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  1. Primary biliary cirrhosis

    MedlinePlus

    ... medlineplus.gov/ency/article/000282.htm Primary biliary cirrhosis To use the sharing features on this page, ... and leads to scarring of the liver called cirrhosis. This is called biliary cirrhosis. Causes The cause ...

  2. The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis.

    PubMed

    Yang, Fan; Wang, Qixia; Wang, Zhaoyue; Miao, Qi; Xiao, Xiao; Tang, Ruqi; Chen, Xiaoyu; Bian, Zhaolian; Zhang, Haiyan; Yang, Yue; Sheng, Li; Fang, Jingyuan; Qiu, Dekai; Krawitt, Edward L; Gershwin, M Eric; Ma, Xiong

    2016-02-01

    Although a variant of primary biliary cirrhosis (PBC) characterized by features of autoimmune hepatitis (AIH) has been recognized for many years, few studies with ample numbers of patients have focused on its natural history. This study aimed to clarify the natural history, prognosis, and response to therapy in a cohort of patients with PBC with AIH features. We retrospectively analyzed 277 PBC patients without AIH features and 46 PBC patients with AIH features seen between September 2004 and April 2014. The 5-year adverse outcome-free survival of PBC patients with AIH features was 58% compared to 81% in PBC patients without AIH features. Multivariate analysis in the patients with AIH features indicated that total bilirubin ≥ 2.70× the upper limit of normal predicted a poor prognosis (p = 0.008, relative risk 8.39, 95% confidence interval (CI) 1.73, 40.73). Combination therapy with ursodeoxycholic acid (UDCA) and immunosuppression provided better short-term responses in PBC patients with AIH features, defined by multiple criteria. Higher aspartate aminotransferase (AST) level at accession suggested better prognosis for PBC patients with AIH features while worse prognosis for PBC patients without AIH features. PBC patients with AIH features differ from those without AIH features in terms of natural history, prognostic indicators, and response to therapy.

  3. Primary biliary cirrhosis.

    PubMed

    Carey, Elizabeth J; Ali, Ahmad H; Lindor, Keith D

    2015-10-17

    Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.

  4. Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation.

    PubMed

    Kang, Yong-Zhen; Sun, Xiao-Ye; Liu, Yi-He; Shen, Zhong-Yang

    2015-02-21

    Although the development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults, autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome has rarely been seen in liver transplant recipients. Here, we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 years after LT. Standard autoimmune serological tests were positive for anti-nuclear and anti-mitochondrial antibodies, and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus. Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis, which confirmed the diagnosis of AIH-PBC overlap syndrome. We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome; a novel type of autoimmune overlap syndrome.

  5. Primary Biliary Cirrhosis

    MedlinePlus

    ... of liver cancer every 6 to 12 months. Health care providers use blood tests, ultrasound, or both to check for signs of ... make the diagnosis of primary biliary cirrhosis. A health care provider uses the test selectively when he or she is concerned that ...

  6. Primary Biliary Cholangitis (Primary Biliary Cirrhosis)

    MedlinePlus

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  7. Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

    PubMed Central

    Watanabe, Takuya; Soga, Kenji; Hirono, Haruka; Hasegawa, Katsuhiko; Shibasaki, Koichi; Kawai, Hirokazu; Aoyagi, Yutaka

    2009-01-01

    AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)]. Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC. PMID:19132775

  8. Association of Primary Biliary Cirrhosis-autoimmune Hepatitis Overlap Syndrome with Immune Thrombocytopenia and Graves' Disease.

    PubMed

    Koyamada, Ryosuke; Higuchi, Takakazu; Kitada, Ayako; Nakagawa, Tomoko; Ikeya, Takashi; Okada, Sadamu; Fujita, Yoshiyuki

    2015-01-01

    A 54-year-old woman suffering from pruritus for five years was diagnosed to have Graves' disease and immune thrombocytopenia (ITP) associated with primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome, which was confirmed histologically after a prompt recovery in the platelet count number following steroid therapy. The association between PBC-AIH overlap syndrome and ITP has been rarely reported and the additional association with Graves' disease has not yet been reported. An underlying global derangement of autoimmunity or shared genetic susceptibility was suspected.

  9. De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis: an unusual cause of late grafts dysfunction.

    PubMed

    Ennaifer, Rym; Ayadi, Hend; Romdhane, Haifa; Cheikh, Meriem; Mestiri, Hafedh; Khalfallah, Taher; Hadj, Najet Bel

    2015-01-01

    De novo autoimmune hepatitis (AIH) is a rare disorder first described in 1998. It occurs in patients who underwent liver transplantation for a different etiology. We present the case of a 56-year-old woman who was diagnosed with primary biliary cirrhosis and had liver transplantation for refractory pruritis. Seven years after transplantation, she presented alterations in the hepatic profile with hypertransaminasemia, elevated alkaline phosphatase and gamma-glutamyl-transferase. Her liver functions test also showed elevated IgG levels. Serum autoantibodies were negative except for antimitochondrial antibodies. Histological findings indicated features of AIH without bile duct damage or loss. She had a pretreatment AIH score of 13 points and a post treatment score of 15 points according to the International AIH Group. The patient was treated effectively with prednisolone and her liver function and globulin levels rapidly returned to normal.

  10. Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome).

    PubMed

    Korkmaz, Huseyin; Bugdaci, Mehmet Sait; Temel, Tuncer; Dagli, Mehmet; Karabagli, Pinar

    2013-04-01

    Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA.

  11. Autoantigens in primary biliary cirrhosis

    PubMed Central

    Jones, D

    2000-01-01

    The automimmune liver disease primary biliary cirrhosis (PBC) is characterised by serum autoantibodies directed at mitochondrial and nuclear antigens (seen in most patients and a subset of patients, respectively). The antimitochondrial antibodies (AMA) characteristic of PBC are directed at members of the 2-oxoacid dehydrogenase components of multienzyme complexes; in particular, the E2 and E3 binding protein (E3BP) components of the pyruvate dehydrogenase complex (PDC). The presence of autoantibodies reactive with PDC-E2 and/or E3BP is strongly predictive of the presence of PBC. Therefore, the detection of these antibodies plays a very important role in the diagnosis of PBC. Originally demonstrated using immunofluorescence approaches, AMA can now be detected by the use of commercially available enzyme linked immunosorbent assays (ELISAs). Although the ELISA based approaches have advantages in terms of laboratory practicality, they are slightly less sensitive for the diagnosis of PBC than immunofluorescence (occasional patients with PBC show reactivity with PDC related antigens not present in the antigen preparations available for use with ELISA). Therefore, immunofluorescence should continue to be available as a complementary diagnostic test for use in occasional patients. In a subset of patients with PBC, autoantibodies are directed at increasingly well characterised nuclear antigens. Antinuclear antibody (ANA) positive patients are typically AMA negative. There are no significant differences in disease phenotype between AMA positive and AMA negative groups. At present, the clinical detection of ANA is mostly by Hep2 immunofluorescence, although ELISA kits for individual nuclear antigens are increasingly becoming available. Key Words: liver cirrhosis • biliary • autoimmunity • autoantibody PMID:11127262

  12. Computed tomography of primary intrahepatic biliary malignancy

    SciTech Connect

    Itai, Y.; Araki, T.; Furui, S.; Yashiro, N.; Ohtomo, K.; Iio, M.

    1983-05-01

    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 dilatation of intra- and extrahepatic ducts, give important clues leading to a correct diagnosis of primary intrahepatic biliary malignancy.

  13. Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy

    PubMed Central

    Purohit, Treta; Cappell, Mitchell S

    2015-01-01

    Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren’s syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva

  14. [Primary biliary cirrhosis and pregnancy].

    PubMed

    Ducarme, G; Bernuau, J; Luton, D

    2014-05-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, asymptomatic during a protracted time, characterized by changes in the small-sized bile ducts near portal spaces. The etiology of PBC is undefined, but immunologic and environmental disturbances may contribute to the disease. Infertility is often associated with PBC and cirrhosis, but pregnancy may well occur in women with PBC and without cirrhosis or in some others with compensated cirrhosis. A pluridisciplinary approach including gastroenterologists and obstetricians is recommended. The patient must be closely monitored throughout her pregnancy with maternal and routine antenatal care. Medical treatment requires ursodeoxycholic acid (UDCA). In non-cirrhotic UDCA-treated women with PBC, pregnancy often follows a normal course with vaginal delivery. In cirrhotic patients, UDCA must be continued during pregnancy, esophageal and gastric varices must be evaluated before pregnancy, and endoscopic ligature is recommended for treating large varices. Additionally, beta-blocker therapy may be associated, especially when variceal rupture occurred previously. Elective cesarean section is recommended in patients with large esophageal or gastric varices because of the potentially increased risk of variceal bleeding during maternal expulsive efforts in case of vaginal delivery.

  15. GWAS in Primary Biliary Cirrhosis

    PubMed Central

    Gulamhusein, Aliya F.; Juran, Brian D.

    2015-01-01

    Genome wide association studies (GWAS) have been a significant technological advance in our ability to evaluate the genetic architecture of complex diseases such as Primary Biliary Cirrhosis (PBC). To date, six large-scale studies have been performed which identified 27 non-HLA risk loci associated with PBC. The identified risk variants emphasize important disease concepts; namely, that disturbances in immunoregulatory pathways are important in the pathogenesis of PBC and that such perturbations are shared among a diverse number of autoimmune diseases – suggesting the risk architecture may confer a generalized propensity to autoimmunity not necessarily specific to PBC. Furthermore, the impact of non-HLA risk variants, particularly in genes involved with IL-12 signaling, and ethnic variation in conferring susceptibility to PBC have been highlighted. While GWAS have been a critical stepping-stone in understanding common genetic variation contributing to PBC, limitations pertaining to power, sample availability, and strong linkage disequilibrium across genes have left us with an incomplete understanding of the genetic underpinnings of disease pathogenesis. Future efforts to gain insight into this missing heritability, the genetic variation that contributes to important disease outcomes and the functional consequences of associated variants will be critical if practical clinical translation is to be realized. PMID:26676814

  16. [PRIMARY BILIARY LIVER CIRRHOSIS: MODERN CONCEPTS].

    PubMed

    Tsimmerman, Ya S

    2015-01-01

    Modern data on primary biliary liver cirrhosis are presented including the definition, prevalence, possible etiological factors, and detailed description of pathogenesis (autoimmune mechanisms, intrahepatic cholestasis, hereditary predisposition, environmental factors) and clinical picture. Also considered are complications and concomitant diseases, methods of laboratory, instrumental and morphological diagnostics, approaches to medicamental treatment and its effectiveness, indications for liver transplantation.

  17. The natural history of primary biliary cirrhosis.

    PubMed

    Imam, Mohamad H; Lindor, Keith D

    2014-08-01

    Our understanding of the natural history of primary biliary cirrhosis (PBC) has been evolving especially following the introduction of ursodeoxycholic acid (UDCA). A clearer understanding of disease pathophysiology and earlier diagnosis with increased prevalence of the disease worldwide has led to increased interest and improved outcomes in patients with PBC. In this article, the authors touch briefly on features of the disease and describe the natural history of PBC prior to and after the introduction of UDCA.

  18. Animal models of primary biliary cirrhosis.

    PubMed

    Wang, Jinjun; Yang, Guo-Xiang; Tsuneyama, Koichi; Gershwin, M Eric; Ridgway, William M; Leung, Patrick S C

    2014-08-01

    Within the last decade, several mouse models that manifest characteristic features of primary biliary cirrhosis (PBC) with antimitochondrial antibodies (AMAs) and immune-mediated biliary duct pathology have been reported. Here, the authors discuss the current findings on two spontaneous (nonobese diabetic autoimmune biliary disease [NOD.ABD] and dominant negative transforming growth factor-β receptor II [dnTGFβRII]) and two induced (chemical xenobiotics and microbial immunization) models of PBC. These models exhibit the serological, immunological, and histopathological features of human PBC. From these animal models, it is evident that the etiology of PBC is multifactorial and requires both specific genetic predispositions and environmental insults (either xenobiotic chemicals or microbial), which lead to the breaking of tolerance and eventually liver pathology. Human PBC is likely orchestrated by multiple factors and hence no single model can fully mimic the immunopathophysiology of human PBC. Nevertheless, knowledge gained from these models has greatly advanced our understanding of the major immunological pathways as well as the etiology of PBC.

  19. Role of cholangiocytes in primary biliary cirrhosis.

    PubMed

    Lleo, Ana; Maroni, Luca; Glaser, Shannon; Alpini, Gianfranco; Marzioni, Marco

    2014-08-01

    Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by selective destruction of intrahepatic cholangiocytes. Mechanisms underlying the development and progression of the disease are still controversial and largely undefined. Evidence suggests that PBC results from an articulated immunologic response against an immunodominant mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC-E2); characteristics of the disease are also the presence of disease-specific antimitochondrial autoantibodies (AMAs) and autoreactive CD4 and CD8 T cells. Recent evidence suggests that cholangiocytes show specific immunobiological features that are responsible for the selective targeting of those cells by the immune system. The immune reaction in PBC selectively targets small sized, intrahepatic bile ducts; although a specific reason for that has not been defined yet, it has been established that the biliary epithelium displays a unique heterogeneity, for which the physiological and pathophysiological features of small and large cholangiocytes significantly differ. In this review article, the authors provide a critical overview of the current evidence on the role of cholangiocytes in the immune-mediated destruction of the biliary tree that characterizes PBC.

  20. Breach of tolerance: primary biliary cirrhosis.

    PubMed

    Wang, Lifeng; Wang, Fu-Sheng; Chang, Christopher; Gershwin, M Eric

    2014-08-01

    In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active disease involves a disruption in several layers of control, including central tolerance, peripheral anergy, a "liver tolerance effect," and the action of T regulatory cells and their related cytokines. Each of these control mechanisms plays a role in preventing an immune response against self, but all of them act in concert to generate effective protection against autoimmunity without compromising the ability of the host immune system to mount an effective response to pathogens. At the same time, genetic susceptibility, environmental factors, including infection agents and xenobiotics, play important roles in breach of tolerance in the development of PBC.

  1. [Environmental factors and primary biliary cirrhosis].

    PubMed

    Chen, L P; Zhao, H; Lyu, B; Cheng, J L

    2016-07-20

    The complex interplay between immune factors and genetic susceptibility plays an essential role in autoimmune diseases. This is especially true for primary biliary cirrhosis (PBC). PBC is an autoimmune cholestatic liver disease characterized by the destruction of the small intrahepatic bile ducts and the presence of high-titer antimitochondrial antibodies (AMA). Among the currently known risk factors, genetic predisposition remains to be the dominant one. However, it is insufficient to explain the different geographic distributions of PBC and the incomplete concordance in identical twins. This suggests an association between specific environmental factors and the development of PBC. Nevertheless, a clear and rational association of environmental factors with primary biliary cirrhosis has not yet been fully elucidated. Our current understanding of the environmental triggers of PBC is limited to numerous suspected factors involved in its development, such as xenobiotics, electrophilic drugs, infection, and other physical, chemical, and even biological factors. Although the factors leading to the breakdown of immune tolerance in PBC are still largely unknown, related geoepidemiological studies may help us better understand the impact of the environment. In addition, a better understanding of the interplay between environmental factors and PBC is the critical step toward improving our management and control of PBC and autoimmunity in general.

  2. Environmental Factors in Primary Biliary Cirrhosis

    PubMed Central

    Juran, Brian D.; Lazaridis, Konstantinos N.

    2014-01-01

    The etiology of the autoimmune liver disease primary biliary cirrhosis (PBC) remains largely unresolved, owing in large part to the complexity of interaction between environmental and genetic contributors underlying disease development. Observations of disease clustering, differences in geographical prevalence, and seasonality of diagnosis rates suggest the environmental component to PBC is strong, and epidemiological studies have consistently found cigarette smoking and history of urinary tract infection to be associated with PBC. Current evidence implicates molecular mimicry as a primary mechanism driving loss of tolerance and subsequent autoimmunity in PBC, yet other environmentally influenced disease processes are likely to be involved in pathogenesis. In this review, the authors provide an overview of current findings and touch on potential mechanisms behind the environmental component of PBC. PMID:25057950

  3. 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.

  4. Diagnosis and management of primary biliary cirrhosis.

    PubMed

    Ali, Ahmad H; Carey, Elizabeth J; Lindor, Keith D

    2014-12-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized histologically by destruction of intrahepatic bile ducts and serologically by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC are increasing. Fatigue and pruritus are common symptoms in PBC, although the proportion of asymptomatic PBC is increasing due to the widespread use of screening biochemical tests and antimitochondrial antibody assays. PBC may eventually lead to cirrhosis and its consequent complications. In the 1980s, PBC was the leading indication for liver transplantation. Ursodeoxycholic acid is the only US FDA-approved therapeutic agent for PBC. Clinical trials have shown that the use of ursodeoxycholic acid in PBC results in reduction of liver biochemistries, a delay in histological progression, a delay in the development of varices and improvement in survival without liver transplantation.

  5. Pulmonary involvement in primary biliary cirrhosis.

    PubMed Central

    Rodriguez-Roisin, R; Pares, A; Bruguera, M; Coll, J; Picado, C; Agusti-Vidal, A; Burgos, F; Rodes, J

    1981-01-01

    The association of pulmonary fibrosis and primary biliary cirrhosis (PBC) remains controversial. To determine the frequency of pulmonary fibrosis in PBC, a carefully selected series of 14 PBC patients, seven patients with Sicca complex, and 14 control subjects have been studied. Seven of the 14 patients with PBC had Sjögren's syndrome, four of whom had some clinical evidence of pulmonary disease. Evaluation of ventilatory capacity, gas transfer factor, arterial blood gases, and lung mechanics were performed. Gas transfer was reduced in patients with PBC associated with Sjögen's syndrome and in patients with the Sicca complex. These results suggest that the respiratory, clinical, ad functional abnormalities found in PBC are related to the presence of an associated Sjögen's syndrome. PMID:7281088

  6. Idiopathic myelofibrosis associated with primary biliary cirrhosis.

    PubMed

    Hernández-Boluda, J C; Jiménez, M; Rosiñol, L; Cervantes, F

    2002-03-01

    A patient with primary biliary cirrhosis (PBC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of PBC was established by liver biopsy, performed after a 2-month history of constitutional symptoms associated with abnormalities of the serum liver enzymes, with typical serum immunological markers being found. Although a favorable response of PBC to prednisone was observed, one and a half year later the patient developed anemia with anisocytosis and poikilocytosis, tear-drop cells, and leukoerythroblastic picture, and IM was diagnosed by bone marrow biopsy. A few months later, a rapid worsening of the patient's clinical condition was noted, with an increase in the constitutional symptoms and need for frequent packed RBC transfusions, and she finally died from an infectious complication. This case represents a new association of IM with an autoimmune disease, supporting the hypothesis of a possible immune basis of IM in some cases.

  7. Risk and Surveillance of Cancers in Primary Biliary Tract Disease

    PubMed Central

    Hrad, Valery; Abebe, Yoftahe; Ali, Syed Haris; Velgersdyk, Jared

    2016-01-01

    Primary biliary diseases have been associated in several studies with various malignancies. Understanding the risk and optimizing surveillance strategy of these malignancies in this specific subset of patients are an important facet of clinical care. For instance, primary sclerosing cholangitis is associated with an increased risk for cholangiocarcinoma (which is very challenging to diagnose) and when IBD is present for colorectal cancer. On the other hand, primary biliary cirrhosis patients with cirrhosis or not responding to 12 months of ursodeoxycholic acid therapy are at increased risk of hepatocellular carcinoma. In this review we will discuss in detail the risks and optimal surveillance strategies for patients with primary biliary diseases. PMID:27413366

  8. Innate immunity and primary biliary cirrhosis.

    PubMed

    Selmi, Carlo; Lleo, Ana; Pasini, Simone; Zuin, Massimo; Gershwin, M Eric

    2009-02-01

    There has been a rapid growth in our understanding of the molecular bases of primary biliary cirrhosis (PBC). These efforts were initiated when the immunodominant mitochondrial autoantigen was cloned and sequenced. Using the recombinant cloned antigen as a tool, research has focused on the effector mechanisms of disease and the uniqueness of the primary target tissue, the intrahepatic bile ducts. Most recently, there have been experimental data suggesting that innate immunity changes may be critical to the initiation and perpetuation of the autoimmune injury, as in the case of the enhanced response of monocytes and memory B cells to infectious stimulation and environmental mimics. These observations are important as they help fill in the many gaps which remain on the most difficult subject of autoimmunity, etiology. Indeed, based on the available data, several experimental models of PBC have been developed. These models illustrate and suggest that PBC can be initiated by several mechanisms, all of which lead to loss of tolerance to the mitochondrial antigens. However, once this adaptive response develops, it appears that much of the subsequent pathology is exacerbated by innate responses. We suggest that future therapeutic efforts in PBC will depend heavily on understanding the nature of this innate immune responses and methodology to blunt their cytotoxicity.

  9. Sarcoidosis and primary biliary cirrhosis with co-existing myositis

    PubMed Central

    Hughes, P.; McGavin, C. R.

    1997-01-01

    In a small number of cases the co-existence of primary biliary cirrhosis and sarcoidosis is assumed from clinical serological and histological findings. A case of sarcoidosis is reported in which the M2 antibody, a highly specific marker for primary biliary cirrhosis, was detected. The patient also developed a severe myositis and a possible overlap syndrome is discussed. 




 PMID:9059489

  10. 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.

  11. Primary cancers of extrahepatic biliary passages

    SciTech Connect

    Mittal, B.; Deutsch, M.; Iwatsuki, S.

    1985-04-01

    The records of 22 patients with cancers of extrahepatic biliary passages (EHBP) were analyzed 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 the data, it is difficult to comment on the effectiveness of chemotherapy. The authors have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed.

  12. Predicting outcome in primary biliary cirrhosis.

    PubMed

    Lammers, Willem J; Kowdley, Kris V; van Buuren, Henk R

    2014-01-01

    Primary biliary cirrhosis (PBC) is a slowly progressive autoimmune liver disease that may ultimately result in liver failure and premature death. Predicting outcome is of key importance in clinical management and an essential requirement for patients counselling and timing of diagnostic and therapeutic interventions. The following factors are associated with progressive disease and worse outcome: young age at diagnosis, male gender, histological presence of cirrhosis, accelerated marked uctopenia in relation to the amount of fibrosis, high serum bilirubin, low serum albumin levels, high serum alkaline phosphatase levels, esophageal varices, hepatocellular carcinoma (HCC) and lack of biochemical response to ursodeoxycholic acid (UDCA). The prognostic significance of symptoms at diagnosis is uncertain. UDCA therapy and liver transplantation have a significant beneficial effect on the outcome of the disease. The Mayo risk score in PBC can be used for estimating individual prognosis. The Newcastle Varices in PBC Score may be a useful clinical tool to predict the risk for development of esophageal varices. Male gender, cirrhosis and non-response to UDCA therapy in particular, are risk factors for development of HCC.

  13. The diagnosis of primary biliary cirrhosis.

    PubMed

    Bowlus, Christopher L; Gershwin, M Eric

    2014-01-01

    Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by the immune mediated destruction of small intrahepatic bile duct epithelial cells leading to cholestasis and cirrhosis. The autoimmune basis of PBC is supported by the highly specific anti-mitochondrial antibodies (AMAs) and autoreactive T cells, the former being the basis for diagnosis in the vast majority of cases. Although a rare disease, the incidence rates of PBC have been increasing, possibly due to increased testing and diagnosis as opposed to a true increase in disease incidence. Presently, most cases are asymptomatic and only suspected based upon routine liver tests. Those with symptoms typically complain of pruritus and fatigue. The diagnosis of PBC is based on the presence of at least 2 of 3 key criteria including a persistently elevated serum alkaline phosphatase, the presence of serum AMAs, and liver histology consistent with PBC. Anti-nuclear antibodies specific to PBC are useful in cases in which AMAs are not detected and may indicate a more aggressive course. Ursodeoxycholic acid is the only proven therapy for PBC and in most cases can delay or prevent disease progression. However, a subgroup of patients does not adequately respond to ursodeoxycholic acid and for whom new therapies are needed.

  14. 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

  15. Aspects of the Pathophysiology of Primary Biliary Cirrhosis.

    PubMed

    Corrigan, Margaret; Hirschfield, Gideon M

    2015-01-01

    Primary biliary cirrhosis is a classical autoimmune liver disease and is present in around 1 in 1,000 women over the age of 40. It has a number of diagnostic characteristics consistent with autoimmune liver injury, in particular, the high specificity of circulating anti-mitochondrial antibodies. Histologically, the disease is reflected as a granulomatous lymphocytic cholangitis that consequently leads to small bile duct loss and cholestasis. Progressive disease is characterised by the development of a biliary cirrhosis, with end-stage features of liver disease ultimately impacting patient outcomes. Studies support a combination of environmental and genetic risk factors that coalesce to lead to loss of immunological tolerance and persistent biliary inflammation. Significant advances have occurred recently in understanding the genetic risk factors for disease, as well as utilising human and murine studies to characterise the nature of the biliary injury and cholestatic response.

  16. Primary biliary cirrhosis: new perspectives in diagnosis and treatment

    PubMed Central

    Prince, M.; Jones, D.

    2000-01-01

    Primary biliary cirrhosis (PBC) is a chronic autoimmune disease characterised by cholestatic liver function tests, antimitochondrial antibodies, and abnormal liver histology. Early descriptions of a rare rapidly progressive disease no longer reflect the more indolent progress often seen today. Many patients have significant long term morbidity through symptoms such as fatigue and itch with a minority progressing to liver failure and need for transplantation. The current data on the diagnosis, clinical progression, and treatment of PBC are reviewed.


Keywords: primary biliary cirrhosis; liver transplantation; pruritus PMID:10727561

  17. Primary biliary cholangitis associated with warm autoimmune hemolytic anemia.

    PubMed

    Gonzalez-Moreno, Emmanuel I; Martinez-Cabriales, Sylvia A; Cruz-Moreno, Miguel A; Borjas-Almaguer, Omar D; Cortez-Hernandez, Carlos A; Bosques-Padilla, Francisco J; Garza, Aldo A; Gonzalez-Gonzalez, Jose A; Garcia-Compean, Diego; Ocampo-Candiani, Jorge; Maldonado-Garza, Hector J

    2016-02-01

    There are many autoimmune diseases associated with primary biliary cholangitis (PBC), known as primary biliary cirrhosis; however, the association between PBC and warm autoimmune hemolytic anemia (wAIHA) has rarely been reported. It is documented that hemolysis is present in over 50% of the patients with chronic liver disease, regardless of the etiologies. Due to the clear and frequent relationship between PBC and many autoimmune diseases, it is reasonable to suppose that wAIHA may be another autoimmune disorder seen in association with PBC. Here we reported a 53-year-old female patient diagnosed with wAIHA associated with PBC.

  18. High frequency of autoantibodies in patients with primary sclerosing cholangitis that bind biliary epithelial cells and induce expression of CD44 and production of interleukin 6

    PubMed Central

    Xu, B; Broome, U; Ericzon, B-G; Sumitran-Holgersson, S

    2002-01-01

    Aim: Sera of patients with autoimmune liver diseases were investigated for the presence of autoantibodies binding to human biliary epithelial cells (BECs). Furthermore, their functional capacity was investigated by testing their capacity to fix complement as well as induce expression of various adhesion molecules and production of cytokines. Methods: Sera from patients with various stages of primary sclerosing cholangitis (PSC; n=30), primary biliary cirrhosis (PBC; n=29), autoimmune hepatitis (AIH; n=25), and normal controls (n=12) were investigated for the presence of antibodies that reacted with unstimulated and cytokine stimulated BECs isolated from a normal healthy liver. To demonstrate organ specificity, lung epithelial cells (LECs) were used as control cells. Antibodies were tested for their functional capacity. Results: Compared with controls (8%), significantly higher numbers of PSC patients (63%, p=0.001), but not PBC (37%, NS) or AIH (16%, NS) patients, had anti-BEC antibodies. In 90% of PSC patients, the autoantibodies reacted only with cytokine stimulated target cells. Lower numbers of PSC (6%), PBC (10%), and AIH (0%) patients had LEC antibodies. Other significant findings were that anti-BEC antibodies were found in (i) PSC patients with either the HLA-DRB1*0301 or DR2 allele compared with those without (p=0.007); and (ii) in PBC patients with end stage disease compared with those without (p=0.018). Furthermore, anti-BEC antibodies from PSC and PBC but not AIH patients induced BECs to produce high levels of the cytokine interleukin 6. IgM and IgG fractions isolated from PSC but not PBC and AIH sera induced significantly increased expression of the cell adhesion molecule CD44. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blot analysis of BEC membranes demonstrated a specific band of 40 kDa with PSC sera and 45, 42, 30, and 33 kDa bands with PBC sera, which were absent in control groups. Conclusion: Thus for the first time we

  19. Autoimmune liver diseases in the Asia-Pacific region: Proceedings of APASL symposium on AIH and PBC 2016.

    PubMed

    Tanaka, Atsushi; Ma, Xiong; Yokosuka, Osamu; Weltman, Martin; You, Hong; Amarapurkar, Deepak N; Kim, Yoon Jun; Abbas, Zaigham; Payawal, Diana A; Chang, Ming-Ling; Efe, Cumali; Ozaslan, Ersan; Abe, Masanori; Mitchell-Thain, Robert; Zeniya, Mikio; Han, Kwang Hyub; Vierling, John M; Takikawa, Hajime

    2016-11-01

    During the 25th annual meeting of the Asia-Pacific Association for the Study of the Liver (APASL 2016) in Tokyo, we organized and moderated an inaugural satellite symposium on the autoimmune liver diseases, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Following the keynote lecture by John M. Vierling (USA), speakers from the Asia-Pacific region provided an up-to-date perspective on the epidemiology, clinical practice and research in AIH and PBC in the Asia-Pacific region. Although epidemiology and clinical features of AIH seem to be similar in East Asia compared to those in western countries, the majority of patients with AIH are detected at an advanced stage and have higher mortality rates in South Asia, indicating an unmet need for earlier diagnosis and the initiation of appropriate immunosuppressive treatment. PBC is more commonly seen in Australia and East Asia. As of 2016, clinical practice guidelines (CPG) for PBC have been published in Japan and China. Ursodeoxycholic acid (UDCA) is recommended as a first-line therapy by both CPG. Nevertheless, one of the unmet therapeutic needs in PBC is the treatment of patients refractory to or intolerant of UDCA. It is of interest that the prevalence of chronic hepatitis B (CHB) in PBC patients was low in Taiwan and mainland China where the prevalence of CHB is very high. In this review, we overview this exciting and epoch-making symposium.

  20. Genetic Contribution to the Pathogenesis of Primary Biliary Cholangitis

    PubMed Central

    Umemura, Takeji; Tanaka, Eiji

    2017-01-01

    Formerly termed primary biliary cirrhosis, primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease characterized by the presence of antimitochondrial antibodies. Ursodeoxycholic acid (UDCA) therapy is the most effective and approved treatment for PBC and leads to a favorable outcome in the vast majority of cases. Although the etiology of PBC has not yet been elucidated, human leukocyte antigen (HLA) class II alleles have been consistently associated with disease onset for decades. Individuals in different geographic regions of the world may have varying susceptibility alleles that reflect indigenous triggering antigens. In this review, we describe the influence of HLA alleles and other gene polymorphisms on PBC along with the results of genome-wide association studies (GWAS) on this disease. PMID:28255561

  1. Primary Biliary Cirrhosis Is a Generalized Autoimmune Epithelitis

    PubMed Central

    Gao, Jun; Qiao, Liang; Wang, Bingyuan

    2015-01-01

    Primary biliary cirrhosis (PBC) is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs) and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs) may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice. PMID:25803105

  2. [Is ursodeoxycholic acid effective in primary biliary cirrhosis?].

    PubMed

    Rada, Gabriel; Mac-Namara, Macarena

    2014-09-24

    Ursodeoxycholic acid is considered as first line treatment in patients with primary biliary cirrhosis. Its mechanism of action in this disease is unknown and there is controversy about its clinical impact. Searching in Epistemonikos database, which is maintained by screening 19 databases, we identified four systematic reviews including 16 studies. We combined the evidence using tables with summary of findings following the GRADE approach and concluded ursodeoxycholic acid may not have any effect on pruritus, and there is uncertainty about its effect on mortality, need for liver transplantation or on any other important outcome for the patient.

  3. Apotopes and innate immune system: novel players in the primary biliary cirrhosis scenario.

    PubMed

    Lleo, Ana; Invernizzi, Pietro

    2013-08-01

    Our understanding of primary biliary cirrhosis has been rapidly growing over the past decade and the disease is now regarded as a model for other female-predominant, organ-specific autoimmune conditions. Primary biliary cirrhosis ensues from a multi-lineage loss of tolerance to the E2 component of the pyruvate dehydrogenase complex. One of the major unanswered questions in the pathogenesis of primary biliary cirrhosis is the specificity of small intrahepatic bile ducts attack while PDC-E2 is present in mitochondria of all nucleated cells. Recent findings suggest that the uniqueness of the primary target tissue, biliary epithelium, may be of considerable importance for understanding primary biliary cirrhosis and that the biliary epithelial cell is more than an innocent victim. Rather, it attracts an immune attack by virtue of the unique apoptotic mechanisms and by the way it handles PDC-E2. Moreover, recent evidence suggests that apoptotic bodies of biliary epithelial cell are able to activate the innate immune system in the presence of anti-mitochondrial antibodies. This review article is intended to provide a critical overview of the role of apoptosis in biliary epithelial cells, the activation of the innate immune system, and its biological and clinical significance in primary biliary cirrhosis.

  4. The immunobiology and pathophysiology of primary biliary cirrhosis.

    PubMed

    Hirschfield, Gideon M; Gershwin, M Eric

    2013-01-24

    Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by clinical homogeneity among patients, an overwhelming female predominance, production of a multilineage immune response to mitochondrial autoantigens, inflammation of small bile ducts, and in some patients the development of fibrosis and cirrhosis. The targets in this disease are small bile ducts, and the prototypic serologic response includes antimitochondrial antibodies (AMAs). Several key observations have greatly advanced our understanding of PBC. First, the multilineage immune response, including AMAs, is directed at the E2 component of the 2-oxo-dehydrogenase pathway, particularly PDC-E2. Second, such autoantibodies may be identified years before the clinical diagnosis of disease. Third, the autoreactive T cell precursor frequency for both CD4 and CD8 cells is significantly higher in liver and regional lymph node than in blood, so the multilineage antimitochondrial response may be required for the development of this disease. Fourth, the apotope of biliary cells contains intact PDC-E2; this apotope, in a setting that includes granulocyte macrophage colony-stimulating factor-stimulated macrophages and AMAs, produces an intense proinflammatory response. Fifth, several mouse models of PBC highlight the importance of loss of tolerance to PDC-E2 as well as a critical role for the interleukin (IL)-12 signaling pathway. Finally, genome-wide association studies suggest an important role for the IL-12 pathway in disease susceptibility. Taken together, these findings have resulted in a better understanding of the mechanism for selective biliary cell destruction and have also suggested unique pathways for therapeutic intervention.

  5. Biliary epithelial expression of pyruvate dehydrogenase complex in primary biliary cirrhosis: an immunohistochemical and immunoelectron microscopic study.

    PubMed

    Nakanuma, Y; Tsuneyama, K; Kono, N; Hoso, M; Van de Water, J; Gershwin, M E

    1995-01-01

    It has been reported recently that there is a unique distribution of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) on biliary epithelial cells in patients with primary biliary cirrhosis (PBC) but not primary sclerosing cholangitis. This distribution has been demonstrated using a mouse monoclonal antibody, coined C355.1. The epitope recognized by C355.1 is near the lipoic acid binding site of PDC-E2. C355.1 inhibits PDC-E2 activity in vitro and, unlike a panel of other monoclonal antibodies against different regions of PDC-E2, appears to bind not only to mitochondria but also to a unique antigen expressed predominantly on the luminal side of biliary epithelial cells in PBC. We have extended these observations by studying the subcellular reactivity of C355.1 using postembedding immunoelectron microscopy on the intrahepatic small bile ducts of PBC livers, extrahepatic biliary obstruction (EBO) livers, and normal livers. We report that the reactivity of C355.1 can be classified into two categories. The first category is characterized by small foci of reaction products that were randomly dispersed in cytoplasm, particularly in supranuclear areas; the ultrastructural characterization of these foci was impossible to define but was similar in PBC and EBO. However, of particular interest was the second category of reactivity, which was characterized by deposition of reaction products around the biliary lumen, including microvilli and adjacent subluminal ectoplasm and secretory substances in the biliary lumen. This staining pattern was frequent in PBC livers, only occasionally evident in EBO livers, and not found in normal livers. These data further define and highlight the unique subcellular distribution of PDC-E2 around the biliary lumen in PBC livers and suggest that this abnormality is related to the pathogenesis of bile duct lesions.

  6. Primary Biliary Cirrhosis and the Nuclear Pore Complex

    PubMed Central

    Duarte-Rey, Carolina; Bogdanos, Dimitrios; Yang, Chen-Yen; Roberts, Krista; Leung, Patrick S.C.; Anaya, Juan-Manuel; Worman, Howard J.; Gershwin, M. Eric

    2012-01-01

    Experimental models of autoimmune diseases have led to the conclusion that an immune response to nuclear antigens is a sentinel marker for loss of tolerance and potential tissue damage. Various proteins are targets of antinuclear antibodies in a variety of autoimmune diseases, ranging from systemic rheumatologic disorders to diseases affecting specific organs such as the liver. Autoantibodies against specific nuclear constituents have also been used as probes to understand the structure and the function of the targeted components and their relevance to disease pathogenesis. Approximately a quarter of patients with primary biliary cirrhosis (PBC) have antibodies targeting proteins of the nuclear pore complex (NPC), a multi-protein structure that mediates molecular transport across the nuclear envelope. Autoantibodies against the integral membrane glycoprotein gp210 and nucleoporin p62 appear to be highly specific for PBC, an autoimmune disease characterized by progressive destruction of intrahepatic biliary epithelial cells. This review discusses the diagnostic and clinical relevance of anti-NPC antibodies in PBC and the possibility that this autoimmune response may arise as a result of molecular mimicry. PMID:22487189

  7. Primary biliary cirrhosis in the era of liver transplantation.

    PubMed

    Raczyńska, Joanna; Habior, Andrzej; Pączek, Leszek; Foroncewicz, Bartosz; Pawełas, Andrzej; Mucha, Krzysztof

    2014-09-29

    Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities.

  8. Early Molecular Stratification of High-risk Primary Biliary Cholangitis.

    PubMed

    Hardie, Claire; Green, Kile; Jopson, Laura; Millar, Ben; Innes, Barbara; Pagan, Sarah; Tiniakos, Dina; Dyson, Jessica; Haniffa, Muzlifah; Bigley, Venetia; Jones, David E; Brain, John; Walker, Lucy J

    2016-12-01

    High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel. Principle component analysis (PCA) demonstrated discrete gene expression clustering between controls and high- and low-risk PBC. High-risk PBC was characterised by up-regulation of genes linked to T-cell activation and apoptosis, INF-γ signalling and leukocyte migration and down-regulation of those linked to the complement pathway. CDKN1a, up-regulated in high-risk PBC, correlated with significantly increased expression of its gene product, the senescence marker p21(WAF1/Cip), by biliary epithelial cells. Our findings suggest high- and low-risk PBC are biologically different from disease outset and senescence an early feature in high-risk disease. Identification of a high-risk 'signal' early from standard FFPE tissue sections has clear clinical utility allowing for patient stratification and second-line therapeutic intervention.

  9. 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.

  10. Obeticholic acid for the treatment of primary biliary cirrhosis.

    PubMed

    Trivedi, Palak J; Hirschfield, Gideon M; Gershwin, M Eric

    2016-01-01

    Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid synthesis and protects against toxic accumulation in models of cholestasis and facilitates hepatic regeneration in preclinical studies. Data from recent Phase II and III controlled trials suggest a therapeutic impact of OCA in PBC biochemical nonresponders, as evidenced by change in proven laboratory surrogates of long-term outcome. Dose-dependent pruritus is a common adverse effect, but may be overcome through dose-titration. Longer term studies are needed with focus on safety and long-term clinical efficacy.

  11. 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

  12. 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

  13. Cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary cirrhosis overlap syndrome.

    PubMed

    González-Moreno, Emmanuel I; Cámara-Lemarroy, Carlos R; Borjas-Almaguer, David O; Martínez-Cabriales, Sylvia A; Paz-Delgadillo, Jonathan; Gutiérrez-Udave, Rodrigo; Ayala-Cortés, Ana S; Ocampo-Candiani, Jorge; Cortéz-Hernández, Carlos A; Maldonado-Garza, Héctor J

    2015-01-01

    Cutaneous amyloidosis is a rare disease characterized by the deposition of amyloid in the dermis. It can be primary or secondary, depending on associated diseases. It has been linked to various autoimmune diseases, including primary biliary cirrhosis. We present the case of a patient with an autoimmune hepatitis-primary biliary cirrhosis overlap syndrome with concomitant cutaneous amyloidosis, a very unusual association, and discuss similar cases and possible pathophysiological implications.

  14. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    SciTech Connect

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E. )

    1988-10-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M{sub r} 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects.

  15. The immunopathology of liver granulomas in primary biliary cirrhosis.

    PubMed

    You, Zhengrui; Wang, Qixia; Bian, Zhaolian; Liu, Yuan; Han, Xiaofeng; Peng, Yanshen; Shen, Lei; Chen, Xiaoyu; Qiu, Dekai; Selmi, Carlo; Gershwin, M Eric; Ma, Xiong

    2012-09-01

    Liver granulomas and elevated serum IgM are commonly observed in patients with primary biliary cirrhosis (PBC) but their pathogenetic significance remains largely unknown. To address this issue we performed an extensive immunostaining and colocalization study of markers associated with dendritic cells and IgM in a large cohort of tissue samples from PBC and control livers as well as from non-hepatic granulomatous diseases. First, the classical dendritic cell CD11c marker is highly expressed and more sensitive than classical hematoxylin-eosin staining in detecting granulomas associated with PBC and other conditions. Second, PBC cases with CD11c-positive granulomas have significantly higher serum IgM levels and earlier disease stages. Third, granulomas from PBC and other diseases demonstrate markers of dendritic cell immaturity, i.e. CD11b, reduced MHC II, IL-23, CCR7 and CD83 expression, and elevated C1q expression. Lastly, B cells and IgM-positive plasma cells are largely represented around PBC granulomas along with macrophages. In conclusion, our comprehensive immunohistochemical study suggests that dendritic cells are key to the pathogenesis of granulomas, regardless of their origin. More specifically, PBC liver granulomas may result from the interaction between immature dendritic cells and IgM.

  16. Primary biliary cirrhosis: Clinical and laboratory criteria for its diagnosis.

    PubMed

    Reshetnyak, Vasiliy Ivanovich

    2015-07-07

    Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts, which is likely to be caused by an autoimmune mechanism with a the presence of serum antimitochondrial antibodies and a potential tendency to progress to cirrhosis. Despite the fact that the etiology of this disease has been unknown so far, there has been a considerable body of scientific evidence that can reveal the clinical and laboratory signs of PBC and the individual components of its pathogenesis and elaborate diagnostic criteria for the disease and its symptomatic therapy. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease. The purpose of this review is to summarize the data available in the literature and the author's findings on clinical and laboratory criteria for the diagnosis of PBC. This review describes the major clinical manifestations of the disease and the mechanisms of its development. It presents the immunological, biochemical, and morphological signs of PBC and their significance for its diagnosis. A great deal of novel scientific evidence for the problem of PBC has been accumulated. However, the inadequate efficiency of therapy for the disease lends impetus to the quest for its etiological factors and to further investigations of its pathogenetic mechanisms and, on this basis, to searches for new methods for its early diagnosis.

  17. Xenobiotics and loss of tolerance in primary biliary cholangitis

    PubMed Central

    Wang, Jinjun; Yang, Guoxiang; Dubrovsky, Alana Mari; Choi, Jinjung; Leung, Patrick SC

    2016-01-01

    Data from genome wide association studies and geoepidemiological studies established that a combination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary cholangitis (PBC). The serologic hallmark of PBC are the presence of high titer anti-mitochondrial autoantibodies (AMA) that recognize the lipoyl domain of the mitochondrial pyruvate dehydrogenase E2 (PDC-E2) subunit. Extensive efforts have been directed to investigate the molecular basis of AMA. Recently, experimental data has pointed to the thesis that the breaking of tolerance to PDC-E2 is a pivotal event in the initial etiology of PBC, including environmental xenobiotics including those commonly found in cosmetics and food additives, suggesting that chemical modification of the PDC-E2 epitope may render its vulnerable to become a neo-antigen and trigger an immune response in genetically susceptible hosts. Here, we will discuss the natural history, genetics and immunobiology of PBC and structural constraints of PDC-E2 in AMA recognition which makes it vulnerable to chemical modification. PMID:26755880

  18. Primary biliary cirrhosis and Sjogren's syndrome: Autoimmune epithelitis

    PubMed Central

    Selmi, Carlo; Meroni, Pier Luigi; Gershwin, M. Eric

    2013-01-01

    Primary biliary cirrhosis (PBC) has been often coined a model autoimmune disease based on the homogeneity amongst patients, the frequency and similarity of antimitochondrial antibodies, including the highly directed immune response to pyruvate dehydrogenase (PDC-E2). A significant number of patients with PBC suffer from sicca and amongst these, there are patients who also have classic Sjogren's syndrome. Indeed, both PBC and Sjogren's syndrome are characterized by inflammation of target epithelial elements. Both diseases can be considered on the basis of a number of other related clinical aspects, including proposed unique apoptotic features of the target tissue, the role of secretory IgA, and the frequency with which both diseases overlap with each other. Indeed, PBC may be considered a Sjogren's syndrome of the liver, whereas Sjogren's syndrome can be equally discussed as PBC of the salivary glands. Dissection of the genetic predispositions for both diseases and especially the molecular basis of effector mechanisms, will become critical elements in developing new therapies. PMID:22178199

  19. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis.

    PubMed

    Granito, Alessandro; Muratori, Paolo; Quarneti, Chiara; Pappas, Georgios; Cicola, Ronny; Muratori, Luigi

    2012-01-01

    Antimitochondrial antibodies are the serological hallmark of primary biliary cirrhosis (PBC). Besides antimitochondrial antibodies, the autoantibody profile of PBC includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in up to 50% of PBC patients. Two immunofluorescence patterns are considered 'PBC-specific': the multiple nuclear dots and rim-like/membranous patterns. The target antigens of the multiple nuclear dots pattern have been identified as Sp100 and promyelocytic leukemia protein, whereas the rim-like/membranous pattern is given by autoantibodies recognizing multiple proteins such as gp210, nucleoporin p62 and the lamin B receptor. Other ANA, especially those already known in the rheumatological setting, such as anticentromere, anti-SSA/Ro and anti-dsDNA antibodies, can be frequently found in PBC, often coexisting in the same patient. In this article, we will report on recent progress in the antigenic characterization of ANA in PBC, their detection with both traditional assays and Western blot/ELISA with molecularly defined nuclear antigens, and we will discuss their clinical significance.

  20. Primary biliary cirrhosis: an orchestrated immune response against epithelial cells.

    PubMed

    Gershwin, M E; Ansari, A A; Mackay, I R; Nakanuma, Y; Nishio, A; Rowley, M J; Coppel, R L

    2000-04-01

    Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis. The serologic hallmark of PBC is the presence of antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex. The mechanisms by which (and if) such antibodies produce liver tissue injury are unknown. However, the presence of these antibodies has allowed detailed immunological definition of the antigenic epitopes, the nature of reactive autoantibodies and the characterization of T-cell responses. Several mechanisms may now be proposed regarding the immune-mediated bile duct damage in PBC, including the possible role of T-cell-mediated cytotoxicity and intracellular interaction between the IgA class of antimitochondrial antibodies and mitochondrial autoantigens. There are major questions which remain unanswered, including, of course, etiology, but also the reasons for female predominance, the absence of PBC in children, the relative ineffectiveness of immunosuppressive drugs, and the specific role of mitochondrial antigens. The data so far provide suggestive evidence that PBC is a mucosal disease; this thesis provides a basis for discussion of etiology via the enterohepatic circulation of toxins and/or infection.

  1. Understanding and Treating Fatigue in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis.

    PubMed

    Jopson, Laura; Dyson, Jessica K; Jones, David E J

    2016-02-01

    Fatigue is a significant problem for patients with primary biliary cirrhosis and although experienced less by patients with primary sclerosing cholangitis, a minority still report significant fatigue. Fatigue is the symptom with the greatest impact on quality of life, particularly when associated with social dysfunction. The pathogenesis of fatigue in cholestatic liver disease is complex, poorly understood, and probably has central and peripheral components. Managing fatigue in cholestatic liver disease presents a challenge for clinicians given the complexity and its numerous associations. This article presents a structured approach to managing fatigue in cholestatic liver disease to improve fatigue severity and quality of life.

  2. Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review.

    PubMed

    Acosta, Andres M; Wiley, Elizabeth Louise

    2016-10-01

    Mixed adenoneuroendocrine carcinomas (MANECs) are composite neoplasms with areas of adenocarcinoma or squamous cell carcinoma intermingled with neuroendocrine carcinoma or neuroendocrine tumor, each composing at least 30% of the neoplasm. MANECs are very infrequent overall, and they are more commonly diagnosed in the appendix, colon, and stomach. Biliary MANECs are particularly rare, and their histogenesis is debated because neuroendocrine cells are seldom identified in the normal biliary tract. They can show one of the 3 different architectural patterns described in Lewin's original classification: collision tumors, combined lesions, or amphicrine neoplasms. The neuroendocrine component is usually of a high grade, with small or large cell cytomorphology, whereas the adenocarcinoma component is either an intestinal or biliary type. Clinical presentation is characterized by locally advanced disease at the time of initial diagnosis. Recent studies suggest that treatment should be guided by the most aggressive histologic component.

  3. Primary biliary cirrhosis and osteoporosis: a case-control study.

    PubMed

    Mounach, Aziza; Ouzzif, Zhor; Wariaghli, Ghizlane; Achemlal, Lahsen; Benbaghdadi, Imane; Aouragh, Aziz; Bezza, Ahmed; El Maghraoui, Abdellah

    2008-01-01

    Osteoporosis is a common complication of chronic liver disease, from cholestatic disorders to autoimmune, alcoholic, and posthepatitic cirrhosis. Osteoporosis appears more striking in patients with primary biliary cirrhosis (PBC) because the disease usually affects elderly women, who are naturally prone to osteoporosis. Our aims were (1) to compare the prevalence of osteoporosis (T-score <-2.5 SD) between PBC patients and a group of age-and sex-matched controls consisting of healthy subjects from the general population; and (2) to identify the main risk factors for the development of bone loss. Thirty-three women with PBC (mean age, 47.3 +/- 10.4 years) and 66 healthy subjects were enrolled in the study. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin, 25-hydroxyvitamin D (25-OH vit D), parathyroid hormone, and osteocalcin. Vertebral fractures were analyzed using vertebral fracture assessment (VFA). The mean T-score was lower in the PBC group compared to healthy controls, with a significant statistical difference (-2.39 +/- 0.93 and -1.47 +/- 0.99 in lumbar spine and total hip, respectively, in the PBC group versus -0.99 +/- 0.51 and -0.56 +/- 1.14 in healthy controls (P < 0.001). The prevalence of osteoporosis was 51.5% in the PBC group versus 22.7% in healthy controls with a statistically significant difference (P = 0.004). BMD of the PBC group was significantly correlated positively with body mass index (BMI) and 25-OH vit D, and negatively with menopausal status, duration of disease, and parathyroid hormone (PTH) levels. Vertebral fractures were present in 9% of the patients. We found that osteoporosis is more prevalent in women with PBC than in the general population. BMI, menopausal status, duration of the disease, and vitamin D deficiency are the main risk factors for osteoporosis in this liver disease.

  4. Gut-liver axis: an immune link between celiac disease and primary biliary cirrhosis.

    PubMed

    Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto

    2013-03-01

    The association between celiac disease and primary biliary cirrhosis is well established. The breakdown of gut-liver axis equilibrium plays a central role in the development of immune disorders involving the small bowel and liver. In celiac disease, immunologically active molecules generated from the cross-linking between tissue transglutaminase and food/bacterial antigens reach the liver through the portal circulation owing to the increased intestinal permeability. A molecular mimicry between bacterial antigens and the pyruvate dehydrogenase E2 component, recognized by antimitochondrial autoantibodies, may have a role in primary biliary cirrhosis pathogenesis. An aberrant intestinal T lymphocyte homing to the liver may contribute to trigger immune hepatic damage. Both celiac disease and primary biliary cirrhosis share several features, including a higher prevalence in females, autoimmune comorbidities and specific autoantibodies. Reciprocal screening for both diseases is recommended, as an early diagnosis with the appropriate treatment can improve the outcome of these patients.

  5. [csapAIH: a function to classify ambulatory care sensitive conditions in the statistical software R].

    PubMed

    Nedel, Fúlvio Borges

    2017-01-01

    Hospitalizations due to ambulatory care sensitive conditions (ACSC) are an indirect indicator of primary health care. A package in the R program was developed in order to automatize the classification of codes of the International Statistical Classification of Diseases and Related Health Problems - 10th Revision (ICD-10), according to the Brazilian list of ACSC, and provide functionalities for the management of the "reduced files" of the inpatient hospital authorization (AIH). The csapAIH package contains a homonym function, which reads the data according to its nature (file or data frame with AIH structure, or a factor with ICD-10 codes) and returns, according to defined options, a databank or vector containing the classification for the hospitalization. This article presents the package and the function csapAIH, its installation mode and use, and examples of its functionalities, which may add quickness, precision and validity to the research of ACSC in Brazil.

  6. The coexistence of Sjögren's syndrome and primary biliary cirrhosis: a comprehensive review.

    PubMed

    Sun, Ying; Zhang, Weici; Li, Baosen; Zou, Zhengsheng; Selmi, Carlo; Gershwin, M Eric

    2015-06-01

    Organ-specific and systemic autoimmune diseases share numerous features and often coexist in the same patient. Autoimmune cholangitis/primary biliary cirrhosis and Sjogren syndrome represent paradigmatic examples of the common grounds of different autoimmunity phenotypes based on similarities in clinical manifestations and immunopathogenesis. In fact, primary biliary cirrhosis and Sjogren's syndrome have both been coined as an autoimmune epithelitis in which apoptosis may be in both cases the key element to explain the organ-specific immune-mediated injury against the biliary and exocrine gland epithelia, respectively. Further, growing evidence supports in both diseases the view that B cells, T cytotoxic cells, and T helper cells are involved in chronic inflammation, likely via the altered expression of pro-inflammatory cytokines. The presence of estrogen receptors on the biliary and exocrine gland epithelia has been advocated as a key to the female predominance encountered in primary biliary cirrhosis and Sjogren's syndrome. Sadly, despite available data, therapeutic approaches remain largely unsatisfactory and recent studies with mechanistic approaches (as in the case of B cell depletion with rituximab) have been of partial benefit only. Future studies should focus on new molecular tools (single-cell transcriptomics, microRNA, epigenetics) to provide unique insights into common mechanisms.

  7. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective

    PubMed Central

    Marchioni Beery, Renée M.; Vaziri, Haleh; Forouhar, Faripour

    2014-01-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease. PMID:26357630

  8. Molecular mimicry in primary biliary cirrhosis. Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2.

    PubMed Central

    Van de Water, J; Turchany, J; Leung, P S; Lake, J; Munoz, S; Surh, C D; Coppel, R; Ansari, A; Nakanuma, Y; Gershwin, M E

    1993-01-01

    Sera from patients with primary biliary cirrhosis (PBC) react with enzymes of the 2-oxo dehydrogenase pathways, particularly PDC-E2. These enzymes are present in all nucleated cells, yet autoimmune damage is confined to biliary epithelial cells. Using a panel of eight mouse monoclonal antibodies and a human combinatorial antibody specific for PDC-E2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing cholangitis, and hepatocarcinoma. The monoclonal antibodies gave typical mitochondrial immunofluorescence on biliary epithelium and on hepatocytes from patients with either PBC, progressive sclerosing cholangitis, or hepatocarcinoma. However, one of eight mouse monoclonal antibodies (C355.1) and the human combinatorial antibody reacted with great intensity and specificity with the luminal region of biliary epithelial cells from patients with PBC. Simultaneous examination of these sections with an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be interpreted as indicating that a molecule cross-reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial cells in PBC. Images PMID:8514873

  9. Molecular mimicry in primary biliary cirrhosis. Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2.

    PubMed

    Van de Water, J; Turchany, J; Leung, P S; Lake, J; Munoz, S; Surh, C D; Coppel, R; Ansari, A; Nakanuma, Y; Gershwin, M E

    1993-06-01

    Sera from patients with primary biliary cirrhosis (PBC) react with enzymes of the 2-oxo dehydrogenase pathways, particularly PDC-E2. These enzymes are present in all nucleated cells, yet autoimmune damage is confined to biliary epithelial cells. Using a panel of eight mouse monoclonal antibodies and a human combinatorial antibody specific for PDC-E2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing cholangitis, and hepatocarcinoma. The monoclonal antibodies gave typical mitochondrial immunofluorescence on biliary epithelium and on hepatocytes from patients with either PBC, progressive sclerosing cholangitis, or hepatocarcinoma. However, one of eight mouse monoclonal antibodies (C355.1) and the human combinatorial antibody reacted with great intensity and specificity with the luminal region of biliary epithelial cells from patients with PBC. Simultaneous examination of these sections with an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be interpreted as indicating that a molecule cross-reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial cells in PBC.

  10. In recurrent primary biliary cirrhosis after liver transplantation, biliary epithelial cells show increased expression of mitochondrial proteins.

    PubMed

    Sasaki, Motoko; Hsu, Maylee; Yeh, Matthew M; Nakanuma, Yasuni

    2015-10-01

    In biliary epithelial lesions in primary biliary cirrhosis (PBC), mitochondrial proteins associated with deregulated autophagy are abnormally expressed. We examined whether this could be used as a diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. We examined the expression of the mitochondrial protein pyruvate dehydrogenase complex-E2 component and cytochrome c oxidase, subunit I (CCO), the autophagy-related marker microtubule-associated protein-light chain 3 (LC3), and p62/sequestosome-1 and the senescence markers p16(Ink4a) and p21(WAF1/Cip1) in small bile ducts and bile ductules in explanted livers from patients with PBC (n = 20) in comparison with liver tissue from control patients (n = 21) and post-transplant samples including recurrent PBC and cellular rejection (n = 28). Intense granular expression of mitochondrial proteins was significantly more frequent in small bile ducts in explanted livers with PBC than in control livers (p < 0.05). Post-transplant samples comprised of three groups: group A (positive for mitochondrial proteins, n = 7), group B (positive for either autophagy-related or senescence markers but negative for mitochondrial proteins, n = 7), and group C (all negative, n = 14). All but one case of group A were clinically and histologically diagnosed as recurrent PBC. In contrast, all cases of group B were diagnosed as cellular rejection. This study suggests that the expression of mitochondrial proteins in small bile ducts may be a useful diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation.

  11. [Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in adults: report of three cases].

    PubMed

    Santos, Oscar Mauricio; Muñoz Ortiz, Edison; Pérez, Camilo; Restrepo, Juan Carlos

    2012-04-01

    Overlap syndromes are cases of liver diseases that share clinical, serological, histological and radiological criteria of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). No definitions have been fully established and therefore there is no solid evidence on the diagnosis and treatment. This article presents the cases of three adult patients with overlapping features of AIH and PSC. Orthotopic liver transplantation was considered the best therapeutic alternative due to advanced disease progression in one patient, while medical treatment was provided in the remaining two patients.

  12. Evaluation of Biliary Calprotectin as a Biomarker in Primary Sclerosing Cholangitis.

    PubMed

    Gauss, Annika; Sauer, Peter; Stiehl, Adolf; Rupp, Christian; Krisam, Johannes; Leopold, Yvonne; Kloeters-Plachky, Petra; Stremmel, Wolfgang; Gotthardt, Daniel

    2016-04-01

    Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts with limited therapeutic options except liver transplantation. Reliable biomarkers to predict the disease course are unavailable, and currently employed disease activity scores such as the Mayo risk score (MRS) have limitations. The present study aims to evaluate biliary calprotectin as a marker of disease activity and prognosis in PSC.This is a monocentric retrospective observational study. Calprotectin concentrations were measured by an enzyme-linked immunosorbent assay in bile samples collected by endoscopic retrograde cholangiography from 106 PSC patients and 20 controls. Biliary calprotectin concentrations were compared between the 2 groups. In PSC patients, results were evaluated with regard to the presence of dominant bile duct stenoses, bile microbiology, MRS, survival free of liver transplantation, and necessity for bile duct interventions in the further disease course.Median (interquartile ranges) biliary calprotectin concentrations were higher in PSC patients than in controls (3646 ng/mL, 249-9748 vs 116 ng/mL, 104-655; P < 0.001). In the PSC cohort, higher biliary calprotectin concentrations were associated with the presence of microbes in bile (P = 0.02), the occurrence of dominant bile duct stenosis at any time in the disease course (P = 0.005), and the necessity for future bile duct interventions (P = 0.02). Patients with biliary calprotectin concentrations above a cut-off of 11,610 ng/mL displayed significantly shorter transplantation-free survival than those with biliary calprotectin concentrations ≤11,610 ng/mL (P < 0.001). Univariate Cox regression analysis revealed high biliary calprotectin concentration (>11,610 ng/mL) as a risk factor of shorter transplantation-free survival of PSC patients (P < 0.001) beside high plasma alkaline phosphatase (ALP) concentration (>142.5 U/L) (P = 0.006), high MRS (≥2) (P < 0

  13. Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment

    PubMed Central

    Leuschner, M; Dietrich, C; You, T; Seidl, C; Raedle, J; Herrmann, G; Ackermann, H; Leuschner, U

    2000-01-01

    BACKGROUND—In some patients with primary biliary cirrhosis, ursodeoxycholic acid causes full biochemical normalisation of laboratory data; in others, indexes improve but do not become normal.
AIMS—To characterise complete and incomplete responders.
METHODS—Seventy patients with primary biliary cirrhosis were treated with ursodeoxycholic acid 10-15 mg/kg/day and followed up for 6-13 years.
RESULTS—In 23 patients (33%) with mainly stage I or II disease, cholestasis indexes and aminotransferases normalised within 1-5 years, except for antimitochondrial antibodies. Histological findings improved. Indexes were not normalised in 47 patients (67%) although the improvement of their biochemical functions parallelled the trend in the first group. In these incomplete responders histological findings improved to a lesser extent. The only difference between the two groups before treatment was higher levels of alkaline phosphatase and γ glutamyl transpeptidase in the incomplete responders. At onset of treatment the discriminant value separating responders from incomplete responders was 660 U/l for alkaline phosphatase and 131 U/l for γ glutamyl transpeptidase. One year later it was 239 and 27 U/l (overall predictive value for responders 92%, for incomplete responders 81%). There were no differences between the two groups concerning immune status, antimitochondrial antibody subtypes, liver histology, or any other data. HLA-B39, DRB1*08, DQB1*04 dominated in both groups.
CONCLUSIONS—In patients with mainly early stages of primary biliary cirrhosis, higher values of alkaline phosphatase and γ glutamyl transpeptidase are the only biochemical indexes which allow discrimination between patients who will completely or incompletely respond to ursodeoxycholic acid treatment.


Keywords: primary biliary cirrhosis; prognostic indexes; full response to ursodeoxycholic acid; incomplete responders; anti-p53 autoantibodies; HLA typing PMID:10601067

  14. A Case of Frontal Fibrosing Alopecia in a Patient with Primary Biliary Cirrhosis and Polymyalgia Rheumatica

    PubMed Central

    Eginli, Ariana N.; Bagayoko, Courtney W.; McMichael, Amy J.

    2016-01-01

    Frontal fibrosing alopecia (FFA) is a form of scarring hair loss that is characterized by hair follicle destruction in a fronto-temporo-parietal distribution. Its etiology is unknown; however, most authors presently favor an immune pathogenesis. Associated autoimmune connective tissue diseases have been reported in patients with FFA. We present a case of FFA in a woman with primary biliary cirrhosis and polymyalgia rheumatica, suggesting an association between these clinical entities and supporting a potential autoimmune etiology of FFA. PMID:27843932

  15. The epidemiology of primary biliary cirrhosis: A survey of mortality in England and Wales

    PubMed Central

    Hamlyn, A. N.; Sherlock, S.

    1974-01-01

    Primary biliary cirrhosis is a rare disease in the general population. Estimates of its true incidence are difficult but since survival time is unaffected by treatment, mortality may reflect important regional and other variations. One hundred and sixty-five death certificates collected in England and Wales over the five-year period 1967-1971 were inspected and confirmed an overwhelming predilection for females. Deaths rose sharply at ages 50-54 in the latter with a peak of 4·1 million−1 year−1, with perhaps a secondary peak at ages 70-74. No relation of mortality with climate, altitude, soil type, annual temperature range, or occupation was found, although outside the UK a broad correlation exists with total cirrhosis deaths. There was a suggestive excess of deaths among married women. The greater frequency of deaths in the London area, a rise in mortality from country to urban areas, a fall-off in deaths from primary biliary cirrhosis in old age, and predominance for social class I suggest a simple relationship with standards of medical care or diagnosis. An `epidemic' of deaths in 1971 is attributed to greater availability of the mitochondrial antibody test in the regions. The importance of familial primary biliary cirrhosis and various models of pathogenesis are discussed. Both constitutional and environmental factors producing the disease must be widely distributed in the population of this country. PMID:4854819

  16. Infliximab as a treatment option for patients with rheumatoid arthritis and primary biliary cirrhosis.

    PubMed

    Dimopoulou, Despoina; Dimitroulas, Theodoros; Akriviadis, Evangelos; Garyfallos, Alexandros

    2015-11-01

    Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease which commonly requires treatment with biologic agents targeting various inflammatory pathways. Tumor necrosis factor alpha is a proinflammatory cytokine which plays a pivotal role not only in the pathogenesis of RA but also in other autoimmune diseases such as primary biliary cirrhosis. The co-existence of more than one autoimmune disorder in the same individual is very challenging in the daily practice as therapy strategies applicable to one disease setting may cause clinical and/or biochemical relapse of the other clinical entity. As a result, treatment options able to control different diseases are highly desirable among rheumatologists and other specialties. In that respect, we present a case of a 61-year-old female patient with RA and concomitant primary biliary cirrhosis with poor clinical response to conventional disease-modifying drugs for RA. The introduction of tumor necrosis factor alpha antagonist infliximab led to significant clinical improvement of RA and to stabilization of liver function. In this case review study, we discuss aspects of pathophysiology of primary biliary cirrhosis associated with tumor necrosis alpha and we review the available data of similar published cases.

  17. Spontaneous Splenic Infarcts in a Cirrhotic Patient with Primary Biliary Cirrhosis

    PubMed Central

    Nehme, Fredy; Rowe, Kyle; Haris, Ahmad; Nassif, Imad

    2017-01-01

    Spontaneous splenic infarction has been rarely reported as a complication of cirrhosis and portal hypertension. We describe the case of a 67-year-old female with past medical history of primary biliary cirrhosis presenting for a 1-day history of left upper quadrant pain. Investigations were in favor of splenic infarcts secondary to portal hypertension. The patient improved with conservative management and no recurrence was noted on further follow-up. Splenic infarction must be kept in mind when a patient with cirrhosis presents with left upper quadrant abdominal pain without a clear source. PMID:28203139

  18. Severe hypophosphatemic osteomalacia with Fanconi syndrome, renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis.

    PubMed

    Bando, Hironori; Hashimoto, Naoko; Hirota, Yushi; Sakaguchi, Kazuhiko; Hisa, Itoko; Inoue, Yoshifumi; Imanishi, Yasuo; Seino, Susumu; Kaji, Hiroshi

    2009-01-01

    A 49-year-old woman was admitted to our hospital for back pain with marked thoracic and extremity deformities leading to bed-rest for three years. She was diagnosed with hypophosphatemic osteomalacia based on her symptoms, X-ray and bone scintigram, high serum alkaline phosphatase level, and low serum levels of both phosphorus and 1,25 dihydroxyvitamin D(3) with inhibition of phosphorus reabsorption. Fanconi syndrome with renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis were related to the pathogenesis of osteomalacia in this case. Several causal diseases may be concomitantly responsible for acceleration of the severity of osteomalacia in this patient.

  19. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.

    PubMed

    Liu, Xiangdong; Invernizzi, Pietro; Lu, Yue; Kosoy, Roman; Lu, Yan; Bianchi, Ilaria; Podda, Mauro; Xu, Chun; Xie, Gang; Macciardi, Fabio; Selmi, Carlo; Lupoli, Sara; Shigeta, Russell; Ransom, Michael; Lleo, Ana; Lee, Annette T; Mason, Andrew L; Myers, Robert P; Peltekian, Kevork M; Ghent, Cameron N; Bernuzzi, Francesca; Zuin, Massimo; Rosina, Floriano; Borghesio, Elisabetta; Floreani, Annarosa; Lazzari, Roberta; Niro, Grazia; Andriulli, Angelo; Muratori, Luigi; Muratori, Paolo; Almasio, Piero L; Andreone, Pietro; Margotti, Marzia; Brunetto, Maurizia; Coco, Barbara; Alvaro, Domenico; Bragazzi, Maria C; Marra, Fabio; Pisano, Alessandro; Rigamonti, Cristina; Colombo, Massimo; Marzioni, Marco; Benedetti, Antonio; Fabris, Luca; Strazzabosco, Mario; Portincasa, Piero; Palmieri, Vincenzo O; Tiribelli, Claudio; Croce, Lory; Bruno, Savino; Rossi, Sonia; Vinci, Maria; Prisco, Cleofe; Mattalia, Alberto; Toniutto, Pierluigi; Picciotto, Antonio; Galli, Andrea; Ferrari, Carlo; Colombo, Silvia; Casella, Giovanni; Morini, Lorenzo; Caporaso, Nicola; Colli, Agostino; Spinzi, Giancarlo; Montanari, Renzo; Gregersen, Peter K; Heathcote, E Jenny; Hirschfield, Gideon M; Siminovitch, Katherine A; Amos, Christopher I; Gershwin, M Eric; Seldin, Michael F

    2010-08-01

    A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 x 10(-11), odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 x 10(-10), OR = 1.63) and 17q12-21 (P = 1.7 x 10(-10), OR = 1.38).

  20. Successful infliximab therapy in a patient with comorbid spondyloarthritis, primary biliary cirrhosis and generalized morphea.

    PubMed

    Resorlu, Hatice; Kılıc, Sevilay; Isık, Selda; Gokmen, Ferhat

    2017-02-23

    The patient in this report was diagnosed simultaneously with primary biliary cirrhosis (PBC), spondyloarthritis, and generalized morphea and was started on infliximab therapy. In addition to an improvement in clinical symptoms with this therapy, an improvement was also observed in laboratory parameters such as cholestatic enzymes, C-reactive protein, and erythrocyte sedimentation rate. Infliximab was well tolerated in this 56-year-old patient. However, further studies must be performed in order to clarify the therapeutic role of TNF-α blockers in, PBC and generalized morphea.

  1. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

    PubMed Central

    Liu, Xiangdong; Invernizzi, Pietro; Lu, Yue; Kosoy, Roman; Lu, Yan; Bianchi, Ilaria; Podda, Mauro; Xu, Chun; Xie, Gang; Macciardi, Fabio; Selmi, Carlo; Lupoli, Sara; Shigeta, Russell; Ransom, Michael; Lleo, Ana; Lee, Annette T; Mason, Andrew L; Myers, Robert P; Peltekian, Kevork M; Ghent, Cameron N; Bernuzzi, Francesca; Zuin, Massimo; Rosina, Floriano; Borghesio, Elisabetta; Floreani, Annarosa; Lazzari, Roberta; Niro, Grazia; Andriulli, Angelo; Muratori, Luigi; Muratori, Paolo; Almasio, Piero L; Andreone, Pietro; Margotti, Marzia; Brunetto, Maurizia; Coco, Barbara; Alvaro, Domenico; Bragazzi, Maria C; Marra, Fabio; Pisano, Alessandro; Rigamonti, Cristina; Colombo, Massimo; Marzioni, Marco; Benedetti, Antonio; Fabris, Luca; Strazzabosco, Mario; Portincasa, Piero; Palmieri, Vincenzo O; Tiribelli, Claudio; Croce, Lory; Bruno, Savino; Rossi, Sonia; Vinci, Maria; Prisco, Cleofe; Mattalia, Alberto; Toniutto, Pierluigi; Picciotto, Antonio; Galli, Andrea; Ferrari, Carlo; Colombo, Silvia; Casella, Giovanni; Morini, Lorenzo; Caporaso, Nicola; Colli, Agostino; Spinzi, Giancarlo; Montanari, Renzo; Gregersen, Peter K; Heathcote, E Jenny; Hirschfield, Gideon M; Siminovitch, Katherine A; Amos, Christopher I; Gershwin, M Eric; Seldin, Michael F

    2011-01-01

    A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38). PMID:20639880

  2. Microscopic polyangiitis associated with primary biliary cirrhosis, Sjogren's syndrome and Hashimoto's thyroiditis.

    PubMed

    Ghorbel, I Ben; Feki, N Bel; Salem, T Ben; Hamzaoui, A; Khanfir, M; Lamloum, M; Miled, M; Houman, M H

    2015-03-01

    The association between microscopic polyangiitis (MPA) and primary biliary cirrhosis (PBC) has seldom been reported. We describe here a patient who presented with sensorimotor neuropathy along with hypothyroidism, renal failure and liver dysfunction. Detection of antinuclear antibodies at a titer of 1/800, anti-SSA, anti-SSB, anti-GP210, anti-microsomial and p-ANCA anti-myeloperoxydase antibodies along with renal, salivary and liver biopsy led to a diagnosis of MPA associated with PBC, Sjogren's syndrome and Hashimoto's thyroiditis.

  3. Prediction of oesophageal varices in patients with primary biliary cirrhosis by non-invasive markers

    PubMed Central

    Gao, Lili; Li, Hanwei; Han, Jun; Zhang, Weihui

    2017-01-01

    Introduction Preliminary data suggested that non-invasive methods could be useful to assess presence of oesophageal varices (OV) in liver cirrhosis. The primary objectives were to investigate non-invasive markers for diagnosing and grading OV in patients with primary biliary cirrhosis. Material and methods This study included a total of 106 consecutive treatment-naive patients with primary biliary cirrhosis (PBC). Results of physical examination, blood tests, and abdominal ultrasound scan (USS) were measured. Performance of non-invasive markers for OV was expressed as sensitivity, specificity, positive, and negative predictive values (PPV, NPV), accuracy, and area under the curve (AUC). Results Oesophageal varices were found in 54 (50.9%) and large OV in 28 of the 106 patients. Variables found to differ significantly between patients with any grade or large and without OV included increased spleen length, increased portal vein diameter, low platelet count, and low levels of albumin or low γ-glutamyltranspeptidase (γ-GTP) values. Area under the receiver operating characteristic curve showed that spleen length (cutoff = 156.0) had AUC 0.753 (95% CI: 0.657–0.849), and high NPV (82.1%) to exclude any grade OV. Large OV could be excluded with NPV 70.6% by spleen length. Conclusions Predictive risk factors that use readily available laboratory results and ultrasound scan results may reliably identify esophageal varices in patients with PBC. PMID:28261290

  4. Non-Invasive Assessment of Liver Fibrosis Progression and Prognosis in Primary Biliary Cholangitis.

    PubMed

    Poupon, Raoul

    2015-01-01

    PBC (formerly known as primary biliary cirrhosis and now named primary biliary cholangitis) is a disease with a wide range of severity and variable rate of progression. The diagnosis of advanced liver fibrosis/cirrhosis portends an increased risk of liver-related morbidity and mortality. Because of its invasiveness, liver biopsy tends to be replaced by non-invasive tools for assessing liver fibrosis, making prognosis and optimising risk stratification for selection of patients, requiring new medical approaches. Many direct or indirect biomarkers have been found to correlate with the severity of liver fibrosis in PBC. They are easy to use but lack sensitivity and reproducibility in individuals with early stage disease. Three main radiologic approaches are currently proposed to assess liver fibrosis: vibration controlled transient elastography (VCTE), acoustic radiation force impulse and magnetic resonance elastography. Data using VCTE are available only for the longitudinal evaluation of liver fibrosis and prognosis in PBC. VCTE outperformed all other non-invasive current surrogate markers of liver fibrosis in PBC. Because of its high acceptability and its ability to predict hepatic decompensation, VCTE could be a useful tool to help allocate cirrhotic patients into different categories of risk. None of the radiologic and serum markers have a perfect accuracy in studies so far published. Concordance between VCTE and serum biomarkers is a prerequisite for a correct prognosis assessment in individuals in clinical practice.

  5. 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

  6. Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis

    PubMed Central

    Bernuzzi, Francesca; Fenoglio, Daniela; Battaglia, Florinda; Fravega, Marco; Gershwin, M. Eric; Indiveri, Francesco; Ansari, Aftab A.; Podda, Mauro; Invernizzi, Pietro; Filaci, Gilberto

    2011-01-01

    The mechanisms that lead to loss of tolerance in autoimmune disease have remained both elusive and diverse, including both genetic predisposition and generic dysregulation of critical mononuclear cell subsets. In primary biliary cirrhosis (PBC), patients exhibit a multilineage response to the E2 component of pyruvate dehydrogenase involving antibody as well as autoreactive CD4 and CD8 responses. Recent data from murine models of PBC have suggested that a critical mechanism of biliary destruction is mediated by liver-infiltrating CD8 cells. Further, the number of autoreactive liver-infiltrating CD4 and CD8 cells is significantly higher in liver than blood in patients with PBC. Based on this data, we have studied the frequencies and phenotypic characterization of both CD4 and CD8 regulatory T cell components in both patients with PBC and age–sex matched controls. Our data is striking and indicate that CD8 Treg populations from PBC patients, but not controls, have significant phenotypic alterations, including increased expression of CD127 and reduced CD39. Furthermore, in vitro induction of CD8 Tregs by incubation with IL10 is significantly reduced in PBC patients. Importantly, the frequencies of circulating CD4+CD25+ and CD8+ and CD28− T cell subpopulations are not significantly different between patients and controls. In conclusion, these data identify the CD8 Treg subset as a regulatory T cell subpopulation altered in patients with PBC. PMID:20638239

  7. Serum Reactivity Against Bacterial Pyruvate Dehydrogenase: Increasing the Specificity of Anti-Mitochondrial Antibodies for the Diagnosis of Primary Biliary Cirrhosis

    PubMed Central

    Miyakawa, Hiroshi; Tanaka, Atsushi; Selmi, Carlo; Hosoya, Naomi; Mataki, Norikazu; Kikuchi, Kentaro; Kato, Takashi; Arai, Junya; Goto, Toshihiro; Gershwin, M. Eric

    2006-01-01

    Antimitochondrial antibodies (AMA) are the serum hallmark of primary biliary cirrhosis (PBC). However, AMA-positivity can be found in non-PBC sera when lower dilutions are used, thus raising issues about the specificity and sensitivity of the test. AMA reacts primarily with the lipoylated domains of pyruvate dehydrogenase-E2 (PDC-E2) which is highly conserved across species, including bacteria. We studied 77 serum samples, including 24 from patients with anti-PDC-E2-positive PBC and 53 controls (16 with autoimmune hepatitis (AIH), 10 with primary sclerosing cholangitis (PSC), and 27 healthy individuals) for their reactivities at serial dilutions (1:10, 1:20 and 1:40) against Escherichia coli DH5 alpha lysate overexpressing human PDC-E2 using immunoblotting (IB). A murine anti-human PDC-E2 monoclonal antibody (mAB) was used as control. We further studied positive sera using adsorption with a synthetic E. coli peptide sharing similarity with human PDC-E2. Finally, we verified whether a unique buffer for E. coli preparation could reduce non-specific serum reactivity. Results demonstrated that 100% of anti-PDC-E2-positive PBC and up to 38% of control sera at 1:10 dilution recognized E. coli PDC-E2 at IB while dilution tests indicated that the overall potency of PBC reactivity was 100-fold higher compared to controls. In fact, a subgroup (20-38%) of non-PBC sera were positive at low titers but lost the reactivity when absorbed with the synthetic E. coli peptide. Finally, our unique buffer reduced the reactivity of non-PBC sera as measured by ELISA. In conclusion, we demonstrated that weak cross-reactivity with E. coli PDC-E2 occurs in non-PBC sera at lower dilutions and that such reactivity is not due to AMA-positivity. The use of a specific buffer might avoid the risk of false positive AMA determinations when E. coli-expressed recombinant antigens are used. PMID:17162370

  8. The relief of bone pain in primary biliary cirrhosis with calcium infusions

    PubMed Central

    Ajdukiewicz, A. B.; Agnew, J. E.; Byers, P. D.; Wills, M. R.; Sherlock, Sheila

    1974-01-01

    Intravenous calcium infusions produced subjective relief of bone pain in 14 patients with primary biliary cirrhosis. The bone pain had developed despite long-term parenteral vitamin D therapy. The pain returned after two to three months, but a subsequent course of infusions again brought relief. Before treatment satisfactory iliac crest bone biopsies were obtained in 11 of the patients and were normal in seven; two patients had biopsies indicating osteomalacia and two osteoporosis. After treatment a repeat biopsy in one of the patients with osteomalacia showed marked reduction in osteoid. The infusion treatment produced no change in plasma calcium concentration, serum phosphate, or serum alkaline phosphatase. Absorption of oral calcium was also unchanged. PMID:4279816

  9. Guillain–Barré syndrome mimics primary biliary cirrhosis-related myopathy

    PubMed Central

    Munday, William R.; DiCapua, Daniel; Vortmeyer, Alexander; Gomez, Jose Luis

    2015-01-01

    Guillain–Barré syndrome (GBS) is an immune-mediated disorder characterized by acute polyneuropathy, ascending paralysis and post infectious polyneuritis. Two-thirds of patients present with a history of recent upper respiratory tract or gastrointestinal infection. The clinical history, neurologic examination and laboratory assessment allow for a straightforward diagnosis in the majority of cases. However, primary biliary cirrhosis (PBC) is known to cause clinically detectable muscular weakness. It is therefore critical to differentiate between PBC-associated muscular weakness and GBS-induced paralysis. Here, we report a patient with a longstanding history of PBC who developed progressive weakness and respiratory failure due to GBS, which clinically mimicked PBC myopathy. This is the first reported association between GBS and PBC. PMID:26634144

  10. 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.

  11. A Case of Primary Biliary Cirrhosis Mimicking Acute Hepatitis B in the Clinic, Republic of Korea

    PubMed Central

    Kwon, Woo Hyuk; Park, Hong Min; Park, Jeong Jun; Lee, Sung Hoon

    2017-01-01

    Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic autoimmune liver disease characterized by progressive bile duct injury. The most common symptoms of this disease include fatigue and pruritus. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibodies, and characteristic histological biopsy findings. We report a case of a patient with PBS, who was initially suspected to be in the window period of hepatitis B by a private doctor in a local clinic based on the detection of isolated immunoglobulin M antibody against hepatitis B core antigen. The presence of this antibody is the most useful index in diagnosing acute hepatitis B (+) by immunoserological test. The final diagnosis of the patient in Good Gang-An Hospital was PBC through additional tests. The patient is receiving outpatient treatment. PMID:28197333

  12. Fungal infection involvement in primary biliary cirrhosis: A review of 2 cases

    PubMed Central

    Wang, Yanyan; Zhao, Zheng; Lu, Hui; Zhang, Jianglin; Huang, Feng

    2017-01-01

    The present study aimed to analyze the imaging, clinical and pathological features of fungal infection involvement in primary biliary cirrhosis (PBC) by retrospectively analyzing and reviewing the features of two patients with fungal infection involvement in PBC. Both patients were female. One patient had a confirmed diagnosis of PBC. The other patient had confirmed Sjogren syndrome and PBC. The two cases of PBC were infected with fungal infection after treatment with hormonal and immunosuppressive agents. RCR of sputum confirmed Pneumocystis spp. infection in the patient with PBC alone. The mucormycosis infection was confirmed in the other patient after pathological examination of a renal biopsy. The state of the illnesses progressed quickly and both patients ultimately succumbed to their conditions. The patient prognosis of fungal infection involvement PBC is poor. Patients treated with long-term hormone and immunosuppressive agents should be monitored. PMID:28352320

  13. 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

  14. The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis.

    PubMed

    Tomiyama, Takashi; Yang, Guo-Xiang; Zhao, Ming; Zhang, Weici; Tanaka, Hajime; Wang, Jing; Leung, Patrick Sc; Okazaki, Kazuichi; He, Xiao-Song; Lu, Qianjin; Coppel, Ross L; Bowlus, Christopher L; Gershwin, M Eric

    2017-03-01

    Exosomes are nanoparticles of endocytic origin, secreted by a myriad of cell populations that are attracting increased attention by virtue of their ability to modulate cell-to-cell communications. They are also attracting attention in a variety of immunological issues, including autoimmunity and, in particular, their ability to regulate cytokine and chemokine activation. Primary biliary cirrhosis (PBC) is considered a model autoimmune disease, which has a highly focused cytotoxic response against biliary epithelial cells. We have isolated exosomes from plasma from 29 patients with PBC and 30 healthy controls (HCs), and studied the effect of these exosomes on co-stimulatory molecule expression and cytokine production in mononuclear cell populations using an ex vivo system. We also identified the microRNA (miRNA) populations in PBC compared to HC exosomes. We report herein that although exosomes do not change cytokine production, they do significantly alter co-stimulatory molecule expression on antigen-presenting populations. Further, we demonstrated that CD86 up-regulated expression on CD14(+) monocytes, whereas CD40 up-regulated on CD11c(+) dendritic cells by exosomes from patients with PBC. In addition, there were differences of miRNA expression of circulating exosomes in patients with PBC. These data have significant importance based on observations that co-stimulatory molecules play a differential role in the regulation of T-cell activation. Our observation indicated that aberrant exosomes from PBC selectively induce expression of co-stimulatory molecules in different subset of antigen-presenting cells. These alterations may involve in pathogenesis of autoimmune liver disease.Cellular & Molecular Immunology advance online publication, 21 September 2015; doi:10.1038/cmi.2015.86.

  15. Innumerable Liver Masses in a Patient with Autoimmune Hepatitis and Primary Sclerosing Cholangitis Overlap Syndrome.

    PubMed

    Gharibpoor, Alireza; Mansour-Ghanaei, Fariborz; Sadeghi, Mahbobe; Gharibpoor, Faeze; Joukar, Farahnaz; Mavaddati, Sara

    2017-02-07

    BACKGROUND In patients with the diagnosis of autoimmune hepatitis (AIH), the presence of cholestatic features raise the possibility of an overlap syndrome with primary sclerosing cholangitis (PSC). Here, we present a unique case with AIH-PSC overlap syndrome and innumerable liver masses. CASE REPORT A 26-year-old man presented with generalized icterus. Based on the serological findings of hypergamainmunoglobulinemia and positive anti-nuclear antibody tests, together with an abnormal cholangiogram, he was diagnosed with overlap syndrome (AIH-PSC). Liver imaging revealed innumerable liver masses with a benign appearance in the pathological evaluation. To rule out the colon abnormalities that usually coexist with such liver masses, colonoscopy was performed and showed no significant changes. The liver masses were nonmalignant and were resolved after immunosuppressant therapy. CONCLUSIONS Because AIH-PSC overlap syndrome is rare, it is suggested that radiological evaluation of the biliary tree should be performed routinely in adults diagnosed with AIH to reduce the missed diagnosis of overlap syndrome and liver masses.

  16. Atypical p-ANCA in PSC and AIH: a hint toward a "leaky gut"?

    PubMed

    Terjung, Birgit; Spengler, Ulrich

    2009-02-01

    Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are enigmatic chronic inflammatory diseases of the liver, which are frequently associated with chronic inflammatory bowel diseases. Both types of liver disease share various distinct autoantibodies such as atypical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), and thus are considered autoimmune disorders with atypical features. The discovery that atypical p-ANCA recognize both tubulin beta isoform 5 in human neutrophils and the bacterial cell division protein FtsZ has renewed the discussion on the potential role of microorganisms in the pathogenesis of both diseases. In this paper, we review the evidence for microbial infection in PSC and AIH and discuss new concepts how cross-recognition between microbial antigens in the gut and host components by the immune system along with stimulation of pattern recognition receptors might give rise to chronic hepatic inflammatory disorders with features of autoimmunity.

  17. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.

    PubMed

    Mells, George F; Floyd, James A B; Morley, Katherine I; Cordell, Heather J; Franklin, Christopher S; Shin, So-Youn; Heneghan, Michael A; Neuberger, James M; Donaldson, Peter T; Day, Darren B; Ducker, Samantha J; Muriithi, Agnes W; Wheater, Elizabeth F; Hammond, Christopher J; Dawwas, Muhammad F; Jones, David E; Peltonen, Leena; Alexander, Graeme J; Sandford, Richard N; Anderson, Carl A

    2011-03-13

    In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻⁸) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC.

  18. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

    PubMed

    Liu, Jimmy Z; Almarri, Mohamed A; Gaffney, Daniel J; Mells, George F; Jostins, Luke; Cordell, Heather J; Ducker, Samantha J; Day, Darren B; Heneghan, Michael A; Neuberger, James M; Donaldson, Peter T; Bathgate, Andrew J; Burroughs, Andrew; Davies, Mervyn H; Jones, David E; Alexander, Graeme J; Barrett, Jeffrey C; Sandford, Richard N; Anderson, Carl A

    2012-10-01

    We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P<5×10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r2>0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

  19. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

    PubMed

    Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona

    2015-03-01

    Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

  20. A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density.

    PubMed

    Tang, Ruqi; Wei, Yiran; Li, Zhiqiang; Chen, Haoyan; Miao, Qi; Bian, Zhaolian; Zhang, Haiyan; Wang, Qixia; Wang, Zhaoyue; Lian, Min; Yang, Fan; Jiang, Xiang; Yang, Yue; Li, Enling; Seldin, Michael F; Gershwin, M Eric; Liao, Wilson; Shi, Yongyong; Ma, Xiong

    2016-02-04

    Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide significant BMD SNPs for association with PBC using two European GWAS data sets (n = 8392), with replication of significant findings in a Chinese cohort (685 cases, 1152 controls). Our analysis identified a novel variant in the intron of the CLDN14 gene (rs170183, Pfdr = 0.015) after multiple testing correction. The three associated variants were followed-up in the Chinese cohort; one SNP rs170183 demonstrated consistent evidence of association in diverse ethnic populations (Pcombined = 2.43 × 10(-5)). Notably, expression quantitative trait loci (eQTL) data revealed that rs170183 was correlated with a decline in CLDN14 expression in both lymphoblastoid cell lines and T cells (Padj = 0.003 and 0.016, respectively). In conclusion, our study identified a novel PBC susceptibility variant that has been shown to be strongly associated with BMD, highlighting the potential of pleiotropy to improve gene discovery.

  1. Contribution of zinc deficiency to insulin resistance in patients with primary biliary cirrhosis.

    PubMed

    Himoto, Takashi; Yoneyama, Hirohito; Kurokochi, Kazutaka; Inukai, Michio; Masugata, Hisashi; Goda, Fuminori; Haba, Reiji; Watanabe, Seishiro; Senda, Shoichi; Masaki, Tsutomu

    2011-12-01

    The relationship between metabolic abnormalities of trace elements and insulin resistance has been established. Recent studies have revealed that insulin resistance is associated with autoimmune responses. The purpose of this study was to examine the correlation between zinc or copper metabolism and insulin resistance in patients with primary biliary cirrhosis (PBC). Sixteen patients with PBC were divided into two groups: early and advanced stage disease. The overall value of the homeostasis model assessment of insulin resistance (HOMA-IR) in patients with advanced stage PBC was significantly higher than that in patients with early stage PBC, although the mean value in advanced stage PBC was significantly lower than that in hepatitis C virus (HCV)-related liver cirrhosis. There was an inverse correlation between serum zinc concentrations and HOMA-IR values in patients with PBC, while we found no correlation between serum copper levels and HOMA-IR values. HOMA-IR values were inversely associated with peripheral platelet counts, indicating the relationship between insulin resistance and hepatic fibrosis. These results suggest that zinc deficiency plays important roles of insulin resistance and subsequent hepatic fibrosis in patients with PBC, although insulin resistance in advanced stage PBC was significantly milder than that in HCV-related liver cirrhosis.

  2. Serological comparative proteomics analysis of mitochondrial autoantibody-negative and -positive primary biliary cirrhosis.

    PubMed

    Deng, Chuiwen; Hu, Chaojun; Wang, Li; Zhang, Shulan; Li, Ping; Wu, Ziyan; Chen, Si; Zhang, Fengchun; Li, Yongzhe

    2015-07-01

    Here, we investigated the pathogenesis of primary biliary cirrhosis (PBC) by using 2D-DIGE to analyze serological differences between anti-mitochondrial antibody (AMA)-positive and -negative PBC patients. The study comprised 30 patients with PBC; 20 AMA-positive and ten AMA-negative patients matched for age, sex, and pathological stage. A screening group (four AMA-positive and four AMA-negative patients) was used for 2D-DIGE. Protein spots that were differently abundant between the two groups were identified via dye intensity and MS. Nine candidate proteins were identified from these spots. Western blotting was used to verify two of the identified proteins, serum amyloid P-component (SAP) and vitronectin (VN). VN levels were significantly higher in the sera of AMA-negative PBC patients (p < 0.01), whereas no significant difference was found between the two groups for SAP. To our knowledge, this is the first study to use serological comparative proteomics to explore differences between AMA-positive and -negative PBC patients. VN levels were higher in AMA-negative PBC patients, and this finding could be related to the more severe bile duct destruction observed in this group.

  3. Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity.

    PubMed

    Xie, Yu-Qing; Ma, Hong-Di; Lian, Zhe-Xiong

    2016-06-01

    Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that develops based upon the interaction of genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified dozens of predisposing variants including HLA, IL12A, and CTLA4 but have been disappointed in identifying a "smoking gun." These discoveries highlight the importance of the genetic background involved in immunological dysregulation. Although concordance rate of PBC in monozygotic (MZ) twins is among the highest reported in autoimmune disorders, incomplete disease concordance in twins associated with differentially expressed genes has been demonstrated. However, little is understood about how environmental aspects contribute to the disease and why middle-aged women are more susceptible. As a result, epigenetic factors, which convert signals indicating environmental changes into dynamic and heritable alterations of transcriptional potential, are getting increased attention by researchers in both basic and clinical studies. Among epigenetic mechanisms, the instability and skewed gene expression in the X chromosome may account for the female preponderance in PBC. In addition, transcriptional regulation of histone modification and DNA methylation underscores potential involvement in disease pathogenesis. High-throughput techniques are being used to identify epigenetic regulators. In this review, we attempt to outline recent progress regarding epigenetics in PBC and other autoimmune diseases.

  4. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies.

    PubMed

    Kar, S P; Seldin, M F; Chen, W; Lu, E; Hirschfield, G M; Invernizzi, P; Heathcote, J; Cusi, D; Gershwin, M E; Siminovitch, K A; Amos, C I

    2013-04-01

    Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P<0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR <0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P=7.38 × 10⁻⁴, FDR=0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P<0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P<0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P<0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that, on further independent replication and functional validation, may provide fresh insights into PBC etiology.

  5. STAT4 gene polymorphisms are associated with susceptibility and ANA status in primary biliary cirrhosis.

    PubMed

    Joshita, Satoru; Umemura, Takeji; Nakamura, Minoru; Katsuyama, Yoshihiko; Shibata, Soichiro; Kimura, Takefumi; Morita, Susumu; Komatsu, Michiharu; Matsumoto, Akihiro; Yoshizawa, Kaname; Ishibashi, Hiromi; Tanaka, Eiji; Ota, Masao

    2014-01-01

    Recent genome-wide association studies suggest that genetic factors contribute to primary biliary cirrhosis (PBC) susceptibility. Although several reports have demonstrated that the interleukin (IL) 12 signaling pathway is involved in PBC pathogenesis, its precise genetic factors have not been fully clarified. Here, we performed an association analysis between IL12A, IL12RB, and signal transducer and activator of transcription 4 (STAT4) genetic variations and susceptibility to PBC. Single nucleotide polymorphisms (SNPs) were genotyped in 395 PBC patients and 458 healthy subjects of Japanese ethnicity and evaluated for associations with PBC susceptibility, anti-nuclear antibody (ANA) status, and anti-mitochondrial antibody (AMA) status. We detected significant associations with PBC susceptibility for several STAT4 SNPs (rs10168266; P = 9.4 × 10(-3), rs11889341; P = 1.2 × 10(-3), rs7574865; P = 4.0 × 10(-4), rs8179673; P = 2.0 × 10(-4), and rs10181656; P = 4.2 × 10(-5)). Three risk alleles (rs7574865; P = 0.040, rs8179673; P = 0.032, and rs10181656; P = 0.031) were associated with ANA status, but not with AMA positivity. Our findings confirm that STAT4 is involved in PBC susceptibility and may play a role in ANA status in the Japanese population.

  6. Oral Tolerance and Pyruvate Dehydrogenase in Patients with Primary Biliary Cirrhosis

    PubMed Central

    Suzuki, Ayako; van de Water, Judy; Gershwin, M. Eric; Jorgensen, Roberta; Angulo, Paul; Lindor, Keith

    2002-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti-mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we hypothesized that feeding the mitochondrial autoantigens of PBC would alter the clinical course and the level of antimitochondrial antibodies. The bovine pyruvate dehydrogenase complex (PDC) was purified and 5 mg fed in gelatin capsules to 6 patients with early stage PBC for 6 months. Antimitochondrial antibodies and liver biochemistries were measured at every 3 months for 12 months. The clinical trial was completed for all patients except for 1 who showed deterioration of pre-existing skin rash during treatment, which disappeared within 2 weeks after treatment was discontinued. However, after 1 year, neither the titers of AMAs nor liver biochemistries were significantly changed by this treatment. This is the first trial to test the efficacy of oral tolerance induction in PBC. However, the data, which limited in scope, did not demonstrate efficacy and further highlights the difficulties in showing continuing evidence of tolerance induction in autoimmunity. PMID:12739782

  7. Prospective randomized crossover trial of combination therapy with bezafibrate and UDCA for primary biliary cirrhosis.

    PubMed

    Itakura, Jun; Izumi, Namiki; Nishimura, Yuki; Inoue, Kazunari; Ueda, Ken; Nakanishi, Hiroyuki; Tsuchiya, Kaoru; Hamano, Kosei; Asahina, Yasuhiro; Kurosaki, Masayuki; Uchihara, Masakatsu; Miyake, Shozo

    2004-08-01

    The aim of this study was to evaluate the effects of the combination therapy with bezafibrate and ursodeoxycholic acid (UDCA) for primary biliary cirrhosis (PBC), compared to UDCA monotherapy. Sixteen patients with compensated PBC were divided randomly into two groups. Group A received treatment with bezafibrate and UDCA for 6 months, while group B received UDCA alone, treatment protocols were then exchanged for another 6 months. The laboratory data was followed every month. The mean levels of alkaline phosphatase (ALP) decreased significantly more in group A than in group B in the first half of the study. Then serum ALP levels were elevated in group A after exchanged the therapy, but fell down in group B. Serum levels of gamma-glutamyl transferase (GGT), immunoglobulin M and triglycerides values were significantly lower in group B than in group A, after changing therapies from monotherapy to combination therapy with bezafibrate and UDCA. The mean levels of ALP, GGT and triglycerides were significantly lower at the end of the combination therapy than those at the end of the monotherapy. The combination therapy with bezafibrate and UDCA significantly improves the laboratory data that specific for PBC in comparison with UDCA monotherapy.

  8. Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis.

    PubMed

    Wang, Li; Han, Qin; Chen, Hua; Wang, Ke; Shan, Guang-liang; Kong, Fang; Yang, Yun-jiao; Li, Yong-zhe; Zhang, Xuan; Dong, Fen; Wang, Qian; Xu, Dong; Hu, Zhao-jun; Wang, Shi-hua; Keating, Armand; Bi, Ya-lan; Zhang, Feng-chun; Zhao, Robert Chun-hua

    2014-10-15

    The objective of this study was to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal stromal/stem cell transplantation (BM-MSCT) for patients with ursodeoxycholic acid (UDCA)-resistant primary biliary cirrhosis (PBC). Ten patients were enrolled in this trial of BM-MSCT. All patients were permitted to concurrently continue their previous UDCA treatment. The efficacy of BM-MSCT in UDCA-resistant PBC was assessed at various time points throughout the 12-month follow up. No transplantation-related side effects were observed. The life quality of the patients was improved after BM-MSCT as demonstrated by responses to the PBC-40 questionnaire. Serum levels of ALT, AST, γ-GT, and IgM significantly decreased from baseline after BM-MSCT. In addition, the percentage of CD8+ T cells was reduced, while that of CD4+CD25+Foxp3+ T cells was increased in peripheral lymphocytic subsets. Serum levels of IL-10 were also elevated. Notably, the optimal therapeutic outcome was acquired in 3 to 6 months and could be maintained for 12 months after BM-MSCT. In conclusion, allogeneic BM-MSCT in UDCA-resistant PBC is safe and appears to be effective.

  9. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies

    PubMed Central

    Kar, SP; Seldin, MF; Chen, W; Lu, E; Hirschfield, GM; Invernizzi, P; Heathcote, J; Cusi, D; Gershwin, ME; Siminovitch, KA; Amos, CI

    2013-01-01

    Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P < 0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR < 0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P = 7.38 × 10−4, FDR = 0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P < 0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P < 0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P < 0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that on further independent replication and functional validation, may provide fresh insights into PBC etiology. PMID:23392275

  10. The Significance of Autoantibody Changes Over Time in Primary Biliary Cirrhosis

    PubMed Central

    Tana, Michele M.; Shums, Zakera; Milo, Jay; Norman, Gary L.; Leung, Patrick S.; Gershwin, M. Eric; Noureddin, Mazen; Kleiner, David E.; Zhao, Xiongce; Heller, Theo; Hoofnagle, Jay H.

    2016-01-01

    Objectives In primary biliary cirrhosis (PBC), the antimitochondrial antibody is a cornerstone of diagnosis, but there have been conflicting reports about the correlation of autoantibodies with disease stage and prognosis. We studied whether autoantibody levels changed over time and sought correlations with clinical outcomes in a cohort of patients with PBC. Methods We tested serial serum samples from patients with PBC at a research institution for several autoantibodies. Long-term clinical follow-up data were used to calculate the slopes (change over time) for autoantibodies, platelet count, Ishak fibrosis score, biopsy copper, and number of portal areas with bile ducts. An adverse clinical outcome was defined as hepatic decompensation, development of hepatocellular carcinoma, liver transplantation, or liver-related death. We performed linear or logistic regression or Fisher exact test as appropriate, adjusting for multiple comparisons. Results Twenty-seven patients with PBC with 145 serum samples were studied. Of the cohort, 85% was white, 81% was female, and median follow-up time was 20 years. Of the autoantibodies tested, only sp100 changed significantly over time. The sp100 slope was inversely associated with the Ishak fibrosis slope (parameter estimate, −0.05; P = .0003). Conclusions While changes in most autoantibodies over time do not seem to correlate with clinical outcomes in PBC, a change in the sp100 autoantibody level may have prognostic utility with respect to the development of fibrosis on liver biopsy. PMID:26386081

  11. Primary Biliary Cirrhosis is Associated With Altered Hepatic microRNA Expression

    PubMed Central

    Padgett, Kerstien A.; Lan, Ruth Y.; Leung, Patrick C.; Lleo, Ana; Dawson, Kevin; Pfeiff, Janice; Mao, Tin K.; Coppel, Ross L.; Ansari, Aftab A.; Gershwin, M. Eric

    2009-01-01

    MicroRNAs (miRNAs) are small RNA molecules that negatively regulate protein coding gene expression and are thought to play a critical role in many biological processes. Aberrant levels of miRNAs have been associated with numerous diseases and cancers, and as such, miRNAs have gain much interests as diagnostic biomarkers, and as therapeutic targets. However, their role in autoimmunity is largely unknown. The aims of this study are to: (1) identify differentially expressed miRNAs in human primary biliary cirrhosis (PBC); (2) validate these independently; and (3) indentify potential targets of differentially expressed miRNAs. We compared the expression of 377 miRNAs in explanted livers form subjects with PBC versus controls with normal liver histology. A total of 35 independent miRNAs were found to be differentially expressed in PBC (p< 0.001). Quantitative PCR was employed to validate down-regulation of microRNA-122a (miR-122a) and miR-26a and the increased expression of miR-328 and miR-299-5p. The predicted targets of these miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress, and metabolism. Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC. PMID:19345069

  12. Environmental pathways to autoimmune diseases: the cases of primary biliary cirrhosis and multiple sclerosis

    PubMed Central

    Selmi, Carlo; Maria Papini, Anna; Pugliese, Piera; Claudia Alcaro, Maria; Gershwin, M. Eric

    2011-01-01

    The pathways leading to autoimmunity remain enigmatic despite numerous lines of experimental inquiry and epidemiological evidence. The mechanisms leading to the initiation and perpetuation of specific diseases such as primary biliary cirrhosis (PBC) or multiple sclerosis (MS) remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. The growing number of genome-wide association studies and the largely incomplete concordance for autoimmune diseases in monozygotic twins concur to support the role of the environment (including infectious agents and chemicals) in the breakdown of tolerance leading to autoimmunity through different mechanisms. In the present article we illustrate the current hypotheses related to an environmental impact on the onset of PBC and MS as two representative conditions investigated with complementary approaches. Indeed, while a role of post-translational antigen modifications has been proposed for MS, this field remain unexplored in PBC where, conversely, most evidence is gathered from geoepidemiology and experimental data on xenobiotics or infectious agents. PMID:22295019

  13. A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis.

    PubMed

    Wang, Lu; Guo, Guan-ya; Wang, Jing-bo; Zhou, Xin-min; Yang, Qiong; Han, Zhe-yi; Li, Qiang; Zhang, Jing-wen; Cai, Yun; Ren, Xiao-li; Zhou, Xia; Chen, Rui-Rui; Shi, Yong-quan; Han, Ying; Fan, Dai-ming

    2015-04-20

    Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA.

  14. Identification of potential cytokine pathways for therapeutic intervention in murine primary biliary cirrhosis.

    PubMed

    Kawata, Kazuhito; Tsuda, Masanobu; Yang, Guo-Xiang; Zhang, Weici; Tanaka, Hajime; Tsuneyama, Koichi; Leung, Patrick; He, Xiao-Song; Knechtle, Stuart; Ansari, Aftab A; Coppel, Ross L; Gershwin, M Eric

    2013-01-01

    Primary biliary cirrhosis (PBC) is considered a model autoimmune disease, with the most highly directed and specific autoantibody in both murine and human autoimmunity, the anti-mitochondrial autoantibody (AMA). However, therapeutic advances in this disease have lagged behind. Herein we have taken advantage of our unique model of murine PBC in which mice immunized with 2-octynoic acid coupled to BSA (2OA-BSA), a compound identified by quantitative structure activity relationships (QSAR) of human AMA binding, develop an intense inflammatory cholangitis with striking similarities to humans with PBC. In particular, we have constructed several unique gene-deleted mice, including mice deleted of IL-12p40, IL-12p35, IFN-γ, IL-23p19, IL-17A, IL-17F and IL-22, immunized these animals with 2OA-BSA and followed the natural history of immunopathology to identify key pathways that might provide clues for successful therapy. Our data indicate that whereas both IL-12/Th1 and IL-23/Th17 are involved in cholangitis, it is the IL-12/Th1 signaling pathway that elicits pathology. In fact, deletion of IFN-γ prevents disease and suppresses autoantibodies. Importantly, deletion of the Th17 cytokines IL-17A and IL-22, but not IL-17F, reduces biliary damage; IL-17A-knockout mice have reduced levels of anti-mitochondrial antibody. We further demonstrate that the production of IFN-γ is significantly decreased in the liver of IL-23p19(-/-), IL-17A(-/-) and IL-22(-/-) mice compared with controls. However, the ability of T cells to produce IFN-γ was not affected in Th17 cytokine-deficient mice. Our data indicate that a deficient Th17 pathway suppresses the accumulation of IFN-γ producing cells in liver during the early phase of cholangitis. In conclusion, whereas IFN-γ has a pivotal role in the early events involved in the pathogenesis of autoimmune cholangitis induced by 2OA-BSA, the IL-23/Th17 pathway potentiates the effects of IL-12/IFN-γ-mediated immunopathology.

  15. Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis.

    PubMed

    Van de Water, J; Gerson, L B; Ferrell, L D; Lake, J R; Coppel, R L; Batts, K P; Wiesner, R H; Gershwin, M E

    1996-11-01

    Whether primary biliary cirrhosis (PBC) recurs after liver transplantation has remained an interesting and controversial issue; rejection, viral hepatitis, and drug effects all may mimic recurrent PBC histologically and biochemically. Furthermore, reliable clinical criteria for PBC recurrence are lacking. In this study, the issue of disease recurrence using a well-characterized monoclonal antibody (MAb), C355.1, that reacts with the immunodominant mitochondrial autoantigen of PBC (pyruvate dehydrogenase complex [PDC-E2]) was addressed. When used in an immunohistochemical assay, C355.1 produces intense apical staining of bile duct epithelium specifically in liver sections of patients with PBC and may be the earliest known marker of PBC. Immunohistochemical and histological analysis of serial liver biopsy specimens of 67 patients pre- and post-orthotopic liver transplantation (OLT), including 38 patients with PBC and 29 non-PBC liver disease controls, was performed. Sections were stained with MAb C355.1 or the control MAb C315 and analyzed to determine whether there was a recurrence of apical reactivity in the bile ducts of the posttransplantation biopsy specimens. The immunohistochemical staining was correlated with the histological findings and serum biochemistries at the time of the biopsy. Our data indicate that a significant number of patients who underwent transplantation for PBC (28 of 38) but not controls (0 of 29) develop a staining pattern of liver bile duct epithelium with MAb C355.1 that is indistinguishable from the pretransplantation pattern. Of the 28 patients with this apical staining pattern, 8 were characterized histologically as possible recurrent PBC, 2 as chronic rejection, 2 as acute rejection, 9 as nonspecific changes, 4 as normal or near normal, and 3 had other histological changes. Only 50% of the patients with apical C355.1 staining had liver enzyme levels suggestive of cholestasis. Thus, there appears to be immunohistochemical evidence that

  16. Phenotyping and auto-antibody production by liver-infiltrating B cells in primary sclerosing cholangitis and primary biliary cholangitis.

    PubMed

    Chung, Brian K; Guevel, Bardia T; Reynolds, Gary M; Gupta Udatha, D B R K; Henriksen, Eva Kristine Klemsdal; Stamataki, Zania; Hirschfield, Gideon M; Karlsen, Tom Hemming; Liaskou, Evaggelia

    2017-02-01

    Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated biliary diseases that demonstrate prominent and restricted genetic association with human leukocyte antigen (HLA) alleles. In PBC, anti-mitochondrial antibodies (AMA) are specific and used as diagnostic biomarkers. PSC-relevant auto-antibodies remain controversial despite a distinct HLA association that mirrors archetypical auto-antigen driven disorders. Herein, we compared antibody-secreting B cells (ASCs) in PSC and PBC liver explants to determine if liver-infiltrating ASCs represent an opportune and novel source of disease-relevant auto-antibodies. Using enzymatic digestion and mechanical disruption, liver mononuclear cells (LIMCs) were isolated from fresh PSC and PBC explants and plasmablast (CD19+CD27+CD38(hi)CD138-) and plasma cell (CD19+CD27+CD38(hi)CD138+) ASCs were enumerated by flow cytometry. We observed 45-fold fewer plasma cells in PSC explants (n = 9) compared to PBC samples (n = 5, p < 0.01) and 10-fold fewer IgA-, IgG- and IgM-positive ASCs (p < 0.05). Liver-infiltrating ASCs from PSC and PBC explants were functional and produced similar concentrations of IgA, IgG and IgM following 2 weeks of culture. Antibody production by PBC ASCs (n = 3) was disease-specific as AMA to pyruvate dehydrogenase complex E2 subunit (PDC-E2) was detected by immunostaining, immunoblotting and ELISA. Antibody profiling of PSC supernatants (n = 9) using full-length recombinant human protein arrays (Cambridge Protein Arrays) revealed reactivities to nucleolar protein 3 (5/9) and hematopoietic cell-specific Lyn substrate 1 (3/9). Array analysis of PBC supernatants (n = 3) detected reactivities to PDC-E2 and hexokinase 1 (3/3). In conclusion, we detected unique frequencies of liver-infiltrating ASCs in PSC and PBC and in so doing, highlight a feasible approach for understanding disease-relevant antibodies in PSC.

  17. Biliary atresia

    PubMed Central

    Chardot, Christophe

    2006-01-01

    Biliary atresia (BA) is a rare disease characterised by a biliary obstruction of unknown origin that presents in the neonatal period. It is the most frequent surgical cause of cholestatic jaundice in this age group. BA occurs in approximately 1/18,000 live births in Western Europe. In the world, the reported incidence varies from 5/100,000 to 32/100,000 live births, and is highest in Asia and the Pacific region. Females are affected slightly more often than males. The common histopathological picture is one of inflammatory damage to the intra- and extrahepatic bile ducts with sclerosis and narrowing or even obliteration of the biliary tree. Untreated, this condition leads to cirrhosis and death within the first years of life. BA is not known to be a hereditary condition. No primary medical treatment is relevant for the management of BA. Once BA suspected, surgical intervention (Kasai portoenterostomy) should be performed as soon as possible as operations performed early in life is more likely to be successful. Liver transplantation may be needed later if the Kasai operation fails to restore the biliary flow or if cirrhotic complications occur. At present, approximately 90% of BA patients survive and the majority have normal quality of life. PMID:16872500

  18. Increased prevalence of primary biliary cirrhosis near Superfund toxic waste sites.

    PubMed

    Ala, Aftab; Stanca, Carmen M; Bu-Ghanim, Moueen; Ahmado, Imad; Branch, Andrea D; Schiano, Thomas D; Odin, Joseph A; Bach, Nancy

    2006-03-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are uncommon liver diseases of unknown etiology. Reported clustering of PBC cases may be due to environmental factors. Individuals with PBC have a high prevalence of thyroid disease and thyroid disease is reportedly more prevalent near Superfund toxic waste sites (SFS). The objective of this study was to examine the prevalence and potential clustering of individuals with PBC and PSC near SFS. De-identified clinical and demographic data were used to determine the observed prevalence for each New York City zip code (n = 174) and borough (n = 5) of patients with PBC (PBC-OLT) or PSC (PSC-OLT) who were listed for liver transplantation. The expected prevalence was calculated using Organ Procurement and Transfer Network (OPTN) and U.S. Census data. Both PBC-OLT patients and patients not listed for liver transplantation (PBC-MSSM) were included in the cluster analysis. Prevalence ratios of PBC-OLT and PSC-OLT cases were compared for each zip code and for each borough with regard to the proximity or density of SFS, respectively. SaTScan software was used to identify clusters of PBC-OLT cases and PBC-MSSM cases. Prevalence ratio of PBC-OLT, not PSC-OLT, was significantly higher in zip codes containing or adjacent to SFS (1.225 vs. 0.670, respectively, P = .025). The borough of Staten Island had the highest prevalence ratio of PBC-OLT cases and density of SFS. Significant clusters of both PBC-OLT and PBC-MSSM were identified surrounding SFS. In conclusion, toxin exposure may be a risk factor influencing the clustering of PBC cases.

  19. Dysregulation of peritoneal cavity B1a cells and murine primary biliary cholangitis

    PubMed Central

    Yang, Yan-Qing; Yang, Wei; Yao, Yuan; Ma, Hong-Di; Wang, Yin-Hu; Li, Liang; Wu, Qingfa; Gershwin, M. Eric; Lian, Zhe-Xiong

    2016-01-01

    Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease with progressive cholestasis and liver fibrosis. Similar to human patients with PBC, p40−/−IL-2Rα−/− mice spontaneously develop severe autoimmune cholangitis. Although there has been considerable work on immune regulation and autoimmunity, there is a relative paucity of work directed at the functional implications of the key peritoneal cavity (PC) B cell subset, coined B1a cells in PBC. We used flow cytometry and high-resolution microarrays to study the qualitative and quantitative characteristics of B cells, particularly B1a cells, in the PC of p40−/−IL-2Rα−/− mice compared to controls. Importantly, B1a cell proliferation was markedly lower as the expression of Ki67 decreased. Meanwhile, the apoptosis level was much higher. These lead to a reduction of B1a cells in the PC of p40−/−IL-2Rα−/− mice compared to controls. In contrast, there was a dramatic increase of CD4+ and CD8+ T cells accompanied by elevated production of IFN-γ. In addition, we found a negative correlation between the frequency of B1a cells and the presence of autoreactive CD8+ T cells in both liver and PC of p40−/−IL-2Rα−/− mice. From a functional perspective, B cells from p40−/−IL-2Rα−/− mice downregulated IL-10 production and CTLA-4 expression, leading to loss of B cell regulatory function. We suggest that the dysfunction of B1a cells in the PC in this murine model of autoimmune cholangitis results in defective regulatory function. This highlights a new potential therapeutic target in PBC. PMID:27105495

  20. Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort

    PubMed Central

    Almasio, Piero Luigi; Licata, Anna; Maida, Marcello; Macaluso, Fabio Salvatore; Costantino, Andrea; Alessi, Nicola; Grimaudo, Stefania; Accardi, Giulia; Caruso, Calogero; Craxi, Antonio

    2016-01-01

    Background Natural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans. Objectives We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy. Methods Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All subjects were treated with Ursodeoxycholic acid at a dose of 15 mg/kg. HLA class II DRB1 alleles were compared with those of 237 healthy control subjects. IL28B genotyping for IL28B rs12979860 C/T and rs80899917 G/T was performed in a sub-group of patients. Results HLA-DRB1*07 (RR 5.3, P = 0.0008) and HLA-DRB1*08 (RR n.c. P = 0.0005) were significantly associated with the risk of PBC development. Patients younger than 45 years had significantly higher alanine aminotransferase (P = 0.038) and alkaline phosphatase levels (P = 0.047) than older cases. In comparison to non-CC rs12979860, patients with CC rs12979860 genotype showed an early histological stage at onset (93.8% vs. 62.5%, P = 0.03). After a mean follow-up of 61 months, three patients died, one underwent liver transplantation and sixteen (21.9%) had progression of the disease. At multivariate analysis, extrahepatic autoimmune disease (P = 0.04), pruritus (P = 0.008) and advanced histological stage (P < 0.0001) were independent risk factors for disease progression. Conclusions HLA-DRB1*07 and HLA-DRB1*08 alleles increase susceptibility to disease development. At onset, higher biochemical activity was observed in younger patients, whereas rs12979860 CC genotype was associated with milder histological stage. Pruritus and coexistence of extrahepatic autoimmune diseases were significantly associated with poorer prognosis. PMID:28070198

  1. Biliary Intraepithelial Neoplasia (BilIN) in Primary Sclerosing Cholangitis: The First Report from Iran

    PubMed Central

    Akbarzadeh, Laleh; Geramizadeh, Bita; Kazemi, Kurosh; Nikeghbalian, Saman; Malekhosseini, Seyedali

    2016-01-01

    Background Primary sclerosing cholangitis (PSC) as one of the most common chronic cholestatic liver diseases is a main predisposing factor for the development of cholangiocarcinoma (CCA). Biliary intraepithelial neoplasia (BilIN) is defined as precancerous bile duct epithelial changes, which can be eventually led to cholangiocarcinoma. There are very few studies about the frequency of BilIN in the patients with PSC and its correlation with paraclinical findings. Objectives In this study, we tried to find the frequency of BilIN in the patients with PSC and correlate its presence with clinicopathologic factors. Methods During two years (2014 - 15) of investigation, 80 explanted livers with the confirmed diagnosis of PSC were studied through precise inspection and thorough sectioning of the explanted livers. These findings were correlated with paraclinical findings to identify any predictor of these neoplastic epithelial changes. Results During the study period of 2 years, among 80 livers with confirmed diagnosis of PSC, there were 43 cases with different types of metaplasia. The frequency of epithelial changes was as below: 29 (35%) for pyloric metaplasia, 9 (10.8%) for mucinous metaplasia, 3 (3.6%) for intestinal metaplasia, 1 (1.2%) for osteoid metaplasia, and 1 (1.2%) for squamous metaplasia. There was no epithelial dysplasia in the study sample; however, according to the most recent reports, mucinous metaplasia is considered as BilIN 1; therefore, there would be 9 cases of BilIN I. There has been no statistically significant difference between PSC cases and those with BilIN in demographic variables, except for bilirubin and CA19-9 which were higher in the PSC cases with BilIN. Conclusions This study showed that the frequency of BilIN was low among Iranian patients with PSC. High bilirubin and CA19-9 can be predictors of the development of bile duct epithelial changes in patients with PSC. PMID:28123440

  2. Interleukin-33 promotes disease progression in patients with primary biliary cirrhosis.

    PubMed

    Sun, Yongqiang; Zhang, Ji-Yuan; Lv, Sa; Wang, Huan; Gong, Man; Du, Ning; Liu, Honghong; Zhang, Ning; Jing, Jing; Zhou, Chao; Zhang, Fan; Wang, Zongren

    2014-01-01

    Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Interleukin-33 (IL-33) is expressed in various non-hematopoietic cells and a certain population of immune cells, and exerts its biological effects by binding to the specific receptor, suppression of tumorigenicity 2 (ST2). A soluble form of ST2 (sST2) has been postulated to act as a decoy receptor for IL-33. In this study, we aimed to investigate the role of IL-33 in the pathogenesis of PBC. The study included 20 healthy controls and 68 patients with PBC. We thus found the increased serum IL-33 levels in PBC patients. Its elevated levels were positively correlated with serum alkaline phosphatase levels (a key parameter for the definition of PBC) and with Child-Pugh scores, which were used to determine the prognosis of liver cirrhosis. Moreover, the serum concentrations of sST2 were significantly higher in PBC patients compared with healthy subjects, irrespective of the disease severity. Importantly, the cells that express IL-33 and/or myeloperoxidase (a marker for neutrophils) were accumulated in the livers of PBC patients, and their number increased with the severity of liver lesions. Lastly, in vitro chemotaxis assays revealed that IL-33 enhanced the migration of neutrophils. These data suggest that IL-33 may affect the progress of PBC by recruiting neutrophils to the liver. This expanded knowledge of IL-33 in PBC patients is important for developing therapeutic strategies (e.g., neutralization of IL-33), selecting optimal clinical management, and predicting prognosis.

  3. Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models.

    PubMed Central

    Jalan, R; Sargentoni, J; Coutts, G A; Bell, J D; Rolles, K; Burroughs, A K; Taylor Robinson, S D

    1996-01-01

    BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) provides biochemical information about phosphorus metabolism. AIM: To assess 31P MRS as a prognostic marker in patients with primary biliary cirrhosis (PBC) in relation to the current clinical prognostic models. PATIENTS AND METHODS: Twenty three patients with PBC of varying functional severity and 16 matched healthy volunteers were studied using in vivo 31P MRS. Spectra were acquired using a 1.5 T spectroscopy system. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) and nucleotide triphosphate (NTP) were calculated. Pugh score, Christensen prognostic index, and R value according to the Mayo model were calculated from the clinical data. RESULTS: The PME/NTP, Pi/NTP, PME/PDE, and PME/Pi ratios and the PME signal height ratio (SHR) were significantly higher, while the PDE/NTP and PDE/SHR were significantly lower in PBC patients compared with healthy volunteers (p < 0.01). Significant correlations were seen between PME/Pi ratio and the prognostic index according to Christensen (r = 0.63, p < 0.001), R value according to the Mayo model (r = 0.45, p < 0.03), and with the Pugh score (r = 0.55, p < 0.007). CONCLUSIONS: This study shows that PME/Pi ratio obtained from 31P MRS correlates well with all three of the commonly used models of prognosis in patients with PBC. A longitudinal study with larger number of patients is required to confirm these findings and elucidate the biochemical changes underlying this phenomenon. PMID:8881826

  4. Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis

    PubMed Central

    Yang, Jun; Yu, Ya-Li; Jin, Yu; Zhang, Ying; Zheng, Chang-Qing

    2016-01-01

    AIM To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type). RESULTS There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes (except ALB), immunological indexes, positive rates of autoantibodies (except SMA), and number of cases of patients with different ANA titers (except the group at a titer of 1:10000) significantly differed between DILI patients and PBC patients. Biochemical indexes, immunological indexes, and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes (n = 30), inflammatory cell infiltration around bile ducts (n = 29), and atypical hyperplasia of small bile ducts (n = 28). DILI manifested mainly as fatty degeneration of hepatocytes (n = 15) and spotty necrosis or loss of hepatocytes (n = 14). CONCLUSION Although DILI and PBC share some similar laboratory tests (biochemical and immunological indexes) and pathological findings, they also show some distinct characteristics, which are helpful to the differential diagnosis of the two diseases. PMID:27672278

  5. Serum cell death biomarkers for prediction of liver fibrosis and poor prognosis in primary biliary cirrhosis.

    PubMed

    Sekiguchi, Tomohiro; Umemura, Takeji; Fujimori, Naoyuki; Shibata, Soichiro; Ichikawa, Yuki; Kimura, Takefumi; Joshita, Satoru; Komatsu, Michiharu; Matsumoto, Akihiro; Tanaka, Eiji; Ota, Masao

    2015-01-01

    The development of simple, noninvasive markers of liver fibrosis is urgently needed for primary biliary cirrhosis (PBC). This study examined the ability of several serum biomarkers of cell death to estimate fibrosis and prognosis in PBC. A cohort of 130 patients with biopsy-proven PBC and 90 healthy subjects were enrolled. We assessed the utility of the M30 ELISA, which detects caspase-cleaved cytokeratin-18 (CK-18) fragments and is representative of apoptotic cell death, as well as the M65 and newly developed M65 Epideath (M65ED) ELISAs, which detect total CK-18 as indicators of overall cell death, in predicting clinically relevant fibrosis stage. All 3 cell death biomarkers were significantly higher in patients with PBC than in healthy controls and were significantly correlated with fibrosis stage. The areas under the receiver operating characteristic curve for the M65 and M65ED assays for differentiation among significant fibrosis, severe fibrosis, and cirrhosis were 0.66 and 0.76, 0.66 and 0.73, and 0.74 and 0.82, respectively. In multivariate analysis, high M65ED (hazard ratio 6.13; 95% confidence interval 1.18-31.69; P = 0.031) and severe fibrosis (hazard ratio 7.45; 95% confidence interval 1.82-30.51; P = 0.005) were independently associated with liver-related death, transplantation, or decompensation. High serum M65ED was also significantly associated with poor outcome in PBC (log-rank test; P = 0.001). Noninvasive cell death biomarkers appear to be clinically useful in predicting fibrosis in PBC. Moreover, the M65ED assay may represent a new surrogate marker of adverse disease outcome.

  6. Trichloroethylene exposure reduces liver injury in a mouse model of primary biliary cholangitis.

    PubMed

    Ray, Jessica L; Kopec, Anna K; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H; Williams, Kurt J; Leung, Patrick S; Gershwin, M Eric; Luyendyk, James P

    2017-01-23

    Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL(+/+) mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model.

  7. Multiple genetic variants associated with primary biliary cirrhosis in a Han Chinese population.

    PubMed

    Dong, Ming; Li, Jinxin; Tang, Ruqi; Zhu, Ping; Qiu, Fang; Wang, Chan; Qiu, Jie; Wang, Lan; Dai, Yaping; Xu, Ping; Gao, Yueqiu; Han, Chongxu; Wang, Yongzhong; Wu, Jian; Wu, Xudong; Zhang, Kui; Dai, Na; Sun, Weihao; Zhou, Jianpo; Hu, Zhigang; Liu, Lei; Jiang, Yuzhang; Nie, Jinshan; Zhao, Yi; Gong, Yuhua; Tian, Ye; Ji, Hualiang; Jiao, Zhijun; Jiang, Po; Shi, Xingjuan; Jawed, Rohil; Zhang, Yu; Huang, Qinghai; Li, Enling; Wei, Yiran; Xie, Wei; Zhao, Weifeng; Liu, Xiang; Zhu, Xiang; Qiu, Hong; He, Gengsheng; Chen, Weichang; Seldin, Michael F; Gershwin, M Eric; Liu, Xiangdong; Ma, Xiong

    2015-06-01

    Multiple genome-wide association studies of primary biliary cirrhosis (PBC) in both European and Japanese ancestries have shown significant associations of many genetic loci contributing to the susceptibility to PBC. Major differences in susceptibility loci between these two population groups were observed. In this study, we examined whether the most significant loci observed in either European and/or Japanese cohorts are associated with PBC in a Han Chinese population. In 1070 PBC patients and 1198 controls, we observed highly significant associations at CD80 (rs2293370, P = 2.67 × 10(-8)) and TNFSF15 (rs4979462, P = 3.86 × 10(-8)) and significant associations at 17q12-21 (rs9303277), PDGFB (rs715505), NF-κB1 (rs7665090), IL12RB2 (rs11209050), and STAT4 (rs7574865; all corrected P values <0.01). However, no association was observed for POU2AF1 (rs4938534), IL12A (rs485499 and rs2366408), IL7R (rs6897932), CXCR5 (rs715412), SOCS1 (rs725613), and TNFRSF1A (rs1800693). STAT4 (rs7574865) was strongly associated after additional control samples were analyzed. Our study is the first large-scale genetic analysis in a Han Chinese PBC cohort. These results do not only reflect that Han Chinese PBC patients share common genetic susceptibility genes with both their Japanese and European counterparts but also suggest a distinctly different genetic susceptibility profile.

  8. Rheumatic disorders and primary biliary cirrhosis: an appraisal of 170 Italian patients

    PubMed Central

    Marasini, B; Gagetta, M; Rossi, V; Ferrari, P

    2001-01-01

    OBJECTIVE—To establish the frequency of connective tissue diseases (CTD) in a cohort of Italian patients with primary biliary cirrhosis (PBC) and to evaluate the availability of a marker for the early identification of the more common associated CTD.
METHODS—One hundred and seventy consecutive patients with histologically diagnosed PBC were screened for the presence of a CTD and/or Raynaud's phenomenon (RP). Patients were classified as having a CTD only if they fulfilled standardised criteria.
RESULTS—Forty seven patients had a CTD. The most common CTD was systemic sclerosis (SSc), found in 21 patients. RP was present in 54 patients, most of whom (n=39) had an associated CTD. The most prevalent autoantibodies included antinuclear antibodies (ANA) with anticentromere (ACA) and speckled patterns (34 and 33 patients, respectively) and extractable nuclear antigens (ENA, 27 patients). However, while the frequencies of ACA and ENA were significantly higher in patients with an associated CTD (p<0.0001 and p<0.005, respectively), no relationship was found for speckled ANA. ACA was the best predictor of a CTD in patients with PBC (odds ratio (OR) 24.5, 95% CI 5.5 to 108.8), followed by the presence of ENA (OR 23.9, 95% CI 5.6 to 101.0) and RP (OR 20.2, 95% CI 5.7 to 71.2).
CONCLUSIONS—Using strict standardised classification criteria we have found that SSc is the most common CTD associated with PBC and that ACA and ENA are strong markers for an associated CTD in patients with PBC.

 PMID:11602476

  9. Primary biliary cirrhosis an epithelitis: evidence of abnormal salivary gland immunohistochemistry.

    PubMed

    Tsuneyama, K; Van De Water, J; Yamazaki, K; Suzuki, K; Sato, S; Takeda, Y; Ruebner, B; Yost, B A; Nakanuma, Y; Coppel, R L; Gershwin, M E

    1997-01-01

    Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology. Nearly 93% of patients with PBC exhibit evidence of focal sialoadenitis. In an earlier study, we reported evidence of aberrant expression of PDC-E2, or a mimeotope, in the salivary glands of patients with PBC that had Sjogren's syndrome. At the time of the previous study, data was not yet available regarding patients with PBC without sicca complaints. Therefore, to investigate the extent of salivary gland involvement in PBC, we collected lip biopsy sections from 9 PBC patients diagnosed as PBC by liver biopsy, without clinical or histologic features of Sjogren's syndrome and 9 PBC patients with established Sjogren's syndrome. Using immunohistochemical staining with both a murine monoclonal antibody. C355.1, and a human combinatorial antibody, SP4, we examined the ducts of these salivary glands for the presence of the characteristic aberrant staining pattern found in patients with PBC. We report that 6/9 PBC patients fulfilling established Sjogren's syndrome criteria and 6/9 PBC patients lacking features of Sjogren's syndrome showed intense staining of the ductal epithelial cells of the salivary gland. These data suggest that the PBC-specific antigen recognized by C355.1 and SP4 in bile duct epithelial cells is expressed aberrantly in the salivary gland in 66% of patients with PBC, independent of Sjogren's syndrome. This finding suggests a common disease process in these two tissues. Further, expression of this molecule may be an early marker of salivary gland involvement in patients with PBC.

  10. Therapy of Primary Biliary Cirrhosis: Novel Approaches for Patients with Suboptimal Response to Ursodeoxycholic Acid.

    PubMed

    Parés, Albert

    2015-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of presumed autoimmune pathogenesis, characterized by the inflammation and damage of the intrahepatic intermediate and small bile ducts, which eventually results in cirrhosis. A number of randomized and observational and pilot studies using several agents were carried out in the 80s, but no clear results or even harmful effects were reported. Over the past 2 decades, increasing evidence indicates that ursodeoxycholic acid (UDCA) - 13 to 16 mg/kg/day--is the treatment of choice for patients with PBC. Biochemical response to UDCA, assessed at 1 year, clearly predicts the long-term outcome, since in UDCA, responders survival is similar to that estimated for the matched control population. However, about 40% of patients have incomplete biochemical response and increased risk of progression and decreased survival free of transplantation. Patients with suboptimal biochemical response to UDCA outline the group in whom further single or combined treatments with UDCA are needed. Accordingly, data on the effect of fibrates alone or in combination with UDCA, and budesonide in combination with UDCA have been reported. The combined treatment of UDCA and fibrates in patients without optimal biochemical response to UDCA improves the degree of cholestasis and may minimize the long-term management of these patients. The results of the combined therapy of UDCA with budesonide are appealing but they should be established in large randomized trials. The effect of new agents such obeticholic acid are promising, since the addition of this farnesoide-X-receptor agonist bile acid in patients with stable UDCA dosage and increased alkaline phosphatase levels results in an improvement of cholestasis as compared to placebo, with a parallel decrease of aminotransferases and immunoglobulin M, as well as one surrogate marker of bile acid synthesis. New molecular therapies are currently being investigated.

  11. Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.

    PubMed

    Combes, Burton; Emerson, Scott S; Flye, Nancy L; Munoz, Santiago J; Luketic, Velimir A; Mayo, Marlyn J; McCashland, Timothy M; Zetterman, Rowen K; Peters, Marion G; Di Bisceglie, Adrian M; Benner, Kent G; Kowdley, Kris V; Carithers, Robert L; Rosoff, Leonard; Garcia-Tsao, Guadalupe; Boyer, James L; Boyer, Thomas D; Martinez, Enrique J; Bass, Nathan M; Lake, John R; Barnes, David S; Bonacini, Maurizio; Lindsay, Karen L; Mills, A Scott; Markin, Rodney S; Rubin, Raphael; West, A Brian; Wheeler, Donald E; Contos, Melissa J; Hofmann, Alan F

    2005-11-01

    This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.

  12. The fingerprint of antimitochondrial antibodies and the etiology of primary biliary cholangitis.

    PubMed

    Shuai, Zongwen; Wang, Jinjun; Badamagunta, Madhu; Choi, Jinjung; Yang, Guoxiang; Zhang, Weici; Kenny, Thomas P; Guggenheim, Kathryn; Kurth, Mark J; Ansari, Aftab A; Voss, John; Coppel, Ross L; Invernizzi, Pietro; Leung, Patrick S C; Gershwin, M Eric

    2017-01-18

    The identification of environmental factors that lead to loss of tolerance has been coined the holy grail of autoimmunity. Our work has focused on the reactivity of antimitochondrial autoantibodies (AMA) to chemical xenobiotics and has hypothesized that a modified peptide within PDC-E2, the major mitochondrial autoantigen, will have been immunologically recognized at the time of loss of tolerance. Herein, we successfully applied intein technology to construct a PDC-E2 protein fragment containing amino acid residues 177-314 of PDC-E2 by joining a recombinant peptide spanning residues 177-252 (PDC-228) with a 62-residue synthetic peptide from 253 to 314 (PP), which encompasses PDC-E2 inner lipoyl domain (ILD). We named this intein-constructed fragment PPL. Importantly, PPL, as well as lipoic acid conjugated PPL (LA-PPL) and xenobiotic 2-octynoic acid conjugated PPL (2OA-PPL), are recognized by AMA. Of great importance, AMA has specificity for the 2OA-modified PDC-E2 ILD peptide backbone distinct from antibodies that react with native lipoylated PDC-E2 peptide. Interestingly, this unique AMA subfraction is of the immunoglobulin M isotype and more dominant in early-stage primary biliary cholangitis (PBC), suggesting that exposure to 2OA-PPL-like compounds occurs early in the generation of AMA. To understand the structural basis of this differential recognition, we analyzed PPL, LA-PPL, and 2OA-PPL using electron paramagnetic resonance spectroscopy, with confirmations by enzyme-linked immunosorbent assay, immunoblotting, and affinity antibody analysis. We demonstrate that the conformation of PDC-E2 ILD is altered when conjugated with 2OA, compared to conjugation with lipoic acid.

  13. Deletion of Galectin-3 Enhances Xenobiotic Induced Murine Primary Biliary Cholangitis by Facilitating Apoptosis of BECs and Release of Autoantigens.

    PubMed

    Arsenijevic, Aleksandar; Milovanovic, Marija; Milovanovic, Jelena; Stojanovic, Bojana; Zdravkovic, Natasa; Leung, Patrick S C; Liu, Fu-Tong; Gershwin, M Eric; Lukic, Miodrag L

    2016-03-21

    Galectin-3 (Gal-3) is a carbohydrate binding lectin, with multiple roles in inflammatory diseases and autoimmunity including its antiapoptotic effect on epithelial cells. In particular, increased expression of Gal-3 in epithelial cells is protective from apoptosis. Based on the thesis that apoptosis of biliary epithelial cells (BECs) is critical to the pathogenesis of Primary Biliary Cholangitis (PBC), we have analyzed the role of Gal-3 in the murine model of autoimmune cholangitis. We took advantage of Gal-3 knockout mice and immunized them with a mimotope of the major mitochondrial autoantigen of PBC, 2-octynoic acid (2-OA) coupled to BSA (2OA-BSA) and evaluated the natural history of subsequent disease, compared to control wild-type mice, by measuring levels of antibodies to PDC-E2, immunohistology of liver, and expression of Gal-3. We report herein that deletion of Gal-3 significantly exacerbates autoimmune cholangitis in these mice. This is manifested by increased periportal infiltrations, bile duct damage, granulomas and fibrosis. Interestingly, the BECs of Gal-3 knockout mice had a higher response to apoptotic stimuli and there were more pro-inflammatory lymphocytes and dendritic cells (DCs) in the livers of Gal-3 knockout mice. In conclusion, Gal-3 plays a protective role in the pathways that lead to the inflammatory destruction of biliary epithelial cells.

  14. Deletion of Galectin-3 Enhances Xenobiotic Induced Murine Primary Biliary Cholangitis by Facilitating Apoptosis of BECs and Release of Autoantigens

    PubMed Central

    Arsenijevic, Aleksandar; Milovanovic, Marija; Milovanovic, Jelena; Stojanovic, Bojana; Zdravkovic, Natasa; Leung, Patrick S.C.; Liu, Fu-Tong; Gershwin, M. Eric; Lukic, Miodrag L.

    2016-01-01

    Galectin-3 (Gal-3) is a carbohydrate binding lectin, with multiple roles in inflammatory diseases and autoimmunity including its antiapoptotic effect on epithelial cells. In particular, increased expression of Gal-3 in epithelial cells is protective from apoptosis. Based on the thesis that apoptosis of biliary epithelial cells (BECs) is critical to the pathogenesis of Primary Biliary Cholangitis (PBC), we have analyzed the role of Gal-3 in the murine model of autoimmune cholangitis. We took advantage of Gal-3 knockout mice and immunized them with a mimotope of the major mitochondrial autoantigen of PBC, 2-octynoic acid (2-OA) coupled to BSA (2OA-BSA) and evaluated the natural history of subsequent disease, compared to control wild-type mice, by measuring levels of antibodies to PDC-E2, immunohistology of liver, and expression of Gal-3. We report herein that deletion of Gal-3 significantly exacerbates autoimmune cholangitis in these mice. This is manifested by increased periportal infiltrations, bile duct damage, granulomas and fibrosis. Interestingly, the BECs of Gal-3 knockout mice had a higher response to apoptotic stimuli and there were more pro-inflammatory lymphocytes and dendritic cells (DCs) in the livers of Gal-3 knockout mice. In conclusion, Gal-3 plays a protective role in the pathways that lead to the inflammatory destruction of biliary epithelial cells. PMID:26996208

  15. Innumerable Liver Masses in a Patient with Autoimmune Hepatitis and Primary Sclerosing Cholangitis Overlap Syndrome

    PubMed Central

    Gharibpoor, Alireza; Mansour-Ghanaei, Fariborz; Sadeghi, Mahbobe; Gharibpoor, Faeze; Joukar, Farahnaz; Mavaddati, Sara

    2017-01-01

    Patient: Male, 26 Final Diagnosis: AIH-PSC overlap syndrome Symptoms: Palpable liver more than 5 cm below the costal margin and both firm and nodular • 8-kg weight loss during the last 2 months • clay-colored stool • dark urine • general fatigue • generalized icterus • light abdominal tenderness in the right upper quadrant with isolated hepatomegaly • loss of appetite • neither spider angioma nor stigmata • no clinical evidence of ascites or lymphadenopathy • non-specific abdominal discomfort • normoactive bowel sound • pruritus Medication: — Clinical Procedure: Lab tests • MRCP • Pathological analysis Specialty: Gastroenterology and Hepatology Objective: Challenging differential diagnosis Background: In patients with the diagnosis of autoimmune hepatitis (AIH), the presence of cholestatic features raise the possibility of an overlap syndrome with primary sclerosing cholangitis (PSC). Here, we present a unique case with AIH-PSC overlap syndrome and innumerable liver masses. Case Report: A 26-year-old man presented with generalized icterus. Based on the serological findings of hypergamainmunoglobulinemia and positive anti-nuclear antibody tests, together with an abnormal cholangiogram, he was diagnosed with overlap syndrome (AIH-PSC). Liver imaging revealed innumerable liver masses with a benign appearance in the pathological evaluation. To rule out the colon abnormalities that usually coexist with such liver masses, colonoscopy was performed and showed no significant changes. The liver masses were nonmalignant and were resolved after immunosuppressant therapy. Conclusions: Because AIH-PSC overlap syndrome is rare, it is suggested that radiological evaluation of the biliary tree should be performed routinely in adults diagnosed with AIH to reduce the missed diagnosis of overlap syndrome and liver masses. PMID:28167813

  16. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family.

  17. 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.

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

    PubMed Central

    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; Schlicht, Erik M; Lammert, Craig; Atkinson, Elizabeth J; Chan, Landon L; de Andrade, Mariza; Balschun, Tobias; Mason, Andrew L; Myers, Robert P; Zhang, Jinyi; Milkiewicz, Piotr; Qu, Jia; Odin, Joseph A; Luketic, Velimir A; Bacon, Bruce R; Bodenheimer Jr, Henry C; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Gregersen, Peter K; Almasio, Piero L; Alvaro, Domenico; Andreone, Pietro; Andriulli, Angelo; Barlassina, Cristina; Battezzati, Pier Maria; Benedetti, Antonio; Bernuzzi, Francesca; Bianchi, Ilaria; Bragazzi, Maria Consiglia; Brunetto, Maurizia; Bruno, Savino; Casella, Giovanni; Coco, Barbara; Colli, Agostino; Colombo, Massimo; Colombo, Silvia; Cursaro, Carmela; Crocè, Lory Saveria; Crosignani, Andrea; Donato, Maria Francesca; Elia, Gianfranco; Fabris, Luca; Ferrari, Carlo; Floreani, Annarosa; Foglieni, Barbara; Fontana, Rosanna; Galli, Andrea; Lazzari, Roberta; Macaluso, Fabio; Malinverno, Federica; Marra, Fabio; Marzioni, Marco; Mattalia, Alberto; Montanari, Renzo; Morini, Lorenzo; Morisco, Filomena; Hani S, Mousa; Muratori, Luigi; Muratori, Paolo; Niro, Grazia A; Palmieri, Vincenzo O; Picciotto, Antonio; Podda, Mauro; Portincasa, Piero; Ronca, Vincenzo; Rosina, Floriano; Rossi, Sonia; Sogno, Ilaria; Spinzi, Giancarlo; Spreafico, Marta; Strazzabosco, Mario; Tarallo, Sonia; Tarocchi, Mirko; Tiribelli, Claudio; Toniutto, Pierluigi; Vinci, Maria; Zuin, Massimo; Ch'ng, Chin Lye; Rahman, Mesbah; Yapp, Tom; Sturgess, Richard; Healey, Christopher; Czajkowski, Marek; Gunasekera, Anton; Gyawali, Pranab; Premchand, Purushothaman; Kapur, Kapil; Marley, Richard; Foster, Graham; Watson, Alan; Dias, Aruna; Subhani, Javaid; Harvey, Rory; McCorry, Roger; Ramanaden, David; Gasem, Jaber; Evans, Richard; Mathialahan, Thiriloganathan; Shorrock, Christopher; Lipscomb, George; Southern, Paul; Tibble, Jeremy; Gorard, David; Palegwala, Altaf; Jones, Susan; Carbone, Marco; Dawwas, Mohamed; Alexander, Graeme; Dolwani, Sunil; Prince, Martin; Foxton, Matthew; Elphick, David; Mitchison, Harriet; Gooding, Ian; Karmo, Mazn; Saksena, Sushma; Mendall, Mike; Patel, Minesh; Ede, Roland; Austin, Andrew; Sayer, Joanna; Hankey, Lorraine; Hovell, Christopher; Fisher, Neil; Carter, Martyn; Koss, Konrad; Piotrowicz, Andrzej; Grimley, Charles; Neal, David; Lim, Guan; Levi, Sass; Ala, Aftab; Broad, Andrea; Saeed, Athar; Wood, Gordon; Brown, Jonathan; Wilkinson, Mark; Gordon, Harriet; Ramage, John; Ridpath, Jo; Ngatchu, Theodore; Grover, Bob; Shaukat, Syed; Shidrawi, Ray; Abouda, George; Ali, Faiz; Rees, Ian; Salam, Imroz; Narain, Mark; Brown, Ashley; Taylor-Robinson, Simon; Williams, Simon; Grellier, Leonie; Banim, Paul; Das, Debashis; Chilton, Andrew; Heneghan, Michael; Curtis, Howard; Gess, Markus; Drake, Ian; Aldersley, Mark; Davies, Mervyn; Jones, Rebecca; McNair, Alastair; Srirajaskanthan, Raj; Pitcher, Maxton; Sen, Sambit; Bird, George; Barnardo, Adrian; Kitchen, Paul; Yoong, Kevin; Chirag, Oza; Sivaramakrishnan, Nurani; MacFaul, George; Jones, David; Shah, Amir; Evans, Chris; Saha, Subrata; Pollock, Katharine; Bramley, Peter; Mukhopadhya, Ashis; Fraser, Andrew; Mills, Peter; Shallcross, Christopher; Campbell, Stewart; Bathgate, Andrew; Shepherd, Alan; Dillon, John; Rushbrook, Simon; Przemioslo, Robert; Macdonald, Christopher; Metcalf, Jane; Shmueli, Udi; Davis, Andrew; Naqvi, Asifabbas; Lee, Tom; Ryder, Stephen D; Collier, Jane; Klass, Howard; Ninkovic, Mary; Cramp, Matthew; Sharer, Nicholas; Aspinall, Richard; Goggin, Patrick; Ghosh, Deb; Douds, Andrew; Hoeroldt, Barbara; Booth, Jonathan; Williams, Earl; Hussaini, Hyder; Stableforth, William; Ayres, Reuben; Thorburn, Douglas; Marshall, Eileen; Burroughs, Andrew; Mann, Steven; Lombard, Martin; Richardson, Paul; Patanwala, Imran; Maltby, Julia; Brookes, Matthew; Mathew, Ray; Vyas, Samir; Singhal, Saket; Gleeson, Dermot; Misra, Sharat; Butterworth, Jeff; George, Keith; Harding, Tim; Douglass, Andrew; Panter, Simon; Shearman, Jeremy; Bray, Gary; Butcher, Graham; Forton, Daniel; Mclindon, John; Cowan, Matthew; Whatley, Gregory; Mandal, Aditya; Gupta, Hemant; Sanghi, Pradeep; Jain, Sanjiv; Pereira, Steve; Prasad, Geeta; Watts, Gill; Wright, Mark; Neuberger, James; Gordon, Fiona; Unitt, Esther; Grant, Allister; Delahooke, Toby; Higham, Andrew; Brind, Alison; Cox, Mark; Ramakrishnan, Subramaniam; King, Alistair; Collins, Carole; Whalley, Simon; Li, Andy; Fraser, Jocelyn; Bell, Andrew; Wong, Voi Shim; Singhal, Amit; Gee, Ian; Ang, Yeng; Ransford, Rupert; Gotto, James; Millson, Charles; Bowles, Jane; Thomas, Caradog; Harrison, Melanie; Galaska, Roman; Kendall, Jennie; Whiteman, Jessica; Lawlor, Caroline; Gray, Catherine; Elliott, Keith; Mulvaney-Jones, Caroline; Hobson, Lucie; Van Duyvenvoorde, Greta; Loftus, Alison; Seward, Katie; Penn, Ruth; Maiden, Jane; Damant, Rose; Hails, Janeane; Cloudsdale, Rebecca; Silvestre, Valeria; Glenn, Sue; Dungca, Eleanor; Wheatley, Natalie; Doyle, Helen; Kent, Melanie; Hamilton, Caroline; Braim, Delyth; Wooldridge, Helen; Abrahams, Rachel; Paton, Alison; Lancaster, Nicola; Gibbins, Andrew; Hogben, Karen; Desousa, Phillipa; Muscariu, Florin; Musselwhite, Janine; McKay, Alexandra; Tan, LaiTing; Foale, Carole; Brighton, Jacqueline; Flahive, Kerry; Nambela, Estelle; Townshend, Paula; Ford, Chris; Holder, Sophie; Palmer, Caroline; Featherstone, James; Nasseri, Mariam; Sadeghian, Joy; Williams, Bronwen; Thomas, Carol; Rolls, Sally-Ann; Hynes, Abigail; Duggan, Claire; Jones, Sarah; Crossey, Mary; Stansfield, Glynis; MacNicol, Carolyn; Wilkins, Joy; Wilhelmsen, Elva; Raymode, Parizade; Lee, Hye-Jeong; Durant, Emma; Bishop, Rebecca; Ncube, Noma; Tripoli, Sherill; Casey, Rebecca; Cowley, Caroline; Miller, Richard; Houghton, Kathryn; Ducker, Samantha; Wright, Fiona; Bird, Bridget; Baxter, Gwen; Keggans, Janie; Hughes, Maggie; Grieve, Emma; Young, Karin; Williams, D; Ocker, Kate; Hines, Frances; Martin, Kirsty; Innes, Caron; Valliani, Talal; Fairlamb, Helen; Thornthwaite, Sarah; Eastick, Anne; Tanqueray, Elizabeth; Morrison, Jennifer; Holbrook, Becky; Browning, Julie; Walker, Kirsten; Congreave, Susan; Verheyden, Juliette; Slininger, Susan; Stafford, Lizzie; O'Donnell, Denise; Ainsworth, Mark; Lord, Susan; Kent, Linda; March, Linda; Dickson, Christine; Simpson, Diane; Longhurst, Beverley; Hayes, Maria; Shpuza, Ervin; White, Nikki; Besley, Sarah; Pearson, Sallyanne; Wright, Alice; Jones, Linda; Gunter, Emma; Dewhurst, Hannah; Fouracres, Anna; Farrington, Liz; Graves, Lyn; Marriott, Suzie; Leoni, Marina; Tyrer, David; Martin, Kate; Dali-kemmery, Lola; Lambourne, Victoria; Green, Marie; Sirdefield, Dawn; Amor, Kelly; Colley, Julie; Shinder, Bal; Jones, Jayne; Mills, Marisa; Carnahan, Mandy; Taylor, Natalie; Boulton, Kerenza; Tregonning, Julie; Brown, Carly; Clifford, Gayle; Archer, Emily; Hamilton, Maria; Curtis, Janette; Shewan, Tracey; Walsh, Sue; Warner, Karen; Netherton, Kimberley; Mupudzi, Mcdonald; Gunson, Bridget; Gitahi, Jane; Gocher, Denise; Batham, Sally; Pateman, Hilary; Desmennu, Senayon; Conder, Jill; Clement, Darren; Gallagher, Susan; Orpe, Jacky; Chan, PuiChing; Currie, Lynn; O'Donohoe, Lynn; Oblak, Metod; Morgan, Lisa; Quinn, Marie; Amey, Isobel; Baird, Yolanda; Cotterill, Donna; Cumlat, Lourdes; Winter, Louise; Greer, Sandra; Spurdle, Katie; Allison, Joanna; Dyer, Simon; Sweeting, Helen; Kordula, Jean; Gershwin, M. Eric; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; Siminovitch, Katherine A.

    2015-01-01

    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. PMID:26394269

  19. Connective tissue diseases in primary biliary cirrhosis: A population-based cohort study

    PubMed Central

    Wang, Li; Zhang, Feng-Chun; Chen, Hua; Zhang, Xuan; Xu, Dong; Li, Yong-Zhe; Wang, Qian; Gao, Li-Xia; Yang, Yun-Jiao; Kong, Fang; Wang, Ke

    2013-01-01

    AIM: To establish the frequency and clinical features of connective tissue diseases (CTDs) in a cohort of Chinese patients with primary biliary cirrhosis (PBC). METHODS: Three-hundred and twenty-two Chinese PBC patients were screened for the presence of CTD, and the systemic involvement was assessed. The differences in clinical features and laboratory findings between PBC patients with and without CTD were documented. The diversity of incidence of CTDs in PBC of different countries and areas was discussed. For the comparison of normally distributed data, Student’s t test was used, while non-parametric test (Wilcoxon test) for the non-normally distributed data and 2 × 2 χ2 or Fisher’s exact tests for the ratio. RESULTS: One-hundred and fifty (46.6%) PBC patients had one or more CTDs. The most common CTD was Sjögren’s syndrome (SS, 121 cases, 36.2%). There were nine cases of systemic sclerosis (SSc, 2.8%), 12 of systemic lupus erythematosus (SLE, 3.7%), nine of rheumatoid arthritis (RA, 2.8%), and 10 of polymyositis (PM, 3.1%) in this cohort. Compared to patients with PBC only, the PBC + SS patients were more likely to have fever and elevated erythrocyte sedimentation rate (ESR), higher serum immunoglobulin G (IgG) levels and more frequent rheumatoid factor (RF) and interstitial lung disease (ILD) incidences; PBC + SSc patients had higher frequency of ILD; PBC + SLE patients had lower white blood cell (WBC) count, hemoglobin (Hb), platelet count, γ-glutamyl transpeptidase and immunoglobulin M levels, but higher frequency of renal involvement; PBC + RA patients had lower Hb, higher serum IgG, alkaline phosphatase, faster ESR and a higher ratio of RF positivity; PBC + PM patients had higher WBC count and a tendency towards myocardial involvement. CONCLUSION: Besides the common liver manifestation of PBC, systemic involvement and overlaps with other CTDs are not infrequent in Chinese patients. When overlapping with other CTDs, PBC patients manifested some

  20. Human combinatorial autoantibodies and mouse monoclonal antibodies to PDC-E2 produce abnormal apical staining of salivary glands in patients with coexistent primary biliary cirrhosis and Sjögren's syndrome.

    PubMed

    Tsuneyama, K; Van de Water, J; Nakanuma, Y; Cha, S; Ansari, A; Coppel, R; Gershwin, M E

    1994-10-01

    An increase in the incidence of Sjögren's syndrome in patients with primary biliary cirrhosis has been noted. Indeed, primary biliary cirrhosis has been described as a ductal disease with involvement not only of the biliary tract but of epithelial ductal cells in other organs. We have previously reported the development of a panel of mouse monoclonal antibodies directed at PDC-E2, the major autoantigen of primary biliary cirrhosis. One such antibody, C355.1, but none of the other monoclonal antibodies, reacted not only with mitochondria but also with the apical region of biliary epithelium of patients with primary biliary cirrhosis but not in similar specimens from patients with other liver disease or normal human liver. In addition, we have reported the development of human combinatorial antibodies specific for PDC-E2; these reagents also reacted uniquely with the biliary epithelium of patients with primary biliary cirrhosis. In this paper, we have performed a similar study and have compared the staining of monoclonal antibody C355.1 and a human combinatorial antibody, SP4, with control monoclonal antibodies with respect to their reactivity of salivary glands in 9 patients with primary biliary cirrhosis associated with Sjögren's syndrome, 11 patients with Sjögren's syndrome alone and 7 control patients. Interestingly, the apical region of the salivary gland epithelial cells of approximately 50% of patients with coexisting primary biliary cirrhosis and Sjögren's syndrome had a staining pattern similar to that seen in primary biliary cirrhosis biliary epithelium. In contrast, we did not observe this reactivity in any patient with Sjögren's syndrome alone or in any control patient.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

    PubMed Central

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. PMID:27621676

  2. SP140L, an Evolutionarily Recent Member of the SP100 Family, Is an Autoantigen in Primary Biliary Cirrhosis.

    PubMed

    Saare, Mario; Hämarik, Uku; Venta, Rainis; Panarina, Marina; Zucchelli, Chiara; Pihlap, Maire; Remm, Anu; Kisand, Kai; Toots, Urve; Möll, Kaidi; Salupere, Riina; Musco, Giovanna; Uibo, Raivo; Peterson, Pärt

    2015-01-01

    The SP100 family members comprise a set of closely related genes on chromosome 2q37.1. The widely expressed SP100 and the leukocyte-specific proteins SP110 and SP140 have been associated with transcriptional regulation and various human diseases. Here, we have characterized the SP100 family member SP140L. The genome sequence analysis showed the formation of SP140L gene through rearrangements of the two neighboring genes, SP100 and SP140, during the evolution of higher primates. The SP140L expression is interferon-inducible with high transcript levels in B cells and other peripheral blood mononuclear cells. Subcellularly, SP140L colocalizes with SP100 and SP140 in nuclear structures that are devoid of SP110, PML, or p300 proteins. Similarly to SP100 and SP140 protein, we detected serum autoantibodies to SP140L in patients with primary biliary cirrhosis using luciferase immunoprecipitation system and immunoblotting assays. In conclusion, our results show that SP140L is phylogenetically recent member of SP100 proteins and acts as an autoantigen in primary biliary cirrhosis patients.

  3. Chondrodermatitis nodularis chronica helicis in a patient with systemic sclerosis associated with primary biliary cirrhosis (Reynolds syndrome): A case report

    PubMed Central

    Giraldo, Walter Alberto Sifuentes; González-García, Carmen; de las Heras Alonso, Elena; de la Puente Bujidos, Carlos

    2014-01-01

    Chondrodermatitis nodularis chronica helicis is a rare non-neoplastic inflammatory and degenerative process of the external ear, characterized by necrobiotic changes in the dermis that extend down to the perichondrium. This condition has been occasionally reported in patients with limited cutaneous systemic sclerosis but not in those with concomitant primary biliary cirrhosis; this association is known as Reynolds syndrome. We report a 70-year-old woman diagnosed with primary biliary cirrhosis at age 47 and with limited cutaneous systemic sclerosis at age 54 who developed a painful ulcerated nodule on the helical rim of the left ear shortly after the last diagnosis. The lesion was excised because of the suspicion of malignancy, but the histopathology was consistent with chondrodermatitis nodularis chronica helicis. Although this condition is infrequent, it is necessary to know, because it may occur in patients with systemic sclerosis and be mistaken for neoplasms, such as basal cell and squamous cell carcinoma, and these patients have an increased risk for the development of skin malignancies. PMID:27708905

  4. The role of Tc-99m IDA hepatobiliary and Tc-99m colloid hepatic imaging in primary biliary cirrhosis

    SciTech Connect

    Aburano, T.; Yokoyama, K.; Shuke, N.; Kinuya, S.; Takayama, T.; Tonami, N.; Hisada, K. )

    1991-01-01

    To assess the presence of primary biliary cirrhosis, 15 patients at various histopathologic stages were studied by Tc-99m IDA hepatobiliary and/or Tc-99m colloid hepatic imaging. In the earlier stages (I and II), seven of eight patients (88%) showed uniform hepatic retention of Tc-99m IDA. Of seven patients in the same stage, however, four (57%) showed no abnormality on Tc-99m colliod imaging. In three of these four negative patients (75%), uniform hepatic retention of Tc-99m IDA was noted. In the later stages (III and IV), all seven patients showed decreased clearance with or without delayed tracer appearance in the intestine and prominent hepatic retention on Tc-99m IDA imaging; with Tc-99m colloid imaging there was enlargement of the spleen and increased activity in the spleen and bone marrow. Thus, Tc-99m IDA imaging is considered to be more useful in revealing this functional disorder at the earlier stage of primary biliary cirrhosis and in evaluating progression from an earlier to a later stage of disease. Tc-99m colloid imaging also effectively evaluated progression.

  5. Smoking as a risk factor for autoimmune liver disease: what we can learn from primary biliary cirrhosis.

    PubMed

    Smyk, Daniel S; Rigopoulou, Eirini I; Muratori, Luigi; Burroughs, Andrew K; Bogdanos, Dimitrios P

    2012-01-01

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients.

  6. Autoantibodies from patients with primary biliary cirrhosis recognize a region within the nucleoplasmic domain of inner nuclear membrane protein LBR.

    PubMed

    Lin, F; Noyer, C M; Ye, Q; Courvalin, J C; Worman, H J

    1996-01-01

    Autoantibodies from rare patients with primary biliary cirrhosis (PBC) recognize LBR, or lamin B receptor, an integral membrane protein of the inner nuclear membrane. Human LBR has a nucleoplasmic, amino-terminal domain of 208 amino acids followed by a carboxyl-terminal domain with eight putative transmembrane segments. Autoantibodies against LBR from four patients with PBC recognized the nucleoplasmic, amino-terminal domain but not the carboxyl-terminal domain. Immunoblotting of smaller fusion proteins demonstrated that these autoantibodies recognized a conformational epitope(s) contained within the stretch of amino acids from 1 to 60. These results, combined with those of previous studies, show that autoepitopes of nuclear membrane proteins are located within their nucleocytoplasmic domains and that autoantibodies from patients with PBC predominantly react with one domain of a protein antigen. This work also provides further characterization of anti-LBR antibodies that have found utility as reagents in cell biology research.

  7. An immunohistochemical and serum ELISA study of type I and III procollagen aminopropeptides in primary biliary cirrhosis.

    PubMed Central

    Davis, B. H.; Madri, J. A.

    1987-01-01

    By means of ELISA methodology, the aminopropeptides of Type I and Type III procollagen were measured in the serum of a group of patients with primary biliary cirrhosis. The corresponding liver biopsies were graded blindly for degrees of fibrosis and inflammation. When available, paraffin-embedded liver specimens underwent immunoperoxidase staining for mature Type I and III collagen as well as the aminopropeptides of Type I and III procollagen. Regardless of the degree of fibrosis or inflammation, serum levels of the aminopropeptide of Type I remained within normal limits. In contrast, serum levels of the aminopropeptide of Type III procollagen were elevated uniformly. Immunohistochemistry demonstrated that the aminopropeptide of Type III procollagen persists extracellularly. This finding may explain the previously reported relationship between levels of inflammation and serum levels of the Type III aminopropeptide. Images Figure 7 Figure 8 PMID:3303951

  8. Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis.

    PubMed

    Van de Water, J; Ansari, A A; Surh, C D; Coppel, R; Roche, T; Bonkovsky, H; Kaplan, M; Gershwin, M E

    1991-01-01

    Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts, high titer autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction. The mechanism by which the autoimmune response is induced, the specificity of damage to the biliary epithelium, and the role of T cells in PBC are still unknown. To address these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with PBC, progressive sclerosing cholangitis, and chronic active hepatitis (CAH). C355.1, much like human autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro. In addition, we have also attempted to develop cloned T cell lines that react with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared with CAH. Although monoclonal C355.1 produced typical mitochondrial fluorescence on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it produced a distinct and intense reactivity when used to stain the bile ducts of patients with PBC. Nine of 13 PBC liver biopsies studied herein contained bile ducts on light microscopy, all of which reacted intensely at a 1:100 culture supernatant dilution of monoclonal C355.1. In contrast, although bile ducts of liver specimens from normals, CAH, and progressive sclerosing cholangitis also reacted with C355.1, such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1:2. More importantly, we generated CD4+, CD8-, alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH, that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.

  9. [Biliary ascariasis].

    PubMed

    Mensing, M; Cruz y Rivero, M A; Alarcon Hernandez, C; Garcia Himmelstine, L; Vogel, H

    1986-06-01

    Biliary ascariasis is a complication of intestinal ascariasis. This results in characteristic findings in the intravenous cholangiocholecystogram and in the sonogram. Characteristic signs of biliary ascariasis are, in the longitudinal section, the "strip sign", "spaghetti sign", "inner tube sign", and in transverse section "a bull's eye in the triple O". The helminth can travel from out of the biliary duct system back into the intestines, so that control examinations can even be negative.

  10. 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

  11. Imaging of autoimmune biliary disease.

    PubMed

    Yeh, Melinda J; Kim, So Yeon; Jhaveri, Kartik S; Behr, Spencer C; Seo, Nieun; Yeh, Benjamin M

    2017-01-01

    Autoimmune biliary diseases are poorly understood but important to recognize. Initially, autoimmune biliary diseases are asymptomatic but may lead to progressive cholestasis with associated ductopenia, portal hypertension, cirrhosis, and eventually liver failure. The three main forms of autoimmune biliary disease are primary biliary cirrhosis, primary sclerosing cholangitis, and IgG4-associated cholangitis. Although some overlap may occur between the three main autoimmune diseases of the bile ducts, each disease typically affects a distinct demographic group and requires a disease-specific diagnostic workup. For all the autoimmune biliary diseases, imaging provides a means to monitor disease progression, assess for complications, and screen for the development of hepatobiliary malignancies that are known to affect patients with these diseases. Imaging is also useful to suggest or corroborate the diagnosis of primary sclerosing cholangitis and IgG4-associated cholangitis. We review the current literature and emphasize radiological findings and considerations for these autoimmune diseases of the bile ducts.

  12. Accurate prediction of death by serial determination of galactose elimination capacity in primary biliary cirrhosis: a comparison with the Mayo model.

    PubMed

    Reichen, J; Widmer, T; Cotting, J

    1991-09-01

    We retrospectively analyzed the predictive accuracy of serial determinations of galactose elimination capacity in 61 patients with primary biliary cirrhosis. Death was predicted from the time that the regression line describing the decline in galactose elimination capacity vs. time intersected a value of 4 mg.min-1.kg-1. Thirty-one patients exhibited decreasing galactose elimination capacity; in 11 patients it remained stable and in 19 patients only one value was available. Among those patients with decreasing galactose elimination capacity, 10 died and three underwent liver transplantation; prediction of death was accurate to 7 +/- 19 mo. This criterion incorrectly predicted death in two patients with portal-vein thrombosis; otherwise, it did better than or as well as the Mayo clinic score. The latter was also tested on our patients and was found to adequately describe risk in yet another independent population of patients with primary biliary cirrhosis. Cox regression analysis selected only bilirubin and galactose elimination capacity, however, as independent predictors of death. We submit that serial determination of galactose elimination capacity in patients with primary biliary cirrhosis may be a useful adjunct to optimize the timing of liver transplantation and to evaluate new pharmacological treatment modalities of this disease.

  13. Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis

    PubMed Central

    Wasik, Urszula; Milkiewicz, Małgorzata; Kempinska-Podhorodecka, Agnieszka; Milkiewicz, Piotr

    2017-01-01

    In response to oxidative stress, nuclear factor (erythroid-derived 2)-like2 (Nrf2) induces expression of cytoprotective genes. The Nrf2 pathway is controlled by microRNAs and Kelch-like ECH-associated protein1 (Keap1). Nrf2 is stabilized when Keap1 is degraded through the autophagy pathway in a p62-dependent manner. The inhibition of autophagy causes protein accumulation, and Keap1 is inactivated by binding to p62. We investigated the role of the Nrf2/Keap1 axis in the amelioration of oxidative stress in primary biliary cholangitis (PBC). Liver specimens from patients with PBC, with (n = 24) or without cirrhosis (n = 14), and from controls (n = 16) were used for molecular analyses. We found that Nrf2 protein levels were elevated in PBC compared to controls, but Nrf2 gene expression was significantly reduced in cirrhotic PBC. Nrf2 target gene products, HO-1 and GCLC proteins, were reduced compared to controls and reduction of Nrf2 gene expression was associated with elevated levels of microRNA-132 and microRNA-34a. Both Keap1 and p62 protein levels were substantially increased in PBC compared to controls. PBC was associated with reduced Nrf2 expression and autophagy deterioration and these impairments were more advanced in patients with cirrhosis. Aberrant Nrf2/Keap1 system integrity may affect self-defence mechanisms against oxidative stress in PBC. PMID:28333129

  14. The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and Ursodeoxycholic Acid Response

    PubMed Central

    Chen, Rui-rui; Li, Yuan-jun; Zhou, Xin-min; Wang, Lu; Xing, Juan; Han, Shuang; Cui, Li-na; Zheng, Lin-hua; Wu, Kai-chun; Shi, Yong-quan; Han, Zhe-yi; Han, Ying; Fan, Dai-ming

    2014-01-01

    Background. Primary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of UDCA treatment. Results. Variant A allele of BSEP rs473351 (dominant model, OR = 2.063; 95% CI, 1.254–3.393; P = 0.004) was highly associated with PBC susceptibility. On the contrary, variant A allele of BSEP rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411–0.928; P = 0.020) provided a protective role and Barcelona evaluation criterion indicated that the frequency of variant allele at BSEP rs2287618 was significantly decreased in UDCA-responsive PBC patients (P = 0.021). Conclusion. These results suggested that BSEP rs473351 was closely associated with the susceptibility of PBC and if people with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory. Larger studies with mixed ethnicity subjects and stratified by clinical and subclinical characteristics are needed to validate our findings. PMID:25392597

  15. 13C-methacetin breath test correlates with clinical indices of liver disease severity in patients with primary biliary cirrhosis.

    PubMed

    Kochel-Jankowska, A; Hartleb, M; Jonderko, K; Kaminska, M; Kasicka-Jonderko, A

    2013-02-01

    This prospective study intended to ascertain if cytochrome P450 dependent liver function is affected in early and late histological stages of primary biliary cirrhosis (PBC). The study included 32 female PBC patients (mean age 55.4 years, range 33-70) and 16 aged-matched healthy women (mean age 52.6 years, range 38-65). In every subject a 13(C)-methacetin breath test (13(C)-MBT) was applied, and the results were related to histological Ludwig's staging system and several indices of liver disease severity comprising the MAYO-1, MAYO-2, MELD, and Child-Pugh score. The 13(C)-MBT differentiated healthy controls from the patients with Ludwig IV and Ludwig III histopathological stages of PBC. The most significant relationships (i.e. explaining >50% of the variance) were found between measurements of the momentary breath 13(C) elimination from 6 to 18 minutes as well as the 15-min or 30-min cumulative elimination and the MAYO-1 or MAYO-2 scores. The breath test poorly correlated with histopathological features of PBC, however, it accurately discriminated cirrhotic from non-cirrhotic patients (momentary breath 13(C) elimination at 40 min, AUROC 0,958). In conclusion, 13(C)-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.

  16. Giant Splenorenal Shunt in a Young Patient with Autoimmune Hepatitis/Primary Biliary Cholangitis Overlap Syndrome and Portal Vein Thrombosis

    PubMed Central

    Castellani, F.; Greco, L.; Manuelli, M.; Manzia, T. M.; Sergiacomi, G.

    2017-01-01

    We present a case of giant Splenorenal Shunt (SRS) associated with portal vein thrombosis in a 37-year-old woman with a twelve-year history of autoimmune hepatitis/primary biliary cholangitis overlap syndrome. At the moment of the CT examination laboratory tests showed creatinine 1.5 mg/dl, bilirubin 1.5 mg/dl, INR 3, and Na 145 mmol/l and the Model End-Stage Liver Disease score was 24. Extensive calcified thrombosis causing complete occlusion of the portal vein lumen and partially occluding the origin of the superior mesenteric vein was present and a small calcified thrombus in the Splenic Vein lumen was also evident. SRS was located among the spleen hilum and the left kidney with a maximum diameter of 3.25 cm and was associated with dilatation of left renal vein and inferior vena cava. After a multidisciplinary evaluation the patient was put on the Regional Liver Transplant waiting list and liver transplantation was performed successfully. Although portal vein thrombosis and SRS are common occurrences in cirrhotic patients, the impact in the natural history of the disease is still unclear. Careful management and accurate imaging protocols are essential in the evaluation of those patients. PMID:28316856

  17. Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis.

    PubMed

    Invernizzi, P; Ransom, M; Raychaudhuri, S; Kosoy, R; Lleo, A; Shigeta, R; Franke, A; Bossa, F; Amos, C I; Gregersen, P K; Siminovitch, K A; Cusi, D; de Bakker, P I W; Podda, M; Gershwin, M E; Seldin, M F

    2012-09-01

    Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.

  18. Polymorphisms of IL12RB2 May Affect the Natural History of Primary Biliary Cholangitis: A Single Centre Study

    PubMed Central

    Wasik, Urszula; Bogdanos, Dimitrios P.

    2017-01-01

    Background. Recent GWAS in primary biliary cholangitis (PBC) showed strong associations with SNPs located within interleukin-12 receptor (IL12R) beta-2 (IL12RB2) gene. Aims. We assessed whether genetic variation of IL12RB2 is associated with laboratory and clinical features of PBC. Methods. Genomic DNA was isolated from 306 patients with PBC and 258 age/gender-matched controls. PBC-specific anti-mitochondrial antibodies (AMA) were tested in all subjects by ELISA. Two SNPs, rs3790567 and rs6679356, of IL12RB2 were genotyped using the MGB-TaqMan SNP assay. Results. Despite comparable age at diagnosis of cirrhotic and noncirrhotic PBC patients, allele A of rs3790567 and allele C of rs6679356 were overrepresented in the former rather than the latter group (p = 0.0009 and p = 0.002, resp.). The risk of cirrhosis at presentation increased when allele A and allele C coexisted. AMA-M2 titres were significantly higher in AA homozygotes of rs3790567 compared to GG homozygotes (132 ± 54 versus 103 ± 62, p = 0.02) and in rs6679356 when C allele was present (p = 0.038). There were no other significant associations between IL12RB2 polymorphisms and laboratory or clinical features. Conclusion. In this first study analyzing phenotypic features of PBC carriers of the IL12RB2 polymorphisms, we found that carriers are more frequently cirrhotic at diagnosis and have significantly higher titres of AMA. PMID:28299343

  19. Classical HLA-DRB1 and DPB1 Alleles Account for HLA Associations with Primary Biliary Cirrhosis

    PubMed Central

    Invernizzi, Pietro; Ransom, Michael; Raychaudhuri, Soumya; Kosoy, Roman; Lleo, Ana; Shigeta, Russell; Franke, Andre; Bossa, Fabrizio; Amos, Christopher I.; Gregersen, Peter K.; Siminovitch, Katherine A.; Cusi, Daniele; de Bakker, Paul I.W.; Podda, Mauro; Gershwin, M. Eric; Seldin, Michael F.

    2012-01-01

    Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with HLA region polymorphisms. To determine if associations can be explained by classical HLA determinants we studied Italian 676 cases and 1440 controls with genotyped with dense single nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (p = 1.59 × 10−11) was the strongest predisposing allele where as DRB1*11 (p = 1.42 × 10−10) was protective. Additionally DRB1*14 and the DPB1 association (DPB1*03:01) (p = 9.18 × 10−7) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC. PMID:22573116

  20. Primary Squamous Cell Carcinoma of the Pancreas as a Cause of Biliary Obstruction

    PubMed Central

    Mehta, Jeet; Nehme, Fredy; Salyers, William

    2016-01-01

    Primary squamous cell carcinoma of the pancreas (SCCP) is a rare neoplasm, given a lack of naturally occurring squamous cells within the pancreas, accounting for only 0.2% of all pancreatic cancers. The etiology is unknown. Symptomatology is non-specific and similar to other pancreatic neoplasms. No non-invasive testing can adequately rule in SCCP, and workup should proceed similarly to any pancreatic mass. Tissue sampling is required for diagnosis and guidance of further management, most commonly by endoscopic ultrasound with fine needle aspirate. SCCP is more aggressive than adenocarcinoma of the pancreas with a median survival of three and ten months for those treated with palliative and surgical intent, respectively. The optimal treatment regimen remains unknown, though the uses of radiation therapy, platinum-based regimens, gemcitabine, and 5-FU have all been reported with favorable results. We present a case of primary SCCP in an 81-year-old female who presented with jaundice. PMID:27909644

  1. Biliary atresia

    MedlinePlus

    ... Elsevier; 2016:chap 356. Suchy FJ. Anatomy, histology, embryology, developmental anomalies, and pediatric disorders of the biliary ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. Carcinoma of the extrahepatic biliary system--results of primary and adjuvant radiotherapy

    SciTech Connect

    Fields, J.N.; Emami, B.

    1987-03-01

    From 1975-1983, 20 patients with primary carcinomas of the gallbladder (GB) or extrahepatic bile ducts (EHBD) were irradiated with curative intent at the Washington University Medical Center and affiliated hospitals. Of the 17 patients with EHBD cancer, one received adjuvant irradiation after gross resection with positive microscopic margins. All others received primary irradiation for unresectable tumors, or for gross residual tumor after incomplete resection. The 8 patients receiving Ir192 implant in addition to external radiation showed improved survival compared to the 9 receiving external only: median 15 months (range 1.5-34 + months) versus 7 months (range 2.5-21 months). Failures were predominantly local-regional, with only one patient showing metastatic spread without known local-regional tumor. Adjuvant radiation therapy was given after cholecystectomy to 3 patients with GB cancers showing tumor extension beyond the serosa or to regional lymphatics. Of these, two survived at 22+ and 27+ months; the third died of local recurrence at 5 1/2 months. Although numbers are small, these results appear to support the use of adjuvant radiotherapy in patients with microscopic residual GB cancer. Aggressive local and regional radiotherapy can add to the quality and length of survival in both patient groups, that is, those with resectable lesions with high likelihood of microscopic residual, and also those with unresectable or gross residual disease after surgery.

  3. Carcinoma of the extrahepatic biliary system--results of primary and adjuvant radiotherapy.

    PubMed

    Fields, J N; Emami, B

    1987-03-01

    From 1975-1983, 20 patients with primary carcinomas of the gallbladder (GB) or extrahepatic bile ducts (EHBD) were irradiated with curative intent at the Washington University Medical Center and affiliated hospitals. Of the 17 patients with EHBD cancer, one received adjuvant irradiation after gross resection with positive microscopic margins. All others received primary irradiation for unresectable tumors, or for gross residual tumor after incomplete resection. The 8 patients receiving Ir192 implant in addition to external radiation showed improved (p = 0.06) survival compared to the 9 receiving external only: median 15 months (range 1.5-34 + months) versus 7 months (range 2.5-21 months). Failures were predominantly local-regional, with only one patient showing metastatic spread without known local-regional tumor. Adjuvant radiation therapy was given after cholecystectomy to 3 patients with GB cancers showing tumor extension beyond the serosa or to regional lymphatics. Of these, two survived at 22+ and 27+ months; the third died of local recurrence at 5 1/2 months. Although numbers are small, these results appear to support the use of adjuvant radiotherapy in patients with microscopic residual GB cancer. Aggressive local and regional radiotherapy can add to the quality and length of survival in both patient groups, that is, those with resectable lesions with high likelihood of microscopic residual, and also those with unresectable or gross residual disease after surgery.

  4. Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease.

    PubMed

    Wunsch, Ewa; Milkiewicz, Małgorzata; Wasik, Urszula; Trottier, Jocelyn; Kempińska-Podhorodecka, Agnieszka; Elias, Elwyn; Barbier, Olivier; Milkiewicz, Piotr

    2015-08-21

    Cholestasis induces adaptive mechanisms protecting the liver against bile acids (BA) toxicity including modulation of BA synthesis. Whether fibroblast growth factor 19 (FGF19) or farnesoid X receptor (FXR) dependent signaling are involved in the regulation of BA homeostasis in primary biliary cirrhosis (PBC) remains unknown. Here we analyzed hepatic expression of FGF19 and other genes relevant to the adaptive response to cholestasis in tissues from non-cirrhotic (n = 24) and cirrhotic (n = 21) patients along with control tissues (n = 21). Moreover we searched for relationships between serum FGF19 and laboratory/clinical findings in 51 patients. Hepatic FGF19 mRNA expression was increased in non-cirrhotic and cirrhotic tissues (9-fold,p = 0.01; 69-fold,p < 0.0001, respectively). Protein levels of FGF19, FGF receptor 4, FXR and short heterodimer partner were increased in cirrhotic livers (9-fold, p < 0.001; 3.5-fold,p = 0.007; 2.4-fold,p < 0.0001; 2.8-fold,p < 0.0001 vs controls, respectively) which was accompanied by down-regulation of CYP7A1 (50% reduction, p = 0.006). Serum and liver levels of FGF19 correlated with worse liver biochemistry, BAs, quality of life and Mayo Risk Score. Serum FGF19 was elevated in UDCA non-responders. We conclude that PBC induces characteristic changes in liver expression of BAs synthesis regulatory molecules. FGF19 correlates with severity of liver disease and can potentially serve as an indicator of chronic cholestatic liver injury.

  5. Analysis of TCR antagonism and molecular mimicry of an HLA-A0201-restricted CTL epitope in primary biliary cirrhosis.

    PubMed

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

    2002-10-01

    Although the etiology and mechanism of primary biliary cirrhosis (PBC) is unknown, growing evidence suggests a major role for T cells. We have recently identified the first CD8 T-cell epitope, amino acid 159-167 of the E2 component of pyruvate dehydrogenase complexes (PDC-E2). To seek for analogue peptide-antagonizing effector function of CTLs specific for this autoantigen, we examined the effector functions of the PDC-E2-specific CTLs against alanine substituted peptides. Furthermore, because molecular mimicry has been postulated as a possible cause of initiating PBC, we carried out studies aimed at identifying naturally occurring peptides for the 159-167 peptide of PDC-E2 that may serve as agonists. An alanine substitution at position 5 of this epitope significantly reduced peptide-specific effector functions of CTLs. Moreover, this analogue peptide inhibited effector functions of the CTLs to the prototype peptide, including cytotoxicity and IFN-gamma production. We also identified a peptide derived from Pseudomonas aeruginosa, which showed a higher binding affinity to the HLA-A*0201 than the prototype peptide. This homologous peptide was recognized by CTLs specific for the prototype epitope on PDC-E2. In conclusion, a modification of the immunodominant autoepitope can be utilized to manipulate the CD8 T-cell responses against the autoantigen PDC-E2. Our finding also supports the thesis that molecular mimicry may be implicated in the initiation of the autoreactive CD8 T-cell responses and has implications for the use of such peptides for immunotherapy.

  6. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients.

    PubMed

    Gershwin, M Eric; Selmi, Carlo; Worman, Howard J; Gold, Ellen B; Watnik, Mitchell; Utts, Jessica; Lindor, Keith D; Kaplan, Marshall M; Vierling, John M

    2005-11-01

    Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC. We enrolled patients with PBC (n = 1032) from 23 tertiary referral centers for liver diseases in the United States and random-digit-dialed controls (n = 1041) matched for sex, age, race, and geographical location. Patients and controls were administered a modified version of the US National Health and Nutrition Examination Study (NHANES III) questionnaire by trained personnel to evaluate associations between PBC and social, demographic, personal and family medical histories, lifestyle, and reproductive factors and the rates of comorbidity in affected individuals. Data indicate that having a first-degree relative with PBC (adjusted odds ratio [AOR] 10.736; 95% confidence interval 4.227-27.268), history of urinary tract infections (AOR 1.511, 95% CI 1.192-1.915), past smoking (AOR 1.569, 95% CI 1.292-1.905), or use of hormone replacement therapies (AOR 1.548, 95% CI 1.273-1.882) were significantly associated with increased risk of PBC. The frequent use of nail polish slightly increased the risk of having PBC. Other autoimmune diseases were found in 32% of cases and 13% of controls (P<0.0001). In conclusion, environmental factors, possibly including infectious agents through urinary tract infections or chemicals contained in cigarette smoke, may induce PBC in genetically susceptible individuals. Exogenous estrogens may also contribute to explain the female predominance of the disease.

  7. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial.

    PubMed

    Rautiainen, Henna; Kärkkäinen, Päivi; Karvonen, A-L; Nurmi, Heimo; Pikkarainen, Pekka; Nuutinen, Hannu; Färkkilä, Martti

    2005-04-01

    Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to III, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15 mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.

  8. Network meta-analysis of randomized controlled trials: efficacy and safety of UDCA-based therapies in primary biliary cirrhosis.

    PubMed

    Zhu, Gui-Qi; Shi, Ke-Qing; Huang, Sha; Huang, Gui-Qian; Lin, Yi-Qian; Zhou, Zhi-Rui; Braddock, Martin; Chen, Yong-Ping; Zheng, Ming-Hua

    2015-03-01

    Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09-1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02-4.83), COC plus UDCA (HR 0.39, 95% CI 0.07-2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05-1.63), or OBS (HR 0.49, 95% CI 0.11-2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59-20.67), COT plus UDCA (OR 2.27, 95% CI 0.15-33.36), COC plus UDCA (OR 1.00, 95% CI 0.09-12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23-17.82), or OBS (OR 3.00, 95% CI 0.53-20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.

  9. Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis.

    PubMed

    Samur, Sumeyye; Klebanoff, Matthew; Banken, Reiner; Pratt, Daniel S; Chapman, Rick; Ollendorf, Daniel A; Loos, Anne M; Corey, Kathleen; Hur, Chin; Chhatwal, Jagpreet

    2017-03-01

    Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. We developed a mathematical model to simulate the lifetime course of PBC patients treated with OCA+UDCA versus UDCA alone. Efficacy data were derived from the phase 3 PBC OCA International Study of Efficacy trial, and the natural history of PBC was informed by published clinical studies. Model outcomes were validated using the PBC Global Study. We found that in comparison with UDCA, OCA+UDCA could decrease the 15-year cumulative incidences of decompensated cirrhosis from 12.2% to 4.5%, hepatocellular carcinoma from 9.1% to 4.0%, liver transplants from 4.5% to 1.2%, and liver-related deaths from 16.2% to 5.7% and increase 15-year transplant-free survival from 61.1% to 72.9%. The lifetime cost of PBC treatment would increase from $63,000 to $902,000 (1,330% increment). The discounted quality-adjusted life years with UDCA and OCA+UDCA were 10.74 and 11.78, respectively, and the corresponding costs were $142,300 and $633,900, resulting in an incremental cost-effectiveness ratio of $473,400/quality-adjusted life year gained. The results were most sensitive to the cost of OCA.

  10. Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: a multicenter study of 664 patients and 1992 healthy controls

    PubMed Central

    Invernizzi, Pietro; Selmi, Carlo; Poli, Francesca; Frison, Sara; Floreani, Annarosa; Alvaro, Domenico; Almasio, Piero; Rosina, Floriano; Marzioni, Marco; Fabris, Luca; Muratori, Luigi; Qi, Lihong; Seldin, Michael F.; Gershwin, M. Eric; Podda, Mauro

    2008-01-01

    Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multi-center case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1,992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and gender, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). Following correction for multiple testing, DRB1*08 (Odds Ratio–OR, 3.3; 95% Confidence Interval–CI, 2.4−4.5) and DRB1*02 (OR 0.9; 95% CI 0.8−1.2) were significantly associated with PBC while alleles DRB1*11 (OR 0.4; 95% CI 0.3−0.4) and DRB1*13 (OR 0.7; 95% CI 0.6−0.9) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. Associated DRB1 alleles were found only in a minority of patients while an additive genetic model is supported by the gene dosage effect for DRB1*11 allele and the interaction of DRB1*11,*13, and *08. Lastly, no significant associations were detected between specific DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. In conclusion, we confirm the role for HLA to determine PBC susceptibility and suggest that the effect of HLA is limited to patient subgroups. We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease. PMID:19003916

  11. S100 protein positive dendritic cells in primary biliary cirrhosis and other chronic inflammatory liver diseases. Relevance to pathogenesis?

    PubMed Central

    Demetris, A. J.; Sever, C.; Kakizoe, S.; Oguma, S.; Starzl, T. E.; Jaffe, R.

    1989-01-01

    A study to determine the location of dendritic cells, in chronic inflammatory liver disease was performed. S100 protein positivity and dendritic cytoplasmic morphology were used to identify dendritic cells. S100 protein positive dendritic cells (S100 + DC) were found inside the basement membrane between biliary epithelial cells of septal bile ducts of livers affected by early stage PBC, but were not present at later stages. S100 + DC also were seen in areas of piecemeal necrosis in chronic active hepatitis of various etiologies. In contrast, intra-epithelial S100 + DC were not found with any consistency in sclerosing cholangitis, secondary biliary cirrhosis, extrahepatic biliary atresia, or chronic liver allograft rejection, all of which are characterized by inflammatory bile duct damage. The possible relevance of DC in the pathogenesis of PBC is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2705505

  12. A Case of Rheumatoid Arthritis and Limited Systemic Sclerosis Overlap Successfully Treated with Tocilizumab for Arthritis and Concomitant Generalized Lymphadenopathy and Primary Biliary Cirrhosis

    PubMed Central

    Saito, Eiko; Sato, Shinji; Nogi, Shinichi; Sasaki, Noriko; Chinen, Naofumi; Honda, Kiri; Wakabayashi, Takayuki; Yamada, Chiho; Nakamura, Naoya; Suzuki, Yasuo

    2014-01-01

    A 57-year-old woman with rheumatoid arthritis (RA) and limited systemic sclerosis (lSSc) was suspected to have lymphadenopathy and primary biliary cirrhosis (PBC). Lymph node biopsy showed reactive follicular lymphadenopathy with intrafollicular plasmacyte infiltration that was interleukin-6 positive by immunohistostaining. Because of gradually worsening arthritis, tocilizumab was administered and arthritis improved markedly. Interestingly, lymphadenopathy and PBC improved simultaneously. This suggested that interleukin-6 might play an important role in reactive lymphadenopathy and PBC associated with RA/lSSc. PMID:24839573

  13. The Distribution and the Fibrotic Role of Elevated Inflammatory Th17 Cells in Patients With Primary Biliary Cirrhosis.

    PubMed

    Shi, TianYan; Zhang, Ting; Zhang, LiNa; Yang, YunJiao; Zhang, HaoZe; Zhang, FengChun

    2015-11-01

    T helper (Th) 17 cells were reported to have the property of proinflammation and profibrosis. We first investigate the levels of Th17 cells in primary biliary cirrhosis (PBC) patients, and then explore their distribution and fibrotic role in the disease.We compared the circulating Th17 and hepatic interleukin (IL)-17-positive cells between patients and healthy controls (HCs) at different disease stages by flow cytometry and immunohistochemistry, respectively. The levels of chemokine (c-c motif) ligand (CCL) 20 were then measured. For exploration of the reason why Th17 cells increased, CD4CD161 populations were sorted and cultured with IL-23 and IL-1β to analyze their proliferation and IL-17 secretions. The serum IL-23 and IL-1β were tested by enzyme-linked immunosorbent assay. The proliferation and expressions of α-smooth muscle actin and IL-8 of hepatic stellate cells (HSCs) were identified after stimulated by different concentrations of IL-17.Circulating and hepatic Th17 cells were elevated in PBC patients compared with HCs. Early PBC patients presented with more Th17 cells in periphery blood and less in the liver than advanced PBC patients. Accordingly, the levels of both serum and hepatic CCL20 for Th17 cells were higher, especially in those with advanced disease. The progenitor of Th17, CD4CD161 cell was increased in PBC. Moreover, the percentage of Th17 cells was positively related with CD4CD161 cell. After stimulation with IL-23 and IL-1β which were improved in PBC patients, CD4CD161 cells from PBC patients expressed more IL-17, although their proliferation were not different between 2 groups. IL-17 can promote the proliferation of HSCs at a dose-dependent method, and also increase the IL-8 expression in a dose/time-dependent way. Anti-IL-17 can neutralize the above reactions.CD4CD161 cells are a source of increased Th17 in PBC patients. With disease progression, Th17 population decreased in the circulation, accompanied by greater accumulation in the

  14. Red Blood Cell Distribution Width to Platelet Ratio is Related to Histologic Severity of Primary Biliary Cirrhosis

    PubMed Central

    Wang, Huan; Xu, Hongqin; Wang, Xiaomei; Wu, Ruihong; Gao, Xiuzhu; Jin, Qinglong; Niu, Junqi

    2016-01-01

    Abstract We aimed to investigate whether red blood cell distribution width (RDW) and RDW to platelet ratio (RPR) were related to the histologic severity of primary biliary cirrhosis (PBC). Seventy-three treatment-naïve PBC patients who had undergone a liver biopsy between January 2010 and January 2015 were enrolled in our study. The patients’ histological stages were based on the classifications of Ludwig and Scheuer. The patients were divided into early stage (Stage I) and advanced stage (Stage II, III, and IV) hepatic fibrosis according to their histological stage. All common patient demographics, clinical characteristics, hematological parameters, liver biochemistry, and antimitochondrial M2 antibody levels (AMA-M2) were retrospectively analyzed, and RDW, RPR, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on the 4 factors (FIB-4) were calculated. A total of 28 (38.4%) patients had early stage PBC, whereas 45 (62.6%) were classified as advanced stage. Regarding age, no significant differences between the early and advanced stages were observed. Patients with advanced stage PBC had significantly higher RDW (13.6 vs 14.4; P = 0.019), conjugated bilirubin (10.1 vs 23.4; P = 0.029), and significantly lower cholinesterase (7901.1 vs 6060.8; P = 0.001) and platelets (212.6 vs 167.0; P = 0.006). However, no significant differences (P > 0.05) in other routine parameters previously evaluated in PBC, including aspartate aminotransferase (AST) and mean platelet volume, were found between the groups. The sensitivity and specificity of RDW were 33.3% and 92.9%, respectively, and the area under the receiver-operating characteristic curve (AUROC) was 0.66. However, the sensitivity and specificity of RPR were 46.7% and 96.4%, respectively, and the corresponding AUROC was 0.74 (P < 0.001). Hence, compared with preexisting indicators, RPR showed a higher AUROC than APRI (0.648; P = 0.035) and FIB-4 (0.682; P

  15. The Distribution and the Fibrotic Role of Elevated Inflammatory Th17 Cells in Patients With Primary Biliary Cirrhosis

    PubMed Central

    Shi, TianYan; Zhang, Ting; Zhang, LiNa; Yang, YunJiao; Zhang, HaoZe; Zhang, FengChun

    2015-01-01

    Abstract T helper (Th) 17 cells were reported to have the property of proinflammation and profibrosis. We first investigate the levels of Th17 cells in primary biliary cirrhosis (PBC) patients, and then explore their distribution and fibrotic role in the disease. We compared the circulating Th17 and hepatic interleukin (IL)-17-positive cells between patients and healthy controls (HCs) at different disease stages by flow cytometry and immunohistochemistry, respectively. The levels of chemokine (c-c motif) ligand (CCL) 20 were then measured. For exploration of the reason why Th17 cells increased, CD4+CD161+ populations were sorted and cultured with IL-23 and IL-1β to analyze their proliferation and IL-17 secretions. The serum IL-23 and IL-1β were tested by enzyme-linked immunosorbent assay. The proliferation and expressions of α-smooth muscle actin and IL-8 of hepatic stellate cells (HSCs) were identified after stimulated by different concentrations of IL-17. Circulating and hepatic Th17 cells were elevated in PBC patients compared with HCs. Early PBC patients presented with more Th17 cells in periphery blood and less in the liver than advanced PBC patients. Accordingly, the levels of both serum and hepatic CCL20 for Th17 cells were higher, especially in those with advanced disease. The progenitor of Th17, CD4+CD161+ cell was increased in PBC. Moreover, the percentage of Th17 cells was positively related with CD4+CD161+ cell. After stimulation with IL-23 and IL-1β which were improved in PBC patients, CD4+CD161+ cells from PBC patients expressed more IL-17, although their proliferation were not different between 2 groups. IL-17 can promote the proliferation of HSCs at a dose-dependent method, and also increase the IL-8 expression in a dose/time-dependent way. Anti-IL-17 can neutralize the above reactions. CD4+CD161+ cells are a source of increased Th17 in PBC patients. With disease progression, Th17 population decreased in the circulation, accompanied by greater

  16. Biliary Dyskinesia.

    PubMed

    Toouli, James

    2002-08-01

    Biliary dyskinesia is a motility disorder that affects the gallbladder and sphincter of Oddi. The motility disorder of the gallbladder is called gallbladder dyskinesia. Patients with this condition present with biliary-type pain, and investigations show no evidence of gallstones in the gallbladder. The diagnosis is made by performing a gallbladder ejection fraction, which is a radionuclide investigation. An abnormal gallbladder ejection fraction has a value less than 40%. Patients with an abnormal gallbladder ejection fraction should undergo cholecystectomy. This procedure has been shown to be effective in curing the symptoms in over 90% of patients. Motility disorder of the sphincter of Oddi is called sphincter of Oddi dysfunction. This disorder is categorized as two distinct types--biliary sphincter of Oddi dysfunction and pancreatic sphincter of Oddi dysfunction. Typically, patients with biliary sphincter of Oddi dysfunction present with biliary-type pain on average 4 to 5 years after having undergone cholecystectomy. Sphincter of Oddi manometry is essential in making a diagnosis of abnormal motility of the sphincter. On manometry, diagnosis of a sphincter of Oddi stenosis should lead to division of the sphincter. Sphincterotomy results in long-term relief of symptoms in more than 80% of patients. Pancreatic sphincter of Oddi dysfunction clinically presents with recurrent episodes of pancreatitis of unknown cause. Having ruled out all of the common causes of pancreatitis, sphincter of Oddi manometry of the pancreatic duct sphincter should be performed. When manometric stenosis is diagnosed, these patients should undergo division of both the biliary and pancreatic duct sphincter. This treatment results in relief of symptoms in more than 80% of patients.

  17. Primary Biliary Cirrhosis

    MedlinePlus

    ... weak, brittle bones that may break more easily. Vitamin deficiencies. A lack of bile affects your digestive system's ... the week to help increase your bone density. Vitamin deficiencies. Your doctor may recommend supplements of vitamins A, ...

  18. Immunolocalization of putative human liver progenitor cells in livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6.

    PubMed

    Crosby, H A; Hubscher, S; Fabris, L; Joplin, R; Sell, S; Kelly, D; Strain, A J

    1998-03-01

    The term oval cell describes small cells with oval nuclei that arise in the periphery of the portal tracts in rat models of hepatocarcinogenesis and injury and can differentiate into either hepatocytes or bile duct cells, ie, are bipotential. The presence of such cells in human liver is controversial. Here, immunolocalization of OV-6 and two biliary markers, cytokeratin 19 (CK-19) and human epithelial antigen 125 (HEA-125) is compared in normal adult human livers and in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) liver sections. CK-19 and HEA-125 stained bile ducts and ductules in normal liver as well as proliferating ductular structures in diseased livers. OV-6 did not label ducts or ductules in normal liver, but in PBC and PSC stained numerous proliferating ductular and periductular cells and lobular hepatocytes. In PBC, discrete OV-6-positive cells with a mature biliary-cell-like morphology were seen integrated into some intact bile ducts as well as occasional small immature oval-like cells. In addition, in PSC, hepatocytes in regenerating lobules were also strongly stained with OV-6, and on close inspection, in both PBC and PSC, oval cells and small hepatocytes at the margins of the lobules were strongly labeled. In contrast to the rat liver, OV-6 and CK-19 staining did not always co-localize. It is proposed that the small OV-6-positive oval cells are analogous to those seen in rat models and may represent human liver progenitor cells that may differentiate into OV-6-positive ductal cells or lobular hepatocytes.

  19. Biliary cystadenoma

    PubMed Central

    Bartolome, Miguel A Hernandez; Ruiz, Sagrario Fuerte; Romero, Israel Manzanedo; Lojo, Beatriz Ramos; Prieto, Ignacio Rodriguez; Alvira, Luis Gimenez; Carreño, Rosario Granados; Esteban, Manuel Limones

    2009-01-01

    The diagnosis of cystadenoma is rare, even more so when located in the extrahepatic bile duct. Unspecific clinical signs may lead this pathology to be misdiagnosed. The need for pathological anatomy in order to distinguish cystadenomas from simple biliary cysts is crucial. The most usual treatment nowadays is resection of the bile duct, together with cholecystectomy and Roux-en-Y reconstruction. PMID:19630118

  20. A possible role of histone-like DNA-binding protein of Streptococcus intermedius in the pathogenesis of bile duct damage in primary biliary cirrhosis.

    PubMed

    Haruta, Ikuko; Kikuchi, Ken; Hashimoto, Etsuko; Kato, Hidehito; Hirota, Katsuhiko; Kobayashi, Makio; Miyake, Yoichiro; Uchiyama, Takehiko; Yagi, Junji; Shiratori, Keiko

    2008-05-01

    Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). It was reported that anti-histone autoantibody was detected in PBC, suggesting that bacterial histone-like DNA-binding protein (HLP) may be involved in the pathogenesis of PBC. To identify bacterial species in PBC to confirm this possibility, serum reactivity to bacterial cells was studied by ELISA. The IgM class Streptococcus intermedius titers were significantly higher in PBC than chronic hepatitis due to hepatitis C virus (CH-C) and healthy subjects. Among the streptococci, S. intermedius was selected for further study. The antigenic peptide of S. intermedius of HLP was synthesized to examine the serum reactivity to Si-HLP. IgM class anti-Si-HLP peptide titers were significantly higher in PBC. Immunoreactivity to anti-Si-HLP was detected in the cytoplasm of biliary epithelial cells and inflammatory cells in the portal area in PBC patients' livers. Streptococci, especially S. intermedius, might play a key role in the pathogenesis of PBC, possibly involving HLP.

  1. In situ nucleic acid hybridization of pyruvate dehydrogenase complex-E2 in primary biliary cirrhosis: pyruvate dehydrogenase complex-E2 messenger RNA is expressed in hepatocytes but not in biliary epithelium.

    PubMed

    Harada, K; Van de Water, J; Leung, P S; Coppel, R L; Nakanuma, Y; Gershwin, M E

    1997-01-01

    Pyruvate dehydrogenase-E2, or a cross-reactive molecule, has been shown by a variety of immunohistochemical methods to be present in increased amounts in biliary epithelial cells (BEC) in primary biliary cirrhosis (PBC). In this study, to further understand the nature of the immunoreactive molecule in BEC, we examined the expression of pyruvate dehydrogenase complex-E2 (PDC-E2) messenger RNA (mRNA) and PDC-E2 protein in sections of livers from patients and controls to help identify the molecule found in BEC. We performed in situ hybridization using an antisense probe against the major epitope of PDC-E2. The data were very striking and suggested that there was no increased production of PDC-E2 in BEC. For example, in livers from patients with PBC, PDC-E2 mRNA was found in periportal hepatocytes in 16 of 17 cases (94%). In contrast, interlobular bile ducts and septal bile ducts had detectable levels of PDC-E2 mRNA in only 1 of 17 (6%) and 3 of 8 (38%) cases, respectively. Interestingly, proliferating bile ductules contained detectable levels of mRNA in 12 of 15 cases (80%). In control liver, periportal hepatocytes were positive in 15 of 17 cases (88%). Interlobular bile ducts, septal bile ducts, and proliferating bile ductules expressed mRNA signals in 4 of 17 (24%), 2 of 10 (20%), and 14 of 16 (88%), respectively. When formalin-fixed, paraffin-embedded sections were examined by immunohistochemical staining with anti-PDC-E2 monoclonal antibody (mAb) C355.1, the interlobular bile ducts showed typical aberrant apical staining in all 10 PBC cases, but 0 of 9 liver controls. Periportal hepatocytes, proliferating bile ductules and infiltrating mononuclear cells stained with C355.1 but in a characteristic mitochondrial staining pattern. The presence of a PDC-E2-like molecule recognized by C355.1 is not reflected by the expression levels of PDC-E2 mRNA in the BEC of patients with PBC.

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

    ClinicalTrials.gov

    2017-01-24

    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

  3. Hepatic nodular lymphoid lesion with increased IgG4-positive plasma cells associated with primary biliary cirrhosis: a report of two cases.

    PubMed

    Calvo, Jessica; Carbonell, Nicolas; Scatton, Olivier; Marzac, Christophe; Ganne-Carrie, Nathalie; Wendum, Dominique

    2015-11-01

    The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as « probable histological feature of IgG4-related disease ». There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified.

  4. Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase complex in primary biliary cirrhosis

    PubMed Central

    1995-01-01

    The extraordinary specificity of bile duct destruction in primary biliary cirrhosis (PBC) and the presence of T cell infiltrates in the portal tracts have suggested that biliary epithelial cells are the targets of an autoimmune response. The immunodominant antimitochondrial response in patients with PBC is directed against the E2 component of pyruvate dehydrogenase (PDC-E2). Hitherto, there have only been limited reports on the characterization and V beta usage of PDC-E2-specific cloned T cell lines. In this study, we examined peripheral blood mononuclear cells (PBMC) for their reactivity to the entire PDC complex as well as to the E1- and E2-specific components. We also examined the phenotype, lymphokine profile, and V beta usage of PDC-specific T cell clones isolated from cellular infiltrates from the livers of PBC patients. We report that PBMC from 16/19 patients with PBC, but not 12 control patients, respond to the PDC-E2 subunit. Interestingly, this response was directed to the inner and/or the outer lipoyl domains, despite the serologic observation that the autoantibody response is directed predominantly to the inner lipoyl domain. Additionally, lymphokine analysis of interleukin (IL) 2/IL-4/interferon gamma production from individual liver-derived autoantigen-specific T cell clones suggests that both T helper cell Th1- and Th2-like clones are present in the liver. Moreover, there was considerable heterogeneity in the T cell receptor for antigen (TCR) V beta usage of these antigen- specific autoreactive T cell clones. This is in contrast to murine studies in which animals are induced to develop autoimmunity by specific immunization and have an extremely limited T cell V beta repertoire. Thus, our data suggest that in human organ-specific autoimmune diseases, such as PBC, the TCR V beta repertoire is heterogenous. PMID:7836925

  5. Biliary Atresia

    PubMed Central

    Bassett, Mikelle D.; Murray, Karen F.

    2011-01-01

    Extrahepatic biliary atresia (EHBA), an inflammatory sclerosing cholangiopathy, is the leading indication for liver transplantation in children. The cause is still unknown, although possible infectious, genetic, and immunologic etiologies have received much recent focus. These theories are often dependent on each other for secondary or coexisting mechanisms. Concern for EHBA is raised by a cholestatic infant, but the differential diagnosis is large and the path to diagnosis remains varied. Current treatment is surgical with an overall survival rate of approximately 90%. The goals of this article are to review the important clinical aspects of EHBA and to highlight some of the more recent scientific and clinical developments contributing to our understanding of this condition. PMID:18496390

  6. Decreased Expression of Vitamin D Receptor Affects an Immune Response in Primary Biliary Cholangitis via the VDR-miRNA155-SOCS1 Pathway

    PubMed Central

    Kempinska-Podhorodecka, Agnieszka; Milkiewicz, Malgorzata; Wasik, Urszula; Ligocka, Joanna; Zawadzki, Michał; Krawczyk, Marek; Milkiewicz, Piotr

    2017-01-01

    Primary biliary cholangitis (PBC) is an immune-mediated cholestatic disease. Vitamin D receptor (VDR)-dependent signaling constrains an inflammatory response by targeting the miRNA155-SOCS1 (suppressor of cytokine signaling 1) axis. The VDR-miRNA155-SOCS1 pathway was investigated in the context of the autoimmune response associated with PBC. Human liver tissues from non-cirrhotic PBC (n = 22), cirrhotic PBC (n = 22), cirrhotic primary sclerosing cholangitis (PSC, n = 13), controls (n = 23), and peripheral blood mononuclear cells (PBMC) obtained from PBC (n = 16) and PSC (n = 10) patients and healthy subjects (n = 11) were used for molecular analyses. VDR mRNA and protein expressions were substantially reduced in PBC livers (51% and 59%, respectively). Correspondingly, the decrease of SOCS1 protein expression in PBC livers, after normalization to a marker of lymphocytes and forkhead family transcriptional regulator box P3 (FOXP3, marker of Treg), was observed, and this phenomenon was accompanied by enhanced miRNA155 expression. In PSC livers, protein expressions of VDR and SOCS1 were comparable to the controls. However, in PBM cells, protein expressions of VDR and SOCS1 were considerably decreased in both PBC and PSC. We demonstrated that VDR/miRNA155-modulated SOCS1 expression is decreased in PBC which may lead to insufficient negative regulation of cytokine signaling. These findings suggest that the decreased VDR signaling in PBC could be of importance in the pathogenesis of PBC. PMID:28146070

  7. Plastic biliary stents for malignant biliary diseases.

    PubMed

    Huibregtse, Inge; Fockens, Paul

    2011-07-01

    Plastic biliary endoprostheses have not changed much since their introduction more than 3 decades ago. Although their use has been challenged by the introduction of metal stents, plastic stents still remain commonly used. Much work has been done to improve the problem of stent obstruction but without substantial clinical success. In this review, the authors discuss the history of plastic biliary stent development and the current use of plastic stents for malignant biliary diseases.

  8. Identification of novel molecules and pathogenic pathways in primary biliary cirrhosis: cDNA array analysis of intrahepatic differential gene expression

    PubMed Central

    Shackel, N; McGuinness, P; Abbott, C; Gorrell, M; McCaughan, G

    2001-01-01

    BACKGROUND—Primary biliary cirrhosis (PBC) is an autoimmune disease in which the pathogenesis of progressive liver injury is poorly understood.
AIM—To provide novel insights into the pathogenesis of PBC related liver injury using cDNA array analysis, which simultaneously examines expression of many genes.
METHODS—Utilising cDNA arrays of 874 genes, PBC was compared with primary sclerosing cholangitis (PSC) associated cirrhosis and non-diseased liver. Differential expression of 10 genes was confirmed by real time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
RESULTS—Array analysis identified many differentially expressed genes that are important in inflammation, fibrosis, proliferation, signalling, apoptosis, and oxidative stress. PBC was associated with increased expression of both Th1 and Th2 type molecules of the immune response. Fibrosis related gene expression featured upregulation of connective tissue growth factor and transforming growth factor beta3. Many more apoptosis associated molecules exhibited increased expression, consistent with apoptosis being a more active and regulated process, in PSC associated cirrhosis than in PBC. Increased expression of many genes of the Wnt and notch pathways implicated these highly conserved and linked pathways in PBC pathogenesis. The observed increases in expression of c-jun, c-myc, and c-fos related antigen 1 are consistent with increased Wnt pathway activity in PBC. Differential expression of four components of the Wnt pathway, Wnt-5a, Wnt-13, FRITZ, and beta-catenin, was confirmed by quantitative RT-PCR.
CONCLUSION—Many genes implicated in intrahepatic inflammation, fibrosis, and regeneration were upregulated in PBC cirrhosis. In particular, increased expression of a number of Drosophila homologues was seen in PBC.


Keywords: primary sclerosing cholangitis; apoptosis; fibrosis; connective tissue growth factor; Wnt; Th1/Th2; brain derived neurotrophic factor; notch

  9. Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study.

    PubMed

    Zhu, Jiangyi; Shi, Yongquan; Zhou, Xinmin; Li, Zengshan; Huang, Xiaofeng; Han, Zheyi; Wang, Jianhong; Wang, Ruian; Ding, Jie; Wu, Kaichun; Han, Ying; Fan, Daiming

    2013-06-01

    The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13-15 mg·kg(-1)·day(-1)) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1-2 but still progressed in patients at stages 3-4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3-4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

  10. Exercise therapy in primary biliary cirrhosis: the importance of moving while sitting on a surgical waiting list—a case study

    PubMed Central

    Hallsworth, Kate; Jopson, Laura; Jones, David E; Trenell, Michael I

    2016-01-01

    Background It is being increasingly recognised that reduced cardiorespiratory fitness is associated with poorer outcomes after major surgery. Exercise limitation and reduced aerobic capacity are common in people with end-stage liver disease. There is limited evidence about the role of exercise therapy in the management of primary biliary cirrhosis (PBC) and no studies have looked at the effect of exercise in people with PBC who are awaiting liver transplantation. This case study is the first to report that personalised exercise therapy improves cardiorespiratory fitness in a patient with PBC without worsening symptoms of severe fatigue. Methods Cardiopulmonary exercise testing was used to assess cardiorespiratory fitness in a patient with end-stage PBC prior to listing for transplantation. A personalised exercise programme was designed to improve cardiorespiratory fitness while the patient was on the transplant waiting list. Results Anaerobic threshold, VO2PEAK and maximum workload all improved with regular exercise. Fatigue levels remained unaltered. Conclusions This patient tolerated and adhered to a personalised exercise programme for a prolonged period of time while awaiting surgery despite significant fatigue and disease burden. Liver transplantation was successfully completed and this woman remains well over 2 years post-surgery. PMID:27429732

  11. The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase

    PubMed Central

    1988-01-01

    Autoantibodies to mitochondrial antigens are characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC), but the precise antigenic determinants recognized by these antibodies have not been defined. Recently, our laboratory identified a 1,370-bp rat liver cDNA clone that coded for a polypeptide recognized specifically by sera from patients with PBC but not by sera from patients with other forms of liver disease. This recombinant protein was identified as the 74-kD M2 mitochondrial inner membrane autoantigen, now known to be dihydrolipoamide acetyltransferase. In the present study, we have identified a 603-bp fragment that codes for a polypeptide containing all of the autoreactivity of the original clone. In addition, based on hydrophobicity/hydrophilicity plots of the amino acid sequence of this polypeptide segment, several peptides were synthesized and tested for reactivity by an inhibition assay using sera from patients with PBC. One peptide, defined by the amino acids AEIETDKATIGFEVQEEGYL, absorbed serum reactivity to the protein product of the original clone. Of particular interest was the finding that this peptide contains the lipoic acid binding site KATIGF of the dihydrolipoamide acetyltransferase found in the inner mitochondrial membrane. Thus, it appears that for this autoantigen, the target of the autoantibodies corresponds to a functional site of the dihydrolipoamide acetyltransferase. PMID:2455013

  12. Cryptic antigenic determinants on the extracellular pyruvate dehydrogenase complex/mimeotope found in primary biliary cirrhosis. A probe by affinity mass spectrometry.

    PubMed

    Yip, T T; Van de Water, J; Gershwin, M E; Coppel, R L; Hutchens, T W

    1996-12-20

    Affinity mass spectrometry (AMS) was used to evaluate the structural diversity of the E2 component of pyruvate dehydrogenase complex (PDC) in normal and diseased liver cells, including those from patients with the autoimmune disease primary biliary cirrhosis (PBC). Two different antibodies to PDC-E2, the immunodominant mitochondrial autoantigen in patients with PBC, were used. AMS was performed directly on frozen liver sections and purified bile duct epithelial cells. Mass spectrometric signals associated with the molecular recognition of PBC-specific antigenic determinants were enhanced by an in situ enzyme-linked signal amplification process. Samples from patients with PBC gave strong positive signals for the antigen(s) recognized by the monoclonal antibody C355.1. Conversely, tissues from normal and disease controls showed only a minimal signal. AMS was used to identify specific antigenic determinants within the E2 component of PDC for comparison with unknown antigenic determinants observed by affinity capture with C355.1 monoclonal antibody from PBC samples. PDC components bound to C355.1 were mapped and identified by mass before dissociation from the E2 component. A similar approach was used to identify unknown antigenic determinants associated with PBC. We believe AMS may be an important new approach with wide application to the identification of molecules associated with a number of disease states.

  13. RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial

    PubMed Central

    Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

    2015-01-01

    Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. Methods and analysis RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. Ethics and dissemination The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants

  14. 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

  15. [Lymphoma of the biliary tract: report of 2 cases].

    PubMed

    Machado, M C; Abdo, E E; Penteado, S; Perosa, M; da Cunha, J E

    1994-01-01

    We report two cases one a primary non Hodgkin lymphoma of the hepatic common duct and the other a secondary involvement of the biliary tract in a patient with a Hodgkin's disease. In the first case a local resection of the biliary lymphoma was undertaken being the patient alive six months after the procedure. The second case died early after the operative biliary external drainage in a septic shock before any specific treatment could be initiated.

  16. Elevated circulating CD14(low)CD16(+) monocyte subset in primary biliary cirrhosis correlates with liver injury and promotes Th1 polarization.

    PubMed

    Peng, Anping; Ke, Peifeng; Zhao, Rong; Lu, Xinyi; Zhang, Cheng; Huang, Xianzhang; Tian, Guangjun; Huang, Jun; Wang, Jinli; Invernizzi, Pietro; Chen, Qubo; Zhuang, Junhua

    2016-11-01

    Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease in which monocytes/macrophages infiltration and skewed T helper type (Th) 1 and Th17 cell responses participate in the development of the disease. Human peripheral blood monocytes are heterogeneous and can be divided into classical CD14(high)CD16(-), intermediate CD14(high)CD16(+), and nonclassical CD14(low)CD16(+) monocyte subsets. Compared to classical monocytes, CD16(+) monocytes are generally termed pro-inflammatory monocytes and play an important pathogenic role in autoimmune diseases. However, little is known about the immunophenotype and immunopathogenic role of peripheral blood CD16(+) monocytes in PBC. Thus, we investigated the phenotype and function of these circulating monocyte subsets from PBC patients. The frequencies of circulating CD14(high)CD16(+) and CD14(low)CD16(+) subpopulation were increased in disease compared with healthy controls. Among them, CD14(low)CD16(+) monocyte subset positively correlated with disease progress, liver damage indicators and serum C-reactive protein, respectively. Furthermore, the frequencies of Th1 and Th17 cells were upregulated and CD14(low)CD16(+) monocyte subset was also positively associated with Th1 cell frequency in PBC. Using a vitro coculture model, we further found that CD14(low)CD16(+) monocytes promoted Th1 cell polarization compared to classical monocytes. Interleukin-12 (IL-12) and direct contact of patient CD4(+)T cell and CD14(low)CD16(+) monocytes, were responsible for CD14(low)CD16(+) monocytes promotion of Th1 cells polarization in PBC. Our study demonstrated that the enhanced CD14(low)CD16(+) monocyte subset participated in fostering liver damage and inflammatory responses, and promoted Th1 cells skewing in PBC.

  17. Diagnosis of Liver Involvement in Primary Sjögren Syndrome

    PubMed Central

    Zeron, Pilar Brito; Retamozo, Soledad; Bové, Albert; Kostov, Belchin Adriyanov; Sisó, Antoni

    2013-01-01

    Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sjögren syndrome (SS). In the 1990s, a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease, liver function and a complete panel of autoantibodies. Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS. The most recent studies have shown that, after eliminating hepatotoxic drugs and fatty liver disease, the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases. The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important, since the two processes require different therapeutic approaches and have different prognoses. With respect to viral infections, chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area, while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries. After eliminating viral hepatitis, primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS. PBC-related SS patients may have a broad spectrum of abnormalities of the liver, including having no clinical or analytical data suggestive of liver disease. Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I), and nearly 10% of these patients have an AIH-PBC overlap. Finally, IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis, especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present. PMID:26355632

  18. 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.

  19. Common controversies in management of biliary strictures

    PubMed Central

    Parsi, Mansour A

    2017-01-01

    Biliary strictures are caused by a heterogeneous group of benign and malignant conditions, each requiring a specific treatment approach. Management of biliary strictures often involves endoscopy either for definite treatment, as a bridge to surgery or for palliative purposes. Endoscopic treatment of various types of biliary strictures is not standardized and there are multiple areas of controversy regarding the best treatment options. These controversies are mainly due to lack of well-designed comparative studies to support a specific therapy. This paper reviews three common areas of controversy in the endoscopic management of biliary strictures. The areas discussed in this editorial include the role of biliary drainage in resectable malignant strictures and whether such drainage should be performed routinely prior to surgery, the best endoscopic palliation for unresectable hilar strictures and whether unilateral or bilateral stenting should be attempted, and the optimal endoscopic management for dominant strictures in patients with primary sclerosing cholangitis. The goal of this editorial is twofold. The first is to review the current literature on management of the aforementioned strictures and offer recommendations based on available evidence. The second goal is to highlight the gaps in our knowledge which in turn can encourage future research on these topics. PMID:28275292

  20. Biliary atresia: Where do we stand now?

    PubMed Central

    Govindarajan, Krishna Kumar

    2016-01-01

    The pathway from clinical suspicion to establishing the diagnosis of biliary atresia in a child with jaundice is a daunting task. However, investigations available help to point towards the correct diagnosis in reasonable time frame. Imaging by Sonography has identified several parameters which can be of utility in the diagnostic work up. Comparison of Sonography with imaging by Nuclear medicine can bring out the significant differences and also help in appropriate imaging. The battery of Biochemical tests, available currently, enable better understanding of the line-up of investigations in a given child with neonatal cholestasis. Management protocols enable standardized care with optimal outcome. The place of surgical management in biliary atresia is undisputed, although Kasai procedure and primary liver transplantation have been pitted against each other. This article functions as a platform to bring forth the various dimensions of biliary atresia. PMID:28083081

  1. Biliary atresia: Where do we stand now?

    PubMed

    Govindarajan, Krishna Kumar

    2016-12-28

    The pathway from clinical suspicion to establishing the diagnosis of biliary atresia in a child with jaundice is a daunting task. However, investigations available help to point towards the correct diagnosis in reasonable time frame. Imaging by Sonography has identified several parameters which can be of utility in the diagnostic work up. Comparison of Sonography with imaging by Nuclear medicine can bring out the significant differences and also help in appropriate imaging. The battery of Biochemical tests, available currently, enable better understanding of the line-up of investigations in a given child with neonatal cholestasis. Management protocols enable standardized care with optimal outcome. The place of surgical management in biliary atresia is undisputed, although Kasai procedure and primary liver transplantation have been pitted against each other. This article functions as a platform to bring forth the various dimensions of biliary atresia.

  2. Choledocholithiasis in anomalous biliary system.

    PubMed

    Leung, L C; Wong, C Y; Wong, C M; Cheung, K K

    1996-06-01

    Although congenital biliary abnormalities are common, preduodenal portal vein is very rare, not to mention preduodenal common bile duct (CBD) which has not been described before in the literature. A case with both anomalies complicated by biliary tract stones is reported. A brief review of embryonic development is also presented to explain the unusual biliary anatomy of this patient.

  3. Diagnosis and Treatment of Biliary Fistulas in the Laparoscopic Era

    PubMed Central

    Crespi, M.; Montecamozzo, G.; Foschi, D.

    2016-01-01

    Biliary fistulas are rare complications of gallstone. They can affect either the biliary or the gastrointestinal tract and are usually classified as primary or secondary. The primary fistulas are related to the biliary lithiasis, while the secondary ones are related to surgical complications. Laparoscopic surgery is a therapeutic option for the treatment of primary biliary fistulas. However, it could be the first responsible for the development of secondary biliary fistulas. An accurate preoperative diagnosis together with an experienced surgeon on the hepatobiliary surgery is necessary to deal with biliary fistulas. Cholecystectomy with a choledocoplasty is the most frequent treatment of primary fistulas, whereas the bile duct drainage or the endoscopic stenting is the best choice in case of minor iatrogenic bile duct injuries. Roux-en-Y hepaticojejunostomy is the extreme therapeutic option for both conditions. The sepsis, the level of the bile duct damage, and the involvement of the gastrointestinal tract increase the complexity of the operation and affect early and late results. PMID:26819608

  4. Biliary and gallbladder dyskinesia.

    PubMed

    George, Josh; Baillie, John

    2007-08-01

    Gallbladder and biliary dyskinesia are conditions that are becoming increasingly recognized due to improved technology. They are motility disorders that affect the gallbladder and sphincter of Oddi (SO), respectively. Gallbladder dyskinesia presents with typical biliary pain in the absence of gallstones. Work-up includes laboratory tests and imaging to rule out gallstones. Further investigation leads to a functional radionuclide study to investigate gallbladder ejection fraction. An ejection fraction of less than 40% is considered abnormal, and patients should be referred for cholecystectomy. Symptom relief after the procedure has been seen in 94% to 98% of patients. The term sphincter of Oddi dysfunction (SOD) describes a collection of pain syndromes that are attributed to a motility disorder of the SO. SOD can be further subdivided into biliary and pancreatic SOD. Patients typically have had a prior cholecystectomy and present with episodic biliary pain. The initial work-up includes laboratory tests and imaging to rule out other structural causes of abdominal pain, such as retained gallstones. Imaging and laboratory studies further subdivide patients into types of SOD. SO manometry (SOM) is the gold standard for assessing biliary dyskinesia and can help stratify patients into one of two groups: SO stenosis versus SO dyskinesia. Those with stenosis (type I SOD) are the most likely to respond to treatment with endoscopic biliary sphincterotomy (EBS). As the vast majority of type I patients (>/= 90%) benefit from EBS, SOM is not necessary. Pancreatic SOD patients can be similarly divided into one of three groups. These patients present with recurrent bouts of abdominal pain and/or pancreatitis in the absence of gallstones or other structural abnormalities. Pancreatic sphincter manometry can help distinguish which patients would benefit from endoscopic pancreatic sphincterotomy. Recurrent stenosis of the opening after endoscopic treatment in these patients may

  5. [Intraductal biliary metastases from colorectal cancer: a report of two cases].

    PubMed

    Tirapu de Sagrario, M G; Baleato González, S; García Figueiras, R; Coessens, A

    2014-01-01

    Intrabiliary metastases are rare, and their imaging characteristics make them easy to confuse with primary biliary tumors, especially with cholangiocarcinoma. We present two cases of patients with histories of colorectal cancer who presented with obstructive jaundice secondary to intraductal metastases. We describe the imaging findings and emphasize the key radiologic manifestations for the differential diagnosis between intrabiliary metastases and primary biliary tumors.

  6. Biliary obstruction - slideshow

    MedlinePlus

    ... anatomy URL of this page: //medlineplus.gov/ency/presentations/100199.htm Biliary obstruction - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 4 Go to slide 2 ...

  7. 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.

  8. External biliary fistula.

    PubMed

    Sharma, A K

    2001-01-01

    A biliary fistula is almost invariably related to gallstone disease and commonly follows a hurried cholecystectomy by an inexperienced surgeon. This catastrophy which is largely preventable, often necessitates repeated surgical intervention and accrues an estimated 5-year mortality rate approaching 30%. Published series only show a slight increase in the incidence (one per 150-200) after laparoscopic cholecystectomy. The injury results from imprecise dissection and inadequate demonstration of the anatomical structures. The diagnosis is usually obvious and persistent tachycardia and hypotension inspite of an adequate intravenous infusion and a normal central venous pressure is another well known indicator of subhepatic collection of bile, which indicates an urgent ultrasonographic scanning of the upper abodmen. ERCP is a useful diagnostic and therapeutic tool when the continuity of the extra-hepatic biliary system has not been disrupted. An endobiliary stent can be placed across the defect in the same sitting, to tide over the immediate crisis and perhaps treat the patient on a permanent basis. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive technique of outlining both the intra and extrahepatic biliary tree, which can provide a better road map of the fistula than an ERCP. The management has to be tailored to the patient's condition and the expertise available. A bilio-enteric anastomosis, performed 4 to 6 months after the initial surgery on a dilated common hepatic duct is more likely to succeed than an operation on a septic, hypoproteinemic patient with sodden, friable, non-dilated bile ducts. On the other hand, waiting for the ducts to dilate in a patient with a complete transection of the bile ducts with complete biliary diversion only leads to depletion of the bile acid pool, severe electrolyte derangement and nutritional failure, leading on to sepsis and death.

  9. Transjugular Insertion of Biliary Stents (TIBS) in Two Patients with Malignant Obstruction, Ascites, and Coagulopathy

    SciTech Connect

    Amygdalos, Michael A.; Haskal, Ziv J.; Cope, Constantin; Kadish, Steven L.; Long, William B.

    1996-03-15

    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 to standard transhepatic drainage.

  10. [Biliary ileus--potential complication of cholecystolithiasis].

    PubMed

    Okolicány, R; Prochotský, A; Skultéty, J; Sekác, J; Mifkovic, A

    2008-11-01

    Biliary ileus is a rare complication of cholecystolithiasis. The condition occurs predominantly in the elderly with incidence rates of 1-4%, according to the literature data. Most commonly, it develops as a complication of cholelithiasis which remained untreated or was managed conservatively, or as a complication of a gallbladder decubitus necrosis. The condition results in a cholecysto-duodenal fistula. In this case, the cholecystolithiasis is latent or is clinically manifested in a third of the patients. A total of 1560 cholecystectomies (1345 L-CHE and 215 conventional CHE) were performed in our clinic during a five-year period. Biliary ileus was an indication for operation only in two subjects, during the studied period. In the both cases, the diagnosis was established intraoperatively, although upon re-examination of the visualization modalities views (upright native abdominal views, CT scans) the authors concluded that the primary cause of the ileus could have already been identified, based on the above views.

  11. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

    PubMed

    Juran, Brian D; Hirschfield, Gideon M; Invernizzi, Pietro; Atkinson, Elizabeth J; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E Jenny; Mason, Andrew L; Myers, Robert P; Milkiewicz, Piotr; Odin, Joseph A; Luketic, Velimir A; Bacon, Bruce R; Bodenheimer, Henry C; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K; Bossa, Fabrizio; Gershwin, M Eric; deAndrade, Mariza; Amos, Christopher I; Lazaridis, Konstantinos N; Seldin, Michael F; Siminovitch, Katherine A

    2012-12-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.

  12. Imaging of malignancies of the biliary tract- an update

    PubMed Central

    2014-01-01

    Malignancies of the biliary tract include cholangiocarcinoma, gallbladder cancers and carcinoma of the ampulla of Vater. Biliary tract adenocarcinomas are the second most common primary hepatobiliary cancer. Due to their slow growing nature, non-specific and late symptomatology, these malignancies are often diagnosed in advanced stages with poor prognosis. Apart from incidental discovery of gall bladder carcinoma upon cholecystectomy, early stage biliary tract cancers are now detected with computed tomography (CT) and magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP). Accurate characterization and staging of these indolent cancers will determine outcome as majority of the patients’ are inoperable at the time of presentation. Ultrasound is useful for initial evaluation of the biliary tract and gallbladder masses and in determining the next suitable modality for further evaluation. Multimodality imaging plays an integral role in the management of the biliary tract malignancies. The imaging techniques most useful are MRI with MRCP, endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and positron emission tomography (PET). In this review we will discuss epidemiology and the role of imaging in detection, characterization and management of the biliary tract malignancies under the three broad categories of cholangiocarcinomas (intra- and extrahepatic), gallbladder cancers and ampullary carcinomas. PMID:25608662

  13. [Mascs of functional disorders of the biliary tract].

    PubMed

    Kazyulin, A N

    2015-01-01

    The survey of its own and literature data describes the clinical "masks" of the primary and second functional disorders of the biliary tract, describes the mechanisms of their formation, which include the plural disturbances of the organs interactions, psycho - emotional and vegetative disturbances, development ofbiliar and pancreatic insufficiency. It is shown that Hymecromone (Odeston) can be successfully used, as the base means, with the treatment of patients with primary and second functional disorders of the biliary tract with different clinical "masks" of this pathology.

  14. Direct cholangiography and biliary drainage.

    PubMed

    Burcharth, F; Kruse, A

    1996-01-01

    Direct cholangiography by percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography has greatly improved diagnostic work-up of patients with known or suspected biliary obstruction. These diagnostic procedures were introduced in Denmark in the early 1970s, and technical refinements and clinical research of the methods were initiated. The Danish contribution led to definition of indications for direct cholangiography and general acceptance of the methods in daily clinical practice; nationally as well as internationally. The transhepatic cholangiography with selective catheterization of the biliary ducts permitted external drainage of obstructed ducts. The disadvantages of this technique inspired the innovation of internal biliary drainage and the invention of the biliary endoprosthesis. The endoscopic approach to the biliary tract and the technical improvements of accessory instruments led to the early introduction of therapeutic procedures, i.e. papillotomy, stone removal, biliary drainage and treatment of strictures and post-traumatic lesions. Experimental and clinical research with endoprostheses improved their function and prevented dislodgment. Clinical research documented that biliary drainage by endoprosthesis is a valuable alternative to surgical bypass in patients with inoperable biliary obstructions. Endoscopic therapeutic procedures for common bile duct stones have almost replaced conventional surgical treatment. Endoluminal imaging techniques are under evaluation and may contribute to future improvements.

  15. Biliary atresia in lampreys.

    PubMed

    Youson, J H

    1993-01-01

    The preceding pages have described an organism that is far removed from mammals on the taxonomic scale of vertebrates but one that has proven to have a unique and most useful system for studies of liver function and, in particular, bile product transport and excretion. It is also an organism in which iron loading can be studied in the liver and other organs and tissues. Many of the events that occur in this animal during its life cycle with regard to bile pigment metabolism as normal programmed phenomena are unparalleled among the vertebrates. In the larval (ammocoete) period of lampreys, there is an intrahepatic gallbladder and a biliary tree that is well equipped for the storage, transport, and elimination of bile products into the intestine for ultimate excretion with the feces. The importance of the patency of these bile ducts to bile excretion is illustrated in one species of lampreys in which the bile ducts of young ammocoetes become infested with larval nematodes to a degree that bile pigment regurgitation into the blood results in a green serum that is identified as biliverdin. Despite having serum levels of biliverdin that would be toxic to humans, these individuals live a complete larval life. The larvae of all lamprey species undergo a phase of metamorphosis in which they transform into adults. During this phase the larval gallbladder, the bile canaliculi of the hepatocytes, and all the intrahepatic bile ducts completely regress in a developmental process called lamprey biliary atresia. The epithelium of the extrahepatic common bile duct transforms and expands into a caudal portion of the endocrine pancreas of the adult. Many of the events of lamprey biliary atresia resemble events occurring during experimental and pathological conditions of mammalian cholestasis, including disruption to the bile-blood barrier (intercellular junctions), accumulation of bile components in the cytoplasmic inclusions, and alteration of the distribution of membrane enzymes

  16. Biliary metastasis in colorectal cancer confers a poor prognosis: case study of 5 consecutive patients

    PubMed Central

    Koh, Frederick Hong-Xiang; Shi, Wang

    2017-01-01

    The biliary duct is an extremely rare site for colon cancer metastasis. It often leads to a diagnostic dilemma, since primary cholangiocarcinoma (potentially treatable with surgery) has a similar presentation. This paper highlights our experience with 5 consecutive patients who had colon malignancy with biliary metastasis, and prognosis of their disease. Five patients, with a history of primary colon cancer since 2010, were identified to have biliary metastasis. Of these, 4 (80.0%) patients were male. The median time to diagnosis of biliary metastasis from diagnosis of colon cancer was 59.2 months (0-70.1 months), and all exhibited symptoms of biliary obstruction or its associated complications. Evaluation of the tumour samples revealed all specimens to be negative for CK7 but positive for CK20, suggestive of a colorectal primary. The median survival of the 5 patients was 23.5 months (1.8-44.5 months) from the diagnosis of biliary metastasis. However, none of their death was related to the direct complication of biliary obstruction. Biliary metastasis is a rare entity for metastatic colon malignancy. Diagnosis may be difficult radiologically, and immunohistochemical staining may help in identification. The overall survival for these patients is dismal. PMID:28317047

  17. Aortic and splanchnic artery aneurysms: Unusual causes of biliary obstruction - A retrospective cohort from literature.

    PubMed

    Tin, Kevin; Sobani, Zain A; Horovitz, Joel; Rahmani, Rabin

    2017-03-01

    Mechanical obstruction of the biliary tree and resultant stasis are the cornerstone of a spectrum of diseases ranging from biliary colic to fulminant cholangitis. Infrequently acquired abnormalities of the abdominal vasculature can lead to biliary obstruction. In 2010, we reported a case of acute cholangitis resulting from compression of extra hepatic bile duct by an abdominal aortic aneurysm (AAA). We subsequently conducted a follow up scoping review of literature to identify other cases of acquired abdominal arterial abnormalities resulting in biliary obstruction looking at their management and outcomes. The articles were independently reviewed by two of the authors and pertinent data was extracted. The data was divided on an anatomic basis into two groups: one with primary aortic pathology and one with splanchnic vessel pathology. We identified 39 cases of biliary obstruction secondary to acquired aortic or splanchnic vessel abnormalities; 16 were caused by AAAs and 23 by splanchnic vessels. The cases were managed via conservative, endoscopic, endovascular or open surgical options based on the available technology and expertise. Although uncommon, recognition of aortic and splanchnic arterial abnormalities as a potential cause of biliary obstruction is important as management entails not only cautious decompression of the biliary tree but also addressing the underlying vascular pathology. We recommend that extrinsic biliary compression by an aneurysm or pseudoaneurysm be considered among the differential diagnosis in patients presenting with biliary obstruction and a known lesion of the abdominal vasculature.

  18. 47Calcium absorption in parenchymatous and biliary liver disease

    PubMed Central

    Whelton, Michael J.; Kehayoglou, A. K.; Agnew, J. E.; Turnberg, L. A.; Sherlock, Sheila

    1971-01-01

    As measured by whole body retention of isotopic calcium given in milk, absorption of calcium was impaired in 10 patients with chronic parenchymal non-biliary liver disease who were icteric. Mean absorption was normal in 15 patients with parenchymal liver disease who were anicteric although some individual patients absorbed less than any of the controls. Depressed absorption of calcium was seen in 10 patients with primary biliary cirrhosis and seven patients with intra- or extra-hepatic biliary obstructive disease. The most likely cause for this malabsorption is reduced bile salt secretion into the intestinal lumen which impairs vitamin D and fat absorption. The finding that parenteral vitamin D increased calcium absorption to normal levels in five patients with primary biliary cirrhosis suggests that deficiency of this vitamin is a major and correctable factor leading to calcium malabsorption in such patients. Precipitation of calcium salts by excess intraluminal fat appears to be a further possible factor reducing calcium absorption in these patients. These findings emphasize the importance of parenteral vitamin D therapy in patients with chronic obstructive biliary diseases. They also suggest that certain patients with chronic parenchymatous liver disease, particularly those who are icteric, may also occasionally require therapy with vitamin D. PMID:5171934

  19. 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.

  20. Primary Biliary Acids Inhibit Hepatitis D Virus (HDV) Entry into Human Hepatoma Cells Expressing the Sodium-Taurocholate Cotransporting Polypeptide (NTCP)

    PubMed Central

    Veloso Alves Pereira, Isabel; Buchmann, Bettina; Sandmann, Lisa; Sprinzl, Kathrin; Schlaphoff, Verena; Döhner, Katinka; Vondran, Florian; Sarrazin, Christoph; Manns, Michael P.; Pinto Marques Souza de Oliveira, Cláudia; Sodeik, Beate; Ciesek, Sandra; von Hahn, Thomas

    2015-01-01

    Background The sodium-taurocholate cotransporting polypeptide (NTCP) is both a key bile acid (BA) transporter mediating uptake of BA into hepatocytes and an essential receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV). In this study we aimed to characterize to what extent and through what mechanism BA affect HDV cell entry. Methods HuH-7 cells stably expressing NTCP (HuH-7/NTCP) and primary human hepatocytes (PHH) were infected with in vitro generated HDV particles. Infectivity in the absence or presence of compounds was assessed using immunofluorescence staining for HDV antigen, standard 50% tissue culture infectious dose (TCID50) assays and quantitative PCR. Results Addition of primary conjugated and unconjugated BA resulted in a dose dependent reduction in the number of infected cells while secondary, tertiary and synthetic BA had a lesser effect. This effect was observed both in HuH-7/NTCP and in PHH. Other replication cycle steps such as replication and particle assembly and release were unaffected. Moreover, inhibitory BA competed with a fragment from the large HBV envelope protein for binding to NTCP-expressing cells. Conversely, the sodium/BA-cotransporter function of NTCP seemed not to be required for HDV infection since infection was similar in the presence or absence of a sodium gradient across the plasma membrane. When chenodeoxycolic acid (15 mg per kg body weight) was administered to three chronically HDV infected individuals over a period of up to 16 days there was no change in serum HDV RNA. Conclusions Primary BA inhibit NTCP-mediated HDV entry into hepatocytes suggesting that modulation of the BA pool may affect HDV infection of hepatocytes. PMID:25646622

  1. Ceruletide analgesia in biliary colic.

    PubMed

    Pardo, A; Celotti, F; De Paolis, C

    1984-10-01

    Ceruletide is a decapeptide isolated from the skin of an Australian frog. Its chemical and biologic relationship to cholecystokinin and its potent relaxant effect on the sphincter of Oddi makes it useful in biliary colic. In this double-blind placebo-controlled experiment, 60 subjects with moderate to severe pain caused by biliary colic were injected with ceruletide, 1 ng/kg iv or with an equal volume of saline solution. Pain in the right hypochondrium, referred pain, and Murphy's sign were scored before and after treatment. Data indicate that ceruletide is effective in biliary colic.

  2. 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

  3. Case-control study on prednisolone combined with ursodeoxycholic acid and azathioprine in pure primary biliary cirrhosis with high levels of immunoglobulin G and transaminases: efficacy and safety analysis.

    PubMed

    Fang, Yu-Qing; Lv, Dong-Xia; Jia, Wei; Li, Jun; Deng, Yong-Qiong; Wang, Yan; Yu, Min; Wang, Gui-Qiang

    2014-10-01

    To the best of our knowledge, this is the first study to address the use of glucocorticoids in the comparatively special population of pure primary biliary cirrhosis (PBC) patients who have high levels of immunoglobulin G (IgG) and transaminases but do not have PBC-autoimmune hepatitis overlap syndrome. Ursodeoxycholic acid (UDCA) is now assumed to be the standard therapy for PBC patients. However, patients treated with UDCA still have a risk of progression to cirrhosis and end-stage liver disease. The most recent European Association for the Study of the Liver guidelines of 2009 declared that further studies on glucocorticoid therapy in this disease should be a priority. Therefore, we designed this 3-year longitudinal retrospective study, which might provide deep insight into the treatment for PBC.The aim of this study was to assess whether the combination of prednisolone, UDCA, and azathioprine was superior to UDCA alone in these PBC patients.Sixty patients were enrolled in this study. Thirty-one patients underwent UDCA monotherapy, and 29 patients were treated with prednisolone, UDCA, and azathioprine. We analyzed their biochemistries, immune parameters, liver synthetic function, and noninvasive assessments of liver fibrosis, as well as treatment efficacy and adverse effects at baseline and at 1, 3, 6, 12, 24, and 36 months.Alkaline phosphatase (ALP), γ-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase levels and the aspartate aminotransferase-to-platelet ratio index (APRI) and S-index improved dramatically in both groups, whereas IgG levels only decreased in the combination group (all P < 0.05). Albumin (ALB) levels decreased in the UDCA group but increased with the combination treatment at 36 months. Significant differences between the 2 groups were observed at 36 months in ALP (P = 0.005), IgG (P = 0.002), ALB (P = 0.002), APRI (P = 0.015), and S-index (P = 0.020). Prednisolone combined with UDCA and

  4. Multidetector CT of emergent biliary pathologic conditions.

    PubMed

    Patel, Neel B; Oto, Aytekin; Thomas, Stephen

    2013-01-01

    Various biliary pathologic conditions can lead to acute abdominal pain. Specific diagnosis is not always possible clinically because many biliary diseases have overlapping signs and symptoms. Imaging can help narrow the differential diagnosis and lead to a specific diagnosis. Although ultrasonography (US) is the most useful imaging modality for initial evaluation of the biliary system, multidetector computed tomography (CT) is helpful when US findings are equivocal or when biliary disease is suspected. Diagnostic accuracy can be increased by optimizing the CT protocol and using multiplanar reformations to localize biliary obstruction. CT can be used to diagnose and stage acute cholecystitis, including complications such as emphysematous, gangrenous, and hemorrhagic cholecystitis; gallbladder perforation; gallstone pancreatitis; gallstone ileus; and Mirizzi syndrome. CT also can be used to evaluate acute biliary diseases such as biliary stone disease, benign and malignant biliary obstruction, acute cholangitis, pyogenic hepatic abscess, hemobilia, and biliary necrosis and iatrogenic complications such as biliary leaks and malfunctioning biliary drains and stents. Treatment includes radiologic, endoscopic, or surgical intervention. Familiarity with CT imaging appearances of emergent biliary pathologic conditions is important for prompt diagnosis and appropriate clinical referral and treatment.

  5. Obstructive Biliary Tract Disease

    PubMed Central

    White, Thomas Taylor

    1982-01-01

    The techniques that have come into general use for diagnosing problems of obstructive jaundice, particularly in the past ten years, have been ultrasonography, computerized tomography, radionuclide imaging, transhepatic percutaneous cholangiography using a long thin needle, transhepatic percutaneous drainage for obstructive jaundice due to malignancy, endoscopic retrograde cannulation of the papilla (ERCP), endoscopic sphincterotomy and choledochoscopy. It is helpful to review obstructive jaundice due to gallstones from a clinical point of view and the use of the directable stone basket for the retrieval of retained stones, choledochoscopy for the same purpose using the rigid versus flexible choledochoscopes and dissolution of stones using various fluids through a T tube. The use of dilation of the sphincter for the treatment of stenosis or stricture of the bile duct is now frowned on; rather, treatment choices are between the use of sphincteroplasty versus choledochoduodenostomy and choledochojejunostomy. Any patient with obstructive jaundice or anyone undergoing manipulation of the bile ducts should have prophylactic antibiotic therapy. The current literature regarding treatment of cancer of the bile ducts is principally devoted to the new ideas relative to treatment of tumors of the upper third, especially the bifurcation tumors that are now being resected rather than bypassed. Tumors of the distal bile duct are still being resected by focal operations. Finally, it is now felt that early operation for congenital biliary atresia and choledochal cysts gives the best prognosis, with preoperative diagnosis now possible with the use of ultrasonography and ERCP. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 8.Figure 9. PMID:7051569

  6. Epithelial–Mesenchymal Interactions in Biliary Diseases

    PubMed Central

    Fabris, Luca; Strazzabosco, Mario

    2013-01-01

    In most cholangiopathies, liver diseases of different etiologies in which the biliary epithelium is the primary target in the pathogenic sequence, the central mechanism involves inflammation. Inflammation, characterized by pleomorphic peribiliary infiltrate containing fibroblasts, macrophages, lymphocytes, as well as endothelial cells and pericytes, is associated to the emergence of “reactive cholangiocytes.” These biliary cells do not possess bile secretory functions, are in contiguity with terminal cholangioles, and are of a less-differentiated phenotype. They have acquired several mesenchymal properties, including motility and ability to secrete a vast number of proinflammatory chemo/cytokines and growth factors along with de novo expression of a rich receptor machinery. These functional properties enable reactive cholangiocytes to establish intimate contacts and to mutually exchange a variety of paracrine signals with the different mesenchymal cell types populating the portal infiltrate. The extensive crosstalk between the epithelial and mesenchymal compartments is the driver of liver repair mechanisms in cholangiopathies, ultimately evolving toward portal fibrosis. Herein, the authors first review the properties of the different cell types involved in their interaction, and then analyze the underlying molecular mechanisms as they relate to liver repair in cholangiopathies. PMID:21344348

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  8. [Biliary atresia and polysplenia syndrome].

    PubMed

    Kerkeni, Yosra; Ksia, Amine; Zitouni, Hayet; Belghith, Mohsen; Lassad, Sahnoun; Krichene, Imed; Mekki, Mongi; Nouri, Abdellatif

    2015-01-01

    Polysplenia syndrome is a rare malformation characterized by the association of multiple rates and other congenital anomalies dominated by cardiac, vascular, intestinal and bile malformations. We report the observation of a patient operated in the neonatal period (3 days) for an upper intestinal obstruction with situs inversus. Surgical exploration noted the presence of multiple rates, a preduodenal vein, a biliary atresia and a duodenal atresia. The surgical procedures performed were a latero-lateral duodeno-duodenostomy and hepatoportoenterostomy of KASAI with simple immediate and delayed outcomes. The follow up was of 23 years. We recall the epidemiological characteristics of this malformative association and we discuss the role played by the prognosis of polysplenia syndrome in the evolution of biliary atresia. The diagnosis and treatment of biliary atresia are always urgent to increase the chances of success of the Kasai, and the chances of prolonged survival with native liver. However, almost all long-term survivors (even anicteric) have biliary cirrhosis, which requires lifelong follow up.

  9. Management of Benign Biliary Strictures

    SciTech Connect

    Laasch, Hans-Ulrich; Martin, Derrick F.

    2002-12-15

    Benign biliary strictures are most commonly a consequence of injury at laparoscopic cholecystectomy or fibrosis after biliary-enteric anastomosis. These strictures are notoriously difficult to treat and traditionally are managed by resection and fashioning of acholedocho- or hepato-jejunostomy. Promising results are being achieved with newer minimally invasive techniques using endoscopic or percutaneous dilatation and/or stenting and these are likely to play an increasing role in the management. Even low-grade biliary obstruction carries the risks of stone formation, ascending cholangitis and hepatic cirrhosis and it is important to identify and treat this group of patients. There is currently no consensus on which patient should have what type of procedure, and the full range of techniques may not be available in all hospitals. Careful assessment of the risks and likely benefits have to be made on an individual basis. This article reviews the current literature and discusses the options available. The techniques of endoscopic and percutaneous dilatation and stenting are described with evaluation of the likely success and complication rates and compared to the gold standard of biliary-enteric anastomosis.

  10. Influence of the Biliary System on Biliary Bacteria Revealed by Bacterial Communities of the Human Biliary and Upper Digestive Tracts.

    PubMed

    Ye, Fuqiang; Shen, Hongzhang; Li, Zhen; Meng, Fei; Li, Lei; Yang, Jianfeng; Chen, Ying; Bo, Xiaochen; Zhang, Xiaofeng; Ni, Ming

    2016-01-01

    Biliary bacteria have been implicated in gallstone pathogenesis, though a clear understanding of their composition and source is lacking. Moreover, the effects of the biliary environment, which is known to be generally hostile to most bacteria, on biliary bacteria are unclear. Here, we investigated the bacterial communities of the biliary tract, duodenum, stomach, and oral cavity from six gallstone patients by using 16S rRNA amplicon sequencing. We found that all observed biliary bacteria were detectable in the upper digestive tract. The biliary microbiota had a comparatively higher similarity with the duodenal microbiota, versus those of the other regions, but with a reduced diversity. Although the majority of identified bacteria were greatly diminished in bile samples, three Enterobacteriaceae genera (Escherichia, Klebsiella, and an unclassified genus) and Pyramidobacter were abundant in bile. Predictive functional analysis indicated enhanced abilities of environmental information processing and cell motility of biliary bacteria. Our study provides evidence for the potential source of biliary bacteria, and illustrates the influence of the biliary system on biliary bacterial communities.

  11. Biopsy - biliary tract

    MedlinePlus

    ... ducts ( cholangiocarcinoma ) Cysts in the liver Liver cancer Pancreatic cancer Swelling and scarring of the bile ducts ( primary ... More Bile Cholangiocarcinoma Cyst Duodenum Hepatic Malignancy MRI Pancreatic cancer Ultrasound X-ray Review Date 2/11/2015 ...

  12. Malignant transformation of biliary adenofibroma: a rare biliary cystic tumor

    PubMed Central

    Zendejas-Mummert, Benjamin; Hartgers, Mindy L.; Venkatesh, Sudhakar K.; Smyrk, Thomas C.; Mahipal, Amit; Smoot, Rory L.

    2016-01-01

    Biliary adenofibromas (BAFs) are rare, benign biliary cystic tumors with potential for malignant transformation. Of the eleven prior cases of BAF reported in the literature, six showed evidence of malignant transformation. We describe the clinical, imaging and pathology features of two cases of malignant BAF and review the existing literature to raise awareness of this entity and provide additional tools for diagnosing this rare tumor Additionally, we identified a loss of function mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor suppressor gene in a malignant caudate lobe BAF, thereby providing potential insight into the molecular pathogenesis of BAF malignant transformation. Although additional cases and longer-term follow-up are needed, our cases suggest that recurrence or metastasis of malignant BAF is not common and that complete surgical resection can be curative. PMID:28078134

  13. A meta-analysis and systematic review: Success of endoscopic ultrasound guided biliary stenting in patients with inoperable malignant biliary strictures and a failed ERCP

    PubMed Central

    Moole, Harsha; Bechtold, Matthew L.; Forcione, David; Puli, Srinivas R.

    2017-01-01

    Abstract Background: In patients with inoperable malignant biliary strictures, endoscopic retrograde cholangiopancreatography (ERCP) guided biliary stenting fails in 5% to 10% patients due to difficult anatomy/inability to cannulate the papilla. Recently, endoscopic ultrasound guided biliary drainage (EUS-BD) has been described. Primary outcomes were to evaluate the biliary drainage success rates with EUS and compare it to percutaneous transhepatic biliary drainage (PTBD). Secondary outcomes were to evaluate overall procedure related complications. Methods: Study selection criteria: Studies evaluating the efficacy of EUS-BD and comparing EUS-BD versus PTBD in inoperable malignant biliary stricture patients with a failed ERCP were included in this analysis. Data collection and extraction: Articles were searched in Medline, PubMed, and Ovid journals. Two authors independently searched and extracted data. The study design was written in accordance to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Subgroup analyses of prospective studies and EUS-BD versus PTBD were performed. Statistical method: Pooled proportions were calculated using fixed and random effects model. I2 statistic was used to assess heterogeneity among studies. Results: Initial search identified 846 reference articles, of which 124 were selected and reviewed. Sixteen studies (N = 528) that met the inclusion criteria were included in this analysis. In the pooled patient population, the percentage of patients that had a successful biliary drainage with EUS was 90.91% (95% CI = 88.10–93.38). The proportion of patients that had overall procedure related complications with EUS-PD was 16.46% (95% CI = 13.20–20.01). The pooled odds ratio for successful biliary drainage in EUS-PD versus PTBD group was 3.06 (95% CI = 1.11–8.43). The risk difference for overall procedure related complications in EUS-PD versus PTBD group was −0.21 (95% CI = −0

  14. Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion The PONCHO trial is designed to show that early laparoscopic cholecystectomy

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

    PubMed Central

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

    2016-01-01

    Background/Aims: 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. Methods: 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. Results: 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. Conclusions: 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. PMID:27097771

  16. 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

  17. Roles of P-glycoprotein, Bcrp, and Mrp2 in biliary excretion of spiramycin in mice.

    PubMed

    Tian, Xianbin; Li, Jun; Zamek-Gliszczynski, Maciej J; Bridges, Arlene S; Zhang, Peijin; Patel, Nita J; Raub, Thomas J; Pollack, Gary M; Brouwer, Kim L R

    2007-09-01

    The multidrug resistance proteins P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and multidrug resistance-associated protein 2 (Mrp2) are the three major canalicular transport proteins responsible for the biliary excretion of most drugs and metabolites. Previous in vitro studies demonstrated that P-gp transported macrolide antibiotics, including spiramycin, which is eliminated primarily by biliary excretion. Bcrp was proposed to be the primary pathway for spiramycin secretion into breast milk. In the present study, the contributions of P-gp, Bcrp, and Mrp2 to the biliary excretion of spiramycin were examined in single-pass perfused livers of male C57BL/6 wild-type, Bcrp-knockout, and Mrp2-knockout mice in the presence or absence of GF120918 (GW918), a P-gp and Bcrp inhibitor. Spiramycin was infused to achieve steady-state conditions, followed by a washout period, and parameters governing spiramycin hepatobiliary disposition were recovered by using pharmacokinetic modeling. In the absence of GW918, the rate constant governing spiramycin biliary excretion was decreased in Mrp2(-) knockout mice (0.0013 +/- 0.0009 min(-1)) relative to wild-type mice (0.0124 +/- 0.0096 min(-1)). These data are consistent with the approximately 8-fold decrease in the recovery of spiramycin in the bile of Mrp2-knockout mice and suggest that Mrp2 is the major canalicular transport protein responsible for spiramycin biliary excretion. Interestingly, biliary recovery of spiramycin in Bcrp-knockout mice was increased in both the absence and presence of GW918 compared to wild-type mice. GW918 significantly decreased the rate constant for spiramycin biliary excretion and the rate constant for basolateral efflux of spiramycin. In conclusion, the biliary excretion of spiramycin in mice is mediated primarily by Mrp2 with a modest P-gp component.

  18. Biliary Dyskinesia in Children: A Systematic Review.

    PubMed

    Santucci, Neha R; Hyman, Paul E; Harmon, Carroll M; Schiavo, Julie H; Hussain, Sunny Z

    2017-02-01

    Cholecystectomy rates for biliary dyskinesia in children are rising in the United States, but not in other countries. Biliary dyskinesia is a validated functional gallbladder disorder in adults, requiring biliary colic in the diagnosis. In contrast, most studies in children require upper abdominal pain, absent gallstones on ultrasound, and an abnormal gallbladder ejection fraction (GBEF) on cholecystokinin-stimulated cholescintigraphy for diagnosis. We aimed to systematically review existing literature in biliary dyskinesia in children, determine the validity and reliability of diagnostic criteria, GBEF, and to assess outcomes following cholecystectomy. We performed a systematic review following the PRISMA checklist and searched 7 databases including PubMed, Scopus, Embase, Ovid, MEDLINE, ProQuest, Web of Science, and the Cochrane library. Bibliographies of articles were screened for additional studies. Our search terms yielded 916 articles of which 28 were included. Three articles were manually added from searched references. We reviewed 31 peer-reviewed publications, all retrospective chart reviews. There was heterogeneity in diagnostic criteria and GBEF values. Outcomes after laparoscopic cholecystectomy varied from 34% to 100% success, and there was no consensus concerning factors influencing outcomes. The observational, retrospective study designs that comprised our review limited interpretation of safety and efficacy of the investigations and treatment in biliary dyskinesia in children. Symptoms of biliary dyskinesia overlapped with functional dyspepsia. There is a need for consensus on symptoms defining biliary dyskinesia, validation of testing required for diagnosis of biliary dyskinesia, and randomized controlled trials comparing medical versus surgical management in children with upper abdominal pain.

  19. [Echographic signs of biliary atresia].

    PubMed

    Tarasiuk, B A; Iaremenko, V V; Babko, S A; Klimenko, E F; Medvedenko, G F

    2004-10-01

    The assessment of echographic features of biliary atresia was conducted in 65 newborn children ageing up to 3 mo. Their characteristic variants were revealed: the absence or reduction in size of gall-bladder, the presence of hyperechogenic triangular formation in V. portae bifurcation (the symptom of "triangular cicatrix"); the thickening of anterior wall of V. portae right branch. The timely and correct establishment of the diagnosis permits a child to survive and serve the hepatic fibrosis prophylaxis. Echohepatography is a sufficiently trustful method of investigation.

  20. Isolation, culture and characterization of biliary epithelial cells from different anatomical levels of the intrahepatic and extrahepatic biliary tree from a mouse.

    PubMed

    Katayanagi, K; Kono, N; Nakanuma, Y

    1998-04-01

    We developed methods to isolate biliary epithelial cells (BECs) from the gallbladder (GB), common bile duct (CBD), intrahepatic large bile duct (ILBD) and small bile duct (ISBD) of a mouse, simultaneously. ILBD and ISBD were cut from the biliary tree after collagenase perfusion of the liver. BECs from all of these biliary segments were cultured as explants on collagen gel. BECs spread from the explants and formed cellular sheets. Areas of these sheets composed entirely of BECs were cut and placed on other gels as subculture, and this continued for 10 passages. Primary and passage cultured BECs on gel were composed of a monolayer of epithelial cells. Passaged cultured BECs in gel formed a spherical cyst lined by a single epithelial layer. Ultrastructurally, microvilli were dense on the luminal surface, and junctional complex and interdigitation was identifiable on the lateral surfaces. These features were similar in both primary and passaged cultured BECs, irrespective of their anatomical origin. Major histocompatibility complex antigens and intercellular adhesion molecule-1 were induced on the basolateral cell membranes of primary and passaged cultured BECs, by interferon-gamma. Although several phenotypic, structural and probable biological features of BECs inherent to each anatomical level may be lost after culture on gel, a combination of this method, several immunological modifications in experimental animals, and addition of immunologically active substances to the culture medium will make the immunopathologic analysis of biliary diseases possible.

  1. Overlap syndromes among autoimmune liver diseases.

    PubMed

    Rust, Christian; Beuers, Ulrich

    2008-06-07

    The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardised definition. Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC. The AIH-PBC overlap syndrome is the most common form, affecting almost 10% of adults with AIH or PBC. Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported. The AIH-PSC overlap syndrome is predominantly found in children, adolescents and young adults with AIH or PSC. Interestingly, transitions from one autoimmune to another have also been reported in a minority of patients, especially transitions from PBC to AIH-PBC overlap syndrome. Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment. Therapy for overlap syndromes is empiric, since controlled trials are not available in these rare disorders. Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes. In end-stage disease, liver transplantation is the treatment of choice.

  2. Radionuclide imaging of the biliary tract

    SciTech Connect

    Henry, R.E.; Daly, M.J.

    1981-01-01

    Cholescintigraphy with technetium-labeled biliary agents has great value in evaluation of the patient with suspected acute cholecystitis. Visualization of the gall bladder virtually excludes acute cholecystitis and obstruction of the cystic duct. Nonvisualization of the gall bladder, however, is not specific for acute cholecystitis and may also occur in some patients with chronic cholecystitis or pancreatitis. Interpretation of gall bladder nonvisualization, therefore, must be correlated with the clinical presentation. Biliary tract imaging is also useful in evaluation of some focal abnormalities within the liver, neonatal jaundice, detection of bile leaks or bile reflux, and biliary-enteric shunts. The role of technetium-labeled biliary agents in the evaluation of patients with jaundice is less clear. Excretion of tracer into the gut excludes complete biliary tract obstruction, but the test may be nonconclusive at higher serum bilirubin levels. If persistent common bile duct activity is observed with delayed excretion into the gut, the diagnosis of partial obstruction may be made, but this procedure will be inconclusive if the common bile duct is not visualized and/or significant hepatocellular disease is present. Ultrasonography and abdominal CT are the preferred tools for the diagnosis of biliary tract obstruction at present, but newer biliary tract agents which achieve better hepatic extraction and greater bile concentration at high serum bilirubin levels may improve the diagnostic efficacy of cholescintigraphy.

  3. Biliary strictures: endoscopic assessment and management

    PubMed Central

    Paranandi, Bharat; Oppong, Kofi W

    2017-01-01

    The diagnosis of biliary strictures can be challenging. Endoscopy has an established role in the diagnosis and therapy of biliary strictures. However, the diagnostic yield from conventional endoscopic retrograde cholangiopancreatography tissue sampling is modest. Improvements in existing technologies as well as the implementation of novel technologies and techniques have the potential to improve the diagnostic performance of endoscopy and expand its therapeutic role. Recent studies have enabled greater clarity about the role of preoperative biliary drainage and the choice of stents in this setting as well as the utility of metal stents in benign and malignant disease. PMID:28261440

  4. Endoscopic palliation of malignant biliary strictures

    PubMed Central

    Salgado, Sanjay M; Gaidhane, Monica; Kahaleh, Michel

    2016-01-01

    Malignant biliary strictures often present late after the window for curative resection has elapsed. In such patients, the goal of therapy is typically focused on palliation. While historically, palliative measures were performed surgically, the advent of endoscopic intervention offers minimally invasive options to provide relief of symptoms, improve quality of life, and in some cases, increase survival of these patients. Some of these therapies, such as endoscopic biliary decompression, have become mainstays of treatment for decades, whereas newer modalities, including radiofrequency ablation, and photodynamic therapy offer additional options for patients with incurable biliary malignancies. PMID:26989459

  5. Sonographic diagnosis of biliary ascariasis.

    PubMed

    Schulman, A; Loxton, A J; Heydenrych, J J; Abdurahman, K E

    1982-09-01

    In a prospective 6 month study, sonographic diagnosis of biliary ascariasis was made in 12 patients: In five, the diagnosis was confirmed by other means, mainly intravenous cholangiography. In three, such confirmation was not sought, but all had proven intestinal infestation. One possible and three definite false-positive diagnoses were made. There were no established false-negative diagnoses. The echogenic, nonshadowing images of the worms were seen in the main bile duct and/or gallbladder as single strips (on one occasion with its digestive tract seen as an anechoic "inner tube"), as multiple strips giving a spaghettilike appearance, as coils, or as more amorphous fragments. Follow-up sonograms were obtained in six patients and showed expulsion of the worms by medical treatment.

  6. Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis.

    PubMed

    Moradpour, D; Altorfer, J; Flury, R; Greminger, P; Meyenberger, C; Jost, R; Schmid, M

    1994-12-01

    We describe a 33-yr-old pregnant woman in whom a primary biliary cirrhosis-like syndrome developed after 2 wk of chlorpromazine therapy. The clinical course was characterized by severe jaundice lasting 22 mo, intense pruritus, fever, steatorrhea, high alkaline phosphatase levels and hypercholesterolemia. Jaundice resolved with initiation of ursodeoxycholic acid therapy, but subclinical cholestasis and low-level inflammatory activity persisted and ultimately evolved into biliary cirrhosis. The pathological substrate of this severe and prolonged cholestatic reaction was found to be the vanishing bile duct syndrome with a marked transient pseudoxanthomatosis.

  7. Endoscopic management of biliary hydatid disease

    PubMed Central

    Akkiz, Hikmet; Akinoglu, Alper; Çolakoglu, Salih; Demiryürek, Haluk; Yagmur, Özgür

    1996-01-01

    Objective To determine the effect of endoscopic sphincterotomy in the management of biliary hydatid disease. Design A case study between January 1992 and December 1994. Setting A university-affiliated hospital in Adana, Turkey. Patients Five patients with biliary hydatid disease, in which the cyst had ruptured into the biliary tree. The follow-up ranged from 3 to 12 months. Intervention Endoscopic sphincterotomy. Main Outcome Measures Morbidity, mortality and recurrence of the disease. Results All patients underwent successful endoscopic sphincterotomy, including removal of daughter cysts. During the follow-up period, ultrasonography and laboratory investigations showed complete cure in all patients. There were no complications due to endoscopic sphincterotomy. Conclusion Endoscopic sphincterotomy is the treatment of choice for the management of hydatid cysts that have ruptured into the biliary tract causing obstructive jaundice. PMID:8697318

  8. Screening and Outcomes in Biliary Atresia: Summary of a National Institutes of Health Workshop

    PubMed Central

    Sokol, Ronald J.; Shepherd, Ross W.; Superina, Riccardo; Bezerra, Jorge A.; Robuck, Patricia; Hoofnagle, Jay H.

    2013-01-01

    Biliary atresia is the most common cause of end-stage liver disease in the infant and is the leading pediatric indication for liver transplantation in the United States. Earlier diagnosis (<30-45 days of life) is associated with improved outcomes following the Kasai portoenterostomy and longer survival with the native liver. However, establishing this diagnosis is problematic because of its rarity, the much more common indirect hyperbilirubinemia that occurs in the newborn period, and the schedule for routine infant health care visits in the United States. The pathogenesis of biliary atresia appears to involve immune-mediated fibro-obliteration of the extrahepatic and intrahepatic biliary tree in most patients and defective morphogenesis of the biliary system in the remainder. The determinants of the outcome of portoenterostomy include the age at surgery, the center's experience, the presence of associated congenital anomalies, and the postoperative occurrence of cholangitis. A number of screening strategies in infants have been studied. The most promising are early measurements of serum conjugated bilirubin and a stool color card given to new parents that alerts them and their primary care provider to acholic stools. This report summarizes a National Institutes of Health workshop held on September 12 and 13, 2006, in Bethesda, MD, that addressed the issues of outcomes, screening, and pathogenesis of biliary atresia. PMID:17661405

  9. Anaesthetic Management of a Patient with Synchronous Kartagener Syndrome and Biliary Atresia

    PubMed Central

    Kendigelen, Pınar; Tütüncü, Ayşe Çiğdem; Erbabacan, Şafak Emre; Kaya, Güner; Altındaş, Fatiş

    2015-01-01

    Kartagener syndrome is an autosomal recessive disorder characterized by primary ciliary dyskinesia accompanied by sinusitis, bronchiectasis, and situs inversus. Synchronous extrahepatic biliary atresia and Kartagener syndrome are very rare. During the preoperative preparation of patients with Kartagener syndrome, special attention is required for the respiratory and cardiovascular system. It is important to provide suitable anaesthetic management to avoid problems because of ciliary dysfunction in the perioperative period. Further, maintaining an effective pain control with regional anaesthetic methods reduces the risk of pulmonary complications. Infants with biliary atresia operated earlier have a higher chance of survival. Hepatic dysfunction and decrease in plasma proteins are important for the kinetics of drugs. In this presentation, the anaesthetic management of patients with synchronous Kartagener syndrome and biliary atresia, both of which are rare diseases, is evaluated. PMID:27366497

  10. Anaesthetic Management of a Patient with Synchronous Kartagener Syndrome and Biliary Atresia.

    PubMed

    Kendigelen, Pınar; Tütüncü, Ayşe Çiğdem; Erbabacan, Şafak Emre; Kaya, Güner; Altındaş, Fatiş

    2015-06-01

    Kartagener syndrome is an autosomal recessive disorder characterized by primary ciliary dyskinesia accompanied by sinusitis, bronchiectasis, and situs inversus. Synchronous extrahepatic biliary atresia and Kartagener syndrome are very rare. During the preoperative preparation of patients with Kartagener syndrome, special attention is required for the respiratory and cardiovascular system. It is important to provide suitable anaesthetic management to avoid problems because of ciliary dysfunction in the perioperative period. Further, maintaining an effective pain control with regional anaesthetic methods reduces the risk of pulmonary complications. Infants with biliary atresia operated earlier have a higher chance of survival. Hepatic dysfunction and decrease in plasma proteins are important for the kinetics of drugs. In this presentation, the anaesthetic management of patients with synchronous Kartagener syndrome and biliary atresia, both of which are rare diseases, is evaluated.

  11. Percutaneous management of postoperative anastomotic biliary strictures.

    PubMed

    Saad, Wael E A

    2008-06-01

    Postoperative anastomotic biliary strictures can occur after surgery in bile ducts belonging to transplanted or native (nontransplanted) livers. The majority of postoperative anastomotic strictures encountered by interventional radiologists are most likely in liver transplant recipients due to the large and growing liver transplant recipient population worldwide compared with patients with native livers and biliary enteric anastomoses. They occur after 2.5 to 13% of liver transplantations and they represent at least one-half of biliary strictures encountered after liver transplantation. Anastomotic biliary strictures are considered technical in nature, accentuated by fibrosis and scarring that may be secondary to, if not exacerbated by, graft ischemia. There are numerous variables in the percutaneous transhepatic balloon dilation protocols applied to treat anastomotic biliary strictures. These include (1) types of balloons, (2) how long balloons are inflated, (3) how frequently patients return for additional dilation sessions, and (4) the interval(s) at which they return. No alteration in these variables has proven to improve long-term patency. In addition, new technology such as cutting balloons and stents has not been fully evaluated to determine their effect on long-term patency. The current article describes the overall theme of balloon dilation protocols for the management of anastomotic biliary strictures and discusses possible future management of such strictures.

  12. Biliary Cast Syndrome in an Opium Inhaler

    PubMed Central

    Dabiri, Reza; Aghdae, Hamid Asadzadeh; Rajabalinia, Hasan; Mohammad Alizadeh, Amir Houshang

    2013-01-01

    Biliary cast syndrome (BCS) is an uncommon complication which is mostly described in orthotopic liver transplantation. However, BCS has also been reported rarely in non-liver transplant patients. We describe a male long-term opium inhaler with BCS who underwent successful endoscopic cast removal by balloon enteroscopy-guided endoscopic retrograde cholangiopancreatography. A 52-year-old man, who was a known case of opium addiction, presented with the chief complaint of epigastric pain for 1 week prior to admission. Routine laboratory evaluation revealed cholestatic liver enzyme elevation. A cholestatic pattern was seen in radiographic modalities. Endoscopic retrograde cholangiopancreatography showed a linear filling defect in the intra- and extrahepatic duct. A long biliary cast was successfully removed using an extractor balloon. After removal of the biliary cast the patient is receiving ursodeoxycholic acid and does not report any problem 4 months after treatment. It seems that biliary dyskinesia due to long-term opium use can be a predisposing factor for biliary cast formation. PMID:24163648

  13. Imaging of autoimmune hepatitis and overlap syndromes.

    PubMed

    Malik, Neera; Venkatesh, Sudhakar K

    2017-01-01

    Autoimmune hepatitis (AIH) is an uncommon, chronic inflammatory, and relapsing liver disease of unknown origin that may lead to liver cirrhosis, hepatocellular carcinoma, liver transplantation, or death. AIH occurs in all age groups and races but can frequently manifest as acute fulminant hepatitis. Clinical presentation of AIH can have features similar to primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC), and these diseases may coexist leading to overlap syndromes. Although histological diagnosis is necessary, imaging features often can demonstrate characteristics that may be helpful to distinguish these diseases. Imaging features of AIH are those of chronic liver disease, and imaging plays important role in detection of complications and ruling out other possible causes of chronic liver disease. Emerging techniques such as elastography provide non-invasive options for diagnosis of significant fibrosis and cirrhosis during clinical follow-up as well as assessment of response to treatment. In this study, we will describe imaging findings in AIH and overlap syndromes.

  14. 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.

  15. Technical tips and troubleshooting of endoscopic biliary drainage for unresectable malignant hilar biliary obstruction.

    PubMed

    Kawakami, Hiroshi; Itoi, Takao; Kuwatani, Masaki; Kawakubo, Kazumichi; Kubota, Yoshimasa; Sakamoto, Naoya

    2015-04-01

    Unresectable malignant hilar biliary obstruction (MHBO) occurs in various diseases, such as cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, pancreatic cancer, and lymph node metastasis of the hilum of the liver. The majority of patients with advanced MHBO are not candidates for surgical resection because of the tumor location in the hepatic hilum and adjacent areas, advanced tumor stage, or comorbidities. Therefore, these patients often have a poor prognosis in terms of survival and quality of life. Most of these patients will require non-surgical, palliative biliary drainage. To date, various biliary drainage techniques for unresectable MHBO (UMHBO) have been reported. Of these techniques, endoscopic biliary drainage is currently considered to be the most safe and minimally invasive procedure. However, endoscopic biliary drainage for UMHBO is still not standardized regarding the optimal stent, drainage area, stenting method, and reintervention technique. Recently, towards standardization of this technique for UMHBO, clinical research and trials including randomized controlled trials have been performed. In this article, we reviewed the most important issues regarding endoscopic biliary drainage for UMHBO, focusing on prospective studies. We also described in detail the techniques and future perspectives of endoscopic biliary drainage in patients with UMHBO.

  16. Portal biliopathy treated with endoscopic biliary stenting.

    PubMed

    Jeon, Sung Jin; Min, Jae Ki; Kwon, So Young; Kim, Jun Hyun; Moon, Sun Young; Lee, Kang Hoon; Kim, Jeong Han; Choe, Won Hyeok; Cheon, Young Koog; Kim, Tae Hyung; Park, Hee Sun

    2016-03-01

    Portal biliopathy is defined as abnormalities in the extra- and intrahepatic ducts and gallbladder of patients with portal hypertension. This condition is associated with extrahepatic venous obstruction and dilatation of the venous plexus of the common bile duct, resulting in mural irregularities and compression of the biliary tree. Most patients with portal biliopathy remain asymptomatic, but approximately 10% of them advance to symptomatic abdominal pain, jaundice, and fever. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography are currently used as diagnostic tools because they are noninvasive and can be used to assess the regularity, length, and degree of bile duct narrowing. Management of portal biliopathy is aimed at biliary decompression and reducing the portal pressure. Portal biliopathy has rarely been reported in Korea. We present a symptomatic case of portal biliopathy that was complicated by cholangitis and successfully treated with biliary endoscopic procedures.

  17. [The endoscopic management of postoperative biliary fistulae].

    PubMed

    Uribarrena, R; Simón, M A; Sebastián, J J; Gomollón, F; Bajador, E; Botella, M T; Cabrera, T

    1994-10-01

    We report a series of 15 patients with a postoperative biliary fistula treated by endoscopic sphincterotomy. The exact location of the bile leak was revealed by ERCP in 13 cases (87%): cystic duct remnant in 6 (39%), intrahepatic biliary tree in 4 (26%), and main bile duct in 3 (20%). In all cases a distal obstacle (ie: retained stones, hydatid material) to bile flow was also found in ERCP. Treatment consisted of endoscopic sphincterotomy and subsequent removal of the distal obstacle, and could be completed in 13 (87%) cases. In our experience the treatment of postoperative biliary fistula with a distal obstruction bile flow by endoscopic sphincterotomy is a safe and effective procedure, and should be recommended as the first option in those patients.

  18. Advanced endoscopic imaging of indeterminate biliary strictures

    PubMed Central

    Tabibian, James H; Visrodia, Kavel H; Levy, Michael J; Gostout, Christopher J

    2015-01-01

    Endoscopic evaluation of indeterminate biliary strictures (IDBSs) has evolved considerably since the development of flexible fiberoptic endoscopes over 50 years ago. Endoscopic retrograde cholangiography pancreatography (ERCP) was introduced nearly a decade later and has since become the mainstay of therapy for relieving obstruction of the biliary tract. However, longstanding methods of ERCP-guided tissue acquisition (i.e., biliary brushings for cytology and intraductal forceps biopsy for histology) have demonstrated disappointing performance characteristics in distinguishing malignant from benign etiologies of IDBSs. The limitations of these methods have thus helped drive the search for novel techniques to enhance the evaluation of IDBSs and thereby improve diagnosis and clinical care. These modalities include, but are not limited to, endoscopic ultrasound, intraductal ultrasound, cholangioscopy, confocal endomicroscopy, and optical coherence tomography. In this review, we discuss established and emerging options in the evaluation of IDBSs. PMID:26675379

  19. Portal biliopathy treated with endoscopic biliary stenting

    PubMed Central

    Jeon, Sung Jin; Min, Jae Ki; Kwon, So Young; Kim, Jun Hyun; Moon, Sun Young; Lee, Kang Hoon; Kim, Jeong Han; Choe, Won Hyeok; Cheon, Young Koog; Kim, Tae Hyung; Park, Hee Sun

    2016-01-01

    Portal biliopathy is defined as abnormalities in the extra- and intrahepatic ducts and gallbladder of patients with portal hypertension. This condition is associated with extrahepatic venous obstruction and dilatation of the venous plexus of the common bile duct, resulting in mural irregularities and compression of the biliary tree. Most patients with portal biliopathy remain asymptomatic, but approximately 10% of them advance to symptomatic abdominal pain, jaundice, and fever. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography are currently used as diagnostic tools because they are noninvasive and can be used to assess the regularity, length, and degree of bile duct narrowing. Management of portal biliopathy is aimed at biliary decompression and reducing the portal pressure. Portal biliopathy has rarely been reported in Korea. We present a symptomatic case of portal biliopathy that was complicated by cholangitis and successfully treated with biliary endoscopic procedures. PMID:27044769

  20. Metabolomic Profiling of Autoimmune Hepatitis: The Diagnostic Utility of Nuclear Magnetic Resonance Spectroscopy.

    PubMed

    Wang, Jia-Bo; Pu, Shi-Biao; Sun, Ying; Li, Zhong-Feng; Niu, Ming; Yan, Xian-Zhong; Zhao, Yan-Ling; Wang, Li-Feng; Qin, Xue-Mei; Ma, Zhi-Jie; Zhang, Ya-Ming; Li, Bao-Sen; Luo, Sheng-Qiang; Gong, Man; Sun, Yong-Qiang; Zou, Zheng-Sheng; Xiao, Xiao-He

    2014-06-30

    Autoimmune hepatitis (AIH) is often confused with other liver diseases because of their shared nonspecific symptoms and serological and histological overlap. This study compared the plasma metabolomic profiles of patients with AIH, primary biliary cirrhosis (PBC), PBC/AIH overlap syndrome (OS), and drug-induced liver injury (DILI) with those of healthy subjects to identify potential biomarkers of AIH. Metabolomic profiling and biomarker screening were performed using proton nuclear magnetic resonance spectroscopy ((1)H NMR) coupled with a partial least-squares discriminant analysis. Compared with the levels in healthy volunteers and other liver disease patients, AIH patients exhibited relatively high levels of plasma pyruvate, lactate, acetate, acetoacetate, and glucose. Such metabolites are typically related to energy metabolism alterations and may be a sign of metabolic conversion to the aerobic glycolysis phenotype of excessive immune activation. Increased aromatic amino acids and decreased branched-chain amino acids were found in the plasma of AIH patients. The whole NMR profiles were stepwise-reduced, and nine metabolomic biomarkers having the greatest significance in the discriminant analysis were obtained. The diagnostic utility of the selected metabolites was assessed, and these biomarkers achieved good sensitivity, specificity, and accuracy (all above 93%) in distinguishing AIH from PBC, DILI, and OS. This report is the first to present the metabolic phenotype of AIH and the potential utility of (1)H NMR metabolomics in the diagnosis of AIH.

  1. 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

  2. How Should Biliary Stones be Managed?

    PubMed Central

    2010-01-01

    Minimally invasive therapy is currently invaluable for the treatment of biliary stones. Clinicians should be familiar with the various endoscopic modalities that have been evolving. I reviewed the treatment of biliary stones from the common practice to pioneering procedures, and here I also briefly summarize the results of many related studies. Lithotripsy involves procedures that fragment large stones, and they can be roughly classified into two groups: intracorporeal modalities and extracorporeal shock-wave lithotripsy (ESWL). Intracorporeal modalities are further divided into mechanical lithotripsy (ML), electrohydraulic lithotripsy, and laser lithotripsy. ESWL can break stones by focusing high-pressure shock-wave energy at a designated target point. Balloon dilation after minimal endoscopic sphincterotomy (EST) is effective for retrieving large biliary stones without the use of ML. Peroral cholangioscopy provides direct visualization of the bile duct and permits diagnostic procedures or therapeutic interventions. Biliary stenting below an impacted stone is sometimes worth considering as an alternative treatment in elderly patients. This article focuses on specialized issues such as lithotripsy rather than simple EST with stone removal in order to provide important information on state-of-the-art procedures. PMID:20559517

  3. Listeria monocytogenes-Associated Biliary Tract Infections

    PubMed Central

    Charlier, Caroline; Fevre, Cindy; Travier, Laetitia; Cazenave, Benoît; Bracq-Dieye, Hélène; Podevin, Juliette; Assomany, Daher; Guilbert, Lydie; Bossard, Céline; Carpentier, Françoise; Cales, Valérie; Leclercq, Alexandre; Lecuit, Marc

    2014-01-01

    Abstract At present, little is known regarding Listeria monocytogenes-associated biliary tract infection, a rare form of listeriosis. In this article, we will study 12 culture-proven cases reported to the French National Reference Center for Listeria from 1996 to 2013 and review the 8 previously published cases. Twenty cases were studied: 17 cholecystitis, 2 cholangitis, and 1 biliary cyst infection. Half were men with a median age of 69 years (32–85). Comorbidities were present in 80%, including cirrhosis, rheumatoid arthritis, and diabetes. Five patients received immunosuppressive therapy, including corticosteroids and anti-tumor necrosis factor biotherapies. Half were afebrile. Blood cultures were positive in 60% (3/5). Gallbladder histological lesions were analyzed in 3 patients and evidenced acute, chronic, or necrotic exacerbation of chronic infection. Genoserogroup of the 12 available strains were IVb (n = 6), IIb (n = 5), and IIa (n = 1). Their survival in the bile was not enhanced when compared with isolates from other listeriosis cases. Adverse outcome was reported in 33% (5/15): 3 deaths, 1 recurrence; 75% of the patients with adverse outcome received inadequate antimicrobial therapy (P = 0.033). Biliary tract listeriosis is a severe infection associated with high mortality in patients not treated with appropriate therapy. This study provides medical relevance to in vitro and animal studies that had shown Listeria monocytogenes ability to survive in bile and induce overt biliary infections. PMID:25319439

  4. 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.

  5. Clinical course and prognosis of pediatric-onset primary sclerosing cholangitis

    PubMed Central

    Färkkilä, Martti; Arola, Johanna; Jaakkola, Tytti; Penagini, Roberto; Kolho, Kaija-Leena

    2015-01-01

    Background The natural history of pediatric-onset primary sclerosing cholangitis (PSC) and overlap with autoimmune hepatitis (PSC/AIH) is poorly known. Objective The aim of this study was to evaluate the clinical outcome of patients with pediatric-onset disease in a tertiary referral center. Methods We traced 33 patients (median age at diagnosis 16 years), with PSC or PSC/AIH in cholangiography and liver histology diagnosed between December 1993 and 2011, at Helsinki University Hospital. Diagnostic procedures and long-term follow-up were reassessed until the end of December 2013. Results PSC was confirmed in all 33 patients; 19 of them had an overlap with AIH. At diagnosis, three of 33 had cirrhosis. Inflammatory bowel disease (IBD) was associated in 76% of the patients, mostly ulcerative colitis (70%); treatment of IBD being a minor determinant of the clinical outcome of liver disease. In the last follow-up (median nine years), all patients were alive, and no malignancy occurred. Most patients (91%) were on ursodeoxycholic acid and 12 PSC/AIH patients on immunosuppression. Endoscopic retrograde cholangiography during follow-up showed a progression of intra-hepatic disease in 12 patients (36%). Four patients (12%) had undergone liver transplantation, and one was listed; no recurrence of the disease in the graft was seen. Conclusion The clinical course and outcome of pediatric-onset PSC and PSC/AIH seem to be favourable in the majority of patients until early adulthood. In about one-third of patients, however, PSC is progressive, challenging the current treatment guidelines and warranting further studies on disease pathogenesis. PMID:27536366

  6. Effect of microsomal enzyme inducers on the biliary excretion of triiodothyronine (T(3)) and its metabolites.

    PubMed

    Vansell, Nichole R; Klaassen, Curtis D

    2002-02-01

    It has been postulated that inducers of UDP-glucuronosyltransferase (UGT) decrease circulating thyroid hormone concentrations by increasing their biliary excretion. The inducers pregnenolone-16 alpha-carbonitrile (PCN), 3-methylcholanthrene (3MC), and Aroclor 1254 (PCB) are each effective at reducing serum thyroxine concentrations. However, only PCN treatment produces a marked increase in serum levels of thyroid-stimulating hormone (TSH), whereas 3MC and PCB cause little to no increase in TSH. Excessive TSH elevation is considered the primary stimulus for thyroid tumor development in rats, yet the mechanism by which enzyme induction leads to TSH elevation is not fully understood. Whereas PCN, 3MC, and PCB all increase microsomal UGT activity toward T(4), only PCN causes an increase in T(3)-UGT activity in vitro. The purpose of this study was to determine whether PCN, which increases serum TSH, causes an increase in the glucuronidation and biliary excretion of T(3) in vivo. Male rats were fed control diet or diet containing PCN (1000 ppm), 3MC (250 ppm), or PCB (100 ppm) for 7 days. Animals were then given [(125)I]-T(3), i.v., and bile was collected for 2 h. Radiolabeled metabolites in bile were analyzed by reverse-phase HPLC with gamma-detection. The biliary excretion of total radioactivity was increased up to 75% by PCN, but not by 3MC or PCB. Of the T(3) excreted into bile, approximately 75% was recovered as T(3)-glucuronide, with remaining amounts represented as T(3)-sulfate, T(2)-sulfate, T(3), and T(2). Biliary excretion of T(3)-glucuronide was increased up to 66% by PCN, while neither 3MC nor PCB altered T(3)-glucuronide excretion. These findings indicate that PCN increases the glucuronidation and biliary excretion of T(3) in vivo, and suggest that enhanced elimination of T(3) may be the mechanism responsible for the increases in serum TSH caused by PCN.

  7. Biliary atresia: From Australia to the zebrafish.

    PubMed

    Davenport, Mark

    2016-02-01

    This review is based upon an invited lecture for the 52nd Annual Meeting of the British Association of Paediatric Surgeons, July 2015. The aetiology of biliary atresia (BA) is at best obscure, but it is probable that a number of causes or pathophysiological mechanisms may be involved leading to the final common phenotype we recognise clinically. By way of illustration, similar conditions to human BA are described, including biliary agenesis, which is the normal state and peculiar final pattern of bile duct development in the jawless fish, the lamprey. Furthermore, there have been remarkable outbreaks in the Australian outback of BA in newborn lambs whose mothers were exposed to and grazed upon a particular plant species (Dysphania glomulifera) during gestation. More recent work using a zebrafish model has isolated a toxic isoflavonoid, now named Biliatresone, thought to be responsible for these outbreaks. Normal development of the bile ducts is reviewed and parallels drawn with two clinical variants thought to definitively have their origins in intrauterine life: Biliary Atresia Splenic Malformation syndrome (BASM) and Cystic Biliary Atresia (CBA). For both variants there is sufficient clinical evidence, including associated anomalies and antenatal detection, respectively, to warrant their aetiological attribution as developmental BA. CMV IgM +ve associated BA is a further variant that appears separate with distinct clinical, histological, and immunohistochemical features. In these it seems possible that this involves perinatal obliteration of a normally formed duct system. Although still circumstantial, this evidence appears convincing enough to perhaps warrant a different treatment strategy. This then still leaves the most common (more than 60% in Western series) variant, now termed Isolated BA, whereby origins can only be alluded to.

  8. Reality named endoscopic ultrasound biliary drainage.

    PubMed

    Guedes, Hugo Gonçalo; Lopes, Roberto Iglesias; de Oliveira, Joel Fernandez; Artifon, Everson Luiz de Almeida

    2015-10-25

    Endoscopic ultrasound (EUS) is used for diagnosis and evaluation of many diseases of the gastrointestinal (GI) tract. In the past, it was used to guide a cholangiography, but nowadays it emerges as a powerful therapeutic tool in biliary drainage. The aims of this review are: outline the rationale for endoscopic ultrasound-guided biliary drainage (EGBD); detail the procedural technique; evaluate the clinical outcomes and limitations of the method; and provide recommendations for the practicing clinician. In cases of failed endoscopic retrograde cholangiopancreatography (ERCP), patients are usually referred for either percutaneous transhepatic biliary drainage (PTBD) or surgical bypass. Both these procedures have high rates of undesirable complications. EGBD is an attractive alternative to PTBD or surgery when ERCP fails. EGBD can be performed at two locations: transhepatic or extrahepatic, and the stent can be inserted in an antegrade or retrograde fashion. The drainage route can be transluminal, duodenal or transpapillary, which, again, can be antegrade or retrograde [rendezvous (EUS-RV)]. Complications of all techniques combined include pneumoperitoneum, bleeding, bile leak/peritonitis and cholangitis. We recommend EGBD when bile duct access is not possible because of failed cannulation, altered upper GI tract anatomy, gastric outlet obstruction, a distorted ampulla or a periampullary diverticulum, as a minimally invasive alternative to surgery or radiology.

  9. Malignant Biliary Obstruction: Evidence for Best Practice

    PubMed Central

    Pu, Leonardo Zorrón Cheng Tao; Singh, Rajvinder; Loong, Cheong Kuan; de Moura, Eduardo Guimarães Hourneaux

    2016-01-01

    What should be done next? Is the stricture benign? Is it resectable? Should I place a stent? Which one? These are some of the questions one ponders when dealing with biliary strictures. In resectable cases, ongoing questions remain as to whether the biliary tree should be drained prior to surgery. In palliative cases, the relief of obstruction remains the main goal. Options for palliative therapy include surgical bypass, percutaneous drainage, and stenting or endoscopic stenting (transpapillary or via an endoscopic ultrasound approach). This review gathers scientific foundations behind these interventions. For operable cases, preoperative biliary drainage should not be performed unless there is evidence of cholangitis, there is delay in surgical intervention, or intense jaundice is present. For inoperable cases, transpapillary stenting after sphincterotomy is preferable over percutaneous drainage. The use of plastic stents (PS) has no benefit over Self-Expandable Metallic Stents (SEMS). In case transpapillary drainage is not possible, Endoscopic Ultrasonography- (EUS-) guided drainage is still an option over percutaneous means. There is no significant difference between the types of SEMS and its indication should be individualized. PMID:26981114

  10. Congenital biliary tract malformation resembling biliary cystadenoma in a captive juvenile African lion (Panthera leo).

    PubMed

    Caliendo, Valentina; Bull, Andrew C J; Stidworthy, Mark F

    2012-12-01

    A captive 3-mo-old white African lion (Panthera leo) presented with clinical signs of acute pain and a distended abdomen. Despite emergency treatment, the lion died a few hours after presentation. Postmortem examination revealed gross changes in the liver, spleen, and lungs and an anomalous cystic structure in the bile duct. Histologic examination identified severe generalized multifocal to coalescent necrotizing and neutrophilic hepatitis, neutrophilic splenitis, and mild interstitial pneumonia, consistent with bacterial septicemia. The abnormal biliary structures resembled biliary cystadenoma. However, due to the age of the animal, they were presumed to be congenital in origin. Biliary tract anomalies and cystadenomas have been reported previously in adult lions, and this case suggests that at least some of these examples may have a congenital basis. It is unclear whether the lesion was an underlying factor in the development of hepatitis.

  11. Eosinophilic Cholangitis—A Challenging Diagnosis of Benign Biliary Stricture

    PubMed Central

    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

    Abstract 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. PMID:26735539

  12. Biliary Atresia: 50 Years after the First Kasai

    PubMed Central

    Wildhaber, Barbara E.

    2012-01-01

    Biliary atresia is a rare neonatal disease of unknown etiology, where obstruction of the biliary tree causes severe cholestasis, leading to biliary cirrhosis and death in the first years of life, if the condition is left untreated. Biliary atresia is the most frequent surgical cause of cholestatic jaundice in neonates and should be evoked whenever this clinical sign is associated with pale stools and hepatomegaly. The treatment of biliary atresia is surgical and currently recommended as a sequence of, eventually, two interventions. During the first months of life a hepatoportoenterostomy (a “Kasai,” modifications of which are discussed in this paper) should be performed, in order to restore the biliary flow to the intestine and lessen further damage to the liver. If this fails and/or the disease progresses towards biliary cirrhosis and life-threatening complications, then liver transplantation is indicated, for which biliary atresia represents the most frequent pediatric indication. Of importance, the earlier the Kasai is performed, the later a liver transplantation is usually needed. This warrants a great degree of awareness of biliary atresia, and the implementation of systematic screening for this life-threatening pathology. PMID:23304557

  13. The safety and efficacy of nasobiliary drainage versus biliary stenting in malignant biliary obstruction

    PubMed Central

    Lin, Huapeng; Li, Shengwei; Liu, Xi

    2016-01-01

    Abstract Background: Preoperative biliary drainage (PBD) has been widely used to treat patients with malignant biliary obstruction. However, it is still unclear which method of PBD (endoscopic nasobiliary drainage or endoscopic biliary stenting) is more effective. Thus, we carried out a meta-analysis to compare the safety and efficacy of endoscopic nasobiliary drainage (ENBD) and endoscopic biliary stenting (EBS) in malignant biliary obstruction in terms of preoperative and postoperative complications. Methods: We conducted a literature search of EMBASE databases, PubMed, and the Cochrane Library to identify relevant available articles that were published in English, and we then compared ENBD and EBS in malignant biliary obstruction patients. The preoperative cholangitis rate, the preoperative pancreatitis rate, the incidence of stent dysfunction, the postoperative pancreatic fistula rate, and morbidity were analyzed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to express the pooled effect on dichotomous variables, and the pooled analyses were performed using RevMan 5.3. Results: Seven published studies (n = 925 patients) were included in this meta-analysis. We determined that patients with malignant biliary obstruction who received ENBD had reductions in the preoperative cholangitis rate (OR = 0.35, 95% CI = 0.25–0.51, P < 0.0001), the postoperative pancreatic fistula rate (OR = 0.38, 95% CI = 0.18–0.82, P = 0.01), the incidence of stent dysfunction (OR = 0.39, 95% CI = 0.28–0.56, P < 0.0001), and morbidity (OR = 0.47, 95% CI = 0.27–0.82, P = 0.008) compared with patients who received EBS. Conclusions: The current meta-analysis suggests that ENBD is better than EBS for malignant biliary obstruction in terms of the preoperative cholangitis rate, the postoperative pancreatic fistula rate, the incidence of stent dysfunction, and morbidity. However, a limitation is that there are no data

  14. Endoscopy and papillotomy in diseases of the biliary tract and pancreas

    SciTech Connect

    Siegel, J.H.

    1980-12-01

    Endoscopic retrograde cholangiography (ERCP), the most advanced of the gastrointestinal endoscopic procedures, provides both specific diagnostic information pertaining to diseases of the biliary tract and pancreas and definitive therapy available only with this modality. ERCP is safe and accurate, establishing a primary diagnosis in 80% of cases and, in experienced hands, cannulation is successful in 98%. In addition to cholangiography, pancreatography has been a significant achievement providing accurate diagnostic yield through direct cannulation and opacification of the pancreatic duct while permitting collection of secretions for cytological evaluation and chemical analyses. The therapeutic extension of ERCP, endoscopic papillotomy (EPT), is successful in 94% of cases in the treatment of common bile duct stones and papillary stenosis, providing comparable results to surgical procedures while reducing morbidity, mortality and convalescence. Because of the accuracy and safety of these procedures, they should be considered early in suspected diseases of the biliary tract and pancreas so that the clinician can establish a specific diagnosis and provide definitive therapy.

  15. [Current aspects of therapy of primary biliary cirrhosis].

    PubMed

    Grassi, M; Manzi, P; Schiffino, L; Raffa, S

    1997-03-01

    The authors expose the epidemiological features of PBC and outline the role of the immunologic disorders in the disease's pathogenesis. The main clinic and laboratory features of the PBC, its course and pathology are also synthesized. The authors describe the drugs employed in the therapy of the PBC: cortisone, azathioprine, metotrexate, chlorambucil, colchicine, D-penicillamine and hydrophilic bile salts; the favourable risk-benefice rate of colchicine, azathioprine and hydrophilic bile salts is outlined, even if they are poorly active on the disease's course. The use of lyposoluble vitamins is stressed, to improve malabsorption's syndromes. At the end the role of orthotopic liver transplant is regarded.

  16. Association of Preoperative Biliary Drainage With Postoperative Outcome Following Pancreaticoduodenectomy

    PubMed Central

    Povoski, Stephen P.; Karpeh, Martin S.; Conlon, Kevin C.; Blumgart, Leslie H.; Brennan, Murray F.

    1999-01-01

    Objective To determine whether preoperative biliary instrumentation and preoperative biliary drainage are associated with increased morbidity and mortality rates after pancreaticoduodenectomy. Summary Background Data Pancreaticoduodenectomy is accompanied by a considerable rate of postoperative complications and potential death. Controversy exists regarding the impact of preoperative biliary instrumentation and preoperative biliary drainage on morbidity and mortality rates after pancreaticoduodenectomy. Methods Two hundred forty consecutive cases of pancreaticoduodenectomy performed between January 1994 and January 1997 were analyzed. Multiple preoperative, intraoperative, and postoperative variables were examined. Pearson chi square analysis or Fisher’s exact test, when appropriate, was used for univariate comparison of all variables. Logistic regression was used for multivariate analysis. Results One hundred seventy-five patients (73%) underwent preoperative biliary instrumentation (endoscopic, percutaneous, or surgical instrumentation). One hundred twenty-six patients (53%) underwent preoperative biliary drainage (endoscopic stents, percutaneous drains/stents, or surgical drainage). The overall postoperative morbidity rate after pancreaticoduodenectomy was 48% (114/240). Infectious complications occurred in 34% (81/240) of patients. Intraabdominal abscess occurred in 14% (33/240) of patients. The postoperative mortality rate was 5% (12/240). Preoperative biliary drainage was determined to be the only statistically significant variable associated with complications (p = 0.025), infectious complications (p = 0.014), intraabdominal abscess (p = 0.022), and postoperative death (p = 0.037). Preoperative biliary instrumentation alone was not associated with complications, infectious complications, intraabdominal abscess, or postoperative death. Conclusions Preoperative biliary drainage, but not preoperative biliary instrumentation alone, is associated with increased

  17. The inflammatory phenotype of the fibrous plate is distinct from the liver and correlates with clinical outcome in biliary atresia.

    PubMed

    Arva, Nicoleta C; Russo, Pierre A; Erlichman, Jessi; Hancock, Wayne W; Haber, Barbara A; Bhatti, Tricia R

    2015-03-01

    Biliary atresia is an inflammatory cholangiopathy of still undetermined etiology. Correlations between histologic findings and clinical outcome in this disease have largely been based on evaluation of liver parenchyma. This study aimed to characterize the pattern of inflammation within the biliary remnant and identify associations between the type and degree of inflammation and clinical outcome as reflected by the transplant-free interval. The inflammation within the fibrous plates and livers of 41 patients with biliary atresia was characterized using immunohistochemical markers and the cell populations were digitally quantified. The type and quantity of cells within the infiltrate were then correlated with length of time from Kasai portoenterostomy until transplant. Histologic and immunohistochemical features of the biliary remnant allowed stratification of patients into "inflammatory plate" and "fibrotic plate" groups. Overall there was no significant difference in transplant-free interval between the two cohorts; however, there was a trend towards a longer time to transplant among patients in the "fibrotic plate" group. In addition, the composition of the inflammatory infiltrate in the fibrous plate was distinctly different from that present in the liver and only the characteristics of the inflammation in the fibrous plate, in particular the number of Foxp3+ T regulatory lymphocytes correlated with clinical outcome. The results of this study support the view of the extra-hepatic biliary tree as the primary site of injury in BA with the changes seen in the liver as secondary manifestations of outflow obstruction. The association between specific inflammatory cell subtypes within the fibrous plate and the length of transplant-free interval also supports the role of the immune system in the initial process of bile duct damage in biliary atresia.

  18. Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

    PubMed Central

    Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott

    2012-01-01

    Abstract. 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. PMID:23214186

  19. 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.

  20. The role of sonography in imaging of the biliary tract.

    PubMed

    Foley, W Dennis; Quiroz, Francisco A

    2007-06-01

    Sonography is the recommended initial imaging test in the evaluation of patients presenting with right upper quadrant pain or jaundice. Dependent upon clinical circumstances, the differential diagnosis includes choledocholithiasis, biliary stricture, or tumor. Sonography is very sensitive in detection of mechanical biliary obstruction and stone disease, although less sensitive for detection of obstructing tumors, including pancreatic carcinoma and cholangiocarcinoma. In patients with sonographically documented cholelithiasis and choledocholithiasis, laparoscopic cholecystectomy with operative clearance of the biliary stone disease is usually performed. In patients with clinically suspected biliary stone disease, without initial sonographic documentation of choledocholithiasis, endoscopic ultrasound or magnetic resonance cholangiopancreatography is the next logical imaging step. Endoscopic ultrasound documentation of choledocholithiasis in a postcholecystectomy patient should lead to retrograde cholangiography, sphincterotomy, and clearance of the ductal calculi by endoscopic catheter techniques. In patients with clinical and sonographic findings suggestive of malignant biliary obstruction, a multipass contrast-enhanced computed tomography (CT) examination to detect and stage possible pancreatic carcinoma, cholangiocarcinoma, or periductal neoplasm is usually recommended. Assessment of tumor resectability and staging can be performed by CT or a combination of CT and endoscopic ultrasound, the latter often combined with fine needle aspiration biopsy of suspected periductal tumor. In patients whose CT scan suggests hepatic hilar or central intrahepatic biliary tumor, percutaneous cholangiography and transhepatic biliary stent placement is usually followed by brushing or fluoroscopically directed fine needle aspiration biopsy for tissue diagnosis. Sonography is the imaging procedure of choice for biliary tract intervention, including cholecystostomy, guidance for

  1. [Tomato peel: rare cause of biliary tract obstruction].

    PubMed

    Hagymási, Krisztina; Péter, Zoltán; Csöregh, Eva; Szabó, Emese; Tulassay, Zsolt

    2011-11-20

    Foreign bodies in the biliary tree are rare causes of obstructive jaundice. Food bezoars are infrequent as well. They can cause biliary obstruction after biliary tract interventions, or in the presence of biliary-bowel fistula or duodenum diverticulum. Food bezoars usually pass the gastrointestinal tract without any symptoms, but they can cause abdominal pain and obstructive jaundice in the case of biliary tract obstruction. Endoscopic retrograde cholangio-pancreatography has the major role in the diagnosis and the treatment of the disease. Authors summarize the medical history of a 91-year-old female patient, who developed vomiting and right subcostal pain due to the presence of tomato peel within the ductus choledochus.

  2. Percutaneous cholangioscopy in obstructed biliary metal stents

    SciTech Connect

    Hausegger, Klaus A.; Mischinger, Hans J.; Karaic, Radenko; Klein, Guenther E.; Kugler, Cristian; Kern, Robert; Uggowitzer, Martin; Szolar, Dieter

    1997-05-15

    Purpose. To reevaluate the reasons for the occlusion of self-expanding biliary metal stents, on the basis of cholangioscopic findings. Methods. Percutaneous transhepatic cholangioscopy (PTCS) was performed in 15 patients with obstructed biliary Wallstents. The reason for stent insertion was a malignant obstruction in 14 patients; 1 had a benign biliary stricture. Conventional noncovered stents had been inserted in 12 patients; in 3 cases a polyurethane-covered prototype Wallstent had been used. Stent occlusions occurred after 1-55 months. PTCS was performed with a 2.3-mm endoscope through an 11 Fr sheath. Biopsies were taken via the working channel of the endoscope. Results. In all patients with noncovered stents the inner surface of the stent was highly irregular with seaweed-like protrusions (biopsy-proven granulation tissue). Stent incorporation varied from absent (n=1) to subtotal (n=8), but was always incomplete, no matter how long the stent had been in place. Tumor ingrowth was histologically proven in 2 patients. One patient had a large occluding concrement at the proximal end of the stent. In patients with covered stents, the inner surface appeared more regular; however, viable granulation tissue was found inside two stents and tumor ingrowth in one of them. Conclusion. PTCS showed that incorporation of the stent is virtually always incomplete. The factors contributing most to stent occlusion are the buildup of granulation tissue, bile sludge, and tumor overgrowth. Stone formation and tumor ingrowth can also be important, although less common causes of occlusion. A polyurethane stent covering could not prevent tumor ingrowth in one patient and the buildup of viable granulation tissue inside the stent in two further patients; mean stent patency in the three patients with such a stent was 3 months.

  3. Current options for management of biliary atresia.

    PubMed

    Gallo, Amy; Esquivel, Carlos O

    2013-03-01

    It is encouraging that we are improving the technical aspects of treatment modalities for biliary atresia. However, it is clear that more needs to be done to best develop new treatment plans while applying the modalities we have (porto-enterostomy or liver transplantation or both) in a way that will afford the best survival and quality-of-life. This review article will discuss a number of points that are vital to improving care and illustrates the need to further scrutinize treatment decisions.

  4. End-to-end ductal anastomosis in biliary reconstruction: indications and limitations.

    PubMed

    Jabłonska, Beata

    2014-08-01

    End-to-end ductal anastomosis is a physiologic biliary reconstruction that is commonly used in liver transplantation and less frequently in the surgical treatment of iatrogenic bile duct injuries. Currently, end-to-end ductal anastomosis is the biliary reconstruction of choice for liver transplantation in most adult patients. In recent years, it has also been performed for liver transplantation in children and in select patients with primary sclerosing cholangitis. The procedure is also performed in some patients with iatrogenic bile duct injuries, as it establishes physiologic bile flow. Proper digestion and absorption as well as postoperative endoscopic access are possible in patients who undergo end-to-end ductal anastomosis. It allows endoscopic diagnostic and therapeutic procedures in patients following surgery. This anastomosis is technically simple and associated with fewer early postoperative complications than the Roux-en-Y hepaticojejunostomy; however, end-to-end ductal anastomosis is not possible to perform in all patients. This review discusses the indications for and limitations of this biliary reconstruction, the technique used in liver transplantation and surgical repair of injured bile ducts, suture types and use of a T-tube.

  5. Percutaneous transhepatic embolization of biliary leakage with N-butyl cyanoacrylate

    PubMed Central

    Carrafiello, Gianpaolo; Ierardi, Anna Maria; Piacentino, Filippo; Cardim, Larissa N

    2012-01-01

    Biliary leakage is a known complication after biliary surgery. In this report, we describe an uncommon treatment of a common biliary complication, wherein we used percutaneous transhepatic injection of N-butyl cyanoacrylate (NBCA) to treat a biliary leak in an 83-year-old patient. PMID:22623810

  6. Anti-Saccharomyces cerevisiae as unusual antibodies in autoimmune hepatitis.

    PubMed

    Fagoonee, S; De Luca, L; De Angelis, C; Castelli, A; Rizzetto, M; Pellicano, R

    2009-03-01

    Autoantibodies are disease markers of autoimmune hepatitis (AIH). Antinuclear antibodies, smooth muscle antibodies, antibodies to liver/kidney microsome type 1, and perinuclear antibodies to neutrophil cytoplasm constitute the ''conventional'' battery of autoantibodies, while an emerging interest to evaluate new autoantibodies as diagnostic or prognostic markers, such as the anti-Saccharomyces cerevisiae antibodies, is detectable (ASCA). This paper focuses mainly on the findings and the potential role of ASCA in AIH. These antibodies are present in 5-6.3% of blood donors and in the gastrointestinal setting, ASCA have been found most often in Crohn's disease and with lower frequency in the course of ulcerative colitis and celiac disease. Furthermore, they have been described, to a lesser extent, in patients with primary sclerosing cholangitis and primary biliary cirrhosis and in AIH. ASCA occur in 20-30% of patients suffering from AIH with a statistically significant increase observed only for IgG ASCA in type 1 AIH. This probably indicates collateral immune reactivities to the primary pathogenic process. The outcome of hepatitis is not influenced by the presence of ASCA. In conclusion, ASCA positivity does not imply that there exists a distinct subgroup of patients with AIH and these autoantibodies are not involved in the pathogenetic mechanism of AIH.

  7. Serum Lipid Levels and the Risk of Biliary Tract Cancers and Biliary Stones: A Population-based Study in China

    PubMed Central

    Andreotti, Gabriella; Chen, Jinbo; Gao, Yu-Tang; Rashid, Asif; Chang, Shih-Chen; Shen, Ming-Chang; Wang, Bing-Sheng; Han, Tian-Quan; Zhang, Bai-He; Danforth, Kim N.; Althuis, Michelle D.; Hsing, Ann W.

    2010-01-01

    Biliary tract cancers, encompassing the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare, but highly fatal malignancies. Gallstones, the predominant risk factor for biliary cancers, are linked with hyperlipidemia. As part of a population-based case-control study conducted in Shanghai, China, we examined the associations of serum lipid levels with biliary stones and cancers. We included 460 biliary cancer cases (264 gallbladder, 141 extrahepatic bile duct, and 55 ampulla of Vater), 981 biliary stone cases, and 858 healthy individuals randomly selected from the population. Participants completed an in-person interview and gave overnight fasting blood samples. Participants in the highest quintile of triglycerides (≥ 160 mg/dl) had a 1.4-fold risk of biliary stones (95% CI=1.1-1.9), a 1.9-fold risk of gallbladder cancer (95% CI=1.3-2.8), and a 4.8-fold risk of bile duct cancer (95% CI=2.8-8.1), compared to the reference group (third quintile: 90-124 mg/dl). Participants in the lowest quintile of high-density lipoprotein (HDL) (< 30 mg/dl) had a 4.2-fold risk of biliary stones (95% CI=3.0-6.0), an 11.6-fold risk of gallbladder cancer (95% CI=7.3-18.5), and a 16.8-fold risk of bile duct cancer (95% CI=9.1-30.9), relative to the reference group (third quintile: 40-49 mg/dl). In addition, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A (apo A) were inversely associated with biliary stones; whereas low levels as well as high levels of total cholesterol, LDL, apo A, and apolipoprotein B (apo B) were associated with excess risks of biliary tract cancers. Our findings support a role for serum lipids in gallstone development and biliary carcinogenesis. PMID:18076041

  8. EUS-guided biliary drainage with placement of a new partially covered biliary stent for palliation of malignant biliary obstruction: a case series.

    PubMed

    Fabbri, C; Luigiano, C; Fuccio, L; Polifemo, A M; Ferrara, F; Ghersi, S; Bassi, M; Billi, P; Maimone, A; Cennamo, V; Masetti, M; Jovine, E; D'Imperio, N

    2011-05-01

    Endoscopic ultrasonography-guided biliary drainage (EUS-BD) has been developed as an alternative drainage technique in patients with obstructive jaundice where endoscopic retrograde cholangiopancreatography (ERCP) has failed. Between July 2008 and December 2009, 16 patients (9 men; median age 79 years) with biliopancreatic malignancy, who were candidates for alternative techniques of biliary decompression because ERCP had been unsuccessful, underwent EUS-BD with placement of a transmural or transpapillary partially covered nitinol self-expandable metal stent (SEMS). EUS-assisted cholangiography was successful in all patients, with definition of the relevant anatomy, but biliary drainage was successfully performed in only 12 (75 %) of the 16 patients (9 choledochoduodenostomies with SEMS placement and 3 biliary rendezvous procedures with papillary SEMS placement), with regression of the cholestasis. No major complications and no procedure-related deaths occurred. There was one case of pneumoperitoneum which was managed conservatively. The median follow-up was 170 days. During the follow-up, eight patients of the 12 patients in whom biliary draining was successful died; four are currently alive. None of the patients required endoscopic reintervention. This series demonstrated that EUS-BD with a partially covered SEMS has a high rate of clinical success and low complication rates, and could represent an alternative choice for biliary decompression.

  9. [The five syndromes of biliary obstruction].

    PubMed

    Praderi, R C; Gil, J

    1999-01-01

    Clinical description of biliary diseases are slightly over a century old. At the end of last century and beginning of the present one, laws were established and clinical syndromes were described; these are still valid at present. Some modern techniques such as ultrasonography confirmed the importance of the Courvoisier-Terrier law. The first syndromatic description was made by two clinicians from Lyon, Bard and Pic, based on autopsy confirmation of clinical features. This paper analyses those rules and exceptions to Courvoisier-Terrier law. Research carried out by Pablo Marizzi, the Argentine surgeon who introduced operatory cholangiography is also analyzed. By means of this technique he was able to study patients better, transforming biliary surgery into a procedure with scientific basis, thanks to imagenological data. The sphincter described by this author turned out to be a radiological artifact due to the use of oily contrast media. Finally the right and left hydrohepatosis syndromes described by Cattell and Braasch in the 1960s are discussed. In 1971 we pointed out our disagreement over jaundice in left hydrohepatosis.

  10. [Antibiotherapy in biliary surgery. Current status].

    PubMed

    Guyot, L; Allouch, P; Legue, E; Estenne, B

    1989-04-01

    Without antibiotherapy, biliary surgery is often followed by infectious complications, possibly serious, indeed life-threatening. Biliary bacteria do are responsible of these complications; mainly E. Coli, Streptococcus faecalis (whose pathogenicity is disputed) and Klebsiella. Bacteroides fragilis and Pseudomonas aeruginosa are restricted to special circumstances. It is often difficult to presee whether bile is infected: some risk factors were emerged by Keighley but their specificity is not excellent; peroperative Gram staining got various results according to the studies. Some prefer to give a systematic antibiotherapy. Preoperative antibiotic treatment should be as short as possible because it does not sterilize bile, but selects resistant bacteria, which induce postoperative complications. It must mainly be aimed at preventing infectious scattering. Surgery is the main part of the treatment. Antibiotic choice has to take into account clinical picture, bacteria (those probably responsible for and their sensibility) and goal of the treatment (prophylactic or curative). Analysis of failures should allow to improve this choice. But only multicenter studies concerning full selected populations of patients are able to prove superiority of one antibiotic to another.

  11. Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

    SciTech Connect

    Fuhrman-Lane, C.; Fujimoto, J.M.

    1982-09-01

    The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

  12. Pregnancy Complicated by Portal Hypertension Secondary to Biliary Atresia

    PubMed Central

    O'Sullivan, O. E.; Crosby, D.; Byrne, B.; Regan, C.

    2013-01-01

    Biliary atresia is a rare idiopathic neonatal cholestatic disease characterized by the destruction of both the intra- and extrahepatic biliary ducts. As the disease is progressive all cases will develop portal fibrosis, cirrhosis, and portal hypertension with the sequelae of varices, jaundice, and eventually liver failure requiring a transplant. Survival rates have improved considerably with many females living well in to be childbearing age. Due to the complexity of the disease these pregnancies are considered, high risk. We report the antenatal, intrapartum, and postpartum managements of a pregnancy complicated by biliary atresia. Furthermore, we highlight the importance of a multidisciplinary team approach in optimizing obstetric care for this high risk group. PMID:24459595

  13. Double Incomplete Internal Biliary Fistula: Coexisting Cholecystogastric and Cholecystoduodenal Fistula

    PubMed Central

    Beksac, Kemal; Erkan, Arman; Kaynaroglu, Volkan

    2016-01-01

    Internal biliary fistula is a rare complication of a common surgical disease, cholelithiasis. It is seen in 0.74% of all biliary tract surgeries and is thought to be a result of repeated inflammatory periods of the gallbladder. In this report we present a case of incomplete cholecystogastric and cholecystoduodenal fistulae in a single patient missed by ultrasonography and endoscopic retrograde cholangiopancreatography and diagnosed intraoperatively. In the literature there is only one report of an incomplete cholecystogastric fistula. To our knowledge this is the first case of double incomplete internal biliary fistulae. PMID:26904348

  14. Advances in the Management of Biliary Tract Cancers

    PubMed Central

    Ciombor, Kristen Keon; Goff, Laura Williams

    2013-01-01

    Biliary tract cancers (BTC), though uncommon, are highly fatal malignancies, and current treatments fail to cure or control the majority of tumors. Given the complexity of the anatomy and often aggressive nature of the disease, multidisciplinary treatment, including palliation, is often required. However, systemic therapy with cytotoxics and/or targeted agents are routinely the mainstay of treatment for patients with advanced biliary tract cancers, and new targets and agents provide hope for this disease. This article focuses on recent advances in the management of biliary tract cancers, with a special focus on the molecular basis for current therapeutic investigation in this disease. PMID:23416860

  15. Timing of cholecystectomy in biliary pancreatitis treatment

    PubMed Central

    Demir, Uygar; Yazıcı, Pınar; Bostancı, Özgür; Kaya, Cemal; Köksal, Hakan; Işıl, Gürhan; Bozdağ, Emre; Mihmanlı, Mehmet

    2014-01-01

    Objective: Gallstone pancreatitis constitutes 40% of all cases with pancreatitis while it constitutes up to 90% of cases with acute pancreatitis. The treatment modality in this patient population is still controversial. In this study, we aimed to compare the results of early and late cholecystectomy for patients with biliary pancreatitis. Material and Methods: Patients treated with a diagnosis of acute biliary pancreatitis in our clinics between January 2000 and December 2011 were retrospectively reviewed. Patients were divided into two groups: Group A, patients who underwent cholecystectomy during the first pancreatitis attack, Group B, patients who underwent an interval cholecystectomy at least 8 weeks after the first pancreatitis episode. The demographic characteristics, clinical symptoms, number of episodes, length of hospital stay, morbidity and mortality data were recorded. All data were evaluated with Statistical Package for the Social Sciences (SPSS) 13.0 for windows and p <0.05 was considered as statistically significant. Results: During the last 12 years, a total of 91 patients with surgical treatment for acute biliary pancreatitis were included into the study. There were 62 female and 29 male patients, with a mean age of 57.9±14.6 years (range: 21–89). A concomitant acute cholecystitis was present in 46.2% of the patients. Group A and B included 48 and 43 patients, respectively. The length of hospital stay was significantly higher in group B (9.4 vs. 6.8 days) (p<0,05). More than half of the patients in Group B were readmitted to the hospital for various reasons. No significant difference was observed between the two groups, one patient died due to heart failure in the postoperative period in group B. Conclusion: In-hospital cholecystectomy after remission of acute pancreatitis is feasible. It will not only result in lower recurrence and complication rates but also shorten length of hospital stay. We recommend performing cholecystectomy during the

  16. Autoimmune hepatitis in a teenage boy: 'overlap' or 'outlier' syndrome--dilemma for internists.

    PubMed

    Talukdar, Arunansu; Khanra, Dibbendhu; Mukherjee, Kabita; Saha, Manjari

    2013-02-08

    An 18-year-old boy presented with upper gastrointestinal bleeding and jaundice. Investigations revealed coarse hepatomegaly, splenomegaly and advanced oesophageal varices. Blood reports showed marked rise of alkaline phosphatase and more than twofold rise of transaminases and IgG. Liver histology was suggestive of piecemeal necrosis, interphase hepatitis and bile duct proliferation. Antinuclear antibody was positive in high titre along with positive antismooth muscle antibody and antimitochondrial antibody. The patient was positive for human leukocyte antigen DR3 type. Although an 'overlap' syndrome exists between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), a cholestatic variant of AIH, a rare 'outlier' syndrome could not be excluded in our case. Moreover, 'the chicken or the egg', AIH or PBC, the dilemma for the internists continued. The patient was put on steroid and ursodeoxycholic acid with unsatisfactory response. The existing international criteria for diagnosis of AIH are not generous enough to accommodate its variant forms.

  17. Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma

    PubMed Central

    Guest, Rachel V; Boulter, Luke; Kendall, Timothy J; Minnis-Lyons, Sarah E; Walker, Robert; Wigmore, Stephen J; Sansom, Owen J; Forbes, Stuart J

    2014-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a treatment refractory malignancy with a high mortality and an increasing incidence worldwide. Recent studies have observed that activation of Notch and AKT signalling within mature hepatocytes is able to induce the formation of tumours displaying biliary lineage markers, thereby raising the suggestion that it is hepatocytes, rather than cholangiocytes or hepatic progenitor cells that represent the cell of origin of this tumour. Here we utilise a cholangiocyte-lineage tracing system to target p53 loss to biliary epithelia and observe the appearance of labelled biliary lineage tumours in response to chronic injury. Consequent to this, up-regulation of native functional Notch signalling is observed to occur spontaneously within cholangiocytes and hepatocytes in this model as well as in human ICC. These data prove that in the context of chronic inflammation and p53 loss, frequent occurrences in human disease, biliary epithelia are a target of transformation and an origin of ICC. PMID:24310400

  18. 21 CFR 876.5010 - Biliary catheter and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... used for temporary or prolonged drainage of the biliary tract, for splinting of the bile duct during healing, or for preventing stricture of the bile duct. This generic type of device may include a...

  19. Improvement of Liver Function, Quality of Life and Survival after Insertion of Endoprosthesis in Advance Malignant Biliary Obstruction.

    PubMed

    Ullah, A A; Rahman, A; Chowdhury, L H; Bhuiya, A H

    2017-01-01

    Obstructive jaundice due to advance malignancy is a fatal problem. It most commonly occurs at the distal common bile duct or at the hilum of liver. Magnetic Resonance Cholangio Pancreatography (MRCP) and Computed Tomography (CT) are most useful in identifying the underlying cause as well as localize the position of the stricture. For those patients with unresectable disease, progressive jaundice constitutes an immediate threat to their survival, in addition to significant loss to their quality of life secondary to pruritus, malaise and cholangitis. Effective and lasting decompression of the biliary tree is a priority and consists of positioning of a biliary endoprosthesis (stent). To observe the improvement of liver function, quality of life and survival after successful insertion of endoprosthesis (stenting) in malignant biliary obstruction, a study was performed in the department of surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from September 2013 to August 2014, in 50 patients with clinically visible jaundice and unresectable disease. There were significant (p<0.001) reductions in the levels of serum bilirubin, serum alkaline phosphatase, serum SGPT and Prothrombin time from the time of admission to 2 weeks and 3 weeks after stenting. Physical and functional quality of life was greatly improved 2-4 weeks after stenting, where emotional quality remained the same throughout the study period. Successful palliation by stenting of malignant biliary obstruction is a priority to achieve improvements in liver function, quality of life and prolong survival. Endoscopic stent placement appears to be safe, well tolerated and can be offered without delay as a primary treatment option for all patients with unresectable malignant biliary lesion.

  20. Management issues in post living donor liver transplant biliary strictures

    PubMed Central

    Wadhawan, Manav; Kumar, Ajay

    2016-01-01

    Biliary complications are common after living donor liver transplant (LDLT) although with advancements in surgical understanding and techniques, the incidence is decreasing. Biliary strictures are more common than leaks. Endoscopic retrograde cholangiopancreatography (ERCP) is the first line modality of treatment of post LDLT biliary strictures with a technical success rate of 75%-80%. Most of ERCP failures are successfully treated by percutaneous transhepatic biliary drainage (PTBD) and rendezvous technique. A minority of patients may require surgical correction. ERCP for these strictures is technically more challenging than routine as well post deceased donor strictures. Biliary strictures may increase the morbidity of a liver transplant recipient, but the mortality is similar to those with or without strictures. Post transplant strictures are short segment and soft, requiring only a few session of ERCP before complete dilatation. Long-term outcome of patients with biliary stricture is similar to those without stricture. With the introduction of new generation cholangioscopes, ERCP success rate may increase, obviating the need for PTBD and surgery in these patients. PMID:27057304

  1. On the mechanical behavior of the human biliary system

    PubMed Central

    Luo, Xiaoyu; Li, Wenguang; Bird, Nigel; Chin, Swee Boon; Hill, NA; Johnson, Alan G

    2007-01-01

    This paper reviews the progress made in understanding the mechanical behaviour of the biliary system. Gallstones and diseases of the biliary tract affect more than 10% of the adult population. The complications of gallstones, i.e. acute pancreatitis and obstructive jandice, can be lethal, and patients with acalculous gallbladder pain often pose diagnostic difficulties and undergo repeated ultrasound scans and oral cholecystograms. Moreover, surgery to remove the gallbladder in these patients, in an attempt to relieve the symptoms, gives variable results. Extensive research has been carried out to understand the physiological and pathological functions of the biliary system, but the mechanism of the pathogenesis of gallstones and pain production still remain poorly understood. It is believed that the mechanical factors play an essential role in the mechanisms of the gallstone formation and biliary diseases. However, despite the extensive literature in clinical studies, only limited work has been carried out to study the biliary system from the mechanical point of view. In this paper, we discuss the state of art knowledge of the fluid dynamics of bile flow in the biliary tract, the solid mechanics of the gallbladder and bile ducts, recent mathematical and numerical modelling of the system, and finally the future challenges in the area. PMID:17457970

  2. Biliary excretion of iron and ferritin in idiopathic hemochromatosis

    SciTech Connect

    Hultcrantz, R.; Angelin, B.; Bjoern-Rasmussen, E.E.; Ewerth, S.; Einarsson, K.

    1989-06-01

    The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.

  3. 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

  4. 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

  5. A comparison between endoscopic ultrasound-guided rendezvous and percutaneous biliary drainage after failed ERCP for malignant distal biliary obstruction

    PubMed Central

    Bill, Jason G.; Darcy, Michael; Fujii-Lau, Larissa L.; Mullady, Daniel K.; Gaddam, Srinivas; Murad, Faris M.; Early, Dayna S.; Edmundowicz, Steven A.; Kushnir, Vladimir M.

    2016-01-01

    Background and study Aims: Selective biliary cannulation is unsuccessful in 5 % to 10 % of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for malignant distal biliary obstruction (MDBO). Percutaneous biliary drainage (PBD) has been the gold standard, but endoscopic ultrasound guided rendezvous (EUSr) have been increasingly used for biliary decompression in this patient population. Our aim was to compare the initial success rate, long-term efficacy, and safety of PBD and EUSr in relieving MDBO after failed ERC Patients and methods: A retrospective study involving 50 consecutive patients who had an initial failed ERCP for MDBO. Twenty-five patients undergoing EUSr between 2008 – 2014 were compared to 25 patients who underwent PBD immediately prior to the introduction of EUSr at our center (2002 – 2008). Comparisons were made between the two groups with regard to technical success, duration of hospital stay and adverse event rates after biliary decompression. Results: The mean age at presentation was 66.5 (± 12.6 years), 28 patients (54.9 %) were female. The etiology of MDBO was pancreaticobiliary malignancy in 44 (88 %) and metastatic disease in 6 (12 %) cases. Biliary drainage was technically successful by EUSr in 19 (76 %) cases and by PBD in 25 (100 %) (P = 0.002). Median length of hospital stay after initial drainage was 1 day in the EUSr group vs 5 days in PBD group (P = 0.02). Repeat biliary intervention was required for 4 patients in the EUSr group and 15 in the PBD group (P = 0.001). Conclusions: Initial technical success with EUSr was significantly lower than with PBD, however when EUSr was successful, patients had a significantly shorter post-procedure hospital stay and required fewer follow-up biliary interventions. Meeting presentations: Annual Digestive Diseases Week 2015 PMID:27652305

  6. Efficacy of multiple biliary stenting for refractory benign biliary strictures due to chronic calcifying pancreatitis

    PubMed Central

    Ohyama, Hiroshi; Mikata, Rintaro; Ishihara, Takeshi; Sakai, Yuji; Sugiyama, Harutoshi; Yasui, Shin; Tsuyuguchi, Toshio

    2017-01-01

    AIM To investigate endoscopic therapy efficacy for refractory benign biliary strictures (BBS) with multiple biliary stenting and clarify predictors. METHODS Ten consecutive patients with stones in the pancreatic head and BBS due to chronic pancreatitis who underwent endoscopic therapy were evaluated. Endoscopic insertion of a single stent failed in all patients. We used plastic stents (7F, 8.5F, and 10F) and increased stents at intervals of 2 or 3 mo. Stents were removed approximately 1 year after initial stenting. BBS and common bile duct (CBD) diameter were evaluated using cholangiography. Patients were followed for ≥ 6 mo after therapy, interviewed for cholestasis symptoms, and underwent liver function testing every visit. Patients with complete and incomplete stricture dilations were compared. RESULTS Endoscopic therapy was completed in 8 (80%) patients, whereas 2 (20%) patients could not continue therapy because of severe acute cholangitis and abdominal abscess, respectively. The mean number of stents was 4.1 ± 1.2. In two (20%) patients, BBS did not improve; thus, a biliary stent was inserted. BBS improved in six (60%) patients. CBD diameter improved more significantly in the complete group than in the incomplete group (6.1 ± 1.8 mm vs 13.7 ± 2.2 mm, respectively, P = 0.010). Stricture length was significantly associated with complete stricture dilation (complete group; 20.5 ± 3.0 mm, incomplete group; 29.0 ± 5.1 mm, P = 0.011). Acute cholangitis did not recur during the mean follow-up period of 20.6 ± 7.3 mo. CONCLUSION Sequential endoscopic insertion of multiple stents is effective for refractory BBS caused by chronic calcifying pancreatitis. BBS length calculation can improve patient selection procedure for therapy. PMID:28101303

  7. Conclusive evidence of endotoxaemia in biliary obstruction

    PubMed Central

    Clements, W; Erwin, P; McCaigue, M; Halliday, I; Barclay, G; Rowlands, B

    1998-01-01

    Background—Endotoxaemia is implicated in the pathophysiology of obstructive jaundice. The EndoCab enzyme linked immunosorbent assay (ELISA) is a novel assay which measures endogenous antibody (IgG) to the inner core region of circulating endotoxins (ACGA). 
Aims—To investigate the significance of endotoxaemia in biliary obstruction using the EndoCab assay and assess the specificity of the humoral response to endotoxin compared with an exogenous antigenic challenge (tetanus toxoid, TT). 
Methods—Three groups of adult male Wistar rats were studied: no operation, sham operation, and bile duct ligation for 21 days (BDL). In the second study, rats rats received prior immunisation with TT. 
Results—In the preliminary experiment, plasma ACGA was significantly increased in the BDL group (306.6 (18.3)% versus 119.9(6.7)% and 105.2 (4.6)% in the sham and no operation groups, respectively; p<0.001). Although the mean endotoxin concentration in the BDL group was greater than that in the control groups this was not significant. There was a strong positive correlation between ACGA and endotoxin concentrations (p=0.0021). In the second study mean ACGA after 21 days of BDL was significantly elevated (267.1 (31.2)% versus 101.6 (21.2)% at baseline, p<0.0001). ACGA was unaffected in the other two groups. TT antibody concentrations fell in all three groups; only in the BDL group was the fall significant (97.6(5.3)% versus 78.8 (4.2)% at baseline, p<0.05). 
Conclusions—The specific rise in ACGA supports the hypothesis that endotoxin has an integral role in the pathophysiology of obstructive jaundice. The production of anticore glycolipid antibodies specifically reflects systemic endotoxaemia in this model. The EndoCab assay provides a novel, sensitive, and specific method for endotoxin detection. 

 Keywords: biliary obstruction; endotoxaemia; EndoCab assay PMID:9536958

  8. Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer

    ClinicalTrials.gov

    2017-02-03

    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

  9. 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

  10. Biliary Tract Anatomy and its Relationship with Venous Drainage

    PubMed Central

    Ramesh Babu, Chittapuram S.; Sharma, Malay

    2013-01-01

    Portal cavernoma develops as a bunch of hepatopetal collaterals in response to portomesenteric venous obstruction and induces morphological changes in the biliary ducts, referred to as portal cavernoma cholangiopathy. This article briefly reviews the available literature on the vascular supply of the biliary tract in the light of biliary changes induced by portal cavernoma. Literature pertaining to venous drainage of the biliary tract is scanty whereas more attention was focused on the arterial supply probably because of its significant surgical implications in liver transplantation and development of ischemic changes and strictures in the bile duct due to vasculobiliary injuries. Since the general pattern of arterial supply and venous drainage of the bile ducts is quite similar, the arterial supply of the biliary tract is also reviewed. Fine branches from the posterior superior pancreaticoduodenal, retroportal, gastroduodenal, hepatic and cystic arteries form two plexuses to supply the bile ducts. The paracholedochal plexus, as right and left marginal arteries, run along the margins of the bile duct and the reticular epicholedochal plexus lie on the surface. The retropancreatic, hilar and intrahepatic parts of biliary tract has copious supply, but the supraduodenal bile duct has the poorest vascularization and hence susceptible to ischemic changes. Two venous plexuses drain the biliary tract. A fine reticular epicholedochal venous plexus on the wall of the bile duct drains into the paracholedochal venous plexus (also called as marginal veins or parabiliary venous system) which in turn is connected to the posterior superior pancreaticoduodenal vein, gastrocolic trunk, right gastric vein, superior mesenteric vein inferiorly and intrahepatic portal vein branches superiorly. These pericholedochal venous plexuses constitute the porto-portal collaterals and dilate in portomesenteric venous obstruction forming the portal cavernoma. PMID:25755590

  11. Biliary tract anatomy and its relationship with venous drainage.

    PubMed

    Ramesh Babu, Chittapuram S; Sharma, Malay

    2014-02-01

    Portal cavernoma develops as a bunch of hepatopetal collaterals in response to portomesenteric venous obstruction and induces morphological changes in the biliary ducts, referred to as portal cavernoma cholangiopathy. This article briefly reviews the available literature on the vascular supply of the biliary tract in the light of biliary changes induced by portal cavernoma. Literature pertaining to venous drainage of the biliary tract is scanty whereas more attention was focused on the arterial supply probably because of its significant surgical implications in liver transplantation and development of ischemic changes and strictures in the bile duct due to vasculobiliary injuries. Since the general pattern of arterial supply and venous drainage of the bile ducts is quite similar, the arterial supply of the biliary tract is also reviewed. Fine branches from the posterior superior pancreaticoduodenal, retroportal, gastroduodenal, hepatic and cystic arteries form two plexuses to supply the bile ducts. The paracholedochal plexus, as right and left marginal arteries, run along the margins of the bile duct and the reticular epicholedochal plexus lie on the surface. The retropancreatic, hilar and intrahepatic parts of biliary tract has copious supply, but the supraduodenal bile duct has the poorest vascularization and hence susceptible to ischemic changes. Two venous plexuses drain the biliary tract. A fine reticular epicholedochal venous plexus on the wall of the bile duct drains into the paracholedochal venous plexus (also called as marginal veins or parabiliary venous system) which in turn is connected to the posterior superior pancreaticoduodenal vein, gastrocolic trunk, right gastric vein, superior mesenteric vein inferiorly and intrahepatic portal vein branches superiorly. These pericholedochal venous plexuses constitute the porto-portal collaterals and dilate in portomesenteric venous obstruction forming the portal cavernoma.

  12. The Timing of Biliary Surgery in Acute Pancreatitis

    PubMed Central

    Ranson, John H. C.

    1979-01-01

    The timing of biliary surgery remains controversial in patients with acute pancreatitis associated with cholelithiasis. Eighty hospital admissions for acute pancreatitis, occurring in 74 patients with cholelithiasis, have therefore been reviewed. Among 22 patients who underwent abdominal surgery during the first week of treatment, there were five deaths (23%) and four patients (18%) who required more than seven days of intensive care. Fifty-eight episodes of pancreatitis were managed nonoperatively during the first week of treatment, with no deaths, although six (10%) required more than seven days of intensive care. Biliary surgery was undertaken later during the same admission in 37 patients, with no deaths. Twenty-one patients were discharged without biliary operation, but seven (33%) developed further pancreatitis. Previously reported prognostic signs were used to divide pancreatitis into 57 “mild” episodes (1.8% mortality) and 23 “severe” episodes (17% mortality). Early (day 0-7) definitive biliary surgery was undertaken in 11 patients with “mild” pancreatitis, with one death (9%), and in six patients with “severe” pancreatitis, with four deaths (67%). In three recent patients with “severe” pancreatitis, early biliary surgery was limited to cholecystostomy, with no deaths. These findings suggest that although early correction of associated biliary disease may be undertaken safely in many patients with “mild” acute pancreatitis, early definitive surgery is hazardous in “severe” pancreatitis and should, if possible, be deferred until pancreatitis has subsided. In most patients biliary surgery should precede hospital discharge. PMID:443917

  13. [Pancreas and biliary tract: recent developments].

    PubMed

    de-Madaria, Enrique

    2014-09-01

    Acute pancreatitis (AP) is a common disease that is associated with significant morbidity and considerable mortality. In this article, developments relating to this disease that were presented in DDW 2014 are reviewed. Pancreatic steatosis could be a cause of recurrent AP. Patients with DM have an increased incidence of AP and pancreatic cancer. The use of anti-TNF drugs in inflammatory bowel disease may protect against the occurrence of AP. The presence of pancreas divisum protects against acute biliary pancreatitis. The PANCODE system for describing local complications of AP has good interobserver agreement, when the new definitions of the revised Atlanta classification are applied. The use of prophylactic antibiotics in early-stage AP predisposes the development of intra-abdominal fungal infections. Fluid sequestration in AP is linked with young age, alcoholism and indicators of systemic inflammatory response syndrome. The most common cause of mortality in AP is early onset of multiple organ failure, not pancreatic necrosis infection. Patients with AP and vitamin D deficiency could benefit from taking vitamin D supplements. Moderate fluid administration in emergencies (500-1000 mL) could be associated with better AP development.

  14. Loss of a Candidate Biliary Atresia Susceptibility Gene, add3a, Causes Biliary Developmental Defects in Zebrafish

    PubMed Central

    Tang, Vivian; Cofer, Zenobia C.; Cui, Shuang; Sapp, Valerie; Loomes, Kathleen M.; Matthews, Randolph P.

    2016-01-01

    ABSTRACT Objectives: Biliary atresia (BA) is a progressive fibroinflammatory cholangiopathy affecting the bile ducts of neonates. Although BA is the leading indication for pediatric liver transplantation, the etiology remains elusive. Adducin 3 (ADD3) and X-prolyl aminopeptidase 1 (XPNPEP1) are 2 genes previously identified in genome-wide association studies as potential BA susceptibility genes. Using zebrafish, we investigated the importance of ADD3 and XPNPEP1 in functional studies. Methods: To determine whether loss of either gene leads to biliary defects, we performed morpholino antisense oligonucleotide (MO) knockdown studies targeting add3a and xpnpep1 in zebrafish. Individuals were assessed for decreases in biliary function and the presence of biliary defects. Quantitative polymerase chain reaction was performed on pooled 5 days postfertilization larvae to assess variations in transcriptional expression of genes of interest. Results: Although both xpnpep1 and add3a are expressed in the developing zebrafish liver, only knockdown of add3a produced intrahepatic defects and decreased biliary function. Similar results were observed in homozygous add3a mutants. MO-mediated knockdown of add3a also showed higher mRNA expression of hedgehog (Hh) targets. Inhibition of Hh signaling rescued biliary defects caused by add3a knockdown. Combined knockdown of add3a and glypican-1 (gpc1), another mediator of Hh activity that is also a BA susceptibility gene, resulted in more severe biliary defects than knockdown of either alone. Conclusions: Our results support previous studies identifying ADD3 as a putative genetic risk factor for BA susceptibility. Our results also provide evidence that add3a may be affecting the Hh pathway, an important factor in BA pathogenesis. PMID:27526058

  15. Complications and management of forgotten long-term biliary stents

    PubMed Central

    Sohn, Se Hoon; Park, Jae Hyun; Kim, Kook Hyun; Kim, Tae Nyeun

    2017-01-01

    AIM To evaluate complications and management outcomes of retained long-term plastic biliary stents. METHODS 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 χ2 tests. Statistical significance was defined as P < 0.05 (two-tailed). RESULTS 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. CONCLUSION The most common complication of retained long-term plastic biliary stents was acute cholangitis associated with CBD stones. Endoscopic management was successfully

  16. Cancers of the pancreas and biliary tract: epidemiological considerations.

    PubMed

    Fraumeni, J F

    1975-11-01

    The epidemiological patterns for pancreatic and biliary cancers reveal more differences than similarities. Pancreatic carcinoma is common in western countries, although 2 Polynesian groups (New Zealand Maoris and native Hawaiians) have the highest rates internationally. In the United States the disease is rising in frequency, predominating in males and in blacks. The rates are elevated in urban areas, but geographic analysis uncovered no clustering of contiguous counties except in southern Louisiana. The origin of pancreatic cancer is obsure, but a twofold increased risk has been documented for cigarette smokers and diabetic patients. Alcohol, occupational agents, and dietary fat have been suspected, but not proven to be risk factors. Except for the rare hereditary form of pancreatitis, there are few clues to genetic predisposition. In contrast, the reported incidence of biliary tract cancer is highest in Latin American populations and American Indians. The tumor predominates in females around the world, except for Chinese and Japanese who show a male excess. In the United States the rates are higher in whites than blacks, and clusters of high-risk counties have been found in the north central region, the southwest, and Appalachia. The distribution of biliary tumors parallels that of cholesterol gallstones, the major risk factor for biliary cancer. Insights into biliary carcinogenesis depend upon clarification of lithogenic influences, such as pregnancy, obesity, and hyperlipoproteinemia, exogenous estrogens, familial tendencies, and ethnic-geographic factors that may reflect dietary habits. Noncalculous risk factors for biliary cancer include ulcerative colitis, clonorchiasis, Gardner's syndrome, and probably certain industrial exposures. Within the biliary tract, tumors of the gallbladder and bile duct show epidemiological distinctions. In contrast to gallbladder cancer, bile duct neoplasms predominate in males; they are less often associated with stones and more

  17. Early biliary complications following pancreaticoduodenectomy: prevalence and risk factors

    PubMed Central

    Malgras, Brice; Duron, Sandrine; Gaujoux, Sébastien; Dokmak, Safi; Aussilhou, Béatrice; Rebours, Vinciane; Palazzo, Maxime; Belghiti, Jacques; Sauvanet, Alain

    2016-01-01

    Background Early biliary complications (EBC) following pancreaticoduodenectomy (PD) are poorly known. This study aimed to assess incidence, predictive factors, and treatment of EBC including bilio-enteric stricture, transient jaundice, biliary leak, and cholangitis. Method From 2007 to 2011, 352 patients underwent PD. Statistical analysis including logistic regression was performed to determine EBC predictive factors. Results 49 patients (14%) developed 51 EBC, including 7(2%) bilio-enteric strictures, 15(4%) transient jaundices, 9(3%) biliary leaks, and 20(6%) cholangitis with no mortality and a 18% reoperation rate. In multivariate analysis, male gender, benign disease, malignancy with preoperative chemoradiation, and common bile duct (CBD) diameter ≤5 mm were predictive of EBC. Of the 7 strictures, all were associated with CBD ≤5 mm and 5(71%) required reoperation. Transient jaundice resolved spontaneously in all 15 cases. Among 8 patients with serum bilirubin level >50 μmol/L (3 mg/dL) at POD3, 7(88%) developed bilio-enteric stricture. Biliary leak resolved spontaneously in 5(56%); otherwise, it required reoperation. Cholangitis recurred after antibiotics discontinuation in 5(25%). Conclusions EBC following PD do not increase mortality. EBC are more frequent with male gender, benign disease, malignancy with preoperative chemoradiation, and CBD ≤5 mm. Transient jaundice or cholangitis has a favorable outcome, whereas bilio-enteric stricture or biliary leak can require reintervention. PMID:27037207

  18. Situs inversus totalis and secondary biliary cirrhosis: a case report

    PubMed Central

    2011-01-01

    Situs inversus totalis is is a congenital anomaly associated with various visceral abnormalities, but there is no data about the relationship between secondary biliary cirrhosis and that condition. We here present a case of a 58 year-old female with situs inversus totalis who was admitted to our clinic with extrahepatic cholestasis. After excluding all potential causes of biliary cirrhosis, secondary biliary cirrhosis was diagnosed based on the patient's history, imaging techniques, clinical and laboratory findings, besides histolopathological findings. After treatment with tauroursodeoxycholic acid, all biochemical parameters, including total/direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gama glutamyl transferase, returned to normal ranges at the second month of the treatment. We think that this is the first case in literature that may indicate the development of secondary biliary cirrhosis in a patient with situs inversus totalis. In conclusion, situs inversus should be considered as a rare cause of biliary cirrhosis in patients with situs inversus totalis which is presented with extrahepatic cholestasis. PMID:21813017

  19. Connection between hyperemesis gravidarum, jaundice or liver dysfunction, and biliary sludge.

    PubMed

    Matsubara, Shigeki; Kuwata, Tomoyuki; Kamozawa, Chihiro; Sakamoto, Yuki; Suzuki, Mitsuaki; Tamada, Kiichi

    2012-02-01

    Jaundice in hyperemesis gravidarum may cause physicians to suspect several underlying diseases. Jaundice appeared in a woman with hyperemesis gravidarum and an ultrasound revealed biliary sludge. Hydration concomitantly ameliorated the symptoms, jaundice and the biliary sludge. Another woman with hyperemesis gravidarum showed elevated aminotransferases, with biliary sludge also being present. Hydration ameliorated the symptoms and liver dysfunction, and reduced the total bilirubin level. Biliary sludge appeared, but was ameliorated according to the symptoms of hyperemesis gravidarum.

  20. [Suprapapilar puncture for biliary access to advanced cancer of the papilla and severe coagulopathy].

    PubMed

    Artifon, E; Couto, D S; Navarro, A

    2009-01-01

    Biliary cannulation to perform endoscopic retrograde cholangiopancreatography (ERCP) may be difficult in patients with advanced papillary cancer, due to anatomical and technical reasons. Sphincterotomy may be contraindicated in severe coagulopathy. We report a recently described technique of suprapapillary puncture for biliary access with use of an Artifon's catheter for biliary access in a high-risk patient with coagulopathy and periampullary neoplasm.

  1. Acute Duodenal Obstruction After Percutaneous Placement of Metallic Biliary Stents: Peroral Treatment with Enteral Stents

    SciTech Connect

    Lopera, Jorge E. Alvarez, Oscar A.; Perdigao, Joseph; Castaneda-Zuniga, Wilfrido

    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.

  2. Endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage after failed endoscopic retrograde cholangiopancreatography: a meta-analysis

    PubMed Central

    Baniya, Ramkaji; Upadhaya, Sunil; Madala, Seetharamprasad; Subedi, Subash Chandra; Shaik Mohammed, Tabrez; Bachuwa, Ghassan

    2017-01-01

    The failure rate of endoscopic retrograde cholangiopancreatography for biliary cannulation is approximately 6%–7% in cases of obstructive jaundice. Percutaneous transhepatic biliary drainage (PTBD) is the procedure of choice in such cases. Endoscopic ultrasound-guided biliary drainage (EGBD) is a novel technique that allows biliary drainage by echoendoscopy and fluoroscopy using a stent from the biliary tree to the gastrointestinal tract. Information in PubMed, Scopus, clinicaltrials.gov and Cochrane review were analyzed to obtain studies comparing EGBD and PTBD. Six studies fulfilled the inclusion criteria. Technical (odds ratio (OR): 0.34; confidence interval (CI) 0.10–1.14; p=0.05) and clinical (OR: 1.48; CI 0.46–4.79; p=0.51) success rates were not statistically significant between the EGBD and PTBD groups. Mild adverse events were nonsignificantly different (OR: 0.36; CI 0.10–1.24; p=0.11) but not the moderate-to-severe adverse events (OR: 0.16; CI 0.08–0.32; p≤0.00001) and total adverse events (OR: 0.34; CI 0.20–0.59; p≤0.0001). EGBD is equally effective but safer than PTBD.

  3. Malignant biliary obstruction: the current role of interventional radiology

    PubMed Central

    Tsetis, Dimitrios; Krokidis, Μiltiadis; Negru, Dragos; Prassopoulos, Panagiotis

    2016-01-01

    Cholangiocarcinoma and pancreatic head cancer are still linked with extremely high 5-year mortality in the western world. The management of such patients is complex and typically requires a multidisciplinary approach in a tertiary care center. Interventional radiology offers minimally invasive, image-guided treatment for a variety of diseases and conditions. Regarding patients with malignant biliary obstruction, IR options are considered for more than two decades as a valid management tool for both operable and non-operable cases. The options include placement of percutaneous transhepatic biliary drains, preoperative embolization of the portal vein and deployment of covered and uncovered biliary stents. The purpose of this review is to describe the current evidence in this continuously evolving field. PMID:26752947

  4. Effects of biliary obstruction on hepatic clearance of bacteria

    SciTech Connect

    Allen, M.O.; Wilton, P.B.; Barke, R.A.; Gerding, D.N.; Forstrom, L.A.; Shafer, R.B.; Vennes, J.A. )

    1989-08-01

    High surgical mortality in patients with obstructive jaundice and sepsis have been attributed to reticuloendothelial system (RES) depression. The purpose of this study was to clarify the effects of mechanical biliary obstruction on RES clearance of pathogenic bacteria by comparing the phagocytic index (K) with the directly measured hepatic uptake of indium 111-labeled bacteria injected into the portal vein of normal dogs and dogs with partial (PBO) or complete biliary obstruction (CBO). No significant difference was observed between the K in normal dogs (0.19 +/- 0.08; n = 6) and that in dogs with PBO (0.24 +/- 0.06; n = 5) or CBO (0.21 +/- 0.03; n = 4). There was no significant difference in uptake of radiolabel by the liver among the three groups of dogs. In our model, biliary obstruction had no effect on hepatic RES function and may not represent a significant determinant of mortality in patients with obstructive jaundice.

  5. Combination of laparoscope and choledochoscope to treat biliary ascariasis

    PubMed Central

    Cai, Ming; Cheng, Ji; Li, Wei; Shuai, Xiaoming; Gao, Jinbo; Cai, Kailin; Wang, Jiliang; Bai, Jie; Rog, Colin; Wang, Guobin; Tao, Kaixiong

    2017-01-01

    Abstract Rationale: Ascariasis is an endemic parasitic disease caused by Ascaris lumbricoides, which severely burdens the healthcare system as well as harms the personal life quality, especially among less developed regions. Biliary ascariasis is a critical complication of intestinal ascariasis with painful and life-threatening manifestations. The exploration of proper strategies as its medical interventions remains largely controversial. Patient concerns: A 16 year-old patient complained of abdominal pain and yellow sclera. Diagnoses: Biliary ascariasis Interventions: Laparoscopic cholecystectomy and bile duct exploration. Outcomes: More than one hundred ascarids were extracted and the patient had been discharged from hospital without any complications. Lessons: The combination of laparoscope and choledochoscope is an efficient method to treat biliary ascariasis, despite of large worm burden in the common bile duct. PMID:28353561

  6. Epidemiology of Biliary Atresia in Korea

    PubMed Central

    2017-01-01

    Biliary atresia (BA) is the major cause of cholestasis and the leading indication for liver transplantation (LT). However, the incidence of BA in Korea has not been reported. The aim of this study was to investigate the incidence and clinical outcomes of BA in Korea. We used the Korean universal health insurance database and extracted data regarding BA patients younger than 18 years of age admitted between 2011 and 2015. The incidence of BA was calculated by dividing the number of BA patients by the number of live births. Two hundred forty infants were newly diagnosed with BA. A total of 963 BA patients younger than 18 years of age were followed up for 5 years. The overall incidence of BA was 1.06 cases per 10,000 live births. The incidence of BA was 1.4 times higher for female patients than for male patients. Additionally, significant seasonal variation was observed; in particular, the incidence of BA was 2 times higher from June through August than from December through February. Congenital anomalies were found in 38 of 240 patients (15.8%). Congenital heart diseases were major associated congenital anomalies (6.3%). Several complications developed during the study period, including cholangitis (24.0%), varix (6.2%), and gastrointestinal bleeding (4.4%). Three hundred and one of the 963 BA patients under 18 years of age (31.3%) received LT for BA. The incidence of BA is higher in Korea than that in Western countries. We also report significant gender-associated differences and seasonal variation with respect to the incidence of BA. PMID:28244293

  7. Biliary excretion of TT virus (TTV).

    PubMed

    Nakagawa, N; Ikoma, J; Ishihara, T; Yasui-Kawamura, N; Fujita, N; Iwasa, M; Kaito, M; Watanabe, S; Adachi, Y

    2000-08-01

    A novel DNA virus (TT virus; TTV) was isolated from a patient with post-transfusion hepatitis of unknown etiology. If TTV replicates in the liver, TTV may appear in the bile. In the present study, to clarify whether fecal-oral infection occur via biliary excretion, the presence of TTV DNA was assessed in paired serum and bile samples collected from 28 patients with obstructive jaundice without parenchymal liver disease. TTV DNA was detected by polymerase chain reaction (PCR) using semi-nested primers, and quantified by Real Time Detection PCR (RTD-PCR). The nucleotide sequence of isolates TTV DNAs was also determined and the sequences were compared between serum and bile samples. Among 28 patients, 7 were positive for TTV DNA in both samples, and 3 and 2 were positive in serum and bile respectively. Of 7 patients positive for TTV DNA in both samples, the TTV DNA titer was higher in serum of 4 patients and in bile of 1 patient. Among 7 patients positive for TTV DNA in serum and bile, 6 had the same sequence in both samples. Multiple distinct types of TTV DNA clones were isolated from serum in 2 patients and from bile in 4 patients. In conclusion, TTV DNA is detected frequently in bile from patients with obstructive jaundice, suggesting a fecal-oral route of infection and high prevalence of asymptomatic TTV carriers. TTV DNA was detected only in serum from some patients, suggesting that replication of TTV may occur in other organs as well as in the liver.

  8. Diet and biliary tract cancer risk in Shanghai, China.

    PubMed

    Nelson, Shakira M; Gao, Yu-Tang; Nogueira, Leticia M; Shen, Ming-Chang; Wang, Bingsheng; Rashid, Asif; Hsing, Ann W; Koshiol, Jill

    2017-01-01

    Trends in biliary tract cancer incidence rates have increased in Shanghai, China. These trends have coincided with economic and developmental growth, as well as a shift in dietary patterns to a more Westernized diet. To examine the effect of dietary changes on incident disease, we evaluated associations between diet and biliary tract cancers amongst men and women from a population-based case-control study in Shanghai, China. Biliary tract cancer cases were recruited from 42 collaborating hospitals in urban Shanghai, and population-based controls were randomly selected from the Shanghai Household Registry. Food frequency questionnaire data were available for 225 gallbladder, 190 extrahepatic bile duct, and 68 ampulla of Vater cancer cases. A total of 39 food groups were created and examined for associations with biliary tract cancer. Interestingly, only four food groups demonstrated a suggested association with gallbladder, extrahepatic bile duct, or ampulla of Vater cancers. The allium food group, consisting of onions, garlic, and shallots showed an inverse association with gallbladder cancer (OR: 0.81, 95% CI: 0.68-0.97). Similar trends were seen in the food group containing seaweed and kelp (OR: 0.79, 95% CI: 0.67-0.96). In contrast, both preserved vegetables and salted meats food groups showed positive associations with gallbladder cancer (OR:1.27, 95% CI: 1.06-1.52; OR: 1.18, 95% CI: 1.02-1.37, respectively). Each of these four food groups showed similar trends for extrahepatic bile duct and ampulla of Vater cancers. The results of our analysis suggest intake of foods with greater anti-inflammatory properties may play a role in decreasing the risk of biliary tract cancers. Future studies should be done to better understand effects of cultural changes on diet, and to further examine the impact diet and inflammation have on biliary tract cancer incidence.

  9. Diet and biliary tract cancer risk in Shanghai, China

    PubMed Central

    Nelson, Shakira M.; Gao, Yu-Tang; Nogueira, Leticia M.; Shen, Ming-Chang; Wang, Bingsheng; Rashid, Asif; Hsing, Ann W.; Koshiol, Jill

    2017-01-01

    Trends in biliary tract cancer incidence rates have increased in Shanghai, China. These trends have coincided with economic and developmental growth, as well as a shift in dietary patterns to a more Westernized diet. To examine the effect of dietary changes on incident disease, we evaluated associations between diet and biliary tract cancers amongst men and women from a population-based case-control study in Shanghai, China. Biliary tract cancer cases were recruited from 42 collaborating hospitals in urban Shanghai, and population-based controls were randomly selected from the Shanghai Household Registry. Food frequency questionnaire data were available for 225 gallbladder, 190 extrahepatic bile duct, and 68 ampulla of Vater cancer cases. A total of 39 food groups were created and examined for associations with biliary tract cancer. Interestingly, only four food groups demonstrated a suggested association with gallbladder, extrahepatic bile duct, or ampulla of Vater cancers. The allium food group, consisting of onions, garlic, and shallots showed an inverse association with gallbladder cancer (OR: 0.81, 95% CI: 0.68–0.97). Similar trends were seen in the food group containing seaweed and kelp (OR: 0.79, 95% CI: 0.67–0.96). In contrast, both preserved vegetables and salted meats food groups showed positive associations with gallbladder cancer (OR:1.27, 95% CI: 1.06–1.52; OR: 1.18, 95% CI: 1.02–1.37, respectively). Each of these four food groups showed similar trends for extrahepatic bile duct and ampulla of Vater cancers. The results of our analysis suggest intake of foods with greater anti-inflammatory properties may play a role in decreasing the risk of biliary tract cancers. Future studies should be done to better understand effects of cultural changes on diet, and to further examine the impact diet and inflammation have on biliary tract cancer incidence. PMID:28288186

  10. [Congenital broncho-biliary fistula: a case report].

    PubMed

    Pérez, Cinthia G; Reusmann, Aixa

    2016-10-01

    Congenital tracheo-or-bronchobiliary fistula or congenital he-patopulmonary fistula is a rare malformation with high morbidity and mortality if the diagnosis is not made early. The tracheo-or-bronchobiliary fistula is a communication between the respiratory (trachea or bronchus) and biliary tract. To date, only 35 cases have been published worldwide. We report a case of a neonate with right pneumonia and bilious fluid in the endotracheal tube. Diagnosis was made using bronchoscopy with fluoroscopy. Videothoracoscopy was used to remove the bronchobiliary fistula. Subsequently, a left he-patectomy with Roux-en-Y biliary-digestive anastomosis was performed as bile ductus hypoplasia was present.

  11. Extrahepatic biliary tract in chinchilla (Chinchilla laniger, Molina).

    PubMed

    Nowak, E; Kuchinka, J; Szczurkowski, A; Kuder, T

    2015-06-01

    The aim of the study was the macromorphological analysis of extrahepatic biliary tract in chinchilla (Chinchilla laniger Molina). Bile ducts, the gall bladder and portal vein were injected with coloured latex. Using the technique of dissection, bile ducts were isolated from the liver lobes. It was found that the cystic duct in this species is rarely single. Hepatic ducts form a system of multiple anastomosing structures running in the hepatoduodenal ligament. Many bile duct openings were observed in the duodenal papilla. The results confirm wide variations of the biliary tract in mammals and may be important for comparative analysis of the morphological differentiation of these structures in small mammals.

  12. Pancreatic Stenting Reduces Post-ERCP Pancreatitis and Biliary Sepsis in High-Risk Patients: A Randomized, Controlled Study

    PubMed Central

    Wu, Hai-En; Li, Qi-Xiang; Wang, Wei; Ou, Wei-Lin; Xia, Harry Hua-Xiang

    2016-01-01

    Background. Endoscopic retrograde cholangiopancreatography (ERCP) is an established treatment modality for bile duct disorders, but patients have a risk of post-ERCP pancreatitis (PEP) and biliary sepsis. Aim. To evaluate the effectiveness and safety of pancreatic stent for prophylaxis of PEP and biliary sepsis in high-risk patients with complicating common bile duct (CBD) disorders. Methods. Two hundred and six patients with complicating confirmed or suspected CBD disorders were randomly assigned to receive ERCP with pancreatic stenting (experimental group) or without stenting (control group). Primary outcome measure was frequency of PEP, and secondary outcome measures included operative time, blood loss, postoperative recovery times, and other ERCP-associated morbidities. Results. Baseline age, sex, CBD etiology, concomitant medical/surgical conditions, cannulation difficulty, and ERCP success were comparable between the two groups (all P > 0.05). Compared to the control group, the experimental group had a significantly lower frequency of PEP (7.7% versus 17.7%, P < 0.05) and positive bile microbial culture (40.4% versus 62.7%, P < 0.05). However, the two groups were similar in operative time, blood loss, postoperative recovery times, and other ERCP-associated morbidities (all P > 0.05). Conclusions. Pancreatic stenting can reduce the occurrence of PEP and biliary sepsis in high-risk patients with complicating CBD disorders but does not increase other ERCP-associated morbidities. This trial is registered with the Chinese Clinical Trial Registry (registration identifier ChiCTR-OCH-14005134). PMID:27057161

  13. The clinical phenotypes of autoimmune hepatitis: A comprehensive review.

    PubMed

    Wang, Qixia; Yang, Fan; Miao, Qi; Krawitt, Edward L; Gershwin, M Eric; Ma, Xiong

    2016-01-01

    Autoimmune hepatitis (AIH) fulfills the generally accepted contemporary criteria of an autoimmune liver disease: the presence of autoantibodies and autoreactive T cells, a female gender bias, association with other autoimmune diseases, response to immunosuppressive therapy and strong associations with the major histocompatibility complex HLA loci. It occurs worldwide in both children and adults and is marked by both etiopathogenic and clinical heterogeneity, differing from the other putative autoimmune liver diseases, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), albeit occasionally presenting with overlapping features of PBC or PSC. Although diagnostic criteria have been established and validated, there are still major issues to be clarified due to its variability, such as autoantibody-negative AIH, drug-induced AIH, AIH sharing features with PBC or PSC, and post-transplant de novo AIH. In view of the diverse presentations and courses, including classical chronic onset, acute and acute severe onset, cirrhosis and decompensated cirrhosis, individualized management of patients is indicated. Each patient should receive a personalized analysis of the benefits and side effect risks of drugs. Herein we describe a comprehensive review of the clinical phenotypes of AIH underscoring its clinical heterogeneity.

  14. Vascular complications in biliary atresia patients undergoing living donor liver transplantation: Analysis of 110 patients over 10 years

    PubMed Central

    Vasavada, Bhavin; Chen, Chao Long

    2015-01-01

    Introduction: Vascular complications are very common in pediatric living donor liver transplants. We present our experience in vascular complications in biliary atresia patients undergoing liver transplantation. Materials and Methods: All the patients who have undergone living donor liver transplant for biliary atresia from January 2003 to March 2013 were retrospectively analyzed. P value < 0.05 was considered to be statistically significant. Results: Total 110 patients have undergone living donor liver transplantation for biliary atresia between January 2003 and March 2013. There were 56 males and 54 females. Median age at transplant was 13.5 months. Eleven were primary transplants and 99 were post KASAI procedure. One hundred left lateral, four left lobe, and four right lobe grafts were used. Twenty-two patients developed vascular complications. Twelve patients developed hepatic artery thrombosis. Eleven patients of hepatic artery thrombosis were managed with redo hepatic artery anastomosis and one patient managed with radial artery interposition graft. Five patients developed portal vein stenosis and were managed by portal vein stenting. Five patients developed portal vein thrombosis and portal vein thrombectomy and re-anastomosis were done. One patient developed stenosis at the site of venous anastomosis and was managed by stenting. One patient developed both hepatic artery thrombosis and portal vein thrombosis and eventually succumbed to these complications. Out of five cases who died in this study, two had vascular complications. Graft/recipient weight ratio (GRWR) greater than 2.5 was significantly associated with vascular complications (P = 0.017). Conclusion: Vascular complications are frequently seen in liver transplantation for biliary atresia. Large for size grafts, weight less than 10 kg, age less than 1 year, and prolonged warm ischemia time is significantly associated with vascular complications. PMID:26166981

  15. Biliary Interventions: Tools and Techniques of the Trade, Access, Cholangiography, Biopsy, Cholangioscopy, Cholangioplasty, Stenting, Stone Extraction, and Brachytherapy.

    PubMed

    Ahmed, Osman; Mathevosian, Sipan; Arslan, Bulent

    2016-12-01

    Therapeutic access to the biliary system is generally limited to endoscopic or percutaneous approaches. A variety of percutaneous transhepatic biliary interventions are applicable for the diagnosis and treatment of biliary system pathologies, the majority of which may be performed in conjunction with one another. The backbone of nearly all of these interventions is percutaneous transhepatic cholangiography for opacification of the biliary tree, after which any number of therapeutic or diagnostic modalities may be pursued. We describe an overview of the instrumentation and technical approaches for several fundamental interventional procedures, including percutaneous transhepatic cholangiography and internal/external biliary drainage, endobiliary biopsy techniques, cholangioscopy, cholangioplasty and biliary stenting, biliary stone extraction, and intraluminal brachytherapy.

  16. Prevention of biliary leakage after partial liver resection using topical hemostatic agents.

    PubMed

    Erdogan, Deha; Busch, Olivier R C; Gouma, Dirk J; van Gulik, Thomas M

    2007-01-01

    Liver resection is widely accepted as the only potentially curative treatment in malignant or benign hepatobiliary lesions. Although not frequent, biliary leakage is a postoperative complication which may have considerable consequences. The field of topical hemostatic agents is rapidly developing, with various products currently available. This article reviews the risk factors associated with biliary leakage and the methods used for testing or prevention of biliary leakage. A literature search was performed using key words related to experimental and clinical studies dealing with biliary leakage. Experimental studies assessed the potential bilio-static effect of different topical hemostatic agents after bile duct reconstruction. Clinical series show biliary leakage rates up to 12%. There is no evidence that flushing of the bile duct system after resection reduces the incidence of biliary leakage. Further controlled studies are needed to clarify the preventive effect of topical hemostatic agents on biliary leakage after liver resection.

  17. A population based analysis of prognostic factors in advanced biliary tract cancer

    PubMed Central

    Renouf, Daniel; Lim, Howard

    2014-01-01

    Background Data regarding prognostic factors in advanced biliary tract cancer (BTC) remains scarce. The aim of this study was to review our institutional experience with cisplatin and gemcitabine in advanced BTC as well as to evaluate potential prognostic factors for overall survival (OS). Material and methods Consecutive patients with advanced BTC who initiated palliative chemotherapy with cisplatin and gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using the pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate and multivariate analyses. Results A total of 106 patients were included in the analysis. Median OS was 8.5 months (95% CI: 6.5-10.5). On univariate analysis, poor ECOG performance status (ECOG PS) at diagnosis, primary tumor location (extra-hepatic cholangiocarcinoma, and unknown biliary cancer), and sites of advanced disease (extra-hepatic metastasis) were significantly associated with worse OS (P<0.001, 0.036 and 0.034, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, and prior stent were not significantly associated with OS. On multivariate analysis, ECOG PS 2/3 was the only predictor of poor OS (P<0.001), while primary location (P=0.089) and sites of advanced disease (P=0.079) had a non-significant trend towards prognostic significance. Conclusions In this population based analysis, a poorer performance status was significantly prognostic of worse OS. Although not significant in our analysis, primary tumor location and sites of advanced disease may also have prognostic relevance. PMID:25436121

  18. Absorption of biliary cobalamin in baboons following total gastrectomy

    SciTech Connect

    Green, R.; Jacobsen, D.W.; Van Tonder, S.V.; Kew, M.C.; Metz, J.

    1982-11-01

    Absorption of radiolabeled cobalamin in baboons was assessed by whole body counting. Retention of biliary cobalamin and an aqueous solution of cyanocobalamin was measured in normal baboons and in baboons after total gastrectomy by using /sup 57/Co-labeled biliary cobalamin and /sup 58/C0-cyanocobalamin, with and without baboon gastric juice containing intrinsic factor. Radiolabeled biliary cobalamin was obtained by intravenous injection of /sup 57/Co-cyanocobalamin in baboons and collection of bile through a cannula placed in the common bile duct. Cobalamin absorption was not completely abolished by gastrectomy and biliary cobalamin was better retained than cyanocobalamin; intrinsic factor enhanced absorption of both forms. After gastrectomy there was steady depletion of liver and serum cobalamin levels, which ceased after a new equilibrium was reached between a progressively diminishing cobalamin loss and the impaired but significant residual level of absorption. These studies in the nonhuman primate provide further information concerning the enterohepatic circulation of cobalamin and suggest that the form of cobalamin in bile may be more readily absorbed than is cyanocobalamin or that bile itself may have an enhancing effect on cobalamin absorption. The data also suggest that physiologically significant amounts of cobalamin may be absorbed in the absence of a gastric source of intrinsic factor.

  19. Laparoscopic surgery for biliary atresia and choledochal cyst.

    PubMed

    Yamataka, Atsuyuki; Lane, Geoffrey J; Cazares, Joel

    2012-08-01

    Minimally invasive surgery in children has evolved to the extent that complex procedures can be performed with safety and outcome comparable with open surgery, with the advantage of minimal scarring. Here we describe the latest laparoscopic techniques used by us at the Juntendo University Hospital, Japan, for treating biliary atresia and choledochal malformation, with presentation of our postoperative management and discussion of preliminary outcomes.

  20. STUDY OF THE EFFECTS OF LYOPHILIZATION ON BILIARY CATATONIA

    DTIC Science & Technology

    pathogenic action of biles in animals. Certain biles producing catatonia before lyophilization lose this property after lyophilization. The same is true...optical density of toxic biles; this optical density also goes down after lyophilization. These results favor the hypothesis that considers the biliary catatonia producing agent as a particularly fragile product.

  1. Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone Formation

    PubMed Central

    Lin, Jing; Shao, Wei-qing; Chen, Zong-you; Zhu, Wen-wei; Lu, Lu; Cai, Duan; Qin, Lun-xiu; Jia, Hu-liang; Lu, Ming; Chen, Jin-hong

    2016-01-01

    The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments. PMID:27484115

  2. Huge biloma after endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy

    PubMed Central

    Alkhateeb, Harith M.; Aljanabi, Thaer J.; Al-azzawi, Khairallh H.; Alkarboly, Taha A.

    2015-01-01

    Background Biliary leak can occur as a complication of biliary surgery, endoscopic retrograde cholangiopancreatography manipulations and endoscopic biliary sphincterotomy. Consequently, bile may collect in the abdominal cavity, a condition called biloma. Rarely, it may reach a massive size. Case presentation A 72-year-old man presented with gastric upset with gradual abdominal distension reaching a large size due to intra-abdominal bile collection (biloma) after endoscopic retrograde cholangiopancreatography plus endoscopic biliary sphincterotomy and stenting for post laparoscopic cholecystectomy common bile duct stricture. This huge biloma was treated by percutaneous insertion of a tube drain for a few days, evacuating the collection successfully without recurrence. Discussion This patient might sustain injury to the common bile duct either by the guide wire or stent, or the injury occurred at the angle between the common bile duct and duodenum during sphincterotomy of the ampulla. Although any of these rents may lead to a bile leak, causing a huge biloma, they could be successfully treated by percutaneous drainage. Conclusions (1) Following endoscopic retrograde cholangiopancreatography, a patient’s complaints should not be ignored. (2) A massive biloma can occur due to such procedures. (3) Conservative treatment with minimal invasive technique can prove to be effective. PMID:26402876

  3. Identification of a plant isoflavonoid that causes biliary atresia

    PubMed Central

    Lorent, Kristin; Gong, Weilong; Koo, Kyung A.; Waisbourd-Zinman, Orith; Karjoo, Sara; Zhao, Xiao; Sealy, Ian; Kettleborough, Ross N.; Stemple, Derek L.; Windsor, Peter A.; Whittaker, Stephen J.; Porter, John R.; Wells, Rebecca G.; Pack, Michael

    2016-01-01

    Biliary atresia (BA) is a rapidly progressive and destructive fibrotic disorder of unknown etiology affecting the extrahepatic biliary tree of neonates. Epidemiological studies suggest that an environmental factor, such as a virus or toxin, is the cause of the disease, although none have been definitively established. Several naturally occurring outbreaks of BA in Australian livestock have been associated with the ingestion of unusual plants by pregnant animals during drought conditions. We used a biliary secretion assay in zebrafish to isolate a previously undescribed isoflavonoid, biliatresone, from Dysphania species implicated in a recent BA outbreak. This compound caused selective destruction of the extrahepatic, but not intrahepatic, biliary system of larval zebrafish. A mutation that enhanced biliatresone toxicity mapped to a region of the zebrafish genome that has conserved synteny with an established human BA susceptibility locus. The toxin also caused loss of cilia in neonatal mouse extrahepatic cholangiocytes in culture and disrupted cell polarity and monolayer integrity in cholangiocyte spheroids. Together, these findings provide direct evidence that BA could be initiated by perinatal exposure to an environmental toxin. PMID:25947162

  4. Management of patients after recovering from acute severe biliary pancreatitis

    PubMed Central

    Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

    2016-01-01

    Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature. PMID:27678352

  5. Role of lipid peroxidation in biliary obstruction in the rat.

    PubMed

    Muriel, P; Suarez, O R

    1994-01-01

    There is poor evidence about the participation of lipoperoxidative processes in liver damage induced by biliary obstruction, thus the aim of this work was to study the role of lipid peroxidation in this model of liver injury. Biliary obstruction was induced in male Wistar rats by ligation of the common bile duct; control animals were sham operated. Rats were sacrificed at different times after surgery. Liver sections were used for glycogen and lipoperoxidation quantification. Markers of liver damage were determined in serum. All serum markers of liver damage increased after 1 day of biliary obstruction. Liver glycogen content decreased 1 day after surgery. On the other hand, lipoperoxidation increased later than markers of liver damage, suggesting that it is a consequence rather than the cause of liver injury. Moreover, administration of colchiceine (a good free-radical scavenger) or vitamin E prevented lipoperoxidation but not liver damage, confirming that lipoperoxidation does not play an important role in liver damage induced by biliary obstruction. This model of liver injury seems to be useful for testing hepatoprotective drugs that do not act as free-radical scavengers.

  6. Regional Differences in Hospitalizations and Cholecystectomies for Biliary Dyskinesia

    PubMed Central

    2013-01-01

    Background/Aims Published studies suggest that socioeconomic factors contribute to increasing cholecystectomy rates for biliary dyskinesia (BD). The aim of this study was to identify factors driving admissions and operations for BD by examining regional variability in hospitalizations and cholecystectomies for this disorder. Methods Annual hospitalizations and cholecystectomy rates for biliary diseases were assessed using the State Inpatient Databases of the Agency for Healthcare Research and Quality based on diagnosis codes for biliary dyskinesia, cholecystolithiasis and cholecystitis. Results Annual admissions for BD varied nearly sevenfold among different states within the United States. Hospitalizations for gallstone disease and its complication showed less variability, differing 2-fold between states. Nearly 70% of admissions for BD and about 85% of admissions for gallstone disease resulted in cholecystectomies. Higher admission rates for BD were best predicted by high overall hospitalization rates, admission rate for gallstone disease and the physician workforce within a state. Cholecystectomy rates for BD were higher in states with low population density and high rates of cholecystectomy for gallstone disease. Conclusions These data suggest that established medical practice patterns significantly contribute to the variability in admissions and operations for biliary dyskinesia. The findings also indicate that lower thresholds for operative interventions are an important determinant in the approach to this disorder. Considering the benign course of functional illnesses, the bar for surgical interventions should be raised rather than lowered; in addition active conservative treatment options should be developed for these patients. PMID:23875106

  7. Endoscopic management of combined malignant biliary and gastric outlet obstruction.

    PubMed

    Nakai, Yousuke; Hamada, Tsuyoshi; Isayama, Hiroyuki; Itoi, Takao; Koike, Kazuhiko

    2017-01-01

    Patients with periampullary cancer or gastric cancer often develop malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO), and combined MBO and GOO is not rare in these patients. Combined MBO and GOO is classified by its location and sequence, and treatment strategy can be affected by this classification. Historically, palliative surgery, hepaticojejunostomy and gastrojejunostomy were carried out, but the current standard treatment is combined transpapillary stent and duodenal stent placement. Although a high technical success rate is reported, the procedure can be technically difficult and duodenobiliary reflux with subsequent cholangitis is common after double stenting. Recent development of endoscopic ultrasound (EUS)-guided procedures enables the management of MBO as well as GOO under EUS guidance. EUS-guided biliary drainage is now increasingly reported as an alternative to percutaneous transhepatic biliary drainage in failed endoscopic retrograde cholangiopancreatography (ERCP), and GOO is one of the major reasons for failed ERCP. In addition to EUS-guided biliary drainage, the feasibility of EUS-guided double-balloon-occluded gastrojejunostomy bypass for MBO was recently reported, and EUS-guided double stenting can potentially become the treatment of choice in the future. However, as each procedure has its advantages and disadvantages, treatment strategy should be selected based on the type of obstruction and the prognosis and performance status of the patient.

  8. Per oral cholangiopancreatoscopy in pancreatico biliary diseases - Expert consensus statements

    PubMed Central

    Ramchandani, Mohan; Reddy, Duvvur Nageshwar; Lakhtakia, Sundeep; Tandan, Manu; Maydeo, Amit; Chandrashekhar, Thoguluva Seshadri; Kumar, Ajay; Sud, Randhir; Rerknimitr, Rungsun; Makmun, Dadang; Khor, Christopher

    2015-01-01

    AIM: To provide consensus statements on the use of per-oral cholangiopancreatoscopy (POCPS). METHODS: A workgroup of experts in endoscopic retrograde cholangiopancreatography (ERCP), endosonography, and POCPS generated consensus statements summarizing the utility of POCPS in pancreaticobiliary disease. Recommendation grades used validated evidence ratings of publications from an extensive literature review. RESULTS: Six consensus statements were generated: (1) POCPS is now an important additional tool during ERCP; (2) in patients with indeterminate biliary strictures, POCS and POCS-guided targeted biopsy are useful for establishing a definitive diagnosis; (3) POCS and POCS-guided lithotripsy are recommended for treatment of difficult common bile duct stones when standard techniques fail; (4) in patients with main duct intraductal papillary mucinous neoplasms (IPMN) POPS may be used to assess extent of tumor to assist surgical resection; (5) in difficult pancreatic ductal stones, POPS-guided lithotripsy may be useful in fragmentation and extraction of stones; and (6) additional indications for POCPS include selective guidewire placement, unexplained hemobilia, assessing intraductal biliary ablation therapy, and extracting migrated stents. CONCLUSION: POCPS is important in association with ERCP, particularly for diagnosis of indeterminate biliary strictures and for intra-ductal lithotripsy when other techniques failed, and may be useful for pre-operative assessment of extent of main duct IPMN, for extraction of difficult pancreatic stones, and for unusual indications involving selective guidewire placement, assessing unexplained hemobilia or intraductal biliary ablation therapy, and extracting migrated stents. PMID:25914484

  9. Histological complete response in a patient with advanced biliary tract cancer treated by gemcitabine/cisplatin/S-1 combination chemotherapy: A case report

    PubMed Central

    Matsubara, Tokuhiro; Nishida, Tsutomu; Tomimaru, Yoshito; Yamamoto, Masashi; Hayashi, Shiro; Nakajima, Sachiko; Fukui, Koji; Dono, Keizo; Adachi, Shiro; Ioka, Tatsuya; Kanai, Masashi; Inada, Masami

    2016-01-01

    A 68-year-old woman was referred to our hospital with increased levels of biliary enzymes. On imaging, the patient was diagnosed with unresectable intrahepatic biliary tract cancer (BTC) with invasion of the portal vein and para-aortic lymph node metastasis (cT3N1M1, cStage IVb) and underwent endoscopic biliary drainage for the biliary stricture prior to therapy. The patient was subsequently enrolled in a phase III randomized trial (UMIN000014371/NCT02182778) and randomly assigned to receive gemcitabine/cisplatin/S-1 (GCS) combination therapy intravenously at doses of 1,000 or 25 mg/m2 on day 1 and orally twice daily at a dose of 80 mg/m2 on days 1–7 every 2 weeks. After 12 cycles of scheduled therapy without uncontrollable adverse effects, the patient achieved a good partial response with chemotherapy. Computed tomography (CT) revealed a marked reduction of the primary and metastatic lesions. In addition,18F-fluorodeoxyglucose-positron emission tomography/CT revealed diminishing abnormal uptake and no macroscopic evidence of factors adversely affecting tumor resectability. Therefore, the patient underwent extended right hepatic lobectomy, lymph node dissection and left hepaticojejunostomy. Finally, histological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. We herein present the case of a patient with intrahepatic BTC who achieved a pathologically complete response following combination chemotherapy with GCS. PMID:28101354

  10. Enzyme pattern of biliary colic: A counterintuitive picture

    PubMed Central

    Resnick, Elad; Shteingart, Shimon; Melamud, Bernardo; Bdolah-Abram, Tali; Zalut, Todd; Reuben, Adrian; Lurie, Yoav

    2016-01-01

    AIM To evaluate the diagnostic value of serial biochemical blood tests in the diagnosis of biliary colic. METHODS Files were reviewed of 1039 patients who were admitted to the Share’e Zedek Medical Center emergency department between the years 2012-2013, and received the coding of acute biliary disease. Of these, the first 100 cases were selected that met the following criteria: (1) a diagnosis of biliary colic or symptomatic cholelithiasis; (2) at least two biochemical blood tests performed; and (3) 18 years of age or older. Patients with other acute biliary diseases were excluded. The biochemical profile of the patients was analyzed as were their clinical and radiological findings. RESULTS Three-quarters of the patients were women, whose average age of 37 years was younger than the average of the men, at 50 years. According to their histories, 47% of the patients had previously known cholelithiasis. Pain in either the right upper quadrant or the epigastrium was the presenting symptom in 93% cases. The greatest change in serum biochemical results was seen during the first day of the patients’ admissions. Alanine aminotransferase (ALT) showed the highest initial rise above the reference range, followed by aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin and alkaline phosphatase (ALKP) - all these increases were statistically significant (P < 0.05). AST showed the sharpest decline followed by bilirubin and ALT. GGT and ALKP did not fall. A sharp rise and fall in liver enzymes, especially during the first day, most prominently in AST and ALT, was seen in 70% percent of cases. In 65% of cases trans-abdominal sonography did not give diagnostic findings. CONCLUSION Serial serum liver enzyme measurements are helpful in the initial diagnosis of acute biliary colic. PMID:28083086

  11. Interval Biliary Stent Placement Via Percutaneous Ultrasound Guided Cholecystostomy: Another Approach to Palliative Treatment in Malignant Biliary Tract Obstruction

    SciTech Connect

    Harding, James Mortimer, Alex; Kelly, Michael; Loveday, Eric

    2010-12-15

    Percutaneous cholecystostomy is a minimally invasive procedure for providing gallbladder decompression, often in critically ill patients. It can be used in malignant biliary obstruction following failed endoscopic retrograde cholangiopancreatography when the intrahepatic ducts are not dilated or when stent insertion is not possible via the bile ducts. In properly selected patients, percutaneous cholecystostomy in obstructive jaundice is a simple, safe, and rapid option for biliary decompression, thus avoiding the morbidity and mortality involved with percutaneous transhepatic biliary stenting. Subsequent use of a percutaneous cholecystostomy for definitive biliary stent placement is an attractive concept and leaves patients with no external drain. To the best of our knowledge, it has only been described on three previous occasions in the published literature, on each occasion forced by surgical or technical considerations. Traditionally, anatomic/technical considerations and the risk of bile leak have precluded such an approach, but improvements in catheter design and manufacture may now make it more feasible. We report a case of successful interval metal stent placement via percutaneous cholecystostomy which was preplanned and achieved excellent palliation for the patient. The pros and cons of the procedure and approach are discussed.

  12. Health Related Quality of Life in Patients with Biliary Atresia Surviving with their Native Liver

    PubMed Central

    Sundaram, Shikha S.; Alonso, Estella M.; Haber, Barbara; Magee, John C.; Fredericks, Emily; Kamath, Binita; Kerkar, Nanda; Rosenthal, Philip; Shepherd, Ross; Limbers, Christine; Varni, James W.; Robuck, Patricia; Sokol, Ronald J.; Liver, Childhood

    2014-01-01

    Objectives To quantify health related quality of life (HRQOL) of patients with biliary atresia with their native livers and compare them with healthy children and patients with biliary atresia post-liver transplant (LT) and to examine the relationship between HRQOL and medical variables. Study design A cross-sectional HRQOL study of patients with biliary atresia with their native livers (ages 2-25 years) was conducted and compared with healthy and post-LT biliary atresia samples using PedsQL™ 4.0 child self and parent proxy reports, a validated measure of physical/psychosocial functioning. Results 221 patients with biliary atresia with native livers (54% female, 67% white) were studied. patient self and parent proxy reports showed significantly poorer HRQOL than healthy children across all domains (p < 0.001), particularly in emotional and psychosocial functioning. Child self and parent proxy HRQOL scores from patients with biliary atresia with their native livers and post-LT biliary atresia were similar across all domains (p=NS). Child self and parent proxy reports showed moderate agreement across all scales, except social functioning (poor to fair agreement). On multivariate regression analysis, black race and elevated total bilirubin were associated with lower Total and Psychosocial HRQOL summary scores. Conclusions HRQOL in patients with biliary atresia with their native livers is significantly poorer than healthy and similar to post-LT biliary atresia children. These findings identify significant opportunities to optimize the overall health of patients with biliary atresia. PMID:23746866

  13. Retrospective analysis of canine gallbladder contents in biliary sludge and gallbladder mucoceles

    PubMed Central

    MIZUTANI, Shinya; TORISU, Shidow; KANEKO, Yasuyuki; YAMAMOTO, Shushi; FUJIMOTO, Shinsuke; ONG, Benedict Huai Ern; NAGANOBU, Kiyokazu

    2016-01-01

    The pathophysiology of canine gallbladder diseases, including biliary sludge, gallbladder mucoceles and gallstones, is poorly understood. This study aimed to evaluate the component of gallbladder contents and bacterial infection of the gallbladder in order to elucidate the pathophysiology of biliary sludge and gallbladder mucoceles. A total of 43 samples of canine gallbladder contents (biliary sludge, 21 and gallbladder mucoceles, 22) were subjected to component analysis by infrared spectroscopy, and the resultant infrared spectra were compared with that of swine mucin. Of the 43 samples, 41 were also evaluated by aerobic and anaerobic bacterial culture. The contents of 20 (95.2%) biliary sludge and 22 (100%) gallbladder mucocele samples exhibited similar infrared spectra as swine mucin. Although biliary sludge and gallbladder mucocele contents exhibited similar infrared spectra, one sample of biliary sludge (4.8%) was determined to be composed of proteins. The rate of bacterial infection of the gallbladder was 10.0% for biliary sludge and 14.3% for gallbladder mucoceles. Almost all of the identified bacterial species were intestinal flora. These results indicate that the principal components of gallbladder contents in both gallbladder mucoceles and biliary sludge are mucins and that both pathophysiologies exhibit low rates of bacterial infection of the gallbladder. Therefore, it is possible that gallbladder mucoceles and biliary sludge have the same pathophysiology, and, rather than being independent diseases, they could possibly represent a continuous disease. Thus, biliary sludge could be considered as the stage preceding the appearance of gallbladder mucoceles. PMID:27990011

  14. Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia

    PubMed Central

    Bezerra, Jorge A.; Spino, Cathie; Magee, John C.; Shneider, Benjamin L.; Rosenthal, Philip; Wang, Kasper S.; Erlichman, Jessi; Haber, Barbara; Hertel, Paula M.; Karpen, Saul J.; Kerkar, Nanda; Loomes, Kathleen M.; Molleston, Jean P.; Murray, Karen F.; Romero, Rene; Schwarz, Kathleen B.; Shepherd, Ross; Suchy, Frederick J.; Turmelle, Yumirle P.; Whitington, Peter F.; Moore, Jeffrey; Sherker, Averell H.; Robuck, Patricia R.; Sokol, Ronald J.

    2015-01-01

    IMPORTANCE Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome. OBJECTIVE To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver. DESIGN, SETTING, AND PATIENTS The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013. INTERVENTIONS Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy. MAIN OUTCOMES AND MEASURES The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events. RESULTS The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P = .43). The adjusted absolute risk difference was 8.7% (95% CI, −10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group (P > .99); however

  15. Prospective study of outcomes after percutaneous biliary drainage for malignant biliary obstruction

    PubMed Central

    Robson, P. C.; Heffernan, N.; Gonen, M.; Thornton, R.; Brody, L. A.; Holmes, R.; Brown, K. T.; Covey, A. M.; Fleischer, D.; Getrajdman, G. I.; Jarnagin, W.; Sofocleous, C.; Blumgart, L.; D’Angelica, M.

    2015-01-01

    Purpose Percutaneous biliary drainage (PBD) is used to relieve malignant bile duct obstruction (MBO) when endoscopic drainage is not feasible. Little is known about the effects of PBD on the quality of life (QoL) in patients with MBO. The aim of this study was to evaluate changes in QoL and pruritus after PBD and to explore the variables that impact these changes. Patients and Methods Eligible patients reported their QoL and pruritus before and after PBD using the Functional Assessment of Cancer Therapy – Hepatobiliary instrument (FACT-HS) and the Visual Analog Scale for Pruritus (VASP). Instruments were completed pre-procedure and at one and four weeks following PBD. Results One hundred and nine (60 male/49 female) patients enrolled, 102 (94%) had unresectable disease. PBD was technically successful (hepatic ducts cannulated at the conclusion of procedure) in all patients. There were two procedure-related deaths. All-cause mortality was 10% (N=11) at 4 weeks and 28% (N=31) at 8 weeks post PBD with a median survival of 4.74 months. The mean FACT-HS scores declined significantly (P<.01) over time (101.3, 94.8, 94.7 at baseline, 1 week, 4 weeks, respectively). The VASP scores showed significant improvement at 1 week with continued improvement at 4 weeks (P<.01). Conclusion PBD improves pruritus but not QoL in patients with MBO and advanced malignancy. There is high early mortality in this population. PMID:20358300

  16. Development of a Swine Benign Biliary Stricture Model Using Endoscopic Biliary Radiofrequency Ablation

    PubMed Central

    2016-01-01

    The large animal model with benign biliary stricture (BBS) is essential to undergo experiment on developing new devices and endoscopic treatment. This study conducted to establish a clinically relevant porcine BBS model by means of endobiliary radiofrequency ablation (RFA). Endoscopic retrograde cholangiography (ERC) was performed on 12 swine. The animals were allocated to three groups (60, 80, and 100 W) according to the electrical power level of RFA electrode. Endobiliary RFA was applied to the common bile duct for 60 seconds using an RFA catheter that was endoscopically inserted. ERC was repeated two and four weeks, respectively, after the RFA to identify BBS. After the strictures were identified, histologic evaluations were performed. On the follow-up ERC two weeks after the procedure, a segmental bile duct stricture was observed in all animals. On microscopic examination, severe periductal fibrosis and luminal obliteration with transmural inflammation were demonstrated. Bile duct perforations occurred in two pigs (100 W, n = 1; 80 W, n = 1) but there were no major complications in the 60 W group. The application of endobiliary RFA with 60 W electrical power resulted in a safe and reproducible swine model of BBS. PMID:27510388

  17. Percutaneous Embolization of Transhepatic Tracks for Biliary Intervention

    SciTech Connect

    Lyon, Stuart M.; Terhaar, Olaf; Given, Mark F.; O'Dwyer, Helena M.; McGrath, Frank P.; Lee, Michael J.

    2006-12-15

    Significant pain can occur after removing transhepatic catheters from biliary access tracks, after percutaneous biliary drainage (PBD) or stenting. We undertook a randomized prospective study to ascertain whether track embolization decreases the amount of pain or analgesic requirement after PBD. Fifty consecutive patients (M:F, 22:28; age range:29-85 years; mean age: 66.3 years) undergoing PBD were randomized to receive track embolization or no track embolization after removal of biliary drainage catheters. A combination of Lipoidol and n-butyl cyanoacrylate were used to embolize transhepatic tracks using an 8F dilator. The patients who did not have track embolization performed had biliary drainage catheters removed over a guide wire. A visual analog scoring (VAS) system was used to grade pain associated with catheter removal, 24 h afterward. A required analgesic score (RAS) was devised to tabulate the analgesia required. No analgesia had a score of 0, oral or rectal nonopiate analgesics had a score of 1, oral opiates had a score of 2, and parenteral opiates had a score of 3. The average VAS and RAS for both groups were calculated and compared.Seven patients were excluded for various reasons, leaving 43 patients in the study group. Twenty-one patients comprised the embolization group and 22 patients comprised the nonembolization group. The mean biliary catheter dwell time was not significantly different (p > 0.05) between the embolization group and nonembolization (mean: 5.4 days vs 6.9 days, respectively). In the nonembolization group, the mean VAS was 3.4. Eight patients required parenteral opiates, three patients required oral opiates, and five patients required oral or rectal analgesics, yielding a mean RAS of 1.6. In the embolization group, the mean VAS was 0.9. No patient required parenteral opiates, six patients required oral opiates, and two patients had oral analgesia. The average RAS was 0.6. Both the VAS and the RAS were significantly lower in the

  18. Phase II study of gemcitabine, oxaliplatin in combination with panitumumab in KRAS wild-type unresectable or metastatic biliary tract and gallbladder cancer

    PubMed Central

    Hezel, A F; Noel, M S; Allen, J N; Abrams, T A; Yurgelun, M; Faris, J E; Goyal, L; Clark, J W; Blaszkowsky, L S; Murphy, J E; Zheng, H; Khorana, A A; Connolly, G C; Hyrien, O; Baran, A; Herr, M; Ng, K; Sheehan, S; Harris, D J; Regan, E; Borger, D R; Iafrate, A J; Fuchs, C; Ryan, D P; Zhu, A X

    2014-01-01

    Background: Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer. Methods: Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0–2 were treated with panitumumab 6 mg kg−1, GEM 1000 mg m−2 (10 mg m−2 min−1) and OX 85 mg m−2 on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival. Results: Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5–24 months) and median overall survival 20.3 months (95% CI 9–25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%. Conclusions: The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer. PMID:24960403

  19. Intrahepatic Biliary Intraductal Oncocytic Papillary Neoplasm/Carcinoma: First Reported Case in Australia and Literature Review.

    PubMed

    Chu, Christopher; Felbel, William; Chu, Francis

    2007-01-01

    Biliary (hepatic and extrahepatic) intraductal papillary mucinous neoplasms and intraductal oncocytic papillary neoplasms/carcinoma are rare neoplasms. Classification of biliary intraductal papillary tumors can be confusing and reports in radiology literature are extremely limited. We describe the first reported case of biliary intraductal oncocytic papillary neoplasms/carcinoma in the liver in Australia. The intraductal nature of such neoplasms can be identified on magnetic resonance imaging and magnetic resonance cholangiopancreatography.

  20. [Biliary ileus: diagnostic and therapeutic aspects. Report of a case].

    PubMed

    Narjis, Y; Chelala, E; Dessily, M; Allé, J-L

    2010-01-01

    We report a rare case of small bowel gallstone obstruction in a patient with cholecystointestinal fistula. Diagnosis of this condition is usually difficult and only achieved at surgery. We review the radiological findings, particularly the CT findings, helpful for diagnosis: ectopic gallstone, biliary gas and fistula. Early preoperative diagnosis could reduce morbidity and mortality. Treatment is surgical with enterolithotomy. There is some controversy over the need to repair the fistula.

  1. Presence of antibodies against self human leukocyte antigen class II molecules in autoimmune hepatitis.

    PubMed

    Yamagiwa, Satoshi; Kamimura, Hiroteru; Takamura, Masaaki; Genda, Takuya; Ichida, Takafumi; Nomoto, Minoru; Aoyagi, Yutaka

    2014-01-01

    Autoimmune hepatitis (AIH) can arise de novo after liver transplantation (LT) for non-autoimmune liver diseases. Considering the identical features of de novo AIH after LT and classical AIH, as well as the importance of anti-human leukocyte antigen (HLA) antibodies in graft rejection, we investigated the presence of circulating anti-HLA class II antibodies in the sera of 35 patients with AIH, 30 patients with primary biliary cirrhosis (PBC), and 30 healthy donors using fluorescent dye-impregnated beads bound to HLA molecules. We then investigated the allele specificity of the antibodies and identified the HLA alleles in each patient using DNA-based HLA typing. We also examined HLA class II expression in liver samples using immunohistochemistry. Anti-HLA class II antibodies were detected significantly more frequently in the patients with AIH (88.1%) than in the patients with PBC (33.3%) or in the healthy donors (13.3%) (both P <0.01). We confirmed that the anti-HLA class II antibodies in the AIH patients showed specificity for several HLA class II alleles, including self HLA class II alleles. Moreover, positive reactivity with anti-self HLA class II antibodies was associated with higher serum transaminase levels. In conclusion, we demonstrated, for the first time, that antibodies against self HLA class II alleles were detectable in patients with AIH. Our results suggest that an antibody-mediated immune response against HLA class II molecules on hepatocytes may be involved in the pathogenesis or acceleration of liver injury in AIH.

  2. Current status of peroral cholangioscopy in biliary tract diseases

    PubMed Central

    Ghersi, Stefania; Fuccio, Lorenzo; Bassi, Marco; Fabbri, Carlo; Cennamo, Vincenzo

    2015-01-01

    Peroral cholangioscopy (POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be performed using a dedicated cholangioscope that is advanced through the accessory channel of a duodenoscope or via the insertion of a small-diameter endoscope directly into the bile duct. POC was first described in the 1970s, but the use of earlier generation devices was substantially limited by the cumbersome equipment setup and high repair costs. For nearly ten years, several technical improvements, including the single-operator system, high-quality images, the development of dedicated accessories and the increased size of the working channel, have led to increased diagnostic accuracy, thus assisting in the differentiation of benign and malignant intraductal lesions, targeting biopsies and the precise delineation of intraductal tumor spread before surgery. Furthermore, lithotripsy of difficult bile duct stones, ablative therapies for biliary malignancies and direct biliary drainage can be performed under POC control. Recent developments of new types of conventional POCs allow feasible, safe and effective procedures at reasonable costs. In the current review, we provide an updated overview of POC, focusing our attention on the main current clinical applications and on areas for future research. PMID:25992189

  3. Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

    SciTech Connect

    Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae Lee, Woo Jin; Woo, Sang Myung; Moon, Sung Ho; Yoo, Tae; Kim, Sang Soo; Kim, Seong Hoon; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-12-01

    Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. Methods and Materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p = .007; 32.1% vs. 26.1%, p = .041; 36.5% vs. 28.2%, p = .049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p < .05). Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.

  4. Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

    PubMed Central

    Asai, Akihiro; Miethke, Alexander; Bezerra, Jorge A.

    2016-01-01

    Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease. PMID:26008129

  5. Scintiscanning in the evaluation of biliary enteric anastomoses

    SciTech Connect

    Tidmore, H.; Ram, M.D.

    1985-03-01

    The evaluation of symptomatic patients who have undergone biliary enteric anastomoses, particularly when the diversion was into the jejunum, is difficult. Conventional techniques for evaluation, such as oral cholecystography (OCG), intravenous cholangiography (IVC), ultrasonography (US), computer-assisted tomography scanning (CT scanning), or endoscopy are not adequate to provide definitive information on the patency of the anastomoses. Hepatobiliary scintiscanning using /sup 99m/Tc-HIDA and BIDA (iminodiacetic acid derivatives) was performed on 12 patients. The patients were from 11 to 72 years of age and included ten men and two women. The scan results were correlated with US, CT scan, percutaneous transhepatic cholangiography (PTC), operative findings, and final diagnosis. Scanning was highly accurate in this group and could be performed successfully even in jaundiced patients (total serum bilirubin level up to 20.0 mg/dl). In patients in whom dilated bile ducts were demonstrated (by US, CT scan, or scintiscan), only the scintiscan revealed the true patency of the anastomoses. The advantages of the technique are that it is simple and noninvasive. Delayed transit of bile (scanning agent) to bowel is a very reliable indication of partial or complete obstruction. Scintiscanning is the only technique that demonstrated the functional state of biliary secretion and excretion into bowel in patients with previous biliary enteric anastomoses.

  6. Species differences in biliary excretion of benzo(a)pyrene

    SciTech Connect

    Weyand, E.H.; Bevan, D.R.

    1986-05-01

    Biliary excretion of benzo(a)pyrene (B(a)P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. (/sup 3/H)-B(a)P, in amounts of approximately 150 ng or 350 ..mu..g, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of (/sup 3/H)-B(a)P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B(a)P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B(a)P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B(a)P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose.

  7. Biliary excretion in dogs: evidence for a molecular weight threshold.

    PubMed

    Yang, Xinning; Gandhi, Yash A; Morris, Marilyn E

    2010-04-16

    Molecular weight (MW) is known as an important factor of biliary excretion in rats, guinea pigs, rabbits and humans. The objective of this study was to evaluate the relationship between the biliary excretion and MW of drugs in dogs. Data on the percentage of dose excreted into bile as parent drug (PD(b)) in dogs were collected from the literature for 134 compounds. Receiver operating characteristic (ROC) curve analysis was utilized to determine whether a MW threshold exists for PD(b). A MW threshold of 375-400 Da was established for anions in dogs, which is similar with the cutoff value observed in rats (400 Da) but lower than the one in humans (475 Da). No MW threshold was found for cations or cations/neutral compounds. A molecular volume threshold of 300A(3) was also determined for anions in dogs, which corresponds to a MW of 394 Da. In conclusion, our analysis suggested the presence of a MW cutoff for anions in dogs, which may be related with the molecular size of a compound. This represents the first report of the influence of MW or molecular volume as a determinant of biliary excretion for a structurally diverse set of compounds in dogs.

  8. Intraluminal radiation therapy in the management of malignant biliary obstruction

    SciTech Connect

    Molt, P.; Hopfan, S.; Watson, R.C.; Botet, J.F.; Brennan, M.F.

    1986-02-01

    Fifteen patients with malignant biliary obstruction from carcinoma of the bile ducts, gallbladder, and pancreas (Group I) or metastatic disease (Group II) were treated with intraluminal radiation therapy (ILRT) at Memorial Sloan-Kettering Cancer Center. In 11 cases ILRT was used as a central boost in combination with 3000 cGy external beam radiation therapy (ERT). No significant treatment toxicity was observed. Cholangiographic response was observed in 2 of 12 evaluable patients. In no patient was long-term relief of jaundice without indwelling biliary stent achieved. Survival from treatment in eight Group I patients treated with ILRT +/- ERT was 3 to 13 months (median, 4.5). Survival in seven similarly treated Group II patients was 0.5 to 8 months (median, 4.0). Additional data for ten similar patients referred for ILRT but treated with ERT alone are presented. Analysis of this and other reports indicate the need for prospective controlled trials of the role of this regimen in the management of malignant biliary obstruction before wider application can be recommended.

  9. Photodynamic therapy for pancreatic and biliary tract carcinoma

    NASA Astrophysics Data System (ADS)

    Pereira, Stephen P.

    2009-02-01

    Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.

  10. [Biliary ileus--a rare complication of cholecystolithiasis].

    PubMed

    Lakyová, L; Radonak, J; Vajó, J; Toncr, I; Kudlác, M

    2007-10-01

    The diagnosis of ileus caused by biliary stones occurs very rarely, with the range of 2 % worldwide. This complication of cholecystolithiasis caused by the stone fistulation into gastrointestinal tract and its subsequent obstruction occurs mostly in elderly and has a high mortality rate. During the course of ten years (1996-2006) in the 2nd surgical clinic FNLP in Kosice, 1640 cholecystectomies and 255 operations, due to the obstruction ileus, were performed. Biliary ileus was recorded in four cases. In two cases, the reason being an obstruction caused by a travelled stone into jejunum, one event was caused by a mechanic wedge of a stone in duodenum and in the last event rectosigma was obturated. The diagnostic is relatively difficult because of a nonspecific symptomatology and often negative anamnesis of previous problems with gallstones. According to literature, the most reliable diagnostic method is computer tomography (CT). In our case, abdominal ultrasonography was successful, which pointed out this diagnosis. Gastroscopy localized the place of obstruction, but not its cause and X-ray image showed aerobilia two times. By the use of magnetic resonance cholangiopancreatography (MRCP) the diagnosis was not positively confirmed. Only in one out of four cases, there was a suspicion of the diagnosis of the biliary ileus, which makes its detectability 25%. The aim of this retrospective analysis is the comparison of diagnostic method-options and their range of success in the diagnosis of acute abdomen in our clinic and the entries in the world literature.

  11. Von Hippel-Lindau disease involving pancreas and biliary system

    PubMed Central

    Zhi, Xu-Ting; Bo, Qi-Yu; Zhao, Feng; Sun, Dong; Li, Tao

    2017-01-01

    Abstract Rationale: Von Hippel-Lindau (VHL) disease is a rare inherited, autosomal-dominant syndrome caused by heterozygous germline mutations in the VHL gene. VHL patients are prone to develop benign and malignant tumors and cysts in multiple organ systems involving kidneys, pancreas and central nervous system (CNS). The varied and complex clinical manifestations and radiological findings of VHL are of interest. Patient concerns: We report a 38-year-old woman with a ten-year history of VHL disease involving both pancreas and biliary system. To the best of our knowledge, direct involvement of the biliary system in VHL disease has never been reported. Diagnoses: The diagnosis was established via computed tomography scan and was confirmed by genetic testing. Interventions: The patient chose to receive conservative treatment and was followed up by magnetic resonance cholangiopancreatography and magnetic resonance imaging examination. Outcomes: Renal angiomas and cysts were found during follow-up and there were no evidence of malignant change of the pancreas and biliary system. Lessons: We described the first case of VHL-associated choledochal cysts and may present new visceral manifestations of VHL disease. Gastroenterologists should be aware of the clinical presentations of this rare disease for early detection of its life-threatening manifestations. PMID:28072736

  12. Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in biliary brush cytology

    PubMed Central

    Keane, Margaret G; Huggett, Matthew T; Chapman, Michael H; Johnson, Gavin J; Webster, George J; Thorburn, Douglas; Mackay, James; Pereira, Stephen P

    2017-01-01

    Background: Biliary brush cytology is the standard method of evaluating biliary strictures, but is insensitive at detecting malignancy. In pancreaticobiliary cancer minichromosome maintenance replication proteins (MCM 2–7) are dysregulated in the biliary epithelium and MCM5 levels are elevated in bile samples. This study aimed to validate an immunocolorimetric ELISA assay for MCM5 as a pancreaticobiliary cancer biomarker in biliary brush samples. Methods: Biliary brush specimens were collected prospectively at ERCP from patients with a biliary stricture. Collected samples were frozen at −80 °C. The supernatant was washed and lysed cells incubated with HRP-labelled anti-MCM5 mouse monoclonal antibody. Test positivity was determined by optical density absorbance. Patients underwent biliary brush cytology or additional investigations as per clinical routine. Results: Ninety-seven patients were included in the study; 50 had malignant strictures. Median age was 65 years (range 21–94) and 51 were male. Compared with final diagnosis the MCM5 assay had a sensitivity for malignancy of 65.4% compared with 25.0% for cytology. In the 72 patients with paired MCM5 assay and biliary brush cytology, MCM5 demonstrated an improved sensitivity (55.6% vs 25.0% P=0.0002) for the detection of malignancy. Conclusions: Minichromosome maintenance replication protein5 is a more sensitive indicator of pancreaticobiliary malignancy than standard biliary brush cytology. PMID:28081547

  13. [External drainage during surgery for biliary lithiasis. Our present attitude (author's transl)].

    PubMed

    Richelme, H; Bourgeon, A; Ferrari, C; Carles, R; Gard, C; Barraya, L

    1982-01-01

    External biliary drainage, the "routine" manner of terminating surgery on the common bile duct, should now become almost obsolete as new methods for operation and exploration during surgery are perfected. A review of cases receiving biliary surgery over a period of 20 years showed that external biliary drainage was conducted in only 4 p. cent of operations on the common bile duct (excluding biliodigestive anastomoses). External biliary drainage should be employed only after due reflection : trans-cystic drainage, the "minor" form, will be indicated less and less as investigational methods during operation develop, while Kehr's drain, the "major" form, will occupy a limited but necessary place in certain cases, primarily in angiocholitis.

  14. Trps1 Regulates Biliary Epithelial-Mesenchymal Transition and Has Roles during Biliary Fibrosis in Liver Grafts: A Preliminary Study

    PubMed Central

    Zhe, Cheng; Yu, Fan; Tian, Ju; Zheng, Shuguo

    2015-01-01

    Objective To investigate the role(s) of Trps1 in non-anastomotic biliary stricture (NABS) following liver transplantation. Methods Immunohistochemical and histological techniques were used to detect Trps1, E-cadherin, CK19, vimentin, α-SMA, and collagen deposition. Human intrahepatic biliary epithelial cells (HIBECs) were infected with a Trps1 adenovirus, or transfected with Trps1 short-interfering RNAs (siRNAs). Reverse transcription polymerase chain reaction (RT-PCR) assays and western blotting were used to determine expression levels of epithelial and mesenchymal markers, and Trps1 in HIBECs. Results Expression of Trps1 and epithelial markers was down-regulated or absent in NABS liver samples. Mesenchymal markers were seen in biliary epithelial cells (BECs), with collagen deposited around the bile duct. Trps1 expression positively correlated with epithelial markers. Expression of epithelial marker mRNAs and proteins in HIBECs decreased with prolonged cold preservation (CP), while mesenchymal marker expression increased. A 12-h CP period led to increased Trps1 mRNA and protein levels. Expression of E-cadherin was increased in HIBECs following Trps1 adenovirus infection and CP/reperfusion injury (CPRI), with vimentin expression levels reduced and CPRI-mediated epithelial-mesenchymal transition (EMT) inhibited. Transfection of HIBECs with Trps1 siRNAs in conjunction with CPRI revealed that E-cadherin expression was decreased, vimentin expression was increased, and CPRI-mediated EMT was promoted. Conclusion Trps1 is involved in NABS pathogenesis following liver transplantation and negatively correlates with BEC EMT and biliary fibrosis in liver grafts. Trps1 demonstrates antagonistic effects that could reverse EMT. PMID:25886207

  15. IL-8 gene polymorphism in acute biliary and non biliary pancreatitis: probable cause of high level parameters?

    PubMed Central

    Ozen, Filiz; Yildirim, Ibrahim Halil; Ozemir, Ibrahim Ali; Ozlu, Can; Alimoglu, Orhan

    2017-01-01

    Backgrounds/Aims Inflammatory mediators of the innate immune response play fundamental roles in the pathogenesis of acute pancreatitis. The correlation between interleukin-8 (IL-8) gene polymorphism with types of acute pancreatitis and severity of pancreatitis, was evaluated in this study. Methods According to the diagnostic criteria, 176 patients with acute pancreatitis were grouped into biliary (n=83) and nonbiliary pancreatitis (n=93). Healthy blood donors (n=100) served as controls. Serum alanine transaminase, aspartate transaminase, total and direct bilirubin, amylase, lypase, white blood cell count and c-reactive protein levels were evaluated to correlate with IL-8 rs4073 (-251T/A) polymorphism, which was analyzed using a real-time polymerase chain reaction method with melting point analysis. Results The IL-8 AA genotype was detected with a significantly higher frequency among the patients with acute biliary pancreatitis having higher alanine transaminase levels than the median range. Homozygote alleles were significantly higher among patients with acute biliary pancreatitis having amylase levels higher than the median range. Conclusions Determination of the frequency of IL-8 polymorphism in acute pancreatitis is informative and provides further evidence concerning the role of IL-8 in laboratory tests. PMID:28317043

  16. Early detection of biliary complications and graft rejection in a non-RH Identitical liver transplant recipient from a non-heart-beating donor: a case report.

    PubMed

    Turiño-Luque, J; Zambudio-Carroll, N; Muffak-Granero, K; Villegas-Herrera, T; Garrote-Lara, D; Ferrón-Orihuela, J-A

    2012-09-01

    Because of a shortage of organs, non-heart-beating donors have been proposed to be a possible source of grafts for orthotopic liver transplantation. Herein, we have presented a blood group A+ patient with primary biliary cirrhosis, who underwent orthotopic liver transplantation from a non-heart-beating blood group A- donor. On day 5 after transplantation the patient displayed a low hemoglobin levels as well as an increased total bilirubin with progressive encephalopathy, hypotension, and oligoanuria on day 11. The patient responded to steroid treatment. We assume the main cause of organ dysfunction was a passenger lymphocyte syndrome (ABO-Rh incompatibility). Biliary complications were detected at a 6-month follow-up visit by increased hepatic enzymes. We thus concluded that it is useful to take Rh group into account.

  17. Regulation of biliary cholesterol secretion in the rat. Role of hepatic cholesterol esterification.

    PubMed Central

    Nervi, F; Bronfman, M; Allalón, W; Depiereux, E; Del Pozo, R

    1984-01-01

    Although the significance of the enterohepatic circulation of bile salts in the solubilization and biliary excretion of cholesterol is well established, little is known about the intrahepatic determinants of biliary cholesterol output. Studies were undertaken to elucidate some of these determinants in the rat. Feeding 1% diosgenin for 1 wk increased biliary cholesterol output and saturation by 400%. Bile flow, biliary bile salt, phospholipid and protein outputs remained in the normal range. When ethynyl estradiol (EE) was injected into these animals, biliary cholesterol output decreased to almost normal levels under circumstances of minor changes in the rates of biliary bile salt and phospholipid outputs. Similarly, when chylomicron cholesterol was intravenously injected into diosgenin-fed animals, biliary cholesterol output significantly decreased as a function of the dose of chylomicron cholesterol administered. Relative rates of hepatic cholesterol synthesis and esterification were measured in isolated hepatocytes. Although hepatic cholesterogenesis increased 300% in diosgenin-fed animals, the contribution of newly synthesized cholesterol to total biliary cholesterol output was only 19 +/- 9%, compared with 12 +/- 6% in control and 15 +/- 5% in diosgenin-fed and EE-injected rats. The rate of oleate incorporation into hepatocytic cholesterol esters was 30% inhibited in diosgenin-fed rats. When EE was injected into these animals, the rate of cholesterol esterification increased to almost 300%. To investigate further the interrelationship between hepatic cholesterol esterification and biliary cholesterol output, we studied 21 diosgenin-fed rats. Six of them received in addition EE and 10 received chylomicron cholesterol. The relationships between biliary cholesterol output as a function of both microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity and hepatic cholesterol ester concentration were significantly correlated in a reciprocal manner. From these

  18. 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

  19. Ursodeoxycholic Acid Ameliorates Intrahepatic Cholestasis Independent of Biliary Bicarbonate Secretion in Vil2(kd/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 HCO3(-) 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.

  20. Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.

    PubMed

    Dumonceau, J-M; Tringali, A; Blero, D; Devière, J; Laugiers, R; Heresbach, D; Costamagna, G

    2012-03-01

    This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy about endoscopic biliary stenting. The present Clinical Guideline describes short-term and long-term results of biliary stenting depending on indications and stent models; it makes recommendations on when, how, and with which stent to perform biliary drainage in most common clinical settings, including in patients with a potentially resectable malignant biliary obstruction and in those who require palliative drainage of common bile duct or hilar strictures. Treatment of benign conditions (strictures related to chronic pancreatitis, liver transplantation, or cholecystectomy, and leaks and failed biliary stone extraction) and management of complications (including stent revision) are also discussed. A two-page executive summary of evidence statements and recommendations is provided. A separate Technology Review describes the models of biliary stents available and the stenting techniques, including advanced techniques such as insertion of multiple plastic stents, drainage of hilar strictures, retrieval of migrated stents and combined stenting in malignant biliary and duodenal obstructions.The target readership for the Clinical Guideline mostly includes digestive endoscopists, gastroenterologists, oncologists, radiologists, internists, and surgeons while the Technology Review should be most useful to endoscopists who perform biliary drainage.

  1. Congenital duplex gallbladder and biliary mucocele associated with partial hepatic cholestasis and cholelithiasis in a cat

    PubMed Central

    Woods, Katharine S.; Brisson, Brigitte A.; Defarges, Alice M.N.; Oblak, Michelle L.

    2012-01-01

    A 6-year-old neutered male domestic shorthair cat was presented for acute onset of vomiting. Exploratory laparotomy identified a duplex gallbladder and left cholecystectomy was performed. Histopathology confirmed biliary mucocele and hepatic cholestasis. While rare, biliary mucoceles should be considered as a differential diagnosis for feline extrahepatic bile duct obstruction. PMID:22942442

  2. Prolonged exposure of cholestatic rats to complete dark inhibits biliary hyperplasia and liver fibrosis.

    PubMed

    Han, Yuyan; Onori, Paolo; Meng, Fanyin; DeMorrow, Sharon; Venter, Julie; Francis, Heather; Franchitto, Antonio; Ray, Debolina; Kennedy, Lindsey; Greene, John; Renzi, Anastasia; Mancinelli, Romina; Gaudio, Eugenio; Glaser, Shannon; Alpini, Gianfranco

    2014-11-01

    Biliary hyperplasia and liver fibrosis are common features in cholestatic liver disease. Melatonin is synthesized by the pineal gland as well as the liver. Melatonin inhibits biliary hyperplasia of bile duct-ligated (BDL) rats. Since melatonin synthesis (by the enzyme serotonin N-acetyltransferase, AANAT) from the pineal gland increases after dark exposure, we hypothesized that biliary hyperplasia and liver fibrosis are diminished by continuous darkness via increased melatonin synthesis from the pineal gland. Normal or BDL rats (immediately after surgery) were housed with light-dark cycles or complete dark for 1 wk before evaluation of 1) the expression of AANAT in the pineal gland and melatonin levels in pineal gland tissue supernatants and serum; 2) biliary proliferation and intrahepatic bile duct mass, liver histology, and serum chemistry; 3) secretin-stimulated ductal secretion (functional index of biliary growth); 4) collagen deposition, liver fibrosis markers in liver sections, total liver, and cholangiocytes; and 5) expression of clock genes in cholangiocytes. In BDL rats exposed to dark there was 1) enhanced AANAT expression/melatonin secretion in pineal gland and melatonin serum levels; 2) improved liver morphology, serum chemistry and decreased biliary proliferation and secretin-stimulated choleresis; and 4) decreased fibrosis and expression of fibrosis markers in liver sections, total liver and cholangiocytes and reduced biliary expression of the clock genes PER1, BMAL1, CLOCK, and Cry1. Thus prolonged dark exposure may be a beneficial noninvasive therapeutic approach for the management of biliary disorders.

  3. Schwannoma of the biliary tract resembling cholangiocarcinoma: A case report and review

    PubMed Central

    Garcia Sanz, I; Muñoz de Nova, JL; Valdés de Anca, A; Martín Pérez, ME

    2016-01-01

    Schwannomas are benign tumours derived from Schwann cells and are extremely rare in the biliary tract. We present the case of a 62-year-old patient with a common bile duct schwannoma that resembled a cholangiocarcinoma. We also review all 17 previously published cases of schwannoma of the biliary tract and discuss the challenges of preoperative diagnosis. PMID:27269434

  4. Incidence of underlying biliary neoplasm in patients after major hepatectomy for preoperative benign hepatolithiasis

    PubMed Central

    Park, Hyeong Min; Cho, Chol Kyoon; Koh, Yang Seok; Kim, Hee Joon; Park, Eun Kyu

    2016-01-01

    Backgrounds/Aims Despite hepatolithiasis being a risk factor for biliary neoplasm including cholangiocarcinoma, the incidence of underlying biliary neoplasm is unknown in patients with preoperative benign hepatolithiasis. The aim of this study was to evaluate the incidence of underlying biliary neoplasm in patients who underwent major hepatectomy for preoperative benign hepatolithiasis. Methods Between March 2005 and December 2015, 73 patients who underwent major hepatectomy for preoperative benign hepatolithiasis were enrolled in this study. The incidence and pathological differentiation of concomitant biliary neoplasm were retrospectively determined by review of medical records. Postoperative complications after major hepatectomy were evaluated. Results Concomitant biliary neoplasm was pathologically confirmed in 20 patients (27.4%). Biliary intraepithelial neoplasia (BIN) was detected in 12 patients (16.4%), and 1 patient (1.4%) had intraductal papillary mucinous neoplasm (IPMN), as the premalignant lesion. Cholangiocarcinoma was pathologically confirmed in 7 patients (9.6%). Preoperative imaging of the 73 patients revealed biliary stricture at the first branch of bile duct in 31 patients (42.5%), and at the second branch of bile duct in 39 patients (53.4%). Postoperative complications developed in 14 patients (19.1%). Almost all patients recovered from complications, including intra-abdominal abscess (9.6%), bile leakage (4.1%), pleural effusion (2.7%), and wound infection (1.4%). Only 1 patient (1.4%) died from aspiration pneumonia. Conclusions The incidence of underlying biliary neoplasm was not negligible in the patients with hepatolithiasis, despite meticulous preoperative evaluations. PMID:28261696

  5. 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

  6. 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

  7. Biliary Duct-to-Duct Reconstruction with a Tunneled Retroperitoneal T-Tube During Liver Transplantation: a Novel Approach to Decrease Biliary Leaks After T-Tube Removal.

    PubMed

    Navez, Julie; Mohkam, Kayvan; Darnis, Benjamin; Cazauran, Jean-Baptiste; Ducerf, Christian; Mabrut, Jean-Yves

    2017-04-01

    The benefit of placing a T-tube for duct-to-duct biliary reconstruction during orthotopic liver transplantation (OLT) remains controversial because it could be associated with specific complications, especially at the time of T-tube removal. While the utility of T-tube during OLT represents an eternal debate, only a few technical refinements of T-tube placement have been described since the report of the original technique by Starzl and colleagues. Herein, we present a novel technique of T-tube placement for duct-to-duct biliary reconstruction during OLT, using a tunneled retroperitoneal route. On the basis of our experience of 305 patients who benefitted from the reported technique, the placement of a tunneled retroperitoneal biliary T-tube appears to be safe and results in a low rate of biliary complications, especially at the time of T-tube removal.

  8. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  9. [Retention jaundice caused by central hepatic hepatoma. Treatment with Kron's extra-anatomic biliary prosthesis].

    PubMed

    Partensky, C; Paliard, P; Maurin, T; Bret, P M

    1983-01-01

    A 31 year-old patient presented with a retention jaundice from a centrally located hepatoma invading the hilum. Because of the patient's age and the severity of the pruritus and jaundice, palliative treatment was performed by percutaneous catheterization of the intrahepatic biliary tracts to drain the right and left hepatic canals. As the hilar stenosis could not be overcome, the external drainage was transformed into internal drainage by implantation of a Kron's biliary prosthesis linking the intrahepatic biliary tracts, following segment III hepatotomy, to the duodenal lumen, with burying of the prosthesis in the gastric antrum region. Jaundice was reduced until death of the patients from metastases 6 months later. This case demonstrates that the use of Kron's biliary prosthesis to perform a biliodigestive shunt from intrahepatic biliary pathways is a valid palliative procedure in patients with limited life expectancies.

  10. Role of endoscopy in the conservative management of biliary complications after deceased donor liver transplantation

    PubMed Central

    Lisotti, Andrea; Fusaroli, Pietro; Caletti, Giancarlo

    2015-01-01

    The clinical outcome of patients receiving liver transplantation could be significantly affected by biliary complications, including strictures, leaks, stones and bilomas; early diagnosis and treatment of these conditions lead to markedly reduction in morbidity and mortality. Therapeutic gold standard is represented by conservative approaches, both endoscopic and percutaneous, based on the type of biliary reconstruction, the local availability of the procedures and specific expertise. In patients with previous transplantation, the difficult biliary access and the possible presence of concomitant complications (mainly strictures) further restrict the efficacy of the endoscopic and percutaneous treatments; on the other hand, surgery should generally be avoided because of the even increased morbidity and mortality due to technical and clinical issues. Here we review the most common biliary complications occurring after liver transplantation and discuss available treatment options including future perspectives such as endoscopic ultrasound-guided biliary access in patients with Roux-en-Y choledocho-jejunostomy or extracorporeal shock wave lithotripsy for difficult stones. PMID:26730271

  11. Late-onset severe biliary bleeding after endoscopic pigtail plastic stent insertion

    PubMed Central

    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

    2017-01-01

    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. PMID:28216982

  12. Somatostatin analogue (octreotide) inhibits bile duct epithelial cell proliferation and fibrosis after extrahepatic biliary obstruction.

    PubMed Central

    Tracy, T. F.; Tector, A. J.; Goerke, M. E.; Kitchen, S.; Lagunoff, D.

    1993-01-01

    Extrahepatic biliary obstruction leads to bile duct epithelial cell proliferation. Somatostatin and its analogue, octreotide, have been shown to inhibit DNA synthesis and proliferation in hepatocytes. We investigated the effect of octreotide on the biliary epithelial cell proliferative responses to biliary obstruction. Male Sprague-Dawley rats underwent common bile duct ligation and subcutaneous injection of either saline or octreotide (6 micrograms/kg) twice daily for 7 days. Morphometric analysis of hepatocytes, bile duct epithelial cells, and periportal connective tissue was performed by computerized point counting. Hepatocyte volume was preserved with octreotide treatment, which also significantly decreased bile duct proliferation and periportal extracellular matrix deposition in response to biliary obstruction compared with saline treated, duct-ligated animals. These results indicate that octreotide prevents the morphological changes that accompany extrahepatic biliary obstruction. Images Figure 1 PMID:8256850

  13. Imaging tests for accurate diagnosis of acute biliary pancreatitis.

    PubMed

    Şurlin, Valeriu; Săftoiu, Adrian; Dumitrescu, Daniela

    2014-11-28

    Gallstones represent the most frequent aetiology of acute pancreatitis in many statistics all over the world, estimated between 40%-60%. Accurate diagnosis of acute biliary pancreatitis (ABP) is of outmost importance because clearance of lithiasis [gallbladder and common bile duct (CBD)] rules out recurrences. Confirmation of biliary lithiasis is done by imaging. The sensitivity of the ultrasonography (US) in the detection of gallstones is over 95% in uncomplicated cases, but in ABP, sensitivity for gallstone detection is lower, being less than 80% due to the ileus and bowel distension. Sensitivity of transabdominal ultrasonography (TUS) for choledocolithiasis varies between 50%-80%, but the specificity is high, reaching 95%. Diameter of the bile duct may be orientative for diagnosis. Endoscopic ultrasonography (EUS) seems to be a more effective tool to diagnose ABP rather than endoscopic retrograde cholangiopancreatography (ERCP), which should be performed only for therapeutic purposes. As the sensitivity and specificity of computerized tomography are lower as compared to state-of-the-art magnetic resonance cholangiopancreatography (MRCP) or EUS, especially for small stones and small diameter of CBD, the later techniques are nowadays preferred for the evaluation of ABP patients. ERCP has the highest accuracy for the diagnosis of choledocholithiasis and is used as a reference standard in many studies, especially after sphincterotomy and balloon extraction of CBD stones. Laparoscopic ultrasonography is a useful tool for the intraoperative diagnosis of choledocholithiasis. Routine exploration of the CBD in cases of patients scheduled for cholecystectomy after an attack of ABP was not proven useful. A significant rate of the so-called idiopathic pancreatitis is actually caused by microlithiasis and/or biliary sludge. In conclusion, the general algorithm for CBD stone detection starts with anamnesis, serum biochemistry and then TUS, followed by EUS or MRCP. In the end

  14. [Reinterventions in classic and laparoscopic surgery of biliary ducts].

    PubMed

    Lese, M; Naghi, I; Pop, C

    2000-01-01

    The study suggests to make a comparative analysis between the complications happened after classic and laparoscopic surgery require a surgical reintervention. The study was realised in the Surgical Department of the Districtual Hospital Baia Mare between 27.04.1997-27.04.1999, which means the precursory year of beginning laparoscopic surgery and the first year with experience in laparoscopic surgery. The conclusions of this study prove that the number of reinterventions after laparoscopic surgery is less than after classic surgery of biliary ducts.

  15. Aetiology of biliary atresia: what is actually known?

    PubMed Central

    2013-01-01

    Biliary atresia (BA) is a rare disease of unknown etiology and unpredictable outcome, even when there has been timely diagnosis and exemplary surgery. It has been the commonest indication for liver transplantation during childhood for the past 20 years. Hence much clinical and basic research has been directed at elucidating the origin and pathology of BA. This review summarizes the current clinical variations of BA in humans, its occasional appearance in animals and its various manifestations in the laboratory as an experimental model. PMID:23987231

  16. Long-term effects of forgotten biliary stents: a case series and literature review.

    PubMed

    Odabasi, Mehmet; Arslan, Cem; Akbulut, Sami; Abuoglu, Haci Hasan; Ozkan, Erkan; Yildiz, Mehmet Kamil; Eris, Cengiz; Gunay, Emre; Tekesin, Kemal; Muftuoglu, Tolga

    2014-01-01

    There are many studies about the biliary stents, however there is a little information about the long-term stayed forgotten biliary stents except a few case reports. We have reported the results of a number of cases with biliary stents that were forgotten or omitted by the patient and the endoscopist. During February 2010 to May 2013, five patients were referred to the general surgery clinic of Haydarpasa Numune Training and Research Hospital, Istanbul Turkey. Past history and medical documents submitted by the patient did not indicate a replacement of the biliary stent in 3 patients. Two patients knew that they had biliary stents. We also conducted a literature review via the PubMed and Google Scholar databases of English language studies published until March 2014 on forgotten biliary stent. There were 3 men and 2 women ranging in age from 22 to 68 years (mean age 41.6 years). Patients presented with pain in the upper abdomen, jaundice, fever, abnormal liver function tests or dilatation of the biliary tract alone or in combination. Patients' demographic findings are presented in Table 1. A review of three cases reported in the English medical literature also discussed. The mean duration of the patency of the stent is about 12 months. The biliary stenting is performed either with plastic or metal stents, studies recommending their replacement after 3-6 months. Patients with long stayed forgotten biliary stents are inevitably treated with surgical intervention. We recommend for all endoscopic retrograde cholangiopancreatography units provide a stent registry system that the stents placed for various therapeutic procedures are not forgotten both by the patient as well as the physician. There should be a deadline for biliary stents in the registry system for each patient.

  17. 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

  18. A case of biliary stones and anastomotic biliary stricture after liver transplant treated with the rendez - vous technique and electrokinetic lithotritor

    PubMed Central

    Pisa, Marta Di; Traina, Mario; Miraglia, Roberto; Maruzzelli, Luigi; Volpes, Riccardo; Piazza, Salvatore; Luca, Angelo; Gridelli, Bruno

    2008-01-01

    The paper studies the combined radiologic and endoscopic approach (rendez vous technique) to the treatment of the biliary complications following liver transplant. The “rendez-vous” technique was used with an electrokinetic lithotripter, in the treatment of a biliary anastomotic stricture with multiple biliary stones in a patient who underwent orthotopic liver transplant. In this patient, endoscopic or percutaneous transhepatic management of the biliary complication failed. The combined approach, percutaneous transhepatic and endoscopic treatment (rendez-vous technique) with the use of an electrokinetic lithotritor, was used to solve the biliary stenosis and to remove the stones. Technical success, defined as disappearance of the biliary stenosis and stone removal, was obtained in just one session, which definitively solved the complications. The combined approach of percutaneous transhepatic and endoscopic (rendez-vous technique) treatment, in association with an electrokinetic lithotritor, is a safe and feasible alternative treatment, especially after the failure of endoscopic and/or percutaneous trans-hepatic isolated procedures. PMID:18473423

  19. Interleukin-32 production associated with biliary innate immunity and proinflammatory cytokines contributes to the pathogenesis of cholangitis in biliary atresia.

    PubMed

    Okamura, A; Harada, K; Nio, M; Nakanuma, Y

    2013-08-01

    Biliary atresia (BA) is thought to be associated with infections by viruses such as Reoviridae and is characterized histologically by fibrosclerosing cholangitis with proinflammatory cytokine-mediated inflammation. Interleukin (IL)-32 affects the continuous inflammation by increasing the production of proinflammatory cytokines. In this study, the role of IL-32 in the cholangitis of BA was examined. Immunohistochemistry for IL-32 and caspase 1 was performed using 21 samples of extrahepatic bile ducts resected from BA patients. Moreover, using cultured human biliary epithelial cells (BECs), the expression of IL-32 and its induction on stimulation with a Toll-like receptor [(TLR)-3 ligand (poly(I:C)] and proinflammatory cytokines was examined. BECs composing extrahepatic bile ducts showing cholangitis expressed IL-32 in BA, but not in controls. Caspase 1 was expressed constantly on BECs of both BA and control subjects. Furthermore, poly(I:C) and proinflammatory cytokines [(IL-1β, interferon (IFN)-γ and tumour necrosis factor (TNF)-α] induced IL-32 expression strongly in cultured BECs, accompanying the constant expression of TLR-3 and caspase 1. Our results imply that the expression of IL-32 in BECs was found in the damaged bile ducts of BA and induced by biliary innate immunity via TLR-3 and proinflammatory cytokines. These findings suggest that IL-32 is involved initially in the pathogenic mechanisms of cholangitis in BA and also plays an important role in the amplification and continuance of periductal inflammatory reactions. It is therefore tempting to speculate that inhibitors of IL-32 could be useful for attenuating cholangitis in BA.

  20. Percutaneous Transhepatic Endobiliary Drainage of Hepatic Hydatid Cyst with Rupture into the Biliary System: An Unusual Route for Drainage

    SciTech Connect

    Inal, Mehmet; Soyupak, Suereyya; Akguel, Erol; Ezici, Hueseyin

    2002-10-15

    The most common and serious complication of hydatid cyst of the liver is rupture into the biliary tract causing obstructive jaundice, cholangitis and abscess. The traditional treatment of biliary-cystic fistula is surgery and recently endoscopic sphincterotomy. We report a case of complex heterogeneous cyst rupture into the biliary tract causing biliary obstruction in which the obstruction and cyst were treated successfully by percutaneous transhepatic endobiliary drainage. Our case is the second report of percutaneous transbiliary internal drainage of hydatid cyst with rupture into the biliary duct in which the puncture and drainage were not performed through the cyst cavity.

  1. Identification of hepatic phospholipidosis inducers in sandwich-cultured rat hepatocytes, a physiologically relevant model, reveals altered basolateral uptake and biliary excretion of anionic probe substrates.

    PubMed

    Ferslew, Brian C; Brouwer, Kim L R

    2014-05-01

    Drug-induced phospholipidosis (PLD) is characterized by phospholipid accumulation within the lysosomes of affected tissues, resulting in lysosomal enlargement and laminar body inclusions. Numerous adverse effects and toxicities have been linked to PLD-inducing drugs, but it remains unknown whether drug-induced PLD represents a distinct toxicity or cellular adaptation. In silico and immortalized cellular models have been used to evaluate the PLD potential of new drugs, but these systems have some limitations. The aims of this study were to determine whether primary sandwich-cultured hepatocytes (SCH) can serve as a sensitive and selective model to evaluate hepatic drug-induced PLD, and to evaluate the impact of PLD on the uptake and biliary excretion of probe substrates, taurocholate (TC) and rosuvastatin (RSV). Rat SCH were cultured for 48 h with prototypic hepatic PLD-inducing drugs, amiodarone (AMD), chloroquine (CHQ), desipramine (DES), and azithromycin (AZI), as well as the renal PLD inducer gentamicin (GTM). LysoTracker Red localization and transmission electron microscopy indicated enlarged lysosomal compartments and laminar body inclusions in SCH treated with AMD, CHQ, DES, and AZI, but not GTM, relative to control. PLD resulted in a 51-92% decrease in the in vitro biliary clearance of both TC and RSV; the biliary excretion index significantly decreased for TC from 88 to 35-73%. These data suggested that PLD significantly reduced both organic anion transporting polypeptide-mediated uptake, and bile salt export pump-mediated biliary transport processes. The current study demonstrates that the rat SCH system is a promising model to study hepatic PLD in vitro. Altered hepatic transport of anionic substrates secondary to drug-induced PLD is a novel finding.

  2. Urinary and biliary metabolites of daidzin and daidzein in rats.

    PubMed

    Yasuda, T; Kano, Y; Saito, K; Ohsawa, K

    1994-10-01

    Examination was made of the urinary and biliary excretion of metabolites of daidzin and daidzein, the major components of roots of Pueraria lobata Ohwi (Leguminosae) in rats. The urine of rats administered daidzin orally contained four major metabolites, daidzein 7,4'-di-O-sulfate (M-1), daidzein 7-O-beta-D-glucuronide (M-2), daidzein 4'-O-sulfate (M-3), daidzein (M-4), as determined from spectroscopic and chemical data. The urine of rats treated with daidzein contained M-2--M-4 in the above metabolites. Total cumulative amounts of the four metabolites excreted in the urine at 48 h following the oral administration of daidzin and daidzein were approximately 4.8% and 4.6% of the doses administered, respectively. The bile of rats administered daidzin orally contained M-1--M-4. Daidzein 7-O-beta-D-glucuronide 4'-O-sulfate (M-5), a major biliary metabolite, was identified by the high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectra. At least daidzin appeared to be hydrolyzed to aglycone after absorption in the body, and as a part of metabolites, M-1--M-4 having free hydroxyl, glucuronided or sulfated hydroxyls at the C-7 position, may then be excreted in the urine and bile.

  3. Percutaneous Management of Biliary Strictures After Pediatric Liver Transplantation

    SciTech Connect

    Miraglia, Roberto Maruzzelli, Luigi; Caruso, Settimo; Riva, Silvia; Spada, Marco; Luca, Angelo; Gridelli, Bruno

    2008-09-15

    We analyze our experience with the management of biliary strictures (BSs) in 27 pediatric patients who underwent liver transplantation with the diagnosis of BS. Mean recipient age was 38 months (range, 2.5-182 months). In all patients percutaneous transhepatic cholangiography, biliary catheter placement, and bilioplasty were performed. In 20 patients the stenoses were judged resolved by percutaneous balloon dilatation and the catheters removed. Mean number of balloon dilatations performed was 4.1 (range, 3-6). No major complications occurred. All 20 patients are symptom-free with respect to BS at a mean follow-up of 13 months (range, 2-46 months). In 15 of 20 patients (75%) one course of percutaneous stenting and bilioplasty was performed, with no evidence of recurrence of BS at a mean follow-up of 15 months (range, 2-46 months). In 4 of 20 patients (20%) two courses of percutaneous stenting and bilioplasty were performed; the mean time to recurrence was 9.8 months (range, 2.4-24 months). There was no evidence of recurrence of BS at a mean follow-up of 12 months (range, 2-16 months). In 1 of 20 patients (5%) three courses of percutaneous stenting and bilioplasty were performed; there was no evidence of recurrence of BS at a mean follow-up of 10 months. In conclusion, BS is a major problem following pediatric liver transplantation. Radiological percutaneous treatment is safe and effective, avoiding, in most cases, surgical revision of the anastomosis.

  4. Single-incision laparoscopic surgery for biliary tract disease

    PubMed Central

    Chuang, Shu-Hung; Lin, Chih-Sheng

    2016-01-01

    Single-incision laparoscopic surgery (SILS), or laparoendoscopic single-site surgery, has been employed in various fields to minimize traumatic effects over the last two decades. Single-incision laparoscopic cholecystectomy (SILC) has been the most frequently studied SILS to date. Hundreds of studies on SILC have failed to present conclusive results. Most randomized controlled trials (RCTs) have been small in scale and have been conducted under ideal operative conditions. The role of SILC in complicated scenarios remains uncertain. As common bile duct exploration (CBDE) methods have been used for more than one hundred years, laparoscopic CBDE (LCBDE) has emerged as an effective, demanding, and infrequent technique employed during the laparoscopic era. Likewise, laparoscopic biliary-enteric anastomosis is difficult to carry out, with only a few studies have been published on the approach. The application of SILS to CBDE and biliary-enteric anastomosis is extremely rare, and such innovative procedures are only carried out by a number of specialized groups across the globe. Herein we present a thorough and detailed analysis of SILC in terms of operative techniques, training and learning curves, safety and efficacy levels, recovery trends, and costs by reviewing RCTs conducted over the past three years and two recently updated meta-analyses. All existing literature on single-incision LCBDE and single-incision laparoscopic hepaticojejunostomy has been reviewed to describe these two demanding techniques. PMID:26811621

  5. Kron's biliary prosthetic bypass in the treatment of neoplastic jaundice.

    PubMed

    Kron, B; Reynier, J

    1985-01-01

    After experimental study in the dog, which showed the material to be highly reliable, an original method of biliary bypass using a silicone prosthesis in the treatment of neoplastic jaundice is introduced. This prosthesis allows the bile duct to be bypassed regardless of the location of the obstacle. This method was used in 150 patients; recession was sufficiently good in 84 of them to confirm good tolerance and the excellence of the results. In fact, good results were recorded in 95% of cases of cancer of the hilum, which is all the more remarkable in consideration of the difficulties involved in these operations. The main postoperative complications are bile fistulas which resolve spontaneously if the precaution of extensively draining the zones of intubation is taken; postoperative comfort is excellent; no constraint is necessary and the operative risk is moderate, this is particularly desirable in patients in a poor general condition. A short prosthesis makes transtumoral intubation possible, and a long prosthesis allows implantation in the digestive tract: stomach, duodenum or first intestinal loop. Postoperative persistence of jaundice is rare if a prosthesis of sufficient diameter is used and if no major bile duct or part of the liver is excluded. Cholangitis is exceptional and indicative of an excluded biliary area.

  6. Targeting Angiogenesis in Biliary Tract Cancers: An Open Option

    PubMed Central

    Simone, Valeria; Brunetti, Oronzo; Lupo, Luigi; Testini, Mario; Maiorano, Eugenio; Simone, Michele; Longo, Vito; Rolfo, Christian; Peeters, Marc; Scarpa, Aldo; Azzariti, Amalia; Russo, Antonio; Ribatti, Domenico; Silvestris, Nicola

    2017-01-01

    Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies. PMID:28212293

  7. The Sea Lamprey as an Etiological Model for Biliary Atresia

    PubMed Central

    Chung-Davidson, Yu-Wen; Yeh, Chu-Yin; Li, Weiming

    2015-01-01

    Biliary atresia (BA) is a progressive, inflammatory, and fibrosclerosing cholangiopathy in infants that results in obstruction of both extrahepatic and intrahepatic bile ducts. It is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult with steatohepatitis and fibrosis in the liver. In this paper, we present new histological evidence and compare the sea lamprey to existing animal models to highlight the advantages and possible limitations of using the sea lamprey to study the etiology and compensatory mechanisms of BA and other liver diseases. Understanding the signaling factors and genetic networks underlying lamprey BA can provide insights into BA etiology and possible targets to prevent biliary degeneration and to clear fibrosis. In addition, information from lamprey BA can be used to develop adjunct treatments for patients awaiting or receiving surgical treatments. Furthermore, the cholestatic adult lamprey has unique adaptive mechanisms that can be used to explore potential treatments for cholestasis and nonalcoholic steatohepatitis (NASH). PMID:26101777

  8. Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers.

    PubMed

    Letelier, Pablo; Riquelme, Ismael; Hernández, Alfonso H; Guzmán, Neftalí; Farías, Jorge G; Roa, Juan Carlos

    2016-05-23

    Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20-22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs.

  9. Biliary Microbiota, Gallstone Disease and Infection with Opisthorchis felineus

    PubMed Central

    Saltykova, Irina V.; Petrov, Vjacheslav A.; Logacheva, Maria D.; Ivanova, Polina G.; Merzlikin, Nikolay V.; Sazonov, Alexey E.; Ogorodova, Ludmila M.; Brindley, Paul J.

    2016-01-01

    Background There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia. Methodology/Principal Findings Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum, bile from participants with opisthorchiasis showed greater numbers of Synergistetes, Spirochaetes, Planctomycetes, TM7 and Verrucomicrobia. Numbers of > 20 phylotypes differed in bile of the O. felineus-infected compared to non-infected participants, including presence of species of the genera Mycoplana, Cellulosimicrobium, Microlunatus and Phycicoccus, and the Archaeans genus, Halogeometricum, and increased numbers of Selenomonas, Bacteroides, Rothia, Leptotrichia, Lactobacillus, Treponema and Klebsiella. Conclusions/Significance Overall, infection with the liver fluke O. felineus modified the biliary microbiome, increasing abundance of bacterial and archaeal phylotypes. PMID:27447938

  10. Targeting Angiogenesis in Biliary Tract Cancers: An Open Option.

    PubMed

    Simone, Valeria; Brunetti, Oronzo; Lupo, Luigi; Testini, Mario; Maiorano, Eugenio; Simone, Michele; Longo, Vito; Rolfo, Christian; Peeters, Marc; Scarpa, Aldo; Azzariti, Amalia; Russo, Antonio; Ribatti, Domenico; Silvestris, Nicola

    2017-02-15

    Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies.

  11. Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers

    PubMed Central

    Letelier, Pablo; Riquelme, Ismael; Hernández, Alfonso H.; Guzmán, Neftalí; Farías, Jorge G.; Roa, Juan Carlos

    2016-01-01

    Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20–22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs. PMID:27223281

  12. ePTFE/FEP-Covered Metallic Stents for Palliation of MalignantBiliary Disease: Can Tumor Ingrowth Be Prevented?

    SciTech Connect

    Hatzidakis, Adam Krokidis, Miltiadis; Kalbakis, Kostantinos; Romanos, Jiannis; Petrakis, Ioannis; Gourtsoyiannis, Nicholas

    2007-09-15

    Purpose. To determine the application and clinical effectiveness of ePTFE/FEP-covered metallic stents for palliation of malignant biliary disease, and to evaluate the efficiency of stent coverage in preventing tumor ingrowth. Methods. During a 3-year period, 36 patients with malignant obstructive jaundice were treated with ePTFE/FEP-covered stents, with or without proximal side holes. The stricture was located in the lower common bile duct (CBD) in 18 cases, the upper CBD in 9, the lower common hepatic duct (CHD) in 6, and the upper CHD in 3 patients. Results.Thirty-seven covered stents were percutaneously implanted. The technical success rate was 97%. Reintervention was required in 6 cases. The 30-day mortality rate was 40%, not procedure-related. Mean survival was 128 days. Primary patency rates were 100%,55.5%, and 25% at 3, 6, and 12 months, respectively, while the assisted patency rate was 100% at 12 months. Stents without side holes had higher primary patency rates compared with those with side holes, where occlusion was always due to tumor ingrowth. Tumor ingrowth did not occur in the completely covered stents. No stent dysfunction due to sludge incrustation was found.Complications were 1 case of arterial laceration that occurred during percutaneous transhepatic cholangiography, and a subcapsular hematoma and 1 case of bile peritonitis, that both occurred during primary stenting. No complications followed the secondary stenting technique. Conclusion. ePTFE/FEP-covered metallic stents are safe and effective for palliation of malignant biliary disease. The presence of the ePTFE/FEP coating is likely to prevent from tumor ingrowth.

  13. 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.

  14. Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake

    SciTech Connect

    Cotting, J.; Zysset, T.; Reichen, J.

    1989-02-01

    To study immediate events during extrahepatic cholestasis, we investigated the effect of short-term biliary obstruction on the bioelectrical sinusoidal-canalicular barrier in the rat using molecular weight-matched uncharged and negatively charged inert solute pairs. The bioelectrical barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a 20-min biliary obstruction both decreased by 61 and 11%, respectively, but only the large molecular weight pair (the inulins) returned to base line after release of the obstruction. Inert solute clearances were increased after short biliary obstruction depending on molecular size and negative charge (ferrocyanide greater than sucrose greater than carboxyinulin greater than inulin), suggesting that both permeability and bioelectrical barriers were affected by obstruction. The hepatic extraction in vivo of a passively transported drug not excreted into bile (D-propranolol) was not affected by obstruction, whereas that of an actively transported drug (glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary obstruction (P less than 0.01). Unidirectional transfer of glycocholate was not affected by short-term biliary obstruction in the situ perfused rat liver; however, 2 min after (14C)glycocholate administration, increased return was observed in hepatic venous effluent in obstructed animals. Our findings demonstrate a loss of the bioelectrical barrier immediately after short-term biliary obstruction. Decreased hepatic extraction in the view of unaltered sinusoidal uptake demonstrates regurgitation of bile into blood during short-term biliary obstruction.

  15. Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake.

    PubMed

    Cotting, J; Zysset, T; Reichen, J

    1989-02-01

    To study immediate events during extrahepatic cholestasis, we investigated the effect of short-term biliary obstruction on the bioelectrical sinusoidal-canalicular barrier in the rat using molecular weight-matched uncharged and negatively charged inert solute pairs. The bioelectrical barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a 20-min biliary obstruction both decreased by 61 and 11%, respectively, but only the large molecular weight pair (the inulins) returned to base line after release of the obstruction. Inert solute clearances were increased after short biliary obstruction depending on molecular size and negative charge (ferrocyanide greater than sucrose greater than carboxyinulin greater than inulin), suggesting that both permeability and bioelectrical barriers were affected by obstruction. The hepatic extraction in vivo of a passively transported drug not excreted into bile (D-propranolol) was not affected by obstruction, whereas that of an actively transported drug (glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary obstruction (P less than 0.01). Unidirectional transfer of glycocholate was not affected by short-term biliary obstruction in the situ perfused rat liver; however, 2 min after [14C]glycocholate administration, increased return was observed in hepatic venous effluent in obstructed animals. Our findings demonstrate a loss of the bioelectrical barrier immediately after short-term biliary obstruction. Decreased hepatic extraction in the view of unaltered sinusoidal uptake demonstrates regurgitation of bile into blood during short-term biliary obstruction.

  16. Iatrogenic Biliary Injuries: Multidisciplinary Management in a Major Tertiary Referral Center

    PubMed Central

    Salama, Ibrahim Abdelkader; Shoreem, Hany Abdelmeged; Saleh, Sherif Mohamed; Hegazy, Osama; Housseni, Mohamed; Abbasy, Mohamed; Badra, Gamal; Ibrahim, Tarek

    2014-01-01

    Background. Iatrogenic biliary injuries are considered as the most serious complications during cholecystectomy. Better outcomes of such injuries have been shown in cases managed in a specialized center. Objective. To evaluate biliary injuries management in major referral hepatobiliary center. Patients & Methods. Four hundred seventy-two consecutive patients with postcholecystectomy biliary injuries were managed with multidisciplinary team (hepatobiliary surgeon, gastroenterologist, and radiologist) at major Hepatobiliary Center in Egypt over 10-year period using endoscopy in 232 patients, percutaneous techniques in 42 patients, and surgery in 198 patients. Results. Endoscopy was very successful initial treatment of 232 patients (49%) with mild/moderate biliary leakage (68%) and biliary stricture (47%) with increased success by addition of percutaneous (Rendezvous technique) in 18 patients (3.8%). However, surgery was needed in 198 patients (42%) for major duct transection, ligation, major leakage, and massive stricture. Surgery was urgent in 62 patients and elective in 136 patients. Hepaticojejunostomy was done in most of cases with transanastomotic stents. There was one mortality after surgery due to biliary sepsis and postoperative stricture in 3 cases (1.5%) treated with percutaneous dilation and stenting. Conclusion. Management of biliary injuries was much better with multidisciplinary care team with initial minimal invasive technique to major surgery in major complex injury encouraging early referral to highly specialized hepatobiliary center. PMID:25435672

  17. A new clarification method to visualize biliary degeneration during liver metamorphosis in Sea Lamprey (Petromyzon marinus).

    PubMed

    Chung-Davidson, Yu-Wen; Davidson, Peter J; Scott, Anne M; Walaszczyk, Erin J; Brant, Cory O; Buchinger, Tyler; Johnson, Nicholas S; Li, Weiming

    2014-06-06

    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.

  18. Biliary tract perforation following percutaneous endobiliary radiofrequency ablation: A report of two cases

    PubMed Central

    ZHOU, CHUANGUO; WEI, BAOJIE; GAO, KUN; ZHAI, RENYOU

    2016-01-01

    Endobiliary radiofrequency ablation (RFA) has recently been recognized as a beneficial treatment option for malignant biliary obstruction using percutaneous or endoscopic approaches. The feasibility and safety of this method has been demonstrated in clinical studies, with pain, cholangitis and asymptomatic biochemical pancreatitis reported as relatively common complications. By contrast, hepatic coma, newly diagnosed left bundle branch block and partial liver infarction have been reported as uncommon complications. Biliary tract perforation is a serious potential complication of percutaneous intraductal RFA, which may result in severe infection, peritonitis or even mortality, and which has not been previously reported in clinical research. The current study presents the first reports of biliary tract perforation in two patients with unresectable malignant biliary obstruction following percutaneous intraductal RFA. Although the patient in case 1 succumbed 12 days after RFA, the minor biliary tract perforation in case 2 was successfully treated by the deployment of a self-expanding metal stent. This study demonstrates that biliary tract perforation should be recognized as a serious potential complication of endobiliary RFA, and that metal stent deployment should be considered as a treatment option for minor biliary tract perforation. PMID:27313699

  19. Liver cyst with biliary communication successfully treated with laparoscopic deroofing: a case report.

    PubMed

    Yamada, Takeshi; Furukawa, Kiyonori; Yokoi, Kimiyoshi; Mamada, Yasuhiro; Kanazawa, Yoshikazu; Tajiri, Takashi

    2009-04-01

    A 56-year-old woman visited our hospital because of high fever and right hypochondralgia. Abdominal computed tomography showed a liver cyst 10 cm in diameter and dilatation of the intrahepatic bile duct. Percutaneous transhepatic drainage of the cyst guided by ultrasonography disclosed that the cyst contained a brown milky fluid, and cystography showed biliary communication. Thus, the cyst was diagnosed as an infectious hepatic cyst with biliary communication. Treatments for liver cysts include aspiration therapy, alcoholic sclerotherapy, laparoscopic fenestration, fenestration by laparotomy, cystojejunostomy, cystectomy, and hepatectomy. Because a simple liver cyst is benign, treatments should be low-risk and minimally invasive; thus, we performed laparoscopic fenestration. Fenestration should not be performed if the case is complicated by infection or biliary communication. Although cystography showed biliary communication, the cyst was not visualized with endoscopic retrograde cholangiography, and we concluded that the biliary communication was small. Operation time was 95 minutes, and blood loss was 10 g. Pathological findings of the liver cyst were consistent with a simple cyst. The postoperative course was good, and the patient left the hospital 10 days after the operation. Eighteen months have passed since the operation, and no recurrent cysts have been detected with computed tomography. This is the second report of liver cyst with biliary communication successfully treated with laparoscopic deroofing. Laparoscopic fenestration is a useful method for treating simple benign liver cysts because of its minimal invasiveness and may be useful in cases with small biliary communication.

  20. Prevention and acute management of biliary injuries during laparoscopic cholecystectomy: Expert consensus statement

    PubMed Central

    Abbasoğlu, Osman; Tekant, Yaman; Alper, Aydın; Aydın, Ünal; Balık, Ahmet; Bostancı, Birol; Coker, Ahmet; Doğanay, Mutlu; Gündoğdu, Haldun; Hamaloğlu, Erhan; Kapan, Metin; Karademir, Sedat; Karayalçın, Kaan; Kılıçturgay, Sadık; Şare, Mustafa; Tümer, Ali Rıza; Yağcı, Gökhan

    2016-01-01

    Gallstone disease is very common and laparoscopic cholecystectomy is one of the most common surgical procedures all over the world. Parallel to the increase in the number of laparoscopic cholecystectomies, bile duct injuries also increased. The reported incidence of bile duct injuries ranges from 0.3% to 1.4%. Many of the bile duct injuries during laparoscopic cholecystectomy are not due to inexperience, but are the result of basic technical failures and misinterpretations. A working group of expert hepatopancreatobiliary surgeons, an endoscopist, and a specialist of forensic medicine study searched and analyzed the publications on safe cholecystectomy and biliary injuries complicating laparoscopic cholecystectomy under the organization of Turkish Hepatopancreatobiliary Surgery Association. After a series of e-mail communications and two conferences, the expert panel developed consensus statements for safe cholecystectomy, management of biliary injuries and medicolegal issues. The panel concluded that iatrogenic biliary injury is an overwhelming complication of laparoscopic cholecystectomy and an important issue in malpractice claims. Misidentification of the biliary system is the major cause of biliary injuries. To avoid this, the “critical view of safety” technique should be employed in all the cases. If biliary injury is identified intraoperatively, reconstruction should only be performed by experienced hepatobiliary surgeons. In the postoperative period, any deviation from the expected clinical course of recovery should alert the surgeon about the possibility of biliary injury. PMID:28149133

  1. 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.

  2. Proposal of a new disease concept "biliary diseases with pancreatic counterparts". Anatomical and pathological bases.

    PubMed

    Nakanuma, Yasuni; Harada, Kenichi; Sasaki, Motoko; Sato, Yasunori

    2014-01-01

    The biliary tract and pancreas are located closely anatomically, and both develop from the endoderm foregut almost at the same time. Interestingly, the lining epithelia of the bile duct and main pancreatic duct show similar morphologies and phenotypes, and both are accompanied by periductal glands. Furthermore, the exocrine pancreatic acini are remnantly found in the peribiliary glands. Based on these findings, it seems plausible that the biliary tract has features of pancreatic elements in addition to the duct system, which is specialized for the drainage of bile secreted by hepatic parenchyma, particularly, hepatocytes. Interestingly, some pancreatic and biliary diseases show similar pathological features and even biological behaviors. For example, extrahepatic cholangiocarcinoma and ductal adenocarcinoma of the pancreas share many clinicopathological features. Both of them are hypothesized to arise from similar preneoplastic and early neoplastic intraepithelial lesions. Intraductal papillary tumors, with frequent mucin hyperproduction, develop in the pancreas (intraductal papillary mucinous neoplasm) and also in the biliary tract (intraductal papillary neoplasm of the bile duct). IgG4-related disease affects the biliary tract (IgG4-related sclerosing cholangitis) and the pancreas (autoimmune pancreatitis) in the same patients, with both showing similar morphologies. Herein, we propose that these non-neoplastic and neoplastic biliary diseases showing similarities to corresponding pancreatic diseases could be included in a new disease concept "biliary diseases with pancreatic counterparts". Based on this new concept, information obtained in biliary tract diseases could be applied to the analysis of pancreatic disease and vice versa, and also novel therapeutical strategies and molecular and genetic studies on pancreatic and biliary diseases may be developed with a unified approach.

  3. Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload

    SciTech Connect

    Gross, J.B. Jr.; Myers, B.M.; Kost, L.J.; Kuntz, S.M.; LaRusso, N.F.

    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 was 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.

  4. Palliation of Malignant Biliary and Duodenal Obstruction with Combined Metallic Stenting

    SciTech Connect

    Akinci, Devrim Akhan, Okan; Ozkan, Fuat; Ciftci, Turkmen; Ozkan, Orhan S.; Karcaaltincaba, Musturay; Ozmen, Mustafa N.

    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 stenting 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.

  5. [Technic, indications and contribution of choledochoscopy in the diagnosis and treatment of biliary diseases].

    PubMed

    Grigoriu, M; Palade, R; Vasile, D; Voiculescu, D; Roman, H

    2003-01-01

    Choledochoscopy it's a common method of intraoperative exploring of the extrahepatic biliary ducts and partially of the intrahepatic ones. He is used both in the open and laparoscopic surgery. We consider the operative cholangiogram, preferably transcystic, as a first step who precedes the endoscopic exploration. The transcystic choledochoscopy has specific and relatively narrow indications: undulated biliary ducts, 1-3 gallstones. The transcholedocian choledochoscopy permit a direct and complete exploration of the biliary ducts. The important diagnostic help that fibrocholedochoscopy gives in, it's accomplished by the possibility of therapeutic maneuvers (especially the gallstones extraction), which offers the quality of a miniinvasive, elegant and harmless treatment technique.

  6. Drug eluting biliary stents to decrease stent failure rates: A review of the literature

    PubMed Central

    Shatzel, Joseph; Kim, Jisoo; Sampath, Kartik; Syed, Sharjeel; Saad, Jennifer; Hussain, Zilla H; Mody, Kabir; Pipas, J Marc; Gordon, Stuart; Gardner, Timothy; Rothstein, Richard I

    2016-01-01

    Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy. PMID:26839648

  7. Tacrolimus Toxicity due to Biliary Obstruction in a Combined Kidney and Liver Transplant Recipient

    PubMed Central

    Burke, Michael T.; Francis, Ross S.

    2017-01-01

    The immunosuppressant tacrolimus has a narrow therapeutic window, necessitating therapeutic drug monitoring to maintain efficacy and minimise toxicity. There are very few reports examining the impact of impaired biliary excretion on tacrolimus blood levels or toxicity. We report the case of a 26-year-old combined liver and kidney transplant recipient, who developed acute biliary obstruction leading to tacrolimus toxicity with very high blood tacrolimus levels. Despite a careful evaluation, no alternative cause was found for her acute kidney injury, and her kidney function returned to previous baseline within several days following treatment of the biliary obstruction and temporary withdrawal of tacrolimus. PMID:28163950

  8. Utility of Stent-Grafts in Treatment of Porto-Biliary Fistula

    SciTech Connect

    Peynircioglu, Bora; Cwikiel, Wojciech

    2006-12-15

    A porto-biliary fistula causing hemobilia is a known complication of percutaneous transhepatic biliary drainage (PTBD). We present two patients with hemobilia secondary to porto-biliary fistula, treated successfully by percutaneous placement of stent-grafts. In one case, the stent-graft was placed in the bile duct, and in the other case, it was placed in the intrahepatic portal vein branch. Hemobilia stopped and there were no complications except a small area of hepatic infarction, distal to the stent-graft in the portal vein.

  9. Excretion of caffeine and its primary degradation products into bile.

    PubMed

    Holstege, A; Kurz, M; Weinbeck, M; Gerok, W

    1993-01-01

    Caffeine, widely consumed in beverages, is known to alter several biliary parameters that can affect gallstone pathogenesis. To address the question whether methylxanthines can act on the luminal side of biliary epithelial cells, we measured caffeine and its primary demethylation products in human bile. Eight patients had an external biliary drainage due to bile duct or gallbladder disease. Two of the patients suffered from histologically confirmed liver cirrhosis. The levels of caffeine, paraxanthine, theobromine, and theophylline were monitored over 10 h in plasma and bile before and after a prior oral dose of caffeine (5 mg/kg b. wt.). Methylxanthines were enriched by an organic extraction procedure and separated by reversed-phase high-performance liquid chromatography. Time-concentration curves in bile paralleled the time-course of methylxanthine levels in blood plasma. Accordingly, values in bile and blood plasma were highly correlated for each methylxanthine measured. Within 1 h after the oral test dose, peak levels of caffeine were obtained in both fluids. Biliary concentrations were either almost equal (caffeine) or lower (dimethylxanthines) than their respective values in blood plasma. The results of our study indicate that minor amounts of caffeine and its primary degradation products are excreted via the bile allowing local interference with epithelial cell metabolism of bile ducts and gallbladder.

  10. Successful Treatment with a Covered Stent and 6-Year Follow-Up of Biliary Complication After Liver Transplantation

    SciTech Connect

    Doros, Attila Nemeth, Andrea; Deak, Akos Pal; Hartmann, Erika; Gerlei, Zsuzsa; Fazakas, Janos; Kobori, Laszlo

    2010-04-15

    The role of covered stent in the management of biliary complications is not yet defined in liver transplant recipients. This Case Report presents a patient with anastomotic stricture and leakage with biloma treated with a covered stent 32 months following liver transplantation. Signs of in-stent restenosis developed 52 months following covered stent placement, which was resolved by balloon dilation. There were no complications during the interventions. The latest follow-up, at 69 months following primary and 19 months following secondary percutaneous intervention, shows a patent covered stent without any clinical or morphological sign of further restenosis. The clinical success with long-term follow-up data suggests that covered stent implantation can be a rational, minimally invasive option for simultaneous treatment of bile duct stenosis and bile leak following liver transplantation in selected cases.

  11. Hepatic progenitor cells of biliary origin with liver repopulation capacity

    PubMed Central

    Boulter, Luke; Tsuchiya, Atsunori; Cole, Alicia M; Hay, Trevor; Guest, Rachel V; Wojtacha, Davina; Man, Tak Yung; Mackinnon, Alison; Ridgway, Rachel A; Kendall, Timothy; Williams, Michael J; Jamieson, Thomas; Raven, Alex; Hay, David C; Iredale, John P; Clarke, Alan R; Sansom, Owen J; Forbes, Stuart J

    2015-01-01

    Summary Hepatocytes and cholangiocytes self renew following liver injury. Following severe injury hepatocytes are increasingly senescent, whether Hepatic Progenitor Cells (HPCs) then contribute to liver regeneration is unclear. Here, we describe a mouse model where Mdm2 is inducibly deleted in over 98% of hepatocytes, causing apoptosis, necrosis and senescence with nearly all hepatocytes expressing p21. This results in florid HPC activation, which is necessary for survival, followed by complete, functional liver reconstitution. HPCs isolated from genetically normal mice, using cell surface markers, were highly expandable and phenotypically stable in vitro. These HPCs were transplanted into adult mouse livers where hepatocyte Mdm2 was repeatedly deleted, creating a non-competitive repopulation assay. Transplanted HPCs contributed significantly to restoration of liver parenchyma, regenerating hepatocytes and biliary epithelia, highlighting their in vivo lineage potency. HPCs are therefore a potential future alternative to hepatocyte or liver transplantation for liver disease. PMID:26192438

  12. An adipo-biliary-uridine axis that regulates energy homeostasis.

    PubMed

    Deng, Yingfeng; Wang, Zhao V; Gordillo, Ruth; An, Yu; Zhang, Chen; Liang, Qiren; Yoshino, Jun; Cautivo, Kelly M; De Brabander, Jef; Elmquist, Joel K; Horton, Jay D; Hill, Joseph A; Klein, Samuel; Scherer, Philipp E

    2017-03-17

    Uridine, a pyrimidine nucleoside present at high levels in the plasma of rodents and humans, is critical for RNA synthesis, glycogen deposition, and many other essential cellular processes. It also contributes to systemic metabolism, but the underlying mechanisms remain unclear. We found that plasma uridine levels are regulated by fasting and refeeding in mice, rats, and humans. Fasting increases plasma uridine levels, and this increase relies largely on adipocytes. In contrast, refeeding reduces plasma uridine levels through biliary clearance. Elevation of plasma uridine is required for the drop in body temperature that occurs during fasting. Further, feeding-induced clearance of plasma uridine improves glucose metabolism. We also present findings that implicate leptin signaling in uridine homeostasis and consequent metabolic control and thermoregulation. Our results indicate that plasma uridine governs energy homeostasis and thermoregulation in a mechanism involving adipocyte-dependent uridine biosynthesis and leptin signaling.

  13. Targeted therapy in biliary tract cancer: 2009 update.

    PubMed

    Tonini, Giuseppe; Virzì, Vladimir; Fratto, Maria Elisabetta; Vincenzi, Bruno; Santini, Daniele

    2009-12-01

    Biliary tract cancers (BTCs) include cholangiocarcinoma (intrahepatic, perihilar and extrahepatic), carcinoma of the gall bladder and ampullary carcinoma. In patients with advanced disease the prognosis is poor. There is not a consensus regarding treatment strategy. Chemotherapy has only limited efficacy. This review summarizes the new approaches for BTC patients and the rationale for targeted therapies. The prognostic factors and the molecular features of BTC are analyzed. The clinical trials evaluating the targeted agents are accurately described, especially those assessing the role of anti-EGFR and antiangiogenic drugs. The ongoing trials are also analyzed. In fact, only the results of these trials will establish which is the most effective agent or combination for this setting.

  14. Biliary Secretion of Quasi-Enveloped Human Hepatitis A Virus

    PubMed Central

    Hirai-Yuki, Asuka; Hensley, Lucinda; Whitmire, Jason K.

    2016-01-01

    ABSTRACT Hepatitis A virus (HAV) is an unusual picornavirus that is released from cells cloaked in host-derived membranes. These quasi-enveloped virions (eHAV) are the only particle type circulating in blood during infection, whereas only nonenveloped virions are shed in feces. The reason for this is uncertain. Hepatocytes, the only cell type known to support HAV replication in vivo, are highly polarized epithelial cells with basolateral membranes facing onto hepatic (blood) sinusoids and apical membranes abutting biliary canaliculi from which bile is secreted to the gut. To assess whether eHAV and nonenveloped virus egress from cells via vectorially distinct pathways, we studied infected polarized cultures of Caco-2 and HepG2-N6 cells. Most (>99%) progeny virions were released apically from Caco-2 cells, whereas basolateral (64%) versus apical (36%) release was more balanced with HepG2-N6 cells. Both apically and basolaterally released virions were predominantly enveloped, with no suggestion of differential vectorial release of eHAV versus naked virions. Basolateral to apical transcytosis of either particle type was minimal (<0.02%/h) in HepG2-N6 cells, arguing against this as a mechanism for differences in membrane envelopment of serum versus fecal virus. High concentrations of human bile acids converted eHAV to nonenveloped virions, whereas virus present in bile from HAV-infected Ifnar1−/− Ifngr1−/− and Mavs−/− mice banded over a range of densities extending from that of eHAV to that of nonenveloped virions. We conclude that nonenveloped virions shed in feces are derived from eHAV released across the canalicular membrane and stripped of membranes by the detergent action of bile acids within the proximal biliary canaliculus. PMID:27923925

  15. Early nasoduodenal feeding for the post-biliary surgical patient.

    PubMed

    Hwang, T L; Huang, S L; Chen, M F

    1991-10-01

    The effects of early postoperative nasoduodenal feeding on nutrition and metabolic response were studied using 24 patients after biliary surgery. The patients were randomly divided into two groups with 12 in each group. Group I was fed via a nasoduodenal tube from the first postoperative day but control group II was not fed until the fourth postoperative day. The hospital blenderized tube feeding diet provided the enteric nutrition (17% protein, 33% fat and 50% carbohydrate). The nutritional status of the 2 groups was compared over a one week period. The changes in nitrogen balance were measured daily for 8 days. The group fed early had a significantly reduced negative nitrogen balance when compared to the group whose feeding was started later. (-1.91 +/- 1.05 g/day vs -5.84 +/- 0.48 g/day). There was no difference in serum albumin and transferrin levels, but serum prealbumin levels in the group fed early were more desirable than those of the control group (from 15.8 +/- 2.5 mg/dl to 28.9 +/- 3.8 mg/dl vs from 18.0 +/- 2.0 mg/dl to 25.9 +/- 3.9 mg/dl). Total lymphocyte count was also better in the group fed early than in the controls (from 1,325 +/- 204 cells/mm3 to 2,655 +/- 584 cells/mm3 vs from 1,277 +/- 188 cells/mm3 to 1,877 +/- 440 cells/mm3). All the patients in group I felt better than those in group II during the study course. These results indicated that those patients provided with early nasoduodenal feeding after a biliary operation displayed a better nitrogen balance, and a faster increase in short half life visceral protein and total lymphocyte count.

  16. The extended Kasai portoenterostomy for biliary atresia: A preliminary report

    PubMed Central

    Ramachandran, Priya; Safwan, Mohamed; Srinivas, Sankaranarayanan; Shanmugam, Naresh; Vij, Mukul; Rela, Mohamed

    2016-01-01

    Aims: In 1955, Professor Morio Kasai first performed a hepatic portoenterostomy. Since then, the procedure has changed the lives of children with biliary atresia (BA). We report our initial experience in performing “extended” Kasai portoenterostomy (KPE), a modification of the original procedure. Materials and Methods: Since 2013, we have used the technique of “extended KPE” and prospectively recorded data on all children undergoing this operation. Data on demographics, clinical features, liver function tests, and perioperative cholangiogram findings were collected. Outcome of KPE was measured by Jaundice Disappearance Rate (JDR) and Native Liver Survival Rate (NLSR). We present our preliminary results from a 30-month period (February 2013 to May 2015). Results: Thirty-one children underwent KPE during this period (19 males) and only 1 child had biliary atresia splenic malformation (BASM). The mean age at KPE was 73 ± 24 days. Five (16.1%) children were more than 90 days old at the time of KPE. Fourteen children cleared jaundice (JDR 45.2%). Eleven (35.5%) children developed episodes of cholangitis, of whom 8 had early cholangitis (within 3 months of the operation). The proportion of children who survived with their own liver 6 months after KPE (NLSR) was 84.2%. Of those children older than 90 days, 2 cleared jaundice and have survived with their native livers for more than 16 months. Conclusion: In our preliminary report of 31 children, we conclude that the extended KPE leads to increased jaundice clearance and improved NLSR in children with BA. PMID:27046977

  17. The Emerging Role of miRNAs and Their Clinical Implication in Biliary Tract Cancer

    PubMed Central

    Ferreira Martins, Nina Nayara; da Silva Oliveira, Kelly Cristina; Braga Bona, Amanda; de Arruda Cardoso Smith, Marília; Ishak, Geraldo; Assumpção, Paulo Pimentel; Burbano, Rommel Rodríguez

    2016-01-01

    Biliary tract cancers are aggressive malignancies that include gallbladder cancer and tumors of intra- and extrahepatic ducts and have a poor prognosis. Surgical resection remains the main curative therapy. Nevertheless, numerous patients experience recurrence even after radical surgery. This scenario drives the research to identify biliary tract cancer biomarkers despite the limited progress that has been made. Recently, a large number of studies have demonstrated that deregulated expression of microRNAs is closely associated with cancer development and progression. In this review, we highlight the role and importance of microRNAs in biliary tract cancers with an emphasis on utilizing circulating microRNAs as potential biomarkers. Additionally, we report several single-nucleotide polymorphisms in microRNA genes that are associated with the susceptibility of biliary tract tumors. PMID:28115929

  18. Biliary reconstruction in living donor liver transplantation with dye injection leakage test and without stent use.

    PubMed

    Ikegami, T; Nishizaki, T; Kishikawa, K; Nomoto, K; Uchiyama, H; Ohta, R; Hiroshige, S; Sugimachi, K

    2001-01-01

    Biliary complication remains a significant source of morbidity and mortality in living donor liver transplantation. From October 1996 to December 1999, 34 patients underwent 35 living donor liver transplantations at Kyushu University Hospital. In the initial twenty cases, anastomotic internal stents were placed. In the most recent fifteen cases, no internal stent was inserted and routine postreconstruction dye injection leakage tests were administered. In recipient biliary reconstruction, hepaticojejunostomy was performed using interrupted sutures without an anastomotic stent. After an intestinal clamp was applied at the anal side of the hepaticojejunostomy, leakage test was done using diluted indigocarmine solution injected into the jejunal loop lumen. Two (13%) of the fifteen recent patients suffered from biliary complications, whereas eight patients (40%) from the former twenty patients suffered from biliary complications. We conclude that the use of the stent was not useful, but the application of the dye injection leakage test was useful.

  19. The Emerging Role of miRNAs and Their Clinical Implication in Biliary Tract Cancer.

    PubMed

    Ferreira Martins, Nina Nayara; da Silva Oliveira, Kelly Cristina; Braga Bona, Amanda; de Arruda Cardoso Smith, Marília; Ishak, Geraldo; Assumpção, Paulo Pimentel; Burbano, Rommel Rodríguez; Calcagno, Danielle Queiroz

    2016-01-01

    Biliary tract cancers are aggressive malignancies that include gallbladder cancer and tumors of intra- and extrahepatic ducts and have a poor prognosis. Surgical resection remains the main curative therapy. Nevertheless, numerous patients experience recurrence even after radical surgery. This scenario drives the research to identify biliary tract cancer biomarkers despite the limited progress that has been made. Recently, a large number of studies have demonstrated that deregulated expression of microRNAs is closely associated with cancer development and progression. In this review, we highlight the role and importance of microRNAs in biliary tract cancers with an emphasis on utilizing circulating microRNAs as potential biomarkers. Additionally, we report several single-nucleotide polymorphisms in microRNA genes that are associated with the susceptibility of biliary tract tumors.

  20. A new method for treating carcinomatous biliary obstruction with intracatheter radium

    SciTech Connect

    Conroy, R.M.; Shahbazian, A.A.; Edwards, K.C.; Moran, E.M.; Swingle, K.F.; Lewis, G.J.; Pribram, H.F.

    1982-04-01

    We describe a new method for relieving biliary obstruction due to malignant solid tumors. The method consists of placement of radium needles in a Ring biliary drainage catheter for three days. After removing the radium needles, the catheter is left in place to allow for repair of irradiated tissues, then it is removed. The object is to leave the patient with a patent biliary tree without a biliary drainage prosthesis. The clinical course of six patients treated by this method is described, and the autopsy findings in three cases are outlined. Three patients died with a serum total bilirubin ranging from 1--4.5 mg/100 ml, two to three months after removing the drainage catheter. Two patients died before the bile drainage catheter could be removed. One patient is alive with a bile drainage catheter in place. Possible modifications in technique and catheters are being considered.

  1. [The surgical treatment of hepatic echinococcosis and of its biliary complications].

    PubMed

    Agnifili, A; Gola, P; Ibi, I; Verzaro, R; Carducci, G; Marino, M; Gianfelice, F; De Bernardinis, G

    1993-09-30

    The authors report the experience of 47 patients submitted to surgery for hepatic hydatidosis. Results from different therapeutic procedures are then compared. Finally, possible biliary complications of the hepatic echinococcosis and their surgical treatment are discussed.

  2. Surgical treatment of incarcerated calculi via laparoscopic bile duct exploration using laparotomy biliary lithotomy forceps

    PubMed Central

    Jiang, H.; Wang, S. Y.; Jin, X. L.; Jin, J. C.; Gu, H. B.; Zhang, F. M.

    2016-01-01

    The present study aimed to investigate the practicability and clinical value of applying laparotomy biliary lithotomy forceps to laparoscopic bile duct exploration (LCBDE) for the surgical treatment of incarcerated calculi. A total of 63 patients were diagnosed with cholecystolithiasis and choledocholithiasis. The present study performed a retrospective analysis of clinical samples from 16 of these patients who had incarcerated calculi at the terminus of the common bile duct, and who had been treated with laparoscopic cholecystectomy and LCBDE. During the procedure, laparotomy biliary lithotomy forceps were used to gently remove the calculi from the common bile duct. Of the surgical procedures that used laparotomy biliary lithotomy forceps, one case was unsuccessful and 15 cases were successful. The results of the present study suggested that it may be clinically advisable to use laparotomy biliary lithotomy forceps to remove incarcerated calculi from the common bile duct during a laparoscopy, since it is easy, economical and effective. PMID:27698730

  3. [COMPARATIVE CHARACTERISTIC OF VARIOUS METHODS OF SIMULATION OF BILIARY PERITONITIS IN EXPERIMENT].

    PubMed

    Nichitaylo, M Yu; Furmanov, Yu O; Gutsulyak, A I; Savytska, I M; Zagriychuk, M S; Goman, A V

    2016-02-01

    In experiment on rabbits a comparative analysis of various methods of a biliary peritonitis simulation was conducted. In 6 animals a biliary peritonitis was simulated, using perforation of a gallbladder, local serous-fibrinous peritonitis have occurred in 50% of them. In 7 animals biliary peritonitis was simulated, applying intraabdominal injection of medical sterile bile in a 5-40 ml volume. Diffuse peritonitis with exudates and stratification of fibrin was absent. Most effective method have appeared that, when intraabdominal injection of bile was done together with E. coli culture in the rate of 0.33 microbal bodies McF (1.0 x 10(8) CFU/ml) on 1 kg of the animal body mass. Diffuse biliary peritonitis have occurred in all 23 animals, including serous-fibrinous one--in 17 (76%), and purulent-fibrinous--in 6 (24%).

  4. A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver

    PubMed Central

    Viil, Janeli; Klaas, Mariliis; Valter, Kadri; Belitškin, Denis; Ilmjärv, Sten; Jaks, Viljar

    2017-01-01

    Cells with slow proliferation kinetics that retain the nuclear label over long time periods–the label-retaining cells (LRCs)–represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in normal non-injured livers and characterized their regenerative properties in vivo and in culture. We found that LLRCs were located in biliary vessels and participated in the regeneration of biliary but not hepatocyte injury. In culture experiments the sorted LLRCs displayed an enhanced self-renewal capacity but a unipotent biliary differentiation potential. Transcriptome analysis revealed a unique set of tumorigenesis- and nervous system-related genes upregulated in LLRCs when compared to non-LRC cholangiocytes. We conclude that the LLRCs established during the normal morphogenesis of the liver do not represent a multipotent primitive somatic stem cell population but act as unipotent biliary progenitor cells. PMID:28084309

  5. Intrahepatic biliary dilatation caused by a small simple hepatic cyst: report of a case.

    PubMed

    Naitoh, Hiroshi; Fukasawa, Takaharu; Fukuchi, Minoru; Kiriyama, Shinsuke; Tabe, Yuichi; Yamauchi, Hayato; Suzuki, Masaki; Yoshida, Tomonori; Sakurai, Shinji; Kuwano, Hiroyuki

    2014-01-01

    Biliary obstruction caused by small simple cysts is very rare. We present a case of biliary dilatation caused by a simple cyst with a 4-cm diameter. The patient was a 75-year-old woman referred to our hospital for evaluation of a cystic tumor associated with peripheral biliary duct dilatation in the left segment of the liver. Computed tomography and magnetic resonance imaging showed that the cyst probably communicated with the intrahepatic bile duct. Malignant tumors, including intrahepatic papillary neoplasms of the bile duct, could not be ruled out; therefore, we performed surgery with the patient's consent. Histopathologic examination of the resected liver showed that the cystic lesion was a simple cyst. The finding that even small simple cysts can obstruct the biliary tract is important for the management of cystic lesions of the liver.

  6. Idiopathic cholangiopathy in a biliary cast syndrome necessitating liver transplantation following head trauma.

    PubMed

    Byrne, Michael F; Chong, Hon I; O'Donovan, Deidre; Sheehan, Katherine M; Leader, Mary B; Kay, Elaine; McCormick, P Aiden; Broe, Patrick; Murray, Frank E; McCormack, Aiden

    2003-04-01

    The development of total biliary casts is very unusual, especially in patients who have not undergone liver transplantation. The aetiology of these casts is uncertain but several factors are believed to play a role, including periods of fasting, haemolysis, cholangitis and recent surgery. Resultant bile stasis and/or gallbladder hypocontractility promote sludge and subsequent stone formation. Here we present the case of a previously well 66-year-old woman who developed a total biliary cast several weeks after being involved in a road traffic accident during which she sustained head injuries but no obvious liver insult. This cast was removed at laparotomy but the patient had resultant diffuse biliary tree abnormalities and persistent cholestasis and subsequently required a liver transplant. The possible aetiologies of biliary cast formation and subsequently cholangiopathy necessitating transplantation in this patient are described.

  7. Partial internal biliary diversion: a solution for intractable pruritus in progressive familial intrahepatic cholestasis type 1.

    PubMed

    Ganesh, Ramaswamy; Suresh, Natarajan; Sathiyasekeran, Malathi; Ramachandran, Priya

    2011-01-01

    Biliary diversion offers a potential option for intractable pruritus in children with chronic cholestatic disorders. Progressive familial intrahepatic cholestasis (PFIC) is an inherited disorder of impaired bile acid transport and excretion, which presents with jaundice and pruritus in the first few months of life and progresses to cirrhosis by infancy or adolescence. We report a child with PFIC type 1 who underwent internal biliary diversion for intractable pruritus and was relieved of his symptoms.

  8. Percutaneous transhepatic biliary drainage in an infant with obstructive jaundice caused by neuroblastoma.

    PubMed

    Saettini, Francesco; Agazzi, Roberto; Giraldi, Eugenia; Foglia, Carlo; Cavalleri, Laura; Morali, Laura; Fasolini, Giorgio; Spotti, Angelica; Provenzi, Massimo

    2015-04-01

    Neuroblastoma presenting with obstructive jaundice is a rare event. Management of this condition includes surgery, chemotherapy, radiotherapy, temporary cholecystostomy tube, endoscopic retrograde cholangiopancreatography (ERCP), and internal biliary drainage (IBD). We herein describe our experience with one infant affected by neuroblastoma presenting with jaundice, who successfully underwent percutaneous transhepatic biliary drainage (PTBD). This report introduces PTBD as a viable treatment option for neuroblastoma and obstructive jaundice and provides a review of the pertinent literature.

  9. [Imbalance of microelements and vitamins in adolescents with diffuse nontoxic goiter and biliary dyskinesia].

    PubMed

    Plekhova, E I; Kashkalda, D A; Volkova, Iu V; Turchina, S I; Kosovtsova, A V; Kostenko, T P

    2014-11-01

    The purpose of the present work was to study the level of microelements and vitamins in adolescents with diffuse nontoxic goiter. It has been shown that comorbid biliary dyskinesia leads to significant dysregulation of vitamin and mineral metabolism: the level of essential elements was decreased and the level of toxic elements was increased. Comorbid biliary dyskinesia in adolescents with diffuse nontoxic goiter was accompanied by a disbalance of vitamins. The changes found in micronutrients have sex differences.

  10. Biliary excretion of diazepam in rats: influence of the route of administration and dosage.

    PubMed

    Phillips, R; Plaa, G L

    1981-01-01

    The biliary excretion of diazepam metabolites was found in rats. Equivalent dosages of diazepam were administered orally and intraperitoneally. The biliary excretion was dose-dependent and was greater following intraperitoneal administration. After intravenous administration, a greater percentage of the diazepam dosage administered was excreted into the bile. Repetitive intravenous administrations yielded results which approached those observed after intraperitoneally administered dosages given as a bolus.

  11. Diagnostic Value of Ultrasound in Detection of Biliary Tract Complications After Liver Transplantation

    PubMed Central

    Potthoff, Andrej; Hahn, Anreas; Kubicka, Stefan; Schneider, Andrea; Wedemeyer, Jochen; Klempnauer, Juergen; Manns, Michael; Gebel, Michael; Boozari, Bita

    2013-01-01

    Background Biliary complications are significant source of morbidity after liver transplantation (LT). Cholangiography is the gold standard for diagnosis and specification of biliary complications. Objectives Detailed analyses of ultrasound (US) as a safe imaging method in this regard are still lacking. Therefore we analyzed systematically the diagnostic value of US in these patients. Patients and Methods Retrospectively, 128 liver graft recipients and their clinical data were analyzed. All patients had a standardized US examination. The findings of US were compared to cholangiographic results in 42 patients. Following statistical analyses were performed: descriptive statistics, sensitivity, specificity, positive and negative predictive values (PPV, NPV). Results 42 patients had 54 different biliary complications (Anastomotic stenosis (AS) n = 33, ischemic type biliary lesions (ITBL) n = 18 and leakage n = 3). US detected n = 22/42 (52%) patients with biliary complications. The sensitivity, specificity, PPV and NPV of US were: 61%, 100%, 100%, 79% (95CI, 36-86%) for ITBL and 24%, 100, 100%, 31% (95CI, 9-46 %) for AS, respectively. Conclusions US examination had no false positive rate. Therefore, it may be helpful as a first screening modality. But for the direct diagnosis of the biliary complication US is not sensitive enough. PMID:23483295

  12. Effects of a hypercholesterolaemia-inducing diet on biliary electrolytes and lipid secretion in the rat.

    PubMed Central

    Monte, M. J.; Jimenez, R.

    1993-01-01

    The effects of a high cholesterol/cholate diet on the biliary secretion of bile acids, cholesterol, phospholipid and inorganic electrolytes in the rat were examined. Wistar rats were fed a hypercholesterolaemia-inducing diet (HID) for 20 days prior to the biliary experiments. Rats fed a standard laboratory diet were used as controls. The HID diet increased plasma cholesterol concentrations and the hepatic content of total, free and esterified cholesterol, without changes in ALP*, ALT and AST plasma activities. Bile flow and biliary secretion of bile acids and inorganic electrolytes were markedly increased in the hypercholesterolaemic animals. The stimulated biliary secretion was due to an increase in both the bile acid-dependent and bile acid-independent fractions of bile flow. An increase in the bile acid pool induced by the administration of exogenous cholic acid/cholesterol would account for these changes in bile flow and inorganic electrolyte secretion. Nevertheless, the increase in the bile acid-independent bile flow could be also related, at least to some extent, to a higher efficiency of bicarbonate transport into bile. The HID diet also increased both cholesterol and phospholipid biliary outputs, whereas it did not modify the relationship between lipid and bile acid secretion. The lithogenic index of bile was reduced in the rats after the HID regimen due to a relatively higher increase in the biliary outputs of phospholipids and bile acids than of cholesterol. PMID:8499321

  13. Predicting when biliary excretion of parent drug is a major route of elimination in humans.

    PubMed

    Hosey, Chelsea M; Broccatelli, Fabio; Benet, Leslie Z

    2014-09-01

    Biliary excretion is an important route of elimination for many drugs, yet measuring the extent of biliary elimination is difficult, invasive, and variable. Biliary elimination has been quantified for few drugs with a limited number of subjects, who are often diseased patients. An accurate prediction of which drugs or new molecular entities are significantly eliminated in the bile may predict potential drug-drug interactions, pharmacokinetics, and toxicities. The Biopharmaceutics Drug Disposition Classification System (BDDCS) characterizes significant routes of drug elimination, identifies potential transporter effects, and is useful in understanding drug-drug interactions. Class 1 and 2 drugs are primarily eliminated in humans via metabolism and will not exhibit significant biliary excretion of parent compound. In contrast, class 3 and 4 drugs are primarily excreted unchanged in the urine or bile. Here, we characterize the significant elimination route of 105 orally administered class 3 and 4 drugs. We introduce and validate a novel model, predicting significant biliary elimination using a simple classification scheme. The model is accurate for 83% of 30 drugs collected after model development. The model corroborates the observation that biliarily eliminated drugs have high molecular weights, while demonstrating the necessity of considering route of administration and extent of metabolism when predicting biliary excretion. Interestingly, a predictor of potential metabolism significantly improves predictions of major elimination routes of poorly metabolized drugs. This model successfully predicts the major elimination route for poorly permeable/poorly metabolized drugs and may be applied prior to human dosing.

  14. Percutaneous Intraductal Radiofrequency Ablation is a Safe Treatment for Malignant Biliary Obstruction: Feasibility and Early Results

    SciTech Connect

    Mizandari, Malkhaz; Pai, Madhava Xi Feng; Valek, Vlastimil; Tomas, Andrasina; Quaretti, Pietro; Golfieri, Rita; Mosconi, Cristina; Ao Guokun; Kyriakides, Charis; Dickinson, Robert; Nicholls, Joanna; Habib, Nagy

    2013-06-15

    Purpose. Previous clinical studies have shown the safety and efficacy of this novel radiofrequency ablation catheter when used for endoscopic palliative procedures. We report a retrospective study with the results of first in man percutaneous intraductal radiofrequency ablation in patients with malignant biliary obstruction. Methods. Thirty-nine patients with inoperable malignant biliary obstruction were included. These patients underwent intraductal biliary radiofrequency ablation of their malignant biliary strictures following external biliary decompression with an internal-external biliary drainage. Following ablation, they had a metal stent inserted. Results. Following this intervention, there were no 30-day mortality, hemorrhage, bile duct perforation, bile leak, or pancreatitis. Of the 39 patients, 28 are alive and 10 patients are dead with a median survival of 89.5 (range 14-260) days and median stent patency of 84.5 (range 14-260) days. One patient was lost to follow-up. All but one patient had their stent patent at the time of last follow-up or death. One patient with stent blockage at 42 days postprocedure underwent percutaneous transhepatic drain insertion and restenting. Among the patients who are alive (n = 28) the median stent patency was 92 (range 14-260) days, whereas the patients who died (n = 10) had a median stent patency of 62.5 (range 38-210) days. Conclusions. In this group of patients, it appears that this new approach is feasible and safe. Efficacy remains to be proven in future, randomized, prospective studies.

  15. Eosinophilic cholangitis is a potentially underdiagnosed etiology in indeterminate biliary stricture

    PubMed Central

    Walter, Dirk; Hartmann, Sylvia; Herrmann, Eva; Peveling-Oberhag, Jan; Bechstein, Wolf O; Zeuzem, Stefan; Hansmann, Martin-Leo; Friedrich-Rust, Mireen; Albert, Jörg G

    2017-01-01

    AIM To investigate presence and extent of eosinophilic cholangitis (EC) as well as IgG4-related disease in patients with indeterminate biliary stricture (IBS). METHODS All patients with diagnosis of sclerosing cholangitis (SC) and histopathological samples such as biopsies or surgical specimens at University Hospital Frankfurt from 2005-2015 were included. Histopathological diagnoses as well as further clinical course were reviewed. Tissue samples of patients without definite diagnosis after complete diagnostic work-up were reviewed regarding presence of eosinophilic infiltration and IgG4 positive plasma cells. Eosinophilic infiltration was as well assessed in a control group of liver transplant donors and patients with primary sclerosing cholangitis. RESULTS one hundred and thirty-five patients with SC were included. In 10/135 (13.5%) patients, no potential cause of IBS could be identified after complete diagnostic work-up and further clinical course. After histopathological review, a post-hoc diagnosis of EC was established in three patients resulting in a prevalence of 2.2% (3/135) of all patients with SC as well as 30% (3/10) of patients, where no cause of IBS was identified. 2/3 patients with post-hoc diagnosis of EC underwent surgical resection with suspicion for malignancy. Diagnosis of IgG4-related cholangitis was observed in 7/135 patients (5.1%), whereas 3 cases were discovered in post-hoc analysis. 6/7 cases with IgG4-related cholangitis (85.7%) presented with eosinophilic infiltration in addition to IgG4 positive plasma cells. There was no patient with eosinophilic infiltration in the control group of liver transplant donors (n = 27) and patients with primary sclerosing cholangitis (n = 14). CONCLUSION EC is an underdiagnosed benign etiology of SC and IBS, which has to be considered in differential diagnosis of IBS. PMID:28246478

  16. Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer: A Systematic Review.

    PubMed

    Park, Joon Oh; Oh, Do-Youn; Hsu, Chiun; Chen, Jen-Shi; Chen, Li-Tzong; Orlando, Mauro; Kim, Jong Seok; Lim, Ho Yeong

    2015-07-01

    Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin.

  17. Endoscopic Ultrasound Guided Rendezvous Drainage of Biliary Obstruction Using a New Flexible 19-Gauge Fine Needle Aspiration Needle

    PubMed Central

    Tang, Zhouwen; Igbinomwanhia, Efehi; Elhanafi, Sherif

    2016-01-01

    Background and Aim. A successful endoscopic ultrasound guided rendezvous (EUS-RV) biliary drainage is dependent on accurate puncture of the bile duct and precise guide wire manipulation across the ampulla of Vater. We aim to study the feasibility of using a flexible 19-gauge fine aspiration needle in the performance of EUS-RV biliary drainage. Method. This is a retrospective case series of EUS-RV biliary drainage procedures at a single center. Patients who failed ERCP during the same session for benign or malignant biliary obstruction underwent EUS-RV using a flexible, nitinol covered, 19-gauge needle for biliary access and guide wire manipulation. Result. 24 patients underwent EUS-RV biliary drainage via extrahepatic access while 1 attempt was via intrahepatic access. The technical success rate was 80%, including 83.3% of cases via extrahepatic access. There was no significant difference in success rate of inpatient and outpatient procedures, benign or malignant indications, or type of guide wire used. Adverse events included mild pancreatitis (3 patients) and cholangitis (1 patient). Conclusion. A flexible 19-gauge needle for biliary access can be safe and effective when used to perform EUS-RV biliary drainage. Direct comparison between the nitinol needle and conventional metal needles in the performance of EUS guided biliary drainage is needed. PMID:27822005

  18. The Biliary Epithelium Gives Rise to Liver Progenitor Cells

    PubMed Central

    Rodrigo-Torres, Daniel; Affò, Silvia; Coll, Mar; Morales-Ibanez, Oriol; Millán, Cristina; Blaya, Delia; Alvarez-Guaita, Anna; Rentero, Carles; José Lozano, Juan; Maestro, Miguel Angel; Solar, Myriam; Arroyo, Vicente; Caballería, Joan; van Grunsven, Leo A.; Enrich, Carlos; Ginès, Pere; Bataller, Ramon; Sancho-Bru, Pau

    2015-01-01

    Severe liver diseases are characterized by expansion of liver progenitor cells (LPC), which correlates with disease severity. However, the origin and role of LPC in liver physiology and in hepatic injury remains a contentious topic. We found that ductular reaction cells in human cirrhotic livers express hepatocyte nuclear factor 1 homeobox B (HNF1β). However, HNF1β expression was not present in newly generated epithelial cell adhesion molecule (EpCAM)-positive hepatocytes. In order to investigate the role of HNF1β- expressing cells we used a tamoxifen-inducible Hnf1βCreER/R26RYfp/LacZ mouse to lineage-trace Hnf1β+ biliary duct cells and to assess their contribution to LPC expansion and hepatocyte generation. Lineage tracing demonstrated no contribution of HNF1β+ cells to hepatocytes during liver homeostasis in healthy mice or after loss of liver mass. After acute acetaminophen or carbon tetrachloride injury no contribution of HNF1β+ cells to hepatocyte was detected. We next assessed the contribution of Hnf1β+ -derived cells following two liver injury models with LPC expansion, a diethoxycarbonyl-1,4-dihydrocollidin (DDC)-diet and a choline-deficient ethionine-supplemented (CDE)-diet. The contribution of Hnf1β+ cells to liver regeneration was dependent on the liver injury model. While no contribution was observed after DDC-diet treatment, mice fed with a CDE-diet showed a small population of hepatocytes derived from Hnf1β+ cells that were expanded to 1.86% of total hepatocytes after injury recovery. Genome-wide expression profile of Hnf1β+ -derived cells from the DDC and CDE models indicated that no contribution of LPC to hepatocytes was associated with LPC expression of genes related to telomere maintenance, inflammation, and chemokine signaling pathways. Conclusion HNF1β+ biliary duct cells are the origin of LPC. HNF1β+ cells do not contribute to hepatocyte turnover in the healthy liver, but after certain liver injury, they can differentiate to

  19. Bile Culture and Susceptibility Testing of Malignant Biliary Obstruction via PTBD

    SciTech Connect

    Yu Haipeng; Guo Zhi Xing Wenge; Guo Xiuying; Liu Fang; Li Baoguo

    2012-10-15

    Purpose: To assess the information obtained by bile culture and susceptibility testing for malignant biliary obstruction by a retrospective one-center study. Methods: A total of 694 patients with malignant biliary obstruction received percutaneous transhepatic biliary drainage during the period July 2003 to September 2010, and subsequently, bile specimens were collected during the procedure. Among the 694 patients, 485 were men and 209 were women, ranging in age from 38 to 78 years (mean age 62 years). Results: A total of 42.9% patients had a positive bile culture (298 of 694). Further, 57 species of microorganisms and 342 strains were identified; gram-positive bacteria accounted for 50.9% (174 of 342) and gram-negative bacteria accounted for 41.5% (142 of 342) of these strains. No anaerobes were obtained by culture during this study. The most common microorganisms were Enterococcus faecalis (41 of 342, 11.9%), Escherichia coli (34 of 342, 9.9%), Klebsiella pneumoniae (28 of 342, 8.2%), Staphylococcus epidermidis (19 of 342, 5.5%), Enterococcus (18 of 342, 5.3%), and Enterobacter cloacae (16 of 342, 4.7%). The percentage of {beta}-lactamase-producing gram-positive bacteria was 27.6% (48 of 174), and the percentage of gram-negative bacteria was 19.7% (28 of 142). The percentage of enzyme-producing Escherichia coli was 61.7% (21 of 34). Conclusion: The bile cultures in malignant biliary obstruction are different from those in the Tokyo Guidelines and other benign biliary obstruction researches, which indicates that a different antibacterial therapy should be applied. Thus, knowledge of the antimicrobial susceptibility data could aid in the better use of antibiotics for the empirical therapy of biliary infection combined with malignant biliary obstruction.

  20. Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer

    PubMed Central

    Kim, Hong-Beum; Cho, Won Jin; Choi, Nam Gyu; Kim, Sung-Soo; Park, Jun Hee; Lee, Hee-Jeong

    2017-01-01

    Purpose Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer. Methods We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell. Results The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC50 of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients. Conclusion These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer. PMID:28090501

  1. Association between green tea/coffee consumption and biliary tract cancer: A population-based cohort study in Japan.

    PubMed

    Makiuchi, Takeshi; Sobue, Tomotaka; Kitamura, Tetsuhisa; Ishihara, Junko; Sawada, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Yamaji, Taiki; Shimazu, Taichi; Tsugane, Shoichiro

    2016-01-01

    Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population-based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45-74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person-years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46-0.97]), and a non-significant trend of decreased risk associated with increased consumption was observed (P-trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non-significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption.

  2. Endoscopic multiple metal stenting for the treatment of enteral leaks near the biliary orifice: A novel effective rescue procedure

    PubMed Central

    Mutignani, Massimiliano; Dioscoridi, Lorenzo; Dokas, Stefanos; Aseni, Paolo; Carnevali, Pietro; Forti, Edoardo; Manta, Raffaele; Sica, Mariano; Tringali, Alberto; Pugliese, Francesco

    2016-01-01

    Between April 2013 and October 2015, 6 patients developed periampullary duodenal or jejunal/biliary leaks after major abdominal surgery. In all patients, percutaneous drainage of the collection or re-operation with primary surgical repair was attempted at first but failed. A fully covered enteral metal stent was placed in all patients to seal the leak. Subsequently, we cannulated the common bile duct and, in some cases, and the main pancreatic duct inserting hydrophilic guidewires through the stent after dilating the stent mesh with a dilatation balloon or breaking the meshes with Argon Plasma Beam. Finally, we inserted a fully covered biliary metal stent to drain the bile into the lumen of the enteral stent. In cases of normal proximal upper gastrointestinal anatomy, a pancreatic plastic stent was also inserted. Oral food intake was initiated when the abdominal drain outflow stopped completely. Stent removal was scheduled four to eight weeks later after a CT scan to confirm the complete healing of the fistula and the absence of any perilesional residual fluid collection. The leak resolved in five patients. One patient died two days after the procedure due to severe, pre-existing, sepsis. The stents were removed endoscopically in four weeks in four patients. In one patient we experienced stent migration causing small bowel obstruction. In this case, the stents were removed surgically. Four patients are still alive today. They are still under follow-up and doing well. Bilio-enteral fully covered metal stenting with or without pancreatic stenting was feasible, safe and effective in treating postoperative enteral leaks near the biliopancreatic orifice in our small series. This minimally invasive procedure can be implemented in selected patients as a rescue procedure to repair these challenging leaks. PMID:27606045

  3. Differentiating biliary atresia from other causes of cholestatic jaundice.

    PubMed

    Robie, Daniel K; Overfelt, Sarah R; Xie, Li

    2014-09-01

    Diagnosis of biliary atresia (BA) in infants presenting with cholestatic jaundice (CJ) requires exploratory surgery with cholangiography. However, the lack of a standardized approach to preoperative evaluation of infants with CJ can lead to a high number of negative surgical explorations. We reviewed our experience with CJ and BA to determine preoperative variables that might reliably identify BA. Infants explored for possible BA over a 5-year period were retrospectively reviewed. Preoperative clinical indices and liver biopsy results were reviewed. Statistical analysis was conducted by Student's t test and Fisher's exact test (P < 0.05). Twenty patients were identified, 10 with BA and 10 without (50% negative exploration rate). Nuclear cholescintigraphy (HIDA) excretion into the gastrointestinal tract was absent in all BA and in 8 of 10 without BA. Hepatomegaly was more common in the BA group (OR = 9.3, P = 0.07). BA had higher mean (± standard error) serum gamma-glutamyl transpeptidase levels (542 ± 130 vs 139 ± 25.8 U/L in non-BA, P = 0.03). There were insignificant differences in sex, type of feeding, TPN exposure and sepsis between the two groups. Although our small sample size limits conclusions, we suggest screening infants with CJ by measuring GGT levels, absence of hepatomegaly, presence of cholic stools and/or excretion on HIDA scan to undergo pecutaneous liver biopsy given the lower likelihood of BA necessary.

  4. Therapeutic implication of HER2 in advanced biliary tract cancer

    PubMed Central

    Cha, Yongjun; Ha, Hyerim; Park, Ji Eun; Bang, Ju-Hee; Jin, Mei Hua; Lee, Kyung-Hun; Kim, Tae-Yong; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Oh, Do-Youn; Bang, Yung-Jue

    2016-01-01

    Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. PMID:27517322

  5. Molecular profiling of biliary tract cancer: a target rich disease

    PubMed Central

    Jain, Apurva

    2016-01-01

    Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 (IDH1), FGFR2, BRAF and HER2/neu genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients. PMID:27747093

  6. Long-Term Placement of Subcutaneous Ruesch-Type Stents for Double Biliary Stenosis in a Living-Donor Liver Transplant Recipient

    SciTech Connect

    Adani, Gian Luigi Baccarani, Umberto; Lorenzin, Dario; Risaliti, Andrea; Como, Giuseppe; Gasparini, Daniele; Sponza, Massimo; Bresadola, Vittorio; Bresadola, Fabrizio

    2007-04-15

    Biliary reconstruction continues to be a major source of morbidity following liver transplantation. The spectrum of biliary complications is evolving due to the increasing number of split-liver and living-donor liver transplantation, which are even associated with a higher incidence of biliary complications. Bile duct strictures are the most common cause of late biliary complications and account for up to 40% of all biliary complications. Optimal therapy for posttransplantation anastomotic biliary strictures remains uncertain and requires a multidisciplinary approach. We report the case of a 54-year-old Caucasian male affected by hepatocarcinoma and hepatitis C-related cirrhosis who underwent right-lobe living-donor liver transplantation from his son complicated by double anastomotic stenosis of the main right hepatic duct and of an accessory biliary duct draining segments 6 and 7 of the graft that was successfully treated by percutaneous transhepatic cholangiography with long-term subcutaneous placement of two internal Ruesch-type biliary stents.

  7. MicroRNA markers for the diagnosis of pancreatic and biliary-tract cancers.

    PubMed

    Kojima, Motohiro; Sudo, Hiroko; Kawauchi, Junpei; Takizawa, Satoko; Kondou, Satoshi; Nobumasa, Hitoshi; Ochiai, Atsushi

    2015-01-01

    It is difficult to detect pancreatic cancer or biliary-tract cancer at an early stage using current diagnostic technology. Utilizing microRNA (miRNA) markers that are stably present in peripheral blood, we aimed to identify pancreatic and biliary-tract cancers in patients. With "3D-Gene", a highly sensitive microarray, we examined comprehensive miRNA expression profiles in 571 serum samples obtained from healthy patients, patients with pancreatic, biliary-tract, or other digestive cancers, and patients with non-malignant abnormalities in the pancreas or biliary tract. The samples were randomly divided into training and test cohorts, and candidate miRNA markers were independently evaluated. We found 81 miRNAs for pancreatic cancer and 66 miRNAs for biliary-tract cancer that showed statistically different expression compared with healthy controls. Among those markers, 55 miRNAs were common in both the pancreatic and biliary-tract cancer samples. The previously reported miR-125a-3p was one of the common markers; however, it was also expressed in other types of digestive-tract cancers, suggesting that it is not specific to cancer types. In order to discriminate the pancreato-biliary cancers from all other clinical conditions including the healthy controls, non-malignant abnormalities, and other types of cancers, we developed a diagnostic index using expression profiles of the 10 most significant miRNAs. A combination of eight miRNAs (miR-6075, miR-4294, miR-6880-5p, miR-6799-5p, miR-125a-3p, miR-4530, miR-6836-3p, and miR-4476) achieved a sensitivity, specificity, accuracy and AUC of 80.3%, 97.6%, 91.6% and 0.953, respectively. In contrast, CA19