hyperplasia (19 %). Stent removal was attempted in 50 patients and was successful without complication in 39 (78 %). Most of the patients in whom stent removal was unsuccessful had migration with hyperplasia. The median patency time of the second stent was 263 days. The stent patency time did not significantly differ between the first and the second stent. Covered SEMSs could be safely removed at the time of stent occlusion. Patency rates were similar for initial stent placement and re-intervention. © Georg Thieme Verlag KG Stuttgart · New York.

Risk factors and clinical indicators for the development of biliary strictures post liver transplant: Significance of bilirubin

PubMed Central

Forrest, Elizabeth Ann; Reiling, Janske; Lipka, Geraldine; Fawcett, Jonathan

2017-01-01

AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland. METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system. In addition, intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures. RESULTS Of 296 liver transplants performed, 285 (96.3%) were from brain dead donors. Biliary strictures developed in 45 (15.2%) recipients. Anastomotic stricture formation (n = 25, 48.1%) was the commonest complication, with 14 (58.3%) of these occurred within 6-mo of transplant. A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17 (37.8%) patients with biliary strictures. Biliary reconstruction was initially or ultimately required in 22 (48.9%) patients. In recipients developing biliary strictures, bilirubin was significantly increased within the first post-operative week (Day 7 total bilirubin 74 μmol/L vs 49 μmol/L, P = 0.012). In both univariate and multivariate regression analysis, Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation. In addition, hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors. CONCLUSION In addition to known risk factors, bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation. PMID:29312864

Autoimmune hepatitis: diagnostic criteria, subclassifications, and clinical features.

PubMed

McFarlane, Ian G

2002-08-01

The diagnosis of AIH depends on the finding of several suggestive features together with careful exclusion of liver diseases of other etiologies. Wherever possible, the diagnosis should be confirmed histologically by an experienced hepatopathologist. Seronegativity for the conventional autoantibodies at presentation does not exclude a diagnosis of AIH. It is important to test for anti-LKM1 antibodies to avoid missing a diagnosis of type 2 AIH, with potentially serious consequences. Although the syndrome is associated with characteristic biochemical abnormalities, and biochemical parameters are commonly used for monitoring response to therapy, it should be borne in mind that neither these nor autoantibody titers are completely reliable indices of disease activity. Although the various systems that have been promulgated for classification of the disease may identify different groups of patients on pathogenetic or clinical criteria and are useful for research purposes, none is yet sufficiently exclusive in terms of defining prognosis or planning treatment strategies to be applicable to the individual patient seen in the clinic. Clinical management should therefore continue to be individually tailored.

Phrenic Long-Term Facilitation Requires PKCθ Activity within Phrenic Motor Neurons

PubMed Central

Devinney, Michael J.; Fields, Daryl P.; Huxtable, Adrianne G.; Peterson, Timothy J.; Dale, Erica A.

2015-01-01

Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKCθ, and that the relevant PKCθ is within phrenic motor neurons. Whereas spinal PKCθ inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKCθ is highly expressed in phrenic motor neurons, and PKCθ knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKCζ, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKCθ plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKCθ is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons. PMID:26019328

Metabolic profile of liver damage in non-cirrhotic virus C and autoimmune hepatitis: A proton decoupled 31P-MRS study.

PubMed

Hakkarainen, Antti; Puustinen, Lauri; Kivisaari, Reetta; Boyd, Sonja; Nieminen, Urpo; Arkkila, Perttu; Lundbom, Nina

2017-05-01

To study liver 31 P MRS, histology, transient elastography, and liver function tests in patients with virus C hepatitis (HCV) or autoimmune hepatitis (AIH) to test the hypothesis that 31 P MR metabolic profile of these diseases differ. 25 patients with HCV (n=12) or AIH (n=13) underwent proton decoupled 31 P MRS spectroscopy performed on a 3.0T MR imager. Intensities of phosphomonoesters (PME) of phosphoethanolamine (PE) and phosphocholine (PC), phosphodiesters (PDE) of glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC), and γ, α and β resonances of adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide phosphate (NADPH) were determined. Liver stiffness was measured by transient elastography. Inflammation and fibrosis were staged according to METAVIR from biopsy samples. Activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALT) and thromboplastin time (TT) were determined from serum samples. PME had a stronger correlation with AST (z=1.73, p=0.04) and ALT (z=1.77, p=0.04) in HCV than in AIH patients. PME, PME/PDE, PE/GPE correlated positively and PDE negatively with inflammatory activity. PE, PC and PME correlated positively with liver function tests. 31 P-MRS suggests a more serious liver damage in HCV than in AIH with similar histopathological findings. 31 P-MRS is more sensitive in detecting inflammation than fibrosis in the liver. Copyright © 2017 Elsevier B.V. All rights reserved.

The first childhood case with coexisting Hashimoto thyroiditis, vitiligo and autoimmune hepatitis.

PubMed

Keskin, Melikşah; Savaş-Erdeve, Şenay; Özbay-Hoşnut, Ferda; Kurnaz, Erdal; Çetinkaya, Semra; Aycan, Zehra

2016-01-01

Hashimoto thyroiditis (HT) is the most common pediatric autoimmune endocrine disorder. It results in autoimmune-mediated thyroid gland destruction and is an organ-specific, typical autoimmune disease. The presence of antithyroid antibodies and the typical pattern on ultrasonography indicate the diagnosis. It is also frequently seen together with other autoimmune disorders including type 1 insulin-dependent diabetes, celiac disease, alopecia and vitiligo. Autoimmune hepatitis (AIH) is a chronic type of liver injury with an immune etiology that can frequently cause end-stage liver disease if left untreated. Autoimmune hepatitis patients may present with hepatitis, and the laboratory tests in the absence of other etiology usually reveal a positive immune serology together with elevated immunoglobulins and abnormal liver histology. It is interesting that HT and AIH are rarely seen together although both have an autoimmune etiology. 14-year-old male who was being followed-up for vitiligo presented with symptoms of a swelling at the neck and fatigue. He was diagnosed with HT after the tests and the liver enzymes were found to be high. The patient was also diagnosed with AIH after tests revealed that the liver enzyme elevation had continued for longer than six months. The thyroid functions and liver enzymes returned to normal and the symptoms decreased after sodium L-thyroxine replacement together with steroid and azathioprine treatment. We present this case as we believe it is the first pediatric patient diagnosed with HT, AIH and vitiligo.

The White-test helps to reduce biliary leakage in liver resection: a systematic review and meta-analysis.

PubMed

Linke, Richard; Ulrich, Frank; Bechstein, Wolf O; Schnitzbauer, Andreas A

2015-01-01

Bile leakage testing may help to detect and reduce the incidence of biliary leakage after hepatic resection. This review was performed to investigate the value of the White-test in identifying intraoperative biliary leakage and avoiding postoperative leakage. A systematic review and meta-analysis was performed. Two researchers performed literature research. Primary outcome measure was the incidence of post-hepatectomy biliary leakage; secondary outcome measure was the ability of detecting intraoperative biliary leakage with the help of the White-test. A total of 4 publications (including original data from our center) were included in the analysis. Evidence levels of the included studies had medium quality of 2b (individual cohort studies including low quality randomized controlled trials). Use of the White-test led to a significant reduction of post-operative biliary leakage [OR: 0.3 (95% CI: 0.14, 0.63), p = 0.002] and led to a significant higher intraoperative detection of biliary leakages [OR: 0.03 (95%CI: 0.02, 0.07), p < 0.00001]. Existing evidence implicates the use of the White-test after hepatic resection to identify bile leaks intraoperatively and thus reduce incidence of post-operative biliary leakage. Nonetheless, there is a requirement for a high-quality randomized controlled trial with adequately powered sample-size to confirm findings from the above described studies and further increase evidence in this field.

Benign Biliary Strictures and Leaks.

PubMed

Devière, Jacques

2015-10-01

The major causes of benign biliary strictures include surgery, chronic pancreatitis, primary sclerosing cholangitis, and autoimmune cholangitis. Biliary leaks mainly occur after surgery and, rarely, abdominal trauma. These conditions may benefit from a nonsurgical approach in which endoscopic retrograde cholangiopancreatography (ERCP) plays a pivotal role in association with other minimally invasive approaches. This approach should be evaluated for any injury before deciding about the method for repair. ERCP, associated with peroral cholangioscopy, plays a growing role in characterizing undeterminate strictures, avoiding both unuseful major surgeries and palliative options that might compromise any further management. Copyright © 2015 Elsevier Inc. All rights reserved.

Regulators of Cholangiocyte Proliferation.

PubMed

Hall, Chad; Sato, Keisaku; Wu, Nan; Zhou, Tianhao; Kyritsi, Konstantina; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco

2017-02-10

Cholangiocytes, a small population of cells within the normal liver, have been the focus of a significant amount of research over the past two decades because of their involvement in cholangiopathies such as primary sclerosing cholangitis and primary biliary cholangitis. This article summarizes landmark studies in the field of cholangiocyte physiology and aims to provide an updated review of biliary pathogenesis. The historical approach of rodent extrahepatic bile duct ligation and the relatively recent utilization of transgenic mice have led to significant discoveries in cholangiocyte pathophysiology. Cholangiocyte physiology is a complex system based on heterogeneity within the biliary tree and a number of signaling pathways that serve to regulate bile composition. Studies have expanded the list of neuropeptides, neurotransmitters, and hormones that have been shown to be key regulators of proliferation and biliary damage. The peptide histamine and hormones, such as melatonin and angiotensin, angiotensin, as well as numerous sex hormones, have been implicated in cholangiocyte proliferation during cholestasis. Numerous pathways promote cholangiocyte proliferation during cholestasis, and there is growing evidence to suggest that cholangiocyte proliferation may promote hepatic fibrosis. These pathways may represent significant therapeutic potential for a subset of cholestatic liver diseases that currently lack effective therapies.

Use of biliary stent in laparoscopic common bile duct exploration.

PubMed

Lyon, Matthew; Menon, Seema; Jain, Abhiney; Kumar, Harish

2015-05-01

It is well supported in the literature that laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis has equal efficacy when compared to ERCP followed by laparoscopic cholecystectomy. Decompression after supra-duodenal choledochotomy is common practice as it reduced the risk of bile leaks. We conducted a prospective non-randomized study to compare outcomes and length of stay in patients undergoing biliary stent insertion versus T-tube drainage following LCBDE via choledochotomy. The study involved 116 patients with choledocholithiasis who underwent LCBDE and decompression of the biliary system by either ante-grade biliary stent or T-tube insertion. A 7 French straight/duodenal curve biliary Diagmed™ stent (9-11 cm) was placed in 82 patients (Biliary Stent Group). T-tube insertion was used for 34 patients (T-tube group). The length of hospital stay and complications for the selected patients were recorded. All trans-cystic common bile duct explorations were excluded from the study. The mean hospital stay for patients who underwent ante-grade biliary stent or T-tube insertion after LBCDE were 1 and 3.4 days, respectively. This is a statistically significant result with a p value of less than 0.001. Of the T-tube group, two patients required laparoscopic washout due to bile leaks, one had ongoing biliary stasis and one reported ongoing pain whilst the T-tube was in situ. A complication rate of 11.2%, this was a significant finding. There were no complications or concerns reported for the Biliary Stent Group. Our results show that there is a significant reduction in length of hospital stay and morbidity for patients that have ante-grade biliary stent decompression of the CBD post laparoscopic choledochotomy when compared T-tube drainage. This implies that ante-grade biliary stent insertion is likely to reduce costs and increase overall patient satisfaction. We support the use of ante-grade biliary stent insertion during LCBDE when primary closure is not preferred.

Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial.

PubMed

Wiggers, Jimme K; Coelen, Robert J S; Rauws, Erik A J; van Delden, Otto M; van Eijck, Casper H J; de Jonge, Jeroen; Porte, Robert J; Buis, Carlijn I; Dejong, Cornelis H C; Molenaar, I Quintus; Besselink, Marc G H; Busch, Olivier R C; Dijkgraaf, Marcel G W; van Gulik, Thomas M

2015-02-14

Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma. Netherlands Trial Register [ NTR4243 , 11 October 2013].

Chlorambucil for patients with primary biliary cirrhosis.

PubMed

Li, Wei Xin; Yan, Xiang; Shi, Chun Rui; Zhang, Ai Ping

2012-09-12

Chlorambucil has been used for patients with primary biliary cirrhosis as it possesses immunosuppressive properties. But it is unknown whether it benefits or harms these patients. To evaluate the beneficial and any harmful effects of chlorambucil for primary biliary cirrhosis patients. Eligible trials were identified by searching the Cochrane Hepato-Biliary Group Controlled Trials Register (March 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2012, Issue 2), MEDLINE (1946 to March 2012), EMBASE (1974 to March 2012), Science Citation Index EXPANDED (1900 to March 2012), The Chinese Biomedical Database (1976 to March 2012), The Chinese Medical Current Contents (1994 to March 2012), The China Hospital Knowledge Database (1994 to March 2012), and a database of ongoing trials (http://www.controlled-trials.com/mrct/) (accessed 6 March 2012). The reference lists of the retrieved publications and review articles were also read through, and pharmaceutical companies known to produce chlorambucil were contacted. Randomised clinical trials, irrespective of language, year of publication, and publication status, comparing chlorambucil at any dose versus placebo, no intervention, another active drug, or one dose of chlorambucil with another dose. We planned to assess continuous data with mean differences (MD), and dichotomous outcomes with relative risk (RR), both with 95% confidence intervals (CI). As we only identified one trial, Fisher's exact tests were employed. Only one randomised trial was identified and included in the review. The bias risk in the trial was high. The trial compared chlorambucil versus no intervention in 24 patients with primary biliary cirrhosis. Fisher's exact test did not show a significant reduction of mortality when comparing chlorambucil with no treatment (0/13 (0%) versus (2/11 (18.2%); P = 0.20). There was no significant difference regarding adverse events for chlorambucil compared with no treatment, but all patients receiving chlorambucil experienced adverse events (13/13 (100%) versus (3/11 (27%); P = 0.1). According to the authors of the trial, chlorambucil led to a significant improvement in mean serum levels of bilirubin (P < 0.05), albumin (P < 0.05), immunoglobulin M (P < 0.01), serum aspartate aminotransferase activity (P < 0.01), and hepatic inflammatory infiltrates (P < 0.01). There is not sufficient evidence to support or reject the use of chlorambucil for patients with primary biliary cirrhosis. Chlorambucil may show benefit in some unvalidated surrogate outcome measures (for example, serum bilirubin and immunoglobulin M levels). Chlorambucil is, however, connected with a number of adverse events. Bone marrow suppression should be noted in particular. Further randomised clinical trials are necessary to assess the benefits and harms of chlorambucil in this indication.

PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

ClinicalTrials.gov

2018-02-08

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

PubMed

Lokich, J J; Kane, R A; Harrison, D A; McDermott, W V

1987-06-01

Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.

Proposal for Standardized Tabular Reporting of Observational Surgical Studies Illustrated in a Study on Primary Repair of Bile Duct Injuries.

PubMed

Cho, Jai Young; Jaeger, Allison R; Sanford, Dominic E; Fields, Ryan C; Strasberg, Steven M

2015-09-01

A standard format for reporting observational surgical studies does not exist. This creates difficulties in comparing studies and in performing synthesis through systematic reviews and meta-analyses. This article proposes a method called "standard tabular reporting" and illustrates its use in a case series of bile duct reconstructions for biliary injuries occurring during cholecystectomy. A database dealing with biliary injuries was constructed in sections. Each section was designed to be turned into a table covering one element of the subject. Whenever possible, American College of Surgeons NSQIP "Classic Variables and Definitions" were used for forming sections and tables. However, most tables are original and specific to biliary injury. The database was populated from clinical records of patients who sustained a biliary injury during cholecystectomy. Tables were created dealing with the following subjects: demographics, index operation, presentation, classification of injury, preoperative risk assessment, preoperative laboratory values, operative repair technique, postoperative complications, and long-term outcomes. Between 1997 and 2013, 122 primary bile duct reconstructions were performed, with 1 mortality and 47 complications. Good long-term results were obtained in 113 (92.6%) patients. No secondary surgical reconstructions have been needed. Presentation of data in a standard format would facilitate comparison and synthesis of observational studies on the same subject. The biliary reconstructive methods used resulted in very satisfactory outcomes. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Cystic tumors of the liver: A practical approach

PubMed Central

Poggio, Paolo Del; Buonocore, Marco

2008-01-01

Biliary cyst tumors (cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver, but differential diagnosis with multiloculated or complicated biliary cysts, atypical hemangiomas, hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography (CT) and magnetic resonance imaging (MRI) are often not diagnostic and in these cases fine needle aspiration (FNA) is used to confirm the presence of atypical biliary cells. FNA, however, lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma, it is important to exclude liver metastasis, of which colonic cancer is the most common primary site. Multiple biliary hamartomas (von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic, but occasionally a percutaneous biopsy may be required. PMID:18595127

Sera of children with hepatitis C infection and anti-liver-kidney microsome-1 antibodies recognize different CYP2D6 epitopes than adults with LKM+/HCV+ sera.

PubMed

Herzog, D; Yamamoto, A M; Jara, P; Maggiore, G; Sarles, J; Alvarez, F

1999-11-01

Liver-kidney microsome type 1 (LKM1) antibodies are specific markers of autoimmune hepatitis (AIH) type 2. Antibodies to LKM1 have been found in 2% to 3% of adults infected with hepatitis C virus (HCV) without AIH. Thirty percent of these antibodies are directed against linear sequences of CYP2D6 protein. LKM1 antibodies in HCV+/LKM1+ sera and in sera of AIH patients do not recognize the same CYP2D6 epitopes. The current study was conducted to determine whether LKM1 antibodies in HCV+/LKM1+ children's sera are the result of the same immune response as the antibodies described in AIH type 2 and in HCV+/LKM1+ adult patients. Sera from 10 HCV+/LKM1+ children were tested against human liver microsomal and cytosolic proteins by Western blot analysis and against synthetic peptides of the CYP2D6 sequence between amino acids 200 and 429 by dot blot. The same sera were tested against radiolabeled CYP2D6 by immunoprecipitation. Four of 10 sera tested by Western blot analysis showed immunoglobulin (Ig) G-type antibodies against CYP2D6, and 2 had antibodies against proteins of 58, 66, and 84 kDa. One of the sera also contained IgM-type anti-66-kDa and 84-kDa proteins. The radioligand test detected anti-CYP2D6 antibodies in 9 of 10 patients. Five of the anti-CYP2D6-positive sera recognized a peptide between amino acids 200 and 429 including amino acids 254-271. Most HCV+/LKM1+ sera from children recognize conformational epitopes of the CYP2D6 antigen, and half recognize linear epitopes. Some HCV+/LKM1+ sera demonstrated antibodies against the AIH type 2 main antigenic site of the CYP2D6. Screening of HCV RNA should be performed before starting treatment of presumed autoimmune hepatitis associated with LKM1.

Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles.

PubMed

Stephens, Camilla; Castiella, Agustin; Gomez-Moreno, Eva M; Otazua, Pedro; López-Nevot, Miguel-Ángel; Zapata, Eva; Ortega-Alonso, Aida; Ruiz-Cabello, Francisco; Medina-Cáliz, Inmaculada; Robles-Díaz, Mercedes; Soriano, German; Roman, Eva; Hallal, Hacibe; Moreno-Planas, José M; Prieto, Martin; Andrade, Raúl J; Lucena, M Isabel

2016-09-01

Positive autoantibody (AAB) titres are commonly encountered in autoimmune hepatitis (AIH) and in a proportion of drug-induced liver injury (DILI) patients. The underlying mechanism for selective AAB occurrence in DILI is unknown, but could be associated with variations in immune-associated genes. Hence, we aimed to analyse human leucocyte antigen (HLA) allele compositions in DILI with positive (+) and negative (-) AAB titres and in AIH patients. High-resolution genotyping of HLA class I (A, B, C) and II (DRB1, DQB1) loci was performed on 207 DILI and 50 idiopathic AIH patients and compared with 885 healthy Spanish controls. Compared with controls, HLA-B*08:01 [44 vs. 9.7%, P=3.7E-13/corrected P-value (Pc)=1.0E-11], C*07:01 (46 vs. 24%, P=6.4E-04/Pc=0.012), DRB1*03:01 (58 vs. 21.5%, P=5.0E-09/Pc=1.0E-07) and DQB1*02:01 (56 vs. 22%, P=6.8E-08/Pc=9.0E-07) were significantly more frequent in AIH patients. The HLA-A*01:01 frequency was increased in the same population, but did not reach significance after Bonferroni's correction (34 vs. 19%, P=0.02/Pc=0.37). Fifty-eight of 207 DILI patients presented positive titres for at least one AAB (predominantly antinuclear antibody 76% and antismooth muscle antibody 28%). There was a tendency towards higher representation of DRB1*14:01 and DQB1*05:03 in DILI AAB+ compared with DILI AAB- (13.8 vs. 4.0%, P=0.02/Pc=0.5; 13.8 vs. 4.7%, P=0.04/Pc=0.5). The presence of HLA alleles B*08:01, C*07:01, DRB1*03:01, DQB1*02:01 and possibly A*01:01 enhances the risk of AIH (type 1) in Spanish patients. These alleles form part of the ancestral haplotype 8.1. HLA-DRB1*14:01 and DQB1*05:03 could potentially increase the risk of positive AAB (particularly antinuclear antibody) in Spanish DILI patients.

Autoantibody detection in type 2 autoimmune hepatitis using a chimera recombinant protein.

PubMed

Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Alvarez, Fernando

2002-04-01

Autoantibodies against cytochrome P450 2D6 (CYP2D6), known as anti-liver/kidney microsome type 1 (LKM1) and/or anti-human formiminotransferase cyclodeaminase, formally known as anti-liver cytosol type 1 (LC1) define type 2 autoimmune hepatitis (AIH). The aims of this work are to develop a sensitive and specific test to detect anti-LKM1 and/or anti-LC1 autoantibodies and to establish the prevalence of anti-LC1. Sera from children with type 2 AIH (n=48) and those from a control group (n=100) were evaluated for anti-LKM1 and anti-LC1 by Enzyme-Linked Immunosorbent Assay (ELISA) and Western blotting. Each serum sample was assayed for reactivity against formiminotransferase cyclodeaminase and CYP2D6 alone or as part of a recombinant chimera protein. By ELISA with recombinant chimera protein, 50 serum samples were positive, 48 from patients with type 2 AIH and 2 from patients with chronic hepatitis C. Twenty-five of 48 (52%) patients studied were positive for both CYP2D6 and LC1 autoantibodies. Anti-LC1, either as the only marker or associated with anti-LKM1, was positive in 34/48 (71%). By Western blotting, anti-LC1 was found in 27/48 (56%) patients. This ELISA technique has proven to be antigen-specific and more sensitive than Western blot for the detection of anti-LC1 and anti-LKM1 autoantibodies. The prevalence of anti-LC1 (71%) confirms it as an important immunomarker in type 2 AIH.

Intraductal Transanastomotic Stenting in Duct-to-Duct Biliary Reconstruction after Living-Donor Liver Transplantation: A Randomized Trial.

PubMed

Santosh Kumar, K Y; Mathew, Johns Shaji; Balakrishnan, Dinesh; Bharathan, Viju Kumar; Thankamony Amma, Binoj Sivasankara Pillai; Gopalakrishnan, Unnikrishnan; Narayana Menon, Ramachandran; Dhar, Puneet; Vayoth, Sudheer Othiyil; Sudhindran, Surendran

2017-12-01

Biliary complications continue to be the "Achilles heel" of living-donor liver transplantation (LDLT). The use of biliary stents in LDLT to reduce biliary complications is a controversial issue. We performed a randomized trial to study the impact of intraductal biliary stents on postoperative biliary complications after LDLT. Of the 94 LDLTs that were performed during a period of 16 months, ABO-incompatible transplants, left lobe grafts, 3 or more bile ducts on the graft, and those requiring bilioenteric drainage were excluded. Eligible patients were randomized to either a study arm (intraductal stent, n = 31) or a control arm (no stent, n = 33) by block randomization. Stratification was done, based on the number of ducts on the graft requiring anastomosis, into single (n = 20) or 2 ducts (n = 44). Ureteric stents of 3F to 5F placed across the biliary anastomosis and exiting into the duodenum for later endoscopic removal at 3 months were used. The primary end point was postoperative bile leak. Bile leak occurred in 15 of 64 (23.4%), the incidence was higher in the stented group compared with the control group (35.5% vs 12.1%; p = 0.03). Multiplicity of bile ducts and stenting were identified as risk factors for bile leak on multivariate analysis (p = 0.031 and p = 0.032). During a median follow-up of 2 years, biliary stricture developed in 9 patients (14.1%). Postoperative bile leak is a significant risk factor for the development of biliary stricture (p = 0.003). Intraductal transanastomotic biliary stenting and multiplicity of graft ducts were identified as independent risk factors for the development of postoperative biliary complications. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Autoimmune hepatitis in childhood: the role of genetic and immune factors.

PubMed

Ferri Liu, Priscila Menezes; de Miranda, Débora Marques; Fagundes, Eleonora Druve Tavares; Ferreira, Alexandre Rodrigues; Simões e Silva, Ana Cristina

2013-07-28

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.

Autoimmune hepatitis in childhood: The role of genetic and immune factors

PubMed Central

Ferri Liu, Priscila Menezes; de Miranda, Débora Marques; Fagundes, Eleonora Druve Tavares; Ferreira, Alexandre Rodrigues; Simões e Silva, Ana Cristina

2013-01-01

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population. PMID:23901220

Spatiotemporal Airy Ince-Gaussian wave packets in strongly nonlocal nonlinear media.

PubMed

Peng, Xi; Zhuang, Jingli; Peng, Yulian; Li, DongDong; Zhang, Liping; Chen, Xingyu; Zhao, Fang; Deng, Dongmei

2018-03-08

The self-accelerating Airy Ince-Gaussian (AiIG) and Airy helical Ince-Gaussian (AihIG) wave packets in strongly nonlocal nonlinear media (SNNM) are obtained by solving the strongly nonlocal nonlinear Schrödinger equation. For the first time, the propagation properties of three dimensional localized AiIG and AihIG breathers and solitons in the SNNM are demonstrated, these spatiotemporal wave packets maintain the self-accelerating and approximately non-dispersion properties in temporal dimension, periodically oscillating (breather state) or steady (soliton state) in spatial dimension. In particular, their numerical experiments of spatial intensity distribution, numerical simulations of spatiotemporal distribution, as well as the transverse energy flow and the angular momentum in SNNM are presented. Typical examples of the obtained solutions are based on the ratio between the input power and the critical power, the ellipticity and the strong nonlocality parameter. The comparisons of analytical solutions with numerical simulations and numerical experiments of the AiIG and AihIG optical solitons show that the numerical results agree well with the analytical solutions in the case of strong nonlocality.

Fatal chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis.

PubMed

Chiba, Tetsuhiro; Goto, Shigemasa; Yokosuka, Osamu; Imazeki, Fumio; Tanaka, Masamichi; Fukai, Kenichi; Takahashi, Yoko; Tsujimura, Hideki; Saisho, Hiromitsu

2004-02-01

We report a 22-year-old female who presented with pyrexia, pancytopenia and liver dysfunction. The patient showed mild liver dysfunction with low-grade fever and mild hepatosplenomegaly 6 years previously, and autoimmune hepatitis (AIH) was diagnosed based on the examination of the laboratory data and liver biopsy. On admission, both markers of Epstein-Barr virus (EBV) and in-situ hybridisation from a liver biopsy specimen indicated chronic active EBV infection (CAEBV). The patient was administered an immunosuppressive agent and antiviral drug added to steroid therapy, but ultimately died from liver failure and virus-associated haemophagocytosis 10 months after the definite diagnosis. Retrospective examination of the serum at the diagnosis of AIH revealed extremely high titres of antibody to EBV, and EBV-DNA was also detectable by polymerase chain reaction. These results suggest the possibility that the patient may already have suffered from CAEBV at the initial diagnosis. We presume that hepatic involvement of CAEBV should be considered as differential diagnosis in cases showing liver dysfunction with clinical and biochemical features observed in AIH.

Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2018-03-22

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Chronic Intermittent Hypoxia Blunts the Expression of Ventilatory Long Term Facilitation in Sleeping Rats.

PubMed

Edge, Deirdre; O'Halloran, Ken D

2015-01-01

We have previously reported that chronic intermittent hypoxia (CIH), a central feature of human sleep-disordered breathing, causes respiratory instability in sleeping rats (Edge D, Bradford A, O'halloran KD. Adv Exp Med Biol 758:359-363, 2012). Long term facilitation (LTF) of respiratory motor outputs following exposure to episodic, but not sustained, hypoxia has been described. We hypothesized that CIH would enhance ventilatory LTF during sleep. We examined the effects of 3 and 7 days of CIH exposure on the expression of ventilatory LTF in sleeping rats. Adult male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5 % O(2) at nadir; SaO(2) ~ 80 %) per hour, 8 h per day for 3 or 7 consecutive days (CIH, N = 7 per group). Corresponding sham groups (N = 7 per group) were subjected to alternating cycles of air under identical experimental conditions in parallel. Following gas exposures, breathing during sleep was assessed in unrestrained, unanaesthetized animals using the technique of whole-body plethysmography. Rats were exposed to room air (baseline) and then to an acute IH (AIH) protocol consisting of alternating periods of normoxia (7 min) and hypoxia (FiO(2) 0.1, 5 min) for 10 cycles. Breathing was monitored during the AIH exposure and for 1 h in normoxia following AIH exposure. Baseline ventilation was elevated after 3 but not 7 days of CIH exposure. The hypoxic ventilatory response was equivalent in sham and CIH animals after 3 days but ventilatory responses to repeated hypoxic challenges were significantly blunted following 7 days of CIH. Minute ventilation was significantly elevated following AIH exposure compared to baseline in sham but not in CIH exposed animals. LTF, determined as the % increase in minute ventilation from baseline following AIH exposure, was significantly blunted in CIH exposed rats. In summary, CIH leads to impaired ventilatory responsiveness to AIH. Moreover, CIH blunts ventilatory LTF. The physiological significance of ventilatory LTF is context-dependent but it is reasonable to consider that it can potentially destabilize respiratory control, in view of the potential for LTF to give rise to hypocapnia. CIH-induced blunting of LTF may represent a compensatory mechanism subserving respiratory homeostasis. Our results suggest that CIH-induced increase in apnoea index (Edge D, Bradford A, O'halloran KD. Adv Exp Med Biol 758:359-363, 2012) is not related to enhanced ventilatory LTF. We conclude that the mature adult respiratory system exhibits plasticity and metaplasticity with potential consequences for the control of respiratory homeostasis. Our results may have implications for human sleep apnoea.

[A study of the value of preoperative biliary-tract drainage in the treatment of periampullary tumours: the DROP-trial].

PubMed

van der Gaag, N A; Gouma, D J

2006-03-04

Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumour is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. More recently, the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. This has raised doubts as to whether biliary drainage should always be performed in these patients. The project referred to above involves a randomised multicentre trial to compare the outcome of a 'preoperative biliary-drainage strategy' (standard strategy) with that of an 'early-surgery' strategy with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

PubMed

Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

2015-09-22

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial.

PubMed

Christensen, E; Neuberger, J; Crowe, J; Altman, D G; Popper, H; Portmann, B; Doniach, D; Ranek, L; Tygstrup, N; Williams, R

1985-11-01

The effect of azathioprine on survival of patients with primary biliary cirrhosis was studied prospectively in a multinational, double-blind, randomized clinical trial including 248 patients of whom 127 received azathioprine and 121 placebo. There were 57 deaths in the azathioprine group and 62 in the placebo group. The actual survival was slightly longer during azathioprine than during placebo treatment. Using Cox multiple regression analysis and adjusting for slight imbalance between the two treatment groups, the therapeutic effect of azathioprine was statistically significant (p = 0.01), with azathioprine reducing the risk of dying to 59% of that observed during placebo treatment (95% confidence interval 40%-90%) or improving survival time by 20 mo in the average patient. Furthermore, azathioprine slowed down progressing incapacitation. Side effects of azathioprine were relatively few. The analysis revealed that the following five variables independently implied poor prognosis: high serum bilirubin, old age, cirrhosis, low serum albumin, and central cholestasis. These factors were combined to a "prognostic index" for prediction of outcome in new patients. The index was validated on independent patient data. On the basis of these results we recommend azathioprine as a routine treatment of primary biliary cirrhosis.

Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

ClinicalTrials.gov

2017-02-10

Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Percutaneous Intraductal Radiofrequency Ablation Combined with Biliary Stent Placement for Nonresectable Malignant Biliary Obstruction Improves Stent Patency but not Survival.

PubMed

Wang, Jianfeng; Zhao, Lizhen; Zhou, Chuanguo; Gao, Kun; Huang, Qiang; Wei, Baojie; Gao, Jun

2016-04-01

Although radiofrequency (RF) ablation has been accepted as a curative treatment modality for solid organ tumors, intraductal RF ablation for malignant biliary obstruction has not been widely described. The aim of this study was to evaluate the feasibility, safety, and efficacy (in terms of stent patency and survival) of intraductal RF ablation combined with biliary stent placement for nonresectable malignant biliary obstruction. A search of the nonresectable malignant extrahepatic biliary obstruction database (179 patients) identified 18 consecutive patients who were treated with biliary intraluminal RF ablation during percutaneous transhepatic cholangiodrainage and inner stent placement (RF ablation group) and 18 patients who underwent inner stent placement without biliary intraluminal RF ablation (control group). The patients were matched for tumor type, location of obstruction, tumor stage, and Child-Pugh class status. Primary endpoints included safety, stent patency time, and survival rates. The secondary endpoint was effectiveness of the technique. The RF ablation and control groups were closely matched in terms of age, diagnosis, presence of metastases, presence of locally advanced tumor, American Society of Anesthesiologists (ASA) grade, and chemotherapy regimen (all P > 0.05). The technical success rate for both groups was 100%. The median time of stent patency in the RF ablation and control groups were 5.8 (2.8-11.5) months and 4.5 (2.4-8.0) months, respectively (Kaplan-Meier analysis: P = 0.03). The median survival times in the RF ablation and control groups were 6.1 (4.8-15.2) months and 5.8 (4.2-16.5) months, with no significant difference according to Kaplan-Meier analysis (P = 0.45). In univariate and multivariate analyses, poorer overall survival was associated with advanced age and presence of metastases (P < 0.05). Intraductal RF ablation combined with biliary stent placement for nonresectable malignant biliary obstruction is safe and feasible and effectively increases stent patency time. However, it does not improve patient survival.

Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis.

PubMed

Choudhuri, K; Gregorio, G V; Mieli-Vergani, G; Vergani, D

1998-11-01

We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.

A case report of osteomalacia unmasking primary biliary cirrhosis.

PubMed

Pawlowska, M; Kapeluto, J E; Kendler, D L

2015-07-01

Osteomalacia, a metabolic bone disease characterized by the inability to mineralize new osteoid, can be caused by vitamin D deficiency. We report a patient with symptomatic, biochemical, and imaging evidence of osteomalacia due to vitamin D deficiency, who as a result of work up for bone disease was diagnosed with early primary biliary cirrhosis. Osteomalacia was treated with high-dose vitamin D and serial bone density scans showed evidence of increasing bone mineral density suggesting osteoid mineralization in response to treatment. The diagnosis of cholestatic liver disease should be considered in all patients presenting with osteomalacia due to vitamin D deficiency, particularly if other cholestatic liver enzymes are elevated in addition to alkaline phosphatase.

Isolated segmental, sectoral and right hepatic bile duct injuries

PubMed Central

Colovic, Radoje B

2009-01-01

The treatment of isolated segmental, sectoral and right hepatic bile duct injuries is controversial. Nineteen patients were treated over a 26-year period. Group one was comprised of 4 patients in whom the injury was primarily repaired during the original surgery; 3 over a T-tube, 1 with a Roux-en-Y. These patients had an uneventful recovery. The second group consisted of 5 patients in whom the duct was ligated; 4 developed infection, 3 of which required drainage and biliary repair. Two patients had good long-term outcomes; the third developed a late anastomotic stricture requiring further surgery. The fourth patient developed a small bile leak and pain which resolved spontaneously. The fifth patient developed complications from which he died. The third group was comprised of 4 patients referred with biliary peritonitis; all underwent drainage and lavage, and developed biliary fistulae, 3 of which resolved spontaneously, 1 required Roux-en-Y repair, with favorable outcomes. The fourth group consisted of 6 patients with biliary fistulae. Two patients, both with an 8-wk history of a fistula, underwent Roux-en-Y repair. Two others also underwent a Roux-en-Y repair, as their fistulae showed no signs of closure. The remaining 2 patients had spontaneous closure of their biliary fistulae. A primary repair is a reasonable alternative to ligature of injured duct. Patients with ligated ducts may develop complications. Infected ducts require further surgery. Patients with biliary peritonitis must be treated with drainage and lavage. There is a 50% chance that a biliary fistula will close spontaneously. In cases where the biliary fistula does not close within 6 to 8 wk, a Roux-en-Y anastomosis should be considered. PMID:19322912

Multicenter study of endoscopic preoperative biliary drainage for malignant distal biliary obstruction

PubMed Central

Sasahira, Naoki; Hamada, Tsuyoshi; Togawa, Osamu; Yamamoto, Ryuichi; Iwai, Tomohisa; Tamada, Kiichi; Kawaguchi, Yoshiaki; Shimura, Kenji; Koike, Takero; Yoshida, Yu; Sugimori, Kazuya; Ryozawa, Shomei; Kakimoto, Toshiharu; Nishikawa, Ko; Kitamura, Katsuya; Imamura, Tsunao; Mizuide, Masafumi; Toda, Nobuo; Maetani, Iruru; Sakai, Yuji; Itoi, Takao; Nagahama, Masatsugu; Nakai, Yousuke; Isayama, Hiroyuki

2016-01-01

AIM: To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary obstruction. METHODS: Multicenter retrospective study was conducted in patients who underwent plastic stent (PS) or nasobiliary catheter (NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedure-related adverse events, stent/catheter dysfunction (occlusion or migration of PS/NBC, development of cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution (bilirubin level < 3.0 mg/dL) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression analysis. RESULTS: In total, 419 patients were included in the study (PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients (46%), bile duct cancer in 172 (41%), gallbladder cancer in three (1%), and ampullary cancer in 50 (12%). The median serum total bilirubin was 7.8 mg/dL and 324 patients (77%) had ≥ 3.0 mg/dL. During the median time to surgery of 29 d [interquartile range (IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio (SHR) = 4.76; 95%CI: 2.44-10.0, P < 0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method (PS or NBC). CONCLUSION: PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored. PMID:27076764

A phenomenological study of fatigue in patients with primary biliary cirrhosis.

PubMed

Jorgensen, Roberta

2006-09-01

This paper reports the findings of research on the lived experience of fatigue in patients with primary biliary cirrhosis - a type of chronic liver disease. Fatigue is a universal phenomenon, commonly associated with both acute and chronic illness, but also seen in healthy individuals. However, it is not often addressed in healthcare encounters despite its disabling nature, perhaps because of the multitude of contributing factors and the lack of effective treatments. It is a common and debilitating symptom in patients with primary biliary cirrhosis. Despite the prevalence of fatigue in this condition, patients' experiences of this symptom have not been researched. An interpretive-phenomenological approach developed by van Manen was chosen and this combines features of descriptive and interpretive phenomenology. Eight participants were interviewed during 2005 about their fatigue experience. Thematic analysis was conducted. Five themes were identified: an unreliable body, fatigue as always present yet insidious, planning a life to conserve energy, struggling to maintain normality and emotional consequences. These themes reflected the unrelenting, intrusive nature of fatigue into the lives of those affected. This research will provide empathic insight into the fatigue experience in this condition and generate communication about coping strategies. It will add to the body of research on fatigue in chronic conditions and may generate ideas for intervention research.

Lack of cilia and differentiation defects in the liver of human foetuses with the Meckel syndrome.

PubMed

Clotman, Frédéric; Libbrecht, Louis; Killingsworth, Murray C; Loo, Christine C K; Roskams, Tania; Lemaigre, Frédéric P

2008-03-01

Meckel syndrome is an autosomal-recessive disease characterized by a combination of renal cysts, anomalies of the central nervous system, polydactyly and ductal plate malformations (DPM), which are hepatic anomalies consisting of excessive and abnormal foetal biliary structures. Among the genomic loci associated with Meckel syndrome, mutations in four genes were recently identified. These genes code for proteins associated with primary cilia and are possibly involved in cell differentiation. The aim of the present work was to investigate the formation of the primary cilia and the differentiation of the hepatic cells in foetuses with Meckel syndrome. Sections of livers from human foetuses with Meckel syndrome were analysed by immunofluorescence, immunohistochemistry and electron microscopy. The primary cilia of the biliary cells were absent in some Meckel foetuses, but were present in others. In addition, defects in hepatic differentiation were observed in Meckel livers, as evidenced by the presence of hybrid cells co-expressing hepatocytic and biliary markers. Defects in cilia formation occur in some Meckel livers, and most cases show DPM associated with abnormal hepatic cell differentiation. Because differentiation precedes the formation of the cilia during liver development, we propose that defective differentiation may constitute the initial defect in the liver of Meckel syndrome foetuses.

The Association between Gravidity and Primary Biliary Cirrhosis

PubMed Central

PARIKH-PATEL, ARTI; GOLD, ELLEN; UTTS, JESSICA; GERSHWIN, M. ERIC

2011-01-01

PURPOSE Primary biliary cirrhosis is an autoimmune disease with female predominance that leads to liver failure. The goal of this study was to identify reproductive risk factors associated with this disease. METHODS We compared 182 cases of PBC with 225 age- and sex-matched friend controls to examine the role of reproductive factors. The survey instrument was developed using standardized questions obtained from the National Health and Nutrition Examination Survey (NHANES) III. RESULTS A total of 126/182 cases (69%) and 141/225 (62.6%) friend controls responded to the survey. More cases than controls reported ever having genitourinary infection [adjusted odds ratio (OR) = 2.12, 95% confidence interval (CI) 1.01, 4.42] among those without a personal or family history of autoimmune disease. The most notable finding was that cases reported significantly more pregnancies than controls (p = 0.008). The adjusted OR for each additional pregnancy among those without a personal or family history of autoimmune disease was 1.40 (95% CI 1.14, 1.7). More controls (24.4%) than cases (16.0%) were nulliparous. Cases reported having five or more children (16.0%) with double the frequency of controls (8.2%). CONCLUSIONS The association reported herein, between primary biliary cirrhosis and gravidity, is particularly significant because of the overwhelming female predominance. PMID:11988415

[Imaging of the intrahepatic biliary tree with thick slice MR cholangiography].

PubMed

Leclerc, J C; Cannard, L; Lefèvre, F; Debelle, L; Béot, S; Boccaccini, H; Bazin, C; Régent, D

2001-02-01

To assess the value of single shot fast spin echo MR sequence (SS-FSE) in the evaluation of the normal and pathologic intrahepatic biliary tree. 418 consecutive patients (457 examinations) referred for clinical and/or biological suspicion of biliary obstruction underwent MR cholangiopancreatography (MRCP). All patients were imaged with a Signa 1.5 T GE MR unit, with High Gradient Field Strength and Torso Phased Array Coil. Biliary ducts were imaged with SS-FSE sequence, coronal and oblique coronal 20 mm thick slices on a 256 x 256 matrix. Total acquisition time was 1 second. Source images were reviewed by two radiologists blinded to clinical information. In case of disagreement, a third radiologist's opinion was requested. In all cases, MRCP results were compared with direct biliary tract evaluation, other imaging studies and clinical and biological follow-up. In all cases, MRCP produced high quality images. Numerous branch of division were observed although the peripheral intrahepatic ducts were well seen in more than 90% in an area 2 cm below the capsule. The number of division was statistically higher when mechanical obstruction was present. Intrahepatic calculi or peripheral cholangiocarcinoma were well detect by MRCP. For the detection of cholangitis, MRCP sensitivity was 87.5% but the positive predictive value was only 57.7% because of a high number of false positive. The diagnosis of primary sclerosing cholangitis must be made only on strict criteria and slightly dilated peripheral bile ducts unconnected to the central ducts in several hepatic segments were a characteristic MR sign of primary sclerosing cholangitis. MRCP can be proposed as a first intention imaging technique for the evaluation of intrahepatic ducts.

Antireflux Versus Conventional Plastic Stent in Malignant Biliary Obstruction: A Prospective Randomized Study.

PubMed

Vihervaara, Hanna; Grönroos, Juha M; Hurme, Saija; Gullichsen, Risto; Salminen, Paulina

2017-01-01

Endoscopic stents are used to relieve obstructive jaundice. The purpose of this prospective randomized study was to compare the patency of antireflux and conventional plastic biliary stent in relieving distal malignant biliary obstruction. All jaundiced patients admitted to hospital with suspected unresectable malignant distal biliary stricture between October 2009 and September 2010 were evaluated for the study. Eligible patients were randomized either to antireflux or conventional plastic stent arms. The primary endpoint was stent patency and the follow-up was continued either until the stent was occluded or until 6 months after the stent placement. At an interim analysis, antireflux stents (ARSs; n = 6) had a significantly shorter median patency of 34 (8-49) days compared with the conventional stent (n = 7) patency of 167 (38-214) days (P = .0003). Based on these results, the study was terminated due to ethical concerns. According to these results, the use of this ARS is not recommended.

Role of endoscopic retrograde cholangiopancreatography in the management of benign biliary strictures: What’s new?

PubMed Central

Ferreira, Rosa; Loureiro, Rui; Nunes, Nuno; Santos, António Alberto; Maio, Rui; Cravo, Marília; Duarte, Maria Antónia

2016-01-01

Benign biliary strictures comprise a heterogeneous group of diseases. The most common strictures amenable to endoscopic treatment are post-cholecystectomy, post-liver transplantation, related to primary sclerosing cholangitis and to chronic pancreatitis. Endoscopic treatment of benign biliary strictures is widely used as first line therapy, since it is effective, safe, noninvasive and repeatable. Endoscopic techniques currently used are dilation, multiple plastic stents insertion and fully covered self-expandable metal stents. The main indication for dilation alone is primary sclerosing cholangitis related strictures. In the vast majority of the remaining cases, temporary placement of multiple plastic stents with/without dilation is considered the treatment of choice. Although this approach is effective, it requires multiple endoscopic sessions due to the short duration of stent patency. Fully covered self-expandable metal stents appear as a good alternative to plastic stents, since they have an increased radial diameter, longer stent patency, easier insertion technique and similar efficacy. Recent advances in endoscopic technique and various devices have allowed successful treatment in most cases. The development of novel endoscopic techniques and devices is still ongoing. PMID:26962404

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2016-10-01

Obeticholic acid (Ocaliva) for primary biliary cholangitis; sofosbuvir 400 mg/velpatasvir 100 mg (Epclusa) for chronic hepatitis C virus infection; and daclizumab (Zinbryta) for relapsing multiple sclerosis.

Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis.

PubMed

Parés, Albert; Cisneros, Laura; Salmerón, Joan M; Caballería, Llorenç; Mas, Antoni; Torras, Albert; Rodés, Juan

2004-06-01

Pruritus is a distressing symptom in patients with primary biliary cirrhosis, and when uncontrollable it is an indication for liver transplantation. Since pruritus can result from unknown substances that accumulate systemically as a consequence of impaired biliary secretion, we have assessed whether a new extracorporeal albumin dialysis (ECAD) procedure, the molecular-adsorbing recirculating system-MARS, has any effect on pruritus of cholestasis. Four patients with primary biliary cirrhosis and resistant pruritus were treated with two 7-h ECAD sessions 1 day apart. Pruritus was recorded from 15 days before the first session, before and after each session, and during the follow-up using a visual analogue scale (VAS). Standard liver tests as well as serum bile acid levels were also measured. There was a clear association between ECAD treatment and relief of itching, which promptly disappeared in two patients, or decreased markedly in the other two. One patient was free of pruritus for 18 months except for short periods with mild pruritus. The second patient experienced amelioration of itching, which almost disappeared completely and recurred mildly 4 months later. In the other two patients pruritus was alleviated markedly after ECAD but gradually recurred. These two patients were treated again 9 and 7 months later with favorable effects on pruritus. The scratching skin lesions improved or disappeared in parallel with the alleviation of itching. The albumin dialysis procedure did not result in liver test changes, except for circulating bile acids, which decreased in all the patients. No significant adverse effects were observed. The ECAD procedure seems to be an effective alternative for the treatment of patients with pruritus of cholestasis who do not respond to other therapeutic methods.

Treatment of benign biliary leaks with transhepatic placement of coated self-expanding metallic stents.

PubMed

Páramo, M; García-Barquín, P; Carrillo, M; Millor Muruzábal, M; Vivas, I; Bilbao, J I

To analyze the safety and efficacy of percutaneous placement of coated self-expanding metallic stents (SEMS) in patients with biliary leaks. This ethics committee at our center approved this study. We retrospectively reviewed all coated SEMS placed between October 2008 and September 2015. We analyzed patient-related factors such as the primary underlying disease, prior hepatic procedures, and clinical outcome. We evaluated the location, the number and type of leak (anastomotic or non-anastomotic), and the characteristics of the interventional procedure (number of stents deployed, location of the stents, technical success, and primary functionality). We recorded the complications registered. We studied 14 patients (11 men and 3 women). The mean follow-up period was 375.5 days (range 15-1920 days). Leaks were postsurgical in 12 patients. One patient developed an arteriobilioportal fistula. In another, the biliary leak occurred secondary to the rupture of the common bile duct after ERCP. A total of 23 coated SEMS were placed, including 21 Fluency ® stents (Bard, Tempe, AZ, USA) and 2 Wallflex ® stents (Boston Scientific, Galway, Republic of Ireland). The technical success of the procedure was considered total in 11 (78.6%) patients, partial in 2 (14.3%) patients, and null in 1 (7.2%) patient. The clinical outcome was good in 13 of the 14 patients. The mean period of primary functionality of the coated SEMS was 331 days (range 15-1920 days). No major complications were observed in 11 (78.6%) patients. Percutaneous placement of coated SEMS for the treatment of benign biliary leaks is safe and efficacious, with a high rate of technical and clinical success and a moderate rate of complications. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparison of intraductal ultrasonography-directed and cholangiography-directed endoscopic retrograde biliary drainage in patients with a biliary obstruction.

PubMed

Rew, Soo-Jung; Lee, Du-Hyeon; Park, Chang-Hwan; Jeon, Jin; Kim, Hyun-Soo; Choi, Sung-Kyu; Rew, Jong-Sun

2016-09-01

Endoscopic retrograde biliary drainage (ERBD) has become a standard procedure in patients with a biliary obstruction. Intraductal ultrasonography (IDUS) has emerged as a new tool for managing extrahepatic biliary diseases. IDUS-directed ERBD can be performed without conventional cholangiography (CC). The goal of this study was to assess the effectiveness and safety of IDUS-directed ERBD compared to CC-directed ERBD in patients with an extrahepatic biliary obstruction. A total of 210 patients who had undergone IDUS-directed ERBD (IDUS-ERBD, n = 105) and CC-directed ERBD (CC-ERBD, n = 105) between October 2013 and April 2014 were analyzed retrospectively. The primary outcome measure was the procedural success rate. Secondary outcome measures included clinical outcomes, total procedure time, radiation exposure time, and overall complication rates. The total technical success rate of ERBD was 100% (105/105) in the IDUS-ERBD and CC-ERBD groups. Mean procedure time was slightly prolonged in the IDUS-ERBD group than that in the CC-ERBD group (32.1 ± 9.9 minutes vs. 28.4 ± 11.6 minutes, p = 0.023). Mean radiation exposure time was one-third less in the IDUS-ERBD group than that in the CC-ERBD group (28.0 ± 49.3 seconds vs. 94.2 ± 57.3 seconds, p < 0.001). No significant differences in complication rates were detected between the groups. IDUS-ERBD was equally effective and safe as CC-ERBD in patients with an extrahepatic biliary obstruction. Although IDUS-ERBD increased total procedure time, it significantly decreased radiation exposure.

Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients.

PubMed

Lau, James Y W; Leow, Chon-Kar; Fung, Terence M K; Suen, Bing-Yee; Yu, Ly-Mee; Lai, Paul B S; Lam, Yuk-Hoi; Ng, Enders K W; Lau, Wan Yee; Chung, Sydney S C; Sung, Joseph J Y

2006-01-01

In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.

Ursodeoxycholic acid for primary biliary cirrhosis.

PubMed

Rudic, Jelena S; Poropat, Goran; Krstic, Miodrag N; Bjelakovic, Goran; Gluud, Christian

2012-12-12

Ursodeoxycholic acid is administered to patients with primary biliary cirrhosis, a chronic progressive inflammatory autoimmune-mediated liver disease with unknown aetiology. Despite its controversial effects, the U.S. Food and Drug Administration has approved its usage for primary biliary cirrhosis. To assess the beneficial and harmful effects of ursodeoxycholic acid in patients with primary biliary cirrhosis. We searched for eligible randomised trials in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform. The literature search was performed until January 2012. Randomised clinical trials assessing the beneficial and harmful effects of ursodeoxycholic acid versus placebo or 'no intervention' in patients with primary biliary cirrhosis. Two authors independently extracted data. Continuous data were analysed using mean difference (MD) and standardised mean difference (SMD). Dichotomous data were analysed using risk ratio (RR). Meta-analyses were conducted using both a random-effects model and a fixed-effect model, with 95% confidence intervals (CI). Random-effects model meta-regression was used to assess the effects of covariates across the trials. Trial sequential analysis was used to assess risk of random errors (play of chance). Risks of bias (systematic error) in the included trials were assessed according to Cochrane methodology bias domains. Sixteen randomised clinical trials with 1447 patients with primary biliary cirrhosis were included. One trial had low risk of bias, and the remaining fifteen had high risk of bias. Fourteen trials compared ursodeoxycholic acid with placebo and two trials compared ursodeoxycholic acid with 'no intervention'. The percentage of patients with advanced primary biliary cirrhosis at baseline varied from 15% to 83%, with a median of 51%. The duration of the trials varied from 3 to 92 months, with a median of 24 months. The results showed no significant difference in effect between ursodeoxycholic acid and placebo or 'no intervention' on all-cause mortality (45/699 (6.4%) versus 46/692 (6.6%); RR 0.97, 95% CI 0.67 to 1.42, I² = 0%; 14 trials); on all-cause mortality or liver transplantation (86/713 (12.1%) versus 89/706 (12.6%); RR 0.96, 95% CI 0.74 to 1.25, I² = 15%; 15 trials); on serious adverse events (94/695 (13.5%) versus 107/687 (15.6%); RR 0.87, 95% CI 0.68 to 1.12, I² = 23%; 14 trials); or on non-serious adverse events (27/643 (4.2%) versus 18/634 (2.8%); RR 1.46, 95% CI 0.83 to 2.56, I² = 0%; 12 trials). The random-effects model meta-regression showed that the risk of bias of the trials, disease severity of patients at entry, ursodeoxycholic acid dosage, and trial duration were not significantly associated with the intervention effects on all-cause mortality, or on all-cause mortality or liver transplantation. Ursodeoxycholic acid did not influence the number of patients with pruritus (168/321 (52.3%) versus 166/309 (53.7%); RR 0.96, 95% CI 0.84 to 1.09, I² = 0%; 6 trials) or with fatigue (170/252 (64.9%) versus 174/244 (71.3%); RR 0.90, 95% CI 0.81 to 1.00, I² = 62%; 4 trials). Two trials reported the number of patients with jaundice and showed a significant effect of ursodeoxycholic acid versus placebo or no intervention in a fixed-effect meta-analysis (5/99 (5.1%) versus 15/99 (15.2%); RR 0.35, 95% CI 0.14 to 0.90, I² = 51%; 2 trials). The result was not supported by the random-effects meta-analysis (RR 0.56, 95% CI 0.06 to 4.95). Portal pressure, varices, bleeding varices, ascites, and hepatic encephalopathy were not significantly affected by ursodeoxycholic acid. Ursodeoxycholic acid significantly decreased serum bilirubin concentration (MD -8.69 µmol/l, 95% CI -13.90 to -3.48, I² = 0%; 881 patients; 9 trials) and activity of serum alkaline phosphatases (MD -257.09 U/L, 95% CI -306.25 to -207.92, I² = 0%; 754 patients, 9 trials) compared with placebo or no intervention. These results were supported by trial sequential analysis. Ursodeoxycholic acid also seemed to improve serum levels of gamma-glutamyltransferase, aminotransferases, total cholesterol, and plasma immunoglobulin M concentration. Ursodeoxycholic acid seemed to have a beneficial effect on worsening of histological stage (random; 66/281 (23.5%) versus 103/270 (38.2%); RR 0.62, 95% CI 0.44 to 0.88, I² = 35%; 7 trials). This systematic review did not demonstrate any significant benefits of ursodeoxycholic acid on all-cause mortality, all-cause mortality or liver transplantation, pruritus, or fatigue in patients with primary biliary cirrhosis. Ursodeoxycholic acid seemed to have a beneficial effect on liver biochemistry measures and on histological progression compared with the control group. All but one of the included trials had high risk of bias, and there are risks of outcome reporting bias and risks of random errors as well. Randomised trials with low risk of bias and low risks of random errors examining the effects of ursodeoxycholic acid for primary biliary cirrhosis are needed.

What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study.

PubMed

Lilford, Richard J; Bentham, Louise M; Armstrong, Matthew J; Neuberger, James; Girling, Alan J

2013-06-20

Evaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. A prospective observational study. 11 UK primary care practices. Patients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). Patients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. Regression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. The LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care.

Primary Gastric Lymphoma Presenting as Acute Pancreatitis: A Case Report.

PubMed

Raj, Mithun; Ghoshal, Uday C; Choudhuri, Gourdas; Mohindra, Samir

2013-07-10

Diffuse large B-cell lymphoma is the commonest form of non-Hodgkin lymphoma. Gastro-intestinal tract and bone marrow are common extra-nodal sites of lymphomatous involvement. A 54-year-old woman presented with acute onset epigastric pain. On evaluation, raised serum amylase and radiological features of acute pancreatitis were detected. Gastroscopy revealed thickened folds in distal stomach, which on histopathology revealed large B-cell lymphoma. Subsequently, the patient developed extra-hepatic biliary obstruction due to peripancreatic lymph nodal mass that was relieved with plastic biliary stenting. Subsequent chemotherapy regime directed against lymphoma led to resolution of lymphoma. In this patient , pancreatitis was the initial presentation of primary gastric lymphoma, which has not been commonly reported and therefore should be considered in the etiological workup.

Mitochondrial antibodies in primary biliary cirrhosis

PubMed Central

Berg, P. A.; Roitt, I. M.; Doniach, D.; Cooper, H. M.

1969-01-01

The effect on the mitochondrial antigen of different agents known to influence the integrity and structure of membranes has been studied using quantitative complement fixation with autoantibodies from the serum of a patient with primary biliary cirrhosis. The susceptibility to proteolytic enzymes suggests that the antigen is a protein. Activity depends upon an association with phospholipids. Addition of phospholipids prevents loss of antigen during artificial ageing of mitochondria at 37°. Activity is lost after treatment with phospholipases or solvents which extract phospholipids. Antigen is also destroyed by surface active agents which dissociate the link with phospholipid but those which weaken bonds between phospholipids and hydrophobic molecules yield fragments of antigen-containing membrane structures which, nonetheless, still react with the mitochondrial autoantibody. ImagesFIG. 2FIG. 4 PMID:5804537

Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

PubMed Central

Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

2013-01-01

Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

A case of polyglandular autoimmune syndrome type III complicated with autoimmune hepatitis.

PubMed

Oki, Kenji; Yamane, Kiminori; Koide, Junko; Mandai, Koichi; Nakanishi, Shuhei; Fujikawa, Rumi; Kohno, Nobuoki

2006-10-01

A 58-year-old woman complaining of finger tremor was referred to our hospital. The diagnosis of Graves' disease was made based on increased free triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (<0.005 microIU/ml) and increased TSH receptor binding antibody activity (70.9%). Serum level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis with piecemeal necrosis. Although antinuclear antibody was negative, these findings indicated that she had autoimmune hepatitis (AIH) according to the criteria of the International Autoimmune Hepatitis Scoring System. Slowly progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti-glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies. This case exhibited an extremely rare combination of three different autoimmune diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and had no known sensitive human leukocyte antigen (HLA) typing or haplotype for these disorders. Although it is common for patients with Graves' disease to exhibit abnormal liver function, it is important to make an accurate diagnosis of AIH because of this life-threatening disorder.

Detection on immunoblot of new proteins from the soluble fraction of the cell recognized either by anti-liver-kidney microsome antibodies type 1 or by anti-liver cytosol antibodies type 1--relationship with hepatitis C virus infection.

PubMed

Ballot, E; Desbos, A; Monier, J C

1996-09-01

Antibodies directed against liver cytosol protein, called anti-liver cytosol type 1 (LC1 Ab), have been described by both immunofluorescence (IF) and immunodiffusion techniques in sera from patients with autoimmune hepatitis (AIH). They have never been found in association with antibodies directed against the hepatitis C virus (HCV), unlike the anti-liver-kidney microsome antibodies type 1 (LKM1 Ab), the serological marker of AIH type 2. This suggests that there are two subgroups of AIH type 2, i.e., HCV-related and non-HCV-related. In this study, immunoblotting experiments were performed using proteins from the soluble phase of the rat liver cell; 141 sera which tested positive for LKM1 Ab by IF, 24 identified as having LC1 Ab by IF, and 50 from blood donors as controls were analyzed. Three bands were stained by LC1 Ab sera more often than by the control sera, and with a statistically significant frequency. These 3 proteins were located at apparent Mr 50,000, 55,000, and 60,000. The LKM1 Ab-positive sera as defined by IF stained six bands with a statistically significant frequency compared to the controls. Their apparent Mr were 35,000, 39,000, 47,000, 50,000, 55,000, and 60,000. LKM1 Ab-positive sera which were anti-HCV negative recognized a 60,000 protein belonging to the soluble phase of the cell, with a statistically significant frequency compared to LKM1 Ab-positive sera which were anti-HCV positive. This 60,000 protein was also recognized by LC1 Ab-positive sera, which were almost always anti-HCV negative. The presence of antibodies against a 60,000 protein from the soluble phase of the cell is discussed in terms of the anti-HCV serological markers found in the sera from patients with AIH.

Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS

PubMed Central

Nichols, Nicole L.; Satriotomo, Irawan; Harrigan, Daniel J.; Mitchell, Gordon S.

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated superoxide dismutase-1 (SOD1G93A), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1G93A (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600µM; 12µL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms preserving/enhancing the capacity for pLTF in MT rats are not known. PMID:26287750

Recruitment and plasticity in diaphragm, intercostal, and abdominal muscles in unanesthetized rats

PubMed Central

Navarrete-Opazo, A.

2014-01-01

Although rats are a frequent model for studies of plasticity in respiratory motor control, the relative capacity of rat accessory respiratory muscles to express plasticity is not well known, particularly in unanesthetized animals. Here, we characterized external intercostal (T2, T4, T5, T6, T7, T8, T9 EIC) and abdominal muscle (external oblique and rectus abdominis) electromyogram (EMG) activity in unanesthetized rats via radiotelemetry during normoxia (Nx: 21% O2) and following acute intermittent hypoxia (AIH: 10 × 5-min, 10.5% O2; 5-min intervals). Diaphragm and T2–T5 EIC EMG activity, and ventilation were also assessed during maximal chemoreceptor stimulation (MCS: 7% CO2, 10.5% O2) and sustained hypoxia (SH: 10.5% O2). In Nx, T2 EIC exhibits prominent inspiratory activity, whereas T4, T5, T6, and T7 EIC inspiratory activity decreases in a caudal direction. T8 and T9 EIC and abdominal muscles show only tonic or sporadic activity, without consistent respiratory activity. MCS increases diaphragm and T2 EIC EMG amplitude and tidal volume more than SH (0.94 ± 0.10 vs. 0.68 ± 0.05 ml/100 g; P < 0.001). Following AIH, T2 EIC EMG amplitude remained above baseline for more than 60 min post-AIH (i.e., EIC long-term facilitation, LTF), and was greater than diaphragm LTF (41.5 ± 1.3% vs. 19.1 ± 2.0% baseline; P < 0.001). We conclude that 1) diaphragm and rostral T2–T5 EIC muscles exhibit inspiratory activity during Nx; 2) MCS elicits greater ventilatory, diaphragm, and rostral T2–T5 EIC muscle activity vs. SH; and 3) AIH induces greater rostral EIC LTF than diaphragm LTF. PMID:24833779

Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.

PubMed

Schepers, Nicolien J; Bakker, Olaf J; Besselink, Marc G H; Bollen, Thomas L; Dijkgraaf, Marcel G W; van Eijck, Casper H J; Fockens, Paul; van Geenen, Erwin J M; van Grinsven, Janneke; Hallensleben, Nora D L; Hansen, Bettina E; van Santvoort, Hjalmar C; Timmer, Robin; Anten, Marie-Paule G F; Bolwerk, Clemens J M; van Delft, Foke; van Dullemen, Hendrik M; Erkelens, G Willemien; van Hooft, Jeanin E; Laheij, Robert; van der Hulst, René W M; Jansen, Jeroen M; Kubben, Frank J G M; Kuiken, Sjoerd D; Perk, Lars E; de Ridder, Rogier J J; Rijk, Marno C M; Römkens, Tessa E H; Schoon, Erik J; Schwartz, Matthijs P; Spanier, B W Marcel; Tan, Adriaan C I T L; Thijs, Willem J; Venneman, Niels G; Vleggaar, Frank P; van de Vrie, Wim; Witteman, Ben J; Gooszen, Hein G; Bruno, Marco J

2016-01-05

Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).

Treatment of Biliary Stricture After Live Donor Liver Transplantation With Combined Metal and Plastic Stent Insertion: A Feasibility and Safety Study.

PubMed

Parlak, Erkan; Koksal, Aydin Seref; Eminler, Ahmet Tarik; Toka, Bilal; Uslan, Mustafa Ihsan

2017-08-01

Fully covered self-expandable metal stents (Fc-SEMSs) have a challenging use in the treatment of anastomosis strictures after live donor liver transplantation (LDLT) because they can occlude secondary branch biliary ducts when placed above the biliary bifurcation. In this study, we evaluated the technical feasibility and safety of combining Fc-SEMSs with plastic stent(s) inserted to the secondary branch biliary ducts for the treatment of anastomosis stricture after LDLT. The study group included 22 patients (12 men, aged 51±11 years) with anastomotic biliary stricture after LDLT. A Fc-SEMS, 8 to 10 mm in diameter, was inserted to the straight, dilated main duct and plastic stent(s) were inserted to the secondary branches to avoid their occlusion. Stents were left in place for 2 months and removed with a stent retrieving forceps. Technical feasibilities, including technical success, successful removal, and adverse events of this novel strategy, were evaluated. Fc-SEMSs were successfuly deployed and removed in all of the cases. Three (13.6%) patients had pain requiring intravenous analgesia and Fc-SEMS had to be removed because of unbearable pain in one of them. Three (13.6%) patients developed cholangitis due to occlusion of unrecognized secondary branch biliary ducts. Primary stricture resolution rate was achieved in 17 (89.5%) of 19 patients. Recurrence was observed in 3 (17.6%) patients after a mean follow-up duration of 154.3±52.6 (range, 104-304) days. Combination of Fc-SEMS and plastic stent(s) is technically feasible and safe for the treatment of anastomotic biliary strictures after LDLT.

What Comes after Ursodeoxycholic Acid in Primary Biliary Cholangitis?

PubMed

Wong, Lin Lee; Hegade, Vinod S; Jones, David E J

2017-01-01

Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by chronic cholestasis. Treatment with the accepted primary therapy ursodeoxycholic acid (UDCA) has been shown to be associated with delayed disease progression probably through reduced impact of cholestatic injury on the target biliary epithelial cells. Patients with inadequate response to UDCA (which can be identified through validated biochemical criteria) are at increased risk of disease progression, need for liver transplantation, and death. Obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a second-line therapy in PBC and has been recently licensed by the Food and Drug Administration and European Medicines Agency for use in patients showing an inadequate response to UDCA or who are unable to tolerate it. Although evidence for biochemical improvement by OCA is compelling, there is, as yet, no evidence that OCA improves hard clinical outcomes or quality of life. In addition, OCA may not be suitable for PBC patients with pruritus as it can worsen the symptom. Other novel agents currently in clinical development may have better side-effect profile. Fibrates have the potential but currently lack high quality evidence to support their routine clinical use in PBC. Symptom management of PBC is challenging and ASBT inhibitors and rituximab are being evaluated for pruritus and fatigue, respectively. © 2017 S. Karger AG, Basel.

Recent advances in the diagnosis and treatment of primary biliary cholangitis

PubMed Central

Huang, Ying-Qiu

2016-01-01

Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients. PMID:27957241

Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC).

PubMed

Ji, Jun Ho; Song, Haa-Na; Kim, Rock Bum; Oh, Sung Yong; Lim, Ho Yeong; Park, Joon Oh; Park, Se Hoon; Kim, Moon Jin; Lee, Soon Il; Ryou, Sung Hyeok; Hwang, In Gyu; Jang, Joung-Soon; Kim, Hong Jun; Choi, Jun Young; Kang, Jung-Hun

2015-03-01

Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known. We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0-2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated. Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as >4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as >100 U/ml) [hazard ratio 1.93 (P = 0.001)]. Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen 19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Toward precision medicine in primary biliary cholangitis.

PubMed

Carbone, Marco; Ronca, Vincenzo; Bruno, Savino; Invernizzi, Pietro; Mells, George F

2016-08-01

Primary biliary cholangitis is a chronic, cholestatic liver disease characterized by a heterogeneous presentation, symptomatology, disease progression and response to therapy. In contrast, clinical management and treatment of PBC is homogeneous with a 'one size fits all' approach. The evolving research landscape, with the emergence of the -omics field and the availability of large patient cohorts are creating a unique opportunity of translational epidemiology. Furthermore, several novel disease and symptom-modifying agents for PBC are currently in development. The time is therefore ripe for precision medicine in PBC. In this manuscript we describe the concept of precision medicine; review current approaches to risk-stratification in PBC, and speculate how precision medicine in PBC might develop in the near future. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Endoscopic bilio-duodenal bypass: outcomes of primary and revision efficacy of combined metallic stents in malignant duodenal and biliary obstructions.

PubMed

Canena, Jorge; Coimbra, João; Carvalho, Diana; Rodrigues, Catarina; Silva, Mário; Costa, Mariana; Horta, David; Mateus Dias, António; Seves, Isabel; Ramos, Gonçalo; Ricardo, Leonel; Coutinho, António Pereira; Romão, Carlos; Veiga, Pedro Mota

2014-11-01

Self-expandable metal stents (SEMSs) can be used for palliation of combined malignant biliary and duodenal obstructions. However, the results of the concomitant stent placement for the duration of the patients' lives, as well as the need for and efficacy of endoscopic revision, are unclear. This study evaluated the clinical effectiveness of SEMS placement for combined biliary and duodenal obstructions throughout the patients' lives and the need for endoscopic revision. This study is a retrospective multicenter study of 50 consecutive patients who underwent simultaneous or sequential SEMS placement for malignant biliary and duodenal obstructions. The data were collected to analyze the sustained relief of obstructive symptoms until the patients' death and the efficacy of endoscopic revision, as well as stent patency, adverse events, survival and prognostic factors for stent patency. Technical and immediate clinical success was achieved in all of the patients. Duodenal stricture occurred before the papilla in 35 patients (70 %), involved the papilla in 11 patients (22 %) and was observed distal to the papilla in four patients (8 %). Initial biliary stenting was performed endoscopically in 42 patients (84 %) and percutaneously in eight patients. After combined stenting, 30 patients (60 %) required no additional intervention until the time of their death. The remaining 20 patients were successfully treated using endoscopic stent reinsertion: nine patients needed biliary revision, three patients needed duodenal restenting and eight patients needed both biliary and duodenal reinsertion. The median duodenal stent patency and median biliary stent patency were 34 and 27 weeks, respectively. The median survival after combined stent placement was 18 weeks. A Cox multivariate analysis showed that duodenal stent obstruction after combined stenting was a risk factor for biliary stent obstruction (hazard ratio 6.85; 95 % confidence interval 1.43-198.98; P = 0.025). Endoscopic bilio-duodenal bypass is clinically effective, and the majority of the patients need no additional intervention until their death. Endoscopic revision is feasible and has a high success rate.

Secondary sclerosing cholangitis in critically ill patients.

PubMed

Peña-Pérez, Carlos Alberto; Ponce-Medrano, Juan Alberto Díaz

2018-01-01

Primary sclerosing cholangitis (PSC) is a rare idiopathic condition with immunopathogenic mechanisms where there is chronic progressive destruction of the biliary tree. Secondary sclerosing cholangitis (SSC) is clinically comparable to PSC, but is caused by specific processes which directly damage the biliary tree; examples include recurrent pancreatitis, bile duct malignancy, congenital bile duct abnormalities. A new cause of SSC has been described during or following significant critical illness associated with severe respiratory insufficiency, vasopressor requirement, shock and sepsis. This condition rapidly progresses to cirrhosis, frequently requiring liver transplantation for definitive management. Copyright: © 2018 Permanyer.

[Total thyroidectomy in patients with amiodarone-induced hyperthyroidism: when does the risk of conservative treatment exceed the risk of surgery?].

PubMed

Meerwein, C; Vital, D; Greutmann, M; Schmid, C; Huber, G F

2014-02-01

Amiodarone plays a pivotal role in the treatment of ventricular and supraventricular arrhythmias. However, amiodarone-induced hyperthyroidism (AIH) is one of the most feared complications, which necessitates interdisciplinary treatment and careful balancing of the risks of conservative treatment against those of total thyroidectomy. In this article we discuss the pharmacological aspects of amiodarone and its diverse effects on the thyroid. Furthermore, we present diagnostic and therapeutic strategies and report our positive experiences with total thyroidectomy in patients with AIH. Particularly in patients for whom continuation of amiodarone treatment is compulsory, a well-timed total thyroidectomy is a reliable therapeutic option, with minimal complication rates and immediate amelioration of symptoms.

Obeticholic Acid

PubMed Central

Smith, Susan M.; Pegram, Angela H.

2017-01-01

Objective: To review the pharmacology, efficacy, and safety of obeticholic acid (OCA) and determine its clinical role relative to other agents in the treatment of patients with primary biliary cholangitis (PBC). Data Sources: A PubMed search (1946 to November 2016) was conducted using the terms INT-747, obeticholic acid, OCA, farnesoid X receptor agonists, FXR agonists, primary biliary cirrhosis, and primary biliary cholangitis. Study Selection and Data Extraction: Phase II and III studies evaluating the use of OCA in PBC patients were included in this review. Data Synthesis: OCA, a farnesoid X receptor (FXR) agonist, is indicated for adult patients with PBC in combination with ursodeoxycholic acid (UDCA) or as monotherapy if unable to tolerate UDCA. Two clinical trials were identified evaluating OCA for the treatment of PBC. Study end points utilized biochemical markers (alkaline phosphatase [ALP] and bilirubin). A phase II study (n = 165) to determine efficacy and safety of OCA at 3 different doses (10 mg, 25 mg, 50 mg) demonstrated statistically significant reductions in ALP (P < .0001 for all OCA groups versus placebo) after 12 weeks. A phase III trial (n = 217) assessed lower OCA doses (5 mg and 10 mg) with a longer study duration (12 months). Statistically significant differences (P < .001) between the 5 to 10 mg group (46%) and the 10 mg group (47%) compared to the placebo group (10%) were found. The primary adverse effect reported in both trials was pruritus. Conclusions: OCA is the first FXR agonist approved for the treatment of PBC. Ongoing research to evaluate clinical outcomes with OCA is currently underway.

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy.

PubMed

Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

2016-07-14

To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

PubMed Central

Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

2016-01-01

AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient’s morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs. PMID:27468198

New classification system for indications for endoscopic retrograde cholangiopancreatography predicts diagnoses and adverse events.

PubMed

Yuen, Nicholas; O'Shaughnessy, Pauline; Thomson, Andrew

2017-12-01

Indications for endoscopic retrograde cholangiopancreatography (ERCP) have received little attention, especially in scientific or objective terms. To review the prevailing ERCP indications in the literature, and to propose and evaluate a new ERCP indication system, which relies on more objective pre-procedure parameters. An analysis was conducted on 1758 consecutive ERCP procedures, in which contemporaneous use was made of an a-priori indication system. Indications were based on the objective pre-procedure parameters and divided into primary [cholangitis, clinical evidence of biliary leak, acute (biliary) pancreatitis, abnormal intraoperative cholangiogram (IOC), or change/removal of stent for benign/malignant disease] and secondary [combination of two or three of: pain attributable to biliary disease ('P'), imaging evidence of biliary disease ('I'), and abnormal liver function tests (LFTs) ('L')]. A secondary indication was only used if a primary indication was not present. The relationship between this newly developed classification system and ERCP findings and adverse events was examined. The indications of cholangitis and positive IOC were predictive of choledocholithiasis at ERCP (101/154 and 74/141 procedures, respectively). With respect to secondary indications, only if all three of 'P', 'I', and 'L' were present there was a statistically significant association with choledocholithiasis (χ 2 (1) = 35.3, p < .001). Adverse events were associated with an unusual indication leading to greater risk of unplanned hospitalization (χ 2 (1) = 17.0, p < .001). An a-priori-based indication system for ERCP, which relies on pre-ERCP objective parameters, provides a more useful and scientific classification system than is available currently.

Primary biliary cirrhosis

MedlinePlus

... stools Itching Poor appetite and weight loss As liver function worsens, symptoms may include: Fluid buildup in the ... your liver is working properly: Albumin blood test Liver function tests (serum alkaline phosphatase is most important) Prothrombin ...

Primary Biliary Cirrhosis

MedlinePlus

... other complications. Increased pressure in the portal vein (portal hypertension). Blood from your intestine, spleen and pancreas enters ... specific complications: Increased pressure in the portal vein (portal hypertension). Your doctor is likely to screen and monitor ...

Randomized controlled trial of perioperative antimicrobial therapy based on the results of preoperative bile cultures in patients undergoing biliary reconstruction.

PubMed

Okamura, Kunishige; Tanaka, Kimitaka; Miura, Takumi; Nakanishi, Yoshitsugu; Noji, Takehiro; Nakamura, Toru; Tsuchikawa, Takahiro; Okamura, Keisuke; Shichinohe, Toshiaki; Hirano, Satoshi

2017-07-01

The high frequency of surgical site infections (SSIs) after hepato-pancreato-biliary (HPB) surgery is a problem that needs to be addressed. This prospective, randomized, controlled study examined whether perioperative prophylactic use of antibiotics based on preoperative bile culture results in HPB surgery could decrease SSI. Participants comprised 126 patients who underwent HPB (bile duct, gallbladder, ampullary, or pancreatic) cancer surgery with biliary reconstruction at Hokkaido University Hospital between August 2008 and March 2013 (UMIN Clinical Trial Registry #00001278). Before surgery, subjects were randomly allocated to a targeted group administered antibiotics based on bile culture results or a standard group administered cefmetazole. The primary endpoint was SSI rates within 30 days after surgery. Secondary endpoint was SSI rates for each operative procedure. Of the 126 patients, 124 were randomly allocated (targeted group, n = 62; standard group, n = 62). Frequency of SSI after surgery was significantly lower in the targeted group (27 patients, 43.5%) than in the standard group (44 patients, 71.0%; P = 0.002). Among patients who underwent pancreaticoduodenectomy and hepatectomy, SSI occurred significantly less frequently in the targeted group (P = 0.001 and P = 0.025, respectively). This study demonstrated that preoperative bile culture-targeted administration of prophylactic antibiotics decreased SSIs following HBP surgery with biliary reconstruction. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge.

PubMed

Kakimoto, Toshiaki; Kanemoto, Hideyuki; Fukushima, Kenjiro; Ohno, Koichi; Tsujimoto, Hajime

2017-02-01

OBJECTIVE To examine bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge. ANIMALS 18 dogs with gallbladder mucocele (GBM group), 8 dogs with immobile biliary sludge (i-BS group), 17 dogs with mobile biliary sludge (m-BS group), and 14 healthy dogs (control group). PROCEDURES Samples of gallbladder contents were obtained by use of percutaneous ultrasound-guided cholecystocentesis or during cholecystectomy or necropsy. Concentrations of 15 bile acids were determined by use of highperformance liquid chromatography, and a bile acid compositional ratio was calculated for each group. RESULTS Concentrations of most bile acids in the GBM group were significantly lower than those in the control and m-BS groups. Compositional ratio of taurodeoxycholic acid, which is 1 of 3 major bile acids in dogs, was significantly lower in the GBM and i-BS groups, compared with ratios for the control and m-BS groups. The compositional ratio of taurocholic acid was significantly higher and that of taurochenodeoxycholic acid significantly lower in the i-BS group than in the control group. CONCLUSIONS AND CLINICAL RELEVANCE In this study, concentrations and fractions of bile acids in gallbladder contents were significantly different in dogs with gallbladder mucocele or immobile biliary sludge, compared with results for healthy control dogs. Studies are needed to determine whether changes in bile acid composition are primary or secondary events of gallbladder abnormalities.

Partial stent-in-stent placement of biliary metallic stents using a short double-balloon enteroscopy.

PubMed

Tsutsumi, Koichiro; Kato, Hironari; Tomoda, Takeshi; Matsumoto, Kazuyuki; Sakakihara, Ichiro; Yamamoto, Naoki; Noma, Yasuhiro; Sonoyama, Takayuki; Okada, Hiroyuki; Yamamoto, Kazuhide

2012-12-07

Endoscopic intervention is less invasive than percutaneous or surgical approaches and should be considered the primary drainage procedure in most cases with obstructive jaundice. Recently, therapeutic endoscopic retrograde cholangiopancreatography (ERCP) using double-balloon enteroscopy (DBE) has been shown to be feasible and effective, even in patients with surgically altered anatomies. On the other hand, endoscopic partial stent-in-stent (PSIS) placement of self-expandable metallic stents (SEMSs) for malignant hilar biliary obstruction in conventional ERCP has also been shown to be feasible, safe and effective. We performed PSIS placement of SEMSs for malignant hilar biliary obstruction due to liver metastasis using a short DBE in a patient with Roux-en-Y anastomosis and achieved technical and clinical success. This procedure can result in quick relief from obstructive jaundice in a single session and with short-term hospitalization, even in patients with surgically altered anatomies.

Systematic review with meta-analysis of studies comparing primary duct closure and T-tube drainage after laparoscopic common bile duct exploration for choledocholithiasis.

PubMed

Podda, Mauro; Polignano, Francesco Maria; Luhmann, Andreas; Wilson, Michael Samuel James; Kulli, Christoph; Tait, Iain Stephen

2016-03-01

With advances in laparoscopic instrumentation and acquisition of advanced laparoscopic skills, laparoscopic common bile duct exploration (LCBDE) is technically feasible and increasingly practiced by surgeons worldwide. Traditional practice of suturing the dochotomy with T-tube drainage may be associated with T-tube-related complications. Primary duct closure (PDC) without a T-tube has been proposed as an alternative to T-tube placement (TTD) after LCBDE. The aim of this meta-analysis was to evaluate the safety and effectiveness of PDC when compared to TTD after LCBDE for choledocholithiasis. A systematic literature search was performed using PubMed, EMBASE, MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials databases for studies comparing primary duct closure and T-tube drainage. Studies were reviewed for the primary outcome measures: overall postoperative complications, postoperative biliary-specific complications, re-interventions, and postoperative hospital stay. Secondary outcomes assessed were: operating time, median hospital expenses, and general complications. Sixteen studies comparing PDC and TTD qualified for inclusion in our meta-analysis, with a total of 1770 patients. PDC showed significantly better results when compared to TTD in terms of postoperative biliary peritonitis (OR 0.22, 95% CI 0.06-0.76, P = 0.02), operating time (WMD, -22.27, 95% CI -33.26 to -11.28, P < 0.00001), postoperative hospital stay (WMD, -3.22; 95% CI -4.52 to -1.92, P < 0.00001), and median hospital expenses (SMD, -1.37, 95% CI -1.96 to -0.77, P < 0.00001). Postoperative hospital stay was significantly decreased in the primary duct closure with internal biliary drainage (PDC + BD) group when compared to TTD group (WMD, -2.68; 95% CI -3.23 to -2.13, P < 0.00001). This comprehensive meta-analysis demonstrates that PDC after LCBDE is feasible and associated with fewer complications than TTD. Based on these results, primary duct closure may be considered as the optimal procedure for dochotomy closure after LCBDE.

Molecular diagnostic testing for primary biliary cholangitis.

PubMed

Gatselis, Nikolaos K; Dalekos, George N

2016-09-01

A reliable liver autoimmune serology for the diagnosis of primary biliary cholangitis (PBC) is of particular importance. Recognition of patients at early stages and prompt treatment initiation may alter the outcome, slow progression, delays liver failure, and improves survival. In this review, we summarize and discuss the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) and our own experience on the current and potential molecular based approaches to the diagnosis of PBC. Expert commentary: Standardization of liver diagnostic serology and clinical governance are two major points as antimitochondrial antibodies are the diagnostic hallmark of the disease and PBC-specific antinuclear antibodies could assist in the diagnosis and estimation of prognosis. New biomarkers such as novel autoantibodies, genetic polymorphisms, metabolomic profiling, micro-RNA and epigenetics may assist to the understanding, diagnosis and management of the disease.

Sidechain biology and the immunogenicity of PDC-E2, the major autoantigen of primary biliary cirrhosis.

PubMed

Mao, Tin K; Davis, Paul A; Odin, Joseph A; Coppel, Ross L; Gershwin, M Eric

2004-12-01

The E2 component of mitochondrial pyruvate dehydrogenase complex (PDC-E2) is the immunodominant autoantigen of primary biliary cirrhosis. Whereas lipoylation of PDC-E2 is essential for enzymatic activity and predominates under normal conditions, other biochemical systems exist that also target the lysine residue, including acylation of fatty acids or xenobiotics and ubiquitinylation. More importantly, the immunogenicity can be affected by derivatization of the lysine residue, as the recognition of lipoylated PDC-E2 by patient autoantibodies is enhanced compared with octanoylated PDC-E2. Furthermore, our laboratory has shown that various xenobiotic modifications of a peptide representing the immunodominant region of PDC-E2 are immunoreactive against patient sera. The only purported regulatory system that prevents the accumulation of potentially autoreactive PDC-E2 is glutathionylation, in which the lysine-lipoic acid moiety is further modified with glutathione during apoptosis. Interestingly, this system is found in several cell lines, including HeLa, Jurkat, and Caco-2 cells, but not in cholangiocytes and salivary gland epithelial cells, both of which are targets for destruction in primary biliary cirrhosis. Hence, the failure of this or other regulatory system(s) may overwhelm the immune system with immunogenic PDC-E2 that can initiate the breakdown of tolerance in a genetically susceptible individual. In this review the authors survey the data available on the biochemical life of PDC-E2, with particular emphasis on the lysine residue and its known interactions with machinery involved in various posttranslational modifications.

Hepatocellular carcinoma in patients with autoimmune liver diseases: two case reports and literature review.

PubMed

Meza-Junco, Judith; Montaño-Loza, Aldo J; Martínez-Benitez, Braulio; Kimura-Hayama, Eric

2007-01-01

Hepatocellular carcinoma has been reported as a rare complication of autoimmune liver diseases. We describe herein two patients with this neoplasia associated with autoimmune hepatitis and primary biliary cirrhosis, and we also review the literature. The first case corresponds to a 49-year-old woman presented for evaluation of right upper abdominal pain. She had been diagnosed with autoimmune hepatitis 4 years before. Alpha-fetoprotein was markedly elevated and an abdominal MRI showed a 10 cm x 9.0 cm mass. She received transarterial chemoembolization, and currently the disease has progressed to the lungs and bones, and she is on supportive care. The second case corresponds to a 68-year-old woman presented for evaluation of a liver mass found in a screening ultrasound. She had been diagnosed with primary biliary cirrhosis 5 years previously. At admission alpha-fetoprotein was 1000 ng/mL and an abdominal MRI revealed a 4 cm x 3 cm liver tumor. She was treated with percutaneous radiofrequency ablation getting complete response, and currently she has no evidence of neoplastic disease. These two patients constitute the only cases of hepatocellular carcinoma associated to autoimmune liver diseases that have been attended in our Institute. These cases highlight that hepatocellular carcinoma secondary to autoimmune hepatitis and primary biliary cirrhosis, although rare, can occur in the absence of coexistent viral hepatitis, or excessive alcohol consumption. The utility of screening for hepatocellular carcinoma in autoimmune liver diseases is still not defined.

Imaging follow-up after liver transplantation

PubMed Central

Rossi, Massimo; Mennini, Gianluca; Melandro, Fabio; Anzidei, Michele; De Vizio, Silvia; Koryukova, Kameliya; Catalano, Carlo

2016-01-01

Liver transplantation (LT) represents the best treatment for end-stage chronic liver disease, acute liver failure and early stages of hepatocellular carcinoma. Radiologists should be aware of surgical techniques to distinguish a normal appearance from pathological findings. Imaging modalities, such as ultrasound, CT and MR, provide for rapid and reliable detection of vascular and biliary complications after LT. The role of imaging in the evaluation of rejection and primary graft dysfunction is less defined. This article illustrates the main surgical anastomoses during LT, the normal appearance and complications of the liver parenchyma and vascular and biliary structures. PMID:27188846

An Update to Hepatobiliary Stents

PubMed Central

Moy, Brian T.; Birk, John W.

2015-01-01

Endoscopic stent placement is a common primary management therapy for benign and malignant biliary strictures. However, continuous use of stents is limited by occlusion and migration. Stent technology has evolved significantly over the past two decades to reduce these problems. The purpose of this article is to review current guidelines in managing malignant and benign biliary obstructions, current endoscopic techniques for stent placement, and emerging stent technology. What began as a simple plastic stent technology has evolved significantly to include uncovered, partially covered, and fully covered self-expanding metal stents (SEMS) as well as magnetic, bioabsorbable, drug-eluting, and antireflux stents.1 PMID:26357636

Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation.

PubMed

Corral, Juan E; Mousa, Omar Y; Krishna, Murli; Levink, Iris J M; Pursell, Khela R; Afsh, Mohammad; Kröner, Paul T; Harnois, Denise M; Wolfsen, Herbert C; Wallace, Michael B; Lukens, Frank J

2018-06-18

 Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators.  25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity.  VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo. © Georg Thieme Verlag KG Stuttgart · New York.

Extrahepatic biliary atresia in a border collie.

PubMed

Schulze, C; Rothuizen, J; van Sluijs, F J; Hazewinkel, H A; van den Ingh, T S

2000-01-01

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.

Biliary plastic stent does not influence the accuracy of endoscopic ultrasound-guided sampling of pancreatic head masses performed with core biopsy needles.

PubMed

Antonini, Filippo; Fuccio, Lorenzo; Giorgini, Sara; Fabbri, Carlo; Frazzoni, Leonardo; Scarpelli, Marina; Macarri, Giampiero

2017-08-01

While the presence of biliary stent significantly decreases the accuracy of endoscopic ultrasound (EUS) for pancreatic head cancer staging, its impact on the EUS-guided sampling accuracy is still debated. Furthermore, data on EUS-fine needle biopsy (EUS-FNB) using core biopsy needles in patients with pancreatic mass and biliary stent are lacking. The aim of this study was to evaluate the influence of biliary stent on the adequacy and accuracy of EUS-FNB in patients with pancreatic head mass. All patients who underwent EUS-guided sampling with core needles of solid pancreatic head masses causing obstructive jaundice were retrospectively identified in a single tertiary referral center. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without biliary stent, was the primary outcome measure. The diagnostic accuracy and complication rate were the secondary outcome measures. A total of 130 patients with pancreatic head mass causing biliary obstruction were included in the study: 74 cases of them were sampled without stent and 56 cases with plastic stent in situ. The adequacy was 96.4% in the stent group and 90.5% in the group without stent (p=0.190). No significant differences were observed for sensitivity (88.9% vs. 85.9%), specificity (100% for both groups), and accuracy (89.3% vs. 86.5%) between those with and without stent, respectively. The accuracy was not influenced by the timing of stenting (<48h or ≥48h before EUS). No EUS-FNB related complications were recorded. The presence of biliary stent does not influence the tissue sampling adequacy, the diagnostic accuracy and the complication rate of EUS-FNB of pancreatic head masses performed with core biopsy needles. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The natural history of autoimmune hepatitis presenting with jaundice.

PubMed

Panayi, Vasilis; Froud, Oliver J; Vine, Louisa; Laurent, Paul; Woolson, Kathy L; Hunter, Jeremy G; Madden, Richard G; Miller, Catherine; Palmer, Jo; Harris, Nicola; Mathew, Joe; Stableforth, Bill; Murray, Iain A; Dalton, Harry R

2014-06-01

Forty percent of patients with autoimmune hepatitis (AIH) present with acute jaundice/hepatitis. Such patients, when treated promptly, are thought to have a good prognosis. The objective of this study was to describe the natural history of AIH in patients presenting with jaundice/hepatitis and to determine whether the diagnosis could have been made earlier, before presentation. This study is a retrospective review of 2249 consecutive patients who presented with jaundice to the Jaundice Hotline clinic, Truro, Cornwall, UK, over 15 years (1998-2013) and includes a review of the laboratory data over a 23-year period (1990-2013). Of the 955 patients with hepatocellular jaundice, 47 (5%) had criterion-referenced AIH: 35 female and 12 male, the median age was 65 years (range 15-91 years); the bilirubin concentration was 139 μmol/l (range 23-634 μmol/l) and the alanine transaminase level was 687 IU/l (range 22-2519 IU/l). Among the patients, 23/46 (50%) were cirrhotic on biopsy; 11/47 (23%) died: median time from diagnosis to death, 5 months (range 1-59); median age, 72 years (range 59-91 years). All 8/11 patients who died of liver-related causes were cirrhotic. Weight loss (P=0.04) and presence of cirrhosis (P=0.004) and varices (P=0.015) were more common among those who died. Among patients who died from liver-related causes, 6/8 (75%) died less than 6 months from diagnosis. Cirrhosis at presentation and oesophageal varices were associated with early liver-related deaths (P=0.011, 0.002 respectively). Liver function test results were available in 33/47 (70%) patients before presentation. Among these patients, 16 (49%) had abnormal alanine transaminase levels previously, and eight (50%) were cirrhotic at presentation. AIH presenting as jaundice/hepatitis was mainly observed in older women: 50% of the patients were cirrhotic, and liver-related mortality was high. Some of these deaths were potentially preventable by earlier diagnosis, as the patients had abnormal liver function test results previously, which had not been investigated.

Percutaneous Transhepatic Biliary Stenting with Uncovered Self-Expandable Metallic Stents in Patients with Malignant Biliary Obstruction – Efficacy and Survival Analysis

PubMed Central

Pranculis, Andrius; Kievišienė, Lina; Vaičius, Artūras; Vanagas, Tomas; Kaupas, Rytis Stasys; Dambrauskas, Žilvinas

2017-01-01

Summary Background The aim of this study was to assess short- and long-term outcomes of malignant biliary obstruction (MBO) treatment by percutaneous transhepatic biliary stenting (PTBS) with uncovered selfexpandable metallic stents (SEMS), and to identify predictors of survival. Material/Methods A nine-year, single-centre study from a prospectively collected database included 222 patients with inoperable MBO treated by PTBS with uncovered nitinol SEMS. Results Technical and clinical success rates were 95.9% and 82.4%, respectively. The total rate of postprocedural complications was 14.4%. The mean durations of the primary and secondary stent patency were 114.7±15.1 and 146.4±21.2 days, respectively. The 30-day mortality rate was 15.3% with no procedure-related deaths. The mean estimated length of survival was 143.3±20.6 days. Independent predictors increasing the risk of death included higher than 115 μmol/L serum bilirubin 2–5 days after biliary stenting (HR 3.274, P=0.019), distal (non-hilar) obstruction of the bile ducts (HR 3.711, P=0.008), Bismuth-Corlette type IV stricture (HR 2.082, P=0.008), obstruction due to gallbladder cancer (HR 31.029, P=0.012) and only partial drainage of liver parenchyma (HR 4.158, P=0.040). Conclusions PTBS with uncovered SEMS is an effective and safe method for palliative treatment of MBO. Serum bilirubin higher than 115 μmol/L 2–5 days after the procedure has a significant negative impact on patients’ survival. Lower survival is also determined by distal bile duct obstruction, Bismuth– Corlette type IV stricture, biliary obstruction caused by gallbladder cancer and when only partial liver drainage is applied. PMID:29662569

Percutaneous Transhepatic Biliary Stenting with Uncovered Self-Expandable Metallic Stents in Patients with Malignant Biliary Obstruction - Efficacy and Survival Analysis.

PubMed

Pranculis, Andrius; Kievišas, Mantas; Kievišienė, Lina; Vaičius, Artūras; Vanagas, Tomas; Kaupas, Rytis Stasys; Dambrauskas, Žilvinas

2017-01-01

The aim of this study was to assess short- and long-term outcomes of malignant biliary obstruction (MBO) treatment by percutaneous transhepatic biliary stenting (PTBS) with uncovered selfexpandable metallic stents (SEMS), and to identify predictors of survival. A nine-year, single-centre study from a prospectively collected database included 222 patients with inoperable MBO treated by PTBS with uncovered nitinol SEMS. Technical and clinical success rates were 95.9% and 82.4%, respectively. The total rate of postprocedural complications was 14.4%. The mean durations of the primary and secondary stent patency were 114.7±15.1 and 146.4±21.2 days, respectively. The 30-day mortality rate was 15.3% with no procedure-related deaths. The mean estimated length of survival was 143.3±20.6 days. Independent predictors increasing the risk of death included higher than 115 μmol/L serum bilirubin 2-5 days after biliary stenting (HR 3.274, P =0.019), distal (non-hilar) obstruction of the bile ducts (HR 3.711, P =0.008), Bismuth-Corlette type IV stricture (HR 2.082, P =0.008), obstruction due to gallbladder cancer (HR 31.029, P =0.012) and only partial drainage of liver parenchyma (HR 4.158, P =0.040). PTBS with uncovered SEMS is an effective and safe method for palliative treatment of MBO. Serum bilirubin higher than 115 μmol/L 2-5 days after the procedure has a significant negative impact on patients' survival. Lower survival is also determined by distal bile duct obstruction, Bismuth- Corlette type IV stricture, biliary obstruction caused by gallbladder cancer and when only partial liver drainage is applied.

Ezetimibe inhibits hepatic Niemann-Pick C1-Like 1 to facilitate macrophage reverse cholesterol transport in mice.

PubMed

Xie, Ping; Jia, Lin; Ma, Yinyan; Ou, Juanjuan; Miao, Hongming; Wang, Nanping; Guo, Feng; Yazdanyar, Amirfarbod; Jiang, Xian-Cheng; Yu, Liqing

2013-05-01

Controversies have arisen from recent mouse studies about the essential role of biliary sterol secretion in reverse cholesterol transport (RCT). The objective of this study was to examine the role of biliary cholesterol secretion in modulating macrophage RCT in Niemann-Pick C1-Like 1 (NPC1L1) liver only (L1(LivOnly)) mice, an animal model that is defective in both biliary sterol secretion and intestinal sterol absorption, and determine whether NPC1L1 inhibitor ezetimibe facilitates macrophage RCT by inhibiting hepatic NPC1L1. L1(LivOnly) mice were generated by crossing NPC1L1 knockout (L1-KO) mice with transgenic mice overexpressing human NPC1L1 specifically in liver. Macrophage-to-feces RCT was assayed in L1-KO and L1(LivOnly) mice injected intraperitoneally with [(3)H]-cholesterol-labeled peritoneal macrophages isolated from C57BL/6 mice. Inhibition of biliary sterol secretion by hepatic overexpression of NPC1L1 substantially reduced transport of [(3)H]-cholesterol from primary peritoneal macrophages to the neutral sterol fraction in bile and feces in L1(LivOnly) mice without affecting tracer excretion in the bile acid fraction. Ezetimibe treatment for 2 weeks completely restored both biliary and fecal excretion of [(3)H]-tracer in the neutral sterol fraction in L1(LivOnly) mice. High-density lipoprotein kinetic studies showed that L1(LivOnly) mice compared with L1-KO mice had a significantly reduced fractional catabolic rate without altered hepatic and intestinal uptake of high-density lipoprotein-cholesterol ether. In mice lacking intestinal cholesterol absorption, macrophage-to-feces RCT depends on efficient biliary sterol secretion, and ezetimibe promotes macrophage RCT by inhibiting hepatic NPC1L1 function.

Plastic biliary stent patency in patients with locally advanced pancreatic adenocarcinoma receiving downstaging chemotherapy.

PubMed

Ge, Phillip S; Hamerski, Christopher M; Watson, Rabindra R; Komanduri, Srinadh; Cinnor, Birtukan B; Bidari, Kiran; Klapman, Jason B; Lin, Cui L; Shah, Janak N; Wani, Sachin; Donahue, Timothy R; Muthusamy, V Raman

2015-02-01

Plastic stents in patients with biliary obstruction caused by pancreatic adenocarcinoma are typically exchanged at 3-month intervals. Plastic stents may have reduced durability in patients receiving chemotherapy. To determine the duration of plastic biliary stent patency in patients undergoing chemotherapy for pancreatic adenocarcinoma. Retrospective, multicenter cohort study. Three tertiary academic referral centers. A total of 173 patients receiving downstaging chemotherapy for locally advanced or borderline resectable pancreatic adenocarcinoma from 1996 to 2013. Placement of 10F or larger plastic biliary stents. Primary outcome was overall duration of stent patency. Secondary outcomes included the incidence of premature stent exchange (because of cholangitis or jaundice) and hospitalization rates. A total of 233 plastic stents were placed, and the overall median duration of stent patency was 53 days (interquartile range [IQR] 25-99 days). Eighty-seven stents were removed at the time of surgical resection, and 63 stents were exchanged routinely per protocol. The remaining 83 stent exchanges were performed for worsening liver function test results, jaundice, or cholangitis, representing a 35.6% rate of premature stent exchange. The median stent patency duration in the premature stent exchange group was 49 days (IQR 25-91 days) with a 44.6% hospitalization rate. The overall rate of cholangitis was 15.0% of stent exchanges, occurring a median of 56 days after stent placement (IQR 26-89 days). Retrospective study. Plastic biliary stents placed during chemotherapy/chemoradiation for pancreatic adenocarcinoma have a shorter-than-expected patency duration, and a substantial number of patients will require premature stent exchange. Consideration should be given to shortening the interval for plastic biliary stent exchange. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Biliary tract visualization using near-infrared imaging with indocyanine green during laparoscopic cholecystectomy: results of a systematic review.

PubMed

Vlek, S L; van Dam, D A; Rubinstein, S M; de Lange-de Klerk, E S M; Schoonmade, L J; Tuynman, J B; Meijerink, W J H J; Ankersmit, M

2017-07-01

Near-infrared imaging with indocyanine green (ICG) has been extensively investigated during laparoscopic cholecystectomy (LC). However, methods vary between studies, especially regarding patient selection, dosage and timing. The aim of this systematic review was to evaluate the potential of the near-infrared imaging technique with ICG to identify biliary structures during LC. A comprehensive systematic literature search was performed. Prospective trials examining the use of ICG during LC were included. Primary outcome was biliary tract visualization. Risk of bias was assessed using ROBINS-I. Secondly, a meta-analysis was performed comparing ICG to intraoperative cholangiography (IOC) for identification of biliary structures. GRADE was used to assess the quality of the evidence. Nineteen studies were included. Based upon the pooled data from 13 studies, cystic duct (Lusch et al. in J Endourol 28:261-266, 2014) visualization was 86.5% (95% CI 71.2-96.6%) prior to dissection of Calot's triangle with a 2.5-mg dosage of ICG and 96.5% (95% CI 93.9-98.4%) after dissection. The results were not appreciably different when the dosage was based upon bodyweight. There is moderate quality evidence that the CD is more frequently visualized using ICG than IOC (RR 1.16; 95% CI 1.00-1.35); however, this difference was not statistically significant. This systematic review provides equal results for biliary tract visualization with near-infrared imaging with ICG during LC compared to IOC. Near-infrared imaging with ICG has the potential to replace IOC for biliary mapping. However, methods of near-infrared imaging with ICG vary. Future research is necessary for optimization and standardization of the near-infrared ICG technique.

The association between biliary tract inflammation and risk of digestive system cancers: A population-based cohort study.

PubMed

Tsai, Tsung-Yu; Lin, Che-Chen; Peng, Cheng-Yuan; Huang, Wen-Hsin; Su, Wen-Pang; Lai, Shih-Wei; Chen, Hsuan-Ju; Lai, Hsueh-Chou

2016-08-01

The relationship between biliary tract inflammation (BTI) and digestive system cancers is unclear. This study aimed to evaluate the association between BTI and the risks of digestive system cancers.Using the Taiwan National Health Insurance claims data, information on a cohort of patients diagnosed with BTI (n = 4398) between 2000 and 2009 was collected. A comparison cohort of sex-, age-, and index year-matched persons without BTI (n = 17,592) was selected from the same database. The disease was defined by the ICD-9-CM. Both cohorts were followed until the end of 2010 and incidences of digestive system cancers were calculated.The results revealed an increase in adjusted hazard ratio (aHR) of biliary tract cancer (24.45; 95% confidence interval [CI]: 9.20-65.02), primary liver cancer (1.53; 95% CI: 1.07-2.18), and pancreatic cancer (3.10; 95% CI: 1.20-8.03) in patients with both gallbladder and BTI. The aHR of stomach cancer was also found to be increased (2.73; 95% CI: 1.28-5.81) in patients with gallbladder inflammation only. There were no differences in esophageal cancer (aHR: 0.82; 95% CI: 0.23-2.87) and colorectal cancer (aHR: 0.92; 95% CI: 0.59-1.45). The aHR for digestive system cancers increased by 3.66 times (95% CI: 2.50-5.35) and 12.20 times (95% CI: 8.66-17.17) in BTI visits frequency averaged 2 to 4 visits per year and frequency averaged ≥5 visits per year, respectively.Patients with BTI have significantly higher risk of digestive system cancers, particularly biliary tract, pancreatic, and primary liver cancers, compared with those who are without it.

The association between biliary tract inflammation and risk of digestive system cancers

PubMed Central

Tsai, Tsung-Yu; Lin, Che-Chen; Peng, Cheng-Yuan; Huang, Wen-Hsin; Su, Wen-Pang; Lai, Shih-Wei; Chen, Hsuan-Ju; Lai, Hsueh-Chou

2016-01-01

Abstract The relationship between biliary tract inflammation (BTI) and digestive system cancers is unclear. This study aimed to evaluate the association between BTI and the risks of digestive system cancers. Using the Taiwan National Health Insurance claims data, information on a cohort of patients diagnosed with BTI (n = 4398) between 2000 and 2009 was collected. A comparison cohort of sex-, age-, and index year-matched persons without BTI (n = 17,592) was selected from the same database. The disease was defined by the ICD-9-CM. Both cohorts were followed until the end of 2010 and incidences of digestive system cancers were calculated. The results revealed an increase in adjusted hazard ratio (aHR) of biliary tract cancer (24.45; 95% confidence interval [CI]: 9.20–65.02), primary liver cancer (1.53; 95% CI: 1.07–2.18), and pancreatic cancer (3.10; 95% CI: 1.20–8.03) in patients with both gallbladder and BTI. The aHR of stomach cancer was also found to be increased (2.73; 95% CI: 1.28–5.81) in patients with gallbladder inflammation only. There were no differences in esophageal cancer (aHR: 0.82; 95% CI: 0.23–2.87) and colorectal cancer (aHR: 0.92; 95% CI: 0.59–1.45). The aHR for digestive system cancers increased by 3.66 times (95% CI: 2.50–5.35) and 12.20 times (95% CI: 8.66–17.17) in BTI visits frequency averaged 2 to 4 visits per year and frequency averaged ≥5 visits per year, respectively. Patients with BTI have significantly higher risk of digestive system cancers, particularly biliary tract, pancreatic, and primary liver cancers, compared with those who are without it. PMID:27495065

Natural killer cells regulate T cell immune responses in primary biliary cirrhosis.

PubMed

Shimoda, Shinji; Hisamoto, Satomi; Harada, Kenichi; Iwasaka, Sho; Chong, Yong; Nakamura, Minoru; Bekki, Yuki; Yoshizumi, Tomoharu; Shirabe, Ken; Ikegami, Toru; Maehara, Yoshihiko; He, Xiao-Song; Gershwin, M Eric; Akashi, Koichi

2015-12-01

The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T- and B-cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver-derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)-γ, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4(+) T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN-γ production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN-γ secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4(+) T cells to become cytopathic. NK cell-mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen-specific T cells, essential for progression of disease. © 2015 by the American Association for the Study of Liver Diseases.

Primary biliary cirrhosis associated with Graves' disease in a male patient.

PubMed

Suzuki, Yuji; Ishida, Kazuyuki; Takahashi, Hiroshi; Koeda, Norihiko; Kakisaka, Keisuke; Miyamoto, Yasuhiro; Suzuki, Akiko; Takikawa, Yasuhiro

2016-04-01

Primary biliary cirrhosis (PBC), which predominantly affects women, has been associated with various autoimmune diseases. Although hypothyroidism accompanying PBC is well documented, the concomitance of PBC and hyperthyroidism is rare. Herein, we report the case of a 62-year-old man who was diagnosed with PBC several years after the development of Graves' disease. This is the first case of a male patient developing PBC with Graves' disease. Both serum alanine aminotransferase levels and serum thyroid hormone levels were normalized after the administration of thiamazole for Graves' disease. However, the cholestatic liver enzyme abnormalities continued, indicating that the PBC was actualized by the administration of thiamazole. After starting ursodeoxycholic acid treatment, cholestatic liver enzyme abnormalities improved. Taken together, when a cholestatic pattern of liver enzymes is observed during follow-up for Graves' disease, an association between Graves' disease and PBC should be considered as a differential diagnosis.

Chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis.

PubMed

Murata, Ken-ya; Ishiguchi, Hiroshi; Ando, Ryuki; Miwa, Hideto; Kondo, Tomoyoshi

2013-12-01

We report a patient with chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis (PBC). Except for minimal biochemical abnormalities, clinical symptoms of PBC were not observed, and we diagnosed our patient with asymptomatic PBC from the results of a liver biopsy. Although the patient noticed little muscle weakness, an electrophysiological study demonstrated slow conduction velocities and prolonged distal latencies, with definite conduction blocks in the median, ulnar, and tibial nerves. The disturbed sensory pattern was asymmetrical, and sensory nerve action potentials were not evoked. From these observations, we diagnosed this patient with chronic inflammatory demyelinating polyneuropathy. Neuropathy associated with PBC is very rare. We must differentiate demyelinating neuropathy with PBC in patients with asymmetrical sensory dominant neuropathy with high immunoglobulin M titers, and investigate for the presence of anti-mitochondrial antibodies to rule out a complication of asymptomatic PBC. Copyright © 2013 Elsevier Ltd. All rights reserved.

What the gastroenterologist does all day. A survey of a state society's practice.

PubMed

Switz, D M

1976-06-01

Members of a state society of gastroenterologist collected information about their pattern of practice. Twenty-two of the 41 members voluntarily kept a list of 25 sequential new patients seen during the spring of 1973. Five hundred and fory-nine diagnoses were accumulated; 369 (67%) of these diagnoses were gastroenterological. The five most common gastroenterological diagnoses were: functional disorder, duodenal ulcer, hiatus hernia, biliary tract disease, and esophagitis. The five most common over-all diagnostic areas were: functional disorder, cardiovascular disease, "other" nongastroenterological diagnoses (including obesity), duodenal ulcer, and endocrine malfunction. Geographically dispersed gastroenterologists in Virginia make more than one-half of their primary diagnoses in the area of their subspecialty interest. The primary gastroenterological problems seen are "upper gut" lesions and biliary tract disease. These observations may be of value in planning education, training, or research activities, especially if verified by a broader sample of gastroenterological practitioners.

A Systems Model for Ursodeoxycholic Acid Metabolism in Healthy and Patients With Primary Biliary Cirrhosis

PubMed Central

Dobbins, RL; O'Connor‐Semmes, RL; Young, MA

2016-01-01

A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population. PMID:27537780

Malignant Hilar Biliary Obstruction: Treatment by Means of Placement of a Newly Designed Y-Shaped Branched Covered Stent.

PubMed

Yun, Jong Hyouk; Jung, Gyoo-Sik; Park, Jung Gu; Kang, Byung Chul; Shin, Dong-Hoon; Yun, Byung Chul; Lee, Sang Uk

2016-04-01

To evaluate the technical feasibility and clinical efficacy of placement of a newly designed Y-shaped branched covered stent for palliative treatment of malignant hilar biliary obstruction. From June 2011 to September 2014, 34 consecutive patients with malignant hilar biliary obstruction underwent percutaneous placement of a Y-shaped branched covered stent for palliative treatment. Technical and clinical success, complications, cumulative patient survival, and stent patency were evaluated. Stent placement was technically successful in all patients. All patients showed adequate biliary drainage on the follow-up cholangiogram. Mean serum bilirubin level (10.9 mg/dl) decreased significantly 1 week (5.7 mg/dl) and 1 month (2.6 mg/dl) after stent placement (p < 0.01). Complications associated with the procedure included hemobilia (n = 3) and biloma (n = 1). During the mean follow-up period of 225 (range 12-820) days, nine patients (26.5%) developed stent occlusion caused by tumor overgrowth (n = 8) and sludge (n = 1). Two of them underwent coaxial placement of a second stent with good results. The median survival time was 281 days and median primary stent patency was 337 days. There were no significant differences in the patient survival and stent patency rates in relation to age, sex, or Bismuth type. Percutaneous placement of the Y-shaped branched covered stent seems to be technically feasible and clinically effective for palliative treatment of malignant hilar biliary obstruction.

Predictors of outcome after reconstructive hepatico-jejunostomy for post cholecystectomy bile duct injuries.

PubMed

Gomes, Rachel M; Doctor, Nilesh H

2015-01-01

Reconstructive hepatico-jejunostomy is recommended for major bile duct injuries (BDIs) during cholecystectomy. Complications of biliary leak, cholangitis, bleeding, anastomotic strictures and biliary cirrhosis remain a major concern affecting a patient's outcome after surgery. The aim of this study was to analyse the results of surgical repair of major BDIs at our institution and identify predictors for the development of major complications. A retrospective study of 57 patients with major BDI after cholecystectomy referred to a tertiary hepato-biliary centre from July 1999 to July 2011 and subsequently managed with reconstructive bilio-enteric anastomosis was performed. Of 57 patents 35 (61.4%) were primary referred. 22 (38.6 %) were secondary referred, of which 17 were for correct reconstructive surgery performed elsewhere and 5 were following attempted endoscopic management. 17 (29.8%) had local and systemic perioperative complications. 13 (22.8%) had major complications (bile leak, bleed, stricture and/or biliary cirrhosis). No association was found between age, type of cholecystectomy, type of injury, vascular injury and occurrence of major complications. Secondarily referred patients after therapeutic interventions (p = 0.010) and reconstructive surgery after repair performed by non-specialists suffered an increased incidence of major complications (p = 0.032). Secondary referral was also an independent predictor of major complications (p = 0.024). Early referral of patients with no previous intervention to a tertiary hepato-biliary center and specialist surgical repair is recommended for improved outcome after reconstructive hepatico-jejunostomy for major BDIs during cholecystectomy.

Autoimmune hepatitis triggered by acute hepatitis A.

PubMed

Tanaka, Hiroto; Tujioka, Hiroto; Ueda, Hiroki; Hamagami, Hiroko; Kida, Youhei; Ichinose, Masakazu

2005-10-14

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (X320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism.

PubMed

Louwerens, Marloes; Appelhof, Bente C; Verloop, Herman; Medici, Marco; Peeters, Robin P; Visser, Theo J; Boelen, Anita; Fliers, Eric; Smit, Johannes W A; Dekkers, Olaf M

2012-12-01

Research on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related symptoms. Furthermore, the relationship between fatigue and the TSH receptor (TSHR)-Asp727Glu polymorphism, a common genetic variant of the TSHR, was analyzed. A cross-sectional study was performed in 278 patients (140 patients treated for differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism (AIH)) genotyped for the TSHR-Asp727Glu polymorphism. The multidimensional fatigue inventory (MFI-20) was used to assess fatigue, with higher MFI-20 scores indicating more fatigue-related complaints. MFI-20 scores were related to disease status and Asp727Glu polymorphism status. AIH patients scored significantly higher than DTC patients on all five MFI-20 subscales (P<0.001), independent of clinical and thyroid hormone parameters. The frequency of the TSHR-Glu727 allele was 7.2%. Heterozygous DTC patients had more favorable MFI-20 scores than wild-type DTC patients on four of five subscales. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue was found in DTC patients only. AIH patients had significantly higher levels of fatigue compared with DTC patients, which could not be attributed to clinical or thyroid hormone parameters. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue in DTC patients should be confirmed in other cohorts.

Gallbladder cancer: epidemiology and outcome

PubMed Central

Hundal, Rajveer; Shaffer, Eldon A

2014-01-01

Gallbladder cancer, though generally considered rare, is the most common malignancy of the biliary tract, accounting for 80%–95% of biliary tract cancers. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis, often proving fatal. Its carcinogenesis follows a progression through a metaplasia–dysplasia–carcinoma sequence. This comprehensive review focuses on and explores the risks, management, and outcomes for primary gallbladder carcinoma. Epidemiological studies have identified striking geographic and ethnic disparities – inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Age, female sex, congenital biliary tract anomalies, and a genetic predisposition represent important risk factors that are immutable. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Mortality rates closely follow incidence; those countries with the highest prevalence of gallstones experience the greatest mortality from gallbladder cancer. Vague symptoms often delay the diagnosis of gallbladder cancer, contributing to its overall progression and poor outcome. Surgery represents the only potential for cure. Some individuals are fortunate to be incidentally found to have gallbladder cancer at the time of cholecystectomy being performed for cholelithiasis. Such an early diagnosis is imperative as a late presentation connotes advanced staging, nodal involvement, and possible recurrence following attempted resection. Overall mean survival is a mere 6 months, while 5-year survival rate is only 5%. The dismal prognosis, in part, relates to the gallbladder lacking a serosal layer adjacent to the liver, enabling hepatic invasion and metastatic progression. Improved imaging modalities are helping to diagnose patients at an earlier stage. The last decade has witnessed improved outcomes as aggressive surgical management and preoperative adjuvant therapy has helped prolong survival in patients with gallbladder cancer. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract. Meanwhile, clarification of the value of prophylactic cholecystectomy should provide an opportunity for secondary prevention. Primary prevention will arrive once the predictive biomarkers and environmental risk factors are more clearly identified. PMID:24634588

The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer

PubMed Central

Zabron, Abigail; Edwards, Robert J.; Khan, Shahid A.

2013-01-01

Cholangiocarcinoma is a fatal cancer of the biliary epithelium and has an incidence that is increasing worldwide. Survival beyond a year of diagnosis is less than 5%, and therapeutic options are few. Known risk factors include biliary diseases such as primary sclerosing cholangitis and parasitic infestation of the biliary tree, but most cases are not associated with any of these underlying diseases. Numerous in vitro and in vivo models, as well as novel analytical techniques for human samples, are helping to delineate the many pathways implicated in this disease, albeit at a frustratingly slow pace. As yet, however, none of these studies has been translated into improved patient outcome and, overall, the pathophysiology of cholangiocarcinoma is still poorly understood. There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease. In this review, we take a bedside-to-bench approach to discussing cholangiocarcinoma and outline research opportunities for the future in this field. PMID:23520144

The Wire-Grasping Method as a New Technique for Forceps Biopsy of Biliary Strictures: A Prospective Randomized Controlled Study of Effectiveness.

PubMed

Yamashita, Yasunobu; Ueda, Kazuki; Kawaji, Yuki; Tamura, Takashi; Itonaga, Masahiro; Yoshida, Takeichi; Maeda, Hiroki; Magari, Hirohito; Maekita, Takao; Iguchi, Mikitaka; Tamai, Hideyuki; Ichinose, Masao; Kato, Jun

2016-07-15

Transpapillary forceps biopsy is an effective diagnostic technique in patients with biliary stricture. This prospective study aimed to determine the usefulness of the wire-grasping method as a new technique for forceps biopsy. Consecutive patients with biliary stricture or irregularities of the bile duct wall were randomly allocated to either the direct or wire-grasping method group. In the wiregrasping method, forceps in the duodenum grasps a guidewire placed into the bile duct beforehand, and then, the forceps are pushed through the papilla without endoscopic sphincterotomy. In the direct method, forceps are directly pushed into the bile duct alongside a guide-wire. The primary endpoint was the success rate of obtaining specimens suitable for adequate pathological examination. In total, 32 patients were enrolled, and 28 (14 in each group) were eligible for analysis. The success rate was significantly higher using the wire-grasping method than the direct method (100% vs 50%, p=0.016). Sensitivity and accuracy for the diagnosis of cancer were comparable in patients with the successful procurement of biopsy specimens between the two methods (91% vs 83% and 93% vs 86%, respectively). The wire-grasping method is useful for diagnosing patients with biliary stricture or irregularities of the bile duct wall.

Does an isolated benign choledochal stricture hide a PSC?

PubMed

De Angelis, Paola; Tambucci, Renato; Romeo, Erminia; Rea, Francesca; Caloisi, Claudia; Caldaro, Tamara; di Abriola, Giovanni Federici; Foschia, Francesca; Torroni, Filippo; Monti, L; Dall'Oglio, Luigi

2013-05-01

Strictures of the extra-hepatic biliary tree are rare in children and have a benign non-traumatic inflammatory origin or are related to idiopathic fibrosing pancreatitis. Primary sclerosing cholangitis (PSC) can manifest as multiple biliary strictures or as a single dominant stricture. We describe the presentation, treatment, and outcome of six cases of isolated benign choledochal stricture (IBCS). All patients underwent magnetic resonance cholangiography (MRC). Five patients underwent diagnostic and therapeutic ERCP, and 4 patients underwent intra-choledochal mini-probe EUS and biopsy. Colonoscopy was performed in suspected ulcerative colitis (UC). We report 6 patients (mean age at diagnosis: four males, 12.1 years; two females, 14.2 years) with IBCS. Clinical onset included 3 cases of acute biliary pancreatitis and obstructive jaundice, one obstructive jaundice, one cholestasis, and one pancreatitis. At diagnosis, MRC confirmed IBCS in all patients. Biliary sphincterotomy, stricture dilation, and stenting were performed in 4 patients. One child underwent hepaticojejunostomy for a type I choledocal cyst. During follow-up (mean: 21 months; range: 1-3 years), all patients were asymptomatic. Four patients developed UC (three pancolitis, one descending colitis). One child developed PSC. IBCS can be successfully treated by therapeutic ERCP. The occurrence of UC could suggest that IBCS is a form of PSC. Copyright © 2013 Elsevier Inc. All rights reserved.

The use of immunosuppression in autoimmune hepatitis: A current literature review.

PubMed

Cropley, Angela; Weltman, Martin

2017-03-01

Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre's approach to treatment of AIH in the context of a contemporary review of the literature.

Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid.

PubMed

Hirschfield, Gideon M; Mason, Andrew; Luketic, Velimir; Lindor, Keith; Gordon, Stuart C; Mayo, Marlyn; Kowdley, Kris V; Vincent, Catherine; Bodhenheimer, Henry C; Parés, Albert; Trauner, Michael; Marschall, Hanns-Ulrich; Adorini, Luciano; Sciacca, Cathi; Beecher-Jones, Tessa; Castelloe, Erin; Böhm, Olaf; Shapiro, David

2015-04-01

We evaluated the efficacy and safety of obeticholic acid (OCA, α-ethylchenodeoxycholic acid) in a randomized controlled trial of patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid therapy. We performed a double-blind study of 165 patients with primary biliary cirrhosis (95% women) and levels of alkaline phosphatase (ALP) 1.5- to 10-fold the upper limit of normal. Patients were randomly assigned to groups given 10 mg, 25 mg, or 50 mg doses of OCA or placebo, once daily for 3 months. Patients maintained their existing dose of ursodeoxycholic acid throughout the study. The primary outcome was change in level of ALP from baseline (day 0) until the end of the study (day 85 or early termination). We also performed an open-label extension of the trial in which 78 patients were enrolled and 61 completed the first year. OCA was superior to placebo in achieving the primary end point. Subjects given OCA had statistically significant relative reductions in mean ALP from baseline to the end of the study (P < .0001 all OCA groups vs placebo). Levels of ALP decreased 21%-25% on average from baseline in the OCA groups and 3% in the placebo group. Sixty-nine percent (68 of 99) of patients given OCA had at least a 20% reduction in ALP compared with 8% (3 of 37) of patients given placebo (P < .0003). Among secondary end points, levels of γ-glutamyl transpeptidase decreased 48%-63%, on average, among subjects given OCA, vs a 7% decrease in the group given placebo; levels of alanine aminotransferase decreased 21%-35% on average among subjects given OCA vs none of the patients given placebo. Pruritus was the principal adverse event; incidence values in the OCA 10 mg, 25 mg, and 50 mg groups were 47% (not significantly different), 87% (P < .0003), and 80% (P < .006), respectively, vs 50% in the placebo group. In the extension study, levels of ALP continued to decrease to a mean level of 202 ± 11 U/L after 12 months vs 285 ± 15 U/L at baseline. Daily doses of OCA, ranging from 10 to 50 mg, significantly reduced levels of ALP, γ-glutamyl transpeptidase, and alanine aminotransferase, compared with placebo, in patients with primary biliary cirrhosis who had inadequate responses to ursodeoxycholic acid. The incidence and severity of pruritus were lowest among patients who received 10 mg/d OCA. Biochemical responses to OCA were maintained in a 12-month open-label extension trial. ClinicalTrials.gov ID: NCT00550862. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Transjugular Insertion of Bare-Metal Biliary Stent for the Treatment of Distal Malignant Obstructive Jaundice Complicated by Coagulopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsauo Jiaywei, E-mail: 80732059@qq.com; Li Xiao, E-mail: simonlixiao@gmail.com; Li Hongcui, E-mail: lihongcui520@126.com

This study was designed to investigate retrospectively the feasibility of transjugular insertion of biliary stent (TIBS) for the treatment of distal malignant obstructive jaundice complicated by coagulopathy. Between April 2005 and May 2010, six patients with distal malignant obstructive jaundice associated with coagulopathy that was unable to be corrected underwent TIBS at our institution for the palliation of jaundice. Patients' medical record and imaging results were reviewed to obtain information about demographics, procedure details, complications, and clinical outcomes. The intrahepatic biliary tract was successfully accessed in all six patients via transjugular approach. The procedure was technically successfully in five ofmore » six patients, with a bare-metal stent implanted after traversing the biliary strictures. One procedure failed, because the guidewire could not traverse the biliary occlusion. One week after TIBS, the mean serum bilirubin in the five successful cases had decreased from 313 {mu}mol/L (range 203.4-369.3) to 146.2 {mu}mol/L (range 95.8-223.3) and had further decreased to 103.6 {mu}mol/L (range 29.5-240.9) at 1 month after the procedure. No bleeding, sepsis, or other major complications were observed after the procedure. The mean survival of these five patients was 4.5 months (range 1.9-5.8). On imaging follow-up, there was no evidence of stent stenosis or migration, with 100 % primary patency. When the risks of hemorrhage from percutaneous transhepatic cholangiodrainage are high, TIBS may be an effective alternative for the treatment of distal malignant obstructive jaundice.« less

Methylene blue-aided cholangioscopy in patients with biliary strictures: feasibility and outcome analysis.

PubMed

Hoffman, A; Kiesslich, R; Bittinger, F; Galle, P R; Neurath, M F

2008-07-01

Chromoendoscopy using methylene blue is employed in the gastrointestinal tract to delineate neoplastic lesions. We tested the value of chromoendoscopy during choledochoscopy for characterization of local inflammation, neoplasias, and other alterations in patients with biliary strictures. Patients with suspected biliary lesions were scheduled for endoscopic retrograde cholangiography with subsequent cholangioscopy. After initial inspection of the bile duct, 15 ml methylene blue (0.1 %) was administered via the working channel of the cholangioscope. Newly appearing circumscribed or unstained lesions were judged according to their macroscopic type and staining features. Methylene-blue-aided diagnosis was compared with either clinical follow-up of the patients or, in some cases, with the results of targeted biopsies. A total of 55 patients [biliary stenosis/cholestasis of unknown origin (n = 24), stenosis after orthotopic liver transplantation (n = 11), primary sclerosing cholangitis (n = 20)] were included. Methylene blue unmasked subtle mucosal changes and permitted macroscopic characterization of circumscribed lesions. Characteristic surface staining patterns were seen in chronic inflammation, dysplasia, and ischemic-type biliary lesions. Nondysplastic mucosa appeared homogeneously stained, whereas scarred strictures showed a weak uptake of methylene blue. In this prospective feasibility study, methylene-blue-aided cholangioscopy was used for the first time to define different staining patterns of the bile duct. The differences in staining patterns identified normal, dysplastic, and inflamed mucosa of the bile duct, as was proved by follow-up or, in some cases, histology. Whereas homogeneous staining predicted the presence of normal mucosa, absence of staining of circumscribed lesions, or diffused staining of such lesions, represented neoplastic changes or inflammation.

Malignant Hilar Biliary Obstruction: Treatment by Means of Placement of a Newly Designed Y-Shaped Branched Covered Stent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yun, Jong Hyouk, E-mail: xell1015@naver.com; Jung, Gyoo-Sik, E-mail: gsjung@medimail.co.kr; Park, Jung Gu

PurposeTo evaluate the technical feasibility and clinical efficacy of placement of a newly designed Y-shaped branched covered stent for palliative treatment of malignant hilar biliary obstruction.MethodsFrom June 2011 to September 2014, 34 consecutive patients with malignant hilar biliary obstruction underwent percutaneous placement of a Y-shaped branched covered stent for palliative treatment. Technical and clinical success, complications, cumulative patient survival, and stent patency were evaluated.ResultsStent placement was technically successful in all patients. All patients showed adequate biliary drainage on the follow-up cholangiogram. Mean serum bilirubin level (10.9 mg/dl) decreased significantly 1 week (5.7 mg/dl) and 1 month (2.6 mg/dl) after stent placement (p < 0.01). Complications associated withmore » the procedure included hemobilia (n = 3) and biloma (n = 1). During the mean follow-up period of 225 (range 12–820) days, nine patients (26.5 %) developed stent occlusion caused by tumor overgrowth (n = 8) and sludge (n = 1). Two of them underwent coaxial placement of a second stent with good results. The median survival time was 281 days and median primary stent patency was 337 days. There were no significant differences in the patient survival and stent patency rates in relation to age, sex, or Bismuth type.ConclusionPercutaneous placement of the Y-shaped branched covered stent seems to be technically feasible and clinically effective for palliative treatment of malignant hilar biliary obstruction.« less

[Extrahepatic biliary atresia: diagnostic methods].

PubMed

Cauduro, Sydney M

2003-01-01

To emphasize the importance of precocious diagnosis of extrahepatic biliary atresia and its direct relationship with the surgical re-establishment of the biliary flow before the second month of life. To discuss several complementary methods with the aim of selecting the ones that present better evidence, and avoiding delays in diagnosis and worse prognostic. Bibliographical researching regarding the period of 1985-2001, in Medline and MdConsult, using the following key words: neo-natal cholestasis; extrahepatic biliary atresia; neo-natal hepatitis. National and foreign articles were also elected based on the bibliography of consulted publications, and when necessary, for better understanding of the theme, opinions emitted in theses and textbooks were referred. The revision of the consulted bibliography led to the assumption that early diagnosis of EHBA and surgical treatment to reestablish the biliary flow up to 60 days of life are fundamental in order to achieve good results. Among several complementary methods of diagnosis, cholangiography by MR, US and the hepatic biopsy are the ones that provide the largest success indexes. The referring of patients bearers of EHBA to centers of references in Brazil, is still made tardily, probably due to lack of enlightenment of the doctors of primary attention, allied to bureaucratic and technological difficulties. The experience in England in relation to the "Yellow Alert" program, allowed that the number of children referred to surgical treatment before the 60 days of life increased significantly. Among the complementary methods, the MR cholangiography, ultrasonography and hepatic biopsy should be used, depending on the technological resources of the diagnosis units.

Aspirin Use Is Associated With Reduced Risk of Occlusion of Metallic Biliary Stents.

PubMed

Jang, Sunguk; Stevens, Tyler; Parsi, Mansour A; Lopez, Rocio; Vargo, John J

2017-03-01

Biliary self-expandable metallic stents (SEMSs) are widely used to treat malignant and benign conditions of bile duct. Despite their lower rate of occlusion and longer patency than plastic stents, SEMSs still have significant rates of occlusion. We aimed to identify factors associated with occlusion of biliary SEMS. We performed a retrospective study of consecutive patients who underwent endoscopic retrograde cholangiopancreatography with biliary SEMS placement at the Cleveland Clinic Foundation from March 2011 to April 2016. We collected clinical, endoscopic, radiographic, and surgical data from medical records and performed multivariable analysis to identify factors associated with SEMS patency. Subjects that received minimal daily dose of 81 mg at the time of stent placement until the end of follow-up were assigned to the aspirin exposure group (n = 157) and compared with subjects with no aspirin exposure (n = 436). Patients were followed for a median 81 days. The primary outcome was hazard ratio for SEMS occlusion requiring an interventional maneuver for biliary drainage. We analyzed data from patients receiving a total of 593 biliary SEMS for treatment of malignant and benign conditions of bile duct. Stent occlusion was observed in 126 cases. Multivariable analysis showed that daily use of aspirin (81 mg or more) was associated with 51% lower risk of stent occlusion than in patients without daily use of aspirin (hazard ratio, 0.49; 95% confidence interval, 0.32-0.75). Furthermore, SEMSs had a longer duration of stent patency in patients in the aspirin exposure group (434.4 days) versus the no aspirin exposure group (339.9 days) (P < .001). Stricture location limited to distal bile duct (in comparison with strictures involving proximal extrahepatic duct) was associated with lower risk of stent occlusion (hazard ratio, 0.39; 95% CI, 0.22-0.71). In an analysis of a large cohort of subjects with metallic biliary stent placement for malignant and benign conditions of bile duct, we associated daily use of aspirin (81 mg or more) with lower risk of SEMS occlusion and longer stent patency duration. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Frey procedure for the treatment of chronic pancreatitis associated with common bile duct stricture.

PubMed

Rebibo, Lionel; Yzet, Thierry; Cosse, Cyril; Delcenserie, Richard; Bartoli, Eric; Regimbeau, Jean-Marc

2013-12-01

The Frey procedure (FP) is the treatment of choice for symptomatic chronic pancreatitis (CP). In cases of biliary stricture, biliary derivation can be performed by choledochoduodenostomy, Roux-en-Y choledochojejunostomy or, more recently, reinsertion of the common bile duct (CBD) into the resection cavity. The objective of the present study was to evaluate the outcomes associated with each of these three types of biliary derivation. We retrospectively analyzed demographic, CP-related, surgical and follow-up data for patients having undergone FP for CP with biliary derivation between 2004 and 2012 in our university medical center. The primary efficacy endpoint was the rate of CBD stricture recurrence. The secondary endpoints were surgical parameters, postoperative complications, postoperative follow-up and the presence of risk factors for secondary CBD stricture. Eighty patients underwent surgery for CP during the study period. Of these, 15 patients received biliary derivation with the FP. Eight of the FPs (53.3%) were combined with choledochoduodenostomy, 4 (26.7%) with choledochojejunostomy and 3 (20.0%) with reinsertion of the CBD into the resection cavity. The mean operating time was 390 minutes. Eleven complications (73.3%) were recorded, including one major complication (6.7%) that necessitated radiologically-guided drainage of an abdominal collection. The mean (range) length of stay was 17 days (8-28) and the median (range) follow-up time was 35.2 months (7.2-95.4). Two patients presented stricture after CBD reinsertion into the resection cavity; one was treated with radiologically-guided dilatation and the other underwent revisional Roux-en-Y choledochojejunostomy. Three patients presented alkaline reflux gastritis (37.5%), one (12.5%) cholangitis and one CBD stricture after FP with choledochoduodenostomy. No risk factors for secondary CBD stricture were identified. As part of a biliary derivation, the FP gave good results. We did not observe any complications specifically related to surgical treatment of the biliary tract. However, CBD reinsertion into the resection cavity appeared to be associated with a higher stricture recurrence rate. In our experience, choledochojejunostomy remains the "gold standard" for the surgical treatment for CBD strictures.

Impact of biliary stents on EUS-guided FNA of pancreatic mass lesions

PubMed Central

Ranney, Nathaniel; Phadnis, Milind; Trevino, Jessica; Ramesh, Jayapal; Wilcox, C. Mel; Varadarajulu, Shyam

2014-01-01

Background Few studies have evaluated the impact of biliary stents on EUS-guided FNA. Aim To compare diagnostic yield of EUS-FNA in patients with or without biliary stents. Design Retrospective study. Setting Tertiary referral center. Patients Patients with obstructive jaundice secondary to solid pancreatic mass lesions who underwent EUS-FNA over 5 years. Main Outcome Measures The primary objective was to compare the diagnostic accuracy of EUS-FNA in patients with or without biliary stents and between patients with plastic stents or self-expandable metal stents (SEMSs). Secondary objectives were to assess the technical difficulty of EUS-FNA by comparing the number of passes required to establish diagnosis and to identify predictors of a false-negative diagnosis. Results Of 214 patients who underwent EUS-FNA, 150 (70%) had biliary stents and 64 (30%) had no stents in place. Of 150 patients with biliary stents, 105 (70%) were plastic and 45 (30%) were SEMSs. At EUS-FNA, the diagnosis was pancreatic cancer in 155 (72%), chronic pancreatitis in 17 (8%), other cancer in 31 (14%), and indeterminate in 11 (5%). There was no difference in rates of diagnostic accuracy between patients with or without stents (93.7% vs 95.3%; P = .73) and between plastic or SEMSs (95.2% vs 95.5%, P = .99), respectively. Median number of passes to diagnosis was not significantly different between patients with or without stents (2 [interquartile ratio range (IQR) = 1–3] vs 2 [IQR = 1–4]; P = .066) and between plastic or SEMS (2.5 [IQR = 1–4] vs 2 [IQR = 1–4], P = .69), respectively. On univariate analysis, EUS-FNA results were false-negative in patients with large pancreatic masses (>3 cm vs <3 cm, 9.35% vs 0.93%, P = .005) that required more FNA passes (<2 vs >2 passes, 0% vs 11.8%, P < .0001). Limitations Retrospective study. Conclusions The presence or absence of a biliary stent, whether plastic or metal, does not have an impact on the diagnostic yield or technical difficulty of EUS-FNA. PMID:22726468

Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte plasma membrane.

PubMed

Muratori, L; Parola, M; Ripalti, A; Robino, G; Muratori, P; Bellomo, G; Carini, R; Lenzi, M; Landini, M P; Albano, E; Bianchi, F B

2000-04-01

Liver/kidney microsomal antibody type 1 (LKM1) is the marker of type 2 autoimmune hepatitis (AIH) and is detected in up to 6% of patients with hepatitis C virus (HCV) infection. It recognises linear and conformational epitopes of cytochrome P450IID6 (CYP2D6) and may have liver damaging activity, provided that CYP2D6 is accessible to effector mechanisms of autoimmune attack. The presence of LKM1 in the plasma membrane was investigated by indirect immunofluorescence and confocal laser microscopy of isolated rat hepatocytes probed with 10 LKM1 positive sera (five from patients with AIH and five from patients with chronic HCV infection) and a rabbit polyclonal anti-CYP2D6 serum. Serum from both types of patient stained the plasma membrane of non-permeabilised cells, where the fluorescent signal could be visualised as discrete clumps. Conversely, permeabilised hepatocytes showed diffuse submembranous/cytoplasmic staining. Adsorption with recombinant CYP2D6 substantially reduced plasma membrane staining and LKM1 immunoblot reactivity. Plasma membrane staining of LKM1 colocalised with that of anti-CYP2D6. Immunoprecipitation experiments showed that a single 50 kDa protein recognised by anti-CYP2D6 can be isolated from the plasma membrane of intact hepatocytes. AIH and HCV related LKM1 recognise CYP2D6 exposed on the plasma membrane of isolated hepatocytes. This observation supports the notion that anti-CYP2D6 autoreactivity may be involved in the pathogenesis of liver damage.

2018 European Thyroid Association (ETA) Guidelines for the Management of Amiodarone-Associated Thyroid Dysfunction.

PubMed

Bartalena, Luigi; Bogazzi, Fausto; Chiovato, Luca; Hubalewska-Dydejczyk, Alicja; Links, Thera P; Vanderpump, Mark

2018-03-01

Treatment with amiodarone is associated with changes in thyroid function tests, but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in apparently normal thyroid glands or in the presence of underlying thyroid abnormalities. AIH does not require amiodarone withdrawal, and is treated with levothyroxine replacement if overt, whereas subclinical forms may be followed without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a form of iodine-induced hyperthyroidism occurring in nodular goitres or latent Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic mechanisms. AIT 1 is best treated with thionamides that may be combined for a few weeks with sodium perchlorate to make the thyroid gland more sensitive to thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has been restored, AIT 2 patients are followed up without treatment, whereas AIT 1 patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite forms of AIT are treated with thionamides. Oral glucocorticoids can be added from the beginning if a precise diagnosis is uncertain, or after a few weeks if response to thionamides alone is poor. The decision to continue or to stop amiodarone in AIT should be individualized in relation to cardiovascular risk stratification and taken jointly by specialist cardiologists and endocrinologists. In the presence of rapidly deteriorating cardiac conditions, emergency thyroidectomy may be required for all forms of AIT.

Biochemical Response to Ursodeoxycholic Acid Predicts Survival in a North American Cohort of Primary Biliary Cirrhosis Patients

PubMed Central

Lammert, Craig; Juran, Brian D.; Schlicht, Erik; Chan, Landon L.; Atkinson, Elizabeth J.; de Andrade, Mariza; Lazaridis, Konstantinos N.

2014-01-01

Background Biochemical response to Ursodeoxycholic Acid among patients with Primary Biliary Cirrhosis remains variable and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with Ursodeoxycholic Acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Methods 398 PBC patients from the Mayo Clinic PBC Genetic Epidemiology (MCPGE) Registry were assessed for Ursodeoxycholic Acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Results 302 (76%) patients were responders and 96 (24%) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (Hazard Ratio (HR): 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR: 1.9) and patients with late stage disease (HR: 2.7) after age and sex adjustment. Conclusions The Toronto criteria are capable of identifying Ursodeoxycholic Acid-treated Primary Biliary Cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival. PMID:24317935

Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis.

PubMed

Mueller, Tobias; Beutler, Claudia; Picó, Almudena Hurtado; Shibolet, Oren; Pratt, Daniel S; Pascher, Andreas; Neuhaus, Peter; Wiedenmann, Bertram; Berg, Thomas; Podolsky, Daniel K

2011-11-01

Pattern recognition receptors (PRRs) orchestrate the innate immune defence in human biliary epithelial cells (BECs). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BECs. We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation. We examined PRR-mediated innate immune responses and protective endotoxin tolerance in primary BECs isolated from patients with primary sclerosing cholangitis (PSC), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT-PCR, Western blots and immunocytochemistry. Functional studies comprised immuno-precipitation Western blots, FACS for endotoxin uptake, and NF-κB activation assays and ELISA for secreted IL-8 and tumour necrosis factor (TNF)-α. Primary BECs from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/IRAK signalling complex. Consecutively, PSC BECs exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper-responsiveness was probably because of the stimulatory effect of abundantly expressed IFN-γ and TNF-α in PSC livers, which stimulated TLR4-mediated endotoxin signalling in BECs, leading to increased TLR4-mediated endotoxin incorporation and impaired inactivation of the TLR4 signalling cascade. As TNF-α inhibition partly restored protective innate immune tolerance, endogenous TNF-α secretion probably contributed to inappropriate endotoxin responses in BECs. Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BECs probably contribute to chronic cholangitis. © 2011 John Wiley & Sons A/S.

Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients.

PubMed

Lammert, Craig; Juran, Brian D; Schlicht, Erik; Chan, Landon L; Atkinson, Elizabeth J; de Andrade, Mariza; Lazaridis, Konstantinos N

2014-10-01

Biochemical response to ursodeoxycholic acid among patients with primary biliary cirrhosis remains variable, and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with ursodeoxycholic acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Three hundred and ninety-eight PBC patients from the Mayo Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Three hundred and two (76 %) patients were responders and 96 (24 %) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR 1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment. The Toronto criteria are capable of identifying ursodeoxycholic acid-treated primary biliary cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival.

Dilation of Strictures in Patients with Inflammatory Bowel Disease: Who, When and How.

PubMed

Coelho-Prabhu, Nayantara; Martin, John A

2016-10-01

Stricture formation occurs in up to 40% of patients with inflammatory bowel disease (IBD). Patients are often symptomatic, resulting in significant morbidity, hospitalizations, and loss of productivity. Strictures can be managed endoscopically in addition to traditional surgical management (sphincteroplasty or resection of the affected bowel segments). About 3% to 5% patients with IBD develop primary sclerosing cholangitis (PSC), which results in stricture formation in the biliary tree, managed for the most part by endoscopic therapies. In this article, we discuss endoscopic management of strictures both in the alimentary tract and biliary tree in patients with IBD and/or PSC. Copyright © 2016 Elsevier Inc. All rights reserved.

Stent patency in patients with distal malignant biliary obstruction receiving chemo(radio)therapy.

PubMed

Haal, Sylke; van Hooft, Jeanin E; Rauws, Erik A J; Fockens, Paul; Voermans, Rogier P

2017-11-01

 Recent literature suggests that chemo(radio)therapy might reduce the patency of plastic stents in patients with malignant biliary obstruction. Whether this might also be valid for other types of stents is unknown. The aim of this study was to determine the influence of chemo(radio)therapy on the patency of fully-covered self-expandable metal stents (FCSEMSs) and plastic stents.  We retrospectively reviewed the electronic medical records of patients with distal malignant biliary obstruction who underwent biliary stent placement between April 2001 and July 2015. Primary outcome was duration of stent patency. Secondary outcome was stent patency at 3 and 6 months. We used Kaplan-Meier survival analyses to compare stent patency rates between patients who received chemo(radio)therapy and patients who did not.  A total of 291 biliary stents (151 metal and 140 plastic) were identified. The median cumulative stent patency of FCSEMSs did not differ between patients receiving chemo(radio)therapy (n = 51) and those (n = 100) who did not ( P  = 0.70, log-rank test). The estimated cumulative stent patency of plastic stents was also comparable in 99 patients without and 41 patients with chemo(radio)therapy ( P  = 0.73, log-rank test). At 3 and 6 months, FCSEMS patency rates were 87 % and 83 % in patients without chemo(radio)therapy and 96 % and 83 % in patients with therapy, respectively. Plastic patency rates were 69 % and 55 % in patients without and 85 % and 39 % in patients with therapy, respectively. After 1 year, 78 % of the FCSEMSs were still patent in patients without chemo(radio)therapy and 69 % of the FCSEMSs were still patent in patients with therapy.  Our data indicate that chemo(radio)therapy does not reduce the patency of biliary fully-covered metal and plastic stents.

Biliary tract instillation of a SMAC mimetic induces TRAIL-dependent acute sclerosing cholangitis-like injury in mice

PubMed Central

Guicciardi, Maria Eugenia; Krishnan, Anuradha; Bronk, Steven F; Hirsova, Petra; Griffith, Thomas S; Gores, Gregory J

2017-01-01

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiopathogenesis characterized by fibrous cholangiopathy of large and small bile ducts. Systemic administration of a murine TNF-related apoptosis-inducing ligand (TRAIL) receptor agonist induces a sclerosing cholangitis injury in C57BL/6 mice, suggesting endogenous TRAIL may contribute to sclerosing cholangitis syndromes. Cellular inhibitor of apoptosis proteins (cIAP-1 and cIAP-2) are negative regulators of inflammation and TRAIL receptor signaling. We hypothesized that if endogenous TRAIL promotes sclerosing cholangitis, then cIAP depletion should also induce this biliary tract injury. Herein, we show that cIAP protein levels are reduced in the interlobular bile ducts of human PSC livers. Downregulation of cIAPs in normal human cholangiocytes in vitro by use of a SMAC mimetic (SM) induces moderate, ripoptosome-mediated apoptosis and RIP1-independent upregulation of proinflammatory cytokines and chemokines. Cytokine and chemokine expression was mediated by the non-canonical activation of NF-κB. To investigate whether downregulation of cIAPs is linked to generation of a PSC-like phenotype, an SM was directly instilled into the mouse biliary tree. Twelve hours after biliary instillation, TUNEL-positive cholangiocytes were identified; 5 days later, PSC-like changes were observed in the SM-treated mice, including a fibrous cholangiopathy of the interlobular bile ducts, portal inflammation, significant elevation of serum markers of cholestasis and cholangiographic evidence of intrahepatic biliary tract injury. In contrast, TRAIL and TRAIL-receptor deficient mice showed no sign of cholangiopathy following SM intrabiliary injection. We conclude that in vivo antagonism of cIAPs in mouse biliary epithelial cells is sufficient to trigger cholangiocytes apoptosis and a proinflammatory response resulting in a fibrous cholangiopathy resembling human sclerosing cholangitis. Therefore, downregulation of cIAPs in PSC cholangiocytes may contribute to the development of the disease. Our results also indicate that inhibition of TRAIL signaling pathways may be beneficial in the treatment of PSC. PMID:28055006

Stent patency in patients with distal malignant biliary obstruction receiving chemo(radio)therapy

PubMed Central

Haal, Sylke; van Hooft, Jeanin E.; Rauws, Erik A. J.; Fockens, Paul; Voermans, Rogier P.

2017-01-01

Background and study aims  Recent literature suggests that chemo(radio)therapy might reduce the patency of plastic stents in patients with malignant biliary obstruction. Whether this might also be valid for other types of stents is unknown. The aim of this study was to determine the influence of chemo(radio)therapy on the patency of fully-covered self-expandable metal stents (FCSEMSs) and plastic stents. Patients and methods  We retrospectively reviewed the electronic medical records of patients with distal malignant biliary obstruction who underwent biliary stent placement between April 2001 and July 2015. Primary outcome was duration of stent patency. Secondary outcome was stent patency at 3 and 6 months. We used Kaplan–Meier survival analyses to compare stent patency rates between patients who received chemo(radio)therapy and patients who did not. Results  A total of 291 biliary stents (151 metal and 140 plastic) were identified. The median cumulative stent patency of FCSEMSs did not differ between patients receiving chemo(radio)therapy (n = 51) and those (n = 100) who did not ( P  = 0.70, log-rank test). The estimated cumulative stent patency of plastic stents was also comparable in 99 patients without and 41 patients with chemo(radio)therapy ( P  = 0.73, log-rank test). At 3 and 6 months, FCSEMS patency rates were 87 % and 83 % in patients without chemo(radio)therapy and 96 % and 83 % in patients with therapy, respectively. Plastic patency rates were 69 % and 55 % in patients without and 85 % and 39 % in patients with therapy, respectively. After 1 year, 78 % of the FCSEMSs were still patent in patients without chemo(radio)therapy and 69 % of the FCSEMSs were still patent in patients with therapy. Conclusion  Our data indicate that chemo(radio)therapy does not reduce the patency of biliary fully-covered metal and plastic stents. PMID:29090242

Primary Biliary Cirrhosis Beyond Ursodeoxycholic Acid.

PubMed

Corpechot, Christophe

2016-02-01

Although ursodeoxycholic acid remains the only approved pharmacotherapy for patients with primary biliary cirrhosis, the better characterization of factors responsible for the poor response to this drug and the emergence of several new putative therapeutic targets now offer significant opportunities to improve the management of patients and our capacity to treat them more efficiently. The availability of novel treatment options, such as fibrates, budesonide, and obeticholic acid, all capable of improving prognostic markers, invites us to reconsider our management and treatment strategies. Early identification of high-risk patients should remain a priority to deliver adjunctive therapies to appropriately selected populations and increase their chances of success. Given the absence of comparative trials, the choice between second-line treatments should be dictated by the biochemical, histological, and expected tolerance profiles. Here the author presents a brief overview of what should be known in this field and proposes a practical approach to facilitate decision making. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Interchange between collagenous and lymphocytic colitis in severe disease with autoimmune associations requiring colectomy: a case report.

PubMed Central

Bowling, T E; Price, A B; al-Adnani, M; Fairclough, P D; Menzies-Gow, N; Silk, D B

1996-01-01

BACKGROUND--Collagenous colitis and lymphocytic colitis present with a similar clinical picture. Whether these conditions are separate entities or whether they represent different pathological stages of the same condition is an unresolved issue. PATIENT--This is a case of collagenous colitis following a fulminant course in which a colectomy was necessary. In the operative specimen the thickened collagen plate, which had been present only two weeks preoperatively had been lost and the pathology was of a lymphocytic colitis. Six months postoperatively this patient developed a CREST syndrome and primary biliary cirrhosis. CONCLUSIONS--This case shows the lability of the collagen plate and the common ground between collagenous and lymphocytic colitis, and presents evidence that these two conditions are different manifestations of the same disease. It also describes for the first time an association between collagenous colitis and CREST syndrome and primary biliary cirrhosis. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8707130

How do we manage post-OLT redundant bile duct?

PubMed

Torres, Victor; Martinez, Nicholas; Lee, Gabriel; Almeda, Jose; Gross, Glenn; Patel, Sandeep; Rosenkranz, Laura

2013-04-28

To address endoscopic outcomes of post-Orthotopic liver transplantation (OLT) patients diagnosed with a "redundant bile duct" (RBD). Medical records of patients who underwent OLT at the Liver Transplant Center, University Texas Health Science Center at San Antonio Texas were retrospectively analyzed. Patients with suspected biliary tract complications (BTC) underwent endoscopic retrograde cholangiopancreatography (ERCP). All ERCP were performed by experienced biliary endoscopist. RBD was defined as a looped, sigmoid-shaped bile duct on cholangiogram with associated cholestatic liver biomarkers. Patients with biliary T-tube placement, biliary anastomotic strictures, bile leaks, bile-duct stones-sludge and suspected sphincter of oddi dysfunction were excluded. Therapy included single or multiple biliary stents with or without sphincterotomy. The incidence of RBD, the number of ERCP corrective sessions, and the type of endoscopic interventions were recorded. Successful response to endoscopic therapy was defined as resolution of RBD with normalization of associated cholestasis. Laboratory data and pertinent radiographic imaging noted included the pre-ERCP period and a follow up period of 6-12 mo after the last ERCP intervention. One thousand two hundred and eighty-two patient records who received OLT from 1992 through 2011 were reviewed. Two hundred and twenty-four patients underwent ERCP for suspected BTC. RBD was reported in each of the initial cholangiograms. Twenty-one out of 1282 (1.6%) were identified as having RBD. There were 12 men and 9 women, average age of 59.6 years. Primary indication for ERCP was cholestatic pattern of liver associated biomarkers. Nineteen out of 21 patients underwent endoscopic therapy and 2/21 required immediate surgical intervention. In the endoscopically managed group: 65 ERCP procedures were performed with an average of 3.4 per patient and 1.1 stent per session. Fifteen out of 19 (78.9%) patients were successfully managed with biliary stenting. All stents were plastic. Selection of stent size and length were based upon endoscopist preference. Stent size ranged from 7 to 11.5 Fr (average stent size 10 Fr); Stent length ranged from 6 to 15 cm (average length 9 cm). Concurrent biliary sphincterotomy was performed in 10/19 patients. Single ERCP session was sufficient in 6/15 (40.0%) patients, whereas 4/15 (26.7%) patients needed two ERCP sessions and 5/15 (33.3%) patients required more than two (average of 5.4 ERCP procedures). Single biliary stent was sufficient in 5 patients; the remaining patients required an average of 4.9 stents. Four out of 19 (21.1%) patients failed endotherapy (lack of resolution of RBD and recurrent cholestasis in the absence of biliary stent) and required either choledocojejunostomy (2/4) or percutaneous biliary drainage (2/4). Endoscopic complications included: 2/65 (3%) post-ERCP pancreatitis and 2/10 (20%) non-complicated post-sphincterotomy bleeding. No endoscopic related mortality was found. The medical records of the 15 successful endoscopically managed patients were reviewed for a period of one year after removal of all biliary stents. Eleven patients had continued resolution of cholestatic biomarkers (73%). One patient had recurrent hepatitis C, 2 patients suffered septic shock which was not associated with ERCP and 1 patient was transferred care to an outside provider and records were not available for our review. Although surgical biliary reconstruction techniques have improved, RBD represents a post-OLT complication. This entity is rare however, endoscopic management of RBD represents a reasonable initial approach.

The Effect of Share 35 on Biliary Complications: an Interrupted Time Series Analysis.

PubMed

Fleming, J N; Taber, D J; Axelrod, D; Chavin, K D

2018-05-16

The purpose of the Share 35 allocation policy was to improve liver transplant waitlist mortality, targeting high MELD waitlisted patients. However, policy changes may also have unintended consequences that must be balanced with the primary desired outcome. We performed an interrupted time series assessing the impact of Share 35 on biliary complications in a select national liver transplant population using the Vizient CDB/RM ™ database. Liver transplants that occurred between October 2012 and September 2015 were included. There was a significant change in the incident-rate of biliary complications between Pre-Share 35 (n=3,018) and Post-Share 35 (n=9,984) cohorts over time (p=0.023, r2=0.44). As a control, a subanalysis was performed throughout the same time period in Region 9 transplant centers, where a broad sharing agreement had previously been implemented. In the subanalysis, there was no change in the incident-rate of biliary complications between the two time periods. Length of stay and mean direct cost demonstrated a change after implementation of Share 35, although they did not meet statistical difference. While the target of improved waitlist mortality is of utmost importance for the equitable allocation of organs, unintended consequences of policy changes should be studied for a full assessment of a policy's impact. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Wire-Grasping Method as a New Technique for Forceps Biopsy of Biliary Strictures: A Prospective Randomized Controlled Study of Effectiveness

PubMed Central

Yamashita, Yasunobu; Ueda, Kazuki; Kawaji, Yuki; Tamura, Takashi; Itonaga, Masahiro; Yoshida, Takeichi; Maeda, Hiroki; Magari, Hirohito; Maekita, Takao; Iguchi, Mikitaka; Tamai, Hideyuki; Ichinose, Masao; Kato, Jun

2016-01-01

Background/Aims Transpapillary forceps biopsy is an effective diagnostic technique in patients with biliary stricture. This prospective study aimed to determine the usefulness of the wire-grasping method as a new technique for forceps biopsy. Methods Consecutive patients with biliary stricture or irregularities of the bile duct wall were randomly allocated to either the direct or wire-grasping method group. In the wire-grasping method, forceps in the duodenum grasps a guide-wire placed into the bile duct beforehand, and then, the forceps are pushed through the papilla without endoscopic sphincterotomy. In the direct method, forceps are directly pushed into the bile duct alongside a guide-wire. The primary endpoint was the success rate of obtaining specimens suitable for adequate pathological examination. Results In total, 32 patients were enrolled, and 28 (14 in each group) were eligible for analysis. The success rate was significantly higher using the wire-grasping method than the direct method (100% vs 50%, p=0.016). Sensitivity and accuracy for the diagnosis of cancer were comparable in patients with the successful procurement of biopsy specimens between the two methods (91% vs 83% and 93% vs 86%, respectively). Conclusions The wire-grasping method is useful for diagnosing patients with biliary stricture or irregularities of the bile duct wall. PMID:27021502

Safety of supramesocolic surgery in patients with portal cavernoma without portal vein decompression. Large single centre experience.

PubMed

Dokmak, Safi; Aussilhou, Béatrice; Sauvanet, Alain; Lévy, Philippe; Plessier, Aurélie; Ftériche, Fadhel S; Farges, Olivier; Vilgrain, Valérie; Valla, Dominique C; Belghiti, Jacques

2016-07-01

Supra-mesocolic surgery (SMS) is complicated in patients with portal vein cavernoma (PC) and portal decompression is recommended. The aim of this study was to report a large single centre of SMS in patients with PC without portal decompression. Between 2006 and 2013, all patients who met inclusion criteria were analyzed retrospectively. The primary endpoint was the feasibility rate, surgical and postoperative outcome. The secondary endpoints were the long-term outcome of patients who underwent biliary bypass for cholangitis. Risk factors for complications were studied. Thirty patients underwent 51 procedures. Pancreatitis was the main etiology of PC (19/30) and biliary obstruction was mainly related to the underlying disease and not to portal cholangiopathy (12/14). All planned procedures were successfully completed. Fourteen patients underwent biliary bypass. Median blood loss (250 ml), transfusion (n = 7), mortality (n = 0), overall morbidity (n = 12) and the median hospital stay (10 days). Good long-term control of cholangitis was achieved in the 9 patients alive with available follow-up. Significant risk factors for complications were a previous abdominal wall scar, previous intra-abdominal surgical field and liver fibrosis. SMS can be safely performed in patients with PC. In patients with risk factors for complications, portal decompression should be discussed. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

A possible involvement of p62/sequestosome-1 in the process of biliary epithelial autophagy and senescence in primary biliary cirrhosis.

PubMed

Sasaki, Motoko; Miyakoshi, Masami; Sato, Yasunori; Nakanuma, Yasuni

2012-03-01

Given autophagy is involved in the pathogenesis in primary biliary cirrhosis (PBC), we examined an involvement of p62 sequestosome-1 (p62), a specific cargo for autophagy, in the process of autophagy and cellular senescence in PBC. We examined immunohistochemically the expression of p62 in livers taken from patients with PBC (n = 46) and control livers (n = 78) and its colocalization with microtubule-associated proteins-light chain 3β (LC3), lysosome-associated membrane protein-1 (LAMP-1) and senescent markers (p16(INK) (4a) and p21(WAF) (1/Cip1) ). We examined the expression of p62 and LC3 in cultured biliary epithelial cells (BECs) treated with various stress. The effect of p62 knockdown with siRNA on stress-induced autophagy and cellular senescence was also assessed. The expression of p62 was specifically seen in cytoplasmic aggregates in BECs in the inflamed and damaged small bile ducts (SBDs) in PBC, when compared with non-inflamed ones in PBC and in control livers (P < 0.01). The co-expression of p62 with LC3, LAMP-1 and senescent markers was seen in the inflamed SBDs in PBC, but the intracytoplasmic localization was different. The expression of p62 and LC3 was significantly upregulated in BECs treated with various stress (P < 0.01) and pretreatment with bafilomycin A1 enhanced the accumulation of p62-positive aggregates in BECs with serum deprivation. The knockdown of p62 decreased stress-induced autophagy and cellular senescence. The aggregation of p62 is specifically increased in the damage bile ducts in PBC and may reflect dysfunctional autophagy, followed by cellular senescence in the pathogenesis of bile duct lesions in PBC. © 2011 John Wiley & Sons A/S.

The Cholangiocyte Glycocalyx Stabilizes the 'Biliary HCO3 Umbrella': An Integrated Line of Defense against Toxic Bile Acids.

PubMed

Maillette de Buy Wenniger, Lucas J; Hohenester, Simon; Maroni, Luca; van Vliet, Sandra J; Oude Elferink, Ronald P; Beuers, Ulrich

2015-01-01

Destruction of cholangiocytes is the hallmark of chronic cholangiopathies such as primary biliary cirrhosis. Under physiologic conditions, cholangiocytes display a striking resistance to the high, millimolar concentrations of toxic bile salts present in bile. We recently showed that a 'biliary HCO3(-) umbrella', i.e. apical cholangiocellular HCO3(-) secretion, prevents cholangiotoxicity of bile acids, and speculated on a role for extracellular membrane-bound glycans in the stabilization of this protective layer. This paper summarizes published and thus far unpublished evidence supporting the role of the glycocalyx in stabilizing the 'biliary HCO3(-) umbrella' and thus preventing cholangiotoxicity of bile acids. The apical glycocalyx of a human cholangiocyte cell line and mouse liver sections were visualized by electron microscopy. FACS analysis was used to characterize the surface glycan profile of cultured human cholangiocytes. Using enzymatic digestion with neuraminidase the cholangiocyte glycocalyx was desialylated to test its protective function. Using lectin assays, we demonstrated that the main N-glycans in human and mouse cholangiocytes were sialylated biantennary structures, accompanied by high expression of the H-antigen (α1-2 fucose). Apical neuraminidase treatment induced desialylation without affecting cell viability, but lowered cholangiocellular resistance to bile acid-induced toxicity: both glycochenodeoxycholate and chenodeoxycholate (pKa ≥4), but not taurochenodeoxycholate (pKa <2), displayed cholangiotoxic effects after desialylation. A 24-hour reconstitution period allowed cholangiocytes to recover to a pretreatment bile salt susceptibility pattern. Experimental evidence indicates that an apical cholangiocyte glycocalyx with glycosylated mucins and other glycan-bearing membrane glycoproteins stabilizes the 'biliary HCO3(-) umbrella', thus aiding in the protection of human cholangiocytes against bile acid toxicity. 2015 S. Karger AG, Basel.

Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study

PubMed Central

Lubner, Sam J.; Mahoney, Michelle R.; Kolesar, Jill L.; LoConte, Noelle K.; Kim, George P.; Pitot, Henry C.; Philip, Philip A.; Picus, Joel; Yong, Wei-Peng; Horvath, Lisa; Van Hazel, Guy; Erlichman, Charles E.; Holen, Kyle D.

2010-01-01

Purpose Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Patients and Methods Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Results Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (< 16) in EGFR intron 1 polymorphism and G>G k-ras Q38 genotype (wild type) were associated with improved outcomes. Conclusion Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer. PMID:20530271

Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study.

PubMed

Lubner, Sam J; Mahoney, Michelle R; Kolesar, Jill L; Loconte, Noelle K; Kim, George P; Pitot, Henry C; Philip, Philip A; Picus, Joel; Yong, Wei-Peng; Horvath, Lisa; Van Hazel, Guy; Erlichman, Charles E; Holen, Kyle D

2010-07-20

Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (< 16) in EGFR intron 1 polymorphism and G>G k-ras Q38 genotype (wild type) were associated with improved outcomes. Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer.

Metal versus plastic stents for drainage of malignant biliary obstruction before primary surgical resection.

PubMed

Song, Tae Jun; Lee, Jae Hoon; Lee, Sang Soo; Jang, Ji Woong; Kim, Jung Wook; Ok, Tae Jin; Oh, Dong Wook; Park, Do Hyun; Seo, Dong Wan; Lee, Sung Koo; Kim, Myung-Hwan; Kim, Song Cheol; Kim, Chul Nam; Yun, Sung Cheol

2016-11-01

Preoperative biliary drainage (PBD) with stent placement has been commonly used for patients with malignant biliary obstruction. In PBD, the placement of fully covered self-expandable metal stents (FCSEMSs) may provide better patency duration and a lower incidence of cholangitis compared with plastic stents. We aimed to evaluate which type of stent showed better outcomes in PBD. In this multicenter, prospective randomized trial, we compared PBD with FCSEMSs versus plastic stents in 86 patients with malignant biliary obstruction between January 2012 and December 2014. Patients with obstructive jaundice were randomly assigned to undergo PBD either with plastic stents or FCSEMS placement. Baseline characteristics were not significantly different between the 2 groups. Endoscopic stent placement was technically successful in all patients. Procedure-related adverse events were not significantly different between the 2 groups (plastic vs FCSEMS group; 16.3% vs 16.3%, P = 1.0). Reintervention was required in 16.3% of the plastic stent group and 14.0% of the FCSEMS group (P = .763). The interval to surgery after PBD (plastic vs FCSEMS group; 14.2 ± 8.3 vs 12.3 ± 6.9 days, P = .426) was not significantly different between groups. Surgery-related adverse events occurred in 43.6% of the plastic stent group and 40.0% of the FCSEMS group (P = .755). In patients with resectable malignant biliary obstruction, the outcomes of PBD with plastic stents and FCSEMSs were similar. Considering the cost-effectiveness, PBD with plastic stents may be preferable to FCSEMS placement. (Clinical trial registration number: NCT01789502.). Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.

Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with,more » or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury compared to rodents. • Primary human hepatocytes largely undergo necrosis in response to BA toxicity. • Cholestatic liver injury in vivo is predominantly necrotic with minor apoptosis. • Rodent models of bile acid toxicity may not recapitulate the injury in man.« less

Cancer Prevention and Control in American Indians/Alaska Natives.

ERIC Educational Resources Information Center

Hampton, James W.

1992-01-01

Examines differences among American Indian tribes and Alaska Natives with regard to incidence and mortality rates for various types of cancer, particularly lung, cervix, breast, biliary, gastric, colorectal, prostate, and primary hepatic cancer. Discusses the influence of genetic and environmental factors, smoking, and inadequate medical…

Identification of HLA-A2–restricted CD8+ Cytotoxic T Cell Responses in Primary Biliary Cirrhosis

PubMed Central

Kita, Hiroto; Lian, Zhe-Xiong; Van de Water, Judy; He, Xiao-Song; Matsumura, Shuji; Kaplan, Marshall; Luketic, Velimir; Coppel, Ross L.; Ansari, Aftab A.; Gershwin, M. Eric

2002-01-01

Primary biliary cirrhosis (PBC) is characterized by an intense biliary inflammatory CD4+ and CD8+ T cell response. Very limited information on autoantigen-specific cytotoxic T lymphocyte (CTL) responses is available compared with autoreactive CD4+ T cell responses. Using peripheral blood mononuclear cells (PBMCs) from PBC, we identified an HLA-A2–restricted CTL epitope of the E2 component of pyruvate dehydrogenase (PDC-E2), the immunodominant mitochondrial autoantigen. This peptide, amino acids 159–167 of PDC-E2, induces specific MHC class I–restricted CD8+ CTL lines from 10/12 HLA-A2+ PBC patients, but not controls, after in vitro stimulation with antigen-pulsed dendritic cells (DCs). PDC-E2–specific CTLs could also be generated by pulsing DCs with full-length recombinant PDC-E2 protein. Furthermore, using soluble PDC-E2 complexed with either PDC-E2–specific human monoclonal antibody or affinity-purified autoantibodies against PDC-E2, the generation of PDC-E2–specific CTLs, occurred at 100-fold and 10-fold less concentration, respectively, compared with soluble antigen alone. Collectively, these data demonstrate that autoantibody, helper, and CTL epitopes all contain a shared peptide sequence. The finding that autoantigen–immune complexes can not only cross-present but also that presentation of the autoantigen is of a higher relative efficiency, for the first time defines a unique role for autoantibodies in the pathogenesis of an autoimmune disease. PMID:11781370

Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI.

PubMed

Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jonas, Eduard

2010-10-01

Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified. Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (C(max) , T(max) and T(1/2) ), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM). Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child-Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child-Pugh scores. Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels. © 2010 International Hepato-Pancreato-Biliary Association.

Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis.

PubMed

Aiba, Yoshihiro; Harada, Kenichi; Komori, Atsumasa; Ito, Masahiro; Shimoda, Shinji; Nakamura, Hitomi; Nagaoka, Shinya; Abiru, Seigo; Migita, Kiyoshi; Ishibashi, Hiromi; Nakanuma, Yasuni; Nishida, Nao; Kawashima, Minae; Tokunaga, Katsushi; Yatsuhashi, Hiroshi; Nakamura, Minoru

2014-05-01

Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC. We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining. Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients. These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Meta-analysis of Duct-to-duct versus Roux-en-Y biliary reconstruction following liver transplantation for primary sclerosing cholangitis.

PubMed

Pandanaboyana, Sanjay; Bell, Richard; Bartlett, Adam J; McCall, John; Hidalgo, Ernest

2015-04-01

This meta-analysis aimed to compare outcomes following bile duct reconstruction in patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation depending on whether duct-to-duct or Roux-en-Y anastomosis was utilized. An electronic search was performed of the MEDLINE, EMBASE, PubMed databases using both subject headings (MeSH) and truncated word searches. Pooled risk ratios and mean difference were calculated using the fixed-effects and random-effects models for meta-analysis. Ten studies including 910 patients met the inclusion criteria. There was no difference in the overall incidence of biliary strictures between the two groups [odds ratio (OR) 1.06 (0.68, 1.66); (P = 0.80)]. The anastomotic stricture rate was similar, [OR 1.18 (0.56, 2.50); (P = 0.67)]. Ascending cholangitis was higher in the Roux-en-Y group [OR 2.91 (1.17, 7.23); (P = 0.02)]. Anastomotic bile leak rates, graft survival, PSC recurrence and number of patients diagnosed with cholangiocarcinoma following transplantation were comparable between both groups. Duct-to-duct and Roux-en-Y reconstruction had comparable outcomes. Both techniques are associated with similar incidence of biliary stricture. The bilioenteric reconstruction was associated with a higher risk of cholangitis. The incidence of de novo cholangiocarcinoma was similar in both groups. Duct-to-duct reconstruction should be considered when feasible in patients with PSC. © 2015 Steunstichting ESOT.

Papillary bile duct dysplasia in primary sclerosing cholangitis.

PubMed

Ludwig, J; Wahlstrom, H E; Batts, K P; Wiesner, R H

1992-06-01

A 62-year-old man with a 20-year history of chronic ulcerative colitis and a 9-year history of primary sclerosing cholangitis (PSC) underwent orthotopic liver transplantation because of symptoms related to PSC and cholangiographic features compatible with a biliary neoplasm. Study of the excised liver revealed papillary mucosal lesions in the common hepatic duct and the right and left hepatic ducts as well as cholangiectases and other features typically associated with PSC. The papillary lesions consisted of abundant fibrovascular stroma covered by biliary epithelium with low-grade and high-grade dysplasia. Some periductal glands were also dysplastic. These features distinguished papillary dysplasia from classic biliary papillomatosis. Only one focus of microinvasion was found; there were no metastases. Among 60 cases of PSC in whom the entire liver could be studied after orthotopic liver transplantation, this was the only instance of unequivocal dysplasia. However, in one specimen, papillary hyperplasia was found. Detailed macroscopic and microscopic rereview of 23 livers from our patients with the longest history of PSC (range, 5-24 years) failed to reveal any additional cases with dysplasia. It is concluded that (a) papillary mucosal lesions in PSC may represent papillary dysplasia without invasion; (b) these lesions may evolve from papillary hyperplasia; (c) the process may be largely, if not entirely, in situ; and (d) the prevalence of dysplasia and carcinoma of bile ducts may be less than the 7%-9% reported in the literature for malignancies associated with PSC.

Can we prevent ischemic-type biliary lesions in donation after circulatory determination of death liver transplantation?

PubMed

Hessheimer, Amelia J; Cárdenas, Andrés; García-Valdecasas, Juan C; Fondevila, Constantino

2016-07-01

The pool of livers for transplantation consists of an increasingly greater proportion of marginal grafts, in particular those arising through donation after circulatory determination of death (DCD). However, a primary factor limiting the use of marginal livers, and, thereby, the applicability of liver transplantation in general, is concern over the subsequent development of ischemic-type biliary lesion (ITBL). ITBL is a devastating complication of liver transplantation; in its most severe forms, recipients suffer frequent infectious complications that require repeated invasive biliary procedures and ultimately result in either retransplantation or death. In the present review article, we discuss our current understanding of ITBL pathogenesis as it pertains to DCD, in particular. We discuss the most relevant theories regarding its development and provide a comprehensive overview of the most promising strategies we have available today to prevent the appearance of ITBL, strategies that may, furthermore, allow us to transplant a greater proportion of marginal livers in the future. Liver Transplantation 22 1025-1033 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

Primary cilia disruption differentially affects the infiltrating and resident macrophage compartment in the liver.

PubMed

Zimmerman, Kurt A; Song, Cheng Jack; Gonzalez-Mize, Nancy; Li, Zhang; Yoder, Bradley K

2018-06-01

Hepatorenal fibrocystic disease (HRFCD) is characterized by cysts in the kidney and liver with associated fibrosis and is the result of defects in proteins required for cilia function or assembly. Previous reports indicate that macrophages, mainly M2-like macrophages, contribute to HRFCD, although the origin of these cells (yolk sac-derived resident macrophages vs. bone marrow-derived infiltrating macrophages) and their contribution to the observed phenotypes are unknown. We utilize a congenital model of cilia dysfunction (IFT88 Orpk ) to study the importance of macrophages in HRFCD. Our data show a rapid expansion of the bile duct region and development of fibrosis between 2 and 4 wk of age. Immunofluorescence microscopy analysis reveals an accumulation of F4/80 + macrophages in regions exhibiting biliary hyperplasia in IFT88 Orpk mice. Flow cytometry data show that cilia dysfunction leads to an accumulation of infiltrating macrophages (CD11b hi , F4/80 lo ) and a reduction of resident macrophage (CD11b lo , F4/80 hi ) number. A majority of the infiltrating macrophages are Ly6c hi profibrogenic macrophages. Along with the accumulation of immune cells, expression of proinflammatory and profibrotic transcripts, including TGF-β, TNF-α, IL-1β, and chemokine (C-C) motif ligand 2, is increased. Quantitative RT-PCR analysis of flow-sorted cells shows enhanced expression of CCL2 in cholangiocytes and enhanced expression of VEGF-A and IL-6 in Ly6c hi macrophages. Genetic inhibition of Ly6c hi macrophage accumulation in IFT88 Orpk FVB CCR2 -/- mice reduced biliary fibrosis but did not affect epithelial expansion. Collectively, these studies suggest that biliary epithelium with defects in primary cilia preferentially recruits Ly6c hi infiltrating macrophages, which promote fibrotic progression in HRFCD pathogenesis. NEW & NOTEWORTHY These studies are the first to address the contribution of the infiltrating and resident macrophage niche during progression of hepatorenal fibrocystic disease (HRFCD). We show that the number of infiltrating macrophages is significantly upregulated in HRFCD mouse models. Finally, we show that prevention of Ly6c hi infiltrating macrophage accumulation significantly reduces biliary fibrosis, but not biliary hyperplasia, suggesting that this population may be responsible for the fibrotic progression of the disease in HRFCD patients.

Cost-effectiveness and clinical efficacy of biliary stents in patients undergoing neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial.

PubMed

Gardner, Timothy B; Spangler, Chad C; Byanova, Katerina L; Ripple, Gregory H; Rockacy, Matthew J; Levenick, John M; Smith, Kerrington D; Colacchio, Thomas A; Barth, Richard J; Zaki, Bassem I; Tsapakos, Michael J; Gordon, Stuart R

2016-09-01

The optimal type of stent for the palliation of malignant biliary obstruction in patients with pancreatic adenocarcinoma undergoing neoadjuvant chemoradiotherapy with curative intent is unknown. We performed a prospective trial comparing 3 types of biliary stents-fully covered self-expandable metal (fcSEMS), uncovered self-expandable metal (uSEMS), and plastic-to determine which best optimized cost-effectiveness and important clinical outcomes. In this prospective randomized trial, consecutive patients with malignant biliary obstruction from newly diagnosed pancreatic adenocarcinoma who were to start neoadjuvant chemoradiotherapy were randomized to receive fcSEMSs, uSEMSs, or plastic stents during the index ERCP. The primary outcomes were time to stent occlusion, attempted surgical resection, or death after the initiation of neoadjuvant therapy, and the secondary outcomes were total patient costs associated with the stent, including the index ERCP cost, downstream hospitalization cost due to stent occlusion, and the cost associated with procedural adverse event. Fifty-four patients were randomized and reached the primary end point: 16 in the fcSEMS group, 17 in the uSEMS group, and 21 in the plastic stent group. No baseline demographic or tumor characteristic differences were noted among the groups. The fcSEMSs had a longer time to stent occlusion compared with uSEMSs and plastic stents (220 vs 74 and 76 days, P < .01), although the groups had equivalent rates of stent occlusion, attempted surgical resection, and death. Although SEMS placement cost more during the index ERCP (uSEMS = $24,874 and fcSEMS = $22,729 vs plastic = $18,701; P < .01), they resulted in higher procedural AE costs per patient (uSEMS = $5522 and fcSEMS = $12,701 vs plastic = $0; P < .01). Conversely, plastic stents resulted in an $11,458 hospitalization cost per patient due to stent occlusion compared with $2301 for uSEMSs and $0 for fcSEMSs (P < .01). In a prospective trial comparing fcSEMSs, uSEMSs, and plastic stents for malignant biliary obstruction in patients undergoing neoadjuvant therapy with curative intent for pancreatic adenocarcinoma, no stent type was superior in optimizing cost-effectiveness, although fcSEMSs resulted in fewer days of neoadjuvant treatment delay and a longer time to stent occlusion. (Clincial trial registration number: NCT01038713.). Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte plasma membrane

PubMed Central

Muratori, L; Parola, M; Ripalti, A; Robino, G; Muratori, P; Bellomo, G; Carini, R; Lenzi, M; Landini, M; Albano, E; Bianchi, F

2000-01-01

BACKGROUND—Liver/kidney microsomal antibody type 1 (LKM1) is the marker of type 2 autoimmune hepatitis (AIH) and is detected in up to 6% of patients with hepatitis C virus (HCV) infection. It recognises linear and conformational epitopes of cytochrome P450IID6 (CYP2D6) and may have liver damaging activity, provided that CYP2D6 is accessible to effector mechanisms of autoimmune attack.
METHODS—The presence of LKM1 in the plasma membrane was investigated by indirect immunofluorescence and confocal laser microscopy of isolated rat hepatocytes probed with 10 LKM1 positive sera (five from patients with AIH and five from patients with chronic HCV infection) and a rabbit polyclonal anti-CYP2D6 serum.
RESULTS—Serum from both types of patient stained the plasma membrane of non-permeabilised cells, where the fluorescent signal could be visualised as discrete clumps. Conversely, permeabilised hepatocytes showed diffuse submembranous/cytoplasmic staining. Adsorption with recombinant CYP2D6 substantially reduced plasma membrane staining and LKM1 immunoblot reactivity. Plasma membrane staining of LKM1 colocalised with that of anti-CYP2D6. Immunoprecipitation experiments showed that a single 50 kDa protein recognised by anti-CYP2D6 can be isolated from the plasma membrane of intact hepatocytes.
CONCLUSIONS—AIH and HCV related LKM1 recognise CYP2D6 exposed on the plasma membrane of isolated hepatocytes. This observation supports the notion that anti-CYP2D6 autoreactivity may be involved in the pathogenesis of liver damage.


Keywords: liver/kidney microsomal antibody type 1; autoimmunity; autoimmune hepatitis; hepatitis C virus infection; confocal microscopy PMID:10716687

Novel Biliary Reconstruction Techniques During Liver Transplantation

PubMed Central

Carmody, Ian C.; Romano, John; Bohorquez, Humberto; Bugeaud, Emily; Bruce, David S.; Cohen, Ari J.; Seal, John; Reichman, Trevor W.; Loss, George E.

2017-01-01

Background: Biliary complications remain a significant problem following liver transplantation. Several surgical options can be used to deal with a significant size mismatch between the donor and recipient bile ducts during the biliary anastomosis. We compared biliary transposition to recipient biliary ductoplasty in cadaveric liver transplant. Methods: A total of 33 reconstructions were performed from January 1, 2005 to December 31, 2013. In the biliary transposition group (n=23), 5 reconstructions were performed using an internal stent (5 or 8 French pediatric feeding tube), and 18 were performed without. Of the 10 biliary ductoplasties, 2 were performed with a stent. All patients were managed with standard immunosuppression and ursodiol. Follow-up ranged from 2 months to 5 years. Results: No patients in the biliary transposition group required reoperation; 1 patient had an internal stent removed for recurrent unexplained leukocytosis, and 2 patients required endoscopic retrograde cholangiography and stent placement for evidence of stricture. Three anastomotic leaks occurred in the biliary ductoplasty group, and 2 patients in the biliary ductoplasty group required reoperation for biliary complications. Conclusion: Our results indicate that biliary reconstruction can be performed with either biliary transposition or biliary ductoplasty. These techniques are particularly useful when a significant mismatch in diameter exists between the donor and recipient bile ducts. PMID:28331447

Clinicopathological features of benign biliary strictures masquerading as biliary malignancy.

PubMed

Wakai, Toshifumi; Shirai, Yoshio; Sakata, Jun; Maruyama, Tomohiro; Ohashi, Taku; Korira, Pavel V; Ajioka, Yoichi; Hatakeyama, Katsuyoshi

2012-12-01

Discrimination between benign and malignant biliary strictures is difficult, with 5.2 to 24.5 per cent of biliary strictures proving to be benign after histological examination of the resected specimen. This study aimed to evaluate the clinicopathological features of benign biliary strictures in patients undergoing resection for presumed biliary malignancy. From January 1990 to August 2010, 5 of 153 (3.3%) patients who had undergone resection after a preoperative diagnosis of biliary malignancy had a final histological diagnosis of benign biliary stricture. The infiltration of immunoglobulin G4-positive plasma cells was evaluated by immunohistochemistry. None of the five patients had a history of trauma or earlier hepatobiliary surgery and all five underwent hemihepatectomy (combined with extrahepatic bile duct resection in three patients). Postoperative morbidity was recorded in two patients (transient cholangitis and biliary fistula), but there was no postoperative mortality. Histological re-examination identified immunoglobulin G4-related sclerosing cholangitis (n = 2) and nonspecific fibrosis/inflammation (n = 3). No preoperative clinical or radiographic features were identified that could reliably distinguish patients with benign biliary strictures from those with biliary malignancies. Although benign biliary strictures are rare, differentiating benign strictures from malignancy remains problematic. Thus, the treatment approach for biliary strictures should remain surgical resection for presumed biliary malignancy.

The use of immunosuppression in autoimmune hepatitis: A current literature review

PubMed Central

Cropley, Angela; Weltman, Martin

2017-01-01

Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre’s approach to treatment of AIH in the context of a contemporary review of the literature. PMID:28288505

A prospective study of radionuclide biliary scanning in acute pancreatitis.

PubMed Central

Neoptolemos, J. P.; Fossard, D. P.; Berry, J. M.

1983-01-01

Early surgery for biliary pancreatitis has resulted in a need for an accurate method of gallstone detection in acute pancreatitis. Fifty patients with acute pancreatitis were studied prospectively to assess the diagnostic value of Radionuclide Biliary Scanning (RBS) performed within 72 hours of an attack. To assess the general accuracy of RBS a further 154 patients with suspected acute cholecystitis or biliary colic were similarly studied. There were 34 patients with biliary pancreatitis and 18 (53%) had a positive scan (no gallbladder seen). There were 16 patients with non-biliary pancreatitis and 5 (31%) had a positive scan. All 51 patients with acute cholecystitis had a positive scan, as did 82% of the 51 patients with biliary colic. There were 52 patients with no biliary or pancreatic disease and none of these had a positive scan. RBS is highly accurate in confirming a diagnosis of acute cholecystitis or biliary colic. However, it cannot be relied on to differentiate between biliary and non-biliary pancreatitis and should certainly not be used as the basis for biliary surgery in these patients. PMID:6859781

Radiopaque biodegradable stent for duct-to-duct biliary reconstruction in pigs.

PubMed

Tanimoto, Yoshisato; Tashiro, Hirotaka; Mikuriya, Yoshihiro; Kuroda, Shintaro; Hashimoto, Masakazu; Kobayashi, Tsuyoshi; Taniura, Tokunori; Ohdan, Hideki

2016-06-01

Biliary stricture is a common cause of morbidity after liver transplantation. We previously developed a duct-to-duct biliary anastomosis technique using a biodegradable stent tube and confirmed the feasibility and safety of biliary stent use. However, the duration and mechanism of biliary stent absorption in the common bile duct remain unclear. Radiopaque biodegradable biliary stents were created using a copolymer of L-lactide and ε-caprolactone (70: 30) and coated with barium sulfate. Stents were surgically implanted in the common bile duct of 11 pigs. Liver function tests and computed tomography (CT) scans were performed postoperatively, and autopsies were conducted 6 months after biliary stent implantation. After the surgery, all 11 pigs had normal liver function and survived without any significant complications such as biliary leakage. A CT scan at 2 months post-procedure showed that the biliary stents were located in the hilum of the liver. The stents were not visible by CT scan at the 6-month follow-up examination. The surgical implantation of radiopaque biodegradable biliary stents in biliary surgery represents a new option for duct-to-duct biliary reconstruction. This technique appears to be feasible and safe and is not associated with any significant biliary complications. The advantage of coated biliary stent use is that it may be visualized using abdominal radiography such as CT.

External biliary drainage following major liver resection for perihilar cholangiocarcinoma: impact on development of liver failure and biliary leakage

PubMed Central

Olthof, Pim B.; Coelen, Robert J.S.; Wiggers, Jimme K.; Besselink, Marc G.H.; Busch, Olivier R.C.; van Gulik, Thomas M.

2016-01-01

Background Preoperative biliary drainage is considered essential in perihilar cholangiocarcinoma (PHC) requiring major hepatectomy with biliary-enteric reconstruction. However, evidence for postoperative biliary drainage as to protect the anastomosis is currently lacking. This study investigated the impact of postoperative external biliary drainage on the development of post-hepatectomy biliary leakage and liver failure (PHLF). Methods All patients who underwent major liver resection for suspected PHC between 2000 and 2015 were retrospectively analyzed. Biliary leakage and PHLF was defined as grade B or higher according to the International Study Group of Liver Surgery (ISGLS) criteria. Results Eighty-nine out of 125 (71%) patients had postoperative external biliary drainage. PHLF was more prevalent in the drain group (29% versus 6%; P = 0.004). There was no difference in the incidence of biliary leakage (32% versus 36%). On multivariable analysis, postoperative external biliary drainage was identified as an independent risk factor for PHLF (Odds-ratio 10.3, 95% confidence interval 2.1–50.4; P = 0.004). Conclusions External biliary drainage following major hepatectomy for PHC was associated with an increased incidence of PHLF. It is therefore not recommended to routinely use postoperative external biliary drainage, especially as there is no evidence that this decreases the risk of biliary anastomotic leakage. PMID:27037204

Mucobilia in Association With a Biliary Cystadenocarcinoma of the Caudate Duct: A Rare Cause of Malignant Biliary Obstruction

PubMed Central

Chamberlain, Ronald S.

2000-01-01

Mucobilia is a rare condition characterized by the accumulation of abundant mucus within the intra- or extrahepatic biliary tree. A variety of hepatobiliary and pancreatic neoplasms are mucin producing and have been associated with the development of mucobilia including biliary mucinosis, biliary papillomatosis, mucin-producing cholangiocarcinoma (MPCC), or cystic neoplasms of the pancreas or biliary tree (cystadenoma or cystadenocarcinoma). We report the case of 46 year-old male with a biliary cystadenocarcinoma of the caudate lobe which resulted in chronic biliary obstruction and relapsing cholangitis. A review of the literature for both mucobilia and biliary cystadenocarcinoma is provided along with a discussion addressing the clinical presentation, diagnosis, treatment, and prognosis for this rare entity. PMID:10674751

T-drain reduces the incidence of biliary leakage after liver resection.

PubMed

Eurich, Dennis; Henze, S; Boas-Knoop, S; Pratschke, J; Seehofer, D

2016-12-01

Biliary leakage is a serious complication after liver resection and represents the major cause of post-operative morbidity. In spite of already identified risk factors, little is known about the role of intra-biliary pressure following liver surgery in the development of biliary leakage. Biliary decompression may have a positive impact and reduce the incidence of biliary leakage at the parenchymal resection site. 397 patients undergoing liver resection without bilioenteric anastomosis were included in the retrospective analysis of the risk factors for the development of biliary leakage focusing on the intra-operative reduction of the biliary pressure by T-tube and liver histology. Among 397 analyzed patients after parenchymal resection, biliary leakage occurred in 39 cases (9.8 %). The extent of parenchymal resection was not associated with the total occurrence of biliary leak (p = 0.626). Lower incidence of biliary leakage from the resection surface was significantly associated with the use of T-tube (4.9 vs. 13.2 %; p = 0.006). In the subgroup analysis, insertion of a T-tube was not associated with a reduction of biliary leakage after anatomical hemihepatectomies (p = 0.103) and extraanatomical liver resection (p = 0.676). However, a high statistical significance could be detected in patients with extended hemihepatectomies (58.3 vs. 3.8 %; p < 0.001). Once biliary leak occurred without T-tube, median hospitalization duration significantly increased compared to patients with biliary decompression and without biliary leak (p < 0.001). The results of our retrospective data analysis suggest a significant beneficial impact of the T-tube on the development of biliary leakage in patients undergoing extended liver surgery.

Indian Health Trends and Services, 1974 Edition.

ERIC Educational Resources Information Center

Public Health Service (DHEW), Washington, DC. Div. of Indian Health.

The American Indian Health Service (AIHS), subsidiary of the Department of Health, Education, and Welfare, is dedicated to elevating the health status of Indian and Alaskan Native peoples by: developing modern health facilities; encouraging Indian acquaintance with and participation in existing programs; being responsive to the concept of…

Pilot study of a novel, large-bore, fully covered self-expandable metallic stent for unresectable distal biliary malignancies.

PubMed

Mukai, Tsuyoshi; Yasuda, Ichiro; Isayama, Hiroyuki; Iwashita, Takuji; Itoi, Takao; Kawakami, Hiroshi; Kogure, Hirofumi; Nakai, Yousuke

2016-09-01

In patients with unresectable malignant distal biliary obstruction, covered self-expandable metallic stents (CSEMS) may remain patent longer than uncovered self-expandable metallic stents as a result of tumor ingrowth prevention. One main cause of recurrent biliary obstruction (RBO) in CSEMS is sludge formation, which can be prevented using a large-bore stent. Therefore, we developed a novel, 12-mm diameter fully covered SEMS (FCSEMS) and investigated its clinical safety, efficacy, and rate of adverse events. This prospective, multicenter pilot study, which ran between June 2011 and November 2012, included 38 consecutive patients with unresectable malignant distal biliary obstruction. All patients underwent endoscopic insertion of our novel stent. Primary endpoint was non-RBO rate 6 months after placement. Technical and functional success rates of the procedures were 100%. Six-month non-RBO rate was 50%, and median time to RBO was 184 days. Median survival time was 241 days. Twelve patients died within 6 months after stent placement without RBO. RBO was observed in 10 patients (26%), with seven experiencing stent occlusion and three experiencing stent migration. Adverse events other than RBO (at <30 days) developed in six patients (16%; cholecystitis, one; pancreatitis, one; hyperamylasemia, one; pancreatic ductitis, one; abdominal pain, two). Stent removal for reintervention was successfully completed in eight patients. Our novel FCSEMS may be safe and effective for managing malignant distal obstruction with an acceptable incidence of adverse events. © 2016 Japan Gastroenterological Endoscopy Society.

Hepatic lesions in 90 captive nondomestic felids presented for autopsy.

PubMed

Bernard, J M; Newkirk, K M; McRee, A E; Whittemore, J C; Ramsay, E C

2015-03-01

Hepatic lesions in nondomestic felids are poorly characterized. The purpose of this study was to evaluate hepatic lesions in 90 captive, nondomestic felids including tigers, cougars, and lions. Hepatic lesions were histologically characterized as vacuolar change (lipidosis or glycogenosis), biliary cysts, biliary hyperplasia, hepatitis, necrosis, neoplasia, fibrosis, veno-occlusive disease, cholestasis, hematoma, congestion, or hemorrhage. Stepwise logistic regression analyses were performed for vacuolar change, benign biliary lesions, hepatitis, lipogranulomas, extramedullary hematopoiesis, and hepatic stellate cell hypertrophy and hyperplasia, with species as the outcome variable. Ninety cats met the inclusion criteria. Seventy livers (78%) contained 1 or more lesions. Hepatocellular vacuolar change (41/90 [46%]) was the most common lesion overall. Extramedullary hematopoiesis, lipogranulomas, and hepatic stellate cell hyperplasia were also common. One snow leopard had veno-occlusive disease. Tigers were more likely than other felids to have no significant hepatic histologic lesions (odds ratio [OR], 12.687; P = .002), and lions were more likely to have biliary cysts (OR, 5.97; P = .021). Six animals (7%) died of hepatic disease: cholangiocellular carcinoma (n = 2) and 1 each of hepatic lipidosis, hepatocellular necrosis, pyogranulomatous hepatitis, and suppurative cholecystitis. Hepatocellular iron and copper accumulations were present in 72 of 90 (80%) and 10 of 90 (11%) sections, respectively. Sinusoidal fibrosis was common (74/90 [82%]) and primarily centrilobular (65/74 [88%]). Hepatocellular iron, copper, and fibrosis were not significantly associated with hepatic lesions. Primary hepatic disease was not a common cause of death in nondomestic felids in this study. © The Author(s) 2014.

[Prognostic value of hepatobiliary functional scintigraphy in diagnosis and after-care of biliary atresia].

PubMed

Rossmüller, B; Porn, U; Schuster, T; Lang, T; Dresel, S; Hahn, K

2000-01-01

To investigate the prognostic relevance of hepatobiliary scintigraphy (HBS) in newborns suffering from biliary atresia (BA) for establishing the primary diagnosis and in the postoperative follow-up after portoenterostomy (Kasai). Twenty newborns with direct hyperbilirubinemia and 6 children after operative treatment of BA (Kasai) underwent HBS with Tc-99m-DEIDA. In patients without intestinal drainage, hepatocellular extraction was estimated visually and calculated semiquantitatively by means of liver/heart-ratio 5 min p.i. 10/20 patients with hyperbilirubinemia did not display biliary drainage; 6 had BA, 3 intrahepatic hypoplasia, and one showed a bile plug syndrome. 4/6 with BA but none of the 4 children with diagnoses other than BA presented with a good extraction. All of the 4 children with BA, who had either pre- or postoperatively a bad extraction, needed liver transplantation due to liver failure. Both of the two newborns with BA and favourable outcome after Kasai had a good extraction in the preoperative HBS and demonstrated good intestinal drainage in the postoperative scan. HBS rules out BA with high accuracy by demonstrating drainage of bile into the intestine. In newborns without drainage a good extraction favours the diagnosis of BA. In newborns with BA a bad extraction seems to indicate a poor postoperative prognosis after Kasai operation. HBS might therefore help to select those children who will not benefit from portoenterostomy. Postoperatively, HBS can easily and quickly confirm the successful hepatobiliary anastomosis by demonstrating biliary drainage into the intestine.

Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis.

PubMed

Baghdasaryan, Anna; Fuchs, Claudia D; Österreicher, Christoph H; Lemberger, Ursula J; Halilbasic, Emina; Påhlman, Ingrid; Graffner, Hans; Krones, Elisabeth; Fickert, Peter; Wahlström, Annika; Ståhlman, Marcus; Paumgartner, Gustav; Marschall, Hanns-Ulrich; Trauner, Michael

2016-03-01

Approximately 95% of bile acids (BAs) excreted into bile are reabsorbed in the gut and circulate back to the liver for further biliary secretion. Therefore, pharmacological inhibition of the ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic liver and bile duct injury. Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - a highly potent and selective ASBT inhibitor - or a chow diet. Liver injury was assessed biochemically and histologically after 4weeks of A4250 treatment. Expression profiles of genes involved in BA homeostasis, inflammation and fibrosis were assessed via RT-PCR from liver and ileum homogenates. Intestinal inflammation was assessed by RNA expression profiling and immunohistochemistry. Bile flow and composition, as well as biliary and fecal BA profiles were analyzed after 1week of ASBT inhibitor feeding. A4250 improved sclerosing cholangitis in Mdr2(-/-) mice and significantly reduced serum alanine aminotransferase, alkaline phosphatase and BAs levels, hepatic expression of pro-inflammatory (Tnf-α, Vcam1, Mcp-1) and pro-fibrogenic (Col1a1, Col1a2) genes and bile duct proliferation (mRNA and immunohistochemistry for cytokeratin 19 (CK19)). Furthermore, A4250 significantly reduced bile flow and biliary BA output, which correlated with reduced Bsep transcription, while Ntcp and Cyp7a1 were induced. Importantly A4250 significantly reduced biliary BA secretion but preserved HCO3(-) and biliary phospholipid secretion resulting in an increased HCO3(-)/BA and PL/BA ratio. In addition, A4250 profoundly increased fecal BA excretion without causing diarrhea and altered BA pool composition, resulting in diminished concentrations of primary BAs tauro-β-muricholic acid and taurocholic acid. Pharmacological ASBT inhibition attenuates cholestatic liver and bile duct injury by reducing biliary BA concentrations in mice. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Plectin controls biliary tree architecture and stability in cholestasis.

PubMed

Jirouskova, Marketa; Nepomucka, Katerina; Oyman-Eyrilmez, Gizem; Kalendova, Alzbeta; Havelkova, Helena; Sarnova, Lenka; Chalupsky, Karel; Schuster, Bjoern; Benada, Oldrich; Miksatkova, Petra; Kuchar, Martin; Fabian, Ondrej; Sedlacek, Radislav; Wiche, Gerhard; Gregor, Martin

2018-05-01

Plectin, a highly versatile cytolinker protein, controls intermediate filament cytoarchitecture and cellular stress response. In the present study, we investigate the role of plectin in the liver under basal conditions and in experimental cholestasis. We generated liver-specific plectin knockout (Ple Δalb ) mice and analyzed them using two cholestatic liver injury models: bile duct ligation (BDL) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. Primary hepatocytes and a cholangiocyte cell line were used to address the impact of plectin on keratin filament organization and stability in vitro. Plectin deficiency in hepatocytes and biliary epithelial cells led to aberrant keratin filament network organization, biliary tree malformations, and collapse of bile ducts and ductules. Further, plectin ablation significantly aggravated biliary damage upon cholestatic challenge. Coincidently, we observed a significant expansion of A6-positive progenitor cells in Ple Δalb livers. After BDL, plectin-deficient bile ducts were prominently dilated with more frequent ruptures corresponding to an increased number of bile infarcts. In addition, more abundant keratin aggregates indicated less stable keratin filaments in Ple Δalb hepatocytes. A transmission electron microscopy analysis revealed a compromised tight junction formation in plectin-deficient biliary epithelial cells. In addition, protein profiling showed increased expression of the adherens junction protein E-Cadherin, and inefficient upregulation of the desmosomal protein desmoplakin in response to BDL. In vitro analyses revealed a higher susceptibility of plectin-deficient keratin networks to stress-induced collapse, paralleled by elevated activation of p38 MAP kinase. Our study shows that by maintaining proper keratin network cytoarchitecture and biliary epithelial stability, plectin plays a critical role in protecting the liver from stress elicited by cholestasis. Plectin is a cytolinker protein capable of interconnecting all three cytoskeletal filament systems and linking them to plasma membrane-bound junctional complexes. In liver, the plectin-controlled cytoskeleton mechanically stabilizes epithelial cells and provides them with the capacity to adapt to increased bile pressure under cholestasis. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Biliary fascioliasis--an uncommon cause of recurrent biliary colics: report of a case and brief review.

PubMed

Al Qurashi, Hesham; Masoodi, Ibrahim; Al Sofiyani, Mohammad; Al Musharaf, Hisham; Shaqhan, Mohammed; All, Gamal Nasr Ahmed Abdel

2012-01-01

Biliary parasitosis is one of the important causes of biliary obstruction in endemic areas, however due to migration and travel the disease is known to occur in non endemic zones as well. The spectrum of biliary fascioliasis ranges from recurrent biliary colics to acute cholangitis. The long term complications are gall stones, sclerosing cholangitis and biliary cirrhosis. We describe fascioliasis as a cause of recurrent biliary colics in a young male necessitating multiple hospitalizations over a period of four years. Investigative profile had been non-contributory every time he was hospitalized for his abdominal pain prior to the current presentation. He never had cholangitis due to the worm in the common bile duct. It was only at endoscopic retrograde cholangiopancreatography (ERCP) biliary fascioliasis was discovered to be the cause of his recurrent biliary colics. After removal of the live Fasciola hepatica from the common bile duct he became symptom free and is attending our clinic for last 11 months now. Clinical spectrum of biliary fascioliasis is discussed in this report.

A novel biliary stent coated with silver nanoparticles prolongs the unobstructed period and survival via anti-bacterial activity

PubMed Central

Yang, Fuchun; Ren, Zhigang; Chai, Qinming; Cui, Guangying; Jiang, Li; Chen, Hanjian; Feng, Zhiying; Chen, Xinhua; Ji, Jian; Zhou, Lin; Wang, Weilin; Zheng, Shusen

2016-01-01

Symptomatic biliary stricture causes life-threatening complications, such as jaundice, recurrent cholangitis and secondary biliary cirrhosis. Fully covered self-expanding metal stents (FCSEMSs) are gaining acceptance for treatments of benign biliary stricture and palliative management of malignant biliary obstructions. However, the high rate of FCSEMS obstruction limits their clinic use. In this study, we developed a novel biliary stent coated with silver nanoparticles (AgNPs) and investigated its efficacy both in vitro and in vivo. We first identified properties of the AgNP complex using ultraviolet detection. The AgNP complex was stable without AgNP agglomeration, and Ag abundance was correspondingly increased with an increased bilayer number. The AgNP biliary stent demonstrated good performance in the spin-assembly method based on topographic observation. The AgNP biliary stent also exhibited a long-term anti-coagulation effect and a slow process of Ag+ release. In vitro anti-bacteria experiments indicated that the AgNP biliary stent exhibited high-efficiency anti-bacterial activity for both short- and long-term periods. Importantly, application of the AgNP biliary stent significantly prolonged the unobstructed period of the biliary system and improved survival in preclinical studies as a result of its anti-microbial activity and decreased granular tissue formation on the surface of the anastomotic biliary, providing a novel and effective treatment strategy for symptomatic biliary strictures. PMID:26883081

Malignant biliary disease: percutaneous interventions.

PubMed

Morgan, R A; Adam, A N

2001-09-01

Interventional radiologists have an important role in the management of patients with malignant biliary obstruction. This article describes the techniques for percutaneous biliary drainage, insertion of biliary endoprostheses, and the management of occluded biliary endoprostheses. Most procedures are performed by using fluoroscopic guidance alone. Ultrasound is also a useful modality for guiding biliary drainage, particularly drainage of the left biliary ducts. Patients should be treated by internal drainage if possible. Metallic endoprostheses can be inserted at the time of the initial biliary drainage procedure. Plastic tubes should be inserted a few days after biliary drainage because of their relatively large size compared with metallic stents. Occluded plastic stents should be replaced. Blocked metallic stents should be treated either by placement of additional overlapping metallic stents or by placement of plastic stents within the metallic stent lumen. Copyright 2001 by W.B. Saunders Company

Drug induced liver injury with analysis of alternative causes as confounding variables.

PubMed

Teschke, Rolf; Danan, Gaby

2018-04-01

Drug-induced liver injury (DILI) is rare compared to the worldwide frequent acute or chronic liver diseases. Therefore, patients included in series of suspected DILI are at high risk of not having DILI, whereby alternative causes may confound the DILI diagnosis. The aim of this review is to evaluate published case series of DILI for alternative causes. Relevant studies were identified using a computerized search of the Medline database for publications from 1993 through 30 October 2017. We used the following terms: drug hepatotoxicity, drug induced liver injury, hepatotoxic drugs combined with diagnosis, causality assessment and alternative causes. Alternative causes as variables confounding the DILI diagnosis emerged in 22 published DILI case series, ranging from 4 to 47%. Among 13 335 cases of suspected DILI, alternative causes were found to be more likely in 4555 patients (34.2%), suggesting that the suspected DILI was probably not DILI. Biliary diseases such as biliary obstruction, cholangitis, choledocholithiasis, primary biliary cholangitis and primary sclerosing cholangitis were among the most missed diagnoses. Alternative causes included hepatitis B, C and E, cytomegalovirus, Epstein-Barr virus, ischemic hepatitis, cardiac hepatopathy, autoimmune hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and alcoholic liver disease. In more than one-third of published global DILI case series, alternative causes as published in these reports confounded the DILI diagnosis. In the future, published DILI case series should include only patients with secured DILI diagnosis, preferentially established by prospective use of scored items provided by robust diagnostic algorithms such as the updated Roussel Uclaf causality assessment method. © 2018 The British Pharmacological Society.

Benign Biliary Strictures: Diagnostic Evaluation and Approaches to Percutaneous Treatment.

PubMed

Fidelman, Nicholas

2015-12-01

Interventional radiologists are often consulted to help identify and treat biliary strictures that can result from a variety of benign etiologies. Mainstays of noninvasive imaging for benign biliary strictures include ultrasound, contrast-enhanced computed tomography and magnetic resonance imaging, magnetic resonance cholangiopancreatography, and computed tomography cholangiography. Endoscopic retrograde cholangiography is the invasive diagnostic procedure of choice, allowing both localization of a stricture and treatment. Percutaneous biliary interventions are reserved for patients who are not candidates for endoscopic retrograde cholangiography (eg, history of distal gastrectomy and biliary-enteric anastomosis to a jejunal roux limb). This review discusses the roles of percutaneous transhepatic cholangiography and biliary drainage in the diagnosis of benign biliary strictures. The methodology for crossing benign biliary strictures, approaches to balloon dilation, management of recalcitrant strictures (ie, large-bore biliary catheters and retrievable covered stents), and the expected outcomes and complications of percutaneous treatment of benign biliary strictures are also addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis.

PubMed

McHugh, Anna; Robe, Amanda J; Palmer, Jeremy M; Jones, David E J

2006-05-01

Autoantibody responses reactive with the E2 and E3BP components of pyruvate dehydrogenase complex (PDC), which characterise primary biliary cirrhosis (PBC) crossreact, precluding the identification, from serological studies, of the antigen to which the principal breakdown of tolerance occurs. Although autoreactive T-cell responses to PDC-E2 have been well characterised it is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC-E3BP. The aims of this study were to characterise autoreactive T-cell responses to PDC-E3BP in PBC and potential factors regulating their expression. Peripheral blood T-cell proliferative responses to purified recombinant human PDC-E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients and control subjects. T-cell proliferative responses to both E2 and E3BP were absent from control subjects (median peak stimulation index (SI) to PDC-E2 1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7-2.1

Acro-osteolysis as an indicator of severity in systemic sclerosis.

PubMed

Arana-Ruiz, Juan Carlos; Amezcua-Guerra, Luis Manuel

2016-01-01

Systemic sclerosis is a rare disease that predominantly affects women. The Medsger severity scale has been used to assess the severity, but it requires expensive and poorly accessible studies and it does not include complications such acrosteolysis, calcinosis, pericardial disease or hypothyroidism that occur on a relatively frequent basis in this disease. There is no study that considers if comorbidities, such as primary biliary cirrhosis, are related to gravity. To determine the correlation between severity and the presence of such complications. 40 patients with systemic sclerosis, dividing them into tertiles according to severity were studied. Dichotomous variables were described using percentages, while dimensional by averages+SD. Statistical inference was performed using chi square test or Kruskal-Wallis test with Dunn post-test, as appropriate. A significance at P<.05 was set. Of all the complications studied there were only differences in severity with acrosteolysis. Within comorbidities, primary biliary cirrhosis is not associated with gravity. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

A Systems Model for Ursodeoxycholic Acid Metabolism in Healthy and Patients With Primary Biliary Cirrhosis.

PubMed

Zuo, P; Dobbins, R L; O'Connor-Semmes, R L; Young, M A

2016-08-01

A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

The clinical expression of primary biliary cirrhosis.

PubMed

Heathcote, J

1997-02-01

Primary biliary cirrhosis (PBC) is likely an autoimmune disease that destroys the interlobular bile ducts. Although the term PBC implies cirrhosis, this is not always present. The condition may be entirely silent clinically, save for the hallmark mitochondrial antibodies in serum. The clinical spectrum of PBC ranges from asymptomatic anicteric cholestasis with or without extrahepatic manifestations to severe cholestasis with decompensated cirrhosis. It is uncertain whether or not the course of this disease is universally fatal. Currently, no specific features have been identified which predict progression from asymptomatic to symptomatic disease, although once hyperbilirubinemia is present, a rising level indicates a poor prognosis. The liver-specific complications include pruritus, abdominal pain, xantholasma, and portal hypertension. The latter is often an early feature, as the portal hypertension is presinusoidal in nature and, when present, does not always reflect the presence of cirrhosis. There are many extrahepatic features of PBC, the most common being metabolic, chiefly hypothyroidism and metabolic bone disease. Other common associations are rheumatologic, renal, pulmonary, neuromuscular, and dermatologic. The non-specific yet distressing symptom of fatigue affects up to two-thirds of PBC subjects, but its etiology remains obscure.

Biliary bypass surgery - Analysis of indications & outcome of different procedures.

PubMed

Hussain Talpur, K Altaf; Mahmood Malik, Arshad; Iqbal Memon, Amir; Naeem Qureshi, Jawed; Khan Sangrasi, Ahmed; Laghari, Abdul Aziz

2013-05-01

This study reports the indications and outcome of various biliary bypass surgical procedures from a single centre over a period of 10 years. This is a prospective observational study conducted over a period of 10 years (January 2001-december 2010). A total of 1500 patients were included, who underwent pancreatico-biliary surgery due to common bile duct (CBD) stones, congenital anomalies of biliary tree, unoperable pancreatico-biliary malignancies, CBD strictures and cases who developed iatrogenic biliary injuries during cholecystectomy (both open & laproscopic) during this period of time. The patients who required biliary bypass surgery were further analysed for indications and outcome. Out of 1500 patients 83(5.53%) required biliary bypass surgical procedures. The CBD stones were observed as the most common indication (25.3%), followed by CBD injuries after open(10.84%) or laproscopic-cholecystectomy (14.46%), carcinoma head of pancreas (12.05%) and CBD obstruction(14.46%) either due to CBD strictures or unknown distal obstruction. Roux-en-Y-hepatico-jejunostomy (26.51%) was the most frequently performed procedure, followed by choledochoduodenostomy and Roux-en-Y choledocho-jejunostomy (i.e. 25.3% and 12.05% respectively). Roux-en-Y biliary bypass procedure was observed to be associated with better outcome in terms of rate of complications as well duration of hospital stay. Biliary bypass surgical procedures are the better options to restore the continuity of biliary system in patients with iatrogenic biliary tree injuries and un-operable pancreatico-biliary malignancy. Roux-en-Y biliary bypass procedure is safe and problem solving method in these cases.

Biliary bypass surgery – Analysis of indications & outcome of different procedures

PubMed Central

Hussain Talpur, K.Altaf; Mahmood Malik, Arshad; Iqbal Memon, Amir; Naeem Qureshi, Jawed; Khan Sangrasi, Ahmed; Laghari, Abdul Aziz

2013-01-01

Objectives: This study reports the indications and outcome of various biliary bypass surgical procedures from a single centre over a period of 10 years. Methods: This is a prospective observational study conducted over a period of 10 years (January 2001-december 2010). A total of 1500 patients were included, who underwent pancreatico-biliary surgery due to common bile duct (CBD) stones, congenital anomalies of biliary tree, unoperable pancreatico-biliary malignancies, CBD strictures and cases who developed iatrogenic biliary injuries during cholecystectomy (both open & laproscopic) during this period of time. The patients who required biliary bypass surgery were further analysed for indications and outcome. Results: Out of 1500 patients 83(5.53%) required biliary bypass surgical procedures. The CBD stones were observed as the most common indication (25.3%), followed by CBD injuries after open(10.84%) or laproscopic-cholecystectomy (14.46%), carcinoma head of pancreas (12.05%) and CBD obstruction(14.46%) either due to CBD strictures or unknown distal obstruction. Roux-en-Y-hepatico-jejunostomy (26.51%) was the most frequently performed procedure, followed by choledochoduodenostomy and Roux-en-Y choledocho-jejunostomy (i.e. 25.3% and 12.05% respectively). Roux-en-Y biliary bypass procedure was observed to be associated with better outcome in terms of rate of complications as well duration of hospital stay. Conclusion: Biliary bypass surgical procedures are the better options to restore the continuity of biliary system in patients with iatrogenic biliary tree injuries and un-operable pancreatico-biliary malignancy. Roux-en-Y biliary bypass procedure is safe and problem solving method in these cases. PMID:24353631

[Liver involvement in coeliac disease].

PubMed

Riestra, S; Fernández, E; Rodrigo, L

1999-12-01

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.

Ursodeoxycholic acid in chronic liver disease.

PubMed Central

de Caestecker, J S; Jazrawi, R P; Petroni, M L; Northfield, T C

1991-01-01

The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome. PMID:1916492

Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity.

PubMed

Hrdlickova, Barbara; Kumar, Vinod; Kanduri, Kartiek; Zhernakova, Daria V; Tripathi, Subhash; Karjalainen, Juha; Lund, Riikka J; Li, Yang; Ullah, Ubaid; Modderman, Rutger; Abdulahad, Wayel; Lähdesmäki, Harri; Franke, Lude; Lahesmaa, Riitta; Wijmenga, Cisca; Withoff, Sebo

2014-01-01

Although genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). lncRNAs are known to show more cell-type specificity than protein-coding genes. We aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AIDs which have been well-defined by Immunochip analysis and by transcriptome analysis across seven populations of peripheral blood leukocytes (granulocytes, monocytes, natural killer (NK) cells, B cells, memory T cells, naive CD4(+) and naive CD8(+) T cells) and four populations of cord blood-derived T-helper cells (precursor, primary, and polarized (Th1, Th2) T-helper cells). We show that lncRNAs mapping to loci shared between AID are significantly enriched in immune cell types compared to lncRNAs from the whole genome (α <0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five different cell types enriched (α <0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, and psoriasis; memory T and CD8(+) T cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis). Furthermore, we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. The observed enrichment of lncRNA transcripts in AID loci implies lncRNAs play an important role in AID etiology and suggests that lncRNA genes should be studied in more detail to interpret GWAS findings correctly. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways.

Endoscopic management of biliary complications following liver transplantation after donation from cardiac death donors.

PubMed

Croome, Kris P; McAlister, Vivian; Adams, Paul; Marotta, Paul; Wall, William; Hernandez-Alejandro, Roberto

2012-09-01

Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.

Emerging Technologies for the Diagnosis of Perihilar Cholangiocarcinoma.

PubMed

Rizvi, Sumera; Eaton, John; Yang, Ju Dong; Chandrasekhara, Vinay; Gores, Gregory J

2018-05-01

The diagnosis of malignant biliary strictures remains problematic, especially in the perihilar region and in primary sclerosing cholangitis (PSC). Conventional cytology obtained during endoscopic retrograde cholangiography (ERC)-guided brushings of biliary strictures is suboptimal due to limited sensitivity, albeit it remains the gold standard with a high specificity. Emerging technologies are being developed and validated to address this pressing unmet patient need. Such technologies include enhanced visualization of the biliary tree by cholangioscopy, intraductal ultrasound, and confocal laser endomicroscopy. Conventional cytology can be aided by employing complementary and advanced cytologic techniques such as fluorescent in situ hybridization (FISH), and this technique should be widely adapted. Interrogation of bile and serum by examining extracellular vesicle number and cargo, and exploiting next-generation sequencing and proteomic technologies, is also being explored. Examination of circulating cell-free deoxyribonucleic acid (cfDNA) for differentially methylated regions is a promising test which is being rigorously validated. The special expertise required for these analyses has to date hampered their validation and adaptation. Herein, we will review these emerging technologies to inform the reader of the progress made and encourage further studies, as well as adaptation of validated approaches. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.

PubMed

Yamaguchi, Tomohiro; Machida, Nozomu; Morizane, Chigusa; Kasuga, Akiyoshi; Takahashi, Hideaki; Sudo, Kentaro; Nishina, Tomohiro; Tobimatsu, Kazutoshi; Ishido, Kenji; Furuse, Junji; Boku, Narikazu; Okusaka, Takuji

2014-09-01

This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

A case of severe osteomalacia caused by Tubulointerstitial nephritis with Fanconi syndrome in asymptomotic primary biliary cirrhosis.

PubMed

Yamaguchi, Shintaro; Maruyama, Tatsuya; Wakino, Shu; Tokuyama, Hirobumi; Hashiguchi, Akinori; Tada, Shinichiro; Homma, Koichiro; Monkawa, Toshiaki; Thomas, James; Miyashita, Kazutoshi; Kurihara, Isao; Yoshida, Tadashi; Konishi, Konosuke; Hayashi, Koichi; Hayashi, Matsuhiko; Itoh, Hiroshi

2015-11-11

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated. In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not been recognized as a result of the renal involvement of PBC. PBC and its rare complication of TIN with Fanconi syndrome should be considered in adult patients with unexplained osteomalacia even in the absence of liver dysfunction.

Clinical significance of isolated biliary candidiasis in patients with unresectable cholangiocarcinoma.

PubMed

Kim, In-Ho; Choi, Jae-Ki; Lee, Dong-Gun; Lee, In Seok; Hong, Tae Ho; You, Young Kyoung; Chun, Ho Jong; Lee, Myung Ah

2016-10-01

The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical significance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture. The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was significantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without [median overall survival (OS): 32 vs 62 days, P=0.011]. Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candidiasis (median OS: 30 vs 49 days, P=0.046). Biliary candidiasis was identified as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated candidiasis (4/19, 21%) showed Candida species in consecutive blood culture until the end of the study, but others showed no candidemia. Isolated biliary candidiasis may be associated with poor prognosis in patients with unresectable cholangiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis.

[BILIARY HYPERTENSION IN CHRONIC PANCREATITIS AND PECULIARITIES OF ITS DIAGNOSIS].

PubMed

Kopchak, V M; Pylypchuk, V I; Khomyak, I V; Pererva, L O; Shevkolenko, G G; Davydenko, N G

2016-02-01

Possibilities of various diagnostic methods for biliary hypertension detection in chronic pancreatitis were analyzed. Biliary hypertension was revealed in 163 (31%) patients, suffering chronic pancreatitis. The laboratory investigations data, ultrasonographic investigation, computer tomography, endoscopic retrograde cholangiopancreatography, magnet-resonance cholangiopancreatography, intraoperative measurement of the biliary ducts width, intraoperative measurement of biliary pressure were applied for diagnosis. Endoscopic retrograde cholangiopancreatography, magnet-resonance cholangiopancreatography and intraoperative measurement of biliary pressure are considered the most sensitive methods for chronic pancreatitis diagnosis.

The association between body mass index and severe biliary infections: a multivariate analysis.

PubMed

Stewart, Lygia; Griffiss, J McLeod; Jarvis, Gary A; Way, Lawrence W

2012-11-01

Obesity has been associated with worse infectious disease outcomes. It is a risk factor for cholesterol gallstones, but little is known about associations between body mass index (BMI) and biliary infections. We studied this using factors associated with biliary infections. A total of 427 patients with gallstones were studied. Gallstones, bile, and blood (as applicable) were cultured. Illness severity was classified as follows: none (no infection or inflammation), systemic inflammatory response syndrome (fever, leukocytosis), severe (abscess, cholangitis, empyema), or multi-organ dysfunction syndrome (bacteremia, hypotension, organ failure). Associations between BMI and biliary bacteria, bacteremia, gallstone type, and illness severity were examined using bivariate and multivariate analysis. BMI inversely correlated with pigment stones, biliary bacteria, bacteremia, and increased illness severity on bivariate and multivariate analysis. Obesity correlated with less severe biliary infections. BMI inversely correlated with pigment stones and biliary bacteria; multivariate analysis showed an independent correlation between lower BMI and illness severity. Most patients with severe biliary infections had a normal BMI, suggesting that obesity may be protective in biliary infections. This study examined the correlation between BMI and biliary infection severity. Published by Elsevier Inc.

Stenting in Malignant Biliary Obstruction.

PubMed

Almadi, Majid A; Barkun, Jeffrey S; Barkun, Alan N

2015-10-01

Decompression of the biliary system in patients with malignant biliary obstruction has been widely accepted and implemented as part of the care. Despite a wealth of literature, there remains a significant amount of uncertainty as to which approach would be most appropriate in different clinical settings. This review covers stenting of the biliary system in cases of resectable or palliative malignant biliary obstruction, potential candidates for biliary drainage, technical aspects of the procedure, as well as management of biliary stent dysfunction. Furthermore, periprocedural considerations including proper mapping of the location of obstruction and the use of antibiotics are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy of preoperative biliary drainage in malignant obstructive jaundice: a meta-analysis and systematic review.

PubMed

Moole, Harsha; Bechtold, Matthew; Puli, Srinivas R

2016-07-11

In patients requiring surgical resection for malignant biliary jaundice, it is unclear if preoperative biliary drainage (PBD) would improve mortality and morbidity by restoration of biliary flow prior to operation. This is a meta-analysis to pool the evidence and assess the utility of PBD in patients with malignant obstructive jaundice. The primary outcome is comparing mortality outcomes in patients with malignant obstructive jaundice undergoing direct surgery (DS) versus PBD. The secondary outcomes include major adverse events and length of hospital stay in both the groups. Studies using PBD in patients with malignant obstructive jaundice were included in this study. For the data collection and extraction, articles were searched in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials & Database of Systematic Reviews, etc. Pooled proportions were calculated using both Mantel-Haenszel method (fixed effects model) and DerSimonian-Laird method (random effects model). Initial search identified 2230 reference articles, of which 204 were selected and reviewed. Twenty-six studies (N = 3532) for PBD in malignant obstructive jaundice which met the inclusion criteria were included in this analysis. The odds ratio for mortality in PBD group versus DS group was 0.96 (95 % CI = 0.71 to 1.29). Pooled number of major adverse effects was lower in the PBD group at 10.40 (95 % CI = 9.96 to 10.83) compared to 15.56 (95 % CI = 15.06 to 16.05) in the DS group. Subgroup analysis comparing internal PBD to DS group showed lower odds for major adverse events (odds ratio, 0.48 with 95 % CI = 0.32 to 0.74). In patients with malignant biliary jaundice requiring surgery, PBD group had significantly less major adverse effects than DS group. Length of hospital stay and mortality rate were comparable in both the groups.

Asymptomatic T-tube remnant in common bile duct.

PubMed

Rozario, A; Thomas, P G; Pais, A; Ravindra, K V; Rao, V

1999-01-01

A 46-year-old lady presented with itching, five years after a primary common bile duct repair following cholecystectomy. Prior to this she underwent an interno-external biliary drainage. At laparotomy the horizontal limb of a T-tube was found in the common hepatic duct. Eleven months after a Roux loop hepatico-jejunostomy she is asymptomatic.

Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-PP) for Patients With Advanced Cancer.

ClinicalTrials.gov

2010-08-02

Ovarian; Melanoma; Renal; Prostate; Colorectal; Endometrial Carcinoma; Cervical Carcinoma; Testicular Cancer; Thyroid Cancer; Small Cell Lung Carcinoma; Mesothelioma; Breast Carcinoma; Esophageal Carcinoma; Gastric Cancer; Pancreatic Carcinoma; Neuroendocrine Cancer; Liver Cancer; Gallbladder Cancer; Biliary Tract Cancer; Anal Carcinoma; Bone Sarcomas; Soft Tissue Sarcomas; Carcinoma of Unknown Origin, Primary

Management of blunt and penetrating biliary tract trauma.

PubMed

Thomson, Benjamin N J; Nardino, Benson; Gumm, Kellie; Robertson, Amanda J; Knowles, Brett P; Collier, Neil A; Judson, Rodney

2012-06-01

Penetrating or blunt injury to the biliary tree remains a rare complication of trauma occurring in 0.1% of trauma admissions. Because of the different presentations, sites of biliary tract injury, and associated organ injury, there are many possible management pathways to be considered. A retrospective analysis of prospectively gathered data was performed for all gallbladder and biliary tract injuries presenting to the trauma service or hepatobiliary unit of the Royal Melbourne Hospital between January 1, 1999, and March 30, 2011. There were 33 biliary injuries in 30 patients (0.1%) among 26,014 trauma admissions. Three of the 30 patients (10%) died. Of 10 gallbladder injuries, 8 were managed with cholecystectomy. There were 23 injuries to the biliary tree. Fourteen patients had injuries to the intrahepatic biliary tree of which seven involved segmental ducts. Of these, four segmental duct injuries required hepatic resection or debridement. Nine patients had injury to the extrahepatic biliary tree of which five required T-tube placement ± bilioenteric anastomosis and one a pancreaticoduodenectomy. Biliary injury is a rare but important consequence of abdominal trauma, and good outcomes are possible when a major trauma center and hepatopancreaticobiliary service coexist. Cholecystectomy remains the gold standard for gallbladder injury. Drainage with or without endoscopic stenting will resolve the majority of intrahepatic and partial biliary injuries. Hepaticojejunostomy remains the gold standard for complete extrahepatic biliary disruption. Hepatic and pancreatic resection are only required in the circumstances of unreconstructable biliary injury. Therapeutic study, level V. Copyright © 2012 by Lippincott Williams & Wilkins.

Biliary papillary neoplasm of the liver.

PubMed

Nakanuma, Y; Sasaki, M; Ishikawa, A; Tsui, W; Chen, T C; Huang, S F

2002-01-01

Biliary papillary neoplasia of the liver characterized by intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk has been sporadically reported, and includes intraductal growing cholangiocarcinoma and biliary papillomatosis. In addition, biliary papillary dysplasia and in situ and microinvasive carcinoma with papillary configuration reported in hepatolithiasis and in other chronic biliary diseases, could be included in this category. Usually, they arise in the intrahepatic large bile ducts, and the neoplastic and non-neoplastic parts of the intrahepatic biliary tree show saccular and segmental dilatation with mucin hypersecretion. This neoplasia frequently shows intraductal spreading and peribiliary glandular involvement. Acute repeated episodes of cholangitis or obstructive jaundice are a frequent clinical manifestation. Gastroenteric metaplasia with aberrant expression of cytokeratin 20, MUC2, MUC5AC, and/or MUC6, is frequent in the neoplastic parts, and biliary epithelial dysplasia with such metaplasia may give rise to in situ and then invasive carcinoma in hepatolithiasis. Interestingly, this type tends to contain foci of mucinous carcinoma elements, and this element may be predominant (mucinous carcinoma). Some may progress to "mucinous biliary cystadenocarcinoma" without ovarian mesenchymal stroma and with intraluminal continuous growth into the neighboring bile duct lumens. Interestingly, the biliary papillary neoplasm resembles histologically, phenotypically and clinically intraductal papillary mucinous neoplasm of the pancreas which is now being established as an infrequent, slow-growing pancreatic neoplasm. Recognition of such biliary papillary neoplasm with respect to the pancreatic equivalent may lead to a better understanding and further studies of the intrahepatic biliary neoplasm.

Linkage of Higher Education with Agricultural Research, Extension and Development in Ethiopia

ERIC Educational Resources Information Center

Belay, Kassa

2008-01-01

High-level agricultural manpower training in Ethiopian institutions of higher education (AIHE)specializing in agriculture and related fields was studied. The study reveals that high-level agricultural manpower training began in the early 1950s and that, at present, the country has seven institutions of higher learning, which train students in…

Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.

PubMed

Wang, Renxue; Liu, Lin; Sheps, Jonathan A; Forrest, Dana; Hofmann, Alan F; Hagey, Lee R; Ling, Victor

2013-08-15

The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice.

[Amiodarone-induced thyrotoxicosis].

PubMed

Bogazzi, Fausto; Tomisti, Luca; Di Bello, Vitantonio; Martino, Enio

2017-03-01

Amiodarone-induced thyroid dysfunction occurs in about 15-20% of patients under amiodarone therapy. Amiodarone-induced hypothyroidism (AIH) can develop in patients with an apparently normal thyroid gland or in those with an underlying chronic autoimmune thyroiditis. On a clinical ground, AIH is not challenging and can be easily treated with L-thyroxine therapy. Amiodarone-induced thyrotoxicosis (AIT) can occur in patients with (AIT 1) or without (AIT 2) an underlying thyroid disease. AIT 1 is a true iodine-induced hyperthyroidism occurring in patients with an underlying thyroid autonomy while AIT 2 is a drug-induced destructive thyroiditis. According to the different pathogenetic mechanism, AIT 2 is treated with glucocorticoids while AIT 1 usually responds to thionamides. Thyroidectomy should be considered when AIT represents an imminent risk for cardiac conditions, when patients require a prompt resolution of thyrotoxicosis or when they do not respond to the medical therapy. An effective collaboration between cardiologists and endocrinologists is crucial in each part of the management of AIT patients, including the evaluation of cardiological conditions with regard to thyroid hormone excess and whether, or not, it is necessary to continue amiodarone therapy.

Risk factors for recurrent symptomatic pigmented biliary stones after percutaneous transhepatic biliary extraction.

PubMed

Kim, Dong Won; Lee, Sang Yun; Cho, Jin-Han; Kang, Myong Jin; Noh, Myung Hwan; Park, Byeong-Ho

2010-07-01

To evaluate risk factors for the recurrence of biliary stones after a percutaneous transhepatic biliary stone extraction. The procedures were performed on 339 patients between July 2004 and December 2008 (54 months). Medical records and images were retrospectively reviewed for 135 patients (mean age, 66.4 years; 83 men and 52 women) who had undergone follow-up for a mean of 13.2 months (range, 3-37 months). To evaluate risk factors for the recurrence of biliary stones, variables were evaluated with univariate and multivariate analyses. Variables included sex, age, stone location, number of stones, stone size, presence of a peripapillary diverticulum, application of antegrade sphincteroplasty, presence of a biliary stricture, largest biliary diameter before the procedure, and gallbladder status. Thirty-three of the 135 patients (24%) had recurrent symptomatic biliary stones and underwent an additional extraction. The mean time to recurrence was 17.2 months +/- 8.7. Univariate analysis of risk factors for recurrence of biliary stones demonstrated that location, number of stones, stone size, application of antegrade sphincteroplasty, presence of a biliary stricture, and biliary diameter were significant factors (P < .05). With use of multivariate analysis, the number of stones (> or =6; relative risk, 64.8; 95% confidence interval: 5.8, 717.6) and stone size (> or =14 mm; relative risk, 3.8; 95% confidence interval: 1.138, 13.231) were determined to be significant risk factors. The independent risk factors for recurrence of symptomatic biliary stones after percutaneous transhepatic biliary stone extraction were a stone size of at least 14 mm and the presence of at least six stones. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

Choledochorraphy (primary repair) versus t-tube drainage after open choledochotomy.

PubMed

Saeed, Nadia; Nasir, Muhammad Tauqeer; Khan, Muhammad Iqbal; Channa, Ghulam Asghar

2012-01-01

T-tube drainage used to be standard practice after surgical choledochotomy, but there is now a tendency in some canters to close the common bile duct primarily. This study was designed to compare the clinical results of primary closure with T-tube drainage after open choledocotomy and assess the safety of primary closure for future application. This study was conducted at surgical Unit-3, ward 26 Jinnah Postgraduate Medical Centre Karachi, from January 2007 to January 2008. Forty patients were included in this study out of which 20 underwent primary closure and 20 T-tube placements. It was Quasi-experimental, non-probability, purposive sampling. Main outcome measures were operating time, duration of hospital stay, and postoperative complications. SPSS-10 was used for data analysis. The age of patients in the study ranged from 29-83 years. There were 3 male while 37 female patients. Group-1 consisted of 20 patients underwent primary closure after choledocotomy, while Group-2 also consisted of 20 patients underwent T-tube drainage after duct exploration. Mean hospital stay in Group-1 patients was 7.63 days while in group 2 it was 13.6 days. Overall complication rate in group 1 was 15%, biliary leakage in 1 (5%), jaundice in 1 (5%), wound infection in 1 (5%). No re-exploration was required in Group-1. In Group-2 overall complication rate was 30%, biliary leakage in 2 (2%), jaundice in 1 (5%), dislodgement of T-tube in 1 (5%), wound infection in 1 (5%), and sepsis in 1 (5%) patients. Re-exploration was done in one patient. Primary closure of Common Bile Duct (CBD) is a safe and cost-effective alternative procedure to routine T-tube drainage after open choledocotomy.

Stools - pale or clay-colored

MedlinePlus

... biliary system. The biliary system is the drainage system of the gallbladder, liver, and pancreas. Considerations The liver ... hepatitis Biliary cirrhosis Cancer or noncancerous (benign) tumors of the liver, biliary system, or pancreas Cysts of the bile ducts Gallstones ...

[Biliary calculi resistant to dissolution with bile acids: their heterogeneous composition and diversity of treatment response].

PubMed

Ruíz de Aguiar, A; Medina, J A; Garrido, G; Villacorta, J; Berenguer, J

1992-05-01

We have studied thirteen biliary stones resistant to biliary acids, using technical methods of stereomicroscopy, scanning electronic microscopy and EDX analyses. We have investigated changes on surface. Three biliary stones did not change and were considered resistant. Seven biliary stones appear partially dissolved and we observed many irregularities on surface and/or concentric dips in relation with cholesterol dissolution. In six cases, biliary pigment alternates with cholesterol. In three cases we observed a calcium carbonate coat on surface. One case included organic fibers. One biliary stone showed cholesterol with spherical bodies of calcium carbonate and pigment. It was a relapsed case of combined treatment. Three stones are composed of small black portions of polymerized calcium bilirubinate, rich in copper and iron. Our results demonstrate that biliary stones previously selected for treatment are a heterogeneous group. Because of this fact we get variable and unpredictable results.

Endoscopic Stent Placement in the Palliation of Malignant Biliary Obstruction

PubMed Central

2011-01-01

Biliary drainage with biliary stent placement is the treatment of choice for palliation in patients with malignant biliary obstruction caused by unresectable neoplasms. In such patients, the endoscopic approach can be initially used with percutaneous radiological intervention. In patients with unresectable malignant distal bile duct obstructions, endoscopic biliary drainage with biliary stent placement has now become the main and least invasive palliative modality, which has been proven to be more effective in >80% of cases with lower morbidity than surgery, and perhaps may provide a survival benefit. In patients with unresectable malignant hilar obstruction, the endoscopic approach for biliary drainage with biliary stent placement has also been considered as the treatment of choice. There is still a lack of clear consensus on the use of covered versus uncovered metal stents in malignant distal bile duct obstructions and plastic versus metal stents and unilateral versus bilateral drainage in malignant hilar obstructions. PMID:22741117

Long-term facilitation of ventilation following acute continuous hypoxia in awake humans during sustained hypercapnia

PubMed Central

Griffin, Harry S; Pugh, Keith; Kumar, Prem; Balanos, George M

2012-01-01

In awake humans, long-term facilitation of ventilation (vLTF) following acute intermittent hypoxia (AIH) is only expressed if CO2 is maintained above normocapnic levels. vLTF has not been reported following acute continuous hypoxia (ACH) and it is not known whether this might be unmasked by elevated CO2. Twelve healthy participants completed three trials. In all trials end-tidal pressure of CO2 was elevated 4–5 mmHg above normocapnic levels. During Trial 1 (AIH) participants were exposed to eight 4 min episodes of hypoxia. During Trial 2 (ACH) participants were exposed to continuous hypoxia for 32 min. In Trial 3 (Control) participants were exposed to euoxia throughout. To assess the contribution of the carotid body (CB) in observed ventilatory responses, CB afferent discharge before and after each trial was transiently inhibited with hyperoxia. Minute ventilation () increased following all trials, but was significantly greater in Trials 1 and 2 when compared with Trial 3 (Trial 1: 4.96 ± 0.87, Trial 2: 5.07 ± 0.7, Trial 3: 2.55 ± 0.98 l min−1, P < 0.05). Hyperoxia attenuated to a similar extent in baseline and recovery in all trials (Trial 1: 3.0 ± 0.57 vs. 3.27 ± 0.68, Trial 2: 1.97 ± 0.62 vs. 2.56 ± 0.62, Trial 3: 2.23 ± 0.49 vs. 2.15 ± 0.55 l min−1, P > 0.05). Data are means ± SEM. In awake humans with elevated CO2, ACH evokes a sustained increase in ventilation that is comparable to that evoked by AIH. However, a gradual positive drift in ventilation in response to elevated CO2 accounts for approximately half of this apparent vLTF. Additionally, our data support the view that the CB is not directly involved in maintaining vLTF. PMID:22826133

The Pathogenesis of Autoimmune Liver Disease.

PubMed

Arndtz, Katherine; Hirschfield, Gideon M

Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives. AILD is associated with the presence of auto-antibodies and higher risks of other non-hepatic auto-immune conditions. Genetic risk association studies have identified HLA and non-HLA risk loci for the development of disease, with some HLA loci providing prognostic information. This re-enforces the concept that genetic predisposition to autoimmunity is important, likely in the context of environmental exposures. Such environmental triggers are unclear but relevant risks include smoking, drug and xenobiotic exposure as well as the complexities of the microbiome. There is evidence for a loss of immune tolerance to self-antigens playing a part in the development of these conditions. In particular the IL-2 and IL-12 regulatory pathways have been implicated in pre-disposing to an unopposed inflammatory response within the liver. Main immunological themes revolve around loss of immune tolerance leading to T-cell mediated injury, imbalance in the regulation of immune cells and defective immune response to foreign antigens. For PBC and PSC, there is then the added complexity of the consequences of cholestasis on hepato-biliary injury, immune regulation and liver fibrosis. Whilst specific disease causes and triggers are still lacking, AILD arises on the background of collective genetic and environmental risk, leading to chronic and abnormal hepato-biliary immune responses. Effective and more rational therapy will ultimately be developed when the multiple pathways to liver injury are better understood. © 2016 S. Karger AG, Basel.

Biliary sphincteroplasty facilitates retrieval of proximally migrated plastic biliary stent.

PubMed

Shah, Dharmesh K; Jain, Samit S; Somani, Piyush O; Rathi, Pravin M

2014-01-01

Proximal migration of biliary stents presents a technical challenge for the therapeutic endoscopist. It may require multiple, complicated corrective procedures resulting in significant morbidity to the patients. In this study we evaluated the utility of balloon biliary sphincteroplasty with CRE (Controlled Radial Expansion) Balloon Dilator on retrieval of proximally migrated biliary stents. We identified patients from our ERCP database who presented with proximal migration of biliary stent, between August 2011 and October 2013. Patients in whom the stent could not be retrieved with conventional methods, balloon sphincteroplasty was performed with a 12 mm CRETM Balloon Dilator (Boston Scientific). Stent removal was attempted with extraction balloon or basket thereafter. We identified 28 patients with proximal migration of biliary stents, placed for benign diseases of the common bile duct. Stent removal was successful in 18 patients (64.28%) with help of an extraction balloon or basket. Of the remaining 10 patients, balloon sphincteroplasty was successfully followed by stent removal in eight patients. Balloon biliary sphincteroplasty increases the success rate of retrieving proximally migrated biliary stents. The procedure is safe, technically easy and yields a good success rate in our experience.

Mechanisms of Enhanced Phrenic Long-Term Facilitation in SOD1G93A Rats

PubMed Central

Satriotomo, Irawan; Grebe, Ashley M.

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model (SOD1G93A), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1G93A rats are not known. Moderate AIH-induced pLTF is normally elicited via cellular mechanisms that require the following: Gq-protein-coupled 5-HT2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that requires the following: Gs-protein-coupled adenosine 2A receptor activation, new TrkB synthesis, and PI3K/Akt signaling (the S pathway). In end-stage male SOD1G93A rats and wild-type littermates, we investigated relative Q versus S pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3 kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats, moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although phrenic motor neuron numbers were decreased in end-stage SOD1G93A rats (∼30% survival; p < 0.001), BDNF and phosphorylated ERK expression were increased in spared phrenic motor neurons (p < 0.05), consistent with increased Q-pathway contributions to pLTF. Our results increase understanding of respiratory plasticity and its potential to preserve/restore breathing capacity in ALS. SIGNIFICANCE STATEMENT Since neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), end life via respiratory failure, the ability to harness respiratory motor plasticity to improve breathing capacity could increase the quality and duration of life. In a rat ALS model (SOD1G93A) we previously demonstrated that spinal respiratory motor plasticity elicited by acute intermittent hypoxia is enhanced at disease end-stage, suggesting greater potential to preserve/restore breathing capacity. Here we demonstrate that enhanced intermittent hypoxia-induced phrenic motor plasticity results from amplification of normal cellular mechanisms versus addition/substitution of alternative mechanisms. Greater understanding of mechanisms underlying phrenic motor plasticity in ALS may guide development of new therapies to preserve and/or restore breathing in ALS patients. PMID:28500219

Eosinophilic Cholangitis--A Challenging Diagnosis of Benign Biliary Stricture: A Case Report.

PubMed

Fragulidis, Georgios Panagiotis; Vezakis, Antonios I; Kontis, Elissaios A; Pantiora, Eirini V; Stefanidis, Gerasimos G; Politi, Aikaterini N; Koutoulidis, Vasilios K; Mela, Maria K; Polydorou, Andreas A

2016-01-01

When confronting a biliary stricture, both benign and malignant etiologies must be carefully considered as a variety of benign biliary strictures can masquerade as hilar cholangiocarcinoma (CCA). Therefore, patients could undergo a major surgery despite the possibility of a benign biliary disease. Approximately 15% to 24% of patients undergoing surgical resection for suspected biliary malignancy will have benign pathology. Eosinophilic cholangitis (EC) is a rare benign disorder of the biliary tract, which can cause obstructive jaundice and can pose a difficult diagnostic task. We present a rare case of a young woman who was referred to our hospital with obstructive painless jaundice due to a biliary stricture at the confluence of the hepatic bile ducts, with a provisional diagnosis of cholangiocarcinoma. Though, during her work up she was found to have EC, an extremely rare benign cause of biliary stricture, which is characterized by a dense eosinophilic infiltration of the biliary tree causing stricturing, fibrosis, and obstruction and which is reversible with short-term high-dose steroids. Despite its rarity, EC should be taken into consideration when imaging modalities demonstrate a biliary stricture, especially if preoperative diagnosis of malignancy cannot be made, in the setting of peripheral eosinophilia and the absence of cardinal symptoms of malignancy.

Endoscopic ultrasound-guided biliary drainage

PubMed Central

Chavalitdhamrong, Disaya; Draganov, Peter V

2012-01-01

Endoscopic ultrasound (EUS)-guided biliary drainage has emerged as a minimally invasive alternative to percutaneous and surgical interventions for patients with biliary obstruction who had failed endoscopic retrograde cholangiopancreatography (ERCP). EUS-guided biliary drainage has become feasible due to the development of large channel curvilinear therapeutic echo-endoscopes and the use of real-time ultrasound and fluoroscopy imaging in addition to standard ERCP devices and techniques. EUS-guided biliary drainage is an attractive option because of its minimally invasive, single step procedure which provides internal biliary decompression. Multiple investigators have reported high success and low complication rates. Unfortunately, high quality prospective data are still lacking. We provide detailed review of the use of EUS for biliary drainage from the perspective of practicing endoscopists with specific focus on the technical aspects of the procedure. PMID:22363114

Utility of Shear Wave Elastography for Differentiating Biliary Atresia From Infantile Hepatitis Syndrome.

PubMed

Wang, Xiaoman; Qian, Linxue; Jia, Liqun; Bellah, Richard; Wang, Ning; Xin, Yue; Liu, Qinglin

2016-07-01

The purpose of this study was to investigate the potential utility of shear wave elastography (SWE) for diagnosis of biliary atresia and for differentiating biliary atresia from infantile hepatitis syndrome by measuring liver stiffness. Thirty-eight patients with biliary atresia and 17 patients with infantile hepatitis syndrome were included, along with 31 healthy control infants. The 3 groups underwent SWE. The hepatic tissue of each patient with biliary atresia had been surgically biopsied. Statistical analyses for mean values of the 3 groups were performed. Optimum cutoff values using SWE for differentiation between the biliary atresia and control groups were calculated by a receiver operating characteristic (ROC) analysis. The mean SWE values ± SD for the 3 groups were as follows: biliary atresia group, 20.46 ± 10.19 kPa; infantile hepatitis syndrome group, 6.29 ± 0.99 kPa; and control group, 6.41 ± 1.08 kPa. The mean SWE value for the biliary atresia group was higher than the values for the control and infantile hepatitis syndrome groups (P < .01). The mean SWE values between the control and infantile hepatitis syndrome groups were not statistically different. The ROC analysis showed a cutoff value of 8.68 kPa for differentiation between the biliary atresia and control groups. The area under the ROC curve was 0.997, with sensitivity of 97.4%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 96.9%. Correlation analysis suggested a positive correlation between SWE values and age for patients with biliary atresia, with a Pearson correlation coefficient of 0.463 (P < .05). The significant increase in liver SWE values in neonates and infants with biliary atresia supports their application for differentiating biliary atresia from infantile hepatitis syndrome.

The bile acid composition of crane gallbladder bile

USGS Publications Warehouse

Serafin, J.A.

1983-01-01

1. The biliary bile acids of the whooping crane (Grus americana) and the Florida sandhill crane (G. canadensis pratensis) have been examined.2. Cholic acid (CA), chenodeoxycholic acid (CDOCA) and lithocholic acid were found in bile from both species of these North American cranes.3. CDOCA and CA were the primary bile acids in both species, together constituting 70% or more of the bile acids by weight.4. The primary bile acids of cranes appear to be the same as those that have been identified in other avian species.

Association between cholesterol gallstones and testosterone replacement therapy in a patient with primary hypogonadism.

PubMed

Squarza, S; Rossi, U G; Torcia, P; Cariati, M

A 16-year-old boy had a past medical history of primary hypogonadism, due to bilateral anorchia. He presented with gallstones located in the gallbladder and a mild dilatation of the intrahepatic biliary tree. The histology study reported cholesterol gallstones. The patient had been treated with testosterone replacement therapy since infancy. We suggest a possible correlation between testosterone replacement therapy and the presence of cholesterol gallstones. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-07-01

Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Primary sclerosing cholangitis

PubMed Central

Silveira, Marina G; Lindor, Keith D

2008-01-01

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC. PMID:18701947

PBC triggers in water reservoirs, coal mining areas and waste disposal sites: from Newcastle to New York.

PubMed

Smyk, Daniel; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Bogdanos, Dimitrios P

2010-01-01

Various environmental factors have been proposed as triggers of primary biliary cirrhosis (PBC), a progressive autoimmune cholestatic liver disease which is characterised by the destruction of the small intrahepatic bile ducts. Support for their pathogenic role in PBC is provided by epidemiological studies reporting familial clustering and clusters of the disease within a given geographical area. The seminal study by Triger reporting that the great majority of PBC cases in the English city of Sheffield drank water from a specific water reservoir, has been followed by studies reporting disease 'hot spots' within a restricted geographic region of the former coal mining area of Newcastle. The New York study reporting an increased risk and significant clustering of PBC cases near toxic federal waste disposal sites has added strength to the notion that environmental factors, possibly in the form of infectious agents or toxic/chemical environmental factors in areas of contaminated land, water or polluted air may play a key role in the development of the disease. This review discusses the findings of reports investigating environmental factors which may contribute to the cause of primary biliary cirrhosis.

Nailfold capillaroscopy in primary biliary cirrhosis: a useful tool for the early diagnosis of scleroderma.

PubMed

Tovoli, Francesco; Granito, Alessandro; Giampaolo, Luca; Frisoni, Magda; Volta, Umberto; Fusconi, Marco; Masi, Chiara; Lenzi, Marco

2014-03-01

Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune diseases, including systemic sclerosis (SSc). In the last years many efforts have been dedicated to the research of widely accepted criteria for the early diagnosis of SSc. Since studies on the prevalence of early SSc in PBC patients are lacking, our aim was to investigate its hitherto unknown prevalence in a large cohort of PBC patients. We studied 80 PBC patients and 72 patients with other chronic liver diseases. Diagnostic workup included research into signs of connective tissue disease, determination of autoantibody profile, and examination of capillary abnormalities through nailfold videocapillaroscopy. Ten PBC patients (12.5%) satisfied diagnostic criteria for early SSc and 5 (6.3%) had definite SSc. None of the patients in the control group were diagnosed either with early or definite SSc. No differences were observed in terms of aminotransferases, alkaline phosphatase, and liver function tests between PBC patients with and without associated SSc. Early SSc is significantly frequent in PBC patients. The detection of early SSc in PBC patients may lead to a prompt treatment of its complications, preventing inabilities and preserving the chance of liver transplantation.

Problems related to CMV infection and biliary atresia.

PubMed

Moore, Samuel W; Zabiegaj-Zwick, Caroline; Nel, Etienne

2012-09-11

Human cytomegalovirus (CMV) infection is related to biliary disease, being cholestatic in its own right. It has also been associated with intrahepatic bile duct destruction and duct paucity, indicating a possible role in extrahepatic biliary atresia pathogenesis and progression. When related to biliary atresia CMV IGM positive patients appear to have more liver damage thus affecting outcome. Methods We carried out a retrospective chart review on 74 patients diagnosed with hepatobiliary disease (2000-2011). included clinical and outcome review as well as evaluation of potential risk factors. Patients were divided into 2 groups those with biliary atresia and those without Biliary atresia (BA). The 2 groups were compared in terms of CMV infection. Of the 74 patients with hepatobiliary disease investigated, 39 (52%) were shown to have Biliary atresia and 35 other cases. 12 of the BA group and 4 of the non-BA were excluded due to lack of data Twenty-seven (69%) of the biliary atresia group had sufficient available data for review. Of these, 21 (78% of the 27) had CMV positivity (IgM/IgG) on testing, with 20 of these being IgM positive versus 8 in the non-biliary atresia group. (p<0.01) Two (7.5%) of 27 BA infants were HIV exposed being born to HIV positive mothers whereas HIV positivity was observed in 7 (35%) of the non-biliary atresia group (p<0.01). Both of these biliary atresia infants were CMV IgM positive. Long- term outcome of the 21 with CMV positivity showed 3 deaths (non-HIV exposed) and a higher rate of severe early liver damage suggesting a poorer outcome in CMV affected patients. This study suggests a correlation between CMV exposure, infection and surgical hepatobiliary disease including biliary atresia affecting outcome.HIV positivity does not preclude Biliary atresia and should be further investigated.

Iodine-131 induced hepatotoxicity in previously healthy patients with Grave's disease.

PubMed

Jhummon, Navina Priya; Tohooloo, Bhavna; Qu, Shen

2013-01-01

To describe the association of the rare and serious complication of liver toxicity in previously healthy Grave's disease (GD) patients after the treatment with radioactive iodine (131)I (RAI). We report the clinical, laboratory and pathologic findings of 2 cases of severe liver toxicity associated with the treatment with RAI in previously healthy patients with GD. Clinical examination and laboratory investigations excluded viral hepatitis, autoimmune hepatitis, granulomatous disease, primary biliary disease, extrahepatic biliary obstruction, and heart failure. Case 1: A previously healthy 52-years old man reportedly having a typical GD but following RAI treatment, concomitantly developed severe liver toxicity that required 1 week of treatment in hospital. Case 2: A previously healthy 34-years old woman is reported as having a typical GD but developed jaundice following RAI treatment that required several weeks of in hospital treatment in the hepato-biliary department. In both cases, the liver dysfunction resolved after intensive treatment with hepato-protective agents. In this report the therapeutic considerations as well as the pathogenetic possibilities are reviewed. To the best of our knowledge, this is the first description of the association observed, which is rare but may be severe and should be considered in any case of thyrotoxicosis where a liver dysfunction develops after the treatment with radioactive iodine (131)I.

Post-cholecystectomy syndrome: spectrum of biliary findings at magnetic resonance cholangiopancreatography

PubMed Central

Girometti, R; Brondani, G; Cereser, L; Como, G; Del Pin, M; Bazzocchi, M; Zuiani, C

2010-01-01

Post-cholecystectomy syndrome (PCS) is defined as a complex of heterogeneous symptoms, consisting of upper abdominal pain and dyspepsia, which recur and/or persist after cholecystectomy. Nevertheless, this term is inaccurate, as it encompasses biliary and non-biliary disorders, possibly unrelated to cholecystectomy. Biliary manifestations of PCS may occur early in the post-operative period, usually because of incomplete surgery (retained calculi in the cystic duct remnant or in the common bile duct) or operative complications, such as bile duct injury and/or bile leakage. A later onset is commonly caused by inflammatory scarring strictures involving the sphincter of Oddi or the common bile duct, recurrent calculi or biliary dyskinesia. The traditional imaging approach for PCS has involved ultrasound and/or CT followed by direct cholangiography, whereas manometry of the sphincter of Oddi and biliary scintigraphy have been reserved for cases of biliary dyskinesia. Because of its capability to provide non-invasive high-quality visualisation of the biliary tract, magnetic resonance cholangiopancreatography (MRCP) has been advocated as a reliable imaging tool for assessing patients with suspected PCS and for guiding management decisions. This paper illustrates the rationale for using MRCP, together with the main MRCP biliary findings and diagnostic pitfalls. PMID:20335441

Broncho-biliary fistula secondary to biliary obstruction and lung abscess in a patient with pancreatic neuro-endocrine tumor.

PubMed

Panda, Dipanjan; Aggarwal, Mayank; Yadav, Vikas; Kumar, Sachin; Mukund, Amar; Baghmar, Saphalta

2016-06-01

We present a case report of broncho-biliary fistula that developed due to the blockage of biliary stent placed during the management of pancreatic neuroendocrine tumor (pNET); diagnosed on high clinical suspicion, percutaneous cholangiogram and contrast enhanced computed tomography (CECT); and successfully treated with percutaneous transhepatic biliary drainage (PTBD). Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Differentiation of pancreatobiliary cancer from benign biliary strictures using neutrophil gelatinase-associated lipocalin.

PubMed

Budzynska, A; Nowakowska-Dulawa, E; Marek, T; Boldys, H; Nowak, A; Hartleb, M

2013-02-01

Aim of the study was to investigate the value of serum and bile neutrophil gelatinase-associated lipocalin (NGAL) for distinguishing malignant strictures caused by cholangiocarcinoma (CCA) or pancreatic cancer from benign biliary strictures. The study was performed prospectively on patients admitted for endoscopic or radiologic biliary decompression. Forty patients with dilated biliary ducts, including 16 cases of CCA, 6 cases of pancreatic cancer, and 18 cases of benign biliary stricture were enrolled. Their sera and bile were collected to measure NGAL. Routine biochemistry including measurement of serum levels of carbohydrate antigens (CA) 19-9 and carcinoembryonic antigen (CEA) was also performed. The serum CA19-9, serum CEA, and bile NGAL levels were significantly increased in patients with malignant strictures as compared with patients with benign biliary diseases. Serum NGAL had no significant value for discriminating between malignant and benign biliary strictures. Bile NGAL levels had a receiver characteristic area under the curve of 0.74, sensitivity 77.3, and specificity 72.2% for discriminating between pancreatobiliary cancer and benign biliary diseases. Bile NGAL and serum CA19-9 were independent parameters and their combined use improved diagnostic accuracy (sensitivity 91%, negative predictive value 85.7%). We conclude that measurement of biliary, but not serum NGAL, may differentiate malignant pancreatobiliary from benign biliary strictures, serving as a complementary biomarker for serum CA19-9.

Current diagnosis and treatment of benign biliary strictures after living donor liver transplantation

PubMed Central

Chang, Jae Hyuck; Lee, Inseok; Choi, Myung-Gyu; Han, Sok Won

2016-01-01

Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation (LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach. PMID:26819525

Endoscopic biliary stent insertion through specialized duodenal stent for combined malignant biliary and duodenal obstruction facilitated by stent or PTBD guidance.

PubMed

Lee, Jong Jin; Hyun, Jong Jin; Choe, Jung Wan; Lee, Dong-Won; Kim, Seung Young; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Lee, Sang Woo

2017-11-01

Endoscopic stenting for combined malignant biliary and duodenal obstruction is technically demanding. However, this procedure can be facilitated when there is guidance from previously inserted stent or PTBD tube. This study aimed to evaluate the feasibility and clinical success rate of endoscopic placement of biliary self-expandable metal stent (SEMS) through duodenal SEMS in patients with combined biliary and duodenal obstruction due to inoperable or metastatic periampullary malignancy. A total of 12 patients with combined malignant biliary and duodenal stricture underwent insertion of biliary SEMS through the mesh of specialized duodenal SEMS from July 2012 to October 2016. Technical and clinical success rate, adverse events and survival after completion of SEMS insertion were evaluated. The duodenal strictures were located in the first portion of the duodenum in four patients (Type I), in the second portion in three patients (Type II), and in the third portion in five patients (Type III). Technical success rate of combined metallic stenting was 91.7%. Insertion of biliary SEMS was guided by previously inserted biliary SEMS in nine patients, plastic stent in one patient, and PTBD in two patients. Clinical success rate was 90.9%. There were no early adverse events after the procedure. Mean survival period after combined metallic stenting was 91.9 days (range: 15-245 days). Endoscopic placement of biliary SEMS through duodenal SEMS is feasible with high success rates and relatively easy when there is guidance. This method can be a good alternative for palliation in patients with combined biliary and duodenal obstruction.

Ablating L-FABP in SCP-2/SCP-x null mice impairs bile acid metabolism and biliary HDL-cholesterol secretion

PubMed Central

Martin, Gregory G.; Atshaves, Barbara P.; Landrock, Kerstin K.; Landrock, Danilo; Storey, Stephen M.; Howles, Philip N.; Kier, Ann B.

2014-01-01

On the basis of their abilities to bind bile acids and/or cholesterol, the physiological role(s) of liver fatty acid-binding protein (L-FABP) and sterol carrier protein (SCP) 2/SCP-x (SCP-2/SCP-x) gene products in biliary bile acid and cholesterol formation was examined in gene-ablated male mice. L-FABP (LKO) or L-FABP/SCP-2/SCP-x [triple-knockout (TKO)] ablation markedly decreased hepatic bile acid concentration, while SCP-2/SCP-x [double-knockout (DKO)] ablation alone had no effect. In contrast, LKO increased biliary bile acid, while DKO and TKO had no effect on biliary bile acid levels. LKO and DKO also altered biliary bile acid composition to increase bile acid hydrophobicity. Furthermore, LKO and TKO decreased hepatic uptake and biliary secretion of high-density lipoprotein (HDL)-derived 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol), while DKO alone had no effect. Finally, LKO and, to a lesser extent, DKO decreased most indexes contributing to cholesterol solubility in biliary bile. These results suggest different, but complementary, roles for L-FABP and SCP-2/SCP-x in biliary bile acid and cholesterol formation. L-FABP appears to function more in hepatic retention of bile acids as well as hepatic uptake and biliary secretion of HDL-cholesterol. Conversely, SCP-2/SCP-x may function more in formation and biliary secretion of bile acid, with less impact on hepatic uptake or biliary secretion of HDL-cholesterol. PMID:25277800

Comparative evaluation of ceftriaxone- and cefotaxime-induced biliary pseudolithiasis or nephrolithiasis: A prospective study in 154 children.

PubMed

Ustyol, L; Bulut, M D; Agengin, K; Bala, K A; Yavuz, A; Bora, A; Demiroren, K; Dogan, M

2017-06-01

Biliary lithiasis, or sludge, and nephrolithiasis have been reported as a possible complication of ceftriaxone therapy. However, no study related to cefotaxime-induced biliary pseudolithiasis or nephrolithiasis was observed in the literature. Therefore, we investigated the comparative formation of biliary pseudolithiasis and nephrolithiasis after cefotaxime and ceftriaxone therapies. The patients treated with ceftriaxone or cefotaxime were enrolled during the study period. Ultrasound imaging of the biliary and urinary tract was performed in all patients before and after the treatment. The patients with a positive sonographic finding at the end of treatment were followed up with monthly ultrasonography for 3 months. The present study showed that abnormal biliary sonographic findings were demonstrated in 18 children (20.9%) treated with ceftriaxone, 13 (15.1%) had biliary lithiasis, 5 (5.8%) had biliary sludge and 1 (1.2%) had nephrolithiasis. Abnormal biliary sonographic findings were demonstrated in only four (5.9%) children treated with cefotaxime who had biliary sludge and only one (1.5%) had nephrolithiasis. It was observed that older age was at significantly higher risk of developing biliary sludge or stone formation. Receiver operating characteristic analysis was performed to determine the residual risk and analysis found that 4.5 years was the cut-off value for age. The present study is unique in the literature for reporting for the first time gall bladder sludge and nephrolithiasis associated with cefotaxime use. Therefore, patients treated with cefotaxime should be monitored for serious complications like patients treated with ceftriaxone. Nevertheless, if third-generation cephalosporin is used, cefotaxime is recommended to be used rather than ceftriaxone.

Pre-operative biliary drainage for obstructive jaundice

PubMed Central

Fang, Yuan; Gurusamy, Kurinchi Selvan; Wang, Qin; Davidson, Brian R; Lin, He; Xie, Xiaodong; Wang, Chaohua

2014-01-01

Background Patients with obstructive jaundice have various pathophysiological changes that affect the liver, kidney, heart, and the immune system. There is considerable controversy as to whether temporary relief of biliary obstruction prior to major definitive surgery (pre-operative biliary drainage) is of any benefit to the patient. Objectives To assess the benefits and harms of pre-operative biliary drainage versus no pre-operative biliary drainage (direct surgery) in patients with obstructive jaundice (irrespective of a benign or malignant cause). Search methods We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2012. Selection criteria We included all randomised clinical trials comparing biliary drainage followed by surgery versus direct surgery, performed for obstructive jaundice, irrespective of the sample size, language, and publication status. Data collection and analysis Two authors independently assessed trials for inclusion and extracted data. We calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals (CI) based on the available patient analyses. We assessed the risk of bias (systematic overestimation of benefit or systematic underestimation of harm) with components of the Cochrane risk of bias tool. We assessed the risk of play of chance (random errors) with trial sequential analysis. Main results We included six trials with 520 patients comparing pre-operative biliary drainage (265 patients) versus no pre-operative biliary drainage (255 patients). Four trials used percutaneous transhepatic biliary drainage and two trials used endoscopic sphincterotomy and stenting as the method of pre-operative biliary drainage. The risk of bias was high in all trials. The proportion of patients with malignant obstruction varied between 60% and 100%. There was no significant difference in mortality (40/265, weighted proportion 14.9%) in the pre-operative biliary drainage group versus the direct surgery group (34/255, 13.3%) (RR 1.12; 95% CI 0.73 to 1.71; P = 0.60). The overall serious morbidity was higher in the pre-operative biliary drainage group (60 per 100 patients in the pre-operative biliary drainage group versus 26 per 100 patients in the direct surgery group) (RaR 1.66; 95% CI 1.28 to 2.16; P = 0.0002). The proportion of patients who developed serious morbidity was significantly higher in the pre-operative biliary drainage group (75/102, 73.5%) in the pre-operative biliary drainage group versus the direct surgery group (37/94, 37.4%) (P < 0.001). Quality of life was not reported in any of the trials. There was no significant difference in the length of hospital stay (2 trials, 271 patients; MD 4.87 days; 95% CI −1.28 to 11.02; P = 0.12) between the two groups. Trial sequential analysis showed that for mortality only a small proportion of the required information size had been obtained. There seemed to be no significant differences in the subgroup of trials assessing percutaneous compared to endoscopic drainage. Authors’ conclusions There is currently not sufficient evidence to support or refute routine pre-operative biliary drainage for patients with obstructive jaundice. Pre-operative biliary drainage may increase the rate of serious adverse events. So, the safety of routine pre-operative biliary drainage has not been established. Pre-operative biliary drainage should not be used in patients undergoing surgery for obstructive jaundice outside randomised clinical trials. PMID:22972086

Hilar cholangiocarcinoma: diagnosis, treatment options, and management

PubMed Central

Soares, Kevin C.; Kamel, Ihab; Cosgrove, David P.; Herman, Joseph M.

2014-01-01

Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6th decade of life. Of the 3,000 cases seen annually in the United States, less than one half of these tumors are resectable. A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. Patients typically present with abdominal pain, pruritis, weight loss, and jaundice. Computed topography (CT), magnetic resonance imaging (MRI), and ultrasound (US) are used to characterize biliary lesions. Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) assess local ductal extent of the tumor while allowing for therapeutic biliary drainage. MRCP has demonstrated similar efficacies to PTC and ERCP in identifying anatomic extension of tumors with less complications. Treatment consists of surgery, radiation, chemotherapy and photodynamic therapy. Biliary drainage of the future liver remnant should be performed to decrease bilirubin levels thereby facilitating future liver hypertrophy. Standard therapy consists of surgical margin-negative (R0) resection with extrahepatic bile duct resection, hepatectomy and en bloc lymphadenectomy. Local resection should not be undertaken. Lymph node invasion, tumor grade and negative margins are important prognostic indicators. In instances where curative resection is not possible, liver transplantation has demonstrated acceptable outcomes in highly selected patients. Despite the limited data, chemotherapy is indicated for patients with unresectable tumors and adequate functional status. Five-year survival after surgical resection of HC ranges from 10% to 40% however, recurrence can be as high as 50-70% even after R0 resection. Due to the complexity of this disease, a multi-disciplinary approach with multimodal treatment is recommended for this complex disease. PMID:24696835

Efficacy and safety of limited endoscopic sphincterotomy before self-expandable metal stent insertion for malignant biliary obstruction

PubMed Central

Nam, Hyeong Seok; Kang, Dae Hwan; Kim, Hyung Wook; Choi, Cheol Woong; Park, Su Bum; Kim, Su Jin; Ryu, Dae Gon

2017-01-01

AIM To evaluate the safety and efficacy of limited endoscopic sphincterotomy (ES) before placement of self-expandable metal stent (SEMS). METHODS This was a retrospective analysis of 244 consecutive patients with unresectable malignant biliary obstruction, who underwent placement of SEMSs following limited ES from December 2008 to February 2015. The diagnosis of malignant biliary obstruction and assessment of patient eligibility for the study was established by a combination of clinical findings, laboratory investigations, imaging and pathological results. All patients were monitored in the hospital for at least 24 h following endoscopic retrograde cholangio pancreatography (ERCP). The incidence of immediate or early post-ERCP complications such as post-ERCP pancreatitis (PEP) and bleeding related to limited ES were considered as primary outcomes. Also, characteristics and complications according to the cancer type were classified. RESULTS Among the 244 patients included, the underlying diagnosis was cholangiocarcinoma in 118 patients, pancreatic cancer in 79, and non-pancreatic or non-biliary malignancies in the remaining 47 patients. Early post-ERCP complications occurred in 9 patients (3.7%), with PEP in 7 patients (2.9%; mild, 6; moderate, 1) and mild bleeding in 2 patients (0.8%). There was no significant association between the incidence of post-ERCP complications and the type of malignancy (cholangiocarcinoma vs pancreatic cancer vs others, P = 0.696) or the type of SEMS used (uncovered vs covered, P = 1.000). Patients who had more than one SEMS placed at the first instance were at a significantly higher risk of post-ERCP complications (one SEMS vs two SEMS, P = 0.031). No other factors were predictive of post-ERCP complications. CONCLUSION Limited ES is feasible and safe, and effectively facilitates the placement of SEMS, without any significant risk of PEP or severe bleeding. PMID:28321164

Revision concepts and distinctive points of the new Japanese classification for biliary tract cancers in comparison with the 7(th) edition of the Union for International Cancer Control and the American Joint Committee on Cancer staging system.

PubMed

Ohtsuka, Masayuki; Miyakawa, Shuichi; Nagino, Masato; Takada, Tadahiro; Miyazaki, Masaru

2015-03-01

The 3(rd) English edition of the Japanese classification of the biliary tract cancers (JC) is now available in this journal. The primary aim of this revision is to provide all clinicians and researchers with a common language of cancer staging at an international level. On the other hand, there are several important issues that should be solved for the optimization of the staging system. Revision concepts and major revision points of the 3(rd) English edition of the JC were reviewed. Furthermore, comparing with the 7(th) edition of staging system developed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), distinctive points in the JC was discussed. In this edition of the JC, the same stage groupings as those in the UICC/AJCC staging system were basically adopted. T, N, and M categories were also identical in principle with those in the UICC/AJCC staging system, although slight modifications were proposed as the "Japanese rules". As distinctive points, perihilar cholangiocarcinomas and ampullary region carcinomas were clearly defined. Intraepithelial tumor was discriminated from invasive carcinoma at ductal resection margins. Classifications of site-specific surgical margin status remained in this edition. Histological classification was based on that in the former editions of the JC, but adopted some parts of the World Health Organization classification. The JC now share its staging system of the biliary tact carcinomas with the UICC/AJCC staging system. Future validation of the "Japanese rules" could provide important evidence to make globally standardized staging system. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Efficacy and safety of limited endoscopic sphincterotomy before self-expandable metal stent insertion for malignant biliary obstruction.

PubMed

Nam, Hyeong Seok; Kang, Dae Hwan; Kim, Hyung Wook; Choi, Cheol Woong; Park, Su Bum; Kim, Su Jin; Ryu, Dae Gon

2017-03-07

To evaluate the safety and efficacy of limited endoscopic sphincterotomy (ES) before placement of self-expandable metal stent (SEMS). This was a retrospective analysis of 244 consecutive patients with unresectable malignant biliary obstruction, who underwent placement of SEMSs following limited ES from December 2008 to February 2015. The diagnosis of malignant biliary obstruction and assessment of patient eligibility for the study was established by a combination of clinical findings, laboratory investigations, imaging and pathological results. All patients were monitored in the hospital for at least 24 h following endoscopic retrograde cholangio pancreatography (ERCP). The incidence of immediate or early post-ERCP complications such as post-ERCP pancreatitis (PEP) and bleeding related to limited ES were considered as primary outcomes. Also, characteristics and complications according to the cancer type were classified. Among the 244 patients included, the underlying diagnosis was cholangiocarcinoma in 118 patients, pancreatic cancer in 79, and non-pancreatic or non-biliary malignancies in the remaining 47 patients. Early post-ERCP complications occurred in 9 patients (3.7%), with PEP in 7 patients (2.9%; mild, 6; moderate, 1) and mild bleeding in 2 patients (0.8%). There was no significant association between the incidence of post-ERCP complications and the type of malignancy (cholangiocarcinoma vs pancreatic cancer vs others, P = 0.696) or the type of SEMS used (uncovered vs covered, P = 1.000). Patients who had more than one SEMS placed at the first instance were at a significantly higher risk of post-ERCP complications (one SEMS vs two SEMS, P = 0.031). No other factors were predictive of post-ERCP complications. Limited ES is feasible and safe, and effectively facilitates the placement of SEMS, without any significant risk of PEP or severe bleeding.

Ursodeoxycholic Acid Ameliorates Intrahepatic Cholestasis Independent of Biliary Bicarbonate Secretion in Vil2kd/kd Mice.

PubMed

Hatano, Ryo; Kawaguchi, Kotoku; Togashi, Fumitaka; Sugata, Masato; Masuda, Shizuka; Asano, Shinji

2017-01-01

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that possesses many pharmacological effects, including increasing bile flow, changing the hydrophobicity of the bile acid pool, and modulation of the immune response. UDCA has been approved for treating cholestatic liver disease, such as primary biliary cholangitis. However, several unanticipated severe side effects of UDCA are observed in cholestatic patients, and its pharmacological benefits remain controversial. We reported that ezrin-knockdown (Vil2 kd/kd ) mice exhibited severe hepatic injury because of a functional disorder in bile duct fluidity and alkalinity regulation, resembling human intrahepatic cholestatic disease. Here we used Vil2 kd/kd mice as a cholestatic model to investigate the pharmacological effects of UDCA. We investigated the effects of oral and parenteral administration of UDCA on Vil2 kd/kd mice. In Vil2 kd/kd mice, fed a 0.5% (w/w) UDCA diet for 3 weeks, hepatic injury was exacerbated, although oral administration of a lower dose of UDCA slightly improved hepatic function in Vil2 kd/kd mice. On the other hand, intraperitoneal administration of UDCA (50 mg/kg/d) ameliorated hepatic function and markedly reduced periductal fibrosis and cholangiocyte proliferation in Vil2 kd/kd mice although biliary pH and HCO 3 - concentration were not improved. The expression levels of inflammatory and profibrotic genes were also significantly decreased in these mice. Furthermore, UDCA prevented cholangiocytes from hydrophobic bile acid-induced cytotoxicity independent of extracellular pH in in vitro experiments. These results suggest that an appropriate dosage of UDCA can ameliorate the intrahepatic cholestasis in Vil2 kd/kd mice without changing the biliary bicarbonate secretion.

Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation.

PubMed

Sampaziotis, Fotios; de Brito, Miguel Cardoso; Madrigal, Pedro; Bertero, Alessandro; Saeb-Parsy, Kourosh; Soares, Filipa A C; Schrumpf, Elisabeth; Melum, Espen; Karlsen, Tom H; Bradley, J Andrew; Gelson, William Th; Davies, Susan; Baker, Alastair; Kaser, Arthur; Alexander, Graeme J; Hannan, Nicholas R F; Vallier, Ludovic

2015-08-01

The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.

Current management of cholangiocarcinoma.

PubMed

Singh, Manoj K; Facciuto, Marcelo E

2012-01-01

Cholangiocarcinoma is the second most common primary hepatobiliary malignancy after hepatocellular carcinoma and remains among the most difficult management problems faced by surgeons. Curative surgery is achieved in only 25% to 30% of patients. Local tumor extent, such as portal vein invasion and hepatic lobar atrophy, does not preclude resection. Long-term survival has been seen only in patients who underwent extensive liver resections, suggesting that bile-duct excision alone is less effective. The majority of patients have unresectable disease, with 20% to 30% incidence of distant metastasis at presentation. Unresectable patients should be referred for nonsurgical biliary decompression, and in potential curative resection candidates the use of biliary stents should be reduced. Liver transplantation provides the option of wide resection margins, expanding the indication of surgical intervention for selected patients who otherwise are not surgical candidates due to lack of functional hepatic reserve. © 2012 Mount Sinai School of Medicine.

[SURGICAL TACTICS IN CHRONIC PANCREATITIS WITH SIGNS OF BILIARY HYPERTENSION].

PubMed

Usenko, O Yu; Kopchak, V M; Pylypchuk, V I; Kopchak, K V; Andronik, S V

2015-08-01

The results of treatment of 84 patients for chronic pancreatitis with the biliary hypertension signs were depicted. In 83 patients operative interventions were performed, and in 1--positive results were achieved after pancreatic cyst puncture under ultrasonographic control. In 51 patients the conduction of Frey operation have permitted to achieve a lower pressure inside biliary system, in 25--the additional procedures were applied for a biliary hypertension elimination. In 20 patients a method of pressure measurement in biliary system was used.

Late-onset severe biliary bleeding after endoscopic pigtail plastic stent insertion.

PubMed

Yasuda, Muneji; Sato, Hideki; Koyama, Yuki; Sakakida, Tomoki; Kawakami, Takumi; Nishimura, Takeshi; Fujii, Hideki; Nakatsugawa, Yoshikazu; Yamada, Shinya; Tomatsuri, Naoya; Okuyama, Yusuke; Kimura, Hiroyuki; Ito, Takaaki; Morishita, Hiroyuki; Yoshida, Norimasa

2017-01-28

Here, we report our experience with a case of severe biliary bleeding due to a hepatic arterial pseudoaneurysm that had developed 1 year after endoscopic biliary plastic stent insertion. The patient, a 78-year-old woman, presented with hematemesis and obstructive jaundice. Ruptured hepatic arterial pseudoaneurysm was diagnosed, which was suspected to have been caused by long-term placement of an endoscopic retrograde biliary drainage (ERBD) stent. This episode of biliary bleeding was successfully treated by transarterial embolization (TAE). Pseudoaneurysm leading to hemobilia is a rare but potentially fatal complication in patients with long-term placement of ERBD. TAE is a minimally invasive procedure that offers effective treatment for biliary bleeding.

Pharmacokinetics and Biliary Excretion of Fisetin in Rats.

PubMed

Huang, Miao-Chan; Hsueh, Thomas Y; Cheng, Yung-Yi; Lin, Lie-Chwen; Tsai, Tung-Hu

2018-06-14

The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague-Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios ( k (%) = AUC conjugate /AUC free-form ) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate ( k BE (%) = AUC bile /AUC plasma ) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.

Biliary hemorrhage after removal of an expandable metallic stent during liver transplantation.

PubMed

Narumi, Shunji; Hakamda, Kenichi; Toyoki, Yoshikazu; Ishido, Keinosuke; Nara, Masaki; Yoshihara, Syuichi; Sasaki, Mutsuo

2008-11-01

The self-expandable metallic stent (SEMS) has become a common device for palliative treatment of malignant biliary obstructions or benign strictures. Despite the ease of placement of SEMSs, their removal has been reported to be very difficult. Here, we report a case with primary sclerosing cholangitis who developed massive hemorrhage after intraoperative removal of a SEMS. Possible living donor liver transplantation (LT) was considered for a 49-year-old female with primary sclerosing cholangitis. However, her general condition did not meet the criteria for LT; therefore, she was referred back to her primary physician. Two years later, she developed jaundice, and her primary physician placed multiple SEMSs, 1 of which was placed across the papilla of Vater. She was evaluated rapidly, and underwent living donor LT. During the operation, the common bile duct was examined and an incision was made. A stent was found firmly embedded in the bile duct. Each wire of the SEMS was pinched and then successfully pulled out 1 by 1. Finally, all parts of the SEMS were removed. Before creating the Roux-en-Y limb, hemorrhage from the remnant bile duct was confirmed by examination of the duodenum and bile duct stump. The bile duct was sewn internally with monofilament stitches and compressed for 10 minutes. Finally, hemostasis was brought about and transplantation was completed successfully. Despite some reports regarding successful endoscopic removal of SEMSs, its removal in patients with portal hypertension coagulopathy is risky. SEMSs should not be placed in patients who are candidates for LT.

Reduced Coffee Consumption Among Individuals with Primary Sclerosing Cholangitis but Not Primary Biliary Cirrhosis

PubMed Central

Lammert, Craig; Juran, Brian D.; Schlicht, Erik; Xie, Xiao; Atkinson, Elizabeth J.; de Andrade, Mariza; Lazaridis, Konstantinos N.

2014-01-01

Background & Aims Coffee consumption has been associated with decreased risk of liver disease and related outcomes. However, coffee drinking has not been investigated among patients with cholestatic autoimmune liver diseases, primary biliary cirrhosis (PBC), or primary sclerosing cholangitis (PSC). We investigated the relationship between coffee consumption and risk of PBC and PSC in a large North American cohort. Methods Lifetime coffee drinking habits were determined from responses to questionnaires from 606 patients with PBC, 480 with PSC, and 564 healthy volunteers (controls). Patients (those with PBC or PSC) were compared to controls utilizing the Wilcoxon rank sum test for continuous variables and c2 method for discrete variables. Logistic regression was used to analyze the estimate the effects of different coffee parameters (time, frequency, and type of coffee consumption) after adjusting for age, sex, smoking status, and education level. Results Patients with PBC and controls did not differ in coffee parameters. However, 24% of patients with PSC had never drank coffee compared to 16% of controls (P<.05), and only 67% were current drinkers compared with 77% of controls (P<.05). Patients with PSC also consumed fewer lifetime cups per month (45 vs 47 for controls, P<.05) and spent a smaller percentage of their lifetime of coffee drinking coffee (46.6% vs 66.7% for controls, P<.05). These differences remained significant in a multivariate model. Among PSC patients with concurrent ulcerative colitis, coffee protected against proctocolectomy (hazard ratio=0.34, P<.001). Conclusions Coffee consumption is lower among patients with PSC, but not PBC, compared to controls. PMID:24440215

Liver stem/progenitor cells in the canals of Hering: cellular origin of hepatocellular carcinoma with bile duct tumor thrombi?

PubMed

Peng, Ningfu; Li, Lequn; Cai, Xiang; Tan, Shaozao; Wu, Ting

2010-12-01

It is generally believed that the invasion of hepatocellular carcinoma (HCC) into the biliary tree ultimately leads to the formation of bile duct tumor thrombi (BDTT). However, recent studies revealed that primary tumor might be small, even undetectable, and there was no histopathologic evidence of direct tumor invasion into bile duct wall in some patients. During the last decade, efforts on stem cell biology may shed light on the pathogenesis of BDTT. Presently, accumulating evidence supports the following notions: (1) the canals of Hering (CoH) are the most likely origin of liver stem/progenitor cells (LSPCs) in adult livers; (2) similar signalling pathways may regulate self-renewal in LSPCs and liver cancer cells, and a substantial proportion of liver tumors may often originate from the transformation of LSPCs; and (3) liver cancer contains rare cells with stem cell-like properties, which could derive from malignant transformation of LSPCs. Herein, we propose that HCC with BDTT, especially with small or undetectable primary lesion and/or no histopathologic evidence for bile duct invasion, might arise from LSPCs residing in the CoH and, possibly, some primary lesions are formed firstly within the intrahepatic biliary tree. When "tumor thrombi" extends mainly along bile duct, there might be "BDTT" alone; when it invades into surrounding parenchyma, there might often be small "primary tumor" with "BDTT". If this holds true, the putative type may be a particular subset of HCC, and most importantly it would facilitate our understanding of stem-cell origin of HCC.

Newborn Screening for Biliary Atresia.

PubMed

Wang, Kasper S

2015-12-01

Biliary atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of biliary obstruction within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child's native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has biliary atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for biliary atresia to improve outcomes. Herein, newborn screening for biliary atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for biliary atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of biliary atresia in the United States. Copyright © 2015 by the American Academy of Pediatrics.

Biodegradable biliary stent implantation in the treatment of benign bilioplastic-refractory biliary strictures: preliminary experience.

PubMed

Mauri, Giovanni; Michelozzi, Caterina; Melchiorre, Fabio; Poretti, Dario; Tramarin, Marco; Pedicini, Vittorio; Solbiati, Luigi; Cornalba, Gianpaolo; Sconfienza, Luca Maria

2013-12-01

To evaluate feasibility, safety, and outcome of patients treated with biodegradable biliary stents for benign biliary stenosis refractory to other treatments. Between March 2011 and September 2012, ten patients (seven men, three women; age 59 ± 7 years) with recurrent cholangitis due to postsurgical biliary stricture, previous multiple unsuccessful (two to five) bilioplasties, and unsuitability for surgical/endoscopic repair underwent percutaneous implantation of a biodegradable biliary stent. Patients were followed-up clinically and with ultrasound at 1, 3 and 6 months, and then at 6-month intervals. Stent implantation was always feasible. No immediate major or minor complications occurred. In all patients, 48-h cholangiographic control demonstrated optimal stent positioning and stenosis resolution. In a median follow-up time of 16.5 months (25th-75th percentiles = 11-20.25 months) no further invasive treatment was needed. Three patients experienced transient episodes of cholangitis. Neither re-stenosis nor dilatation of the biliary tree was documented during follow-up. No stent was visible at the 6-month follow-up. Percutaneous placement of biodegradable biliary stents represents a new option in treating benign biliary stenoses refractory to treatment with bilioplasty. This technique seems to be feasible, effective and free from major complications. Further investigations are warranted to confirm our preliminary results.

Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

NASA Astrophysics Data System (ADS)

Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott; Xu, Ronald X.

2012-11-01

We encapsulate indocyanine green (ICG) in poly[(D,L-lactide-co-glycolide)-co-PEG] diblock (PLGA-PEG) microballoons for real-time fluorescence and hyperspectral imaging of biliary anatomy. ICG-loaded microballoons show superior fluorescence characteristics and slower degradation in comparison with pure ICG. The use of ICG-loaded microballoons in biliary imaging is demonstrated in both biliary-simulating phantoms and an ex vivo tissue model. The biliary-simulating phantoms are prepared by embedding ICG-loaded microballoons in agar gel and imaged by a fluorescence imaging module in a Da Vinci surgical robot. The ex vivo model consists of liver, gallbladder, common bile duct, and part of the duodenum freshly dissected from a domestic swine. After ICG-loaded microballoons are injected into the gallbladder, the biliary structure is imaged by both hyperspectral and fluorescence imaging modalities. Advanced spectral analysis and image processing algorithms are developed to classify the tissue types and identify the biliary anatomy. While fluorescence imaging provides dynamic information of movement and flow in the surgical region of interest, data from hyperspectral imaging allow for rapid identification of the bile duct and safe exclusion of any contaminant fluorescence from tissue not part of the biliary anatomy. Our experiments demonstrate the technical feasibility of using ICG-loaded microballoons for biliary imaging in cholecystectomy.

Extrahepatic biliary atresia: current concepts and future directions.

PubMed

de Carvalho, Elisa; Ivantes, Cláudia Alexandra Pontes; Bezerra, Jorge A

2007-01-01

To provide an updated review on extrahepatic biliary atresia, focusing mainly on its etiopathogenesis, diagnosis, treatment and prognosis. MEDLINE and PubMed databases were searched using the following keywords: biliary atresia, etiopathogenesis, diagnosis, treatment, prognosis, children. Extrahepatic biliary atresia is the main indication for liver transplantation among pediatric patients. As to its etiology, cytomegalovirus, reovirus and rotavirus have been widely investigated as possible triggers of the immunomediated obstruction of the biliary tree. The immune response, especially the predominant TH1 and interferon-gamma responses, genetic susceptibility and disorders related to the embryonic development of the biliary tree can play a role in the etiopathogenesis of extrahepatic biliary atresia. Yet today, portoenterostomy is the only available treatment, with better results when performed in the first 2 months of life. As to prognosis, all untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo liver transplantation. Extrahepatic biliary atresia is still the major indication for pediatric liver transplantation, and to change this scenario some more light should be shed upon the etiopathogenesis of biliary atresia in different disease phenotypes. Future research into the role of interferon-gamma and of other cytokines is necessary in order to assess whether these aspects should be potential targets for therapeutic intervention.

Surgical Management of Benign Biliary Stricture in Chronic Pancreatitis: A Single-Center Experience.

PubMed

Ray, Sukanta; Ghatak, Supriyo; Das, Khaunish; Dasgupta, Jayanta; Ray, Sujay; Khamrui, Sujan; Sonar, Pankaj Kumar; Das, Somak

2015-12-01

Biliary stricture in chronic pancreatitis (CP) is not uncommon. Previously, all cases were managed by surgery. Nowadays, three important modes of treatment in these patients are observation, endoscopic therapy, and surgery. In the modern era, surgery is recommended only in a subset of patients who develop biliary symptoms or those who have asymptomatic biliary stricture and require surgery for intractable abdominal pain. We want to report on our experience regarding surgical management of CP-induced benign biliary stricture. Over a period of 5 years, we have managed 340 cases of CP at our institution. Bile duct stricture was found in 62 patients. But, surgical intervention was required in 44 patients, and the remaining 18 patients were managed conservatively. Demographic data, operative procedures, postoperative complications, and follow-up parameters of these patients were collected from our prospective database. A total 44 patients were operated for biliary obstruction in the background of CP. Three patients were excluded, so the final analysis was based on 41 patients. The indication for surgery was symptomatic biliary stricture in 27 patients and asymptomatic biliary stricture with intractable abdominal pain in 14 patients. The most commonly performed operation was Frey's procedure. There was no inhospital mortality. Thirty-five patients were well at a mean follow-up of 24.4 months (range 3 to 54 months). Surgery is still the best option for CP-induced benign biliary stricture, and Frey's procedure is a versatile operation unless you suspect malignancy as the cause of biliary obstruction.

Noninvasive Imaging of the Biliary System Relevant to Percutaneous Interventions

PubMed Central

Thomas, Stephen; Jahangir, Kayleen

2016-01-01

Clinical data such as history, physical examination, and laboratory tests are useful in identifying patients with biliary obstruction and biliary sources of infection. However, if intervention is planned, noninvasive imaging is needed to confirm the presence, location, and extent of the disease process. Currently, the most commonly available and used noninvasive modalities are ultrasound (US), computed tomography (CT), magnetic resonance (MR), and nuclear medicine hepatobiliary scintigraphy (HIDA). US is quick, portable, readily available, and is commonly the first imaging modality used when biliary pathology is suspected. It is excellent in the detection of cholelithiasis and acute cholecystitis but is limited in detecting choledocholithiasis. CT is excellent at detecting infected postoperative fluid collections, bilomas, biliary obstruction, and biliary infection but is limited in the detection of cholelithiasis. Therefore, US may be more useful than CT for the initial screening of acute biliary disease. MR has inherent advantages over CT, as it does not use ionizing radiation, can be done without intravenous contrast, and its detection of cholelithiasis is not affected by the internal composition of the stone. Magnetic resonance cholangiopancreatography can be used to determine the cause and location of biliary obstruction but is limited in the detection of small stones and the evaluation of the biliary tract near the ampulla. HIDA is used to evaluate for cholecystitis, biliary obstruction, and bile leaks. The main limitation is its lack of anatomical detail, and it is therefore frequently performed in conjunction with other described modalities. PMID:27904246

Ablating L-FABP in SCP-2/SCP-x null mice impairs bile acid metabolism and biliary HDL-cholesterol secretion.

PubMed

Martin, Gregory G; Atshaves, Barbara P; Landrock, Kerstin K; Landrock, Danilo; Storey, Stephen M; Howles, Philip N; Kier, Ann B; Schroeder, Friedhelm

2014-12-01

On the basis of their abilities to bind bile acids and/or cholesterol, the physiological role(s) of liver fatty acid-binding protein (L-FABP) and sterol carrier protein (SCP) 2/SCP-x (SCP-2/SCP-x) gene products in biliary bile acid and cholesterol formation was examined in gene-ablated male mice. L-FABP (LKO) or L-FABP/SCP-2/SCP-x [triple-knockout (TKO)] ablation markedly decreased hepatic bile acid concentration, while SCP-2/SCP-x [double-knockout (DKO)] ablation alone had no effect. In contrast, LKO increased biliary bile acid, while DKO and TKO had no effect on biliary bile acid levels. LKO and DKO also altered biliary bile acid composition to increase bile acid hydrophobicity. Furthermore, LKO and TKO decreased hepatic uptake and biliary secretion of high-density lipoprotein (HDL)-derived 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol), while DKO alone had no effect. Finally, LKO and, to a lesser extent, DKO decreased most indexes contributing to cholesterol solubility in biliary bile. These results suggest different, but complementary, roles for L-FABP and SCP-2/SCP-x in biliary bile acid and cholesterol formation. L-FABP appears to function more in hepatic retention of bile acids as well as hepatic uptake and biliary secretion of HDL-cholesterol. Conversely, SCP-2/SCP-x may function more in formation and biliary secretion of bile acid, with less impact on hepatic uptake or biliary secretion of HDL-cholesterol. Copyright © 2014 the American Physiological Society.

Long-term outcomes and risk factors of biliary stent dysfunction after endoscopic double stenting for malignant biliary and duodenal obstructions.

PubMed

Matsumoto, Kazuyuki; Kato, Hironari; Tsutsumi, Koichiro; Mizukawa, Sho; Yabe, Syuntaro; Seki, Hiroyuki; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Yamamoto, Naoki; Horiguchi, Shigeru; Kuwaki, Kenji; Okada, Hiroyuki

2017-07-01

Few reports describe the endoscopic double-stenting procedure for malignant biliary and duodenal obstructions. We evaluated the clinical outcomes from double stenting, and analyzed the risk factors for biliary stent dysfunction following double stenting. Eighty-one patients who underwent endoscopic double stenting for malignant biliary and duodenal obstructions were retrospectively analyzed. We determined the stent dysfunction rate and the biliary stent dysfunction risk factors, and analyzed the endoscopic reintervention results. Overall survival time and survival time following double stenting were 365 (38-1673) days and 73 (20-954) days, respectively. After double stenting, the 3-month and 6-month duodenal stent dysfunction rates were 14% and 41%, respectively. Reintervention technical success rate was 100% (10/10), and mean gastric outlet obstruction scoring system scores improved from 0.7 to 2.4 points (P < 0.001). The 3-month and 6-month biliary stent dysfunction rates were 26% and 41%, respectively. The reintervention technical and clinical success rates were 95% (20/21) and 81% (17/21), respectively. Risk factors for biliary stent dysfunction following double stenting were events associated with duodenal stent dysfunction (odds ratio [OR], 11.1; 95% confidence interval [CI], 2.09-87.4; P = 0.0044) and the biliary stent end's location (OR, 6.93; 95% CI, 1.37-40.2; P = 0.0019). Some patients had stent dysfunction irrespective of the survival period after double stenting. Endoscopic reintervention was technically feasible and clinically effective even after double stenting. Duodenal stent dysfunction and biliary stent end's location were risk factors for biliary stent dysfunction. © 2017 Japan Gastroenterological Endoscopy Society.

Percutaneous biliary covered stent insertion in patients with malignant duodenobiliary obstruction.

PubMed

Lee, Eunsol; Gwon, Dong Il; Ko, Gi-Young; Sung, Kyu-Bo; Yoon, Hyun-Ki; Shin, Ji Hoon; Kim, Jin Hyoung; Ko, Heung Kyu; Song, Ho-Young

2015-02-01

Although the use of polytetrafluoroethylene (PTFE)-covered biliary stents has proven to be feasible for the treatment of benign and malignant biliary disease, less is known regarding the outcomes of percutaneous placement of a covered stent in patients with malignant duodenobiliary obstruction. To investigate the technical and clinical efficacy of the percutaneous placement of a PTFE-covered biliary stent in patients with malignant duodenobiliary obstruction. From April 2007 to September 2012, the medical records of 45 consecutive patients with malignant duodenobiliary obstruction were retrospectively reviewed. All percutaneous biliary stent deployment was performed using PTFE-covered stents, whereas duodenal stent insertion was performed either fluoroscopically or endoscopically using covered or uncovered stents. Biliary stent deployment was technically successful in all patients. None of the stents migrated after deployment. Procedure-related minor complications, including self-limiting hemobilia, occurred in three (7%) patients. Successful internal drainage was achieved in 39 (87%) of the 45 patients. The median survival time after biliary stent placement was 62 days (95% confidence interval, 8-116 days), and the cumulative stent patency rates at 1, 3, 6, and 12 months were 96%, 92%, 75%, and 38%, respectively. The causes of biliary stent dysfunction included stent occlusion caused by a subsequently inserted duodenal stent (n = 7), food impaction (n = 3), and sludge incrustation (n = 1). One patient developed acute cholecystitis 131 days after biliary stent placement and underwent percutaneous transhepatic gallbladder drainage. Percutaneous insertion of a PTFE-covered stent is a safe and effective method for palliative treatment of patients with malignant duodenobiliary obstruction. If possible, subsequent biliary stent insertion is preferable in order to prevent possible biliary stent dysfunction caused by subsequent insertion of a duodenal stent. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Analysis of soluble factors in conditioned media derived from primary cultures of cirrhotic liver of biliary atresia.

PubMed

Yamazaki, Taisuke; Wakai, Mariko; Enosawa, Shin; Tokiwa, Takayoshi

2017-06-01

Biliary atresia (BA) is a rare and serious liver disease in newborn infants. Previously, we reported that non-parenchymal cell (NPC) fractions from cirrhotic liver of BA may contain hepatic stem/progenitor cells in primary culture of NPC fractions. In this study, NPC fractions were subjected to primary or passage culture and found that clusters of hepatocyte-like cells appear even without adding hepatocyte growth factor (HGF) to the culture medium, but not in their passage culture used as a control. Based on these findings, conditioned media (CMs) were collected and soluble factors in the CMs were analyzed in order to elucidate the mechanism of the appearance of hepatocyte-like cells or their clusters. A large amount of active HGF consisting of α and β chains was detected in CMs derived from primary culture, but not in CMs from passage culture, as determined by western blot analysis, bone morphogenetic protein (BMP)-4, oncostatin M (OSM), and transforming growth factor (TGF)-β1 were not detected in any of the CMs. The number of hepatocyte-like cells in primary culture tended to decrease following treatment with the HGF receptor c-Met inhibitor, SU11274 in a dose-dependent manner. Furthermore, the clusters of hepatocyte-like cells tended to increase in size and number when freshly isolated NPC fractions were cultured in the presence of 10% of CMs collected after 3-4 wk of primary culture. In conclusion, these findings indicate that CMs derived from primary culture of NPC fractions of BA liver contain a large amount of active HGF, which may activate hepatic stem/progenitor cells and promote the appearance of hepatocyte-like cells or their clusters through HGF/c-Met signaling. The present study would lead to cell therapy using the patient's own cells for the treatment of BA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eriguchi, Takahisa; Takeda, Atsuya; Sanuki, Naoko

Purpose: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. Methods and Materials: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. Results: Fifty patients with 55 tumors weremore » irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. Conclusions: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.« less

Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators.

PubMed

Zhang, Hai-Chun; Hu, Rong-Fei; Zhu, Ting; Tong, Ling; Zhang, Qiu-Qin

2016-06-14

To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%). The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value.

Functional Self-Expandable Metal Stents in Biliary Obstruction

PubMed Central

Kwon, Chang-Il; Ko, Kwang Hyun; Hahm, Ki Baik

2013-01-01

Biliary stents are widely used not only for palliative treatment of malignant biliary obstruction but also for benign biliary diseases. Each plastic stent or self-expandable metal stent (SEMS) has its own advantages, and a proper stent should be selected carefully for individual condition. To compensate and overcome several drawbacks of SEMS, functional self-expandable metal stent (FSEMS) has been developed with much progress so far. This article looks into the outcomes and defects of each stent type for benign biliary stricture and describes newly introduced FSEMSs according to their functional categories. PMID:24143314

[Calculi formation and biliary hydrodynamics].

PubMed

Zou, S Q

1990-09-01

In this study, 167 white rabbits were divided into 5 groups to observe the effects of biliary stricture and infection on the formation of bile duct stones and the pathophysiological changes of the biliary tract. It was found that there was a gradient of static hydraulic pressure along biliary tract and the pressure was directly proportional to hepatic blood flow. In the rabbits with bile duct stone formation, the activity of SDH, ATP ase and glycogen (PAS) in the mucosa of biliary tract was low and that of LDH was high. In the biliary tract wall damaged by infection and choledocholithiasis, a frame work consisting of polysaccharide protein, mucin, and mucoid polymer was observed and the authors considered it as one of causing factors in the formation of the stones.

Early pregnancy factor (EPF) as a marker for detecting subclinical embryonic loss in clomiphene citrate-treated women.

PubMed

Shahani, S K; Moniz, C L; Gokral, J S; Meherji, P K

1995-05-01

A discrepancy exists between the apparently normal ovulation and the pregnancy rates in women treated with clomiphene citrate (CC). Our previous studies have indicated that immuno-suppressive "early pregnancy factor" (EPF) is a novel marker to detect subclinical embryonic loss in infertile women. In the present study EPF was used as a marker to detect subclinical embryonic loss in women treated with CC with/without gonadotropins. In some of the women treated with CC, conception was assisted by artificial insemination with husband's semen (AIH). Our results have indicated that fertilization occurred (EPF + ve) in 47.7% (52/109) of women treated with CC with/without gonadotropins; 13.46% (7/52) retained the fetus and continued pregnancy till full term, whereas 78.9% (41/52) did not retain the fetuses. In the group where after stimulation, conception was assisted by AIH, fertilization was observed in 38.24% (26/68), retention in 11.54% (3/26) but subclinical embryonic loss was observed in 80.8% (21/26) cases. Thus, our results have indicated that subclinical embryonic loss may account for some of the discrepancy observed between the apparently normal ovulation and the pregnancy rates in women treated with clomiphene citrate.

Preoperative biliary drainage by plastic or self-expandable metal stents in patients with periampullary tumors: results of a randomized clinical study

PubMed Central

Olsson, Greger; Frozanpor, Farshad; Lundell, Lars; Enochsson, Lars; Ansorge, Christoph; Del Chiaro, Marco; Reuterwall-Hansson, Marcus; Shetye, Alysha; Arnelo, Urban

2017-01-01

Background and study aims  Preoperative biliary drainage in patients with periampullary tumors and jaundice has been popularized to improve the quality of life and minimize the risks associated with subsequent radical surgery. The aim of this study was to investigate the possible superiority of self-expandable metal stents (SEMS) over plastic stents, by comparing the amount of bacteria in intraoperatively collected bile and using this variable as a proxy for the efficacy of the respective biliary drainage modalities. Patients and methods  In this randomized clinical trial, 92 patients with obstructive jaundice were enrolled; 45 were allocated to the plastic stent group and 47 to the SEMS group. The primary outcome was the extent and magnitude of biliary bacterial growth at the time of surgical exploration. Secondary outcomes were: macroscopic grading of inflammation of the stented bile ducts, occurrence of adverse events after stenting, stent dysfunction, recognized surgical complexities, and incidence of postoperative complications. Results  The patients were well matched regarding clinical and disease-specific characteristics. At surgery, there were no group differences in the bacterial amount and composition of the bile cultures or the perceived difficulty of surgical dissection. During the preoperative biliary drainage period, more instances of stent dysfunction requiring stent replacement were recorded in the plastic stent group (19 % vs. 0 %; P  = 0.03). Postoperative complications in patients who underwent curative surgery were more common in patients with plastic stents (72 % vs. 52 %), among which clinically significant leakage from the pancreatic anastomoses seemed to predominate (12 % vs. 3.7 %); however, none of these differences in postoperative adverse events reached statistical significance. Conclusion  This randomized clinical study was unable to demonstrate any superiority of SEMS in the efficacy of preoperative bile drainage, as assessed by the amount of bacteria in the intraoperatively collected bile. However, some data in favor of SEMS were observed among the clinical secondary outcomes variables (preoperative stent exchange rates) without increases in local inflammatory reactions. PMID:28879225

Palliation of Malignant Biliary and Duodenal Obstruction with Combined Metallic Stenting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akinci, Devrim, E-mail: akincid@hotmail.com; Akhan, Okan; Ozkan, Fuat

2007-11-15

Purpose. The purpose of this study is to evaluate the efficacy of palliation of malignant biliary and duodenal obstruction with combined metallic stenting under fluoroscopy guidance. Materials and Methods. A retrospective analysis of 9 patients (6 men and 3 women) who underwent biliary and duodenal stenting was performed. The mean age of patients was 61 years (range: 42-80 years). The causes of obstruction were pancreatic carcinoma in 7 patients, cholangiocellular carcinoma in one, and duodenal carcinoma in the other. Biliary and duodenal stents were placed simultaneously in 4 patients. In other 5 patients dudodenal stents were placed after biliary stentingmore » when the duodenal obstruction symptoms have developed. In two patients duodenal stents were advanced via transgastric approach. Results. Technical success rate was 100 %. After percutaneous biliary drainage and stenting bilirubin levels decreased to normal levels in 6 patients and in remaining 3 patients mean reduction of 71% in bilirubin levels was achieved. Tumoral ingrowth occurred in one patient and percutaneous biliary restenting was performed 90 days after the initial procedure. Of the 9 patients, 6 patients were able to tolerate solid diet, whereas 2 patients could tolerate liquid diet and one patient did not show any improvement. Mean survival periods were 111 and 73 days after biliary and duodenal stenting, respectively. Conclusion. Combined biliary and duodenal stent placement which can be performed under fluoroscopic guidance without assistance of endoscopy is feasible and an effective method of palliation of malignant biliary and duodenal obstructions. If transoral and endoscopic approaches fail, percutaneous gastrostomy route allows duodenal stenting.« less

CT biliary cystoscopy of gallbladder polyps

PubMed Central

Lou, Ming-Wu; Hu, Wei-Dong; Fan, Yi; Chen, Jin-Hua; E, Zhan-Sen; Yang, Guang-Fu

2004-01-01

AIM: CT virtual endoscopy has been used in the study of various organs of body including the biliary tract, however, CT virtual endoseopy in diagnosis of gallbladder polyps has not yet been reported. This study was to evaluate the diagnostic value of CT virtual endoscopy in polyps of the gallbladder. METHODS: Thirty-two cases of gallbladder polyps were examined by CT virtual endoscopy, ultrasound, CT scan with oral biliary contrast separately and confirmed by operation and pathology. CT biliary cystoscopic findings were analyzed and compared with those of ultrasound and CT scan with oral biliary contrast, and evaluated in comparison with operative and pathologic findings in all cases. RESULTS: The detection rate of gallbladder polyps was 93.8%(90/96), 96.9%(93/96) and 79.2%(76/96) for CT cystoscopy, ultrasound and CT scan with oral contrast, respectively. CT biliary cystoscopy corresponded well with ultrasound as well as pathology in demonstrating the location, size and configuration of polyps. CT endoscopy was superior to ultrasound in viewing the polyps in a more precise way, 3 dimensionally from any angle in space, and showing the surface in details. CT biliary cystoscopy was also superior to CT scan with oral biliary contrast in terms of observation of the base of polyps for the presence of a pedicle, detection rates as well as image quality. The smallest polyp detected by CT biliary cystoscopy was measured 1.5 mm×2.2 mm×2.5 mm. CONCLUSION: CT biliary cystoscopy is a non-invasive and accurate technique for diagnosis and management of gallbladder polyps. PMID:15069726

Percutaneous transhepatic cholangiography and intraductal radiofrequency ablation combined with biliary stent placement for malignant biliary obstruction.

PubMed

Li, Teng-Fei; Huang, Guo-Hao; Li, Zhen; Hao, Chang-Fu; Ren, Jian-Zhuang; Duan, Xu-Hua; Zhang, Kai; Chen, Chen; Han, Xin-Wei; Jiao, De-Chao; Zhang, Meng-Fan; Wang, Yan-Li

2015-05-01

To determine the safety and feasibility of percutaneous transhepatic cholangiography (PTC) and intraductal radiofrequency (RF) ablation combined with biliary stent placement for malignant biliary obstruction. Data from patients with unresectable malignant biliary obstruction who underwent PTC, intraductal RF ablation, and biliary stent placement (n = 12) or PTC and biliary stent placement only (control group; n = 14) were reviewed. Postoperative complications, jaundice remission, and stent patency were assessed. All procedures were successful. No severe complications (eg, biliary bleeding, perforation) occurred. Two experimental group patients developed cholangitis, which resolved with conservative treatment. The 1-week jaundice remission and 3-month stent patency rates were similar in both groups, but the 6-month stent patency rate was higher in the experimental group (P < .05). In the experimental group, one death occurred as a result of gastrointestinal hemorrhage (unrelated to stent placement) by 3 months, and there were two cases of recurrent jaundice by 6 months. The latter two patients underwent repeat PTC, ablation, and stent placement. In the control group, one death occurred as a result of hepatic failure caused by progressive jaundice at 3 months, and another death resulted from disseminated intravascular coagulation caused by jaundice recurrence at 138 days after stent placement. In addition, seven patients developed jaundice recurrence (50-151 d after stent placement). PTC and repeat stent placement were performed in these patients. Percutaneous transhepatic cholangiography and intraductal RF ablation combined with biliary stent placement for malignant biliary obstruction is safe and feasible and effectively prolongs stent patency time. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Risk factors for isolated biliary atresia, National Birth Defects Prevention Study, 1997-2002.

PubMed

The, Natalie S; Honein, Margaret A; Caton, Alissa R; Moore, Cynthia A; Siega-Riz, Anna Maria; Druschel, Charlotte M

2007-10-01

Biliary atresia is a rare birth defect that affects 1 in 12,000 to 1 in 19,500 live births. We used data from the National Birth Defects Prevention Study, a multistate case-control study, to identify potential risk factors for isolated biliary atresia (no additional unrelated major birth defects diagnosed). Infants were identified from eight states from 1997 to 2002, with clinical information abstracted from medical records. Potential risk factors assessed include: demographic factors, seasonality, preterm birth, maternal smoking, maternal alcohol use, maternal illicit drug use, maternal health, maternal medication use, maternal vitamin use, and maternal nutrition. Infants of non-Hispanic black mothers were more likely to have biliary atresia than infants of non-Hispanic white mothers (adjusted odds ratio (aOR) = 2.29, 95% confidence interval (CI) 1.07-4.93) and infants conceived during the spring season were more likely to have biliary atresia than infants conceived in winter (aOR = 2.33, 95%CI 1.05-5.16). Low intakes of vitamin E, copper, phosphorus, and beta tocopherol were associated with the occurrence of isolated biliary atresia (borderline significance). Low iron intake had a borderline inverse association with biliary atresia. While this analysis provides support for previous reports of a possible association between seasonal variation and the occurrence of biliary atresia, more data are needed to evaluate whether the seasonal variation is related to infectious agents. The role of nutrients in the development of biliary atresia remains unclear. Further studies of genetic, infectious, and nutrient exposures and the association of biliary atresia are warranted. 2007 Wiley-Liss, Inc

Reversible surgical model of biliary inflammation and obstructive jaundice in mice.

PubMed

Kirkland, Jacob G; Godfrey, Cody B; Garrett, Ryan; Kakar, Sanjay; Yeh, Benjamin M; Corvera, Carlos U

2010-12-01

Common bile duct (CBD) ligation is used in animal models to induce biliary inflammation, fibrosis, and cholestatic liver injury, but results in a high early postoperative mortality rate, probably from traumatic pancreatitis. We modified the CBD ligation model in mice by placing a small metal clip across the lower end of the CBD. To reverse biliary obstruction, a suture was incorporated within the clip during its placement. The suture and clip were removed on postoperative d 5 or 10 for biliary decompression. After 5 d of biliary obstruction, the gallbladder showed an 8-fold increase in wall thickness and a 17-fold increase in tissue myeloperoxidase activity. Markedly elevated serum levels of alkaline phosphatase and bilirubin indicated injury to the biliary epithelium and hepatocytes. Early postoperative (d 0-2) survival was 100% and later (d 3-5) survival was 85% (n=54 mice). We successfully reversed biliary obstruction in 20 mice (37%). Overall survival after reversal was 70%. In surviving mice, biliary decompression was complete, inflammation was reduced, and jaundice resolved. Histologic features confirmed reduced epithelial damage, edema, and neutrophil infiltration. Our technique minimized postoperative death, maintained an effective inflammatory response, and was easily reversible without requiring repeat laparotomy. This reversible model can be used to further define molecular mechanisms of biliary inflammation, fibrosis, and liver injury in genetically altered mice. Copyright © 2010. Published by Elsevier Inc.

Biliary complications after right lobe living donor liver transplantation: a single-centre experience

PubMed Central

Yaprak, Onur; Dayangac, Murat; Akyildiz, Murat; Demirbas, Tolga; Guler, Necdet; Bulutcu, Fisun; Bassullu, Nuray; Akun, Elif; Yuzer, Yildiray; Tokat, Yaman

2012-01-01

Background Biliary complications that developed after right lobe liver transplantation from living donors were studied in a single centre. Methods From 2004 to 2010, 200 consecutive living donor right lobe liver transplantations were performed. The database was evaluated retrospectively. Biliary complications were diagnosed according to clinical, biochemical and radiological tests. The number of biliary ducts in the transplanted graft, the surgical techniques used for anastomosis, biliary strictures and bile leakage rates were analysed. Results Of a total of 200 grafts, 117 invloved a single bile duct, 77 had two bile ducts and in six grafts there were three bile ducts. In 166 transplants, the anastomosis was performed as a single duct to duct, in 21 transplants double duct to ducts, in one transplant, three duct to ducts and in 12 transplants as a Roux-en-Y reconstruction. In all, 40 bile leakages (20%) and 17 biliary strictures (8.5%) were observed in 49 patients resulting in a total of 57 biliary complications (28.5%). Seventeen patients were re-operated (12 as a result of bile leakages and five owing to biliary strictures). Conclusion Identification of more than one biliary orifice in the graft resulted in an increase in the complication rates. In grafts containing multiple orifices, performing multiple duct-to-duct (DD) or Roux-en-Y anastomoses led to a lower number of complications. PMID:22151451

Endoscopic Biliary Stenting Versus Percutaneous Transhepatic Biliary Stenting in Advanced Malignant Biliary Obstruction: Cost-effectiveness Analysis.

PubMed

Sun, Xin Rong; Tang, Cheng Wu; Lu, Wen Ming; Xu, Yong Qiang; Feng, Wen Ming; Bao, Yin; Zheng, Yin Yuan

2014-05-01

This study aims to compare the clinical outcomes and costs between endoscopic biliary stenting (EBS) and percutaneous transhepatic biliary stenting (PTBS). We randomly assigned 112 patients with unresectable malignant biliary obstruction 2006 and 2011 to receive EBS or PTBS with self-expandable metal stent (SEMS) as palliative treatment. PTBS was successfully performed in 55 patients who formed the PTBS group (failed in 2 patients). EBS was successfully performed in 52 patients who formed the EBS group (failed in 3 patients). The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the BBS group (P < 0.05). There was no significant difference in effectiveness of biliary drainage (P = 0.9357) or survival time between two groups (P = 0.6733). Early complications occurred in PTBS group was significantly lower than in EBS group (3/55 vs 11/52, P = 0.0343). Late complications in the EBS group did not differ significantly from PTBS group (7/55 vs 9/52, P = 0.6922). The survival curves in the two groups showed no significant difference (P = 0.5294). Conclusions: 3.

TOKYO criteria 2014 for transpapillary biliary stenting.

PubMed

Isayama, Hiroyuki; Hamada, Tsuyoshi; Yasuda, Ichiro; Itoi, Takao; Ryozawa, Shomei; Nakai, Yousuke; Kogure, Hirofumi; Koike, Kazuhiko

2015-01-01

It is difficult to carry out meta-analyses or to compare the results of different studies of biliary stents because there is no uniform evaluation method. Therefore, a standardized reporting system is required. We propose a new standardized system for reporting on biliary stents, the 'TOKYO criteria 2014', based on a consensus among Japanese pancreatobiliary endoscopists. Instead of stent occlusion, we use recurrent biliary obstruction, which includes occlusion and migration. The time to recurrent biliary obstruction was estimated using Kaplan-Meier analysis with the log-rank test. We can evaluate both plastic and self-expandable metallic stents (uncovered and covered). We also propose specification of the cause of recurrent biliary obstruction, identification of complications other than recurrent biliary obstruction, indication of severity, measures of technical and clinical success, and a standard for clinical care. Most importantly, the TOKYO criteria 2014 allow comparison of biliary stent quality across studies. Because blocked stents can be drained not only using transpapillary techniques but also by an endoscopic ultrasonography-guided transmural procedure, we should devise an evaluation method that includes transmural stenting in the near future. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

[Trimming with argon plasma of self-expanding metal stents: report of 7 cases].

PubMed

Jury, Gastón; Amieva, Leandro; López, Fagalde Rafael; Jury, Rubén

2014-06-01

The use of self-expandable enteral stents for palliation of malignant stenosis may present the complication of concealing the ampulla of Vater behind the metallic mesh. Anchoring in the duodenal wall (distal or partial migration) may also be a complication of biliary metallic stents and therefore may cause difficulty in gaining access to the biliary tract. In these cases of difficult access, a fenestration on the prosthesis ( biliary or enteral) can be created to allow reaching the obstructed biliary tract by means of argon plasma (AP). Were retrospectively analysed 7 cases. Under endoscopic vision, AP was directed to filgurate and cut 6 biliary prosthesis and a duodenal stent. Fulguration and cut of biliary stent was performed in 5 cases of distal partial migration and cholangitis. In one case of obstruction caused by distal migration inside the duodenal stent light, cutting of the biliary stent was performed. A window was created in the enteral prosthesis in order to access the ampulla of Vater and place a biliary tract prosthesis. All cases were resolved successfully and without complications. We conclude that the use of AP to fulgurate and cut nitinol prosthesis was effective and presented no complications in this series.

A novel keratin18 promoter that drives reporter gene expression in the intrahepatic and extrahepatic biliary system allows isolation of cell-type specific transcripts from zebrafish liver

PubMed Central

Wilkins, Benjamin J.; Gong, Weilong; Pack, Michael

2015-01-01

Heritable and acquired biliary disorders are an important cause of acute and chronic human liver disease. Biliary development and physiology have been studied extensively in rodent models and more recently, zebrafish have been used to uncover pathogenic mechanisms and potential therapies for these conditions. Here we report development of novel transgenic lines labeling the intrahepatic and extrahepatic biliary system of zebrafish larvae that can be used for lineage tracing and isolation of biliary-specific RNAs from mixed populations of liver cells. We show that GFP expression driven by a 4.4 kilobase promoter fragment from the zebrafish keratin18 (krt18) gene allows visualization of all components of the developing biliary system as early as 3 days post-fertilization. In addition, expression of a ribosomal fusion protein (EGFP-Rpl10a) in krt18:TRAP transgenic fish allows for enrichment of translated biliary cell mRNAs via translating ribosome affinity purification (TRAP). Future studies utilizing these reagents will enhance our understanding of the morphologic and molecular processes involved in biliary development and disease. PMID:24394404

A new clarification method to visualize biliary degeneration during liver metamorphosis in sea lamprey (Petromyzon marinus)

USGS Publications Warehouse

Chung-Davidson, Yu-Wen; Davidson, Peter J.; Scott, Anne M.; Walaszczyk, Erin J.; Brant, Cory O.; Buchinger, Tyler; Johnson, Nicholas S.; Li, Weiming

2014-01-01

Biliary atresia is a rare disease of infancy, with an estimated 1 in 15,000 frequency in the southeast United States, but more common in East Asian countries, with a reported frequency of 1 in 5,000 in Taiwan. Although much is known about the management of biliary atresia, its pathogenesis is still elusive. The sea lamprey (Petromyzon marinus) provides a unique opportunity to examine the mechanism and progression of biliary degeneration. Sea lamprey develop through three distinct life stages: larval, parasitic, and adult. During the transition from larvae to parasitic juvenile, sea lamprey undergo metamorphosis with dramatic reorganization and remodeling in external morphology and internal organs. In the liver, the entire biliary system is lost, including the gall bladder and the biliary tree. A newly-developed method called “CLARITY” was modified to clarify the entire liver and the junction with the intestine in metamorphic sea lamprey. The process of biliary degeneration was visualized and discerned during sea lamprey metamorphosis by using laser scanning confocal microscopy. This method provides a powerful tool to study biliary atresia in a unique animal model.

Proposed standards for reporting outcomes of treating biliary injuries.

PubMed

Cho, Jai Young; Baron, Todd H; Carr-Locke, David L; Chapman, William C; Costamagna, Guido; de Santibanes, Eduardo; Dominguez Rosado, Ismael; Garden, O James; Gouma, Dirk; Lillemoe, Keith D; Angel Mercado, Miguel; Mullady, Daniel K; Padbury, Robert; Picus, Daniel; Pitt, Henry A; Sherman, Stuart; Shlansky-Goldberg, Richard; Tornqvist, Bjorn; Strasberg, Steven M

2018-04-01

There is no standard nor widely accepted way of reporting outcomes of treatment of biliary injuries. This hinders comparison of results among approaches and among centers. This paper presents a proposal to standardize terminology and reporting of results of treating biliary injuries. The proposal was developed by an international group of surgeons, biliary endoscopists and interventional radiologists. The method is based on the concept of "patency" and is similar to the approach used to create reporting standards for arteriovenous hemodialysis access. The group considered definitions and gradings under the following headings: Definition of Patency, Definition of Index Treatment Periods, Grading of Severity of Biliary Injury, Grading of Patency, Metrics, Comparison of Surgical to Non Surgical Treatments and Presentation of Case Series. A standard procedure for reporting outcomes of treating biliary injuries has been produced. It is applicable to presenting results of treatment by surgery, endoscopy, and interventional radiology. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

[Primary sclerosing cholangitis associated with Sjögren's syndrome, retroperitoneal fibrosis and chronic pancreatitis. Report of a case].

PubMed

Barreda, F; Contardo, C; León, A; Navarrete, J; Figueroa, R; Attanasio, F

1989-01-01

Primary Sclerosing Cholangitis (PSC) is an unusual chronic, cholestatic disease of unknown etiology, more frequently seen in young adults in close relationship with Chronic Ulcerative Colitis. We report the case of a 30 year old woman, coming from the peruvian amazon with PSC associated with Sjögren Syndrome, Chronic Pancreatitis and Retroperitoneal Fibrosis, without colonic involvement. She was treated with external biliary drainage and controlled for 12 months. In this paper, clinical, biochemical, radiological, histological and therapeutic features are reviewed as well as its possible immunologie autoimmune origin.

Ursodeoxycholic acid in the treatment of liver diseases.

PubMed Central

Saksena, S.; Tandon, R. K.

1997-01-01

Ursodeoxycholic acid is a dihydroxy bile acid with a rapidly expanding spectrum of usage in acute and chronic liver diseases. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholeresis. Its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis as an adjunct to medical therapy has been well established. Newer indications include its use in the management of chronic hepatitis, cirrhosis, post liver transplant rejection, graft-versus-host disease and acute viral hepatitis, where it not only relieves symptoms of cholestasis but also arrests ongoing hepatocyte necrosis. PMID:9122101

[Correction of indigestion in chronic biliary pancreatitis].

PubMed

Trukhan, D I; Tarasova, L V

2013-01-01

Chronic pancreatitis (CP) is one of the most urgent and investigated problems in gastroenterology. Despite the variety of the spectrum of etiologic, pathogenetic and provoking factors for CP, one of the leading causes of disease pathology is pathology of biliary tract. A key element in the treatment of CP is a correction of the digestive system, with biliary pancreatitis feature that distinguishes it from other forms of pancreatitis, is a combination of exocrine pancreatic insufficiency with chronic biliary insufficiency. The variety of biochemical and immunological effects of ursodeoxycholic acid (UDCA) can treat it with biliary pancreatitis as the drug of etiological, pathogenetic and substitution therapy. UDCA (Ursosan) in combination with modern mini-microspheroidal polyfermental drugs significantly improves the clinical efficacy of the correction of the digestive system in biliary pancreatitis.

Endoscopic management with inside stent for proximal benign biliary stricture after laparoscopic cholecystectomy.

PubMed

Sasahira, Naoki; Isayama, Hiroyuki; Kogure, Hirofumi; Tsujino, Takeshi; Koike, Kazuhiko

2012-05-01

Endoscopic placement of a plastic stent is the standard drainage for a symptomatic benign biliary stricture. Although a removable fully covered self-expandable metal stent has been applied for distal benign biliary stricture, placement of a plastic stent remains the standard treatment for proximal benign biliary stricture. Placement of a plastic stent above the papilla (inside stent) is an alternative to the conventional method because of its preventive effect against the dysfunction of the stent in patients with proximal benign biliary stricture. © 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.

Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review

PubMed Central

Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

2015-01-01

Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

Acute Duodenal Obstruction After Percutaneous Placement of Metallic Biliary Stents: Peroral Treatment with Enteral Stents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopera, Jorge E.; Alvarez, Oscar A.; Perdigao, Joseph

2003-09-15

Three patients with malignant biliary obstruction were treated with placement of metallic biliary stents. Two patients had known partial duodenal stenosis but had no symptoms of gastrointestinal obstruction. The patients developed symptomatic duodenal obstruction early after biliary metallic stent placement. The symptomatic duodenal obstructions were successfully treated with peroral placement of duodenal stents, which obviated the need for surgical intervention.

Complications of Nonoperative Management of High-grade Blunt Hepatic Injuries

DTIC Science & Technology

2005-11-01

cholangiopancreatography (ERCP) and stenting of biliary leaks, and CT scan-guided drainage of hepatic or perihepatic abscesses or biliary collections by...1 B). Stenting was successful in decreasing the biliary leak, but repeat ERCP was required for increased serum bilirubin, pain, and fever...Finally, failure of percutaneous drainage techniques or biliary stenting may require operative intervention. In summary, although patients with high

Iodine-131 induced hepatotoxicity in previously healthy patients with Grave’s disease

PubMed Central

2013-01-01

Objective To describe the association of the rare and serious complication of liver toxicity in previously healthy Grave’s disease (GD) patients after the treatment with radioactive iodine 131I (RAI). Case presentation We report the clinical, laboratory and pathologic findings of 2 cases of severe liver toxicity associated with the treatment with RAI in previously healthy patients with GD. Clinical examination and laboratory investigations excluded viral hepatitis, autoimmune hepatitis, granulomatous disease, primary biliary disease, extrahepatic biliary obstruction, and heart failure. Case 1: A previously healthy 52-years old man reportedly having a typical GD but following RAI treatment, concomitantly developed severe liver toxicity that required 1 week of treatment in hospital. Case 2: A previously healthy 34-years old woman is reported as having a typical GD but developed jaundice following RAI treatment that required several weeks of in hospital treatment in the hepato-biliary department. In both cases, the liver dysfunction resolved after intensive treatment with hepato-protective agents. In this report the therapeutic considerations as well as the pathogenetic possibilities are reviewed. Conclusion To the best of our knowledge, this is the first description of the association observed, which is rare but may be severe and should be considered in any case of thyrotoxicosis where a liver dysfunction develops after the treatment with radioactive iodine 131I. PMID:23497434

MR imaging and MR cholangiopancreatography of cholangiocarcinoma developing in printing company workers.

PubMed

Koyama, Koichi; Kubo, Shoji; Ueki, Ai; Shimono, Taro; Takemura, Shigekazu; Tanaka, Shogo; Kinoshita, Masahiko; Hamano, Genya; Miki, Yukio

2017-05-01

To retrospectively investigate magnetic resonance (MR) imaging findings of occupational cholangiocarcinoma (oCC) occurring among workers in printing companies in Japan, compared to those of non-occupational cholangiocarcinoma (nCC), primary sclerosing cholangitis (PSC), and age-matched normal controls (NORs). Participants comprised 27 consecutive patients (oCC, n = 5; nCC, n = 8; PSC, n = 6; NOR, n = 8) who underwent MR imaging between May 2009 and October 2012. MR imaging was evaluated with respect to tumor characteristics, abnormal MR cholangiographic findings (PSC-like findings), bile duct stricture, and signal changes of the hepatic parenchyma. Tumors were detected in all nCCs and four oCCs. Tumors displayed a mass-forming type in all nCCs and two oCCs, and an intraductal growth type in two oCCs. Abnormal cholangiographic findings were detected in all oCCs and PSCs, but not in any nCCs or NORs. All oCCs and seven nCCs showed biliary strictures longer than 1 cm; five PSCs showed biliary strictures shorter than 1 cm. Both intra- and extrahepatic biliary strictures were detected in three PSCs and two oCCs. Peripheral hepatic hyperintensity on T2-weighted imaging was detected in two nCCs, two PSCs, and two oCCs. These results indicated that MR imaging of oCC showed findings of both PSC and nCC.

Perioperative Management of Hilar Cholangiocarcinoma.

PubMed

Poruk, Katherine E; Pawlik, Timothy M; Weiss, Matthew J

2015-10-01

Cholangiocarcinoma is the most common primary tumor of the biliary tract although it accounts for only 2 % of all human malignancies. We herein review hilar cholangiocarcinoma including its risk factors, the main classification systems for tumors, current surgical management of the disease, and the role chemotherapy and liver transplantation may play in selected patients. We performed a comprehensive literature search using PubMed, Medline, and the Cochrane library for the period 1980-2015 using the following MeSH terms: "hilar cholangiocarcinoma", "biliary cancer", and "cholangiocarcinoma". Only recent studies that were published in English and in peer reviewed journals were included. Hilar cholangiocarcinoma is a disease of advanced age with an unclear etiology, most frequently found in Southeast Asia and relatively rare in Western countries. The best chance of long-term survival and potential cure is surgical resection with negative surgical margins, but many patients are unresectable due to locally advanced or metastatic disease at diagnosis. As a result of recent efforts, new methods of management have been identified for these patients, including preoperative portal vein embolism and biliary drainage, neoadjuvant chemotherapy with subsequent transplantation, and chemoradiation therapy. Current management of hilar cholangiocarcinoma depends on extent of the tumor at presentation and includes surgical resection, liver transplantation, portal vein embolization, and chemoradiation therapy. Our understanding of hilar cholangiocarcinoma has improved in recent years and further research offers hope to improve the outcome in patients with these rare tumors.

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

PubMed

Al-Kawas, Firas; Aslanian, Harry; Baillie, John; Banovac, Filip; Buscaglia, Jonathan M; Buxbaum, James; Chak, Amitabh; Chong, Bradford; Coté, Gregory A; Draganov, Peter V; Dua, Kulwinder; Durkalski, Valerie; Elmunzer, B Joseph; Foster, Lydia D; Gardner, Timothy B; Geller, Brian S; Jamidar, Priya; Jamil, Laith H; Keswani, Rajesh N; Khashab, Mouen A; Lang, Gabriel D; Law, Ryan; Lichtenstein, David; Lo, Simon K; McCarthy, Sean; Melo, Silvio; Mullady, Daniel; Nieto, Jose; Bayne Selby, J; Singh, Vikesh K; Spitzer, Rebecca L; Strife, Brian; Tarnaksy, Paul; Taylor, Jason R; Tokar, Jeffrey; Wang, Andrew Y; Williams, April; Willingham, Field; Yachimski, Patrick

2018-02-14

The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Comparative Proteomics Reveals Novel Components at the Plasma Membrane of Differentiated HepaRG Cells and Different Distribution in Hepatocyte- and Biliary-Like Cells

PubMed Central

Woods, Alisa G.; Lazar, Catalin; Radu, Gabriel L.; Darie, Costel C.; Branza-Nichita, Norica

2013-01-01

Hepatitis B virus (HBV) is a human pathogen causing severe liver disease and eventually death. Despite important progress in deciphering HBV internalization, the early virus-cell interactions leading to infection are not known. HepaRG is a human bipotent liver cell line bearing the unique ability to differentiate towards a mixture of hepatocyte- and biliary-like cells. In addition to expressing metabolic functions normally found in liver, differentiated HepaRG cells support HBV infection in vitro, thus resembling cultured primary hepatocytes more than other hepatoma cells. Therefore, extensive characterization of the plasma membrane proteome from HepaRG cells would allow the identification of new cellular factors potentially involved in infection. Here we analyzed the plasma membranes of non-differentiated and differentiated HepaRG cells using nanoliquid chromatography-tandem mass spectrometry to identify the differences between the proteomes and the changes that lead to differentiation of these cells. We followed up on differentially-regulated proteins in hepatocytes- and biliary-like cells, focusing on Cathepsins D and K, Cyclophilin A, Annexin 1/A1, PDI and PDI A4/ERp72. Major differences between the two proteomes were found, including differentially regulated proteins, protein-protein interactions and intracellular localizations following differentiation. The results advance our current understanding of HepaRG differentiation and the unique properties of these cells. PMID:23977166

Endoductal tissue sampling of biliary strictures through endoscopic retrograde cholangiopan creatography (ERCP).

PubMed

Pugliese, V; Antonelli, G; Vincenti, M; Gatteschi, B

1997-01-01

Pathological proof of malignant in biliary strictures is useful in the preoperative setting as it helps define therapeutic planning and prognosis, and reduces the length of the subsequent surgical intervention. However, it is difficult to obtain. The aim of this study was to evaluate the yield of histological and cytological examination of endobiliary samples obtained during endoscopic retrograde cholangiopancreatography (ERCP). Endobiliary forceps biopsy and brush cytology were performed during ERCP examination in 52 consecutive patients, 36 with malignant and 16 with benign strictures. Histology and cytology turned out to have the same sensitivity (53%). The gain in sensitivity achieved by combining the two techniques was limited, reaching a value of 61%. The specificity, however, was 100% for both methods. Most of the few complications observed were due to sphincterotomy and subsided spontaneously or with medical treatment. However, one patient experienced a serous complication and chose to be treated by surgical intervention. The complication was caused by forceps biopsy. This study shows that 1) sampling of biliary strictures during ERCP is the primary approach to tissue diagnosis; 2) brush cytology alone is sufficient in clinical practice; 3) forceps biopsy must always be used to sample intra-ampullary strictures but should be considered as a secondary step to sample strictures located more proximally, in the bile ducta, if previous cytology was negative.

Clinicopathological Features of Type 2 Autoimmune Pancreatitis in Japan: Results of a Multicenter Survey.

PubMed

Notohara, Kenji; Nishimori, Isao; Mizuno, Nobumasa; Okazaki, Kazuichi; Ito, Tetsuhide; Kawa, Shigeyuki; Egawa, Shinichi; Kihara, Yasuyuki; Kanno, Atsushi; Masamune, Atsushi; Shimosegawa, Tooru

2015-10-01

The aim of the study was to clarify clinicopathological features of type 2 autoimmune pancreatitis (AIP) in Japan; a multicenter survey was carried out. The first screening collected patients with pancreatitis whose pancreatic tissue samples were available and who fulfilled at least 1 of the following 3 criteria as possible type 2 AIP: (1) histological presence of granulocytic epithelial lesion, (2) age of 50 years or younger, and (3) association of ulcerative colitis, Sjogren syndrome, and/or primary biliary cirrhosis. Patients with histologically confirmed type 1 AIP were also collected as a control. Clinical information was gathered by questionnaire. A histological re-evaluation identified 8 patients with type 2 AIP and 20 with type 1 AIP. Three of the latter had intralobular neutrophilic infiltration. Factors more frequent in type 2 included age younger than 40 years, abdominal pain, and elevation of serum amylase and lipase, whereas patients with type 1 more frequently showed jaundice, elevated serum IgG and IgG4, presence of autoantibodies, association of IgG4-related disease, sclerosing cholangitis and diabetes mellitus, and imaging findings of intrapancreatic biliary stenosis and extrapancreatic biliary dilatation. The clinical features of type 2 AIP in Japan were similar to those of western countries. Intralobular neutrophilic infiltration in type 1 is a potential pitfall, especially in the biopsy-based diagnosis.

The Role of Endoscopic Biliary Drainage without Sphincterotomy in Gallstone Patients with Cholangitis and Suspected Common Bile Duct Stones Not Detected by Cholangiogram or Intraductal Ultrasonography

PubMed Central

Goong, Hyeon Jeong; Moon, Jong Ho; Lee, Yun Nah; Choi, Hyun Jong; Choi, Seo-Youn; Choi, Moon Han; Kim, Min Jin; Lee, Tae Hoon; Park, Sang-Heum; Lee, Hae Kyung

2017-01-01

Background/Aims Treatment for cholangitis without common bile duct (CBD) stones has not been established in patients with gallstones. We investigated the usefulness of endoscopic biliary drainage (EBD) without endoscopic sphincterotomy (EST) in patients diagnosed with gallstones and cholangitis without CBD stones by endoscopic retrograde cholangiopancreatography (ERCP) and intraductal ultrasonography (IDUS). Methods EBD using 5F plastic stents without EST was performed prospectively in patients with gallstones and cholangitis if CBD stones were not diagnosed by ERCP and IDUS. After ERCP, all patients underwent laparoscopic cholecystectomy. The primary outcomes were clinical and technical success. The secondary outcomes were recurrence rate of biliary events and procedure-related adverse events. Results Among 187 patients with gallstones and cholangitis, 27 patients without CBD stones according to ERCP and IDUS received EBD using 5F plastic stents without EST. The stents were maintained in all patients until laparoscopic cholecystectomy, and recurrence of cholangitis was not observed. After cholecystectomy, the stents were removed spontaneously in 12 patients and endoscopically in 15 patients. Recurrence of CBD stones was not detected during the follow-up period (median, 421 days). Conclusions EBD using 5F plastic stents without EST may be safe and effective for the management of cholangitis accompanied by gallstones in patients without CBD stones according to ERCP and IDUS. PMID:28104896

Imaging and radiological interventions in extra-hepatic portal vein obstruction

PubMed Central

Pargewar, Sudheer S; Desai, Saloni N; Rajesh, S; Singh, Vaibhav P; Arora, Ankur; Mukund, Amar

2016-01-01

Extrahepatic portal vein obstruction (EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension (PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt (PSS) and revision of PSS. PMID:27358683

Comparative proteomics reveals novel components at the plasma membrane of differentiated HepaRG cells and different distribution in hepatocyte- and biliary-like cells.

PubMed

Petrareanu, Catalina; Macovei, Alina; Sokolowska, Izabela; Woods, Alisa G; Lazar, Catalin; Radu, Gabriel L; Darie, Costel C; Branza-Nichita, Norica

2013-01-01

Hepatitis B virus (HBV) is a human pathogen causing severe liver disease and eventually death. Despite important progress in deciphering HBV internalization, the early virus-cell interactions leading to infection are not known. HepaRG is a human bipotent liver cell line bearing the unique ability to differentiate towards a mixture of hepatocyte- and biliary-like cells. In addition to expressing metabolic functions normally found in liver, differentiated HepaRG cells support HBV infection in vitro, thus resembling cultured primary hepatocytes more than other hepatoma cells. Therefore, extensive characterization of the plasma membrane proteome from HepaRG cells would allow the identification of new cellular factors potentially involved in infection. Here we analyzed the plasma membranes of non-differentiated and differentiated HepaRG cells using nanoliquid chromatography-tandem mass spectrometry to identify the differences between the proteomes and the changes that lead to differentiation of these cells. We followed up on differentially-regulated proteins in hepatocytes- and biliary-like cells, focusing on Cathepsins D and K, Cyclophilin A, Annexin 1/A1, PDI and PDI A4/ERp72. Major differences between the two proteomes were found, including differentially regulated proteins, protein-protein interactions and intracellular localizations following differentiation. The results advance our current understanding of HepaRG differentiation and the unique properties of these cells.

Study of LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)

ClinicalTrials.gov

2017-09-05

Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Carcinoma, Ductal, Breast; Melanoma; Solid Tumors; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas

Low Measured Hepatic Artery Flow Increases Rate of Biliary Strictures in Deceased Donor Liver Transplantation: An Age-Dependent Phenomenon.

PubMed

Kim, Peter T W; Fernandez, Hoylan; Gupta, Amar; Saracino, Giovanna; Ramsay, Michael; McKenna, Gregory J; Testa, Giuliano; Anthony, Tiffany; Onaca, Nicholas; Ruiz, Richard M; Klintmalm, Goran B

2017-02-01

This study was conducted to determine effect of lower measured hepatic arterial (HA) flow (<400 mL/min) on biliary complications and graft survival after deceased donor liver transplantation. Hepatic artery is the main blood supply to bile duct and lack of adequate HA flow is thought to be a risk factor for biliary complications. A retrospective review of 1300 patients who underwent deceased donor liver transplantation was performed. Patients with arterial complications were excluded to eliminate potential contribution to biliary complications from HA thrombosis. Patients were divided into low (<400 mL/min; N = 201) and high (≥400 mL/min; N = 1099) HA flow groups. Incidence of biliary complications and graft survival were analyzed. HA flows less than 400 mL/min were associated with increased rate of biliary strictures in younger donors (<50 years old), and in patients with duct-to-duct anastomoses (P = 0.028). Lower HA flows were associated with decreased graft survival (P = 0.013). Donor older than 50 years was associated with increased rate of biliary strictures (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.14-2.45; P = 0.0085) and graft failure (HR, 1.68; 95% CI, 1.35-2.1; P <0.0001) on multivariate analyses. HA flow less than 400 mL/min was associated with biliary strictures (HR, 1.53; 95% CI, 1.04-2.24; P = 0.0297) on univariate analysis only. HA flow less than 400 mL/min was associated with higher rate of biliary strictures in younger donors with duct-to-duct reconstruction and lower graft survival. A consideration should be given to increase the intraoperative HA flow to prevent biliary strictures in such patients.

Percutaneous imaging-guided interventions for acute biliary disorders in high surgical risk patients

PubMed Central

Donkol, Ragab Hani; Latif, Nahed Abdel; Moghazy, Khaled

2010-01-01

AIM: To evaluate the efficacy of percutaneous imaging-guided biliary interventions in the management of acute biliary disorders in high surgical risk patients. METHODS: One hundred and twenty two patients underwent 139 percutaneous imaging-guided biliary interventions during the period between January 2007 to December 2009. The patients included 73 women and 49 men with a mean age of 61 years (range 35-90 years). Fifty nine patients had acute biliary obstruction, 26 patients had acute biliary infection and 37 patients had abnormal collections. The procedures were performed under computed tomography (CT)- (73 patients), sonographic- (41 patients), and fluoroscopic-guidance (25 patients). Success rates and complications were determined. The χ2 test with Yates’ correction for continuity was applied to compare between these procedures. A P value < 0.05 was considered significant. RESULTS: The success rates for draining acute biliary obstruction under CT- , fluoroscopy- or ultrasound-guidance were 93.3%, 62.5% and 46.1%, respectively with significant P values (P = 0.026 and 0.002, respectively). In acute biliary infection, successful drainage was achieved in 22 patients (84.6%). The success rates in patients drained under ultrasound- and CT-guidance were 46.1% and 88.8%, respectively and drainage under CT-guidance was significantly higher (P = 0.0293). In 13 patients with bilomas, percutaneous drainage was successful in 11 patients (84.6%). Ten out of 12 cases with hepatic abscesses were drained with a success rate of 83.3%. In addition, the success rate of drainage in 12 cases with pancreatic pseudocysts was 83.3%. The reported complications were two deaths, four major and seven minor complications. CONCLUSION: Percutaneous imaging-guided biliary interventions help to promptly diagnose and effectively treat acute biliary disorders. They either cure the disorders or relieve sepsis and jaundice before operations. PMID:21160698

Low symptomatic premature stent occlusion of multiple plastic stents for benign biliary strictures: comparing standard and prolonged stent change intervals.

PubMed

Lawrence, Christopher; Romagnuolo, Joseph; Payne, K Mark; Hawes, Robert H; Cotton, Peter B

2010-09-01

Benign biliary strictures are typically managed endoscopically whereby an increasing size or number of plastic stents is placed at ERCP. Stents are often changed every 3 to 4 months based on the known median patency of a single biliary stent, but patency data for multiple biliary stents are lacking. To assess the incidence of occlusion-free survival of multiple plastic biliary stents and the rate of premature occlusion if left in longer than 6 months. Retrospective. Tertiary-care medical center (Charleston, SC). Consecutive patients who received multiple plastic stents for benign nonhilar biliary strictures from 1994 to 2008 were identified. Exchange of multiple plastic biliary stents within 6 months (group 1) or 6 months or longer (group 2) after placement. Symptomatic stent occlusion. Seventy-nine patients with nonhilar extrahepatic benign biliary stricture underwent 125 ERCPs with multiple plastic biliary stents. Stents were scheduled for removal/exchange within 6 months in 52 patients (86 ERCPs) compared with after 6 months in 22 patients (26 ERCPs). The median interval between multiple stent placement and removal/exchange was 90 days for group 1 and 242 days for group 2. Premature stent occlusion occurred in 4 of 52 (7.7%) patients in group 1 versus 1 of 22 (4.5%) in group 2, with significantly longer occlusion-free survival in group 2 (log-rank P < .0001). Retrospective study at a single tertiary referral center. Multiple plastic biliary stents for benign nonhilar strictures were associated with a low rate of premature symptomatic stent occlusion at more than 6 months and a longer occlusion-free survival. Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Clinical Study on Using 125I Seeds Articles Combined with Biliary Stent Implantation in the Treatment of Malignant Obstructive Jaundice.

PubMed

Wang, Tao; Liu, Sheng; Zheng, Yan-Bo; Song, Xue-Peng; Sun, Bo-Lin; Jiang, Wen-Jin; Wang, Li-Gang

2017-08-01

Aim: To study the feasibility and curative effect of 125 I seeds articles combined with biliary stent implantation in the treatment of malignant obstructive jaundice. Patients and Methods: Fifty patients with malignant obstructive jaundice were included. Twenty-four were treated by biliary stent implantation combined with intraluminal brachytherapy by 125 I seeds articles as the experimental group, while the remaining 26 were treated by biliary stent implantation only as the control group. The goal of this study was to evaluate total bilirubin, direct bilirubin and tumor markers (cancer antigen (CA)-199, CA-242 and carcinoembryonic antigen (CEA)), as well as biliary stent patency status and survival time before and after surgery. Results: Jaundice improved greatly in both groups. The decreases of CA-199 and CA-242 had statistical significance (p=0.003 and p=0.004) in the experimental group. The ratio of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (p=0.048). The biliary stent patency time in the experimental group was 1~15.5 (mean=9.84) months. The biliary stent patency time in the control group was 0.8~9 (mean=5.57) months, which was statistically significant (p=0.018). The median survival time was 10.2 months in the experimental group, while 5.4 months in control group (p<0.05). Conclusion: 125 I seeds articles combined with biliary stent implantation significantly prolongs biliary stent patency time and survival time for patients with malignant obstructive jaundice possibly by inhibiting the proliferation of vascular endothelial cells and the growth of tumor. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross, J.B. Jr.; Myers, B.M.; Kost, L.J.

1989-01-01

We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles wasmore » confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload.« less

Bile duct reconstruction by a young surgeon in living donor liver transplantation using right liver graft.

PubMed

Kim, Jong Man; Cho, Wontae; Kwon, Choon Hyuck David; Joh, Jae-Won; Park, Jae Berm; Ko, Justin Sangwook; Gwak, Mi Sook; Kim, Gaab Soo; Kim, Sung Joo; Lee, Suk-Koo

2014-09-01

Biliary strictures and bile leaks account for the majority of biliary complications after living donor liver transplantation (LDLT). The aim of this study was to examine differences in biliary complications after adult LDLTs were performed by an experienced senior surgeon and an inexperienced junior surgeon. Surgeries included bile duct reconstruction after adult LDLT using a right liver graft, and risk factors for biliary stricture were identified. We retrospectively reviewed the medical records of 136 patients who underwent LDLT in order to identify patients who developed biliary complications. The senior surgeon performed 102 surgeries and the junior surgeon performed 34 surgeries. The proportion of patients with biliary stricture was similar between the senior and the junior surgeons (27.5% vs 26.5%; P = 0.911). However, the incidence of biliary leakage was higher in patients of the junior surgeon than in those of the senior surgeon (23.5% vs 2.9%; P = 0.001). The frequency of percutaneous drainage was also higher for the junior surgeon than the senior surgeon because of the junior surgeon's high leakage rate of the drainage. When the junior surgeon performed bile duct anastomosis, biliary leakage occurred in 7 patients between the 11th and 20th cases. However, biliary leakage occurred in only 1 case thereafter. Bile duct reconstruction performed by beginner surgeons in LDLT using right lobe grafts should be cautiously monitored and observed by a senior surgeon until an inexperienced junior surgeon has performed at least 20 cases, because of the high incidence of biliary leakage related to surgeon's inexperience in bile duct reconstructions in LDLT.

Percutaneous Transhepatic Biliary Drainage in the Management of Postsurgical Biliary Leaks in Patients with Nondilated Intrahepatic Bile Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cozzi, Guido, E-mail: guido.cozzi@istitutotumori.mi.it; Severini, Aldo; Civelli, Enrico

2006-06-15

Purpose. To assess the feasibility of percutaneous transhepatic biliary drainage (PTBD) for the treatment of postsurgical biliary leaks in patients with nondilated intrahepatic bile ducts, its efficacy in restoring the integrity of bile ducts, and technical procedures to reduce morbidity. Methods. Seventeen patients out of 936 undergoing PTBD over a 20-year period had a noncholestatic liver and were retrospectively reviewed. All patients underwent surgery for cancer and suffered a postsurgical biliary leak of 345 ml/day on average; 71% were in poor condition and required permanent nutritional support. An endoscopic approach failed or was excluded due to inaccessibility of the bilemore » ducts. Results. Established biliary leaks and site of origin were diagnosed an average of 21 days (range 1-90 days) after surgery. In all cases percutaneous access to the biliary tree was achieved. An external (preleakage) drain was applied in 7 cases, 9 patients had an external-internal fistula bridging catheter, and 1 patient had a percutaneous hepatogastrostomy. Fistulas healed in an average of 31 days (range 3-118 days ) in 15 of 17 patients (88%) following PTBD. No major complications occurred after drainage. Post-PTBD cholangitis was observed in 6 of 17 patients (35%) and was related to biliary sludge formation occurring mostly when drainage lasted >30 days and was of the external-internal type. Median patient survival was 17.7 months and in all cases the repaired biliary leaks remained healed. Conclusions. PTBD is a feasible, effective, and safe procedure for the treatment of postsurgical biliary leaks. It is therefore a reliable alternative to surgical repair, which entails longer hospitalization and higher costs.« less

Primary biliary cirrhosis: From bench to bedside

PubMed Central

Kouroumalis, Elias; Notas, George

2015-01-01

Primary biliary cirrhosis (PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient’s genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. PMID:26261733

Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population.

PubMed

Mella, J G; Roschmann, E; Maier, K P; Volk, B A

1995-02-01

The major histocompatibility complex class II alleles at the HLA-DPB1 locus were investigated in 32 German Caucasoid patients with primary biliary cirrhosis (PBC) and compared with those from 47 normal control patients using molecular genotyping techniques. The second exon of the HLA-DPB1 gene was amplified by polymerase chain reaction (PCR) and hybridized with 25 sequence-specific oligonucleotides (SSOs) to assign the HLA-DPB1 alleles on the basis of known sequence variations, according to the protocols of the Eleventh International Histocompatibility Workshop. A strong association of PBC was found with the allele HLA-DPB1*0301. The allele HLA DPB1*0301 was present in 50% (16 of 32) of the patients with PBC compared with 13% (6 of 47) of normal controls (P corrected < .015), whereas the other HLA-DPB1 alleles showed no significant differences in both groups. The relative risk (RR) estimate for the allele HLA-DPB1*0301 was 6.8 (95% confidence limits: 2.27 to 20.57). In summary, this study clearly demonstrates an association of PBC with the HLA-DPB1*0301 allele in German Caucasoids and may add new data to the immunogenetic background of PBC, suggesting a contribution of the HLA-DPB1 gene to the genetic susceptibility of the disease.

Recurrent Primary Biliary Cirrhosis: Peritransplant Factors and Ursodeoxycholic Acid Treatment Post-Liver Transplant

PubMed Central

Guy, Jennifer E.; Qian, Peiqing; Lowell, Jeffrey A.; Peters, Marion G.

2014-01-01

Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known. PMID:16184542

Primary cancers of extrahepatic biliary passages.

PubMed

Mittal, B; Deutsch, M; Iwatsuki, S

1985-04-01

We analyzed the records of 22 patients with cancers of extrahepatic biliary passages (EHBP) to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From our data, it is difficult to comment on the effectiveness of chemotherapy. We have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed.

Primary biliary cirrhosis-specific antimitochondrial antibodies in neonatal haemochromatosis.

PubMed

Smyk, Daniel S; Mytilinaiou, Maria G; Grammatikopoulos, Tassos; Knisely, A S; Mieli-Vergani, Giorgina; Bogdanos, Dimitrios P; Vergani, Diego

2013-01-01

Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC). To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child). The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.

T-EUS for Gastrointestinal Disorders: A Multicenter Registry

ClinicalTrials.gov

2017-02-16

Cholangiocarcinoma; Pancreatic Cancer; Bile Duct Cancer; Biliary Stricture; Biliary Obstruction; Stent Obstruction; Proximal Duct Stricture; Distal Duct Stricture; Ampullary Cancer; Biliary Sphincter Stenosis; Impacted Stones; Chronic Pancreatitis; Peri-ampullary Diverticula; Altered Anatomy

Biliary system

MedlinePlus

The biliary system creates, moves, stores, and releases bile into the duodenum . This helps the body digest food. It also assists ... from the liver to the duodenum. The biliary system includes: The gallbladder Bile ducts and certain cells ...

Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.

PubMed

Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru

2015-07-01

The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Pancreaticobiliary maljunction and biliary cancer.

PubMed

Kamisawa, Terumi; Kuruma, Sawako; Tabata, Taku; Chiba, Kazuro; Iwasaki, Susumu; Koizumi, Satomi; Kurata, Masanao; Honda, Goro; Itoi, Takao

2015-03-01

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Japanese clinical practice guidelines on how to deal with PBM were made in 2012, representing a world first. According to the 2013 revision to the diagnostic criteria for PBM, in addition to direct cholangiography, diagnosis can be made by magnetic resonance cholangiopancreatography (MRCP), 3-dimensional drip infusion cholangiography computed tomography, endoscopic ultrasonography (US), or multiplanar reconstruction images by multidetector row computed tomography. In PBM, the common channel is so long that sphincter action does not affect the pancreaticobiliary junction, and pancreatic juice frequently refluxes into the biliary tract. Persistence of refluxed pancreatic juice injures epithelium of the biliary tract and promotes cancer development, resulting in higher rates of carcinogenesis in the biliary tract. In a nationwide survey, biliary cancer was detected in 21.6% of adult patients with congenital biliary dilatation (bile duct cancer, 32.1% vs. gallbladder cancer, 62.3%) and in 42.4% of PBM patients without biliary dilatation (bile duct cancer, 7.3% vs. gallbladder cancer, 88.1%). Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of pancreaticobiliary ducts, a common channel ≥6 mm long, and occlusion of communication during contraction of the sphincter. Once the diagnosis of PBM is established, immediate prophylactic surgery is recommended. However, the surgical strategy for PBM without biliary dilatation remains controversial. To detect PBM without biliary dilatation early, MRCP is recommended for patients showing gallbladder wall thickening on screening US under suspicion of PBM.

Relationship Between Bile Duct Reconstruction and Complications in Living Donor Liver Transplantation.

PubMed

Miyagi, S; Kawagishi, N; Kashiwadate, T; Fujio, A; Tokodai, K; Hara, Y; Nakanishi, C; Kamei, T; Ohuchi, N; Satomi, S

2016-05-01

In living donor liver transplantation (LDLT), the recipient bile duct is thin and short. Bile duct complications often occur in LDLT, with persistent long-term adverse effects. Recently, we began to perform microsurgical reconstruction of the bile duct. The purpose of this study was to investigate the relationship between bile duct reconstruction methods and complications in LDLT. From 1991 to 2014, we performed 161 LDLTs (pediatric:adult = 90:71; left lobe:right lobe = 95:66). In this study, we retrospectively investigated the initial bile duct complications in LDLT and performed univariate and multivariate analyses to identify the independent risk factors for complications. The most frequent complication was biliary stricture (9.9%), followed by biliary leakage (6.8%). On univariate and multiple logistic regression analysis, the independent risk factors for biliary stricture were bile leakage (P = .0103) and recurrent cholangitis (P = .0077). However, there were no risk factors for biliary leakage on univariate analysis in our study. The reconstruction methods (hepaticojejunostomy or duct-to-duct anastomosis) and reconstruction technique (with or without microsurgery) were not risk factors for biliary stricture and leakage. In this study, the most frequent complication of LDLT was biliary stricture. The independent risk factors for biliary stricture were biliary leakage and recurrent cholangitis. Duct-to-duct anastomosis and microsurgical reconstruction of the bile duct were not risk factors for biliary stricture and leakage. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical usefulness of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis

PubMed Central

Torisu, Yuichi; Nakano, Masanori; Takano, Keiko; Nakagawa, Ryo; Saeki, Chisato; Hokari, Atsushi; Ishikawa, Tomohisa; Saruta, Masayuki; Zeniya, Mikio

2017-01-01

AIM To evaluate the therapeutic effects of ursodeoxycholic acid (UDCA) on autoimmune hepatitis (AIH). METHODS A total 136 patients who were diagnosed with AIH were included in our study. All of the patients underwent a liver biopsy, and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores. Initial treatment included UDCA monotherapy (Group U, n = 48) and prednisolone (PSL) monotherapy (Group P, n = 88). Group U was further classified into two subgroups according to the effect of UDCA: Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse (Subgroup U1, n = 34) and patients who additionally received PSL during follow-up (Subgroup U2, n = 14). We compared the clinical and histological findings between each groups, and investigated factors contributing to the response to UDCA monotherapy. RESULTS In Group U, 34 patients (71%) achieved and maintained remission over 49 (range: 8-90) mo (Subgroup U1) and 14 patients (29%) additionally received PSL (Subgroup U2) during follow-up. Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse (15 and 35 mo after the start of treatment). The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up, and PSL was added during 7 (range: 2-18) mo. Compared with Subgroup U2, Subgroup U1 had significantly lower alanine aminotransferase (ALT) levels at onset (124 IU/L vs 262 IU/L, P = 0.023) and a significantly higher proportion of patients with mild inflammation (A1) on histological examination (70.6% vs 35.7%, P = 0.025). When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy, only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference (P = 0.013). CONCLUSION To prevent adverse events related to corticosteroids, UDCA monotherapy for AIH needs to be considered in patients with a serum ALT level of 200 IU/L or lower. PMID:28105259

Arterio-biliary fistula as rare complication of chemoradiation therapy for intrahepatic cholangiocarcinoma

PubMed Central

Hayano, Koichi; Miura, Fumihiko; Amano, Hodaka; Toyota, Naoyuki; Wada, Keita; Kato, Kenichiro; Takada, Tadahiro; Asano, Takehide

2010-01-01

Significant hemobilia due to arterio-biliary fistula is a very rare complication of chemoradiation therapy (CRT) for unresectable intrahepatic cholangiocarcinoma (ICC). Here we report a case of arterio-biliary fistula after CRT for unresectable ICC demonstrated by angiographic examinations. This fistula was successfully treated by endovascular embolization. Hemobilia is a rare complication, but arterio-biliary fistula should be considered after CRT of ICC. PMID:21160700

Percutaneous transhepatic biliary stenting vs. surgical bypass in advanced malignant biliary obstruction: cost- effectiveness analysis.

PubMed

Yao, Li Qin; Tang, Cheng Wu; Zheng, Yin Yuan; Feng, Wen Ming; Huang, San Xiong; Bao, Ying

2013-01-01

This study aims to compare the clinical outcomes and costs between percutaneous transhepatic biliary stenting (PTBS) and surgical bypass. We randomly assigned 142 patients with unresectable malignant biliary obstruction between 2005 and 2010 to receive PTBS or surgical bypass as palliative treatment. PTBS was successfully performed in 70 patients who formed the PTBS group (failed in 7 patients). Sixty five patients underwent surgical bypass treatment. Additional gastrojejunostomy was performed in five patients. The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the surgical group (p<0.05). There was no significant difference in effectiveness of biliary drainage (p=0.9307) or survival time between two groups (p=0.4826). Early complications of PTBS group was significantly lower than surgical group (3/75 vs. 11/65, p=0.0342). Late complication in PTBS group did not differ significantly from surgical group (9/70 vs. 6/65, p=0.6823). The survival curves in the two groups showed no significant difference (p=0.1032). PTBD is a better palliative treatment than surgical bypass for unresectable malignant biliary obstruction for its high effectiveness of biliary drainage and acceptable expense and complication.

Antireflux Metal Stent as a First-Line Metal Stent for Distal Malignant Biliary Obstruction: A Pilot Study.

PubMed

Hamada, Tsuyoshi; Isayama, Hiroyuki; Nakai, Yousuke; Togawa, Osamu; Takahara, Naminatsu; Uchino, Rie; Mizuno, Suguru; Mohri, Dai; Yagioka, Hiroshi; Kogure, Hirofumi; Matsubara, Saburo; Yamamoto, Natsuyo; Ito, Yukiko; Tada, Minoru; Koike, Kazuhiko

2017-01-15

In distal malignant biliary obstruction, an antireflux metal stent (ARMS) with a funnel-shaped valve is effective as a reintervention for metal stent occlusion caused by reflux. This study sought to evaluate the feasibility of this ARMS as a first-line metal stent. Patients with nonresectable distal malignant biliary obstruction were identified between April and December 2014 at three Japanese tertiary centers. We retrospectively evaluated recurrent biliary obstruction and adverse events after ARMS placement. In total, 20 consecutive patients were included. The most common cause of biliary obstruction was pancreatic cancer (75%). Overall, recurrent biliary obstruction was observed in seven patients (35%), with a median time to recurrent biliary obstruction of 246 days (range, 11 to 246 days). Stent occlusion occurred in five patients (25%), the causes of which were sludge and food impaction in three and two patients, respectively. Stent migration occurred in two patients (10%). The rate of adverse events associated with ARMS was 25%: pancreatitis occurred in three patients, cholecystitis in one and liver abscess in one. No patients experienced nonocclusion cholangitis. The ARMS as a first-line biliary drainage procedure was feasible. Because the ARMS did not fully prevent stent dysfunction due to reflux, further investigation is warranted.

Repair of a mal-repaired biliary injury: a case report.

PubMed

Aldumour, Awad; Aseni, Paolo; Alkofahi, Mohmmad; Lamperti, Luca; Aldumour, Elias; Girotti, Paolo; De Carlis, Luciano-Gregorio

2009-05-14

Iatrogenic bile-duct injury post-laparoscopic cholecystectomy remains a major serious complication with unpredictable long-term results. We present a patient who underwent laparoscopic cholecystectomy for gallstones, in which the biliary injury was recognized intraoperatively. The surgical procedure was converted to an open one. The first surgeon repaired the injury over a T-tube without recognizing the anatomy and type of the biliary lesion, which led to an unusual biliary mal-repair. Immediately postoperatively, the abdominal drain brought a large amount of bile. A T-tube cholangiogram was performed. Despite the contrast medium leaking through the abdominal drain, the mal-repair was unrecognized. The patient was referred to our hospital for biliary leak. Ultrasound and cholangiography was repeated, which showed an unanatomical repair (right to left hepatic duct anastomosis over the T-tube), with evidence of contrast medium coming out through the abdominal drain. Eventually the patient was subjected to a definitive surgical treatment. The biliary continuity was re-established by a Roux-en-Y hepatico-jejunostomy, over transanastomotic external biliary stents. The patient is now doing well 4 years after the second surgical procedure. In reviewing the literature, we found a similar type of injury but we did not find a similar surgical mal-repair. We propose an algorithm for the treatment of early and late biliary injuries.

Repair of a mal-repaired biliary injury: A case report

PubMed Central

Aldumour, Awad; Aseni, Paolo; Alkofahi, Mohmmad; Lamperti, Luca; Aldumour, Elias; Girotti, Paolo; Carlis, Luciano Gregorio De

2009-01-01

Iatrogenic bile-duct injury post-laparoscopic cholecystectomy remains a major serious complication with unpredictable long-term results. We present a patient who underwent laparoscopic cholecystectomy for gallstones, in which the biliary injury was recognized intraoperatively. The surgical procedure was converted to an open one. The first surgeon repaired the injury over a T-tube without recognizing the anatomy and type of the biliary lesion, which led to an unusual biliary mal-repair. Immediately postoperatively, the abdominal drain brought a large amount of bile. A T-tube cholangiogram was performed. Despite the contrast medium leaking through the abdominal drain, the mal-repair was unrecognized. The patient was referred to our hospital for biliary leak. Ultrasound and cholangiography was repeated, which showed an unanatomical repair (right to left hepatic duct anastomosis over the T-tube), with evidence of contrast medium coming out through the abdominal drain. Eventually the patient was subjected to a definitive surgical treatment. The biliary continuity was re-established by a Roux-en-Y hepatico-jejunostomy, over transanastomotic external biliary stents. The patient is now doing well 4 years after the second surgical procedure. In reviewing the literature, we found a similar type of injury but we did not find a similar surgical mal-repair. We propose an algorithm for the treatment of early and late biliary injuries. PMID:19437572

Plastic Biliary Stent Occlusion: Factors Involved and Possible Preventive Approaches

PubMed Central

Donelli, Gianfranco; Guaglianone, Emilio; Di Rosa, Roberta; Fiocca, Fausto; Basoli, Antonio

2007-01-01

Endoscopic biliary stenting is today the most common palliative treatment for patients suffering from obstructive jaundice associated with malignant hepatobiliary tumors or benign strictures. However, recurrent jaundice, with or without cholangitis, is a major complication of a biliary endoprosthesis insertion. Thus, stent removal and replacement with a new one frequently occurs as a consequence of device blockage caused by microbial biofilm growth and biliary sludge accumulation in the lumen. Factors and mechanisms involved in plastic stent clogging arising from epidemiological, clinical and experimental data, as well as the possible strategies to prevent biliary stent failure, will be reviewed and discussed. PMID:17456835

DOE Office of Scientific and Technical Information (OSTI.GOV)

Close, Orrie N.; Akinwande, Olaguoke; Varma, Rakesh K.

Postoperative biliary complications following extensive hepatic resections are complex, often requiring a multidisciplinary team approach. We describe a case of a free bile duct leak following extended right hepatectomy and surgical hepaticojejunostomy treated with percutaneous transhepatic hepaticojejunostomy in which a radiofrequency guidewire was used to gain enteral access. A modified internal/external biliary catheter was left in place. The patient was enrolled in a benign biliary stricture protocol, and 8 months later, the catheter was removed following a normal cholangiogram and biliary manometric perfusion testing. At 3-month follow-up after catheter removal, the patient is asymptomatic with no clinical, biochemical, or radiographic evidencemore » of biliary leak or obstruction.« less

Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer

ClinicalTrials.gov

2018-03-22

Adenocarcinoma Metastatic; Biliary Tract Cancer; Adenocarcinoma of the Biliary Tract; Adenocarinoma Locally Advanced; Non-Resectable Hepatocellular Carcinoma; Intrahepatic Bile Duct Carcinoma; Extrahepatic Bile Duct Carcinoma

Biliary Tract Disorders, Gallbladder Disorders, and Gallstone Pancreatitis

MedlinePlus

... biliary disorders? What is the biliary tract? Enfermedades de la Vesicula y de la Via Biliar, Pancreatitis Biliar - Ricardo Morgenstern, MD and Ruben Acosta, MD Enfermedades de la Vesicula y de la Via Biliar, Pancreatitis ...

Pancreatic Calculus Causing Biliary Obstruction: Endoscopic Therapy for a Rare Initial Presentation of Chronic Pancreatitis.

PubMed

Shetty, Anurag J; Pai, C Ganesh; Shetty, Shiran; Balaraju, Girisha

2015-09-01

Biliary obstruction in chronic calcific pancreatitis (CCP) is often caused by inflammatory or fibrotic strictures of the bile duct, carcinoma of head of pancreas or less commonly by compression from pseudocysts. Pancreatic calculi causing ampullary obstruction and leading to obstructive jaundice is extremely rare. The medical records of all patients with CCP or biliary obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) over 4 years between 2010-2014 at Kasturba Medical College, Manipal were analyzed. Five patients of CCP with impacted pancreatic calculi at the ampulla demonstrated during ERCP were identified. All 5 presented with biliary obstruction and were incidentally detected to have CCP when evaluated for the same; 3 patients had features of cholangitis. All the patients were managed successfully by endoscopic papillotomy and extraction of pancreatic calculi from the ampulla with resolution of biliary obstruction. Pancreatic calculus causing ampullary obstruction, though very rare, should be considered as a possibility in patients with CCP complicated by biliary obstruction. Endoscopic therapy is affective in the resolution of biliary obstruction in such patients.

Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr-/-) mouse model with hepato-biliary pathology.

PubMed

Bodewes, Frank A J A; van der Wulp, Mariëtte Y M; Beharry, Satti; Doktorova, Marcela; Havinga, Rick; Boverhof, Renze; James Phillips, M; Durie, Peter R; Verkade, Henkjan J

2015-07-01

Cftr(-/-tm1Unc) mice develop progressive hepato-biliary pathology. We hypothesize that this liver pathology is related to alterations in biliary bile hydrophobicity and bile salt metabolism in Cftr(-/-tm1Unc) mice. We determined bile production, biliary and fecal bile salt- and lipid compositions and fecal bacterial composition of C57BL/6J Cftr(-/-tm1Unc) and control mice. We found no differences between the total biliary bile salt or lipid concentrations of Cftr(-/-) and controls. Compared to controls, Cftr(-/-) mice had a ~30% higher bile production and a low bile hydrophobicity, related to a ~7 fold higher concentration of the choleretic and hydrophilic bile salt ursocholate. These findings coexisted with a significantly smaller quantity of fecal Bacteroides bacteria. Liver pathology in Cftr(-/-tm1Unc) is not related to increased bile hydrophobicity. Cftr(-/-) mice do however display a biliary phenotype characterized by increased bile production and decreased biliary hydrophobicity. Our findings suggest Cftr dependent, alterations in intestinal bacterial biotransformation of bile salts. Copyright © 2014. Published by Elsevier B.V.

Side-by-side placement of bilateral endoscopic metal stents for the treatment of postoperative biliary stricture.

PubMed

Kaino, Seiji; Sen-Yo, Manabu; Shinoda, Shuhei; Kawano, Michitaka; Harima, Hirofumi; Suenaga, Shigeyuki; Sakaida, Isao

2017-02-01

Postoperative biliary strictures are usually complications of cholecystectomy. Endoscopic plastic stent prosthesis is generally undertaken for treating benign biliary strictures. Recently, fully covered metal stents have been shown to be effective for treating benign distal biliary strictures. We present the case of a 53-year-old woman with liver injury in which imaging studies showed a common hepatic duct stricture. Endoscopic retrograde cholangiopancreatography also confirmed the presence of a common hepatic duct stricture. Temporally fully covered metal stents with dilated diameters of 6 mm were placed in a side-by-side fashion in the left and right hepatic ducts, respectively. We removed the stents 2 months after their placement. Subsequent cholangiography revealed an improvement in the biliary strictures. Although we were apprehensive about the fully covered metal stents obstructing the biliary side branches, we noted that careful placement of the bilateral metal stents did not cause any complications. Side-by-side deployment of bilateral endoscopic fully covered metal stents can be one of the safe and effective therapies for postoperative biliary stricture.

The immunogenetics of primary biliary cirrhosis: A comprehensive review.

PubMed

Webb, G J; Siminovitch, K A; Hirschfield, G M

2015-11-01

Primary biliary cirrhosis (PBC), a classic autoimmune liver disease, is characterised by a progressive T cell predominant lymphocytic cholangitis, and a serologic pattern of reactivity in the form of specific anti-mitochondrial antibodies (AMA). CD4+ T cells are particularly implicated by PBC's cytokine signature, the presence of CD4+ T cells specific to mitochondrial auto-antigens, the expression of MHC II on injured biliary epithelial cells, and PBC's coincidence with other similar T cell mediated autoimmune conditions. CD4+ T cells are also central to current animal models of PBC, and their transfer typically also transfers disease. The importance of genetic risk to developing PBC is evidenced by a much higher concordance rate in monozygotic than dizygotic twins, increased AMA rates in asymptomatic relatives, and disproportionate rates of disease in siblings of PBC patients, PBC family members and certain genetically defined populations. Recently, high-throughput genetic studies have greatly expanded our understanding of the gene variants underpinning risk for PBC development, so linking genetics and immunology. Here we summarize genetic association data that has emerged from large scale genome-wide association studies and discuss the evidence for the potential functional significance of the individual genes and pathways identified; we particularly highlight associations in the IL-12-STAT4-Th1 pathway. HLA associations and epigenetic effects are specifically considered and individual variants are linked to clinical phenotypes where data exist. We also consider why there is a gap between calculated genetic risk and clinical data: so-called missing heritability, and how immunogenetic observations are being translated to novel therapies. Ultimately whilst genetic risk factors will only account for a proportion of disease risk, ongoing efforts to refine associations and understand biologic links to disease pathways are hoped to drive more rational therapy for patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biliary Bile Acids in Primary Biliary Cirrhosis: Effect of Ursodeoxycholic Acid

PubMed Central

Combes, Burton; Carithers, Robert L.; Maddrey, Willis C.; Munoz, Santiago; Garcia-Tsao, Guadalupe; Bonner, Gregory F.; Boyer, James L.; Luketic, Velimir A.; Shiffman, Mitchell L.; Peters, Marion G.; White, Heather; Zetterman, Rowen K.; Risser, Richard; Rossi, Stephen S.; Hofmann, Alan F.

2014-01-01

Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10–12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean ± SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 ± 18.6, 31.5 ± 15.5, 8.0 ± 9.3, 0.3 ± 1.0, and 0.6 ± 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%–64%) than with taurine (36%–48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%–31%) fell (P < .05). Administered UDCA was also conjugated predominantly with glycine (87%). PMID:10347103

Biliary wound healing, ductular reactions, and IL-6/gp130 signaling in the development of liver disease

PubMed Central

Demetris, A J; III, John G Lunz; Specht, Susan; Nozaki, Isao

2006-01-01

Basic and translational wound healing research in the biliary tree lag significantly behind similar studies on the skin and gastrointestinal tract. This is at least partly attributable to lack of easy access to the biliary tract for study. But clinical relevance, more interest in biliary epithelial cell (BEC) pathophysiology, and widespread availability of BEC cultures are factors reversing this trend. In the extra-hepatic biliary tree, ineffectual wound healing, scarring and stricture development are pressing issues. In the smallest intra-hepatic bile ducts either impaired BEC proliferation or an exuberant response can contribute to liver disease. Chronic inflammation and persistent wound healing reactions in large and small bile ducts often lead to liver cancer. General concepts of wound healing as they apply to the biliary tract, importance of cellular processes dependent on IL-6/gp130/STAT3 signaling pathways, unanswered questions, and future directions are discussed. PMID:16773708

A selective cyclooxygenase-2 inhibitor (Etodolac) prevents spontaneous biliary tumorigenesis in a hamster bilioenterostomy model.

PubMed

Kitasato, Amane; Kuroki, Tamotsu; Adachi, Tomohiko; Ono, Shinichiro; Tanaka, Takayuki; Tsuneoka, Noritsugu; Hirabaru, Masataka; Takatsuki, Mitsuhisa; Eguchi, Susumu

2014-01-01

Secondary biliary carcinomas are associated with persistent reflux cholangitis after bilioenterostomy. Cyclooxygenase-2 (COX-2) has been a target for cancer prevention. The aim of this study was to evaluate the chemopreventive efficacy of long-term treatment with a selective COX-2 inhibitor medication during the natural course after bilioenterostomy without chemical induction. Syrian golden hamsters which underwent choledochojejunostomy were randomly divided into two groups: the control group (n = 31), which was fed a normal diet, and the etodolac group (n = 33), which was fed 0.01% etodolac (a selective COX-2 inhibitor) mixed in the meal. The hamsters were killed at the postoperative weeks 20-39, 40-59, 60-79, or 80-100. Biliary neoplasms, cholangitis, proliferating cell nuclear antigen labeling index (PCNA-LI) of the biliary epithelium, and prostaglandin E2 (PGE2) production were evaluated. The occurrence rates of biliary neoplasm were 43.8 and 15.2% in the control and etodolac groups, respectively (p < 0.05). The incidence of biliary neoplasm increased as time progressed in the control group, whereas it remained at a low level throughout the experimental period in the etodolac group. PGE2 products tended to be lower in the etodolac group, and PCNA-LI was significantly lower in the etodolac group (p < 0.01). These results suggest that the medication etodolac suppresses cell proliferation of the biliary epithelium, thereby preventing biliary carcinogenesis. Etodolac is expected to prevent secondary biliary carcinogenesis caused by persistent reflux cholangitis after bilioenterostomy. © 2014 S. Karger AG, Basel.

Utilization of Reflex Testing for Direct Bilirubin in the Early Recognition of Biliary Atresia.

PubMed

Lam, Leo; Musaad, Samarina; Kyle, Campbell; Mouat, Stephen

2017-05-01

Delayed diagnosis of biliary atresia is an important cause of pediatric end-stage liver failure and liver transplantation. We sought to determine whether direct bilirubin is underutilized by retrospectively reviewing patients with biliary atresia. Further, we aimed to determine the role of reflex testing for direct bilirubin in patients suspected for jaundice. The time intervals between total bilirubin and direct bilirubin measurements were retrospectively reviewed in patients with biliary atresia. We also audited the results of two major laboratories that had implemented reflex testing for direct bilirubin. We evaluated the clinical impact and cost of reflex testing in infants with increased direct bilirubin (>1.5 mg/dL; >25 μmol/L). In patients with known biliary atresia, an isolated total bilirubin measurement preceded direct bilirubin measurement in 46% (40/87) of patients; with a median delay of 19 days (interquartile range 3-44 days). In the community setting, direct bilirubin had a higher clinical specificity for biliary atresia than in the hospital setting. Reporting direct bilirubin results in 1591 infants younger than 2 weeks of age in the community was associated with three admissions to the hospital, one of whom was diagnosed with biliary atresia. The cost for the two laboratories for direct-bilirubin testing was estimated at US$3200 (NZ$4600) for each newly diagnosed case of biliary atresia. We identified underutilization of direct bilirubin as a cause of delay in the recognition of biliary atresia and show that reflex testing for direct bilirubin in jaundiced infants is a cost-effective solution. © 2017 American Association for Clinical Chemistry.

Intraduodenal infusion of cyanidin-3-glucoside transiently promotes triglyceride excretion into bile in rats.

PubMed

Hashimoto, Naoto; Han, Kyu-Ho; Fukushima, Michihiro

2017-02-01

Flavonoids purportedly have a role in improving lipid metabolism. In our preliminary study, highly concentrated flavonoid metabolites appeared in bile juice in rats, which also contains various lipids. Biliary flavonoid metabolites generally have amphiphilic properties, may influence lipid solubility, and possibly contribute to the improvement of dyslipidemia. However, the influence of biliary flavonoid metabolites on the biliary lipid profile is not well known. Therefore, we hypothesized that the amphiphilic property of biliary flavonoid metabolites alters biliary lipid profiles. To estimate the influence of flavonoids on the biliary lipid profile, we laparotomized rats under anesthesia, intraduodenally injected them with cyanidin-3-glucoside chloride (C3G) or quercetin, and analyzed their biliary metabolite concentrations for 2 hours. Concentrations of C3G and quercetin metabolites peaked at 30 minutes after the injection; those of quercetin were 6 to 10 times higher than those of C3G throughout the sampling period up to 2 hours. Biliary triglyceride (TG) concentrations were higher in the C3G group at 30 and 45 minutes; biliary cholesterol and phospholipid concentrations were lower in the quercetin group at 30 minutes than those in the control group. Hepatic TG content after the 2-hour sampling was lower in the C3G group than in the control group. These results suggest that C3G, but not quercetin, may transiently promote TG excretion into bile, with a reduction in hepatic TG content. This C3G effect may be involved in improvement of TG metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunohistochemical analyses of cell cycle progression and gene expression of biliary epithelial cells during liver regeneration after partial hepatectomy of the mouse.

PubMed

Fukuda, Tatsuya; Fukuchi, Tomokazu; Yagi, Shinomi; Shiojiri, Nobuyoshi

2016-05-20

The liver has a remarkable regeneration capacity, and, after surgical removal of its mass, the remaining tissue undergoes rapid regeneration through compensatory growth of its constituent cells. Although hepatocytes synchronously proliferate under the control of various signaling molecules from neighboring cells, there have been few detailed analyses on how biliary cells regenerate for their cell population after liver resection. The present study was undertaken to clarify how biliary cells regenerate after partial hepatectomy of mice through extensive analyses of their cell cycle progression and gene expression using immunohistochemical and RT-PCR techniques. When expression of PCNA, Ki67 antigen, topoisomerase IIα and phosphorylated histone H3, which are cell cycle markers, was immunohistochemically examined during liver regeneration, hepatocytes had a peak of the S phase and M phase at 48-72 h after resection. By contrast, biliary epithelial cells had much lower proliferative activity than that of hepatocytes, and their peak of the S phase was delayed. Mitotic figures were rarely detectable in biliary cells. RT-PCR analyses of gene expression of biliary markers such as Spp1 (osteopontin), Epcam and Hnf1b demonstrated that they were upregulated during liver regeneration. Periportal hepatocytes expressed some of biliary markers, including Spp1 mRNA and protein. Some periportal hepatocytes had downregulated expression of HNF4α and HNF1α. Gene expression of Notch signaling molecules responsible for cell fate decision of hepatoblasts to biliary cells during development was upregulated during liver regeneration. Notch signaling may be involved in biliary regeneration.

Radiological interventions in malignant biliary obstruction

PubMed Central

Madhusudhan, Kumble Seetharama; Gamanagatti, Shivanand; Srivastava, Deep Narayan; Gupta, Arun Kumar

2016-01-01

Malignant biliary obstruction is commonly caused by gall bladder carcinoma, cholangiocarcinoma and metastatic nodes. Percutaneous interventions play an important role in managing these patients. Biliary drainage, which forms the major bulk of radiological interventions, can be palliative in inoperable patients or pre-operative to improve liver function prior to surgery. Other interventions include cholecystostomy and radiofrequency ablation. We present here the indications, contraindications, technique and complications of the radiological interventions performed in patients with malignant biliary obstruction. PMID:27247718

Frey procedure combined with biliary diversion in chronic pancreatitis.

PubMed

Merdrignac, Aude; Bergeat, Damien; Rayar, Michel; Harnoy, Yann; Turner, Kathleen; Courtin-Tanguy, Laetitia; Boudjema, Karim; Meunier, Bernard; Sulpice, Laurent

2016-11-01

The Frey procedure has become the standard operative treatment in chronic painful pancreatitis. Biliary diversion could be combined when associated with common bile duct obstruction. The aim of the present study was to evaluate the impact of the type of biliary diversion combined with the Frey procedure on late morbidity. The data from consecutive patients undergoing the Frey procedure and having a minimum follow-up of 2 years were extracted from a maintained prospective database. The mean endpoint was the rate of secondary biliary stricture after the Frey procedure combined with biliary diversion (bilioenteric anastomosis or common bile duct reinsertion in the resection cavity). Between 2006 and 2013, 55 consecutive patients underwent the Frey procedure. Twenty-nine patients had common bile duct obstruction (52.7%). The technique of biliary diversion resulted in bilioenteric anastomosis in 19 patients (65.5%) and common bile duct reinsertion in 10 patients (34.5%). Preoperative characteristics and early surgical outcomes were comparable. Pain control was similar. There was significantly more secondary biliary stricture after common bile duct reinsertion than after bilioenteric anastomosis (60% vs 11%, P = .008). Combined bilioenteric anastomosis during the Frey procedure is an efficient technique for treating common bile duct obstruction that complicates chronic painful pancreatitis. Bilioenteric anastomosis was associated with less secondary biliary stricture than common bile duct reinsertion in the pancreatic resection cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis.

PubMed

Lenz, Philipp; Eckelskemper, Franziska; Erichsen, Thomas; Lankisch, Tim; Dechêne, Alexander; Lubritz, Gabriele; Lenze, Frank; Beyna, Torsten; Ullerich, Hansjörg; Schmedt, Andre; Domagk, Dirk

2014-09-14

To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis. We performed a prospective study of 127 patients who underwent endoscopic retrograde cholangiopancreatography, for various biliary disorders, at 3 tertiary referral centers in Germany from July 2011 through July 2012 (ClinicalTrials.gov: NCT01109550). Bile, buccal, and stool samples were collected. When indicated, endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections. Candida species were detected in 38 of the 127 bile samples (29.9%). By multivariate analysis patients' age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis (P < 0.05). Patients with immunosuppression (P = 0.058) and recent long-term antibiotic therapy (> 7 d) (P = 0.089) tend to be at risk for biliary candidiasis. One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically. Of Candida subspecies detected, 36.7% were azole-resistant, such as C glabrata. Eight patients received anti-mycotic therapy, based on our algorithm. Of these, 3 had cancer with biliary tract involvement, 2 had secondary sclerosing cholangitis, 1 had retroperitoneal fibrosis, and 5 had septicemia. In all patients contamination was ruled out by smears of the endoscope channel. Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders. Our suggested algorithm facilitates the further clinical management.

Biliary atresia: evaluation on two distinct periods at a reference pediatric service.

PubMed

Queiroz, Thais Costa Nascentes; Ferreira, Alexandre Rodrigues; Fagundes, Eleonora Druve Tavares; Roquete, Mariza Leitão Valadares; Penna, Francisco José

2014-01-01

Biliary atresia is a progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree that presents with biliary obstruction exclusively in the neonatal period. To assess the differences regarding age at referral, age at surgery, duration of propaedeutics and waiting time for surgery between two groups of infants in different periods. Retrospective study of infants diagnosed with biliary atresia on two periods: 1983-1993 and 1998-2011. Biliary atresia was diagnosed in 129 infants, being 48 in casuistic I and 81 in casuistic II. The median age at admission was 94 and 60 days, respectively (P = 0.0001). On evaluating patients who had undergone portoenterostomy before 120 days of age, no difference was observed regarding the duration of propaedeutics or waiting time for surgery (P = 0.15), but difference was found when comparing the age at surgery (P = 0.002). Among those infants with no biliary flow and without liver transplantation or death after 18 post-operative months, the estimated probability of survival was 44.6% and 38.7% in casuistics I and II, respectively. In casuistic I, all infants who showed biliary flow were alive during the observation period and, in casuistic II, 80.3% were alive after 7 years of follow-up. Even though patients were admitted and treated earlier, it is clear that surgery could be done sooner. Delay in referral and timely propaedeutics were the main contributors.

Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

2014-09-01

Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

Invariant natural killer T cells trigger adaptive lymphocytes to churn up bile.

PubMed

Joyce, Sebastian; Van Kaer, Luc

2008-05-15

How innate immune response causes autoimmunity has remained an enigma. In this issue of Cell Host & Microbe, Mattner et al. demonstrate that invariant natural killer T cells activated by the mucosal commensal Novosphingobium aromaticivorans precipitate chronic T cell-mediated autoimmunity against small bile ducts that mirrors human primary biliary cirrhosis. These findings provide a mechanistic understanding of the role of innate immunity toward a microbe in the development of autoimmunity.

Spontaneous external biliary fistula uncomplicated by gallstones.

PubMed Central

Birch, B. R.; Cox, S. J.

1991-01-01

External biliary fistulae are rare. Only 65 cases have been reported in the literature and in each instance gallstones were a complicating factor. We report in this paper the first case of spontaneous external (cholecystocutaneous) biliary fistula uncomplicated by gallstones. PMID:2068038

Complications and management of forgotten long-term biliary stents.

PubMed

Sohn, Se Hoon; Park, Jae Hyun; Kim, Kook Hyun; Kim, Tae Nyeun

2017-01-28

To evaluate complications and management outcomes of retained long-term plastic biliary stents. Endoscopic plastic biliary stent placement was performed in 802 patients at Yeungnam University Hospital between January 2000 and December 2014. Follow-up loss with a subsequently forgotten stent for more than 12 mo occurred in 38 patients. We retrospectively examined the cause of biliary stent insertion, status of stents, complications associated with biliary stents and management outcomes of long-term plastic biliary stents. Continuous variables were analyzed using the t test. Observed frequencies in subsets of the study population were compared using Fisher's exact test and χ 2 tests. Statistical significance was defined as P < 0.05 (two-tailed). Mean age of patients was 73.7 ± 12 years and male-to-female ratio was 2.2:1. Indications of plastic biliary stent insertion were bile duct stones (63.2%, 24/38) and benign bile duct stricture (52.6%, 20/38). Mean duration of retained plastic stent was 22.6 ± 12.2 mo, and in 10 cases (26.3%), stents were retained for more than 24 mo. Common bile duct (CBD) stones or sludge were found in most cases (92.1%, 35/38). The most common complication was acute cholangitis (94.7%, 36/38). Stent removal by endoscopic approach was successfully performed in 92.1% (35/38) of the cases. In 3 cases, an additional plastic stent was inserted alongside the previous stent due to failure of the stent removal. Endoscopic removal of bile duct stones was successful in 73.7% (28/38) of the cases. When patients were divided into two groups by duration of stent placement (12 to 24 mo vs over 24 mo), there were no differences in the development of cholangitis, presence of biliary stones, and success rate of endoscopic removal of stones and biliary stents. The most common complication of retained long-term plastic biliary stents was acute cholangitis associated with CBD stones. Endoscopic management was successfully performed in most cases.

Availability of hospital dental care services under sedation or general anesthesia for individuals with special needs in the Unified Health System for the State of Minas Gerais (SUS-MG), Brazil.

PubMed

Santos, Jacqueline Silva; Valle, Déborah Andrade; Palmier, Andréa Clemente; do Amaral, João Henrique Lara; de Abreu, Mauro Henrique Nogueira Guimarães

2015-02-01

This study identified the demographic characteristics of individuals and dental treatment care under sedation/general anesthesia in a hospital environment in the Unified Health System in the State of Minas Gerais (SUS-MG). All Hospitalization Authorizations (AIHs) for Dental Treatment for Patients with Special Needs procedures were evaluated between July 2011 and June 2012. Demographic and health care variables for treatment were also assessed. Hospitalization rates per 10,000 inhabitants, and health care coverage provided in the state of Minas Gerais and in each of the Broader Health Regions were calculated. Descriptive analysis of data was carried out by calculating the central trend and variability frequency and measurements. All 1,063 AIHs paid during the study period were evaluated, which is equivalent to a rate of 0.54 hospitalizations per 10,000 individuals. The majority of the patients were adult, male, diagnosed with mental or behavioral disorders and resident in 27.7% of the municipalities in Minas Gerais. The procedures were performed in 39 municipalities and the care coverage was equal to 1.58%. The study reveals a classic demographic and clinical profile of patient attendance. Difficulties in establishing a network of dental care were identified.

[The Hospital Information System of the Brazilian National Unified Health System: a preliminary evaluation of performance in monitoring RhD hemolytic disease of the newborn].

PubMed

Lobato, Gustavo; Reichenheim, Michael Eduardo; Coeli, Claudia Medina

2008-03-01

This study aimed to evaluate the adequacy of the Hospital Information System of the National Unified Health System (SIH-SUS) in identifying cases of RhD hemolytic disease of the newborn (HDN) at the Fernandes Figueira Institute (IFF/FIOCRUZ) from 1998 to 2003. Neonatal records, data from the Medical Archives, and AIH (Hospital Admissions Authorization Form) data consolidated in the SIH-SUS were analyzed. Cases were identified according to the following fields: principal diagnosis, secondary diagnosis, and procedure performed. During the period studied, 194 cases of HDN were diagnosed. The Medical Archives registered 148 newborns with HDN, however only 147 AIHs were issued and 145 consolidated in the SIH-SUS. Among these 145 cases, 84 cited HDN as the principal diagnosis, while secondary diagnosis identified 38 additional cases and the procedures performed failed to identify any further cases. Thus, the SIH-SUS identified only 122 (62.9%) of the 194 cases of HDN treated at the IFF/FIOCRUZ. Although it is necessary to evaluate other units, the SIH-SUS does not appear to be reliable for monitoring HDN. Additional studies are essential for employing secondary administrative data in the context of epidemiological surveillance.

Preoperative biliary drainage in hilar cholangiocarcinoma: When and how?

PubMed Central

Paik, Woo Hyun; Loganathan, Nerenthran; Hwang, Jin-Hyeok

2014-01-01

Hilar cholangiocarcinoma is a tumor of the extrahepatic bile duct involving the left main hepatic duct, the right main hepatic duct, or their confluence. Biliary drainage in hilar cholangiocarcinoma is sometimes clinically challenging because of complexities associated with the level of biliary obstruction. This may result in some adverse events, especially acute cholangitis. Hence the decision on the indication and methods of biliary drainage in patients with hilar cholangiocarcinoma should be carefully evaluated. This review focuses on the optimal method and duration of preoperative biliary drainage (PBD) in resectable hilar cholangiocarcinoma. Under certain special indications such as right lobectomy for Bismuth type IIIA or IV hilar cholangiocarcinoma, or preoperative portal vein embolization with chemoradiation therapy, PBD should be strongly recommended. Generally, selective biliary drainage is enough before surgery, however, in the cases of development of cholangitis after unilateral drainage or slow resolving hyperbilirubinemia, total biliary drainage may be considered. Although the optimal preoperative bilirubin level is still a matter of debate, the shortest possible duration of PBD is recommended. Endoscopic nasobiliary drainage seems to be the most appropriate method of PBD in terms of minimizing the risks of tract seeding and inflammatory reactions. PMID:24634710

Therapeutic approaches for portal biliopathy: A systematic review

PubMed Central

Franceschet, Irene; Zanetto, Alberto; Ferrarese, Alberto; Burra, Patrizia; Senzolo, Marco

2016-01-01

Portal biliopathy (PB) is defined as the presence of biliary abnormalities in patients with non-cirrhotic/non-neoplastic extrahepatic portal vein obstruction (EHPVO) and portal cavernoma (PC). The pathogenesis of PB is due to ab extrinseco compression of bile ducts by PC and/or to ischemic damage secondary to an altered biliary vascularization in EHPVO and PC. Although asymptomatic biliary abnormalities can be frequently seen by magnetic resonance cholangiopancreatography in patients with PC (77%-100%), only a part of these (5%-38%) are symptomatic. Clinical presentation includes jaundice, cholangitis, cholecystitis, abdominal pain, and cholelithiasis. In this subset of patients is required a specific treatment. Different therapeutic approaches aimed to diminish portal hypertension and treat biliary strictures are available. In order to decompress PC, surgical porto-systemic shunt or transjugular intrahepatic porto-systemic shunt can be performed, and treatment on the biliary stenosis includes endoscopic (Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy, balloon dilation, stone extraction, stent placement) and surgical (bilioenteric anastomosis, cholecystectomy) approaches. Definitive treatment of PB often requires multiple and combined interventions both on vascular and biliary system. Liver transplantation can be considered in patients with secondary biliary cirrhosis, recurrent cholangitis or unsuccessful control of portal hypertension. PMID:28018098

Anatomical Variations of the Biliary Tree Found with Endoscopic Retrograde Cholagiopancreatography in a Referral Center in Southern Iran.

PubMed

Taghavi, Seyed Alireza; Niknam, Ramin; Alavi, Seyed Ehsan; Ejtehadi, Fardad; Sivandzadeh, Gholam Reza; Eshraghian, Ahad

2017-10-01

BACKGROUND Anatomical variations in the biliary system have been proven to be of clinical importance. Awareness of the pattern of these variations in a specific population may help to prevent and manage biliary injuries during surgical and endoscopic procedures. Knowledge of the biliary anatomy will be also of great help in planning the drainage of adequate percentage of liver parenchyma in endoscopic or radiological procedures. METHODS All consecutive patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) from April 2013 to April 2015 at Nemazee Hospital, a referral center in the south of Iran, were included in this cross-sectional study. The patients with previous hepatic or biliary surgery, liver injury or destructive biliary disease were excluded from the study. All ERCPs were reviewed by two expert gastroenterologists in this field. The disagreed images by the two gastroenterologists were excluded. Huang classification was used for categorizing the different structural variants of the biliary tree, and the frequency of each variant was recorded. RESULTS Totally, 362 patients (181 men and 181 women) were included in the study. 163 patients (45%) had type A1 Huang classification (right dominant), which was the most prevalent type among our patients. 55% of them had non-right dominant anatomy. The result of the Chi-square test revealed that there was no statistically significant difference between the men and women regarding the anatomical variations (p = 0.413). CONCLUSION The anatomical variation in the biliary system among Iranian patients is comparable to other regions of the world. Significant proportions of our patients are non-right dominant and may need bilateral biliary drainage.

Wisteria floribunda agglutinin-sialylated mucin core polypeptide 1 is a sensitive biomarker for biliary tract carcinoma and intrahepatic cholangiocarcinoma: a multicenter study.

PubMed

Shoda, Junichi; Matsuda, Atsushi; Shida, Takashi; Yamamoto, Masakazu; Nagino, Masato; Tsuyuguchi, Toshio; Yasaka, Takahiro; Tazuma, Susumu; Uchiyama, Kazuhisa; Unno, Michiaki; Ohkohchi, Nobuaki; Nakanuma, Yasuni; Kuno, Atsushi; Narimatsu, Hisashi

2017-02-01

Wisteria floribunda agglutinin (WFA)-sialylated mucin core polypeptide 1 (MUC1) was investigated as a new glycoprotein marker for cholangiocarcinoma (CC) using glycoproteomics technologies. In this multicenter study, WFA-sialylated MUC1 levels in serum and bile samples were measured to determine their diagnostic capability in biliary tract carcinoma (BTC) and intrahepatic (Ih) CC. The study included 244 patients with BTC, 59 patients with IhCC, 287 patients with benign biliary tract diseases, and 44 control subjects. Serum WFA-sialylated MUC1 levels were significantly higher in patients with either BTC or IhCC than in control subjects and those with benign biliary tract diseases. Patients with IhCC showed higher WFA-sialylated MUC1 levels than patients with tumors at other sites. No significant differences in WFA-sialylated MUC1 levels were found with regard to cancer stage or tissue type. Receiver operating characteristic curve analysis showed that WFA-sialylated MUC1 was superior to carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for the diagnosis of benign biliary tract diseases, BTC, and IhCC, as well as for stage I and II carcinomas. Significantly higher levels of biliary WFA-sialylated MUC1 were observed in BTC/IhCC than in benign biliary tract diseases. The diagnostic capability of biliary WFA-sialylated MUC1 was also superior to that of CA19-9, and diagnostic sensitivity was higher than that of biliary cytology for BTC/IhCC. WFA-sialylated MUC1 is a useful novel biomarker for BTC/IhCC. In the future, this measurement should be applied in the clinical setting.

Treatment and outcome of traumatic biliary injuries in children.

PubMed

Soukup, Elizabeth S; Russell, Katie W; Metzger, Ryan; Scaife, Eric R; Barnhart, Douglas C; Rollins, Michael D

2014-02-01

Traumatic biliary tract injuries in children are rare but may result in significant morbidity. The objective of this study was to review the occurrence of traumatic biliary tract injuries in children, management strategies, and outcome. We conducted a retrospective review of patients with biliary tract injury using the trauma registry at our level 1 pediatric trauma center from 2002-2012. Twelve out of 13,582 trauma patients were identified, representing 0.09% of all trauma patients. All were secondary to blunt trauma. Mean age was 9.7 years [range 4-15], and mean Injury Severity Score was 31 ± 14, with overall survival of 92%. Biliary injuries included major ductal injury (6), minor ductal injury with biloma (4), gallbladder injury (2), and intrahepatic ductal injury (1). Major ductal injuries were managed by endoscopic retrograde cholangiopancreatography (ERCP) and biliary stent (5) and Roux-en-Y hepaticojejunostomy (1). Associated gallbladder injury was managed by cholecystectomy. In addition, the associated biloma was managed with percutaneous drainage (7), laparoscopic drainage (2), or during laparotomy (3). Two patients with ductal injuries developed late strictures after initial management with ERCP and stent placement. One of the two patients ultimately required a left hepatectomy, and the other has been managed conservatively without evidence of cholangitis. Two patients required placement of additional drains and prolonged antibiotics for superinfection following biloma drainage. Biliary tract injuries are rare in children, and many are amenable to adjunctive therapy, including ERCP and biliary stent placement with or without placement of a peritoneal drain. Patients with a discrete ductal injury are at higher risk for stricture and require close follow up. Hepaticojejunostomy remains the definitive repair for large extrahepatic biliary tract injuries or transections. © 2014.

Complex bile duct injuries: management

PubMed Central

Ardiles, V.; Pekolj, J.

2008-01-01

Background. Laparoscopic cholecystectomy is the present treatment of choice for patients with gallbladder stones, despite its being associated with a higher incidence of biliary injuries compared with the open procedure. Injuries occurring during the laparoscopic approach seem to be more complex. A complex biliary injury is a disease that is difficult to diagnose and treat. We considered complex injuries: 1) injuries that involve the confluence; 2) injuries in which repair attempts have failed; 3) any bile duct injury associated with a vascular injury; 4) or any biliary injury in association with portal hypertension or secondary biliary cirrhosis. The present review is an evaluation of our experience in the treatment of these complex biliary injuries and an analysis of the international literature on the management of patients. PMID:18695753

A multicenter, randomized, double-blind trial comparing the efficacy and safety of TUDCA and UDCA in Chinese patients with primary biliary cholangitis

PubMed Central

Ma, Hong; Zeng, Minde; Han, Ying; Yan, Huiping; Tang, Hong; Sheng, Jifang; Hu, Heping; Cheng, Liufang; Xie, Qing; Zhu, Youfu; Chen, Guofeng; Gao, Zhiliang; Xie, Wen; Wang, Jiyao; Wu, Shanming; Wang, Guiqiang; Miao, Xiaohui; Fu, Xiaoqing; Duan, Liping; Xu, Jie; Wei, Lai; Shi, Guangfeng; Chen, Chengwei; Chen, Minhu; Ning, Qin; Yao, Chen; Jia, Jidong

2016-01-01

Abstract Aim: Tauroursodeoxycholic acid (TUDCA) is a taurine conjugated form of ursodeoxycholic acid (UDCA) with higher hydrophility. To further evaluate the efficacy and safety of TUDCA for primary biliary cholangitis (PBC), we performed this study on Chinese patients. Methods: 199 PBC patients were randomly assigned to either 250 mg TUDCA plus UDCA placebo or 250 mg UDCA plus TUDCA placebo, 3 times per day for 24 weeks. The primary endpoint was defined as percentage of patients achieving serum alkaline phosphatase (ALP) reduction of more than 25% from baseline. Results: At week 24, 75.97% of patients in the TUDCA group and 80.88% of patients in the UDCA group achieved a serum ALP reduction of more than 25% from baseline (P = 0.453). The percentage of patients with serum ALP levels declined more than 40% following 24 weeks of treatment was 55.81% in the TUDCA group and 52.94% in the UDCA group (P = 0.699). Both groups showed similar improvement in serum levels of ALP, aspartate aminotransferase, and total bilirubin (P > 0.05). The proportion of patients with pruritus/scratch increased from 1.43% to 10.00% in UDCA group, while there's no change in TUDCA group (P = 0.023). Both drugs were well tolerated, with comparable adverse event rates between the 2 groups. Conclusions: TUDCA is safe and as efficacious as UDCA for the treatment of PBC, and may be better to relieve symptoms than UDCA. PMID:27893675

Biliary atresia: lessons learned from the voluntary German registry.

PubMed

Leonhardt, J; Kuebler, J F; Leute, P J; Turowski, C; Becker, T; Pfister, E-D; Ure, B; Petersen, C

2011-03-01

Aim of the study was to carry out a 5-year survey of German patients with biliary atresia (BA) and to launch a discussion regarding the feasibility of voluntary registries in unregulated healthcare systems. A retrospective analysis of German BA patients born between 2001 and 2005, based on data collected from the voluntary European Biliary Atresia Registry (EBAR), was carried out and supplemented by data from all BA patients who underwent liver transplantation at the only 4 pediatric transplantation centers (pLTx) in Germany which are so far not registered at EBAR. Survival rates were calculated using Kaplan-Meier analysis and compared by Cox regression to determine the predictive value of age at surgery and the influence of the center size (fewer or more than 5 patients/study period) on overall survival and survival with native liver. A critical review of the 148 German EBAR charts revealed that 11 patients (7.4%) had no biliary atresia. The remaining 137 patients from EBAR together with 46 BA patients who underwent LTx without prior registration at EBAR were evaluated with a median follow-up of 39 months (range: 25-85 months). 29 hospitals performed a total of 159 Kasai procedures, but only 7 centers treated 5 or more patients (116 patients, range: 5-68), and 22 hospitals performed less than 5 KP (43 patients, range: 1-4). Primary LTx was performed in 21 patients (11.5%) and 3 patients died without surgical intervention. 16 patients were lost to follow-up (8.7%). Overall survival after 2 years was 83.3% (139 patients), including 105 patients (63%) who had undergone LTx and 34 patients (20.3%) with native liver. 28 patients died (16.7%), 8 after LTx (5.8%). The experience of the center was the only factor with a significant predictive value for jaundice-free survival with native liver (p=0.001). 25% of all German BA patients were not registered at EBAR, and 29 clinics were involved in the surgical management of BA patients. Therefore a new approach consisting of an internet-based decentralized registry for rare neonatal liver diseases is outlined which could improve the future management of patients with BA. The centralization of such patients at experienced centers with higher caseloads is necessary in Germany and would improve the outcome of patients with biliary atresia. © Georg Thieme Verlag KG Stuttgart · New York.

A systematic review and meta-analysis of randomized trials and prospective studies comparing covered and bare self-expandable metal stents for the treatment of malignant obstruction in the digestive tract.

PubMed

Yang, Zhiping; Wu, Qiong; Wang, Fang; Ye, Xiaofei; Qi, Xingshun; Fan, Daiming

2013-01-01

Self-expandable metal stents (SEMS) are widely used for the palliative treatment of malignant gastrointestinal obstruction. Our aim was to evaluate the evidence comparing covered and bare SEMS in the digestive tract using meta-analytical techniques. A literature search was performed using PubMed, Cochrane Library, and Embase databases for comparative studies assessing the two types of stents. The primary outcomes of interest were stent patency and patient survival; second outcomes included technical success, clinical success, tumor ingrowth, tumor overgrowth, and stent migration. A random-effects model was conducted. Pooled analysis was done separately based on the different segments of the digestive tract. Eleven studies (8 randomized controlled trials and 3 prospective cohort studies) including a total of 1376 patients were identified. Covered SEMS were equivalent to bare SEMS in terms of technical success, clinical success, stent patency (gastroduodenal obstruction: HR =0.87, 95% CI 0.53-1.42; colorectal obstruction: HR =0.89, 95% CI 0.18-4.45; biliary obstruction: HR =0.73, 95% CI 0.41-1.32) and survival rates (esophageal obstruction: HR =1.80, 95% CI 0.73-4.44; gastroduodenal obstruction: HR =0.83, 95% CI 0.55-1.26; biliary obstruction: HR =0.99, 95% CI 0.77-1.28), although bare stents were more prone to tumor ingrowth (esophageal obstruction: RR =0.10, 95% CI 0.01-0.77; gastroduodenal obstruction: RR =0.12, 95% CI 0.03-0.55; colorectal obstruction: RR =0.21, 95% CI 0.06-0.70; biliary obstruction: RR =0.21, 95% CI 0.06-0.69), whereas covered stents had the higher risk of stent migration (gastroduodenal obstruction: RR =5.01, 95% CI 1.53-16.43; colorectal obstruction: RR =11.70, 95% CI 2.84-48.27; biliary obstruction: RR =8.11, 95% CI 1.47-44.76) and tumor overgrowth (biliary obstruction: RR =2.03, 95% CI 1.08-3.78). Both covered and bare SEMS are comparable in efficacy for the palliative treatment of malignant obstruction in the digestive tract. Each type of the stents has its own merit and demerit relatively.

Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis

PubMed Central

Lenz, Philipp; Eckelskemper, Franziska; Erichsen, Thomas; Lankisch, Tim; Dechêne, Alexander; Lubritz, Gabriele; Lenze, Frank; Beyna, Torsten; Ullerich, Hansjörg; Schmedt, Andre; Domagk, Dirk

2014-01-01

AIM: To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis. METHODS: We performed a prospective study of 127 patients who underwent endoscopic retrograde cholangiopancreatography, for various biliary disorders, at 3 tertiary referral centers in Germany from July 2011 through July 2012 (ClinicalTrials.gov: NCT01109550). Bile, buccal, and stool samples were collected. When indicated, endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections. RESULTS: Candida species were detected in 38 of the 127 bile samples (29.9%). By multivariate analysis patients’ age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis (P < 0.05). Patients with immunosuppression (P = 0.058) and recent long-term antibiotic therapy (> 7 d) (P = 0.089) tend to be at risk for biliary candidiasis. One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically. Of Candida subspecies detected, 36.7% were azole-resistant, such as C glabrata. Eight patients received anti-mycotic therapy, based on our algorithm. Of these, 3 had cancer with biliary tract involvement, 2 had secondary sclerosing cholangitis, 1 had retroperitoneal fibrosis, and 5 had septicemia. In all patients contamination was ruled out by smears of the endoscope channel. CONCLUSION: Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders. Our suggested algorithm facilitates the further clinical management. PMID:25232260

Biliary versus alcohol-related infected pancreatic necrosis: similarities and differences in the follow-up.

PubMed

Reszetow, Jacek; Hać, Stanisław; Dobrowolski, Sebastian; Stefaniak, Tomasz; Wajda, Zdzisław; Gruca, Zbigniew; Sledziński, Zbigniew; Studniarek, Michał

2007-10-01

Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis. Data concerning survivors' quality of life and pancreatic functions are scarce. Follow-up of the patients with alcohol and biliary etiology of IPN treated with open necrosectomy was performed. Twenty-eight survivors after operative treatment (Bradley procedure) of IPN were followed up 24 to 96 months after discharge from the hospital (10 biliary and 18 alcohol patients). Their exocrine and endocrine pancreatic functions and quality of life (Functional Assessment of Chronic Illness Therapy scale) were evaluated. Pancreatic tissue remaining after necrosectomy was visualized by use of contrast-enhanced computed tomography (CT). In 44.4% of alcohol-induced IPN patients, the presence of the whole pancreas was shown on the follow-up CT, contrary to the biliary group, where the partial lack of the pancreas was observed in all cases. Pancreatic tissue calcifications were present on CT in 8 patients of alcohol-induced acute pancreatitis group only. Median stool elastase 1 concentrations were 318.1 U/mL in the biliary group and 238.3 U/mL in the alcohol-induced group (not significant). The Functional Assessment of Chronic Illness Therapy scale showed significantly higher social/family and emotional well-being in patients with biliary acute necrotizing pancreatitis. Patients after alcohol-induced IPN had lower quality of life compared with biliary etiology. Biliary and alcohol-induced IPN patients after surgical treatment have nonsignificant differences of endocrine and exocrine pancreatic functions.

Tea consumption and the risk of biliary tract cancer: a systematic review and dose-response meta-analysis of observational studies.

PubMed

Xiong, Jianping; Lin, Jianzhen; Wang, Anqiang; Wang, Yaqin; Zheng, Ying; Sang, Xinting; Xu, Yiyao; Lu, Xin; Zhao, Haitao

2017-06-13

Recent studies have shown that tea consumption is associated with the reduced incidence of some types of cancer, possibly including biliary tract cancer. However, the epidemiological evidences for the association with risk of biliary tract cancer are contradictory. Thus, we performed meta-analysis of published observational studies to assess the association between tea consumption and risk of biliary tract cancer. Relevant studies were identified by searching PubMed, EMBASE, and ISI Web of Science published before October 2016. The Newcastle-Ottawa Scale was used to evaluate the quality of included studies, and publication bias was evaluated using funnel plots, and Begg's and Egger's tests. This meta-analysis includes eight studies comprising 18 independent reports. The incidence of biliary tract cancer reduced about 34% (significantly) for tea intake group in comparison with never intake group (summary odds ratio [OR] = 0.66; 95% confidence interval [CI] = 0.48-0.85). Additionally, an inverse relationship between tea intake and risk of biliary tract cancer was statistically significant in women (OR = 0.65; 95 % CI = 0.47-0.83), but not in men (OR = 0.86; 95% CI = 0.58-1.13). Dose- response analysis indicated that the risk of biliary tract cancer decreased by 4% with each additional cup of tea one day (relative risk [RR] = 0.96, 95% CI = 0.93-0.98, p = 0.001). In summary, tea intake is associated with decreased risk of biliary tract cancer, especially for women.

Perioperative Management of Hilar Cholangiocarcinoma

PubMed Central

Poruk, Katherine E.; Pawlik, Timothy M.

2016-01-01

Background Cholangiocarcinoma is the most common primary tumor of the biliary tract although it accounts for only 2 % of all human malignancies. We herein review hilar cholangiocarcinoma including its risk factors, the main classification systems for tumors, current surgical management of the disease, and the role chemotherapy and liver transplantation may play in selected patients. Methods We performed a comprehensive literature search using PubMed, Medline, and the Cochrane library for the period 1980–2015 using the following MeSH terms: “hilar cholangiocarcinoma”, “biliary cancer”, and “cholangiocarcinoma”. Only recent studies that were published in English and in peer reviewed journals were included. Findings Hilar cholangiocarcinoma is a disease of advanced age with an unclear etiology, most frequently found in Southeast Asia and relatively rare in Western countries. The best chance of long-term survival and potential cure is surgical resection with negative surgical margins, but many patients are unresectable due to locally advanced or metastatic disease at diagnosis. As a result of recent efforts, new methods of management have been identified for these patients, including preoperative portal vein embolism and biliary drainage, neoadjuvant chemotherapy with subsequent transplantation, and chemoradiation therapy. Conclusion Current management of hilar cholangiocarcinoma depends on extent of the tumor at presentation and includes surgical resection, liver transplantation, portal vein embolization, and chemoradiation therapy. Our understanding of hilar cholangiocarcinoma has improved in recent years and further research offers hope to improve the outcome in patients with these rare tumors. PMID:26022776

Covered versus Uncovered Self-Expandable Metal Stents for Managing Malignant Distal Biliary Obstruction: A Meta-Analysis.

PubMed

Li, Jinjin; Li, Tong; Sun, Ping; Yu, Qihong; Wang, Kun; Chang, Weilong; Song, Zifang; Zheng, Qichang

2016-01-01

To compare the efficacy of using covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (UCSEMSs) to treat objective jaundice caused by an unresectable malignant tumor. We performed a comprehensive electronic search from 1980 to May 2015. All randomized controlled trials comparing the use of CSEMSs and UCSEMSs to treat malignant distal biliary obstruction were included. The analysis included 1417 patients enrolled in 14 trials. We did not detect significant differences between the UCSEMS group and the CSEMS group in terms of cumulative stent patency (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.19-4.53; p = 0.93, I2 = 0%), patient survival (HR 0.77, 95% CI 0.05-10.87; p = 0.85, I2 = 0%), overall stent dysfunction (relative ratio (RR) 0.85, M-H, random, 95% CI 0.57-1.25; p = 0.83, I2 = 63%), the overall complication rate (RR 1.26, M-H, fixed, 95% CI 0.94-1.68; p = 0.12, I2 = 0%) or the change in serum bilirubin (weighted mean difference (WMD) -0.13, IV fixed, 95% CI 0.56-0.3; p = 0.55, I2 = 0%). However, we did detect a significant difference in the main causes of stent dysfunction between the two groups. In particular, the CSEMS group exhibited a lower rate of tumor ingrowth (RR 0.25, M-H, random, 95% CI 0.12-0.52; p = 0.002, I2 = 40%) but a higher rate of tumor overgrowth (RR 1.76, M-H, fixed, 95% CI 1.03-3.02; p = 0.04, I2 = 0%). Patients with CSEMSs also exhibited a higher migration rate (RR 9.33, M-H, fixed, 95% CI 2.54-34.24; p = 0.008, I2 = 0%) and a higher rate of sludge formation (RR 2.47, M-H, fixed, 95% CI 1.36-4.50; p = 0.003, I2 = 0%). Our meta-analysis indicates that there is no significant difference in primary stent patency and stent dysfunction between CSEMSs and UCSEMSs during the period from primary stent insertion to primary stent dysfunction or patient death. However, when taking further management for occluded stents into consideration, CSEMSs is a better choice for patients with malignant biliary obstruction due to their removability.

Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators

PubMed Central

Zhang, Hai-Chun; Hu, Rong-Fei; Zhu, Ting; Tong, Ling; Zhang, Qiu-Qin

2016-01-01

AIM: To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. METHODS: One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. RESULTS: LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%). CONCLUSION: The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value. PMID:27298571

Interventional Endoscopy Database for Pancreatico-biliary, Gastrointestinal and Esophageal Disorders

ClinicalTrials.gov

2017-02-16

Ampullary Cancer; Duodenal Cancer; Bile Duct Cancer; Bile Duct Disorders; Gallstones; Obstructive Jaundice; Pancreatic Disorders (Noncancerous); Colorectal Cancer; Esophageal Cancer; Barrett's Esophagus; Gastric Malignancies; Pancreatic Cancer; Pediatric Gastroenterology; Cholangiocarcinoma; Pancreatic Pseudocysts; Acute and Chronic Pancreatitis; Recurrent Pancreatitis; Cholangitis; Bile Leak; Biliary Strictures; Pancreatic Divisum; Biliary and Pancreatic Stones; Choledocholithiasis

Biliary Ascariasis: MR Cholangiography Findings in Two Cases

PubMed Central

Hwang, Cheol Mok; Ha, Hyun Kwon; Kim, Pyo Nyun; Lee, Moon-Gyu

2001-01-01

We describe the imaging features of two cases of biliary ascariasis. Ultrasonography and CT showed no specific abnormal findings, but MR cholangiography clearly demonstrated an intraductal linear filling defect that led to the correct diagnosis. MR cholangiography is thus a useful technique for the diagnosis of biliary ascariasis. PMID:11752990

Hilar biliary neurofibroma without neurofibromatosis: case report with contrast-enhanced ultrasound findings.

PubMed

Guo, Huan-Ling; Chen, Li-da; Wang, Zhu; Huang, Yang; Liu, Jin-Ya; Shan, Quan-Yuan; Xie, Xiao-Yan; Lu, Ming-de; Wang, Wei

2016-10-01

Solitary neurofibroma located in the hilum of the liver is extremely rare, particularly without neurofibromatosis. We herein report a case of hilar biliary neurofibroma without signs of von Recklinghausen's disease. A 36-year-old man was admitted to our department with progressive jaundice. The case was diagnosed as hilar cholangiocarcinoma based on preoperative imaging. The patient consequently received a Roux-en-Y hepaticojejunostomy and was confirmed with neurofibroma pathologically. This is the first reported imaging finding of hilar biliary neurofibroma using contrast-enhanced ultrasound, emphasizing the differential diagnosis of biliary tumors.

Resolution of Metallic Biliary Stent Allergic Reaction After Partial Stent Removal in a Patient with Nickel Sensitivity.

PubMed

Esparaz, Anthony M; Ahmed, Muneeb

2017-07-01

Local and systemic reactions to implanted metallic devices, particularly to those containing nickel, are well documented. Metal ions are released due to exposure of the metal to blood, proteins, other body fluids, and sheer mechanical stress. Metal ions then complex with native proteins and become antigens, which can elicit hypersensitivity reactions. Another case report depicts a specific allergic complication (early stent occlusion) related to metallic biliary stent implantation. We present a case of allergic symptoms, associated with eating, in a patient who developed nickel sensitivity after biliary metal stent placement confirmed by allergic skin testing to the same metallic biliary stent placed one year earlier. Symptoms resolved following partial removal of the non-epithelialized portion of the biliary stent.

Laparoscopic Transcystic Treatment Biliary Calculi by Laser Lithotripsy

PubMed Central

Jin, Lan; Zhang, Zhongtao

2016-01-01

Background and Objectives: Laparoscopic transcystic common bile duct exploration (LTCBDE) is a complex procedure requiring expertise in laparoscopic and choledochoscopic skills. The purpose of this study was to investigate the safety and feasibility of treating biliary calculi through laparoscopic transcystic exploration of the CBD via an ultrathin choledochoscope combined with dual-frequency laser lithotripsy. Methods: From August 2011 through September 2014, 89 patients at our hospital were treated for cholecystolithiasis with biliary calculi. Patients underwent laparoscopic cholecystectomy and exploration of the CBD via the cystic duct and the choledochoscope instrument channel. A dual-band, dual-pulse laser lithotripsy system was used to destroy the calculi. Two intermittent laser emissions (intensity, 0.12 J; pulse width 1.2 μs; and pulse frequency, 10 Hz) were applied during each contact with the calculi. The stones were washed out by water injection or removed by a stone-retrieval basket. Results: Biliary calculi were removed in 1 treatment in all 89 patients. No biliary tract injury or bile leakage was observed. Follow-up examination with type-B ultrasonography or magnetic resonance cholangiopancreatography 3 months after surgery revealed no instances of retained-calculi–related biliary tract stenosis. Conclusion: The combined use of laparoscopic transcystic CBD exploration by ultrathin choledochoscopy and dual-frequency laser lithotripsy offers an accurate, convenient, safe, effective method of treating biliary calculi. PMID:27904308