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Sample records for 1b chronic hepatitis

  1. Replication of a chronic hepatitis B virus genotype F1b construct.

    PubMed

    Hernández, Sergio; Jiménez, Gustavo; Alarcón, Valentina; Prieto, Cristian; Muñoz, Francisca; Riquelme, Constanza; Venegas, Mauricio; Brahm, Javier; Loyola, Alejandra; Villanueva, Rodrigo A

    2016-03-01

    Genotype F is one of the less-studied genotypes of human hepatitis B virus, although it is widely distributed in regions of Central and South American. Our previous studies have shown that HBV genotype F is prevalent in Chile, and phylogenetic analysis of its full-length sequence amplified from the sera of chronically infected patients identified it as HBV subgenotype F1b. We have previously reported the full-length sequence of a HBV molecular clone obtained from a patient chronically infected with genotype F1b. In this report, we established a system to study HBV replication based on hepatoma cell lines transfected with full-length monomers of the HBV genome. Culture supernatants were analyzed after transfection and found to contain both HBsAg and HBeAg viral antigens. Consistently, fractionated cell extracts revealed the presence of viral replication, with both cytoplasmic and nuclear DNA intermediates. Analysis of HBV-transfected cells by indirect immunofluorescence or immunoelectron microscopy revealed the expression of viral antigens and cytoplasmic viral particles, respectively. To test the functionality of the ongoing viral replication further at the level of chromatinized cccDNA, transfected cells were treated with a histone deacetylase inhibitor, and this resulted in increased viral replication. This correlated with changes posttranslational modifications of histones at viral promoters. Thus, the development of this viral replication system for HBV genotype F will facilitate studies on the regulation of viral replication and the identification of new antiviral drugs.

  2. Therapy for treatment-refractory chronic hepatitis C virus genotype 1b infection: A retrospective analysis

    PubMed Central

    Cindoruk, Mehmet; Karakan, Tarkan; Unal, Selahattin

    2005-01-01

    Background: The most effective current therapy for hepatitis C virus (HCV) infection is the combination of pegylated interferon (peg-IFN) plus ribavirin (RBV). Objective: The aim of this retrospective analysis was to determine the rateof response to this therapy, and the factors affecting outcome, in patients with treatment-refractory chronic HCV genotype l b. Methods: The records of patients with chronic HCV infection and HCV geno-type1b who failed (nonresponse or relapse) previous treatment with standard interferon (IFN) + RSV were retrospectively analyzed for demographic data, virologic load, liver histology, biochemistry, treatment-related adverse effects (AEs), and the effects of dose reduction during treatment with peg-IFN + RBV for 48 weeks. Early virologic response (EVR) was defined as ≥2-log (copies/mL) decrease from baseline in serum HCV RNA concentration or the absence of detectable serum HCV RNA at treatment week 12. End-of-treatment response (ETR) was defined as the absence of detectable serum HCV RNA at treatment week 48. Sustained virologic response (SVR) was defined as the absence of detectable serum HCV RNA 24 weeks after treatment was discontinued. Factors affecting treatment outcome were determined using correlation analyses. Results: Data from the files of 17 patients (12 men, 5 women; mean [SD] age, 48 [2] years) were analyzed. EVR was achieved in 7 patients; however, viral breakthrough occurred in 2 of these patients during the treatment period, and 5 of these patients discontinued treatment because of severe treatment-related AEs (depression [1 patient] and neutropenia [4]). Seven patients achieved ETR, but HCV infection relapsed during the follow-up period. Three (18%) patients achieved SVR. Data concerning previous patterns of response to IFN + RBV therapy were available in 10 patients. Of these, 3 of 6 patients who had experienced relapse with the previous treatment achieved SVR with peg-IFN + RBV; neither of the 2 patients with

  3. Delayed Viral Clearance after 6-Week Treatment with Peginterferon Plus Ribavirin in a Patient with Chronic Hepatitis C Virus Genotype 1b

    PubMed Central

    Sato, Akira; Ishii, Toshiya; Adachi, Kayo; Takahashi, Hideaki; Sano, Fumiaki; Matsumoto, Nobuyuki

    2016-01-01

    Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy. Spontaneous clearance of hepatitis C virus RNA can occur following antiviral failure in patients with persistently low viral loads, and virological follow-up is therefore necessary in chronic hepatitis C virus infection, even after antiviral failure. PMID:27721727

  4. Twenty four-week peginterferon plus ribavirin after interferon-β induction for genotype 1b chronic hepatitis C

    PubMed Central

    Okushin, Hiroaki; Morii, Kazuhiko; Uesaka, Koichi; Yuasa, Shiro

    2010-01-01

    AIM: To investigate the possibility of shortening the duration of peginterferon (Peg-IFN) plus ribavirin (RBV) combination therapy by incorporating interferon-β (IFN-β) induction therapy. METHODS: A one treatment arm, cohort prospective study was conducted on seventy one patients. The patients were Japanese adults with genotype 1b chronic hepatitis C, HCV-RNA levels of ≥ 5.0 Log IU/mL or 100 KIU/mL, and platelet counts of ≥ 90 000/μL. The treatment regimen consisted of a 2 wk course of twice-daily administration of IFN-β followed by 24 wk Peg-IFN plus RBV combination therapy. We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS: The patients, including 44% males, were characterized by an median age of 63 years (range: 32-78 years), an median platelet count of 13.9 (range: 9.1-30.6) × 104/μL, 62% IFN-naïve, and median HCV-RNA of 6.1 (range: 5.1-7.2) Log IU/mL. The sustained virologic response (SVR) rates were 34% (Peg-IFN: 1-24 wk, n = 61, 95% confidence interval (CI): 24%-47%) and 55% (Peg-IFN: 20-24 wk, n = 31, 95% CI: 38%-71%, P < 0.001; vs Peg-IFN: 1-19 wk). The SVR rate when the administration was discontinued early was 13% (Peg-IFN: 1-19 wk, n = 30, 95% CI: 5%-30%), and that when the administration was prolonged was 50% (Peg-IFN: 25-48 wk, n = 10, 95% CI: 24%-76%, P < 0.05; vs Peg-IFN: 1-19 wk). In the patients who received 20-24 wk of Peg-IFN plus RBV, only the higher platelet count (≥ 130 000/μL) was significantly correlated with the SVR (odds ratio: 11.680, 95% CI: 2.3064-79.474, P = 0.0024). In 45% (14/31) of the patients with a higher platelet count (≥ 130 000/μL) before therapy, the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-β, and their SVR rate was 93% (13/14) after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION: These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV

  5. HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127) and ribavirin for treatment-naïve patients with chronic hepatitis C virus genotype-1b infection

    PubMed Central

    Sarrazin, Christoph; Castelli, Francesco; Andreone, Pietro; Buti, Maria; Colombo, Massimo; Pol, Stanislas; Calinas, Filipe; Puoti, Massimo; Olveira, Antonio; Shiffman, Mitchell; Stern, Jerry O; Kukolj, George; Roehrle, Michael; Aslanyan, Stella; Deng, Qiqi; Vinisko, Richard; Mensa, Federico J; Nelson, David R

    2016-01-01

    The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2) in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including those ineligible for peginterferon (HCVerso2). Patients without cirrhosis were randomized to 16 weeks (Arm 1; n=208 HCVerso1, n=213 HCVerso2) or 24 weeks (Arm 2; n=211 in both studies) of faldaprevir + deleobuvir + ribavirin. Patients with compensated cirrhosis received open-label faldaprevir + deleobuvir + ribavirin for 24 weeks (Arm 3; n=51, n=72). Primary endpoints were comparisons of adjusted sustained virologic response (SVR) rates with historical rates: 71% (HCVerso1) and 68% (HCVerso2). Adjusted SVR12 rates were significantly greater than historical controls for Arms 1 and 2 in HCVerso2 (76%, 95% confidence interval [CI] 71–81, P=0.002; 81%, 95% CI 76–86, P<0.0001) and Arm 2 in HCVerso1 (81%, 95% CI 77–86, P<0.0001), but not for Arm 1 of HCVerso1 (72%, 95% CI 66–77, P=0.3989). Unadjusted SVR12 rates in Arms 1, 2, and 3 were 71.6%, 82.5%, and 72.5%, respectively, in HCVerso1 and 75.6%, 82.0%, and 73.6%, respectively, in HCVerso2. Virologic breakthrough and relapse occurred in 24-week arms in 8%–9% and 1% of patients, respectively, and in 16-week arms in 7%–8% and 9%–11% of patients, respectively. The most common adverse events were nausea (46%–61%) and vomiting (29%–35%). Adverse events resulted in discontinuation of all medications in 6%–8% of patients. In treatment-naïve patients with hepatitis C virus genotype-1b infection, with or without cirrhosis, faldaprevir + deleobuvir + ribavirin treatment for 24 weeks resulted in adjusted SVR12 rates significantly higher than historical controls. Both studies were registered in ClinicalTrials.gov (NCT01732796, NCT01728324). PMID:27920566

  6. HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127) and ribavirin for treatment-naïve patients with chronic hepatitis C virus genotype-1b infection.

    PubMed

    Sarrazin, Christoph; Castelli, Francesco; Andreone, Pietro; Buti, Maria; Colombo, Massimo; Pol, Stanislas; Calinas, Filipe; Puoti, Massimo; Olveira, Antonio; Shiffman, Mitchell; Stern, Jerry O; Kukolj, George; Roehrle, Michael; Aslanyan, Stella; Deng, Qiqi; Vinisko, Richard; Mensa, Federico J; Nelson, David R

    2016-01-01

    The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2) in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including those ineligible for peginterferon (HCVerso2). Patients without cirrhosis were randomized to 16 weeks (Arm 1; n=208 HCVerso1, n=213 HCVerso2) or 24 weeks (Arm 2; n=211 in both studies) of faldaprevir + deleobuvir + ribavirin. Patients with compensated cirrhosis received open-label faldaprevir + deleobuvir + ribavirin for 24 weeks (Arm 3; n=51, n=72). Primary endpoints were comparisons of adjusted sustained virologic response (SVR) rates with historical rates: 71% (HCVerso1) and 68% (HCVerso2). Adjusted SVR12 rates were significantly greater than historical controls for Arms 1 and 2 in HCVerso2 (76%, 95% confidence interval [CI] 71-81, P=0.002; 81%, 95% CI 76-86, P<0.0001) and Arm 2 in HCVerso1 (81%, 95% CI 77-86, P<0.0001), but not for Arm 1 of HCVerso1 (72%, 95% CI 66-77, P=0.3989). Unadjusted SVR12 rates in Arms 1, 2, and 3 were 71.6%, 82.5%, and 72.5%, respectively, in HCVerso1 and 75.6%, 82.0%, and 73.6%, respectively, in HCVerso2. Virologic breakthrough and relapse occurred in 24-week arms in 8%-9% and 1% of patients, respectively, and in 16-week arms in 7%-8% and 9%-11% of patients, respectively. The most common adverse events were nausea (46%-61%) and vomiting (29%-35%). Adverse events resulted in discontinuation of all medications in 6%-8% of patients. In treatment-naïve patients with hepatitis C virus genotype-1b infection, with or without cirrhosis, faldaprevir + deleobuvir + ribavirin treatment for 24 weeks resulted in adjusted SVR12 rates significantly higher than historical controls. Both studies were registered in ClinicalTrials.gov (NCT01732796, NCT01728324).

  7. Chronic Hepatitis C

    PubMed Central

    Jang, Jae Young

    2011-01-01

    The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual's antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specific inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fibrosis progression, the incidence of cirrhosis, and hepatocellular carcinoma. PMID:21814590

  8. Update on chronic viral hepatitis

    PubMed Central

    Walsh, K; Alexander, G

    2001-01-01

    Many recent and significant advances in the field of chronic viral hepatitis, including therapy, suggest that an update on chronic hepatitis is timely.
Chronic hepatitis B virus infection remains a significant worldwide cause of liver cirrhosis and hepatocellular carcinoma, despite the wide availability of a long established and effective vaccine. Transmission occurs via perinatal, sexual, and parenteral routes (particularly intravenous drug abuse and although blood products still carry a risk, this is now extremely low in Western countries). Only a minority of infected adult cases develop chronic hepatitis but in children under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic liver injury ranges from mild inflammation to end stage liver cirrhosis. Interferon alfa has been the mainstay of treatment for patients with active disease but nucleoside analogues (lamivudine and adefovir) are now available with similar efficacy. Patients with end stage liver disease and hepatocellular carcinoma can be offered transplantation but infection in the graft is commonplace. The combination of hepatitis B immunoglobulin and newer antiviral drugs reduce the incidence and severity of graft infection significantly.
The hepatitis C virus epidemic of the latter half of the 20th century now affects more than 1% of populations worldwide. This RNA virus is spread parenterally and is becoming the leading indication for liver transplantation. The majority of patients develop chronic hepatitis, which may be progressive, evolving to significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20% cases after decades. Treatment with the combination of interferon alfa and ribavirin is successful in up to 40% cases. Liver transplantation is a therapeutic option for some but graft infection is universal and often complicated by progressive liver fibrosis. A vaccine remains a remote prospect so that prevention is crucial.
Hepatitis D virus infection

  9. Organic Anion–Transporting Polypeptide 1b2 (Oatp1b2) Is Important for the Hepatic Uptake of Unconjugated Bile Acids: Studies in Oatp1b2-Null Mice

    PubMed Central

    Csanaky, Iván L.; Lu, Hong; Zhang, Youcai; Ogura, Kenichiro; Choudhuri, Supratim; Klaassen, Curtis D.

    2011-01-01

    The organic anion–transporting polypeptide 1b family (Oatp1b2 in rodents and OATP1B1/1B3 in humans) is liver-specific and transports various chemicals into the liver. However, the role of the Oatp1b family in the hepatic uptake of bile acids (BAs) into the liver is unknown. Therefore, in Oatp1b2-null mice, the concentrations of BAs in plasma, liver, and bile were compared with wild-type (WT) mice. It was first determined that livers of the Oatp1b2-null mice were not compensated by altered expression of other hepatic transporters. However, the messenger RNA of Cyp7a1 was 70% lower in the Oatp1b2-null mice. Increased expression of fibroblast growth factor 15 in intestines of Oatp1b2-null mice might be responsible for decreased hepatic expression of Cyp7a1 in Oatp1b2-null mice. The hepatic concentration and biliary excretion of conjugated and unconjugated BAs were essentially the same in Oatp1b2-null and WT mice. The serum concentration of taurine-conjugated BAs was essentially the same in the two genotypes. In contrast, the serum concentrations of unconjugated BAs were 3–45 times higher in Oatp1b2-null than WT mice. After intravenous administration of cholate to Oatp1b2-null mice, its clearance was 50% lower than in WT mice, but the clearance of taurocholate was similar in the two genotypes. Conclusion This study indicates that Oatp1b2 has a major role in the hepatic uptake of unconjugated BAs. PMID:20949553

  10. Eltrombopag in chronic hepatitis C

    PubMed Central

    Mihăilă, Romeo-Gabriel; Cipăian, Remus-Călin

    2014-01-01

    Chronic hepatitis C is a public health problem worldwide. Unfortunately, not all patients may benefit from antiviral therapy due to thrombocytopenia. Its causes are represented by portal hypertension and platelet sequestration in the spleen, decreased serum levels or activity of thrombopoietin, the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon. Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients. Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner. Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia. Its indication for other hemopathies or situations (like thrombocytopenia secondary to chemo- or radiotherapy, acute leukemia, myelodysplastic syndroms, acquired and hereditary bone marrow failure, and platelet donors) is under study. Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment. We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus, highlighting the benefits and mentioning possible adverse effects. In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery. Eltrombopag is a solution for many of these patients, which allows them receiving antiviral therapy and sometimes getting a sustained virological response, but they must be well monitored to prevent possible thromboembolic or bone marrow complications or liver failure occurrence. PMID:25253952

  11. Chronic urticaria following acute hepatitis A.

    PubMed

    Griffin, Paul M; Kevat, Dev A S; McCarthy, James S; Woods, Marion L

    2012-09-18

    Urticaria has a documented association with the prodromal phases of hepatitis A, B and, although still contentious, likely hepatitis C. Despite the documented association there are few actual reported cases of urticaria occurring with hepatitis A infection and in all of the cases reported so far the urticaria preceded the diagnosis of hepatitis A and was acute rather than chronic. We describe a case of urticaria occurring following acute infection with hepatitis A, which persisted beyond 6 weeks and therefore was by definition chronic. Although chronic urticaria has been reported to be associated with other forms of viral hepatitis, to the best of our knowledge this has not been reported previously with hepatitis A.

  12. Detergent-induced activation of the hepatitis C virus genotype 1b RNA polymerase.

    PubMed

    Weng, Leiyun; Kohara, Michinori; Wakita, Takaji; Shimotohno, Kunitada; Toyoda, Tetsuya

    2012-04-01

    Recently, we found that sphingomyelin bound and activated hepatitis C virus (HCV) 1b RNA polymerase (RdRp), thereby recruiting the HCV replication complex into lipid raft structures. Detergents are commonly used for resolving lipids and purifying proteins, including HCV RdRp. Here, we tested the effect of detergents on HCV RdRp activity in vitro and found that non-ionic (Triton X-100, NP-40, Tween 20, Tween 80, and Brij 35) and twitterionic (CHAPS) detergents activated HCV 1b RdRps by 8-16.6 folds, but did not affect 1a or 2a RdRps. The maximum effect of these detergents was observed at around their critical micelle concentrations. On the other hand, ionic detergents (SDS and DOC) completely inactivated polymerase activity at 0.01%. In the presence of Triton X-100, HCV 1b RdRp did not form oligomers, but recruited more template RNA and increased the speed of polymerization. Comparison of polymerase and RNA-binding activity between JFH1 RdRp and Triton X-100-activated 1b RdRp indicated that monomer RdRp showed high activity because JFH1 RdRp was a monomer in physiological conditions of transcription. Besides, 502H plays a key role on oligomerization of 1b RdRp, while 2a RdRps which have the amino acid S at position 502 are monomers. This oligomer formed by 502H was disrupted both by high salt and Triton X-100. On the contrary, HCV 1b RdRp completely lost fidelity in the presence of 0.02% Triton X-100, which suggests that caution should be exercised while using Triton X-100 in anti-HCV RdRp drug screening tests.

  13. [Occult hepatitis B virus infection in chronic hepatitis C].

    PubMed

    Jang, Jae Young; Park, Eui Ju

    2013-09-01

    Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.

  14. Chronic hepatitis E: A brief review.

    PubMed

    Murali, Arvind R; Kotwal, Vikram; Chawla, Saurabh

    2015-09-08

    Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E.

  15. Advances in therapeutics for chronic hepatitis B.

    PubMed

    Yang, Ninghan; Bertoletti, Antonio

    2016-03-01

    Chronic hepatitis B infection remains a major disease burden globally, and leads to high risk of hepatocellular carcinoma development. Current therapies of nucleot(s)ide analogues and interferon alpha treatment remain limited in their efficacy. Several key findings in the hepatitis B virus (HBV) life cycle have led to the development of novel antiviral drugs to inhibit viral replication and persistence. In addition, recent studies on HBV-specific innate and adaptive immune responses have advanced development of immunotherapy to restore immune mediated virus control in chronic hepatitis B patients. In this review, we discuss potential new therapeutic strategies targeting HBV or the host immune system that might lead to a sustained cure for chronic hepatitis B.

  16. Chronic viral hepatitis: the histology report.

    PubMed

    Guido, Maria; Mangia, Alessandra; Faa, Gavino

    2011-03-01

    In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice.

  17. Serum alphaphetoprotein in chronic hepatitis. Scintigraphic correlations.

    PubMed

    Gheorghe, N; Boerescu, I; Ciuntu, L; Coman, M; Boroş, I

    1986-01-01

    On studying a number of 59 patients with chronic active hepatitis and with hepatic cirrhosis, with 37% and 41% cases respectively our research-works have proved increased serum AFP concentrations varying between 30-45 ng/ml, their values being much larger in active hepatic cirrhosis. The significant increase in aminotransferase and bilirubin has been correlated with a more severe stage of the hepatic disease. The gamma glutamyltranspeptidase (GGTP) assays for 9 of the 17 cases with active chronic hepatitis and for 17 cases with alcoholic hepatitis have shown a 6-15 times increase of this enzyme as compared to the other cases. Very high values of AFP, ranging between 300-900 ng/ml, have been found in the hepatic adenocirrhosis cases. A certain correlation between the AFP modifications and the scintigraphy has been found in 5 of the cases with malignant changes, in contrast with the AFP low and sporadic increase in the case of other gastrointestinal tract tumors. The scintigraphic modifications have been evident with low or multiple lacunary fixations, in considerable sizes and forms, with irregular edges, their dimensions, depending upon the disease evolution stage.

  18. Withdrawal from chronic cocaine up-regulates 5-HT1B receptors in the rat brain.

    PubMed

    Przegaliński, Edmund; Czepiel, Klaudia; Nowak, Ewa; Dlaboga, Daniel; Filip, Małgorzata

    2003-11-20

    In the present study we examined the effect of prolonged treatment with cocaine (a sensitization and discrimination paradigm) on the expression of serotonin (5-HT)(1B) receptors in rat brain structures using a quantitative autoradiographic analysis. To estimate the distribution of 5-HT(1B) receptors in several brain coronal sections, we used [N-methyl-(3)H]GR 125743, a 5-HT(1B/1D) receptor antagonist, in the presence of ketanserin (a drug used to block 5-HT(1D) receptors). The binding of [N-methyl-(3)H]GR 125743 in the areas containing dopamine cell bodies (the ventral tegmental area, the substantia nigra) and terminals (the nucleus accumbens shell and core, but not in the caudate-putamen) and in the subiculum of the hippocampus was increased after withdrawal from repeated cocaine in both the discrimination and the sensitization paradigms, either being effective as confirmed by behavioral experiments. Neither acute cocaine injection nor the psychostimulant challenge following its repeated administration affected the binding of [N-methyl-(3)H]GR 125743 in the above brain areas. Our results indicate that withdrawal from chronic cocaine induces up-regulation of 5-HT(1B) receptors in a number of rat brain structures.

  19. Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form

    PubMed Central

    Schuermans, Wim; Orlent, Hans; Desombere, Isabelle; Descheemaeker, Patrick; Van Vlierberghe, Hans; Geerts, Anja; Verhelst, Xavier; Reynders, Marijke; Padalko, Elizaveta

    2016-01-01

    As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis. PMID:27563879

  20. [Chronic hepatitis and occult HCV infection].

    PubMed

    Kowala-Piaskowska, Arleta; Mozer-Lisewska, Iwona; Pham, Tram N Q; Michalak, Tomasz I

    2010-01-01

    Hepatitis C virus (HCV) was discovered in 1989. HCV is a positive single-strand RNA. We all have thought, that HCV can replicate only in liver tissue, but now we know, that HCV can replicate in extrahepatic tissue as well. In about 48-86% of HCV infected patients, chronic hepatitis C (CHC) has been noticed and eventually, after tens of years, liver insufficiency, cirrhosis or hepatocellular carcinoma. The current recommended treatment for CHC is a combination of pegylated-interferon alpha and Ribavirin. Presently it is known, that HCV infection can persist as an occult infection. RNA HCV can be detected in patients after successful treatment for CHC or spontaneous elimination. Persistent HCV replication in hepatocytes or lymphoid cells would likely lead to continuous antigenic stimulation of the immune system. This prolonged replication may contribute to the immune tolerance of HCV, impairment of immune response and even further virus persistence. This occult infection grows more important in transplantation.

  1. Chronic hepatitis C and liver transplantation.

    PubMed

    Davis, Gary L

    2004-01-01

    Chronic hepatitis C virus (HCV) is a worldwide health problem. Approximately 4 million people in the United States are chronically infected with HCV. The incidence of infection peaked between 2 and 3 decades ago, and we are now beginning to see an increase in the complications of cirrhosis from HCV. This trend is expected to continue for another 2 to 3 decades. Survival is poor once complications of cirrhosis, such as liver failure or hepatocellular carcinoma, ensue, and liver transplantation is often the only option. Complications of chronic HCV are the most common indication for liver transplantation, accounting for more than 40% of transplants performed in the United States and Europe. HCV recurs in all patients and rapid development of hepatic fibrosis is very common. Several strategies have been proposed to reduce the risk of graft loss from recurrent HCV infection after transplantation, as the progression of the resulting liver disease is rapid. Although antiviral treatment is successful in some patients, it is extremely difficult to administer and requires dose reductions in the majority of cases. Retransplantation in the current era of the Model for End-Stage Liver Disease (MELD) system for prioritizing listing for transplant is associated with very low survival rates at a high cost. Furthermore, the system raises difficult ethical issues of utilization of limited resources and fairness to other transplant candidates.

  2. [Clinical practice guideline for diagnosis and treatment of chronic hepatitis virus hepatitis B. Grupo Colaborativo en Hepatitis B].

    PubMed

    2011-01-01

    This guide sets out the technical criteria for the diagnosis and treatment of chronic hepatitis secondary to viral hepatitis B. The guide intend to reduce the morbidity and mortality of this disease. The Guide give practical definitions to help understand the terminology, describe epidemiology, risk factors, and clinical aspects and the diagnosis of chronic hepatitis B. Finally the guide give recommendations for the management including special circumstances such as patients with cirrhosis, patients coinfected with HIV or coinfected with hepatitis C. The recommendations of the guide become the national guide for the management of chronic hepatitis B

  3. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    PubMed

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

  4. Chronic hepatitis: a retrospective study in 34 dogs.

    PubMed Central

    Fuentealba, C; Guest, S; Haywood, S; Horney, B

    1997-01-01

    The aims of this study were to characterize the histological changes observed in 34 accessioned cases of canine chronic hepatitis and to correlate these changes with the clinical pathological data. Cases of chronic hepatitis were subdivided into 6 categories: chronic active hepatitis (10/34), chronic persistent hepatitis (7/32), chronic cholestatic hepatitis (6/34), fibrosing hepatitis with cirrhosis (3/34), chronic cholangiohepatitis (3/34), and miscellaneous secondary hepatitis (5/34). Iron accumulation was a consistent finding in all livers examined. Although all cases of chronic hepatitis had elevated liver enzymes, no correlation was detected between biochemical parameters and the severity of morphologic changes. Similarly, no correlation was detected between rhodanine staining for copper and morphologic or biochemical indicators of cholestasis. However, presence of copper correlated well with reticulo-fibrosis (r = 0.8) and bile duct hyperplasia, suggesting that changes in the hemodynamics of the hepatic acini due to fibrosis could influence storage of copper. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. PMID:9187802

  5. Prevention and Management of Chronic Hepatitis B

    PubMed Central

    Bhat, Mamatha; Ghali, Peter; Deschenes, Marc; Wong, Philip

    2014-01-01

    Chronic hepatitis B virus (HBV) infection affects an estimated 370 million people worldwide. HBV is endemic throughout the world, and insidiously causes liver damage over years and decades without any warning symptoms or signs. Up to 25–35% of infected individuals eventually die due to complications of liver cirrhosis and hepatocellular carcinoma (HCC) induced by HBV. Screening those individuals at risk of acquiring hepatitis B, and universal vaccination for prevention, would help in limiting the spread and public health repercussions of the virus. Although many new antiviral therapies have been developed for the management of hepatitis B, they still do not offer the possibility of cure. Most individuals who begin oral suppressive therapy will be indefinitely treated. Continuous suppression of HBV replication in individuals with advanced liver disease prolongs life, decreases the need for liver transplantation, and potentially reduces the risk for HCC. In this clinical review, we present a practical approach to prevention of HBV, its natural history and life cycle, as well as its management. PMID:26622990

  6. Hepatitis

    MedlinePlus

    ... clotting problems or chronic liver disease. previous continue Hepatitis B and Hepatitis C Although hep A is a ... does — through direct contact with infected body fluids. Hepatitis B and C are even more easily passed in ...

  7. Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

    PubMed

    Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

    2014-05-12

    We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

  8. [Syndrome of overlap: Chronic hepatitis C/autoimmune hepatitis: fact or fancy?].

    PubMed

    Antonaci, Salvatore; Giannelli, Gianluigi; Simone, Barbara; Vella, Francesco Saverio

    2005-01-01

    Non-organ specific autoantibodies are common in patients with chronic hepatitis C, making differential diagnosis difficult between viral, autoimmune forms and hepatitis C/autoimmune hepatitis overlap syndrome. The lack of additional criteria of autoimmunity in most patients leads to the definition of a "false" hepatitis C-autoimmune hepatitis overlap syndrome, while the "true" overlap syndrome occurs in a very few number of subjects. In patients with "false" overlap syndrome the first choice therapy is based on the administration of interferon plus ribavirin. On the contrary, first-line therapy with corticosteroids should be restricted to the "true" hepatitis overlap syndrome with the new therapeutic option of interferon/corticosteroid association.

  9. Fatigue in patients with chronic hepatitis C.

    PubMed

    Poynard, T; Cacoub, P; Ratziu, V; Myers, R P; Dezailles, M H; Mercadier, A; Ghillani, P; Charlotte, F; Piette, J C; Moussalli, J

    2002-07-01

    In numerous studies of symptoms in patients with chronic hepatitis C there has been no systematic assessment of both fatigue and extrahepatic manifestations. Our objective was to assess the prevalence of fatigue in patients with hepatitis C virus (HCV) infection, and to identify associations between fatigue and clinical and biological hepatic and extrahepatic manifestations. We studied 1614 patients. Data were prospectively recorded during the first visit of patients infected with HCV and the prevalence of fatigue and its association with dermatological, rheumatological, neurological and nephrological manifestations; diabetes; arterial hypertension; auto-antibodies, and cryoglobulinaemia were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunological, virological, and histological factors associated with the presence of fatigue. Fatigue was present in 53% of patients (95% confidence interval 51-56). In 17% of patients (95% confidence interval 15-19) fatigue was severe, impairing activity. Five other extrahepatic manifestations had a prevalence above 10% including, in decreasing order: arthralgia, paresthesia, myalgia, pruritus, and sicca syndrome. In univariate and multivariate analyses, fatigue, in comparison with the absence of fatigue, was associated with female gender, age over 50 years, cirrhosis, depression and purpura. Independent of these associations, fatigue was associated with arthralgia, myalgia, paresthesia, sicca syndrome and pruritus. The prevalence of fibromyalgia (as defined by the association of fatigue with arthralgia or myalgia) was 19% (95% confidence interval 17-21). There was no significant association between fatigue and the following characteristics: viral load or genotype, alcohol consumption, abnormal thyroid function, and type and level of cryoglobulinaemia. Hence, fatigue is the most frequent extrahepatic manifestation in patients infected with HCV. Fatigue is independently associated with female

  10. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

    PubMed Central

    Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

    2017-01-01

    Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities

  11. High prevalence of hepatitis C virus (HCV) genotype 2 in Italian patients with chronic liver disease.

    PubMed

    Sartori, M; Andorno, S; Avogadro, E; Ballarè, M; La Terra, G; Leone, F; Quaglia, V; Fortina, G; Aglietta, M

    1996-01-01

    The prevalence of different genotypes of Hepatitis C virus may vary between geographic areas and it is possible that various genotypes have different pathogenic characteristics. Therefore, 90 consecutive Italian patients anti-Hepatitis C Virus positive with a broad spectrum of chronic liver disease, have been analysed to observe prevalence of various genotypes of Hepatitis C Virus. Genotyping was performed by polymerase chain reaction with a set of nested biotinylated primers, located in 5'UTR region. Genotype 1b and genotype 2a were the most commonly encountered (respectively, 50% and 37%) whereas other genotypes were rare. The unexpected high prevalence of genotype 2a allowed direct comparison of clinical characteristics and response to therapy between patients with genotype 2a and those with 1b. Genotype 1b was more prevalent than 2a in patients over 60 years (29 vs 12) and in those with more severe liver disease (34 vs 16). In a univariate analysis, genotype 2a was associated with less severe liver disease (p = 0.02) and younger age (p = 0.018), in comparison with genotype 1b. Patients with genotype 2a responded to interferon alpha therapy better than those with 1b (p = 0.007). In a multivariate analysis, only younger age was associated with genotype 2a. Genotype 2a (in comparison with 1b) and absence of cirrhosis were independent predictors of response to interferon alpha. In conclusion, genotype 2a is playing an emerging role in younger Italian patients and seems more sensitive than 1b to interferon alpha therapy.

  12. [Using hepatomaks forte in the treatment of chronic alcoholic hepatitis].

    PubMed

    Linevskiĭ, Iu V; Linevskaia, K Iu; Voronin, K A

    2013-01-01

    Installed significantly more pronounced positive effect on clinical manifestations and laboratory indicators of liver in patients with chronic alcoholic hepatitis who received within 4 weeks of basal therapy in conjunction with Gepatomax Forte in comparison with a group of patients with chronic alcoholic hepatitis who received during the same time only basic therapy. Side adverse effects in the group of patients receiving Gepatomax Forte were not registered.

  13. Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors

    PubMed Central

    Saludes, Verónica; Bracho, Maria Alma; Valero, Oliver; Ardèvol, Mercè; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Martró, Elisa

    2010-01-01

    Background Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy −especially among genotype 1 infected patients−, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Methodology Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1–E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A “leave-one-out” cross-validation method was used to assess the reliability of the discriminant models. Principal Findings Lower alanine transaminase levels (ALT, p = 0.009), a higher number of quasispecies variants in the E1–E2 region (number of haplotypes, nHap_E1–E2) (p = 0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p = 0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1–E2, and gamma-glutamyl transferase and ALT levels. Conclusions and Significance Discriminant analysis has been shown as a useful tool to predict treatment outcome using

  14. HCV NS3Ag: a reliable and clinically useful predictor of antiviral outcomes in genotype 1b hepatitis C virus-infected patients.

    PubMed

    Ren, S; Jin, Y; Huang, Y; Ma, L; Liu, Y; Meng, C; Guan, S; Xie, L; Chen, X

    2016-07-01

    Since hepatitis C virus (HCV) non-structural 3 (NS3) protease inhibitor (PI) combined with pegylated interferon/ribavirin (PR) has been approved for chronic HCV genotype (GT) 1b infection, a reliable and clinically useful predictor combining with serum HCV RNA to predict early virologic response, breakthrough, and relapse is important during HCV antiviral treatment. We evaluated the role of HCV NS3 antigen (HCV NS3Ag) on the prediction of virologic response in patients with HCV GT1b during PR or PR/simeprevir (triple) therapy. Three hundred patients were recruited, and HCV RNA and HCV NS3Ag were tested at baseline and weeks 2, 4, 12, 24, 48, and 72. NS3Ag and HCV RNA were significantly related (r(2) = 0.67) in the whole patient selection. The kinetic pattern of HCV RNA and HCV NS3Ag during triple treatment was similar. HCV NS3Ag levels in the triple group closely followed those of HCV RNA; the r(2) values were 0.756 (baseline), 0.837 (2 weeks), 0.989 (4 weeks), and 0.993 (12 weeks), respectively. For patients treated with PR, the positive and negative predictive values (PPVs and NPVs) for viral response were 96.31 % and 67.19 %, respectively, at week 4 by using the decrease of NS3Ag (dHCV NS3Ag) combined with HCV RNA. At week 12, the PPV was similar at 94.16 %, while the NPV reached 87.26 %. The PPV and NPV for the prediction of relapse and breakthrough were 90.6 % and 76.7 %, respectively. HCV NS3Ag is a valuable marker and could be a supplementary predictor of HCV RNA for the prediction of antiviral response, breakthrough, or relapse during HCV antiviral treatment.

  15. Cytokine profiles and hepatic injury in occult hepatitis C versus chronic hepatitis C virus infection.

    PubMed

    Mousa, N; Eldars, W; Eldegla, H; Fouda, O; Gad, Y; Abousamra, N; Elmasry, E; Arafa, M

    2014-01-01

    Occult hepatitis C virus (HCV) infection is a new entity that should be considered when diagnosing patients with abnormal liver functions of unknown origin. This work was carried out to evaluate T-helper 1/T-helper 2 (Th1/Th2) cytokine profiles in patients with occult HCV infection versus chronic hepatitis C (CHC) infection, also to investigate any association between theses cytokines and liver histological features in both groups. Serum levels of Th1 cytokines (IL-2, IFN-gamma) and Th2 (IL-4 and IL-10) were measured in 35 patients with occult HCV infection compared to 50 patients with chronic hepatitis C infection and 30 healthy controls. We have found that Th1 cytokines were significantly increased in patients with CHC infection than in both occult HCV infection and control groups (p less than 0.001). On the other hand, serum IL-4 levels were higher in occult HCV infection than in CHC and control groups (p less than 0.001). Furthermore, serum IL-10 levels were higher in both patient groups vs control group (pless than 0.001), with no significant difference between CHC and occult HCV groups. Finally, only serum IL-10 levels were significantly higher among patients with high activity (A2-A3) than those with low activity (A0-A1) in both CHC and occult HCV groups (p=0.038, p=0.025, respectively). Patients with occult HCV infection exhibited a distinct immunoregulatory cytokine pattern that is shifted towards the Th2 arm.

  16. Chronic hepatitis caused by persistent parvovirus B19 infection

    PubMed Central

    2010-01-01

    Background Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions. Case Presentation Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection. Conclusions In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual aetiology of chronic hepatitis

  17. The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1

    PubMed Central

    Shu, Nan; Hu, Mengyue; Ling, Zhaoli; Liu, Peihua; Wang, Fan; Xu, Ping; Zhong, Zeyu; Sun, Binbin; Zhang, Mian; Li, Feng; Xie, Qiushi; Liu, Xiaodong; Liu, Li

    2016-01-01

    Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation. PMID:27624558

  18. Genotype characterization of occult hepatitis B virus strains among Egyptian chronic hepatitis C patients.

    PubMed

    Kishk, R; Atta, H Aboul; Ragheb, M; Kamel, M; Metwally, L; Nemr, N

    2014-03-13

    Chronic hepatitis C virus (HCV) infection combined with occult hepatitis B virus (HBV) infection has been associated with increased risk of hepatitis, cirrhosis and hepatocellular carcinoma. This study aimed to determine the prevalence of occult HBV infection among Egyptian chronic HCV patients, the genotype and occurrence of surface gene mutations of HBV and the impact of co-infection on early response to treatment. The study enrolled 162 chronic HCV patients from Ismailia Fever Hospital, Egypt, who were HBV surface antigen-negative. All patients were given clinical assessment and biochemical, histological and virological examinations. HBV-DNA was detectable in sera from 3 patients out of the 40 patients who were positive for hepatitis B core antibody. These 3 patients were responsive to combination therapy at treatment week 12; only 1 of them had discontinued therapy by week 24. HBV genotype D was the only detectable genotype in those patients, with absence of "a" determinant mutations among those isolates.

  19. Characteristics of an outpatient chronic hepatitis B virus infection cohort

    PubMed Central

    de Assis, Danyenne Rejane; Tenore, Simone de Barros; Pinho, João Renato Rebello; Lewi, David Salomão; Ferreira, Paulo Roberto Abrão

    2015-01-01

    ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID:26154539

  20. High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    Wang, Yan-Yan; Qi, Lu-Nan; Zhong, Jian-Hong; Qin, Hong-Gui; Ye, Jia-Zhou; Lu, Shi-Dong; Ma, Liang; Xiang, Bang-De; Li, Le-Qun; You, Xue-Mei

    2017-01-01

    To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection. PMID:28181486

  1. [Chronic active hepatitis: clinical, biochemical, and histopathologic correlation].

    PubMed

    Subauste, M C

    1989-01-01

    A retrospective study over 26 female patients with chronic active hepatitis was made. The mean age was 39 years old, the mean length of illness of 8 months; 5 patients had positive markers for hepatitis B. Patients were selected with the grade of histological activity: 8 patients had a mild form from disease (2A) and 16 with a severe one (2B). The predominant group was 2B. Severe inflammatory infiltration was the hallmark and multiobulillar necrosis, bridging, eosinophils and hiperplasia of kuppfer cells were found only in this group. Clinical features range from hepatic manifestations to systemic ones. Chronic active hepatitis may present with cholestasis, but the latter is not always related with the grade of activity. Group 2B had elevated aminotransferases and a low concentration for protrobine.

  2. Antiviral therapy for chronic hepatitis B: a review.

    PubMed

    Hanazaki, Kazuhiro

    2004-03-01

    Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 100 countries, persistent HBV infection is still a serious problem worldwide, causing an estimated annual death rate of one million. It may take several decades until the effect of vaccination will be translated into reduced transmission and morbidity. Meanwhile, patients with persistent HBV infection require better antiviral therapeutic modalities than are currently available. It is well accepted that antiviral therapy for chronic hepatitis B is effective to improve prognosis of patients with HBV by preventing development of hepatitis state and HCC. The therapeutic endpoints for hepatitis B treatment are: 1) sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss, 2) decrease of serum HBV DNA of an undetectable level by a non-PCR method, 3) remission of disease, as shown by normalization of ALT, 4) improvement in liver histology, and 5) reduction of the acute exacerbation, cirrhosis, and HCC. In the present, the antiviral treatment of hepatitis B consists of either interferon alpha or oral lamivudine alone or in combination with existing therapy. Each major antiviral drug of interferon alpha and lamivudine has pros and cons, and effect of combination therapy of both drugs is also still limited. More powerful and safe new antiviral therapies are required to achieve final goal of these therapeutic endpoints. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Therapeutic options for managing hepatitis infection after liver transplantation (LT

  3. Chronic Liver Disease in Peru: Role of Viral Hepatitis

    DTIC Science & Technology

    1994-01-01

    ceruloplasmin, ferritin, iron, antinuclear anti- by one-third of subjects) in 48% of chronic liver bodies (ANA), and antimitochondrial antibodies to rule...Rebagliati (R.F.) and Naval Medical Research Institute Detachment (I.A.P.), Lima, Peru The prevalence of antibodies to hepatitis C virus 19921. To...development of serologic assays for the abuse, defined as being repeatedly intoxicated at least detection of antibody to hepatitis C virus (anti-HCV

  4. Ultrasonographic findings in cattle and buffaloes with chronic hepatic fascioliosis.

    PubMed

    Tharwat, Mohamed

    2012-10-01

    The purpose of this study was to characterize the ultrasonographic findings in cattle and buffaloes with chronic hepatic fascioliosis. To the best of the author's knowledge, this report is the first to document ultrasonographic findings in buffaloes with chronic hepatic fascioliosis. Ultrasonographic findings included distended gallbladders with either homogenous or heterogeneous contents, edema of the gallbladder walls, which ranged from mild or moderate to severe and bile duct mineralization. In 78% of the buffaloes, there was an ultrasonographic picture of hepatic fibrosis in which heterogeneous and hyperechogenic hepatic parenchymas with multiple echogenic foci were imaged. Other ultrasonographic findings included peritoneal, pleural and pericardial effusions. Two cows and one buffalo were slaughtered and examined postmortem. Hence, it was possible to verify distended gallbladders, edema of the gallbladder wall, calcified bile ducts, cholestasis and hepatic fibrosis by using ultrasonography in the cows and buffaloes with chronic hepatic fascioliosis. The procedure offers a useful supplement to clinical, hematological and biochemical examinations on the diagnosis of this condition.

  5. Infrequent Clinical Assessment of Chronic Hepatitis B Patients in United States General Healthcare Settings.

    PubMed

    Spradling, Philip R; Xing, Jian; Rupp, Loralee B; Moorman, Anne C; Gordon, Stuart C; Teshale, Eyasu T; Lu, Mei; Boscarino, Joseph A; Trinacty, Connie M; Schmidt, Mark A; Holmberg, Scott D

    2016-11-01

    Among 2338 chronic hepatitis B patients followed during 2006-2013 in the Chronic Hepatitis Cohort Study, 78% had ≥1 alanine aminotransferase and 37% had ≥1 hepatitis B virus DNA level assessed annually. Among cirrhotic patients, 46% never had hepatic imaging. Patients in this cohort were insufficiently monitored for disease activity and hepatocellular carcinoma.

  6. The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients

    PubMed Central

    Bokharaei-Salim, Farah; Salehi-Vaziri, Mostafa; Sadeghi, Farzin; Esghaei, Maryam; Monavari, Seyed Hamidreza; Alavian, Seyed Moayed; Fakhim, Shahin; Keyvani, Hossein

    2016-01-01

    Background The hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries. Objectives The aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients. Patients and Methods A total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Results In this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006). Conclusions The data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in

  7. Randomized trial of combined triple therapy comprising two types of peginterferon with simeprevir in patients with hepatitis C virus genotype 1b.

    PubMed

    Tamori, Akihiro; Yoshida, Kanako; Kurai, Osamu; Kioka, Kiyohide; Hai, Hoang; Kozuka, Ritsuzo; Motoyama, Hiroyuki; Kawamura, Etsushi; Hagihara, Atsushi; Uchida-Kobayashi, Sawako; Morikawa, Hiroyasu; Enomoto, Masaru; Murakami, Yoshiki; Kawada, Norifumi

    2016-12-01

    Simeprevir (SMV) is a potent, macrocyclic hepatitis C virus (HCV) non-structural 3/4 A protease inhibitor. This prospective study compared the efficacy and safety of SMV in combination with peginterferon α2a + ribavirin (P2aR) and with peginterferon α2b + ribavirin (P2bR) in Japanese patients with HCV genotype 1b infection.

  8. Fentanyl pharmacokinetics is not dependent on hepatic uptake by organic anion-transporting polypeptide 1B1 in human beings.

    PubMed

    Ziesenitz, Victoria C; König, Sonja K; Mahlke, Nina; Jantos, Ricarda; Skopp, Gisela; Weiss, Johanna; Haefeli, Walter E; Mikus, Gerd

    2013-07-01

    A recent study investigating the pharmacokinetics of fentanyl in Sprague-Dawley rats suggested fentanyl to be a substrate of rat organic anion-transporting polypeptide Oatp. In human beings, the most important OATP for the pharmacokinetics of many drugs is OATP1B1. Therefore, genetic variants of OATP1B1 (SLCO1B1) might modulate fentanyl pharmacokinetics and efficacy in human beings. Sixteen healthy male and female volunteers, homozygous for SLCO1B1*1a (genetic wild-type) (n = 11) or *15 (deficient haplotype carrying the single-nucleotide polymorphisms rs2306283 and rs4149056 and exhibiting altered transport activity; n = 5), were included in this randomized crossover study. The participants received fentanyl (5 μg/kg) intravenously alone or with the OATP inhibitor rifampicin (600 mg single oral dose). The pharmacokinetics of fentanyl and norfentanyl were determined by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In addition, fentanyl uptake in vitro was evaluated in OATP1B1 overexpressing HEK293 cells and compared to a mock-transfected cell line. In the clinical trial, fentanyl clearance was 18.8 ± 8.2 mL/min. kg in SLCO1B1*1a and 19.5 ± 1.8 mL/min/kg in SLCO1B1*15 carriers and not significantly different between the genotypes. During rifampicin, fentanyl clearance was 15.0 ± 4.4 mL/min/kg in SLCO1B1*1a and 16.7 ± 5.9 mL/min/kg in SLCO1B1*15 carriers (p > 0.5). In addition, in vitro data also indicate that fentanyl is not transported by OATP1B1. In conclusion, our data indicate that OATP1B1 has no impact on fentanyl pharmacokinetics in human beings.

  9. Chronic Hepatitis C Infection in a Rural Medicaid HMO

    ERIC Educational Resources Information Center

    Calvert Jr., James F.; Goldenberg, Paula C.; Schock, Cathy

    2005-01-01

    Chronic hepatitis C infection (CHCI) is an increasingly common problem, affecting about 2% of the US population. The cost and complexity of treatment and difficulties in communicating with the infected population are of concern to insurers and health planners. Purpose: To describe the clinical features of patients with CHCI in a rural…

  10. High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection.

    PubMed

    Castillo, Inmaculada; Bartolomé, Javier; Quiroga, Juan Antonio; Carreño, Vicente

    2013-08-01

    Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.

  11. Hepatic folate metabolism in the chronic alcoholic monkey

    SciTech Connect

    Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

    1981-05-01

    To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of /sup 3/H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected.

  12. Nutritional support treatment for severe chronic hepatitis and posthepatitic cirrhosis.

    PubMed

    Qin, Huimin; Li, Hongtao; Xing, Mingyou; Wu, Chunming; Li, Guojun; Song, Jianxin

    2006-01-01

    The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT)+PN; group C subject to CT+EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-bil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P<0.05). Compared with group D, the values of TP and Alb were increased significantly in group E (P<0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

  13. Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment

    PubMed Central

    Ding, Shengyuan; Li, Li

    2015-01-01

    The striatonigral projection is a striatal output pathway critical to motor control, cognition, and emotion regulation. Its axon terminals in the substantia nigra pars reticulata (SNr) express a high level of serotonin (5-HT) type 1B receptors (5-HT1BRs), whereas the SNr also receives an intense 5-HT innervation that expresses 5-HT transporters, providing an anatomic substrate for 5-HT and selective 5-HT reuptake inhibitor (SSRI)-based antidepressant treatment to regulate the striatonigral output. In this article we show that 5-HT, by activating presynaptic 5-HT1BRs on the striatonigral axon terminals, potently inhibited the striatonigral GABA output, as reflected in the reduction of the striatonigral inhibitory postsynaptic currents in SNr GABA neurons. Functionally, 5-HT1BR agonism reduced the striatonigral GABA output-induced pause of the spontaneous high-frequency firing in SNr GABA neurons. Equally important, chronic SSRI treatment with fluoxetine enhanced this presynaptic 5-HT1BR-mediated pause reduction in SNr GABA neurons. Taken together, these results indicate that activation of the 5-HT1BRs on the striatonigral axon terminals can limit the motor-promoting GABA output. Furthermore, in contrast to the desensitization of 5-HT1 autoreceptors, chronic SSRI-based antidepressant treatment sensitizes this presynaptic 5-HT1BR-mediated effect in the SNr, a novel cellular mechanism that alters the striatonigral information transfer, potentially contributing to the behavioral effects of chronic SSRI treatment. PMID:25787955

  14. [Interdisciplinary aspects of and new drugs for chronic hepatitis B].

    PubMed

    Horváth, Gábor

    2013-07-21

    Hepatitis B virus infection is a significant health problem worldwide. The prevalence of HBsAg positivity is about 0.5-0.7% in Hungary. Liver cirrhosis and/or hepatocellular carcinoma develops in 15-40% of chronic hepatitis B virus infected patients without treatment. The ultimate goal of treatment would be to clear the virus from the infected subject; however, in practice, we can usually achieve long term suppression of viral replicaton with consequent prevention of the progression of liver disease, and reduction of the risk of the development of liver cirrhosis and hepatocellular carcinoma. Currently, there are two different treatment strategies for patients with chronic hepatitis B virus infection: therapy of finite duration with interferon or long-term treatment with nucleot(s)ide analogues. Entecavir and tenofovir are the two most effective nucleot(s)ide analogues with high barrier to resistance, thus, they can be confidently used as first-line treatments. Lamivudine engenders very high rates of resistance; adefovir is less efficacious than entecavir or tenofovir, and also engendering higher rates of resistance, thus none of them are recommended for initiation of a new treatment. Tenofovir is the treatment option in cases with lamivudine resistance, because entecavir has an unfavourable resistance-profile in this group of patients. Interferon is contraindicated during pregnancy. Should treatment of chronic hepatitis B virus infection be necessary during pregnancy, tenofovir, listed by the FDA as pregnancy category B drug, is to be preferred. Nucleot(s)ide analogues may be used to reduce the risk of intra-uterine and perinatal transmission of hepatitis B virus, which may occur in a proportion of newborns from highly viremic mothers, despite active and passive immunization. Similarly, tenofovir is recommended in the last trimester of pregnancy for women with high viremia. The risk of reactivation of chronic hepatitis B virus infection is high in HBsAg positive

  15. Causes of thrombocytopenia in chronic hepatitis C viral infection.

    PubMed

    Osada, Makoto; Kaneko, Makoto; Sakamoto, Minoru; Endoh, Masumi; Takigawa, Koichi; Suzuki-Inoue, Katsue; Inoue, Osamu; Satoh, Kaneo; Enomoto, Nobuyuki; Yatomi, Yutaka; Ozaki, Yukio

    2012-06-01

    We retrospectively studied 89 patients with chronic hepatitis C virus (HCV) infection, including 50 chronic hepatitis (CH) cases, 18 liver cirrhosis (LC) cases, and 21 LC with hepatocellular carcinoma (LC + HCC) cases, with regard to various factors related with thrombocytopenia. The platelet count decreased with the stage advancement of liver diseases. Multiple regression analysis revealed that splenomegaly and von Willebrand factor (vWF) were explanatory variables that correlated with thrombocytopenia. Splenomegaly appears to be the most responsible factor, although there are a considerable number of thrombocytopenic cases without splenomegaly, suggesting other factors may also be responsible. The vWF level is inversely correlated with the platelet count. Soluble thrombomodulin, a marker of endothelial dysfunction, increases with the advancement of liver fibrosis. It is positively correlated with vWF and inversely with the platelet count. Our present results imply that vascular endothelial dysfunction is also involved in thrombocytopenia during chronic HCV infection.

  16. Use of antiviral therapy in patients with chronic hepatitis C

    PubMed Central

    Dragomiretskaya, Natalia; Izha, Anna; Kalinichenko, Nikolay; Szark-Eckardt, Mirosława; Klimczyk, Mariusz; Cieślicka, Mirosława; Muszkieta, Radosław; Prusik, Krzysztof; Napierała, Marek; Żukowska, Hanna

    2015-01-01

    Introduction The presence of background HCV infection cannot be overestimated in view of the prevalence of chronic hepatitis C and the risk of adverse outcomes of this disease. Purpose of this study was to evaluate the effectiveness of the combined use of antiviral therapy (Roferon + Vero-Ribavirin) and resort factors in patients with chronic hepatitis C in the phase of replication. Material and methods We observed 48 patients with chronic hepatitis C; the minimum level of activity of the process defined the phase of replication. Markers of HCV infection were determined by enzyme linked immunosorbent assay (ELISA) (a-HCV and HCV-Ig M). HCV RNA was determined twice by the polymerase chain reaction (PCR). Genotyping of hepatitis C virus was performed. Biochemical blood analysis and the study of HCV infection markers were carried out four times. Results of therapy were assessed immediately after the end of the resort (spa) treatment, then at 3, 6 and 12 months after starting treatment. At 12 months after starting treatment, all the observed patients had persistent clinical and biochemical remission. Elimination of the virus from the blood was noted in 56% of the control group and 74% of patients in the study group. Conclusions For patients with moderately active HCV, the replication phase was characterized by asthenic-vegetative syndrome (100% of patients) with severe depression (22.92%), pain (77.08%) and dyspeptic syndrome (33.33%), moderate hypertransferaseemia (100%), slightly pronounced cholestasis (33% of patients), and signs of mesenchymal-inflammatory response.

  17. Hepatitis B-Related Concerns and Anxieties Among People With Chronic Hepatitis B in Australia

    PubMed Central

    Hajarizadeh, Behzad; Richmond, Jacqui; Ngo, Naomi; Lucke, Jayne; Wallace, Jack

    2016-01-01

    Background The psychological wellbeing of people with chronic hepatitis B (CHB) may be negatively affected due to the chronic and transmissible nature of the disease, and possible serious complications (e.g. cirrhosis and liver cancer). There are limited data investigating concerns and anxieties among people living with CHB. Objectives This study examined feelings about having hepatitis B among people with CHB, including hepatitis B-related concerns and anxieties. Patients and Methods Using convenience sampling, people with CHB attending four public liver clinics and one general practice in three Australian jurisdictions between April and September 2013 completed a self-administered questionnaire about their feelings about having hepatitis B. Results Ninety-three people completed the survey. Mean age was 45 years, 57% were men, and 93% were born overseas (75% from Asia). Seventy-six percent of participants reported having hepatitis B-related concerns and anxieties. The most common concerns were of developing liver cancer (57%), and infecting other people (53%). Thirty-five percent of participants were unwilling to talk to anyone about their hepatitis B while 25% changed how they lived as a result of having hepatitis B. Lower educational level was associated with feeling scared of hepatitis B (adjusted Odds Ratio [OR]: 4.04; 95%CI: 1.09, 14.90; P = 0.04), and an unwillingness to talk to anyone about hepatitis B (adjusted OR: 4.41; 95%CI: 1.09, 17.83; P = 0.04). Very good English proficiency was associated with a higher likelihood of participants changing how they lived (adjusted OR: 12.66; 95%CI: 2.21, 72.42; P < 0.01), and seeing life differently as a result of having hepatitis B (adjusted OR: 21.10; 95%CI: 3.70, 120.19; P < 0.01). Health professionals were the key person for 34% of participants in helping them cope with having hepatitis B, while 18% reported that no one supported them. Conclusions Hepatitis B-related concerns and anxieties are prevalent among

  18. The association between indirect bilirubin levels and liver fibrosis due to chronic hepatitis C virus infection.

    PubMed

    Cengiz, Mustafa; Yılmaz, Guldal; Ozenirler, Seren

    2014-08-01

    We proposed to evaluate the association between serum indirect bilirubin levels and liver fibrosis in patients with chronic hepatitis C (CHC) genotype 1b. Biopsy proven CHC genotype 1b patients' demographics, clinical and histopathological characteristics were evaluated. Logistic regression analysis was done to evaluate the clinical, laboratory and demographic features of the histologically proven liver fibrosis in CHC patients. A total of 112 biopsy proven CHC genotype 1b patients were enrolled into the study. Liver fibrosis scores were measured by using Ishak fibrosis scores and were divided into two groups; fibrosis scores ≤ 2 were categorized as mild fibrosis, 82 patients (73.2%), whereas fibrosis scores >2 were categorized as advanced fibrosis group, 30 patients (26.8%). Patients with advanced fibrosis had lower indirect bilirubin levels than the mild fibrosis group (0.28 ± 0.02 mg/dl vs. 0.44 ± 0.032 mg/dl, p<0.001, respectively). Indirect bilirubin level was negatively correlated with advanced fibrosis scores (r=-0.416 and p<0.001). In multivariate logistic regression analysis, low indirect bilirubin level was an independent predicting factor of advanced liver fibrosis (OR: 0.001, 95% CI: 0.0-0.005, p<0.001). There is an inverse relationship between indirect bilirubin levels and advanced liver fibrosis caused by CHC genotype 1b.

  19. Comparative study between occult hepatitis C virus infection and chronic hepatitis C.

    PubMed

    Pardo, M; López-Alcorocho, J M; Rodríguez-Iñigo, E; Castillo, I; Carreño, V

    2007-01-01

    We have recently described the presence of occult hepatitis C virus (HCV) infection (HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA) in patients with persistently abnormal liver function tests of unknown aetiology. The aim of this study was to compare the characteristics of patients with occult HCV infection vs those of patients with chronic hepatitis C. We compared clinical features of 68 patients with occult HCV infection and 69 untreated chronic HCV patients (anti-HCV and serum HCV-RNA positive), matched for age, gender, duration of abnormal liver function tests and body mass index. Aspartate aminotransferase and alanine aminotransferase were higher (P < 0.001) in chronic HCV, but cholesterol and triglycerides were significantly higher in patients with occult HCV infection (P < 0.001 and P = 0.002). Chronic HCV patients had higher gamma-globulin (P = 0.005), alpha-foetoprotein (P < 0.001) and iron (P < 0.001) levels. Percentage of patients with necroinflammatory activity and fibrosis was higher (P < 0.001) in chronic HCV than in occult HCV infection. Mean percentage of infected hepatocytes was higher (P = 0.001) in chronic HCV (10.1%) than in occult HCV infection (5.3%). This occult HCV infection is a milder disease than chronic HCV, and this could be related to the significantly lower number of infected hepatocytes observed in occult HCV.

  20. The clinical outcomes of chronic hepatitis C in South Korea

    PubMed Central

    Ok, Kyeong Sam; Jeong, Sook-Hyang; Jang, Eun Sun; Kim, Young Seok; Lee, Youn Jae; Kim, In Hee; Cho, Sung Bum; Bae, Si Hyun; Lee, Han Chu

    2016-01-01

    Abstract This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region. From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival. During the median follow-up of 39.0 months (range 18.0–81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150  × 109/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002). The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy. PMID:27583874

  1. Hepatic miR-29ab1 expression modulates chronic hepatic injury

    PubMed Central

    Kogure, Takayuki; Costinean, Stefan; Yan, Irene; Braconi, Chiara; Croce, Carlo; Patel, Tushar

    2012-01-01

    MicroRNAs (miRNAs) are small, regulatory non-coding RNAs that have potent effects on gene expression. Several miRNA are deregulated in cellular processes involved in human liver diseases and regulation of cellular processes. Recent studies have identified the involvement of miR-29 in hepatic fibrosis and carcinogenesis. Although several targets of miR-29 have been identified, there is limited information regarding the cell-type specific roles of miR-29 in the liver, and we sought to evaluate the role of this miRNA in hepatic pathobiology. We report the generation of a tissue–specific knockout mouse to evaluate the role of miR-29 in hepatic fibrosis and carcinogenesis in response to injury. We hypothesized that miR-29 contributes to the hepatocyte driven response to chronic cellular injury that results in fibrosis. In support of this hypothesis, fibrosis and mortality were enhanced in miR29 knockout mice in response to carbon tetrachloride. Genome-wide gene expression analysis identified an over-representation of genes associated with fibrosis. The oncofetal RNA H19 was modulated in a miR-29 dependent manner following exposure to carbon tetrachloride in vivo. The impact of a hepatocyte specific miR-29 knockout on survival following chronic hepatic injury in vivo implicates this miRNA as a potential target for intervention. These results provide evidence of the involvement of miR-29 in chronic hepatic injury, and suggest a role for deregulated hepatocyte expression of miR-29 in the response to hepatic injury, fibrosis and carcinogenesis. PMID:22469499

  2. [Hepatitis non-A, non-B: epidemiological significance in acute viral hepatitis and chronic active hepatitis of hepatological consultation].

    PubMed

    Jmelnitzky, A C; Basualdo, J A; Belloni, P O; Ponce de León, H H; García, C; Curciarello, J

    1987-01-01

    157 acute viral hepatitis and 60 chronic active ones have been analyzed focusing on NANB etiology. HAV was implicated in 36.3% of the hole acute viral hepatitis sample, HBV in 29.3%, and HNANBV was presumed as etiology in 31.2%, 5 patients (3.2%) had acute infection by HAV, on previous one by HBV, except for Epstein-Barr virus, no other test for viruses were determined (CMV, HSV, etc.). Male/female ratio was 1.4:1, 1.9:1, and 1.4:1 for HAV, HBV and HNANBV acute hepatitis respectively; HAV was the main etiology in the 0-9 age group (72.2%) although it only represents 11.5% of the sample; small occurrence of HAV hepatitis were found in patients over 40 (8.8%); HBV was clearly prevalent in patients over 50 (65.2%); the highest concentration of NANB etiology was found between 20-39 years old, but it was represented in all age-groups. Out of 49 NANB acute hepatitis, 12.2% had related transfusional antecedents, 12.2% belonged to health care worker group, and 4.1% had a close family NANB hepatitis contact; 71.5% had no reported antecedent. Viral source was presumably implicated in 75.0% of chronic active hepatitis, 25.0% attributable to HNANBV. Results seem not feasible to transfer to general population due to the facts that most patients were of specialized consult, and pediatric assistance is unusual to the authors practice.

  3. Chronic hepatitis C: This and the new era of treatment

    PubMed Central

    Bertino, Gaetano; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Demma, Shirin; Ruggeri, Maria Irene; Scuderi, Laura; Malaguarnera, Giulia; Bertino, Nicoletta; Rapisarda, Venerando; Di Carlo, Isidoro; Toro, Adriana; Salomone, Federico; Malaguarnera, Mariano; Bertino, Emanuele; Malaguarnera, Michele

    2016-01-01

    Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. PMID:26807205

  4. Management of chronic hepatitis B in an HIV-positive patient with 3TC-resistant hepatitis B virus.

    PubMed

    Ristig, Maria; Drechsler, Henning; Crippin, Jeffrey; Lisker-Melman, Mauricio; Tebas, Pablo

    2003-09-01

    Chronic viral hepatitis has emerged as one of the leading causes of morbidity and mortality among HIV-positive patients. These individuals are at risk for aggressive chronic active hepatitis, cirrhosis, and hepatocellular carcinoma, and eventually, death. Currently available therapies for hepatitis B are limited and include interferon-alpha, lamivudine (3TC), and adefovir. Tenofovir (TDF), a recently approved drug for the treatment of HIV, is also active against hepatitis B. We report the case of a HIV-positive patient with liver cirrhosis secondary to chronic hepatitis B virus (HBV) with evidence of resistance to 3TC. The patient was initially accepted as a liver transplant candidate. However, when TDF was added to his treatment, a remarkable virologic and histopathologic improvement was achieved. The patient was subsequently removed from the liver transplant program and has not suffered from any further hepatic complications.

  5. Chronic hepatitis B in children in Gothenburg, Sweden.

    PubMed

    Söderström, A; Lindh, M; Eriksson, K; Horal, P; Krantz, M; Kristiansson, B; Lindberg, J; Norkrans, G

    1999-01-01

    Sweden is a low prevalence area for hepatitis B, but the number of chronic carriers has increased during the last decade due to immigration. Out of a total of 120 children with identified chronic hepatitis B in Gothenburg, Sweden, 93 were investigated during the 2-year period 1994-95. The children had a mean age of 10.9 years and originated from 21 different countries. Most infections were discovered during various screening programmes after arrival in Sweden. A total of 90 of the 93 children were HBV-DNA positive by Amplicor HBV Monitor (Roche Diagnostics) and 58% (54/93) were HBeAg positive. All children either originated from areas with a high or medium prevalence of HBV infection (81/93, 87%) or were born in Sweden to mothers originating from high or medium prevalence countries (12/93, 13%). Three of these 12 children were vertically infected in spite of adequate immunoprophylaxis and 8 were born to mothers with undiscovered chronic HBV infection. In all, 34 children had mothers who were HBsAg positive. No overt case of transmission was notified in day-care centres or schools, or from a child to a non-immune parent. None of the children reported any symptoms of liver disease, but 38% (35/93) had elevated aminotransferases. Therefore, screening programmes are essential to identify chronic HBV infection in children in order to prevent transmission and to find individuals at risk of progressive liver damage who should be considered for treatment.

  6. Antiviral Natural Products Against Chronic Hepatitis B: Recent Developments.

    PubMed

    Parvez, Mohammad K; Arbab, Ahmed H; Al-Dosari, Mohammed S; Al-Rehaily, Adnan J

    2016-01-01

    Hepatitis B virus (HBV) is inherently a hepatotropic virus that causes acute and chronic hepatitis in about one-third of world population. Of the estimated 360 million chronically infected individuals, more than one million die of liver cirrhosis, fulminant liver failure or hepatocellular carcinoma (HCC) every year. Though there is an effective vaccine available, failure to protection because of vaccine-escape viral mutants in some population is also reported. Moreover, all the currently approved antiviral drugs have their limitations, too. Interferon (IFN-α) has limited efficacy and a high incidence of adverse side-effects in a proportion of chronic patients. Nucleos(t)ide analogs like, lamivudine, adefovir, tenofovir and entecavir are very effective in treating chronic hepatitis B (CHB), but long-term therapy eventually leads to drug-resistance. As an alternative approach, natural or plant products have provided promising therapeutics in modern pharma industry. Owing to their characteristics of high chemical diversity and biochemical specificity, natural products offer great promises as potentially effective antiviral drugs. A broad spectrum of phytochemicals including flavonoids (e.g., Vogonin), terpenes (e.g., Artemisinin), alkaloids (e.g., Oxymatrine), polyphenolics (e.g., geraniin), saponins (e.g., Astragaloside IV) and lignans (e.g., Helioxanthin) has been isolated and investigated for anti-HBV activities in vitro as well as in vivo. Nevertheless, these promising compounds have different and overlapping mechanisms of action by either inhibiting viral antigens secretion or suppression of DNA replication. The present article reviews the recent developments in anti-HBV natural products.

  7. Hepatic encephalopathy in acute-on-chronic liver failure.

    PubMed

    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  8. Recent Advances in Antiviral Therapy for Chronic Hepatitis C

    PubMed Central

    Tamori, Akihiro; Enomoto, Masaru; Kawada, Norifumi

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide health problem. Chronic infection induces continuous inflammation in the liver, progression of hepatic fibrosis, eventual cirrhosis, and possible hepatocellular carcinoma. Eradication of the virus is one of the most important treatment aims. A number of promising new direct-acting antivirals (DAAs) have been developed over the past 10 years. Due to their increased efficacy, safety, and tolerability, interferon-free oral therapies with DAAs have been approved for patients with HCV, including those with cirrhosis. This review introduces the characteristics and results of recent clinical trials of several DAAs: NS3/4A protease inhibitors, NS5A inhibitors, and NS5B inhibitors. DAA treatment failure and prognosis after DAA therapy are also discussed. PMID:27022210

  9. Lamivudine treatment in patients with chronic hepatitis B and cirrhosis.

    PubMed

    Haché, Chantal; Villeneuve, Jean-Pierre

    2006-09-01

    Chronic hepatitis B is a common disease and approximately 20% of infected patients with compensated cirrhosis will decompensate over 5 years. If untreated, the survival of decompensated cirrhosis is poor (15% at 5 years). The extent of hepatitis B virus (HBV) replication, as assessed by serum HBV-DNA level, is a strong predictor of the risk of disease progression and hepatocellular carcinoma. This provides a rationale for antiviral therapy to arrest progression of liver disease. Lamivudine is a pyrimidine analogue that inhibits HBV-DNA reverse transcriptase. It decreases HBV replication, normalises alanine aminotransferase levels and reduces hepatic inflammation and fibrosis in patients with chronic hepatitis B. This article will focus on the use of lamivudine in patients with HBV-cirrhosis. In patients with compensated HBV-cirrhosis, a randomised, placebo-controlled trial has shown that lamivudine significantly reduced the rate of disease progression and hepatocellular carcinoma development over a 3-year period. In patients with decompensated cirrhosis, treatment with lamivudine can produce spectacular improvements of liver function, but the improvement is slow and a clinical benefit is usually not observed until after at least 3-6 months of treatment. A major drawback of lamivudine treatment is the development of resistance, observed in 15-20% of patients after 1 year and up to 70% after 5 years of continued treatment. Thus, patients with HBV-cirrhosis treated with lamivudine should have regular monitoring of serum HBV-DNA levels and prompt institution of additional antiviral therapy if viral breakthrough is observed. Adefovir, tenofovir and entecavir have demonstrated efficacy in patients with lamivudine resistance. In patients with decompensated cirrhosis, in whom the development of resistance can be fatal, combination therapy (such as lamivudine plus adefovir) may prove more effective than monotherapy and this issue needs further study.

  10. Functional connectivity alterations in patients with chronic hepatitis C virus infection: A multimodal MRI study.

    PubMed

    Kharabian Masouleh, S; Herzig, S; Klose, L; Roggenhofer, E; Tenckhoff, H; Kaiser, T; Thöne-Otto, A; Wiese, M; Berg, T; Schroeter, M L; Margulies, D S; Villringer, A

    2017-03-01

    Chronic hepatitis C virus (HCV) infection is associated with fatigue and depression. Cognitive impairments are also reported in a smaller number of HCV-positive patients. Recent studies linked HCV to low-grade inflammation in brain. Here, we test the hypothesis that chronic HCV is associated with 3T-neuroimaging-derived grey matter volume (GMV) and functional connectivity alterations in a sample of chronic HCV (1b), without severe liver disease. Regional GMV and resting-state fMRI-derived eigenvector centrality (EC) were compared between 19 HCV-positive patients and 23 healthy controls (all females, 50-69 and 52-64 years, respectively), controlling for white matter hyperintensities and age. Standard tests were used to assess fatigue, depression and cognitive performance. Also, liver fibrosis stage and viral load were quantified among patients. In comparison with controls, HCV-positive patients had higher scores in fatigue and depression, and worse alertness scores. The groups performed similarly in other cognitive domains. We report higher EC in a cluster in the right anterior superior parietal lobule in patients, while no differences are found in GMV. Post hoc functional connectivity analysis showed increased connectivity of this cluster with primary and secondary somatosensory cortex, and temporal and occipital lobes in patients. Higher mean EC in the superior parietal cluster, adjusted for mean framewise displacement, was associated with better memory and attention performance, but not with fatigue, depression, viral load or level of liver fibrosis, among patients. These results suggest a compensatory mechanism in chronic hepatitis C and explain equivocal results in the literature about cognitive deficits in infected persons. Further studies should define the relation of these connectivity changes to the brain's inflammatory activity.

  11. Chronic hepatitis B: management challenges in resource-poor countries.

    PubMed

    Nwokediuko, Sylvester Chuks

    2011-10-01

    Sylvester Chuks Nwokediuko, Department of Medicine, University of Nigeria Teaching Hospital, Ituku OzallaChronic infection with hepatitis B virus (HBV) is a global public health problem because of its worldwide distribution and its potential to cause sequelae. HBV is most prevalent in China, South East Asia, sub-Saharan Africa, and the Amazon basin of South America where health care resources are most limited. Numerous challenges exist for effective management of chronic HBV infection, particularly in resource-limited regions. These challenges include lack of accurate prevalence data, absence of a surveillance program, and poor political will of governments in resource-poor countries to enforce effective measures to control the disease. There is a lack of understanding regarding HBV infec-tion by both the general public and health care providers. A better understanding of the pathogenesis and treatment of this condition is necessary. The acute shortage of trained medical manpower necessary for accurate diagnosis and treatment of chronic hepati-tis B (CHB) in resource-poor countries is a formidable challenge. The condition is com-plicated by the continuing efflux of medical graduates from low-income economies to richer countries. The most critical problem in the management of CHB is the high cost of laboratory tests and drugs. Drugs are also not readily available. Other challenges in the manage-ment of CHB include stigmatization of patients, co-infection with other viruses, lack of management guidelines, and absence of an effective patient referral system. To address these challenges, governments of resource-poor nations must be committed to budg-etary allocation for the implementation of health programs. It is necessary to provide awareness campaigns, health education, proper screening of blood and blood products for transfusion, active screening, intensification of existing childhood immunization, technical and financial assistance from wealthier nations, and

  12. Effects of He-Ne laser acupuncture-point irradiation on serology hepatitis virus markers in chronic hepatitis B

    NASA Astrophysics Data System (ADS)

    Wang, Yue-lan; Huang, Bing-chen; Ni, Liu-da

    1993-03-01

    For most of the patients with chronic hepatitis B the immunologic function is deficient. Immunopotentiation and immunoregulation can be used as effective treatments. Laser irradiation can potentiate the cellular immune function of the human body and has good effects on improving clinical symptoms, cutting short the process of diseases, and promoting HBsAg negative change. Thereby we have a randomized opportunity to study the effect of He-Ne laser acupoint irradiation on serological HBV markers (HBVM) in chronic hepatitis B (CHB).

  13. Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis

    PubMed Central

    Kamar, Nassim; Lhomme, Sébastien; Abravanel, Florence; Marion, Olivier; Peron, Jean-Marie; Alric, Laurent; Izopet, Jacques

    2016-01-01

    Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection. PMID:27537905

  14. Egy-Score as a Noninvasive Score for the Assessment of Hepatic Fibrosis in Chronic Hepatitis C: A Preliminary Approach

    PubMed Central

    Alboraie, Mohamed; Khairy, Marwa; Elsharkawy, Aisha; Elsharkawy, Marwa; Asem, Noha; El-Seoud, Amany R. Abo; Elghamry, Fathy G.; Esmat, Gamal

    2014-01-01

    Background and Aims: Egy-Score is a new noninvasive score for prediction of severe hepatic fibrosis in patients with chronic liver diseases. The aim of this study was to validate Egy-Score as a noninvasive score for predicting stage of hepatic fibrosis in a group of Egyptian chronic hepatitis C patients. Patients and Methods: One hundred Egyptian patients with chronic hepatitis C were enrolled. Mean age was 40.25 ± 9.39 years. They were subjected to CA19-9, alpha-2-macroglobulin, total bilirubin, platelet count and albumin, liver biopsy, and histopathological staging of hepatic fibrosis according to METAVIR scoring system as part of their assessment for treatment. Egy-Score was calculated according to the following formula: Egy-Score = 3.52 + 0.0063 × CA19-9 + 0.0203 × age + 0.4485 × alpha-2-macroglobulin + 0.0303 × bilirubin – 0.0048 × platelet – 0.0462 × albumin. Egy-Score results were correlated to the stage of hepatic fibrosis. Results: Egy-Score correlates positively with the stage of hepatic fibrosis (F0–F4). Egy-Score was able to differentiate significant hepatic fibrosis, severe hepatic fibrosis, and cirrhosis accurately. Cutoff values of Egy-Score were 2.91850 (for significant fibrosis), 3.28624 (for severe fibrosis), and 3.67570 (for cirrhosis). Sensitivity, specificity, and areas-under-ROC curve (AUROCs) were 75.8%, 68.42%, and 0.776 (for significant fibrosis “≥F2”), 91.67%, 77.63%, and 0.875 (for severe fibrosis “≥F3”), and 81.82%, 86.52%, and 0.874 (for cirrhosis “F4”), respectively. Conclusion: Egy-Score is a useful noninvasive panel of surrogate biomarkers that could accurately predict different stages of hepatic fibrosis in patients with chronic hepatitis C. PMID:24976280

  15. Management of Antiviral Resistance in Chronic Hepatitis B

    PubMed Central

    Lim, Young-Suk

    2017-01-01

    The primary goal of therapy for chronic hepatitis B (CHB) is to prevent liver disease progression. Hepatitis B surface antigen (HBsAg) seroclearance or seroconversion is regarded as an optimal endpoint to discontinue treatment. However, HBsAg seroclearance occurs very rarely with nucleos(t)ide analog (NUC) treatment, and long-term, almost indefinite, NUC treatment is required for the majority of patients. In patients with drug-resistant hepatitis B virus (HBV), a combination of tenofovir disoproxil fumarate (TDF) and entecavir (ETV), which is currently regarded as the strongest combination therapy against HBV, would be potentially safe to prevent the emergence of additional HBV resistance mutations. However, long-term tolerance data are lacking, and cost may be an issue for combination therapies. Several recent, well-designed, randomized controlled trials have shown that TDF mono-therapy provides similar antiviral efficacy compared with the combination of TDF and ETV. Furthermore, no additional HBV resistance mutations emerged during TDF monotherapy for up to 96 weeks. Considering a comparable antiviral efficacy, extremely low risk of TDF-resistance, lower cost, and better safety potential, TDF monotherapy would be a reasonable choice for the treatment of drug-resistant patients with CHB. PMID:28183162

  16. Hepatitis B antigen in hepatocytes of chronic active liver disease.

    PubMed

    Kawanishi, H

    1979-04-01

    To study the morphologic interrelation of hepatocytes with the replication of hepatitis B vius (HBV) and immunocompetent cells in chronic active liver disease(CALD), organ cultures were prepared from liver biopsy specimens. Replication of hepatitis B core antigen (HBcAg) appears to occur in the nucleus of the hepatocyte in close association with intranuclear electron-dense strands and sometimes intranucleolar matrixes (likely HBcAg genomes), and cytoplasmic maturation of the HBcAg takes place in the preautolytic condition of host hepatocytes. Immunocompetent cells became progressively autolyzed in the early period of cultures. No difference in progression of hepatocyte injury in tissues from normal subjects and from hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients with CALD may suggest that intracellular synthesis of HBV alone is not cytopathic to host hepatocytes. This model is promising for the study of HBV replication and development, and also for testing the efficacy of new antiviral agents against the virus.

  17. [Evidence-based medicine: treatment of chronic hepatitis C. Liege Study Group on Viral Hepatitis].

    PubMed

    Delwaide, J; Gérard, C

    2000-05-01

    The Hepatitis C virus (HCV) infects nearly 170 million people in the world. The major characteristic of virus C is its tendency to chronicity in more than 85% of cases. Generally asymptomatic, HCV infection may also evolve with time to cirrhosis and hepatocellular carcinoma. During the last few years, HCV-related end-stage cirrhosis has become the first cause of liver transplantation. In 10 years only, very significant progress has been made in the knowledge of the virus, not only in the field of diagnosis but also in therapy. Several consensus conferences taking last discoveries into account have been organized in order to promote recommendations useful for the management of hepatitis C patients. The aim of this short overview is to summarize practical recommendations that emerged recently from consensus meetings.

  18.  Association between hepatitis B virus and chronic kidney disease: a systematic review and meta-analysis.

    PubMed

    Fabrizi, Fabrizio; Donato, Francesca M; Messa, Piergiorgio

     Background. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection with hepatitis B virus impacts on the development and progression of chronic kidney disease.

  19. Liver steatosis in children with chronic hepatitis B and C

    PubMed Central

    Pokorska-Śpiewak, Maria; Kowalik-Mikołajewska, Barbara; Aniszewska, Małgorzata; Pluta, Magdalena; Walewska-Zielecka, Bożena; Marczyńska, Magdalena

    2017-01-01

    Abstract Only scarce data on liver steatosis in children with chronic hepatitis B and C (CHB and CHC) are available. The objective of this study was to evaluate the prevalence, predictors, and impact of hepatic steatosis on children with CHB and CHC. A total of 78 patients aged 11.5 ± 3.4 years were included: 30 (38%) had CHB, and 48 (62%) had CHC. Steatosis was scored on a 5-point scale, as follows: absent; minimal (≤5% hepatocytes affected), mild (6–33%), moderate (34–66%), and severe (>66%). Stepwise logistic regression was used to determine the factors associated with steatosis and moderate-to-severe steatosis. Steatosis was observed in 4/30 (13%) patients with CHB and 13/48 (27%) patients with CHC (P = 0.17). Moderate-to-severe steatosis was observed in 6/78 (8%) patients: 1/30 (3%) had CHB and 5/48 (10%) had CHC (P = 0.40). The body mass index (BMI) z-score was positively associated with the presence of steatosis in children with CHB (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.02–10.64). In CHC, steatosis occurred more frequently in patients with hepatitis C virus genotype 3 compared with other genotypes (P = 0.002). In patients with non-3 genotype hepatitis C virus, steatosis was associated with the stage of fibrosis (OR = 3.35, 95% CI: 1.01–11.07) and inversely associated with the duration of infection (OR = 0.74, 95% CI: 0.55–0.97). Moderate-to-severe steatosis was positively associated with the BMI z-score (OR = 3.62, 95% CI: 1.22–10.75) and stage of fibrosis (OR = 3.89, 95% CI: 1.05–14.47). Steatosis is a common finding in children with chronic viral hepatitis. It is associated with metabolic factors in CHB, whereas in patients with CHC, metabolic and viral factors may have a combined effect, leading to more advanced grades of steatosis in children with higher BMI z-scores. Moderate-to-severe steatosis is a predictor of advanced fibrosis in children with CHC. PMID:28099338

  20. Prediction of fibrosis progression in chronic viral hepatitis

    PubMed Central

    2014-01-01

    Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools. PMID:25320725

  1. Altered T cell costimulation during chronic hepatitis B infection.

    PubMed

    Barboza, Luisa; Salmen, Siham; Peterson, Darrell L; Montes, Henry; Colmenares, Melisa; Hernández, Manuel; Berrueta-Carrillo, Leidith E; Berrueta, Lisbeth

    2009-01-01

    T-cell response to hepatitis B virus (HBV) is vigorous, polyclonal and multi-specific in patients with acute hepatitis who ultimately clear the virus, whereas it is narrow and inefficient in patients with chronic disease, where inappropriate early activation events could account for viral persistence. We investigated the induction of activation receptors and cytokine production in response to HBcAg and crosslinking of CD28 molecules, in CD4+ cells from a group of chronically infected patients (CIP) and naturally immune subjects (NIS). We demonstrated that CD4+ cells from CIP did not increase levels of CD40L and CD69 following stimulation with HBcAg alone or associated to CD28 crosslinking, in contrast to subjects that resolved the infection (p<0.01). Furthermore, CD4+ cells from CIP produced elevated levels of IL-10 in response to HBcAg. These results suggest that a predominant inhibitory environment may be responsible for altered T cell costimulation, representing a pathogenic mechanism for viral persistence.

  2. Natural regression of fibrosis in chronic hepatitis B

    PubMed Central

    Ohkoshi, Shogo; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko; Kamimura, Kenya; Yano, Masahiko

    2016-01-01

    The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B (CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBeAg seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma (HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been (pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosis-induced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue. PMID:27350724

  3. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B.

    PubMed

    Villeneuve, J P; Condreay, L D; Willems, B; Pomier-Layrargues, G; Fenyves, D; Bilodeau, M; Leduc, R; Peltekian, K; Wong, F; Margulies, M; Heathcote, E J

    2000-01-01

    The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweighed by serious side effects and by the risk of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients with chronic hepatitis B and decompensated cirrhosis with lamivudine 100 mg or 150 mg orally once daily. Pretreatment, all were positive for HBV-DNA in serum. Ten had Child-Pugh class B and 25 had Child-Pugh class C liver disease. Seven patients underwent liver transplantation within 6 months of treatment initiation, 5 patients died within 6 months, and 23 patients were treated for at least 6 months (mean = 19 months). In a majority of these 23 cases, there was a slow but marked improvement in liver function, which was most apparent after 9 months of treatment, with a decrease in serum bilirubin from 67 +/- 13 to 30 +/- 4 micromol/L (P <.05, baseline vs. 9 months), an increase in serum albumin from 27 +/- 1 to 34 +/- 1g/L (P <.05), and a decrease in Child-Pugh score from 10.3 +/- 0.4 to 7.5 +/- 0.5 (P <.05). Three patients developed resistance to lamivudine because of a mutation in the YMDD motif, but liver function did not deteriorate. We conclude that inhibition of viral replication with lamivudine results in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term benefits remain uncertain.

  4. Association between inherited monogenic liver disorders and chronic hepatitis C

    PubMed Central

    Piekuse, Linda; Kreile, Madara; Zarina, Agnese; Steinberga, Zane; Sondore, Valentina; Keiss, Jazeps; Lace, Baiba; Krumina, Astrida

    2014-01-01

    AIM: To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS: This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Case-control analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail. PMID:24575168

  5. Effect of Hepatitis C Virus Genotype 1b Core and NS5A Mutations on Response to Peginterferon Plus Ribavirin Combination Therapy.

    PubMed

    Nakamoto, Shingo; Imazeki, Fumio; Arai, Makoto; Yasui, Shin; Nakamura, Masato; Haga, Yuki; Sasaki, Reina; Kanda, Tatsuo; Shirasawa, Hiroshi; Yokosuka, Osamu

    2015-09-07

    We examined whether hepatitis C virus (HCV) genotype 1b core- and NS5A-region mutations are associated with response to peginterferon α-2b plus ribavirin combination therapy. A total of 103 patients with high HCV genotype 1b viral loads (≥ 100 KIU/mL) were treated with the combination therapy. Pretreatment mutations in the core region and interferon sensitivity determining region (ISDR) in the NS5A region were analyzed. In univariate analysis, arginine and leucine at positions 70 and 91 in the core region, defined as double wild (DW)-type, were associated with early virologic response (p = 0.002), sustained virologic response (SVR) (p = 0.004), and non-response (p = 0.005). Non-threonine at position 110 was associated with SVR (p = 0.004). Multivariate analysis showed the following pretreatment predictors of SVR: hemoglobin level ≥ 14 g/dL (odds ratio (OR) 6.2, p = 0.04); platelet count ≥ 14 × 10⁴/mm³ (OR 5.2, p = 0.04); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio < 0.9 (OR 6.17, p = 0.009); DW-type (OR 6.8, p = 0.02); non-threonine at position 110 (OR 14.5, p = 0.03); and ≥ 2 mutations in the ISDR (OR 12.3, p = 0.02). Patients with non-DW-type, non-threonine at position 110, and < 2 ISDR mutations showed significantly lower SVR rates than others (11/45 (24.4%) vs. 27/37 (73.0%), respectively; p < 0.001). SVR can be predicted through core and NS5A region mutations and host factors like hemoglobin, platelet count, and AST/ALT ratio in HCV genotype 1b-infected patients treated with peginterferon and ribavirin combination therapy.

  6. High Prevalence of Hepatitis C Virus Genotype 1b Infection in a Small Town of Argentina. Phylogenetic and Bayesian Coalescent Analysis

    PubMed Central

    Golemba, Marcelo D.; Di Lello, Federico A.; Bessone, Fernando; Fay, Fabian; Benetti, Silvina; Jones, Leandro R.; Campos, Rodolfo H.

    2010-01-01

    Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina). A total of 89 out of 1814 blood samples collected from people living in Wheelwright, were positive for HCV infection. The highest prevalence (4.9%) was observed in people older than 50 years, with the highest level for the group aged between 70–79 years (22%). The RFLP analyses showed that 91% of the positive samples belonged to the HCV-1b genotype. The E1/E2 and NS5B genes were sequenced, and their phylogenetic analysis showed that the HCV-1b sequences from Wheelwright were monophyletic. Bayesian coalescent-based methods were used to estimate substitution rates and time of the most recent common ancestor (tMRCA). The mean estimated substitution rates and the tMRCA for E1/E2 with and without HVR1 and NS5B were 7.41E-03 s/s/y and 61 years, 5.05E-03 s/s/y and 58 years and 3.24E-03 s/s/y and 53 years, respectively. In summary, the tMRCA values, the demographic model with constant population size, and the fact that the highest prevalence of infection was observed in elder people support the hypothesis that the HCV-1b introduction in Wheelwright initially occurred at least five decades ago and that the early epidemic was characterized by a fast rate of virus transmission. The epidemic seems to have been controlled later on down to the standard transmission rates observed elsewhere. PMID:20090919

  7. High prevalence of hepatitis C virus genotype 1b infection in a small town of Argentina. Phylogenetic and Bayesian coalescent analysis.

    PubMed

    Golemba, Marcelo D; Di Lello, Federico A; Bessone, Fernando; Fay, Fabian; Benetti, Silvina; Jones, Leandro R; Campos, Rodolfo H

    2010-01-18

    Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina).A total of 89 out of 1814 blood samples collected from people living in Wheelwright, were positive for HCV infection. The highest prevalence (4.9%) was observed in people older than 50 years, with the highest level for the group aged between 70-79 years (22%). The RFLP analyses showed that 91% of the positive samples belonged to the HCV-1b genotype. The E1/E2 and NS5B genes were sequenced, and their phylogenetic analysis showed that the HCV-1b sequences from Wheelwright were monophyletic. Bayesian coalescent-based methods were used to estimate substitution rates and time of the most recent common ancestor (tMRCA). The mean estimated substitution rates and the tMRCA for E1/E2 with and without HVR1 and NS5B were 7.41E-03 s/s/y and 61 years, 5.05E-03 s/s/y and 58 years and 3.24E-03 s/s/y and 53 years, respectively. In summary, the tMRCA values, the demographic model with constant population size, and the fact that the highest prevalence of infection was observed in elder people support the hypothesis that the HCV-1b introduction in Wheelwright initially occurred at least five decades ago and that the early epidemic was characterized by a fast rate of virus transmission. The epidemic seems to have been controlled later on down to the standard transmission rates observed elsewhere.

  8. Antiviral Therapy in Chronic Hepatitis B With Mild Acute Exacerbation

    PubMed Central

    Lin, Su; Ye, Qiaoxia; Wang, Mingfang; Wu, Yinlian; Weng, Zhiyuan; Zhu, Yueyong

    2017-01-01

    Background The aim of this study was to assess the efficacy and safety of peginterferon α-2a (pegIFN) and nucleos(t)ide analogues (NA) treatments in patients with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B (CHB) with mild acute exacerbation (AE). Methods Treatment-naive HBeAg-positive CHB patients with AE who received pegIFN or NA (entecavir (ETV) or telbivudine (LDT)) therapies were retrospectively selected. The HBeAg seroconversion rate, hepatitis B surface antigen (HBsAg) loss rate and the cost-effectiveness of different treatments were compared. Results A total of 63 patients with pegIFN therapy and 78 with NA (38 with ETV and 40 with LDT) therapy were included. The HBsAg loss rate was significantly higher in the pegIFN group when compared with the NA group (on week 96: 9/63 (14.29%) vs. 1/78 (1.28%), P = 0.005). No significant difference in hepatitis B virus (HBV) DNA negativity or the HBeAg/HBsAg seroconversion rate was found between ETV and LDT group. One year of pegIFN therapy resulted in 18.56 quality-adjusted life years (QALYs) per patient, and the incremental cost per additional QALY gained was $3,709. Conclusions PegIFN therapy is safe in HBeAg-positive CHB patients with mild AE, as it results in a higher HBsAg loss rate and longer QALYs than NA therapy. PMID:28270871

  9. Children with Chronic Hepatitis B in the US and Canada

    PubMed Central

    Schwarz, Kathleen B; Cloonan, Yona Keich; Ling, Simon C.; Murray, Karen F.; Rodriguez-Baez, Norberto; Schwarzenberg, Sarah Jane; Teckman, Jeffrey; Ganova-Raeva, Lilia; Rosenthal, Philip

    2015-01-01

    Objectives To test the hypothesis that children with chronic hepatitis B (CHB) living in the US and Canada would also have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles. Study design Clinical characteristics of children enrolled in the HBRN were collected from 7 US and Canadian centers. Results Children (n=343) with an age range of 1.0 – 17.8 years were enrolled; 78% of the children were Asian, 55% were adopted and 97% had international origins with either the child or a parent born in one of 31 countries. The majority had hepatitis B virus (HBV) genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (<1%). Children with genotype B or C were Asian (98% and 96%), more consistently hepatitis B e antigen (HBeAg) positive (95% and 82%), had higher median HBV DNA levels (8.2 and 8.3 log10 IU/mL), and less frequently had elevated alanine aminotransferase values (43% and 57%) compared with children with other genotypes. The percentage of HBeAg positivity and of those with HBV DNA ≥6 log10 IU/mL declined with age. Conclusions The majority of children in the HBRN have HBV genotypes which reflect their international origins. Clinical and laboratory data differ substantially by patient age and HBV genotype. Use of these data can help drive the development of optimal strategies to manage and treat children with CHB. PMID:26364985

  10. Hepatitis B virus replication in steroid-treated severe HBsAg-positive chronic active hepatitis.

    PubMed

    Davis, G L; Czaja, A J; Taswell, H F; Ludwig, J; Go, V L

    1985-02-01

    To determine the effect of corticosteroids on the replication of hepatitis B virus and to assess the relationship between virus replication and prognosis, the behavior of serum and tissue HBcAg was evaluated in 16 patients with severe HBsAg-positive chronic active hepatitis who were treated with prednisone and followed for up to 10 years (mean +/- SEM, 66 +/- 9 months). Hepatitis B virus replication was assessed in serum by a solid-phase radioimmunoassay of Dane particle-associated HBcAg and in liver tissue by indirect immunoperoxidase staining for HBcAg. Despite the presence of severe inflammatory activity, only low levels of hepatitis B virus replication were demonstrated. Mean serum HBcAg levels were low at accession and remained essentially unchanged or gradually decreased during corticosteroid therapy. Serum HBcAg appeared in only one patient in whom no virus replication was detected prior to therapy. HBeAg was frequently detected at low titers by radioimmunoassay when serum HBcAg was undetectable. Loss of HBcAg preceded loss of HBeAg by radioimmunoassay, and disappearance of both markers was a prerequisite for sustained histologic remission. In eight patients, inflammation was present despite absence of serum or tissue HBcAg; in three of these, disease activity continued after loss of HBeAg. We conclude that low levels of hepatitis B virus replication may be associated with severe inflammatory activity, and these levels are not increased by long-term corticosteroid therapy. Inflammation can continue despite loss of HBeAg and absence of detectable virus replication.

  11. A noninvasive diagnostic model to assess nonalcoholic hepatic steatosis in patients with chronic hepatitis B

    PubMed Central

    Ou, Hongjie; Cai, Shaohang; Liu, Ying; Xia, Muye; Peng, Jie

    2016-01-01

    Objective: The objective of this study was to develop a noninvasive diagnostic test for nonalcoholic hepatic steatosis in patients with chronic hepatitis B (CHB) by using routinely available clinical markers. Methods: A retrospective study of patients with CHB, with or without hepatic steatosis (fatty change) who were diagnosed with controlled attenuation parameter (CAP) measured by transient elastography were included. Patient information was analyzed on lifestyle; laboratory tests, including serum lipid levels; blood pressure; blood uric acid; and medical history of type 2 diabetes mellitus (T2DM). Results: A total of 1312 patients were included in the study; 618 patients had confirmed hepatic steatosis. The CAP levels were significantly correlated with patient height (p < 0.001), weight (p < 0.001), waistline measurement (p < 0.001), hipline measurement (p < 0.001), and diastolic blood pressure (DBP) (p < 0.001). Multivariate logistic regression analysis resulted in the development of an equation for the diagnostic of simple steatosis: the fatty liver (FL) test. The area under the receiver operating characteristic (AUROC) curve of the FL test was 0.79 (p < 0.001) in the training group and 0.82 in the validation group. When the FL test was >−0.425, the sensitivity, specificity, positive likelihood ratio (LR) and negative LR were 74.72%, 72.12%, 2.68, and 0.35 respectively. The average FL test result was −0.54 ± 1.26 in patients with CHB without hypertension, and 0.42 ± 1.35, 1.12 ± 1.65, and 1.98 ± 1.22 in patients with hypertension grade 1, 2, and 3, respectively (p < 0.001). Conclusion: This study has demonstrated a noninvasive test for hepatic steatosis in patients with CHB. PMID:28203279

  12.  Acute hepatitis E mimicking a flare of disease in a patient with chronic autoimmune hepatitis.

    PubMed

    Calisti, Giorgio; Irish, Dianne N; Ijaz, Samreen; Tedder, Richard S; Moore, Kevin

     Acute hepatitis E is becoming increasingly recognised in Europe with up to 40% of the population in Southern France being exposed to the virus, which is harboured in pigs. Patients with known liver disease may present with acute hepatitis E and present a diagnostic challenge. For example patients with autoimmune hepatitis (AIH) who are immunosuppressed and contract hepatitis E may be at increased risk of developing chronicity due to concurrent immunosuppression. Importantly, the diagnosis may be missed with the infection misdiagnosed as an autoimmune flare, and immunosuppression increased by the attending physician, thus enhancing the risk of chronicity of infection leading to progressive liver injury in immunocompromised patients. We report a case of acute hepatitis E in a patient with AIH and discuss the features that helped us differentiating it from an autoimmune flare.

  13. [The CYP1B1 and CYP2F1 genes polymorphisms frequency in three ethnic groups of Bashkortostan and chronic obstructive pulmonary disease patients].

    PubMed

    Korytina, G F; Akhmadishina, L Z; Viktorova, T V

    2010-01-01

    Chronic obstructive pulmonary disease is a multifactorial respiratory disorder. Members of the cytochrome P450 family catalyze the oxidative metabolism of exogenous chemicals and activate their substrates into reactive intermediates that may initiate lung injury. The aim of this study was to learn interethnic variation in frequency distribution patterns of CYP1B1 and CYP2F1 genes polymorphic markers and to analyse its association withchronic obstructive pulmonary disease. The polymorphic markers Leu432Val(CYP1B1) and c.14_15insC(CYP2F1) were studied at chronic obstructive pulmonary disease patients (Russian (N=169), Tatar (N=137)) and cases of healthy individuals (Russian (N=191), Tatar (N=198) and Bashkir (N=78)), residents of Bashkortostan by PCR-RFLP method. It was shown that the CYP2F1 gene genotype frequency distribution patterns differed between three ethnic groups (chi2 = 21.29, df=4, P = 0.0001), because of high frequency of c.14_15insC/c.14_15insC genotype in Tatars (6.38%). On the other hand, high frequency (39.74%) of normal/ c.14_15insC genotype was appeared in Bashkirs. Association analysis of CYP2F1 geneinsertion variant with chronic obstructive pulmonary disease have shown high frequency (87.5%) of normal allele in Tatars patients with very severe stage and manifestation of chronic obstructive pulmonary disease after 55 years (chi2 = 3.964, df=1, P = 0.046; OR = = 2.268). It was shown that allele and genotype frequency distribution of Leu432ValCYP1B1 gene not differed between Russian, Tatar and Bashkir ethnic groups. We did not find any association of Leu432Val CYP1B1 gene with chronic obstructive pulmonary disease.

  14. Nonalcoholic Fatty Liver Disease in Chronic Hepatitis B and C Patients from Western Amazon

    PubMed Central

    Nascimento, A. C. M.; Maia, D. R.; Neto, S. M.; Lima, E. M.; Twycross, M.; Baquette, R. F.; Lobato, C. M. O.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of histological conditions, extending from simple steatosis to end-stage liver failure. The aim of this study was to examine the prevalence of NAFLD and its associations in chronic hepatitis B and C patients. Methods. We included all patients diagnosed with chronic hepatitis B and C who underwent a liver biopsy between January 2010 and October 2011 (n = 104). Parameters studied included hepatitis type, anthropometric data, histologic, hepatic, metabolic and lipid assessments, presence of hypertension and viral load. Results. Hepatitis B was presented in 28.8% (n = 30) of patients, while hepatitis C was presented in 71.2% (n = 74). In addition, hepatic steatosis was present in 25% (n = 26) of the patients. Steatosis was frequently found in hepatitis C patients (31.1%; 25% n = 23), but infrequently in hepatitis B patients (10%; n = 3) (P = 0.024). It was also found that steatosis was frequently present in hepatitis C patients with intense fibrosis (52.94%) (P = 0.025). Discussion. Our results suggest that steatosis is a common feature in patients with viral chronic hepatitis, and that it plays a different role in each type of hepatitis. PMID:22934189

  15. 78 FR 63218 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Chronic Hepatitis C Virus... availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection: Developing Direct... of development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C....

  16. Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

    PubMed Central

    2010-01-01

    Background The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area. Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population. Methods We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing. Results Sixty-two point seven (62.7%) of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4%) and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C) genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -31T (rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer. Conclusions The H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was not associated with

  17. The PD-1/PD-L1 (B7-H1) Pathway in Chronic Infection-Induced Cytotoxic T Lymphocyte Exhaustion

    PubMed Central

    Hofmeyer, Kimberly A.; Jeon, Hyungjun; Zang, Xingxing

    2011-01-01

    Cytotoxic CD8 T lymphocytes (CTLs) play a pivotal role in the control of infection. Activated CTLs, however, often lose effector function during chronic infection. PD-1 receptor and its ligand PD-L1 of the B7/CD28 family function as a T cell coinhibitory pathway and are emerging as major regulators converting effector CTLs into exhausted CTLs during chronic infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and other pathogens capable of establishing chronic infections. Importantly, blockade of the PD-1/PD-L1 pathway is able to restore functional capabilities to exhausted CTLs and early clinical trials have shown promise. Further research will reveal how chronic infection induces upregulation of PD-1 on CTLs and PD-L1 on antigen-presenting cells and other tissue cells and how the PD-1/PD-L1 interaction promotes CTLs exhaustion, which is crucial for developing effective prophylactic and therapeutic vaccination against chronic infections. PMID:21960736

  18. Molecular characterization of hepatitis B virus X gene in chronic hepatitis B patients

    PubMed Central

    2012-01-01

    Background HBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease. Methods HBV-X gene was sequenced from chronic hepatitis B patient samples, analyzed by phylogeny and genotyped. Nucleotide and aminoacid diversity was determined calculating intragenetic distances. Mutations at 127, 130 and 131 aminoacids were considered in relation to liver disease. Results The most prevalent genotype detected in this cohort was F (F1 and F4), followed by D and A. Most of the samples corresponding to genotypes A and F1 were HBeAg(+) and for genotypes D and F4, HBeAg(−) samples were represented in a higher percentage. Intragenetic distance values were higher in HBeAg(−) than in positive samples for all genotypes, and lower in overlapped regions, compared to single codification ones. Nucleotide and aminoacid diversities were higher in HBeAg(−), than in HBeAg(+) samples. Conclusions Independently of the infecting genotypes, mutations at any of 127, 130 and/or 131 aminoacid positions and HBeAg(−) status were associated with mild liver disease in this cohort. PMID:22769058

  19. SERUM MARKERS FOR ASSESSING LIVER FIBROSIS IN EGYPTIAN PA- TIENTS WITH CHRONIC HEPATITIS B AND C CO-INFECTION VERSUS CHRONIC HEPATITIS C.

    PubMed

    Mobarak, Lamiaa

    2016-04-01

    Chronic hepatitis B and C can progress to hepatic fibrosis and cirrhosis. The stage of liver fibrosis is critical for decision of treatment and prediction of outcomes, as life threatening complications highly develop in cirrhotic patients. The aim of this study was to evaluate the diagnostic accuracy of non-invasive serum markers in the assessment of liver fibrosis in patients with combined chronic hepatitis B and C versus those with chronic hepatitis C. This study included 2 groups; Gl: combined chronic hepatitis B & C, which included 71 patients and G2: chronic hepatitis C, which included 70 patients. Liver biopsy results from both groups were recorded. Three validated blood indices Fibro Q, Fibro alpha, and Biotechnology Research Center (BRC) were tested for optimal cut off values for assessing liver fibrosis in both groups. The results showed that the area under receiver operating characteristic curves (AUROC) for Fibro Q in differentiating significant fibrosis (> F2) from non-significant fibrosis (≤ F2) was 0.79 (95% CI: 0.60-0.89) in the first group and 0.85 (95% CI: 0.71-0.98) in the second group. AUROC for BRC was 0.76 (95% CI: 0.63-0.89) in the first group and 0.75 (CI: 0.60-0.89) in the second group. Fibro alpha performed less in both groups based on AUROC 0.69 and 0.68 in the first and second group respectively.

  20. Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury.

    PubMed

    Nicoll, Amanda; Moore, David; Njoku, Dolores; Hockey, Brad

    2012-11-06

    Volatile anaesthetic agents are known to cause acute hepatitis and fulminant hepatic failure in susceptible individuals. Four patients were identified with prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method (RUCAM) drug causality scale was used to determine the likelihood of volatile anaesthetics causing the chronic liver injury. We describe four cases of volatile anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth followed a more typical pattern of acute hepatitis; however, resolution took a few months. These cases all occurred with modern volatile anaesthetics, predominantly sevoflurane, and all cases were proven with specific antibody tests, liver histology and a drug causality scale. This is the first report of chronic liver injury due to volatile anaesthetic exposure.

  1. Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury

    PubMed Central

    Nicoll, Amanda; Moore, David; Njoku, Dolores; Hockey, Brad

    2012-01-01

    Volatile anaesthetic agents are known to cause acute hepatitis and fulminant hepatic failure in susceptible individuals. Four patients were identified with prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method (RUCAM) drug causality scale was used to determine the likelihood of volatile anaesthetics causing the chronic liver injury. We describe four cases of volatile anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth followed a more typical pattern of acute hepatitis; however, resolution took a few months. These cases all occurred with modern volatile anaesthetics, predominantly sevoflurane, and all cases were proven with specific antibody tests, liver histology and a drug causality scale. This is the first report of chronic liver injury due to volatile anaesthetic exposure. PMID:23131606

  2. Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections.

    PubMed

    Rehermann, Barbara; Bertoletti, Antonio

    2015-02-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause a large proportion of acute and chronic liver disease worldwide. Over the past decades many immunological studies defined host immune responses that mediate spontaneous clearance of acute HBV and HCV infection. However, host immune responses are also relevant in the context of treatment-induced clearance of chronic HBV and HCV infection. First, the pretreatment level of interferon-stimulated genes as well as genetic determinants of innate immune responses, such as single nucleotide polymorphisms near the IFNL3 gene, are strong predictors of the response to interferon-alpha (IFN-α)-based therapy. Second, IFN-α, which has been a mainstay of HBV and HCV therapy over decades, and ribavirin, which has also been included in interferon-free direct antiviral therapy for HCV, modulate host immune responses. Third, both IFN-α-based and IFN-α-free treatment regimens of HBV and HCV infection alter the short-term and long-term adaptive immune response against these viruses. Finally, treatment studies have not just improved the clinical outcomes, but also provided opportunities to study virus-host interaction. This review summarizes our current knowledge on how a patient's immune response affects the treatment outcome of HBV and HCV infection and how innate and adaptive immune responses themselves are altered by the different treatment regimens.

  3. SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing the chronicity of hepatitis.

    PubMed

    Han, Jian; Lei, Yaxin; Liu, Lin; Liu, Peng; Xia, Junke; Zhang, Yulin; Zeng, Hang; Wang, Lin; Wang, Ling; Zhuang, Hui

    2014-01-01

    This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.

  4. Quantitative assessment of fibrosis and steatosis in liver biopsies from patients with chronic hepatitis C

    PubMed Central

    Zaitoun, A; Al, M; Awad, S; Ukabam, S; Makadisi, S; Record, C

    2001-01-01

    Backgrounds—Hepatic fibrosis is one of the main consequences of liver disease. Both fibrosis and steatosis may be seen in some patients with chronic hepatitis C and alcoholic liver disease (ALD). Aims—To quantitate fibrosis and steatosis by stereological and morphometric techniques in patients with chronic hepatitis C and compare the results with a control group of patients with ALD. In addition, to correlate the quantitative features of fibrosis with the Ishak modified histological score. Materials and methods—Needle liver biopsies from 86 patients with chronic hepatitis C and from 32 patients with alcoholic liver disease (disease controls) were analysed by stereological and morphometric analyses using the Prodit 5.2 system. Haematoxylin and eosin and Picro-Mallory stained sections were used. The area fractions (AA) of fibrosis, steatosis, parenchyma, and other structures (bile duct and central vein areas) were assessed by stereological method. The mean diameters of fat globules were determined by morphometric analysis. Results—Significant differences were found in the AA of fibrosis, including fibrosis within portal tract areas, between chronic hepatitis C patients and those with ALD (mean (SD): 19.14 (10.59) v 15.97 (12.51)). Portal and periportal (zone 1) fibrosis was significantly higher (p = 0.00004) in patients with chronic hepatitis C compared with the control group (mean (SD): 9.04 (6.37) v 3.59 (3.16)). Pericentral fibrosis (zone 3) occurred in both groups but was significantly more pronounced in patients with ALD. These results correlate well with the modified Ishak scoring system. However, in patients with cirrhosis (stage 6) with chronic hepatitis C the AA of fibrosis varied between 20% and 74%. The diameter of fat globules was significantly lower in patients with hepatitis C (p = 0.00002) than the ALD group (mean (SD): 14.44 (3.45) v 18.4 (3.32)). Microglobules were more frequent in patients with chronic hepatitis C than in patients with ALD

  5. Clinical features of acute hepatitis E super-infections on chronic hepatitis B

    PubMed Central

    Chen, Chong; Zhang, Shu-Ye; Zhang, Dan-Dan; Li, Xin-Yan; Zhang, Yu-Ling; Li, Wei-Xia; Yan, Jing-Jing; Wang, Min; Xun, Jing-Na; Lu, Chuan; Ling, Yun; Huang, Yu-Xian; Chen, Liang

    2016-01-01

    AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV). METHODS This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes. RESULTS The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with

  6. Impact of schistosomiasis on increase incidence of occult hepatitis B in chronic hepatitis C patients in Egypt.

    PubMed

    Omar, Hanan H; Taha, Samaa A; Hassan, Wafaa H; Omar, Hamdy H

    2017-02-09

    Co-infection of schistosomiasis, HBV and HCV is common in countries where schistosomiasis is endemic. Occult hepatitis B occurs in patients at high risk for HBV infection (e.g., patients on hemodialysis, patients receiving blood transfusions). Schistosomal infection is a risk factor of HBV infection that can increase the incidence of occult hepatitis B. We aimed to determine the prevalence of occult hepatitis B in chronic hepatitis C patients with and without schistosomiasis and to assess the effect of schistosomal infection on the increased risk of exposure to HBV infection and to occult hepatitis B. Two hundred chronic hepatitis C patients who were negative for HBsAg participated. All patients were tested for the following: Anti-schistosome antibodies, Anti-HBc, serum HBV DNA, CBC and liver function. The prevalence of occult hepatitis B in CHC patients with/without schistosomiasis were 12.8% and 8.5% (P=0.042), respectively. Next, 63.8% of CHC patients with schistosomiasis were exposed to HBV infection (Anti-HBc +ve) during their lifetime. In conclusion, the prevalence of occult hepatitis B is higher in CHC patients with schistosomiasis compared to those without schistosomiasis. Periodic laboratory investigations of Schistosoma mansoni, HBV and HCV are recommended for the early detection of the infection and, especially in endemic areas, to avoid infection complications.

  7. [Correction of dyslipidemia in patients with chronic hepatitis C, combined with diabetes type 2].

    PubMed

    Derbak, M; Boldizhar, P

    2014-01-01

    The article shows the results of treatment of 118 patients with chronic hepatitis C (CHC) which is associated with type 2 diabetes mellitus (DM). When planning therapeutic interventions in chronic hepatitis C in patients with diabetes, it is considered the presence of visceral obesit , dyslipidemia, and hepatic steatosis. The efficacy of different treatment regimens was studied. Found that the usage of ursodeoxycholic acid and ademetionin in HCV patients with diabetes type 2 receiving standard antiviral therapy (SAVT), significantly make a positive effect on the level of dyslipidemia. The normalization of lipid profile allows for a full course of SAVT, which reduces the frequency of relapse. It is also noted that the simultaneous use of ademetionin and ursodeoxycholic acid in treatment of chronic hepatitis C leads to a reduction of side effects of SAVT. Metabolic therapy may be recommended for patients with chronic hepatitis C in combination with type 2 diabetes in case of SAVT, and at its contraindications or intolerance.

  8. [The diagnostic role of chemokines and their receptors in chronic hepatitis C].

    PubMed

    Sysoev, K A; Chukhlovin, A B; Totolian, A A

    2013-02-01

    The chronic hepatitis C is characterized by the increase of inflammatory disorders and progression of fibrosis of liver The corresponding immunologic mechanisms of hepatic lesions are still undiscovered. The actual review presents the analysis of scientific publications and genuine research data concerning the role of chemokines in pathogenesis of chronic hepatitis C. The chemokines are small cationic proteins enhancing transit and precipitation of migrating cells (leucocytes mainly) in tissues and organs. The significant role of chemokines in tissue homeostasis, in case of inflammation, wound healing and cell proliferation is demonstrated. The particular kinds of chemokines are produced by different types of cells and impact target cells through their specific receptors. According the data of various studies, chemokines and chemokine receptors of CC-families and CXC-families are involved in fibrosing processes and anti-inflammatory activation of hepatic-biliary system under chronic hepatitis C. The diversity of producers and targets of chemokines in liver is very pronounced: hepatocytes, stellar cells, endothelium cells, macrophages (Kupffer cells), dendritic cells, lymphocytes and monocytes. The review considers pathogenesis of chronic hepatitis C from the standpoint of participation of chemokines and chemokine receptors at different stages of cellular transit. The most important cellpopulations involved into pathologic changes under chronic hepatitis C are characterized. The decrease of expression of such gens as CCR1, CCR2, CCR3, and CCR5 in blood leucocytes deserves additional studies to establish their diagnostic values as a marker of disorders of immune system in patients with chronic hepatitis C.

  9. Reduced serum hepcidin levels in patients with chronic hepatitis C

    PubMed Central

    Girelli, Domenico; Pasino, Michela; Goodnough, Julia B.; Nemeth, Elizabeta; Guido, Maria; Castagna, Annalisa; Busti, Fabiana; Campostrini, Natascia; Martinelli, Nicola; Vantini, Italo; Corrocher, Roberto; Ganz, Tomas; Fattovich, Giovanna

    2009-01-01

    Background/Aims Patients with chronic hepatitis C (CHC) often have increased liver iron, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is the major regulator of iron metabolism and inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin). Methods Using a recently validated immunoassay, we measured s-hepcidin levels in 81 untreated CHC patients and 57 controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score. Results S-hepcidin was significantly lower in CHC patients than in controls (geometric means with 95% confidence intervals: 33.7, 21.5–52.9 vs. 90.9, 76.1–108.4 ng/mL, respectively; p < 0.001). In CHC patients, s-hepcidin significantly correlated with serum ferritin and histological total iron score, but not with s-interleukin-6. After stratification for ferritin quartiles, s-hepcidin increased significantly across quartiles in both controls and CHC patients (chi for trend, p < 0.001). However, in CHC patients, s-hepcidin was significantly lower than in controls for each corresponding quartile (analysis of variance, p < 0.001). Conclusions These results, together with very recent studies in animal and cellular models, indicate that although hepcidin regulation by iron stores is maintained in CHC, the suppression of this hormone by hepatitis C virus is likely an important factor in liver iron accumulation in this condition. PMID:19729219

  10. Disease burden of chronic hepatitis C among immigrants in Canada.

    PubMed

    Chen, W; Krahn, M

    2015-12-01

    Immigrants with chronic hepatitis C (CHC) in Canada have doubled risk of hepatocellular carcinoma. To measure the burden of CHC among immigrants in Canada. A decision analytic model was developed to compare immigrants with CHC and age-matched immigrants without CHC for survival years, quality-adjusted life-years (QALYs) and medical costs per life year. Hepatitis C epidemiology among immigrants was based on hepatitis C prevalence in their home countries. A cohort of immigrant patients was retrospectively followed up to estimate fibrosis stage distribution, treatment patterns and prognosis of compensated cirrhosis. Other model variables were based on published sources. Base case analysis, one-way sensitivity analysis and probabilistic sensitivity analysis were performed to measure the burden of CHC and assess the impact of uncertainty associated with model variables on the burden of CHC. CHC could reduce survival by 9.6 years [95% credible interval (CI): 8.0-10.9 years], reduce QALYs by 9.5 years (95% CI: 6.0-13.8 years) and increase medical costs per life year by $1950 (95% CI: $1518 to $2486, 2006 Canadian dollars). Because nearly half of immigrants with CHC were not diagnosed until the development of cirrhosis, the burden of CHC was highly sensitive to the risks of liver-related complications and mortality but insensitive to pegylated interferon plus ribavirin. The burden of CHC among immigrants in Canada is substantial mainly due to liver-related complications and mortality. The delay in diagnosis was another important contributor to the burden of CHC among immigrants.

  11. Dysregulation of male sex hormones in chronic hepatitis C patients.

    PubMed

    El-Serafi, A T; Osama, S; El-Zalat, H; EL-Deen, I M

    2016-02-01

    Chronic hepatitis C (HCV) infection is a serious problem all over the world and has a special importance in Egypt, where the prevalence of infection is 14.7% of population. In males, HCV is associated with sexual dysfunction and changes in the semen parameters. This study aimed at estimation of a panel of the most important related hormones in the serum of patients and illustration of their correlation to the routine laboratory investigations. The four studied hormones showed alteration in the patients in comparison with the controls. While androstenedione, prolactin and testosterone were significantly increased in patients, dehydroepiandrosterone sulphate was decreased. These changes in the hormones were not related to the liver functions, pathological grade or even viral load. We hypothesised a model of how HCV can induce these hormonal changes and recommended to add these hormones to the follow-up panel of male patients with HCV.

  12. Association between celiac disease and chronic hepatitis C

    PubMed Central

    Casella, Giovanni; Viganò, Davide; Romano Settanni, Carlo; Morelli, Olivia; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio

    2016-01-01

    Celiac disease is characterized by a gluten-induced damage of the small bowel in sensitive individuals that may cause malabsorption. Non-intestinal inflammatory diseases may trigger immunologic gluten intolerance in susceptible people and the HCV virus may be considered as a suitable candidate. Interferon therapy could precipitate symptom onset in subjects with silent celiac disease. In fact, symptoms such as diarrhea, anemia, and weight loss may occur during interferon therapy and are associated with serological positivity of anti-tranglutaminase antibodies. To date, considering the available literature data, it is very difficult to support a firm association between HCV chronic hepatitis and celiac disease. Thus, such a serological screening in HCV patients before starting interferon therapy should not be recommended. However, serology for celiac disease must be considered in patients who develop diarrhea and/or weight loss during such therapy. PMID:27458507

  13. Effects of chronic social defeat on behavioral and neural correlates of sociality: Vasopressin, oxytocin and the vasopressinergic V1b receptor.

    PubMed

    Litvin, Yoav; Murakami, Gen; Pfaff, Donald W

    2011-06-01

    Chronic social stress in rodents produces behavioral and neuroendocrine patterns analogous to symptoms associated with psychopathologies in humans. Chronic social defeat in mice has been used to study the genetic and epigenetic precursors of stress-related social disorders. The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) are released in central targets to modulate anti- and pro-social behaviors, respectively. AVP binds to V1a and V1b receptors (V1bRs) in discrete brain regions related to anxiety, depression and affiliative behaviors. Recent evidence suggests that V1bRs are involved in stress and anxiety and may be an attractive target for the treatment of associated disorders. In the present series of experiments, we aimed to evaluate the effects of chronic social defeat stress on: 1) anxiety-related behaviors in a social investigation paradigm and their potential modulation by an acute dose of SSR149415, a V1bR antagonist; 2) AVP and Fos protein levels in the paraventricular nucleus of the hypothalamus (PVN) and; 3) AVP- and OT-receptor (OTR) mRNA levels in brain regions associated with sociality. When compared to undefeated animals, socially defeated mice exhibited an anxiogenic behavioral profile towards a novel male conspecific, with SSR149415 partly attenuating these effects. Histochemistry using immunofluorescence showed defeat produced significant elevations of Fos and double labeling of AVP and Fos proteins in the paraventricular nucleus of the hypothalamus (PVN). SSR149415 attenuated the effects of defeat on Fos and AVP/Fos double labeling, consistent with an anxiolytic effect. Defeated mice showed elevated levels of OTR mRNA levels in the lateral septum (LS) in addition to increased V1bR and OTR mRNA in the medial amygdala (MeA). We suggest the involvement of V1bRs and OTRs in a circuit involving the PVN, MeA and LS in the effects of defeat on sociality. SSR149415 attenuated anxiogenesis in the social investigation model and both Fos and

  14. My treatment approach to chronic hepatitis C virus.

    PubMed

    Shiffman, Mitchell L; Long, April G; James, Amy; Alexander, Phillip

    2014-07-01

    The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014, the standard of care and new backbone of HCV treatment is the polymerase inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype 1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV). In patients with cirrhosis or extrahepatic manifestations of HCV who cannot tolerate PEGINF, we use 12 weeks of SOF and simeprevir. The latter is less costly and more effective than SOF and RBV for 24 weeks. Our treatment approach in all patients with genotype 2 is SOF and RBV for 12 weeks. Hepatitis C virus genotype 3 is now the most costly and difficult to cure. Our approach to treatment-naive patients with genotype 3 is SOF and RBV for 24 weeks. In patients who have previously undergone PEGINF and RBV treatment, we use PEGINF, SOF, and RBV for 12 weeks, which is equally if not more effective and less costly than SOF and RBV for 24 weeks. Patients with cirrhosis who cannot tolerate PEGINF should be treated for 24 weeks with SOF and RBV, although the sustained virologic response is suboptimal.

  15. Features of chronic hepatitis in alcoholics. A survey in Milan.

    PubMed

    Adelasco, L; Monarca, A; Dantes, M; Moioli, M G; Vinci, M; Croce, G; Tavani, E; Natangelo, R; Lucchelli, P D

    1987-10-01

    A study was carried out to confirm the pathogenetic role of ethanol in the development of chronic active hepatitis (CAH) and to assess if previous or current superimposed hepatitis B virus (HBV) infection could be relevant to the course of alcoholic liver disease (ALD). We examined clinical and laboratory reports of 57 alcoholics with biopsy-proven CAH. Serum and/or tissue HBV markers and the presence or absence of cirrhosis were investigated. Alcohol was the only aetiological factor present in a small group of CAH, with or without histological findings suggestive of alcoholic damage. Age, sex and survival were similar among the subgroups of CAH with and without previous or current HBV infection and among the subgroups of CAH with and without associated histological alcoholic features. Among the laboratory data, the AST/ALT ratio was higher in CAH without previous or current HBV infection. The mean age was comparable in CAH patients with and without cirrhosis, whereas the cumulative 5-year survival was worse in CAH with cirrhosis (87% vs. 49%). These data suggest a difference in alcohol susceptibility in our subjects.

  16. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  17. Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein.

    PubMed

    Matsushima, Soichiro; Maeda, Kazuya; Kondo, Chihiro; Hirano, Masaru; Sasaki, Makoto; Suzuki, Hiroshi; Sugiyama, Yuichi

    2005-09-01

    Until recently, it was generally believed that the transport of various organic anions across the bile canalicular membrane was mainly mediated by multidrug resistance-associated protein 2 (MRP2/ABCC2). However, a number of new reports have shown that some organic anions are also substrates of multidrug resistance 1 (MDR1/ABCB1) and/or breast cancer resistance protein (BCRP/ABCG2), implying MDR1 and BCRP could also be involved in the biliary excretion of organic anions in humans. In the present study, we constructed new double-transfected Madin-Darby canine kidney II (MDCKII) cells expressing organic anion-transporting polypeptide 1B1 (OATP1B1)/MDR1 and OATP1B1/BCRP, and we investigated the transcellular transport of four kinds of organic anions, estradiol-17beta-d-glucuronide (EG), estrone-3-sulfate (ES), pravastatin (PRA), and cerivastatin (CER), to identify which efflux transporters mediate the biliary excretion of compounds using double-transfected cells. We observed the vectorial transport of EG and ES in all the double transfectants. MRP2 showed the highest efflux clearance of EG among these efflux transporters, whereas BCRP-mediated clearance of ES was the highest in these double transfectants. In addition, two kinds of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, CER and PRA, were also substrates of all these efflux transporters. The rank order of the efflux clearance of PRA mediated by each transporter was the same as that of EG, whereas the contribution of MDR1 to the efflux of CER was relatively greater than for PRA. This experimental system is very useful for identifying which transporters are involved in the biliary excretion of organic anions that cannot easily penetrate the plasma membrane.

  18. Redox mechanisms in hepatic chronic wound healing and fibrogenesis

    PubMed Central

    Novo, Erica; Parola, Maurizio

    2008-01-01

    Reactive oxygen species (ROS) generated within cells or, more generally, in a tissue environment, may easily turn into a source of cell and tissue injury. Aerobic organisms have developed evolutionarily conserved mechanisms and strategies to carefully control the generation of ROS and other oxidative stress-related radical or non-radical reactive intermediates (that is, to maintain redox homeostasis), as well as to 'make use' of these molecules under physiological conditions as tools to modulate signal transduction, gene expression and cellular functional responses (that is, redox signalling). However, a derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, can play a significant role in the pathogenesis of major human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis. This review has been designed to first offer a critical introduction to current knowledge in the field of redox research in order to introduce readers to the complexity of redox signalling and redox homeostasis. This will include ready-to-use key information and concepts on ROS, free radicals and oxidative stress-related reactive intermediates and reactions, sources of ROS in mammalian cells and tissues, antioxidant defences, redox sensors and, more generally, the major principles of redox signalling and redox-dependent transcriptional regulation of mammalian cells. This information will serve as a basis of knowledge to introduce the role of ROS and other oxidative stress-related intermediates in contributing to essential events, such as the induction of cell death, the perpetuation of chronic inflammatory responses, fibrogenesis and much more, with a major focus on hepatic chronic wound healing and liver fibrogenesis. PMID:19014652

  19. A comparison of the fibrotic potential of nonalcoholic fatty liver disease and chronic hepatitis C.

    PubMed

    Charlotte, Fréderic; Le Naour, Gilles; Bernhardt, Carole; Poynard, Thierry; Ratziu, Vlad

    2010-08-01

    In nonalcoholic fatty liver disease the amount of fibrosis for individual histologic stages is unknown. To better understand the fibrotic potential of nonalcoholic fatty liver disease, we compared the amount of fibrosis in nonalcoholic fatty liver disease versus chronic hepatitis C virus patients. The area of fibrosis for equivalent fibrosis stages was measured by micromorphometry in 70 nonalcoholic fatty liver disease and 70 matched, untreated, chronic hepatitis C virus controls. The area of fibrosis correlated with Brunt stage (r = 0.71; P < .001) in nonalcoholic fatty liver disease and METAVIR stage (r = 0.58; P < .001) in chronic hepatitis C virus. Mean area of fibrosis was similar in nonalcoholic fatty liver disease and chronic hepatitis C virus patients (7.77% versus 7.70%). Although chronic hepatitis C virus patients displayed higher area of fibrosis in early disease (no or mild fibrosis), nonalcoholic fatty liver disease and chronic hepatitis C virus patients had similar area of fibrosis in more advanced disease (7.83% versus 8.06%, respectively; P = .86 for bridging fibrosis; and 16.62% versus 12.98%, respectively; P = .29 for cirrhosis). The area of fibrosis was similar in Brunt stage 3 nonalcoholic fatty liver disease and METAVIR stage 2 chronic hepatitis C virus, the usual threshold for initiating therapy. The area of steatosis declined with increasing fibrosis stages confirming the early loss of liver fat with progressive fibrosis in nonalcoholic fatty liver disease. Fibrosis is as abundant in nonalcoholic fatty liver disease as in chronic hepatitis C virus, especially in the advanced stages of the disease. The fibrotic potential of nonalcoholic fatty liver disease is as severe as that of chronic hepatitis C virus.

  20. The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors

    PubMed Central

    Duncan, Marilyn J.; Hester, James M.; Hopper, Jason A.; Franklin, Kathleen M.

    2010-01-01

    Age-related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5-HT1B receptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin-releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin-selective reuptake inhibitor, fluoxetine, would attenuate the age-related changes in SCN VIP mRNA expression and 5-HT1B receptors. In situ hybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age-related increase in SCN 5-HT1B receptors at ZT6, and decreases SCN 5-HT1B receptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5-HT1B receptors are differentially regulated; the age-related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment. PMID:20525077

  1. Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

    PubMed Central

    Cho, Junhyeon; Lee, Sang Soo; Choi, Yun Suk; Jeon, Yejoo; Chung, Jung Wha; Baeg, Joo Yeong; Si, Won Keun; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

    2016-01-01

    AIM To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans. PMID:27895431

  2. Hepatitis B virus reverse transcriptase mutations in treatment Naïve chronic hepatitis B patients.

    PubMed

    Singla, Bhupesh; Chakraborti, Anuradha; Sharma, Bal Krishan; Kapil, Shweta; Chawla, Yogesh K; Arora, Sunil K; Das, Ashim; Dhiman, Radha K; Duseja, Ajay

    2013-07-01

    Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome lead to decreased susceptibility to nucleos(t)ide analogs approved for treatment of HBV infection. The aim of this study was to detect and analyze pre-existing HBV RT mutations in treatment naïve patients with chronic hepatitis B. Seventy one chronic HBV treatment naïve patients were enrolled from January 2009 to June 2011. HBV RT sequence analysis was done by using direct bidirectional sequencing of semi-nested PCR products. HBV genotypes were determined by multiplex PCR. Genotype D was found in 64 patients (90.1%) followed by genotype C and A which were present in 5 (7.0%) and 2 (2.8%) patients respectively. The results of the RT sequence analysis showed mutations in 34 (47.9%) patients. The rtH248N mutation was the most common mutation, accounting for 47.1% patients. Other common mutations included rtD263E/S, rtM129L, rtF122L/V/I, rtS135Y/H, rtQ149K, rtL91I, rtH126R, rtC256S/G, rtY257W, rtS259T and rtE271D, which were present in 26.5% (9/34), 29.4% (10/34), 20.6% (7/34), 20.6% (7/34), 20.6% (7/34), 17.6% (6/34), 14.7% (5/34), 14.7% (5/34), 11.8% (4/34), 11.8% (4/34) and 11.8% (4/34) patients respectively. The known primary drug resistance mutations were found in 3 (8.8%) patients. The present study shows the presence of RT amino acid substitutions in treatment-naïve patients with chronic hepatitis B, which may decrease susceptibility to available oral antiviral drugs. On the basis of the finding of this study, genotypic testing is recommended before the start of therapy in naïve patients, so that suitable antiviral drugs can be prescribed.

  3. Ophthalmological side effects of interferon therapy of chronic hepatitis C

    PubMed Central

    Medhat, Eman; Esmat, Gamal; Hamza, Eman; Abdel Aziz, Amr; Fouad Fathalah, Waleed; Zakaria, Zeinab; Mostafa, Sameh

    2016-01-01

    Background Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity. Methods We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment. Results IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy. Conclusions Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately it’s asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important. PMID:27275462

  4. Molecular Testing in the Diagnosis and Management of Chronic Hepatitis B

    PubMed Central

    Valsamakis, Alexandra

    2007-01-01

    Hepatitis B virus (HBV) is an enveloped virus with a small (3.2-kb) partially double-stranded DNA genome that causes acute and chronic infections. The impact of these infections on public health worldwide is enormous, with an estimated prevalence of 2 billion acute infections and 360 million chronic infections globally. This review focuses on chronic hepatitis B and the molecular assays used in its diagnosis and management. Background information, including that about features of the hepatitis B virion, viral replication, and epidemiology of infection, that is important for understanding chronic hepatitis B and molecular diagnostic tests for HBV is provided. To facilitate an understanding of the utility of molecular testing for chronic hepatitis B, the four stages of chronic hepatitis B infection that are currently recognized, as well as an additional entity, occult hepatitis B, that can be diagnosed only by sensitive nucleic acid amplification methods, are reviewed in detail, including available therapeutic agents. The molecular diagnostic content focuses on tests for HBV DNA quantification, genotyping, and mutation detection (including precore/core promoter and antiviral resistance mutations). The discussion of these tests encompasses their current utility and performance characteristics, drawing from current clinical guidelines and other studies from the literature. In recognition of the continual evolution of this field, the final section describes emerging molecular markers with future diagnostic potential. PMID:17630333

  5. Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel.

    PubMed

    Soriano, Vincent; Puoti, Massimo; Peters, Marion; Benhamou, Yves; Sulkowski, Mark; Zoulim, Fabien; Mauss, Stefan; Rockstroh, Juergen

    2008-07-31

    Nearly 10% of the estimated 36 million people having HIV worldwide suffer from chronic hepatitis B virus (HBV) infection. The advent of new antiviral agents against HBV and the recent availability of improved molecular diagnostic tools have revolutioned the management of HIV/HBV coinfected patients. The present study represents an update of the current knowledge about HBV/HIV coinfection and an intent to provide practical advise about how to give the best care to HIV-infected persons with chronic hepatitis B.

  6. Superiority of Interferon-Free Regimens for Chronic Hepatitis C

    PubMed Central

    Younossi, Zobair M.; Stepanova, Maria; Esteban, Rafael; Jacobson, Ira; Zeuzem, Stefan; Sulkowski, Mark; Henry, Linda; Nader, Fatema; Cable, Rebecca; Afendy, Mariam; Hunt, Sharon

    2017-01-01

    Abstract Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients. Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy—Fatigue, Chronic Liver Disease Questionnaire— HCV, Work Productivity and Activity—Specific Health Problem) before, during, and after treatment. A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to −24.4% by treatment week 12, up to −8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to −7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs. IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores. PMID:28207507

  7. [Chronic hepatitis non-A, non-B hepatitis: a clinical and morphologic study].

    PubMed

    da Silva, L C; Coêlho, M E; Pessôa, M G; Carrilho, F J; Cançado, E L; Muszkat, R M; da Fonseca, L E; Antonelli, R; Alves, V A; Gayotto, L C

    1989-01-01

    Few data on chronic non-A, non-B hepatitis (NANB-CH) have been published so far in our country. We have studied 85 patients classified into four groups: I. post-transfusional (PT), 35 patients (41.2%); II. risk group (GR), including health professionals and drug addicts, 11 (12.9%); III. sporadic with a well defined beginning (EBD), 19 (22.4%) and IV. sporadic with ill-defined beginning (END), 20 (23.5%). The mean age in group I was significantly higher than in groups II and III. A polyphasic pattern of serum aminotransferases and severe histological forms were observed in all groups. It is concluded that the way of infection has probably no prognostic importance.

  8. Development of chronic hepatitis B infection in a hepatitis B vaccine responder.

    PubMed

    Sadlier, Corinna; Madden, Keeva; O'Gorman, Sean; Crowley, Brendan; Bergin, Colm

    2017-04-01

    The Hepatitis B vaccine is highly effective for the prevention of hepatitis B (HBV) infection. We report the development of chronic HBV infection (Genotype F) in a vaccinated immunocompetent individual with an anti-HBsAb of 35 mIU/mL post completion of vaccine series. HBV vaccine is based on recombinant proteins of genotype-A and D (predominant genotypes in Europe). It may not be as effective for the prevention of more genetically diverse viruses such as genotype F (predominant genotype in Central and South America). Healthcare providers and patients should be aware that the HB vaccine does not confer 100% protection against HBV infection, even in the setting of protective antibody levels. Partners of individuals infected with non-A or -D genotypes should be advised to consider additional precautions to prevent transmission even in the setting protective antibody levels. Surveillance of circulating HBV genotypes should be undertaken to inform public health policy in relation to prevention of HB in high-risk groups such as men who have sex with men.

  9. [Therapeutic approach to chronic hepatitis B and C in the dawn of the third millenium].

    PubMed

    Adler, M; Bourgeois, N

    2001-06-01

    We try to illustrate the latest developments in epidemiology, pathogenesis and natural history of hepatitis B and C virus infection. Practical management of the patient with chronic B and C liver disease is presented. Universal hepatitis B vaccination should be encouraged in order to reduce to zero morbidity and mortality attributable to liver disease and its complications. Patients at risk for hepatitis B or C infection should be screened and notified about their evolutive risk and the therapeutic possibilities.

  10. 75 FR 55797 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Chronic Hepatitis C Virus... availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection: Developing Direct... specific steps in the hepatitis C virus (HCV) replication cycle. The guidance outlines the types...

  11. Chronic Hepatitis C: An Overview of Evidence on Epidemiology and Management from a Brazilian Perspective

    PubMed Central

    Castro, Rodolfo; Perazzo, Hugo; Grinsztejn, Beatriz; Veloso, Valdilea G.; Hyde, Chris

    2015-01-01

    Chronic hepatitis C remains one of the main causes of chronic liver disease worldwide and presents a variable natural history ranging from minimal changes to advanced fibrosis and cirrhosis and its complications, such as development of hepatocellular carcinoma. Approximately, 1.45 million people are estimated to be infected by HCV in Brazil representing a major public health issue. The aim of this paper was to review the epidemiology and management of chronic hepatitis C from a Brazilian perspective. The management of chronic hepatitis C has been challenged by the use of noninvasive methods to stage liver fibrosis as an alternative to liver biopsy and the high cost of new interferon-free antiviral treatments. Moreover, the need of cost-effectiveness analysis in hepatitis C and the recent changes in treatment protocols were discussed. PMID:26693356

  12. [Chronic hepatitis C infection--eradication of the virus].

    PubMed

    Ben Ari, Ziv

    2014-07-01

    Hepatitis C virus (HCV) infection, a worldwide public health problem affecting 180 million patients, is Likely the cause of chronic hepatitis, liver cirrhosis, liver failure, and hepatocellular carcinoma. In Israel it is estimated that 100,000 people are infected with HCV, 25% are diagnosed and 20-22% were treated with antiviral agents. Advances in our understanding of the HCV lifecycle have led to development of direct acting antiviral agents (DAAs) therapies capable of increasing significantly the curative SVR rates in patients with HCV. New standard-of-care treatment has been approved in 2011 for HCV genotype 1 that has markedly improved treatment results, based on a triple combination of pegylated IFN-alpha, ribavirin, and either telaprevir or boceprevir, two inhibitors of the HCV protease. Two new oral antiviral agents, simeprevir and sofosbuvir, have already been approved and are now available. Other antiviral agents will be available during 2014-2015 and many others, are in phase II or III clinical development. The results of nine phase-3 interferon-free combination regimens of DAAs were reported in the NEJM 2014. These studies demonstrated unequivocal superiority of such regimens over the standard-of-care treatment with an SVR rate of > or = 90% in HCV genotype 1 and 2, naïve, experienced and cirrhotics patients. Interferon-free regimens are associated with lower rate and severity of side effects and a shorter duration of treatment. A number of unanswered questions remain treating special populations, the role of ribavirin, genotype 3, the role of HCV resistance, and how to re-treat failures of treatment. The Ministry of Health wills have to consider: 1. HCV screening in high risk populations. 2. The strategic choices based on cost issues (the predicted costs of the new oral DAAs is extremely high) and on the severity of the liver disease.

  13. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... liver disease that ranges in severity from a mild illness lasting a few weeks to a serious, lifelong... chronic infection, which places infected persons at risk for liver cirrhosis, liver cancer or... health services to prevent additional harm to the liver (e.g., hepatitis A virus and hepatitis B...

  14. Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C

    PubMed Central

    Sultana, Camelia; Oprişan, Gabriela; Teleman, Monica Delia; Dinu, Sorin; Oprea, Cristiana; Voiculescu, Mihai; Ruta, Simona

    2016-01-01

    AIM To determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients. METHODS One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5' allelic discrimination assay; Applied Biosystems). RESULTS Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P < 0.001), urban residence (P = 0.004), IL28B CC genotype (P < 0.001), absence of core mutations (P = 0.005), achievement of rapid virologic response (P < 0.001) and early virological response (P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P < 0.001), absence of core substitutions (P = 0.04) and IL28B CC genotype (P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%. CONCLUSION HCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease. PMID:27729747

  15. Determination of risk factors for hepatitis B and C in male patients suffering from chronic hepatitis

    PubMed Central

    Qureshi, Huma; Arif, Ambreen; Riaz, Kashif; Alam, Syed Ejaz; Ahmed, Waquaruddin; Mujeeb, Syed Abdul

    2009-01-01

    Background Hepatitis B and C is common in Pakistan and various risk factors are attributable to its spread. One thousand and fifty consecutive male cases suffering from chronic liver disease (327 HBV and 723 HCV) were selected from the OPD of public sector hospital and a private clinic dealing exclusively with the liver patients. To compare the results 723 age and gender matched controls were selected from the blood transfusion services of the public sector hospital. A standard questionnaire was filled for all patients and controls which included the information on possible risk factors. Findings Family history of liver disease was significantly higher (43% and 34%) in HBV and HCV positive cases as compared to 5% in controls [odds ratio 15.6; 95% Confidence Interval CI: 10.1 -- 24.1, 10.9; 95% Confidence Interval CI: 7.3 -- 16.4] and same trend was seen for death due to liver disease in the family. Majority 74% hepatitis B positive cases had their shaves done at communal barbers but this practice was equally prevalent amongst controls (68%), thus negating it as a possible risk factor, but there is a significant risk with p < 0.05 associated with HCV in male that get their shave in barber. Very strong association of the disease was found with history of dental treatment (38% HCV 36% HBV and 21% controls) [Odd ratio 2.3; 95% CI: 1.8-3.0, Odd ratio 2.1; 95% CI: 1.5-2.8], surgery (23% HCV cases,14% HBV cases and 12% controls), history of blood transfusion was significantly higher in HCV (6%) as compared to controls (2.1%) [Odd ratio 2.9; 95% CI: 1.5-5.5]. History of taking injections for various ailments by the general practitioners (over 90% patients in both hepatitis B and C cases) was significantly higher as compared to 75% in controls [Odds ratio 3.8, 6.9; 95% CI: 2.4-6.1, 4.5-10.4] but hospitalization was not significant in HBV and HCV cases. Conclusion Injections, surgery and dental treatment appear as major risk factors for the transmission of hepatitis B and C

  16. Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B.

    PubMed

    Perrillo, Robert; Buti, Maria; Durand, Francois; Charlton, Michael; Gadano, Adrian; Cantisani, Guido; Loong, Che-Chuan; Brown, Kimberly; Hu, Wenhua; Lopez-Talavera, Juan Carlos; Llamoso, Cyril

    2013-08-01

    For patients undergoing liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease, the current standard of care for preventing reinfection of the allograft is nucleoside analogue therapy combined with hepatitis B immune globulin (HBIG). Entecavir has demonstrated high efficacy and a favorable safety profile for chronic hepatitis B (CHB) treatment, but data for patients undergoing HBV-related LT are limited. This study assessed the safety and efficacy of entecavir combined with various HBIG regimens after CHB-related LT. In this phase 3b, single-arm, open-label study, 65 patients undergoing LT for CHB-related liver disease with an HBV DNA load <172 IU/mL at LT received entecavir (1.0 mg daily) for 72 weeks after LT. The primary endpoint was the proportion of evaluable patients (treated for ≥4 weeks) with virological recurrence (HBV DNA level ≥50 IU/mL) through week 72. Concomitant HBIG therapy was received by 64 of the 65 enrolled patients, and 44% of these patients received high-dose HBIG (any HBIG dose in the specified interval ≥10,000 IU). Through week 72, all 61 patients evaluable for the efficacy analysis had undetectable HBV DNA. The Kaplan-Meier estimate of patients without hepatitis B surface antigen (HBsAg) recurrence at week 72 was 0.9655. Two patients experienced a reappearance of HBsAg, but both remained HBV DNA(-) until the last follow-up. The frequency and nature of adverse events were consistent with those expected for this patient population. Serum creatinine increments ≥0.3 mg/dL and ≥0.5 mg/dL occurred in 62% and 39% of the patients, respectively, and all of these patients received calcineurin inhibitor therapy. In conclusion, in this population of patients treated with entecavir after CHB-related LT, entecavir was well tolerated and effective in maintaining viral suppression, even in individuals who experienced a reappearance of HBsAg.

  17. If You Have Chronic Hepatitis B Virus (HBV) Infection

    MedlinePlus

    ... B immune globulin (HBIG) and started on the hepatitis B vaccine series within 12 hours of birth to prevent ... testing and should receive the first dose of hepatitis B vaccine at this same visit after the blood is ...

  18. When Someone Close to You Has Chronic Hepatitis B

    MedlinePlus

    ... the United States, all infants should begin the Hepatitis B vaccine series at birth. In addition, the vaccine is ... their health. If a person has never gotten Hepatitis B, then the vaccine will protect them against the disease. However, if ...

  19. Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B.

    PubMed

    Moucari, Rami; Marcellin, Patrick

    2011-01-01

    HBsAg is a very important clinical test that might not only indicate active hepatitis B virus (HBV) infection but might also be used to predict clinical and treatment outcome. Clearance of HBsAg in patients with chronic HBV infection is associated with a much better clinical outcome, although surveillance for early detection of hepatocellular carcinoma (HCC) should continue. HBV DNA quantification is currently used for selecting candidates for therapy, monitoring response to therapy and detecting the emergence of drug resistance. Assays for HBsAg quantification are less expensive than HBV DNA and fully automated with a high throughput capacity. HBsAg titering may be a useful tool to manage patients with chronic HBV, to more clearly define which patients may, and more importantly, may not, benefit from treatment. Baseline and on-treatment HBsAg quantification may help to refine future treatment algorithms for both immune-modulator therapy and nucleos(t)ide analogues. Both HBV markers provide complementary information on the status of HBV infection. However, the relevance of serum HBsAg levels and its use as a reliable replacement for both covalently closed circular DNA and HBV DNA remain unclear.

  20. Factors associated with serum retinol, x-tocopherol, carotenoids, and selenium in Hispanics with problems of HIV, chornis hepatitis, chronic hepatitis C, and drug use

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C inf...

  1. Distribution of natural resistance to NS3 protease inhibitors in hepatitis C genotype 1a separated into clades 1 and 2 and in genotype 1b of HIV-infected patients.

    PubMed

    Bagaglio, S; Uberti-Foppa, C; Messina, E; Merli, M; Hasson, H; Andolina, A; Galli, A; Lazzarin, A; Morsica, G

    2016-04-01

    Naturally occurring resistance-associated variants (RAVs) within the protease domain of hepatitis C virus (HCV) genotype (G) 1a separated into clades 1 and 2, and G1b were investigated in 59 HIV/HCV coinfected patients. RAVs were detected in 10/23 G1a/clade 1 and 1/19 G1b (p 0.0059). A similar frequency of RAVs was found when comparing G1a/clade 2 and G1b (p 0.1672). A cross-resistance to the macrocyclic compounds simeprevir and paritaprevir was detected in two G1a/clade 2 and 1 G1b sequences and none of G1a/clade 1 sequences. The simultaneous characterization of subtype and natural RAVs by population analysis of the NS3 domain by may add important information for anti-HCV treatment strategies including protease inhibitors.

  2. Chronic Hepatitis E Infection in a Persistently Immunosuppressed Patient Unable to Be Eliminated after Ribavirin Therapy

    PubMed Central

    Miyoshi, Masato; Kakinuma, Sei; Tanabe, Yoko; Ishii, Koji; Li, Tian-Cheng; Wakita, Takaji; Tsuura, Yukio; Watanabe, Hideki; Asahina, Yasuhiro; Watanabe, Mamoru; Ikeda, Takaaki

    2016-01-01

    Recent case reports have shown that hepatitis E virus (HEV) infection can cause chronic hepatitis in immunosuppressed or immunocompromised patients. A 37-year-old woman suffered from prolonged elevation of aminotransferases after chemotherapy for Burkitt's lymphoma and was diagnosed with chronic hepatitis E due to a transfusion during chemotherapy. After an 8-month administration of ribavirin, complete HEV clearance was not achieved, likely due to prolonged hypogammaglobulinemia. This case indicates that HEV infection should be ruled out during liver dysfunction in immunosuppressed or immunocompromised patients and suggests that an alternative therapeutic strategy for such patients will be needed. PMID:27725541

  3. Interferon-induced thyroiditis during treatment of chronic hepatitis C.

    PubMed

    Kozielewicz, Dorota; Halota, Waldemar

    2012-01-01

    Thyroid function disorders affect between 5% and 15% of patients treated with IFNα and RBV for chronic hepatitis C. Women and patients with thyroid peroxidase antibodies (TPOAb) found before the treatment are at risk of developing the disorders (46.1% vs. 5.4%). The spectrum of IFNα-induced thyroiditis (IIT) includes two groups. Disorders with an autoimmune background are: presence of thyroid autoantibodies without clinical disease, Hashimoto's disease and Graves' disease. The second group comprises diseases caused by the direct toxic effect of IFNα on the thyroid gland, i.e. destructive thyroiditis and non-autoimmune hypothyroidism. Thyroid diseases are not an absolute contraindication for IFNα and RBV therapy. In patients diagnosed with thyroid dysfunction, before the antiviral therapy it is necessary to achieve euthyreosis. Thyroid function disorders may occur at any moment of the therapy. The earliest have been observed in the 4th week of treatment, and the latest 12 months after its termination. During the therapy, in order to diagnose IIT early, it is recommended to determine TSH level every 2-3 months depending on the presence of TPOAb before the treatment. The diagnosis and treatment of thyroid function disorders should be conducted in co-operation with an endocrinologist.

  4. Hepatitis B virus genotypes among chronic hepatitis B patients reporting at Korle-Bu teaching hospital, Accra, Ghana

    PubMed Central

    Dongdem, Anthony Zunuo; Dzodzomenyo, Mawuli; Asmah, Richard Harry; Nyarko, Kofi Mensah; Nortey, Priscillia; Agyei, Adwoa; Adjei, David Nana; Kenu, Ernest; Adjei, Andrew Anthony

    2016-01-01

    Introduction Knowledge of hepatitis B virus (HBV) genotype is an important predictive variable which might have an impact in management and treatment of patients with chronic hepatitis B infection. In Ghana very little information is available on hepatitis B genotypes. This study was conducted to determine the distribution of HBV genotypes circulating among chronic hepatitis B patients reporting at the Korle-Bu Teaching Hospital (KBTH), Accra, Ghana. Methods Blood samples (10 ml) were collected from 250 consenting patients. DNA was extracted and amplified using polymerase chain reaction technique. Restriction fragment length polymorphism (RFLP) was used for the detection of genotypes. Results Out of the 250 chronic hepatitis B patients who were HBsAg positive, 91 (36.4%) were males aged 29.8 ± 9.1 and 159 (63.6%) females aged 33± 12.1 years. HBV DNA was detected in 111 (44.4%) but only 58 (52%) of these were typeable. These were classified as genotype A, 8 (7.2%); genotype D, 3 (2.7%) and genotype E, 47 (42.3%). Our results did not show any association between the infecting genotype and age (X2= 0.923; p-value=0.623) or gender (X2= 0.283, p= 0.579). Conclusion Consistent with similar studies worldwide, the results suggest that genotypes A, D and E were the genotypes circulating among chronic hepatitis B patients who reported to the Korle-Bu Teaching Hospital with genotype E being the most predominant and therefore constitutes an important public health concern. We recommend further epidemiological studies to understand the implication of genotype E in terms of disease progression and treatment. PMID:28210373

  5. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    PubMed Central

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-01-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host’s immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host’s immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far. PMID:27635192

  6. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection.

    PubMed

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-07-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  7. Patients with Haemoglobinopathies and Chronic Hepatitis C: A Real Difficult to Treat Population in 2016?

    PubMed Central

    Zachou, Kalliopi; Arvaniti, Pinelopi; Gatselis, Nikolaos K.; Azariadis, Kalliopi; Papadamou, Georgia; Rigopoulou, Eirini; Dalekos, George N.

    2017-01-01

    Background & objectives In the past, patients with haemoglobinopathies were at high risk of acquiring hepatitis C virus (HCV) due to multiple transfusions before HCV screening. In these patients, the coexistence of haemochromatosis and chronic hepatitis C (CHC) often leads to more severe liver disease. We assessed the HCV prevalence, clinical characteristics and outcome in this setting with particular attention to the response to treatment including therapies with the new direct acting antivirals (DAAs). Methods The medical records of 81 consecutive patients followed the last 15 years were reviewed retrospectively. Results 43/81 (53%) patients were anti-HCV positive including 31/43 (72.1%) with CHC (HCV-RNA positive; age 25±7 years; 45.2% with genotype 1b; 19.4% cirrhotics; baseline ferritin 887 ng/ml; range: 81–10.820). Thirty patients received IFN-based therapy with or without ribavirin with sustained virological response (SVR) in 14/30 (46.7%). Eleven patients (9 non-responders to IFN-based therapies, one in relapse and one naïve) received treatment with DAAs (SVR: 100%). 3/11 patients increased their transfusion needs while 1/11 reported mild arthralgias. No drug-drug interactions between DAAs and chelation agents were observed as attested by the stability of ferritin levels during treatment. Conclusions More than 1/3 of patients with haemoglobinopathies suffered from CHC. Response rates to IFN-based treatment seem to be similar to other patients with CHC, while most importantly, treatment with DAAs was excellent and safe even in difficult to treat patients (most null responders with severe fibrosis) suggesting that this group of HCV patients should no longer be regarded as a difficult to treat. PMID:28101309

  8. Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Dahal, Sumit; Upadhyay, Smrity; Banjade, Rashmi; Dhakal, Prajwal; Khanal, Nabin; Bhatt, Vijaya Raj

    2017-01-01

    Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant

  9. Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment

    PubMed Central

    Aygen, Bilgehan; Yildiz, Orhan; Akhan, Sila; Gunal, Ozgur; Taheri, Serpil; Zararsiz, Gokmen; Sayan, Murat; Rustemoglu, Aydin; Altinok, Elif Sargin

    2014-01-01

    Background Interleukin (IL) 28B single nucleotide polymorphisms may play a role in the clearance of hepatitis C virus (HCV). We aimed to evaluate the treatment response of chronic HCV infection patients to pegile interferon (pegIFN) and ribavirin treatment with regard to IL28B rs12979860 C/T polymorphism. Methods A total of 186 patients (mean age, 55.6 ± 10 years; 65.1% female) who underwent pegIFN and ribavirin treatment for chronic HCV infection were studied. We analyzed demographics, HCV genotype, baseline alanine aminotransferase (ALT) levels, histopathological data, viral load before treatment and at 4, 12, 24, 48, and 72 weeks from the treatment start, and IL28B genotype. IL28B polymorphism was genotyped using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in all the subjects. Results One hundred forty-five (86.8%) patients were infected with viral genotype 1b, and 13.2% were infected with viral genotype 4. The rates of C/C, C/T, and T/T genotypes were 22.6%, 52.7%, and 24.7% respectively. The percentage of patients with a viral load over 400,000 IU/mL was higher in the C/T group (P = 0.020). Of the patients, 44.6% provided sustained virological response (SVR) to pegIFN and ribavirin combination treatment. The frequency of T allele was 41% in patients with SVR, whereas 59% patients provided no response (P < 0.001). SVR was obtained in 66.7%, 42.9%, and 28.3% of CC, CT, and TT groups (P = 0.001). The rates of rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and SVR were higher in the CC group than other groups (P = 0.216, P < 0.001, P = 0.001, P = 0.001, respectively). The relapse and null response (NR) rates were higher in TT group and partial response rate (PR) was higher in CT group. Conclusions IL28B rs12979860 C/T gene polymorphism affects the response to antiviral treatment in the patients with chronic HCV genotypes 1b and 4 infections. PMID:27785282

  10. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

    PubMed Central

    Amin, Kawa; Rasool, Aram H; Hattem, Ali; Al-Karboly, Taha AM; Taher, Taher E; Bystrom, Jonas

    2017-01-01

    AIM To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease. METHODS Levels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other. PMID:28293081

  11. Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B1 B cells

    PubMed Central

    Hayakawa, Kyoko; Formica, Anthony M.; Colombo, Matthew J.; Shinton, Susan A.; Brill-Dashoff, Joni; Morse, Herbert C.; Li, Yue-Sheng; Hardy, Richard R.

    2016-01-01

    A common feature of B cell chronic lymphocytic leukemia (CLL) is chromosomal loss of 13q14, containing the miR15a/16-1 locus controlling B cell proliferation. However, CLL etiology remains unclear. CLL is an adult leukemia with an incidence that increases with advancing age. A unique feature of CLL is biased B cell antigen receptor (BCR) usage, autoreactivity with polyreactivity, and CD5 expression, all suggest a role for the BCR in driving CLL pathogenesis. Among human CLLs, BCRs autoreactive with non-muscle myosin IIA (AMyIIA) are recurrent. Here we identify an unmutated AMyIIA BCR in mouse, with distinctive CDR3 segments capable of promoting leukemogenesis. B cells with this AMyIIA BCR are generated by BCR-dependent signaling during B-1 fetal/neonatal development with CD5 induction, but not in adults. These early-generated AMyIIA B1 B cells self-renew, increase during aging, and can progress to become monoclonal B cell lymphocytosis, followed by aggressive CLL in aged mice, often with loss of a chromosomal region containing the miR15a/16-1 locus of varying length, as in human CLL. Thus, the ability to generate this defined autoreactive BCR by B1 B cells is a key predisposing step in mice, promoting progression to chronic leukemia. PMID:27055869

  12. Antiviral therapies for chronic hepatitis C virus infection with cirrhosis.

    PubMed

    Nakamoto, Shingo; Kanda, Tatsuo; Shirasawa, Hiroshi; Yokosuka, Osamu

    2015-05-18

    Patients who are infected with hepatitis C virus (HCV) and also have advanced fibrosis or cirrhosis have been recognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents (DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5A inhibitors and HCV NS5B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatment-naïve patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in null-responders and in patients with cirrhosis. Interferon-free regimens in combination with ribavirin and

  13. Chronic hepatitis E virus infection in a pediatric female liver transplant recipient.

    PubMed

    Passos-Castilho, Ana Maria; Porta, Gilda; Miura, Irene K; Pugliese, Renata P S; Danesi, Vera L B; Porta, Adriana; Guimarães, Teresa; Seda, João; Antunes, Eduardo; Granato, Celso F H

    2014-12-01

    We describe a case of chronic hepatitis E virus (HEV) infection in a 13-year-old female liver transplant recipient with recurrent increased aminotransferase levels and acute cellular rejection. This finding demonstrates that chronic HEV infection can occur and should be further investigated in immunocompromised patients in Latin America.

  14. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

    PubMed

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-09-14

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

  15. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

    PubMed Central

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully. PMID:27649152

  16. Clinical Advances in Fibrosis Progression of Chronic Hepatitis B and C

    PubMed Central

    Wu, Ye-Jiao; Xu, Ming-Yi; Lu, Lun-Gen

    2014-01-01

    Chronic liver diseases, such as chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are characterized by the presence of liver fibrosis, which may ultimately lead to cirrhosis. The progression of fibrosis is associated with various factors. Here, we review recent advances in the study of factors related to the progression rate of CHB- and CHC-induced fibrosis. Identification of these factors and establishment of a scoring system for cirrhosis risk are particularly important for predicting cirrhosis development, planning individualized treatment, and preventing fibrosis progression. PMID:26357628

  17. Adverse effects of oral antiviral therapy in chronic hepatitis B

    PubMed Central

    Kayaaslan, Bircan; Guner, Rahmet

    2017-01-01

    Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a “Black Box” warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment. PMID:28261380

  18. Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice.

    PubMed

    Rogers, Arlin B; Boutin, Samuel R; Whary, Mark T; Sundina, Nataliya; Ge, Zhongming; Cormier, Kathleen; Fox, James G

    2004-01-01

    Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.

  19. Spontaneous and antiviral-induced cutaneous lesions in chronic hepatitis B virus infection

    PubMed Central

    Grigorescu, Ioana; Dumitrascu, Dan Lucian

    2014-01-01

    AIM: To describe spontaneous, or interferon (IFN)- or immunization-induced skin lesions in hepatitis B virus (HBV) infection. METHODS: A comprehensive literature search of all the papers presenting case reports of dermatological lesions in patients with chronic HBV infection was carried out. We included only patients with histologically proven skin lesions that appeared in the normal course of hepatitis B infection, or after immunization for hepatitis B or antiviral treatment. RESULTS: We found 44 papers on this topic, reporting 151 cases. About 2% of patients with hepatitis B infection, mainly men, presented with skin lesions. Among patients with chronic hepatitis B, vasculitis and essential mixed cryoglobulinemia seemed to be the most frequent skin lesion (53.3%), followed by papular changes, rashes and Gianotti-Crosti syndrome, skin carcinoma and Henoch-Schönlein purpura were rare. IFN treatment seemed to be effective against HBV-associated and immunoglobulin-complex-mediated disease (vasculitis). Two cutaneous lesions (lichen planus and granuloma annulare) were described after hepatitis B vaccination. Systemic lupus and lupus-like lesions were the most frequently encountered lesions after antiviral treatment. Immunosuppressive and steroid therapy ameliorates lichen planus lesions in 50% of cases. CONCLUSION: Vasculitis was the most frequent spontaneous skin lesion found in chronic hepatitis B. Lichen planus was most frequent after immunization and lupus/lupus-like lesions after IFN. PMID:25400473

  20. Noninvasive scoring system for significant inflammation related to chronic hepatitis B

    PubMed Central

    Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

    2017-01-01

    Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (−) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (−) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system. PMID:28281521

  1. Noninvasive scoring system for significant inflammation related to chronic hepatitis B

    NASA Astrophysics Data System (ADS)

    Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

    2017-03-01

    Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (‑) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (‑) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system.

  2. Noninvasive scoring system for significant inflammation related to chronic hepatitis B.

    PubMed

    Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

    2017-03-10

    Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (-) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (-) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system.

  3. The Prevalence of Hepatitis C Virus Core Amino Acid 70 Substitution and Genotypes of Polymorphisms Near the IFNL3 Gene in Iranian Patients With Chronic Hepatitis C

    PubMed Central

    Kadjbaf, Danesh; Keshvari, Maryam; Alavian, Seyed Moayed; Pouryasin, Ali; Behnava, Bita; Salimi, Shima; Mehrnoush, Leila; Karimi Elizee, Pegah; Sharafi, Heidar

    2016-01-01

    Background Molecular studies have demonstrated that the hepatitis C virus (HCV) genotype and host genetics play predictive roles in the management of patients infected with HCV. Objectives This study aimed to investigate the HCV genotype, core amino acid (aa) 70 substitution, and polymorphisms near the IFNL3 gene (including rs12979860 and rs8099917) among Iranian patients with chronic hepatitis C (CHC). Patients and Methods In this cross-sectional study, the molecular profiles of the HCV genotype, core aa 70 substitution, and rs12979860 and rs8099917 polymorphisms and plasma HCV RNA levels were determined in 429 CHC patients including 141 hemophilic, 84 thalassemic, and 204 non-hemophilic, non-thalassemic patients. Results The hepatitis C virus subtype 1a was the most common subtype in the study population. Core aa substitution Arg70Gln was strongly associated with cirrhosis (OR = 2.49; 95% CI = 1.13 - 5.50; P = 0.020). Core aa 70 substitutions were more frequently observed in patients with the HCV subtype 1b than in patients with any other HCV subtypes (P < 0.001). Core aa 70 substitutions were also more common in patients with the rs12979860 TT genotype than in patients with non-TT genotypes (17.3% vs. 8.5%, P = 0.022) and also in rs8099917 non-TT genotypes than in the TT genotype (14.0% vs. 7.0%, P = 0.026). The HCV genotypes and rs8099917 polymorphisms were correlated in which HCV subtype 1b was in favor of rs8099917 GG and HCV subtype 3a favored rs8099917 TT (P = 0.021). Furthermore, the rs12979860 TT and rs8099917 GG genotypes showed significantly lower HCV RNA levels than the other genotypes (P < 0.001). Conclusions There is an as yet unexplained association between HCV and host parameters with unknown mechanisms in patients with chronic HCV infection. The assessments of core aa 70 substitution and polymorphisms near the IFNL3 gene could offer promising steps to improve the management of patients with HCV. PMID:27630727

  4. Serum levels of soluble CD30 in chronic hepatitis B virus infection

    PubMed Central

    FATTOVICH, G; VINANTE, F; GIUSTINA, G; MOROSATO, L; ALBERTI, A; RUOL, A; PIZZOLO, G

    1996-01-01

    There is evidence that both cellular and humoral components of the immune response are required for viral clearance to occur in chronic hepatitis B. Recent studies demonstrated that CD30 molecule, a member of the tumour necrosis factor superfamily of membrane cytokine receptors, is expressed on, and released as a soluble molecule (sCD30) by activated T cells producing T helper 2 (Th2) cytokines, which modulate antibody responses. To better characterize the immunoregulatory mechanisms in chronic hepatitis B virus (HBV) infection, sCD30 values were evaluated by an ELISA in 90 hepatitis B surface (HBsAg)-positive patients with chronic hepatitis, selected on the basis of active viral replication and biochemical activity. At presentation abnormal levels (>20 U/ml) of sCD30 were detected in 57 (63%) out of 90 patients with chronic hepatitis B, and median value was significantly higher in this group of patients compared with that of healthy HBsAg carriers (26.7 versus 10.5 U/ml, P < 0.000 05) and with normal controls (26.7 versus 3 U/ml, P < 0.000 01). Sequential studies of chronic hepatitis B did confirm the association of raised sCD30 levels with the active phase of the illness. On the other hand, a significant decrease was noted when sCD30 levels at diagnosis and after termination of HBV replication and biochemical remission of hepatitis were compared in 10 untreated patients (median, 28 U/ml at entry versus 8 U/ml at remission, P < 0.01) and in six patients responding to interferon-alpha therapy (median, 29.5 U/ml at entry versus 6 U/ml at remission, P < 0.05). The high serum sCD30 levels reported during the active phase of HBsAg-positive chronic hepatitis suggest a certain degree of immune competence of these patients, at least with respect to a Th2-type response. These data are in agreement with recent serologic surveys showing that most chronic hepatitis B patients do demonstrate ongoing humoral immune response to HBV antigens, using novel immunoassays designed to

  5. Trends in the Incidence Rates of Chronic Hepatitis B in Poland in the Years 2005 - 2013

    PubMed Central

    Stawinska-Witoszynska, Barbara; Zysnarska, Monika; Krzywinska-Wiewiorowska, Małgorzata; Wojtyła-Buciorab, Paulina; Krzyzaniak, Alicja; Wieckowska, Barbara

    2016-01-01

    Background The prevalence of newly-diagnosed cases of chronic hepatitis is decisive for the overall incidence rate of hepatitis B observed in Poland. Objectives We aimed to determine the chronic hepatitis B incidence trends in Poland, taking into consideration the ages, genders, and environments of the patients. Methods The study is based on aggregated data from Polish descriptive epidemiological studies for the period of 2005 to 2013 (i.e., hepatitis B incidence numbers and ratios, including mixed HBV and HCV infections) as published in the annual bulletins Choroby zakazne i zatrucia w Polsce (Infectious diseases and poisonings in Poland] drawn up by the laboratory for the monitoring and analysis of epidemiological status of the department of epidemiology at the national institute of public health - national institute of hygiene (NIPH-NIH). Poland, a central European country situated in the humid continental climate zone, is classified as a highly developed country. In the analyzed period, the Polish population consisted of about 38 million people, more than 19 million of whom were women, and more than 18 million of whom were men. Among European countries, Poland has the smallest number of national and ethnic minorities. For the purposes of epidemiological supervision, a special definition of acute hepatitis B was adopted in Poland in 2005, which facilitated separate registration of acute and chronic cases. Results A significantly increasing chronic hepatitis B incidence trend was observed in the population of Poland, with considerable increases in incidence rates for both men and women alike. The incidence rates for inhabitants of both urban and rural areas also showed an increasing tendency. Chronic hepatitis B occurred more frequently in men and in urban areas. For each of the five-year age groups encompassing patients between 20 and 54 years of age, the increase in the incidence rate proved to be significant. Conclusions The registered increase in the

  6. Re-designing Orem's Self-care Theory for Patients with Chronic Hepatitis

    PubMed Central

    Hasanpour-Dehkordi, Ali; Mohammadi, Nooredin; Nikbakht-Nasrabadi, Alireza

    2016-01-01

    Background: Hepatitis is an inflammatory disease which has many adverse effects on patients’ life because of its chronic nature. Since Orem's theory of self-care is a grounded theory, the concepts and applications of this theory in patients with chronic hepatitis who have special needs may lead to some challenges. The purpose of this study was to explore self-care in patients with chronic hepatitis. Methods/Design: A directed content analysis was used in this qualitative study. Participants were recruited from a metropolitan area. Data were collected through semi-structured interviews. The verbatim transcripts of the participants’ interviews were analyzed according to directed content analysis. Results: In this study, four themes, suggested by Orem, were drawn from the data according to directed content analysis. The codes generated from the data were classified into concepts and then the concepts were assigned into these four themes. These themes were needs in the matrix of time and place, self-care agency, need for change in self-care and consequences of hepatitis. Conclusion: The use of Orem's self-care theory cannot meet the need for self-care in hepatitis patients because these patients have vital sexual, respect and belonging, physical, economical, and psychological-behavioral needs, and lack adequate knowledge about self-care. Consequently, the specific self-care model developed in this study helps health professionals identify self-care activities in patients with chronic hepatitis. PMID:27803560

  7. Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats

    PubMed Central

    2010-01-01

    Background Non-alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH) could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms. Results High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha) levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin), which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways. Conclusions Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance. PMID:20653983

  8. [Prevalence of the genotypes of the hepatitis C virus in Spanish drug addicts with chronic hepatitis C. Spanish Group for the Study of Viral Hepatitis in HIV Positive Patients].

    PubMed

    Bravo, R; Soriano, V; García-Samaniego, J; González, J; Castro, A; Colmenero, M; Carballo, E; Mas, A; González-Lahoz, J

    1996-10-01

    The hepatitis C virus (HCV) shows a wide genetic variability. The different variants of HCV have been classified into 9 types and different subtypes. Some genotypes have a characteristic geographic distribution and seem to be associated with precise ways of contagion. Serum samples from 107 spanish patients with chronic hepatitis C were studied, which were distributed as follows: 88 parenteral drug addicts (PDA) and a control group of 19 subjects made up by 4 transfused, 5 probably sexually infected and 10 with unknown contagion source (sporadic cases). HCV typing was made by means of the PCR method and later hybridization analysis with complementary probes of different types and subtypes of HCV exposed on a smooth surface (Inno-LiPA). A total to 105 (98.4%) patients had their viruses genotypes. There was more than one genotype in the same subject (co-infection) in 43.8% of cases and co-infection 1a + 1b was the most common (82.7%). While not reaching a statistic significance, co-infections were more frequent in PDA (47.1%) than in the remaining patients (27.8%). In the infected patients with only one genotype, the most common genotype was 1a, both in PDA (22.9%) and in subjects with transfusional HCV, sexual or sporadic (38.9%). In decreasing frequency came genotypes 1b (13.3%) and 3a (11.4%). Other genotypes were very uncommon (2a and 4) or were absent (2b and 5) as unique infections. In conclusion, genotypes non-1b of HCV, mainly 1a and to a lesser extent 3a, are the most common in a spanish population made up mainly by young persons with risk antecedents for HIV infection, particularly PDA. Furthermore, co-infection with HCV genotypes is frequent in this population.

  9. Higher all-cause hospitalization among patients with chronic hepatitis C: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2013.

    PubMed

    Teshale, E H; Xing, J; Moorman, A; Holmberg, S D; Spradling, P R; Gordon, S C; Rupp, L B; Lu, M; Boscarino, J A; Trinacity, C M; Schmidt, M A; Xu, F

    2016-10-01

    In the United States, hospitalization among patients with chronic hepatitis C virus (HCV) infection is high. The healthcare burden associated with hospitalization is not clearly known. We analysed data from the Chronic Hepatitis Cohort Study, an observational cohort of patients receiving care at four integrated healthcare systems, collected from 2006 to 2013 to determine all-cause hospitalization rates of patients with chronic HCV infection and the other health system patients. To compare the hospitalization rates, we selected two health system patients for each chronic HCV patient using their propensity score (PS). Propensity score matching was conducted by site, gender, race, age and household income to minimize differences attributable to these characteristics. We also compared primary reason for hospitalization between chronic HCV patients and the other health system patients. Overall, 10 131 patients with chronic HCV infection and 20 262 health system patients were selected from the 1 867 802 health system patients and were matched by PS. All-cause hospitalization rates were 27.4 (27.0-27.8) and 7.4 (7.2-7.5) per 100 persons-year (PY) for chronic HCV patients and for the other health system patients, respectively. Compared to health system patients, hospitalization rates were significantly higher by site, gender, age group, race and household income among chronic HCV patients (P < 0.001). Compared to health system patients, chronic HCV patients were more likely to be hospitalized from liver-related conditions (RR = 24.8, P < 0.001). Hence, patients with chronic HCV infection had approximately 3.7-fold higher all-cause hospitalization rate than other health system patients. These findings highlight the incremental costs and healthcare burden of patients with chronic HCV infection associated with hospitalization.

  10. Tolerability and efficacy of pegylated consensus interferon-α in the treatment of chronic hepatitis C

    PubMed Central

    Ding, Yan-Hua; Liu, Bin; Zhang, Xin; Sun, Li; Zhang, Hong; Luo, Hua; Sun, Yan-Fu; Liu, Cheng-Jiao; Zhang, Qi; Cao, Yu-Chen; Chen, Hong; Niu, Jun-Qi

    2017-01-01

    This study aimed to explore and evaluate the tolerability and antiviral activity of pegylated recombinant human consensus interferon-α (PEG-CIFN) in adults with hepatitis C virus (HCV) infection. A total of 48 adult subjects chronically infected with HCV were divided into five groups, which were treated separately with PEG-CIFN 1.0 µg/kg (n=10), 1.5 µg/kg (n=10), 2.0 µg/kg (n=9) or 3.0 µg/kg (n=10), or pegylated IFN α-2a (Pegasys) 180 µg (n=9) as controls. Symptoms were observed and laboratory results collected to monitor adverse reactions, adjust drug dosage and evaluate tolerability. The thrombocytopenic effects in all PEG-CIFN dose groups were less than that of pegylated IFN α-2a (at week 14, P<0.05). The rapid virologic response of the PEG-CIFN 1.5, 2.0 and 3.0 µg/kg groups and the pegylated IFN α-2a group were significantly higher than that of the PEG-CIFN 1.0 µg/kg group (P<0.05). Patients who had HCV genotype 1b infections had relatively high responses. The early virologic response of the PEG-CIFN 1.0, 1.5 and 2.0 µg/kg groups and the pegylated IFN α-2a group were 30, 90, 88.8 and 88.8% respectively. PEG-CIFN is well tolerated, and was found to have dose-dependent effectiveness in subjects with chronic hepatitis C. Virological response rates between PEG-CIFN 1.5 or 2.0 µg/kg, and pegylated IFNα-2a were similar, and not significantly different. It is concluded that 1.5 µg/kg PEG-CIFN may be the clinically recommended dose. PEG-CIFN is superior to pegylated IFN α-2a in maintaining platelet levels. PMID:28123460

  11. Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B

    PubMed Central

    Enomoto, Masaru; Morikawa, Hiroyasu; Tamori, Akihiro; Kawada, Norifumi

    2014-01-01

    Infection with hepatitis B virus is an important health problem worldwide: it affects more than 350 million people and is a leading cause of liver-related morbidity, accounting for 1 million deaths annually. Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver. An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease. Liver biopsy has been considered the gold standard for diagnosing disease, grading necroinflammatory activity, and staging fibrosis. However, liver biopsy is unsuitable for repeated evaluations because it is invasive and can cause major complications, including death. Several noninvasive evaluations have been introduced for the assessment of liver fibrosis: serum biomarkers, combined indices or scores, and imaging techniques including transient elastography, acoustic radiation force impulse, real-time tissue elastography, and magnetic resonance elastography. Here, we review the recent progress of noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. Most noninvasive evaluations for liver fibrosis have been validated first in patients with chronic hepatitis C, and later in those with chronic hepatitis B. The establishment of a noninvasive assessment of liver fibrosis is urgently needed to aid in the management of this leading cause of chronic liver disease. PMID:25232240

  12. Chronic hepatitis B in 2014: Great therapeutic progress, large diagnostic deficit

    PubMed Central

    Niederau, Claus

    2014-01-01

    This review analyzes progress and limitations of diagnosis, screening, and therapy of patients with chronic hepatitis B infection. A literature review was carried out by framing the study questions. Vaccination in early childhood has been introduced in most countries and reduces the infection rate. Treatment of chronic hepatitis B can control viral replication in most patients today. It reduces risks for progression and may reverse liver fibrosis. The treatment effect on development of hepatocellular carcinoma is less pronounced when cirrhosis is already present. Despite the success of vaccination and therapy chronic hepatitis B remains a problem since many infected patients do not know of their disease. Although all guidelines recommend screening in high risk groups such as migrants, these suggestions have not been implemented. In addition, the performance of hepatocellular cancer surveillance under real-life conditions is poor. The majority of people with chronic hepatitis B live in resource-constrained settings where effective drugs are not available. Despite the success of vaccination and therapy chronic hepatitis B infection remains a major problem since many patients do not know of their disease. The problems in diagnosis and screening may be overcome by raising awareness, promoting partnerships, and mobilizing resources. PMID:25206267

  13. Epidemiology of acute and chronic hepatitis B virus infection in Norway, 1992-2009

    PubMed Central

    2011-01-01

    Background Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk groups (intravenous drug users (IDUs), Men who have Sex with Men (MSM), immigrants and contacts of known carriers). We describe the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of current risk groups and recommend preventive measures. Methods We used case based data from the national surveillance system on acute and chronic hepatitis B. The Norwegian Statistics Bureau provided population and migration data and the Norwegian Institute for Alcohol and Drug Research the estimated number of active IDUs between 2002-2007. Incidence rates (IR) and incidence rate ratios (IRR) for acute hepatitis B and notification rates (NR) and notification rate ratios (NRR) for chronic hepatitis B with 95% confidence intervals were calculated. Results The annual IR of acute hepatitis B ranged from 0.7/100,000 (1992) to 10.6/100,000 (1999). Transmission occurred mainly among IDUs (64%) or through sexual contact (24%). The risk of acquiring acute hepatitis B was highest in people aged 20-29 (IRR = 6.6 [3.3-13.3]), and in males (IRR = 2.4 [1.7-3.3]). We observed two peaks of newly reported chronic hepatitis B cases in 2003 and 2009 (NR = 17.6/100,000 and 17.4/100,000, respectively). Chronic hepatitis B was more likely to be diagnosed among immigrants than among Norwegians (NRR = 93 [71.9-120.6]), and among those 20-29 compared to those 50-59 (NRR = 5.2 [3.5-7.9]). Conclusions IDUs remain the largest risk group for acute hepatitis B. The observed peaks of chronic hepatitis B are related to increased immigration from high endemic countries and screening and vaccination of these groups is important to prevent further spread of infection. Universal screening of pregnant women should be introduced. A universal vaccination strategy should be considered, given the high cost of reaching the

  14. Diurnal variation in 5-HT1B autoreceptor function in the anterior hypothalamus in vivo: effect of chronic antidepressant drug treatment

    PubMed Central

    Sayer, Tamsin J O; Hannon, Serina D; Redfern, Peter H; Martin, Keith F

    1999-01-01

    Intracerebral microdialysis was used to examine the function of the terminal 5-hydroxytryptamine (5-HT) autoreceptor in the anterior hypothalamus of anaesthetized rats at two points in the light phase of the light–dark cycle.Infusion of the 5-HT1A/1B agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU24969) 0.1, 1.0 and 10 μM through the microdialysis probe led to a concentration-dependent decrease (49, 56 and 65% respectively) in 5-HT output. The effect of RU24969 (1 and 5 μM) was prevented by concurrent infusion of methiothepin (1 and 10 μM) into the anterior hypothalamus via the microdialysis probe. Infusion of methiothepin alone (1.0 and 10 μM) increased (15 and 142% respectively) 5-HT output.Infusion of RU24969 (5 μM) through the probe at mid-light and end-light resulted in a quantitatively greater decrease in 5-HT output at end-light compared with mid-light.Following treatment with either paroxetine hydrochloride (10 mg kg−1 i.p.) or desipramine hydrochloride (10 mg kg−1 i.p.) for 21 days the function of the terminal 5-HT1B autoreceptor was more markedly attenuated at end-light.The data show that, as defined by the response to RU24969, the function of the 5-HT1B receptors that control 5-HT output in the anterior hypothalamus is attenuated following chronic desipramine or paroxetine treatment in a time-of-day-dependent manner. PMID:10372820

  15. Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

    PubMed Central

    Perumpail, Ryan B.; Cholankeril, George

    2016-01-01

    Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome. PMID:27847658

  16. Influence of Hepatic Inflammation on FibroScan Findings in Diagnosing Fibrosis in Patients with Chronic Hepatitis B.

    PubMed

    Zeng, Xianghua; Xu, Cheng; He, Dengming; Zhang, Huiyan; Xia, Jie; Shi, Dairong; Kong, Lingjun; He, Xiaoqin; Wang, Yuming

    2015-06-01

    Hepatic inflammation may affect the performance of FibroScan. This prospective study investigated the influence of hepatic inflammation on liver stiffness measurement (LSM) values by assessing FibroScan and liver biopsy findings in 325 patients with chronic hepatitis B. Liver fibrosis and inflammation were classified into five stages (S0-S4) and grades (G0-G4) according to the Scheuer scoring system. LSM values were correlated with fibrosis stage and inflammation grade (r = 0.479, p < 0.001, and r = 0.522, p < 0.001, respectively). Although LSM values increased in parallel with inflammation grade, no significant differences were found between patients with significant fibrosis (S2-S4) (p > 0.05). For inflammation grades G0, G1, G2 and G3, areas under receiver operating characteristic curves of FibroScan for significant fibrosis were 0.8267 (p < 0.001), 0.6956 (p < 0.001), 0.709 (p = 0.0012) and 0.6947 (p = 0.137), respectively. Inflammation has a significant influence on LSM values in patients with chronic hepatitis B with mild fibrosis, but not in those with significant fibrosis.

  17. Screening for chronic hepatitis B among Asian/Pacific Islander populations--New York City, 2005.

    PubMed

    2006-05-12

    Chronic hepatitis B virus (HBV) infection is the most common cause of cirrhosis and liver cancer worldwide. In Asian and western Pacific countries where HBV is endemic, estimated prevalence of chronic HBV infection ranges from 2.4%-16.0%, and liver cancer is a leading cause of mortality. Although population-based prevalence data for Asians/ Pacific Islanders (A/PIs) living in the United States are lacking, they are believed to constitute a sizeable percentage of persons with chronic HBV infection in the United States, a country of low endemicity. To assess the prevalence of chronic HBV infection among A/PI populations living in New York City, the Asian American Hepatitis B Program (AAHBP) conducted a seroprevalence study among persons who participated in an ongoing hepatitis B screening, evaluation, and treatment program. The results indicated that approximately 15% of participants who had not been previously tested had chronic HBV infection; all were born outside the United States. Screening programs are needed in A/PI communities in the United States to identify persons with chronic HBV infection so that they can be referred for appropriate medical management to prevent cirrhosis and liver cancer and so that their susceptible household and sex contacts can receive hepatitis B vaccine.

  18. Evolving New Strategies for the Medical Management of Chronic Hepatitis B Virus Infection

    PubMed Central

    Zhou, Tianlun; Anbarasan, Nikhil; Gish, Robert

    2016-01-01

    Is a cure for chronic hepatitis B virus (HBV) infection possible? Hepatitis C virus infection is now routinely cured medically. There is a growing expectation that new drugs for the management of chronic HBV infection should provide substantial benefit over and above that of current chronic HBV medications, if not be curative. Although the definition of medically induced cure for chronic HBV infection varies, most include sustained off-drug absence of viremia and negativity for other virologic markers. There are currently more than 29 drugs in the pipeline being tested for the management of chronic HBV infection. This article discusses the potential drugs with respect to their possible contributions to achieving medically induced cure. PMID:28035197

  19. Interleukin-12 induction of Th1 cytokines is important for viral clearance in chronic hepatitis B.

    PubMed Central

    Rossol, S; Marinos, G; Carucci, P; Singer, M V; Williams, R; Naoumov, N V

    1997-01-01

    Interleukin-12, a cytokine with an important role against intracellular pathogens, promotes Th1 cell development, cellmediated cytotoxicity, and interferon-gamma production. We investigated the immunoregulatory role of IL-12 in 72 chronic hepatitis B virus (HBV) carriers, 33 of whom were monitored longitudinally during interferon-alpha treatment. Serum levels of IL-12 heterodimer, IL-12 p40 subunit, IL-4, and Th1 cytokines were determined by specific ELISAs, and hepatitis B core antigen-specific T cell response by a proliferation assay. Chronic HBV carriers had higher serum levels of IL-12 and IL-12 p40 in comparison with controls (P < 0.01), suggesting that IL-12 production is not impaired. The longitudinal analysis revealed a further substantial increase (> 2.5x baseline level) of bioactive IL-12 and Th1 cytokines in patients who cleared HBV and seroconverted to anti- hepatitis B e, unlike the 23 nonresponders with persistent HBV replication (P < 0.01). The IL-12 peak followed the peak of hepatocytolysis by 9.8+/-2.8 wk and occurred either before or simultaneously with hepatitis B e seroconversion. Hepatitis B core antigen-specific T cell proliferation closely correlated with hepatocytolysis and increased significantly in all patients (8 responders and 15 nonresponders) who developed hepatitis flare, irrespective of the virological outcome. These results provide in vivo evidence that IL-12 may have an important role for viral clearance in chronic HBV infection. PMID:9185527

  20. Progress in the treatment of chronic hepatitis B: long-term experience with adefovir dipivoxil.

    PubMed

    Delaney, William E

    2007-05-01

    Most chronic hepatitis B patients do not undergo a curative response to interferon-alpha or nucleoside/nucleotide-based regimens and require long-term therapy. Long-term safety, efficacy and resistance profiles of hepatitis B virus (HBV) drugs are therefore crucial issues for patient management. Adefovir dipivoxil is a nucleotide prodrug indicated for the treatment of patients with hepatitis B e antigen positive or hepatitis B e antigen negative chronic hepatitis B, lamivudine-resistant HBV infection, HBV infection pre- or post-liver transplantation, or HlV co-infection. Long-term data from clinical trials of up to 5 years duration of adefovir dipivoxil have recently become available and are reviewed here. These data demonstrate that adefovir dipivoxil therapy results in sustained efficacy and safety in the majority of patients after multiple years of treatment. The efficacy of adefovir dipivoxil in treating lamivudine-resistant HBV and the delayed emergence of adefovir resistance are key factors contributing to the durable response achieved in broad groups of chronic hepatitis B patients.

  1. Hepatitis B antigen and auto-antibodies in chronic liver diseases in Hong Kong.

    PubMed

    Lee, A K

    1975-06-01

    The frequency of occurrence of hepatitis B antigen (HBAg) and certain tissue autoantibodies [antinuclear antibody (ANA), smooth muscle antibody (SMA) and mitochondrial antibody (MIA)] were studied with the microtiter complement fixation and immunofluorescence techniques respectively in a group of patients suffering from chronic liver diseases. These were chronic hepatitis (30), cirrhosis of the liver (66) and hepatocellular carcinoma, mostly with underlying cirrhosis (100). A group of closely matched hospital in-patients served as controls. HBAg was found in high frequency in the patients with liver disease (60% in chronic hepatitis, 36.4% in cirrhosis and 49% in hepatocellular carcinoma) whereas tissue auto-antibodies were found in lower frequencies (16.7%, 10.6% and 13% in the three groups respectively). However, in both the frequency was significantly higher than that in the controls (9.2% for HBAg and 0.8% for auto-antibodies). There was a negative correlation between HBAg and tissue auto-antibodies in the group of patients with liver disease when taken as a whole (x2=14.3, P less than 0.001). These results suggest a possible aetiological role played by hepatitis virus B in hepatocellular carcinoma through chronic hepatitis and cirrhosis in Hong Kong while the mutual exclusion between HBAg and auto-antibodies supports the hypothesis of heterogeneity in the aetiology of chronic liver diseases. The patients with auto-antibodies may belong to the auto-immune category but no definate conclusion can be reached until the role played by hepatitis virus A in chronic liver diseases is clarified when more reliable techniques for its identification are available.

  2. Liver transient elastography (Fibroscan): a place in the management algorithms of chronic viral hepatitis.

    PubMed

    Scott, David R; Levy, Miriam T

    2010-01-01

    Treatment guidelines are continuously evolving in chronic viral hepatitis, taking into consideration our greater understanding of natural history and therapeutic efficacy and safety. Key in the decision making process is an assessment of liver injury. Traditionally, liver biopsy has provided this information; however, this is an invasive procedure and not completely reliable. Liver transient elastography (Fibroscan) is exciting new technology that allows estimation of hepatic fibrosis through measurement of liver stiffness. It is acceptably accurate, safe, cheap, quick and widely applicable, and can reduce the need for liver biopsy in chronic hepatitis. In chronic hepatitis C, it can identify those most likely to benefit from treatment, as well as those with cirrhosis who require more specific care. In chronic hepatitis B, it could screen groups previously excluded from treatment (normal alanine aminotransferase and low DNA) to identify the subgroup that would benefit from therapy. It cannot replace biopsy in all settings, but it will narrow the group who do require biopsy, and provide information on liver damage in patients for whom biopsy would probably not have been considered.

  3. [Efficiency of remaxol in preventing unwanted side effects of the antiviral therapy in patients with chronic hepatitis C].

    PubMed

    Baranova, I P; Zykova, O A; Krasnova, L I; Romantsov, M G; Nikol'skaia, M V; Aftaeva, L N

    2013-01-01

    The article briefly addresses issues pertaining to the problem of complications encountered in antiviral therapy of patients with chronic hepatitis C. Data on the effectiveness of remaxol as a means of preventing the development of complication in patients with chronic viral hepatitis C in early stages of antiviral treatment.

  4. Sofosbuvir-based therapy for patients with chronic hepatitis C: Early experience of its efficacy and safety in Korea

    PubMed Central

    Cho, Yuri; Cho, Eun Ju; Lee, Jeong-Hoon; Yu, Su Jong; Yoon, Jung-Hwan

    2015-01-01

    Background/Aims The previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein. Methods Data on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin. Results This retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naïve patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy. Conclusions In a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy. PMID:26770924

  5. Assessment of IL-28: rs12979860 and rs8099917 Polymorphisms in a Cohort of Cuban Chronic HCV Genotype 1b Patients

    PubMed Central

    Palenzuela Gardón, Daniel; Guillen, Isabel Alicia; Fernández, Julio R.; Camacho, Hamlet; Estevez, Zurina Cinza; Dueñas, Santiago; Alvares-Lajonchere, Liz; Amador, Yalena; Martinez-Donato, Gillian; Han, Junsong; Zhang, Zhiming; Zhang, Xiaona; Gao, Yang; Campaña, Juan Roca; Novoa, Lidia I.

    2016-01-01

    Hepatitis C virus (HCV) is a significant global public health problem with >185 million infections worldwide. A series of genome-wide association studies (GWAS) has identified IL-28B polymorphisms as a predictor of sustained virologic response (SVR), as well as spontaneous clearance in chronic HCV genotype 1 patients. The objective of this work was to evaluate the prevalence of IL-28B rs12979860 and rs8099917 polymorphisms in Cuban chronic HCV patients. The study cohort included 73 chronic HCV patients treated with concomitant administration of CIGB-230 and nonpegylated IFN-α plus ribavirin (non-pegIFN-α/R) antiviral therapy. The genotype distribution of IL-28B rs12979860CC, -CT, and -TT was 29, 41, and 30%, respectively, and the distribution for rs8099917TT, -TG, and -GG was 63, 31, and 5%, respectively. The allele frequencies for rs12979860C and -T alleles were 51 and 49%, respectively, and for rs8099917G and -T alleles, the values were 21 and 79%, respectively. SVR rates were 55, 42, and 35% for rs12979860CC, -CT, and -TT, respectively, and 52, 30, and 25% for rs8099917TT, -GT, and -GG, respectively. The combined assessment of both single nucleotide polymorphisms (SNPs) resulted in 3 major genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TT, and rs12979860CT/rs8099917GG) with a frequency of 30.1, 21.9, and 20.5%, respectively. In patients with heterozygous variant rs12979860CT, the additional genotyping of rs8099917 contributed to increase the SVR rate. It is concluded that in Cuban HCV-infected patients, the responder homogeneous variant rs8099917TT is the most frequent genotype. The simultaneous genotyping of 2 IL-28B SNPs could improve the prediction of SVR contributing to better therapeutic decisions and treatment management. PMID:28058039

  6. HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment

    PubMed Central

    Sarrazin, Christoph; Manns, Michael; Calleja, Jose Luis; Garcia-Samaniego, Javier; Forns, Xavier; Kaste, Renee; Bai, Xiaofei; Wu, Jing; Stern, Jerry O.

    2016-01-01

    This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and ‘other’ (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%–83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%–76.7%), including most CPA (11/16) patients with Week 4 HCV RNA <25 IU.mL-1 (target detected or not detected) and most CPB (8/9) patients with Week 4 HCV RNA <25 IU.mL-1 (target not detected); 0/4 CPB patients with Week 4 HCV RNA <25 IU.mL-1 (target detected) achieved SVR12. The most common AEs in both groups were nausea, diarrhoea and vomiting. Serious AEs were observed in 9 (53%) CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53–61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response

  7. Dual Infection with Hepatitis B and Epstein-Barr Virus Presenting with Severe Jaundice, Coagulopathy, and Hepatitis B Virus Chronicity Outcome

    PubMed Central

    Rao, Sirish C.; Ashraf, Imran; Mir, Fazia; Samiullah, Sami; Ibdah, Jamal A.; Tahan, Veysel

    2017-01-01

    Patient: Female, 34 Final Diagnosis: HBV and EBV dual infection Symptoms: Jaundice • fatigue • anorexia • subjective weight loss Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Hepatitis B virus (HBV) has been reported as a coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Case Report: A 34-year-old female presented to our clinic with epigastric pain and severe acute hepatitis manifested as jaundice associated with hyperbilirubinemia, elevated transaminases, and coagulopathy. The patient was diagnosed with acute HBV with Epstein-Barr virus (EBV) coinfection leading to subsequent chronic hepatitis B. Conclusions: To our knowledge, this patient case is the first reported case of HBV and EBV coinfection reported in the literature. HBV and EBV coinfection may cause severe acute hepatitis with HBV chronicity. PMID:28202897

  8. Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma.

    PubMed

    Murata, Miki; Yoshida, Katsunori; Yamaguchi, Takashi; Matsuzaki, Koichi

    2014-11-07

    Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.

  9. OCCULT AND PREVIOUS HEPATITIS B VIRUS INFECTION ARE NOT ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN US PATIENTS WITH CHRONIC HEPATITIS C

    PubMed Central

    Lok, Anna S.; Everhart, James E.; Di Bisceglie, Adrian M.; Kim, Hae-Young; Hussain, Munira; Morgan, Timothy R.

    2011-01-01

    Background & Aim Previous studies have suggested that prior exposure to hepatitis B virus (HBV) infection may increase the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The aim of this study was to compare the prevalence of previous or occult HBV infection in a cohort of HBsAg-negative patients with histologically advanced chronic hepatitis C in the United States who did or did not develop HCC. Methods Stored sera from 91 patients with HCC and 182 matched controls who participated in the HALT-C Trial were tested for anti-HBc, anti-HBs and HBV DNA. Frozen liver samples from 28 HCC cases and 55 controls were tested for HBV DNA by real-time PCR. Results Anti-HBc (as a marker of previous HBV infection) was present in the serum of 41.8% HCC cases and 45.6% controls (P=0.54); anti-HBc alone was present in 16.5% of HCC cases and 24.7% of controls. HBV DNA was detected in the serum of only one control subject and no patient with HCC. HBV DNA (as a marker of occult HBV infection) was detected in the liver of 10.7% HCC cases and 23.6% controls (P=0.18). Conclusion Although almost half the patients in the HALT-C Trial had serological evidence of previous HBV infection there was no difference in prevalence of anti-HBc in serum or HBV DNA in liver between patients who did or did not develop HCC. In the United States, neither previous nor occult HBV infection is an important factor in HCC development among patients with advanced chronic hepatitis C. PMID:21374690

  10. Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis

    SciTech Connect

    D'Arienzo, A.; Celentano, L.; Scuotto, A.; Di Siervi, P.; Lombardi, V.; Squame, G.; Mazzacca, G.

    1988-07-01

    In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function tests were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.

  11. Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience

    PubMed Central

    CLEO Study Group; Ascione, Antonio; Adinolfi, Luigi Elio; Amoroso, Pietro; Andriulli, Angelo; Armignacco, Orlando; Ascione, Tiziana; Babudieri, Sergio; Barbarini, Giorgio; Brogna, Michele; Cesario, Francesco; Citro, Vincenzo; Claar, Ernesto; Cozzolongo, Raffaele; D’Adamo, Giuseppe; D’Amico, Emilio; Dattolo, Pellegrino; De Luca, Massimo; De Maria, Vincenzo; De Siena, Massimo; De Vita, Giuseppe; Di Giacomo, Antonio; De Marco, Rosanna; De Stefano, Giorgio; De Stefano, Giulio; Di Salvo, Sebastiano; Di Sarno, Raffaele; Farella, Nunzia; Felicioni, Laura; Fimiani, Basilio; Fontanella, Luca; Foti, Giuseppe; Furlan, Caterina; Giancotti, Francesca; Giolitto, Giancarlo; Gravina, Tiziana; Guerrera, Barbara; Gulminetti, Roberto; Iacobellis, Angelo; Imparato, Michele; Iodice, Angelo; Iovinella, Vincenzo; Izzi, Antonio; Liberti, Alfonso; Leo, Pietro; Lettieri, Gennaro; Luppino, Ileana; Marrone, Aldo; Mazzoni, Ettore; Messina, Vincenzo; Monarca, Roberto; Narciso, Vincenzo; Nosotti, Lorenzo; Pellicelli, Adriano Maria; Perrella, Alessandro; Piai, Guido; Picardi, Antonio; Pierri, Paola; Pietromatera, Grazia; Resta, Francesco; Rinaldi, Luca; Romano, Mario; Rossini, Angelo; Russello, Maurizio; Russo, Grazia; Sacco, Rodolfo; Sangiovanni, Vincenzo; Schiano, Antonio; Sciambra, Antonio; Scifo, Gaetano; Simeone, Filomena; Sullo, Annarita; Tarquini, Pierluigi; Tundo, Paolo; Vallone, Alfredo

    2016-01-01

    AIM To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings. METHODS This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL). RESULTS All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin. PMID:27574549

  12. Hepatitis

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Hepatitis KidsHealth > For Teens > Hepatitis Print A A A ... to a liver condition called hepatitis . What Is Hepatitis? The liver is one of the body's powerhouses. ...

  13. Hepatitis

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  14. Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum

    PubMed Central

    Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

    2016-01-01

    Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients. PMID:27977668

  15. Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum.

    PubMed

    Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

    2016-12-01

    Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients.

  16. Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome.

    PubMed

    Mauss, S; Berger, F; Schober, A; Moog, G; Heyne, R; John, C; Pape, S; Hueppe, D; Pfeiffer-Vornkahl, H; Alshuth, U

    2013-04-01

    Autoantibodies in hepatitis C virus-infected patients may indicate autoimmune hepatitis or other immune-mediated diseases. This may impact safety and efficacy of interferon-based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched-pair analysis was performed matching one autoantibody-positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.

  17. Impact of the IL-10 Promoter Gene Polymorphisms in the Severity of Chronic Hepatitis B Infection

    PubMed Central

    Ghaleh Baghi, Sahand; Alavian, Seyed Moayed; Mehrnoush, Leila; Salimi, Shima

    2015-01-01

    Background: Interleukin-10 (IL-10) is an important anti-inflammatory cytokine. The polymorphisms of its promoter gene have been considered to be related with the chronicity of hepatitis B infection. Objectives: The aim of this study was to evaluate the polymorphisms at different positions in the IL-10 promoter gene in patients with chronic hepatitis B. Patients and Methods: Totally, 166 patients with chronic hepatitis B infection were enrolled. Genotypes at different positions (i.e. -819, - 592, and - 1082) in the IL-10 gene promoter were determined. Results: The C/A genotype at position -592, C/T genotype at position -819, and GCC/ATA haplotype of the IL-10 gene promoter were significantly more common in the patients with cirrhosis. The genotypes were significantly different between the hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients at position -592 (C/A and C/C), position -819 (C/C and C/T), and position -1082 (A/A and G/A). Conclusions: Some IL-10 promoter gene polymorphisms predisposed the infected hepatitis B virus cases to cirrhosis in our study population. PMID:26300930

  18. Oral mucosa alterations in chronic hepatitis and cirrhosis due to HBV or HCV infection.

    PubMed

    Sulka, Agnieszka; Simon, Krzysztof; Piszko, Paweł; Kalecińska, Ewa; Dominiak, Marzena

    2006-03-01

    The aim of the study was to evaluate the character of lesions within oral mucosa in patients suffering from chronic hepatitis and cirrhosis of the liver due to either HBV or HCV infection. A total of 74 patients treated at the Clinic of Infectious Diseases in Wrocław for chronic hepatitis B (20 patients, group I) and for chronic hepatitis C (23 patients group III) and cirrhosis of the liver due to HBV (15 patients , group II) and HCV (16 patients, group IV) infection. The control group comprised 29 healthy subjects. Lesions within the oral mucosa found on clinical examinations were confirmed with a histopathological evaluation. Patients suffering from chronic hepatitis B revealed leukoplakia (1/20), melanoplakia (1/20), petechiae (1/20), 17 patients from this group did not show any changes. Patients suffering from chronic hepatitis C revealed leukoplakia (6/23), Delbanco's disease (2/23), melanoplakia (1/23), lichen planus (1/23), petechiae (1/23), 12 patients from this group did not show any changes. Patients suffering from cirrhosis of the liver due of HBV infection revealed leukoplakia (3/15) petechiae (2/15), Delbanco's disease (1/15), angular cheilitis (1/15), aphthae (1/15), 7 patients from this group did not reveal any changes. Patients suffering from cirrhosis of the liver due of HCV infection revealed petechiae (2/16), melanoplakia (1/16), candidosis (1/16), labial herpes (1/16), 11 patients from this group did not reveal any changes. In control group we observed leukoplakia (3/29), Delbanco's disease (1/29), labial herpes (1/29), petechiae (1/29), and 23 subjects did not present pathological lesions within the oral mucosa. Results indicate the lack of connection between chronic HBV and HCV infection as well as the stage of the disease with the incidence and character of oral lesions in oral mucosa.

  19. Expression of the hepatitis B virus genome in chronic hepatitis B carriers and patients with hepatocellular carcinoma

    SciTech Connect

    Bowyer, S.M.; Dusheiko, G.M.; Schoub, B.D.; Kew, M.C.

    1987-02-01

    The authors examined the methylation status of CCGG sites in hepatitis B virus (HBV) DNA to determine whether methylation could be responsible for the selective expression of the HBV surface gene in chronic hepatitis B infection and hepatocellular carcinoma. Infected liver tissue from patients with low levels of viral replication was analyzed for HBV DNA copy number per haploid cell genome. Total cellular DNA, with sufficient HBV DNA, was digested with the restriction endonucleases Msp I and Hpa II, to determine whether the HBV DNA was methylated, or HindIII, to determine whether the HBV DNA was integrated or episomal. The cleavage fragments were analyzed by Southern blotting and hybridization to /sup 32/P-labeled HBV DNA. In replicative chronic hepatitis B, hypomethylation of the HBV genome correlated with HBV expression in both virions and infected tissue. In carriers with nonreplicative infection, it was difficult to ascertain the role of methylation as copy number was low. HBV DNA copy number was also low in 17 out of 29 of the rumor tissues tested and as many as 14 out of 16 of the adjacent non-neoplastic tissues tested. Integrated sequences were hypermethylated in the PLC/PRF/5 cell line and in six of the tumor tissues suggesting that methylation plays a role in HBV gene repression. However, since DNA from five other tumors was hypomethylated, the belief that methylation per se is an absolute determinant of HBV core gene repression does not hold for human hepatocellular carcinoma tissue.

  20. Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation

    PubMed Central

    Bility, Moses T.; Nio, Kouki; Li, Feng; McGivern, David R.; Lemon, Stanley M.; Feeney, Eoin R.; Chung, Raymond T.; Su, Lishan

    2016-01-01

    The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV–induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV–induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis. PMID:28000758

  1. Chronic hepatitis C infection-induced liver fibrogenesis is associated with M2 macrophage activation.

    PubMed

    Bility, Moses T; Nio, Kouki; Li, Feng; McGivern, David R; Lemon, Stanley M; Feeney, Eoin R; Chung, Raymond T; Su, Lishan

    2016-12-21

    The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV-induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV-induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis.

  2. [Clinical and immunological features of acute hepatitis B in patients with concomitant chronic toxic liver damage].

    PubMed

    Furyk, E; Ryabokon, E

    2013-02-01

    The article presents information obtained during the survey in 64 patients with acute hepatitis B. We show that acute hepatitis B in patients with concomitant chronic toxic liver characterized by a marked imbalance of cytokine status due to a lower level of interleukin-2 and a higher content of interleukin-8, the highest levels of nitrite content, spontaneous oxidative modifications of blood proteins and the lowest content of L -arginine in the blood serum in the dynamics of disease compared with patients without this concomitant factor. In the period of convalescence these changes in patients with acute hepatitis B with concomitant chronic toxic liver characterized combined with higher cytolysis of liver cells, often circulating in the blood of HBsAg seroconversion and less frequently with the advent of anti-HBeAg.

  3. DNA-binding antibodies and hepatitis B markers in acute and chronic liver disease.

    PubMed Central

    Kingham, J G; Rassam, S; Ganguly, N; Mcguire, M J; Nasrat, B; Holgate, S T; Triger, D R; Wright, R

    1978-01-01

    A Farr technique has been used to assay antibodies to double-stranded DNA in the serum of patients with acute and chronic liver disease and carriers of HBsAg from the United Kingdom and Iraq. These antibodies were found in all groups from both countries. The highest levels were found in chronic active hepatitis and cirrhosis. In the Iraqi patients there was a strongly positive correlation between DNA-binding antibody levels and the presence of hepatitis B markers but not with disease activity. In the patients from the United Kingdom there was little correlation with disease activity and none with autoantibodies. Ninety-five per cent of asymptomatic carriers of HBsAG had elevated DNA-binding antibodies. It is suggested that hepatitis B-specific DNA might be one trigger to DNA antibody formation, though in liver disease a variety of factors are clearly operative. PMID:309808

  4. Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

    PubMed

    Li, Xi; Wiesen, Eric; Diorditsa, Sergey; Toda, Kohei; Duong, Thi Hong; Nguyen, Lien Huong; Nguyen, Van Cuong; Nguyen, Tran Hien

    2016-02-03

    Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine.

  5. Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C

    PubMed Central

    Manolakopoulos, Spilios; Zacharakis, George; Zissis, Miltiadis; Giannakopoulos, Vassilis

    2016-01-01

    Daclatasvir (Daklinza™), a new oral direct-acting antiviral, is an inhibitor of hepatitis C virus NS5A protein and has recently been approved in the United States, Europe and Japan in chronic hepatitis C. It shows potent pangenotypic activity and moderately high genetic barrier to resistance improving the sustained virological response (SVR) rates. In COMMAND phase 2 trials, daclatasvir demonstrated high SVR rates in HCV genotype 1-4 chronically infected patients treated with peginterferon-a (pegIFNα) plus ribavirin (RBV). Furthermore, it produced even higher response rates in all-oral combination with sofosbuvir, an interferon-free regimen, with or without ribavirin, in patients with advanced liver disease, HCV/HIV coinfection, liver transplantation in ALLY studies and other real-world studies. This narrative review provides information on the pharmacological properties, role, efficacy and safety of daclatasvir-containing regimens in chronic hepatitis C patients. Daclatasvir administered once-daily in combination with sofosbuvir is an effective 12-week treatment in adult patients with chronic hepatitis C and is generally safe and well tolerated. PMID:27366028

  6. Myasthenia Crisis Induced by Pegylated-Interferon in Patient With Chronic Hepatitis C

    PubMed Central

    Baik, Su Jung; Kim, Tae Hun; Kim, Hye In; Rhie, Jeong Yeon

    2016-01-01

    Abstract Myasthenia gravis is occasionally associated with thymoma that needs surgical resection and may progress to severe respiratory failure. We experienced a rare case of myasthenia crisis during antiviral therapy for chronic hepatitis C, in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care. A 47-year-old-male patient complained of sudden diplopia 1 week after stopping 11-week administration of pegylated-interferon and ribavirin for chronic hepatitis C. Ophthalmologic examinations revealed ptosis on the right eyelid and restricted right eye movement. Myasthenia gravis was confirmed by positive repetitive nerve stimulation test and positive serum antiacetylcholine receptor antibody test, and mediastinal thymoma was found on chest CT scan. The ocular myasthenia gravis progressed to respiratory failure even after discontinuing antiviral treatment but eventually recovered with thymectomy, anticholinesterase administration, steroid pulse therapy, and prolonged ventilator care. We describe the clinical features of this life-threatening complication of interferon treatment along with previous myasthenia crisis cases by interferon for chronic hepatitis C. In patients with chronic hepatitis C who is going to receive interferon-based antiviral treatment, physicians need to keep in mind the potential life-threatening manifestations of myasthenia gravis before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability. PMID:27227948

  7. Is liver biopsy still needed in children with chronic viral hepatitis?

    PubMed Central

    Pokorska-Śpiewak, Maria; Kowalik-Mikołajewska, Barbara; Aniszewska, Małgorzata; Pluta, Magdalena; Marczyńska, Magdalena

    2015-01-01

    Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods. PMID:26576098

  8. Sofosbuvir and Simeprevir Treatment of a Stem Cell Transplanted Teenager With Chronic Hepatitis C Infection.

    PubMed

    Fischler, Björn; Priftakis, Peter; Sundin, Mikael

    2016-06-01

    There have been no previous reports on the use of interferon-free combinations in pediatric patients with chronic hepatitis C infection. An infected adolescent with severe sickle cell disease underwent stem cell transplantation and subsequent treatment with sofosbuvir and simeprevir during ongoing immunosuppression. Despite the emergence of peripheral edema as a side effect, treatment was continued with sustained antiviral response.

  9. Is liver biopsy still needed in children with chronic viral hepatitis?

    PubMed

    Pokorska-Śpiewak, Maria; Kowalik-Mikołajewska, Barbara; Aniszewska, Małgorzata; Pluta, Magdalena; Marczyńska, Magdalena

    2015-11-14

    Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

  10. Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck.

    PubMed

    Kosinska, Anna D; Liu, Jia; Lu, Mengji; Roggendorf, Michael

    2015-02-01

    Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model.

  11. High Dose of Lamivudine and Resistance in Patients with Chronic Hepatitis B

    PubMed Central

    Wani, Hamid Ullah; Al Kaabi, Saad; Singh, Rajvir; John, Anil; Derbala, Moutaz; Al-Mohannadi, Muneera J.

    2014-01-01

    Background. Lamivudine is the most affordable drug used for chronic hepatitis B and has a high safety profile. With the daily dose of 100 mg there is progressive appearance of resistance to lamivudine therapy. In our study we used 150 mg of lamivudine daily as a standard dose which warrants further exploration for the efficacy of the drug. Aims of the Study. To assess the efficacy of lamivudine 150 mg daily on resistance in patients with chronic hepatitis B. Methods. This retrospective study consists of 53 patients with chronic hepatitis B treated with 150 mg of lamivudine daily. The biochemical and virological response to the treatment were recorded at a 1-year and 2-, 3-, 4-, and 5-year period and time of emergence of resistance to the treatment was noted. Results. The mean age of the patients was 54 years with 80% being males. The resistance to lamivudine 150 mg daily at 1 year and 2, 3, and 5 years was 12.5%, 22.5%, 37.5%, and 60%, respectively, which is much less compared to the standard dose of 100 mg of lamivudine. Conclusions. Lamivudine is safe and a higher dose of 150 mg daily delays the resistance in patients with chronic hepatitis B. PMID:25349729

  12. High dose of Lamivudine and resistance in patients with chronic hepatitis B.

    PubMed

    Wani, Hamid Ullah; Al Kaabi, Saad; Sharma, Manik; Singh, Rajvir; John, Anil; Derbala, Moutaz; Al-Mohannadi, Muneera J

    2014-01-01

    Background. Lamivudine is the most affordable drug used for chronic hepatitis B and has a high safety profile. With the daily dose of 100 mg there is progressive appearance of resistance to lamivudine therapy. In our study we used 150 mg of lamivudine daily as a standard dose which warrants further exploration for the efficacy of the drug. Aims of the Study. To assess the efficacy of lamivudine 150 mg daily on resistance in patients with chronic hepatitis B. Methods. This retrospective study consists of 53 patients with chronic hepatitis B treated with 150 mg of lamivudine daily. The biochemical and virological response to the treatment were recorded at a 1-year and 2-, 3-, 4-, and 5-year period and time of emergence of resistance to the treatment was noted. Results. The mean age of the patients was 54 years with 80% being males. The resistance to lamivudine 150 mg daily at 1 year and 2, 3, and 5 years was 12.5%, 22.5%, 37.5%, and 60%, respectively, which is much less compared to the standard dose of 100 mg of lamivudine. Conclusions. Lamivudine is safe and a higher dose of 150 mg daily delays the resistance in patients with chronic hepatitis B.

  13. Chronic Hepatitis C and Antiviral Treatment Regimens: Where Can Psychology Contribute?

    ERIC Educational Resources Information Center

    Evon, Donna M.; Golin, Carol E.; Fried, Michael W.; Keefe, Francis J.

    2013-01-01

    Objective: Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology…

  14. EPIDEMIOLOGICAL FEATURES OF CHRONIC VIRUS HEPATITIS B AND C IN THE REPUBLIC SAKHA (YAKUTIA).

    PubMed

    Gerasimova, V V; Maksimova, N R; Levakoval, A; Zhebrun, A B; Mukomolov, S L

    2015-01-01

    High disease burden of chronic virus hepatitis B and C of population in the Republic Sakha (Yakutia) is subject to referring it to endemic territories due to these infections. For a 15-year-old period the disease has been registered at higher rates in the Russian Federation.

  15. Chronic hepatitis B and C: Exploring perceived stigma, disease information, and health-related quality of life.

    PubMed

    Drazic, Yvonne Nelly; Caltabiano, Marie Louise

    2013-06-01

    Research indicates that chronic hepatitis C affects people's quality of life, but such reports are scarce about hepatitis B. This Australian study explored whether perceived stigma and satisfaction with received information and care were related to health-related quality of life in people with chronic hepatitis B or C. A questionnaire was constructed comprising demographic questions and existing scales to measure the variables. The 77 participants were recruited through various online channels. The median age was 48 years, 74% had hepatitis C, 60% were female, and 73% were Caucasian. Participants with Hepatitis B reported substantially less perceived stigma than those with Hepatitis C, but there was no significant difference between the two groups in health-related quality of life. Participants with Hepatitis C reported higher satisfaction with received information. The results highlight specific aspects to consider in the care of people with chronic hepatitis. For example, people with hepatitis B do not seem to enjoy better health-related quality of life despite lower perceived stigmatization. Therefore, these patients may require other improvements in service delivery such as the provision of more culturally appropriate information and education about chronic hepatitis B.

  16. Studying the association of microRNA-210 level with chronic hepatitis B progression.

    PubMed

    Song, G; Jia, H; Xu, H; Liu, W; Zhu, H; Li, S; Shi, J; Li, Z; He, J; Chen, Z

    2014-04-01

    We studied the relationship between hypoxia and microRNA-210 (miR-210) levels, the miR-210 levels in patients with hepatitis B and the roles of miR-210 in liver inflammation. We used the concanavalin A (Con A) murine hepatitis model and inflammation, hypoxia and miR-210 levels were examined. In these patients, we studied serum miR-210 levels and clinical indexes related to hepatitis in 90 patients with different stages of chronic hepatitis B and 30 controls. Two functional assays of miR-210 in vitro under hypoxic condition were conducted. The animal experiments indicated that the liver and serum miR-210 levels significantly increased with liver hypoxia and inflammation. In humans, serum miR-210 levels enhanced with hepatitis severity and were related to serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB) and prothrombin activity (PTA) levels. The miR-210 functional assays showed that miR-210 elevation might be related to the decreases in HepG2.2.15 cell dehydrogenase activity and HBV replication under hypoxic conditions. Because the liver inflammation causes liver hypoxia which also results in liver and serum miR-210 level elevation, the serum miR-210 level may serve as a molecular biomarker for the severity of hepatitis and increases in liver miR-210 that we see may be a response of hepatocytes to hypoxia during hepatitis progression.

  17. Structural Characteristics of Gastric Cell Populations in Chronic Gastritis and Chronic Hepatitis under Conditions of Helicobacter pylori Persistence.

    PubMed

    Lapii, G A; Bakarev, M A; Nepomnyashchikh, G I; Kapustina, V I; Nepomnyashchikh, D L; Vinogradova, E V; Postnikova, O A

    2016-02-01

    Helicobacter pylori persistence in patients with chronic gastritis is associated with a complex of nonspecific structural reactions, the type of these reactions correlates with the severity of infection: catarrhal fibrotic changes in the gastric mucosa predominate in cases with manifest colonization, while the absence of H. pylori is associated with predominance of fibrotic process. Analysis of the incidence of some pathomorphological phenomena (degeneration, atrophy, metaplasia, and dysplasia of the surface epithelium) shows no relationship between the presence of H. pylori and colonization intensity. In all patients with chronic hepatitis, the gastric mucosa is involved in the pathological process; fibrosis (gastropathy) was the most common process. No appreciable correlations between the structural changes and hepatitis activity and the presence of H. pylori were detected.

  18. Non invasive assessment of liver fibrosis in chronic hemodialysis patients with viral hepatitis C

    PubMed Central

    Arrayhani, Mohamed; Sqalli, Tarik; Tazi, Nada; El Youbi, Randa; Chaouch, Safae; Aqodad, Nourdin; Ibrahimi, Sidi Adil

    2015-01-01

    The liver biopsy has long been the "gold standard" for assessing liver fibrosis in patients with hepatitis C. It's an invasive procedure which is associated with an elevated bleeding, especially in chronic hemodialysis patients. Main goal is to assess liver fibrosis in chronic hemodialysis with HCV by Fibroscan and by biological scores (APRI, Forns and Fib-4), and to measure the correlation between these tests. Cross-sectional study including all chronic hemodialysis patients with hepatitis C virus, in two public hemodialysis centers of Fez. All patients were evaluated for liver fibrosis using noninvasive methods (FibroScan and laboratory tests). Subsequently, the correlation between different tests has been measured. 95 chronic hemodialysis were studied, twenty nine patients (30.5%) with chronic hepatitis C. The average age was 52.38 ± 16.8 years. Nine liver fibrosis cases have been concluded by forns score. Fibroscan has objectified significant fibrosis in 6 cases. On the other side APRI has objectified sgnifivant fibrosis only in 3 cases. The Fib-4 showed severe fibrosis in five cases. The results have been most consistent between APRI and Fib-4, followed by Fibroscan and Forns, then APRI and FibroScan. PMID:26958136

  19. Non invasive assessment of liver fibrosis in chronic hemodialysis patients with viral hepatitis C.

    PubMed

    Arrayhani, Mohamed; Sqalli, Tarik; Tazi, Nada; El Youbi, Randa; Chaouch, Safae; Aqodad, Nourdin; Ibrahimi, Sidi Adil

    2015-01-01

    The liver biopsy has long been the "gold standard" for assessing liver fibrosis in patients with hepatitis C. It's an invasive procedure which is associated with an elevated bleeding, especially in chronic hemodialysis patients. Main goal is to assess liver fibrosis in chronic hemodialysis with HCV by Fibroscan and by biological scores (APRI, Forns and Fib-4), and to measure the correlation between these tests. Cross-sectional study including all chronic hemodialysis patients with hepatitis C virus, in two public hemodialysis centers of Fez. All patients were evaluated for liver fibrosis using noninvasive methods (FibroScan and laboratory tests). Subsequently, the correlation between different tests has been measured. 95 chronic hemodialysis were studied, twenty nine patients (30.5%) with chronic hepatitis C. The average age was 52.38 ± 16.8 years. Nine liver fibrosis cases have been concluded by forns score. Fibroscan has objectified significant fibrosis in 6 cases. On the other side APRI has objectified sgnifivant fibrosis only in 3 cases. The Fib-4 showed severe fibrosis in five cases. The results have been most consistent between APRI and Fib-4, followed by Fibroscan and Forns, then APRI and FibroScan.

  20. Hepatitis E virus of subtype 3i in chronically infected kidney transplant recipients in southeastern France.

    PubMed

    Moal, Valérie; Gérolami, René; Ferretti, Audrey; Purgus, Raj; Devichi, Patricia; Burtey, Stéphane; Colson, Philippe

    2014-11-01

    Hepatitis E virus (HEV) is a leading cause of waterborne acute hepatitis in developing countries. In Europe, HEV causes a zoonotic disease and is hyperendemic in southern France. Four HEV genotypes (1 to 4) have been defined, and the most used classification divides them into 24 subtypes. Autochthonous European HEV strains belong in majority to genotype 3. Subtypes 3c, 3f, and 3e are representative of the HEV diversity in France. HEV causes chronic hepatitis in solid-organ transplant recipients in Europe, and viral characteristics associated with chronicity are poorly documented. We sequenced 343-nucleotide-long HEV genomic fragments from the serum of eight chronically infected kidney transplant recipients and a near-full-length genome in one case. We identified in four patients (50%) HEV of subtype 3i, not described previously in France. If shorter genomic fragments were used in phylogenetic analyses, these HEV sequences were clustered with open reading frame 2 (ORF2) fragments labeled as subtype 3c. At least five of the eight HEV 3i sequences recovered from humans in our phylogenetic analyses were from chronically infected kidney transplant recipients. These data show that the description of the prevalence and geographical distribution of HEV subtypes may be partially inaccurate and that criteria for classification as 3i and 3c should be clarified. Extended molecular virology analyses are required to improve knowledge of HEV epidemiology and determinants of chronic HEV infection.

  1. Depression in patients with chronic hepatitis B: an experience on individual solution- focused therapy.

    PubMed

    Arvand, Jinous; Shafiabadi, Abdollah; Falsafinejad, Mohammad Reza; Naderi, Nosratollah

    2012-01-01

    Hepatitis B, as a chronic disorder that may be associated with several psychiatric disorders, such as depression, and decrease quality of life of affected patients. One of the most important consequences of psychiatric problems is reduced patient compliance with prolonged therapeutic regimens. Psychotherapy, such as solution- focused therapy, may help these patients to resolve psychiatric problems, increase quality of life and completion of therapeutic regimens. Solution-focused therapy is effective for patients when developing effective coping responses to the stressors associated with chronic diseases. In this study, the process and effects of solution-focused therapy on depression of 2 patients with chronic hepatitis B have been described. They received solution focused therapy for 5 sessions, each session 1 hour once a week. This technique was helpful to decrease symptoms and signs of depression within 5 weeks.

  2. Reelin Expression in Human Liver of Patients with Chronic Hepatitis C Infection

    PubMed Central

    Carotti, Simone; Perrone, Giuseppe; Amato, Michelina; Gentilucci, Umberto Vespasiani; Righi, Daniela; Francesconi, Maria; Pellegrini, Claudio; Zalfa, Francesca; Zingariello, Maria; Picardi, Antonio; Muda, Andrea Onetti; Morini, Sergio

    2017-01-01

    Reelin is a secreted extracellular glyco-protein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV). On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis. A Knodell score was used to stage liver fibrosis. Hepatic stellate cells/myofibroblast immunohistochemical markers (CRBP-1, alpha-SMA) were also evaluated. As further confirmed by colocalization experiments (Reelin +CRBP-1), Reelin protein was expressed by hepatic stellate cells/myofibroblasts, and a significant positive correlation was found between Reelin expression and the stage of liver fibrosis (P=0.002). Moreover, Reelin correlated with CRBP-1 positive cells (P=0.002), but not with alpha-SMA, suggesting that Reelin should not be regarded as a marker of hepatic stellate cells/myofibroblasts differentiation but rather as a functional protein expressed during some phases of liver fibrosis. Furthermore, Disabled-1 (Dab1), a Reelin adaptor protein, was expressed in cells of ductular reaction suggesting a paracrine role for Reelin with regards these elements. In conclusion, Reelin was expressed by human hepatic stellate cells/myofibroblasts and the number of these cells increased significantly in the lobule as the liver fibrosis progressed, suggesting a role for Reelin in the activation of hepatic stellate cells/myofibroblasts during liver injury. Reelin may potentially be incorporated into liver injury evaluations in combination with other histological data. PMID:28348420

  3. Role of mouse hepatitis virus (MHV) receptor murine CEACAM1 in the resistance of mice to MHV infection: studies of mice with chimeric mCEACAM1a and mCEACAM1b.

    PubMed

    Hirai, Asuka; Ohtsuka, Nobuhisa; Ikeda, Toshio; Taniguchi, Rie; Blau, Dianna; Nakagaki, Keiko; Miura, Hideka S; Ami, Yasushi; Yamada, Yasuko K; Itohara, Shigeyoshi; Holmes, Kathryn V; Taguchi, Fumihiro

    2010-07-01

    Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV) infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele. mCEACAM1a (1a) has a 10- to 100-fold-higher receptor activity than does mCEACAM1b (1b). To explore the hypothesis that MHV susceptibility is due to the different MHV receptor activities of 1a and 1b, we established a chimeric C57BL/6 mouse (cB61ba) in which a part of the N-terminal immunoglobulin (Ig)-like domain of the mCeacam1a (1a) gene, which is responsible for MHV receptor function, is replaced by the corresponding region of mCeacam1b (1b). We compared the MHV susceptibility of these chimeric mice to that of SJL and B6 mice. B6 mice that are homozygous for 1a are highly susceptible to MHV-A59 infection, with a 50% lethal dose (LD(50)) of 10(2.5) PFU, while chimeric cB61ba mice and SJL mice homozygous for 1ba and 1b, respectively, survived following inoculation with 10(5) PFU. Unexpectedly, cB61ba mice were more resistant to MHV-A59 infection than SJL mice as measured by virus replication in target organs, including liver and brain. No infectious virus or viral RNA was detected in the organs of cB61ba mice, while viral RNA and infectious virus were detected in target organs of SJL mice. Furthermore, SJL mice produced antiviral antibodies after MHV-A59 inoculation with 10(5) PFU, but cB61ba mice did not. Thus, cB61ba mice are apparently completely resistant to MHV-A59 infection, while SJL mice permit low levels of MHV-A59 virus replication during self-limited, asymptomatic infection. When expressed on cultured BHK cells, the mCEACAM1b and mCEACAM1ba proteins had similar levels of MHV-A59 receptor activity. These results strongly support the hypothesis that although alleles of mCEACAM1 are the principal determinants of

  4. The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection.

    PubMed

    Menne, Stephan; Cote, Paul J

    2007-01-07

    This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, and for the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and

  5. New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant.

    PubMed

    Fabrizi, Fabrizio; Martin, Paul; Messa, Piergiorgio

    2016-05-01

    The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group (n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients undergoing

  6. Extensive Psoriasis Induced by Pegylated Interferon Alfa-2a and Ribavirin in the Treatment of Chronic Hepatitis C

    PubMed Central

    Kim, Gun-Wook; Jwa, Seung-Wook; Song, Margaret; Kim, Hoon-Soo; Kim, Byung-Soo; Kim, Moon-Bum

    2013-01-01

    A 56-year-old man with chronic hepatitis C was treated with pegylated interferon alfa-2a in combination with ribavirin. However, psoriatic lesions appeared and worsened dramatically during therapy. Because of the extensive skin eruptions, he stopped therapy for chronic hepatitis C and subsequently started narrow-band ultraviolet B phototherapy and topical calcipotriol/betamethasone dipropionate ointment. After this, the psoriasis improved in a slow but comprehensive manner. Our case suggests that physicians should keep in mind the possibility of psoriasis as a side effect of interferon treatment for chronic hepatitis C. PMID:24371397

  7. Serum hepatitis C virus RNA and hepatitis B virus DNA in non-A, non-B post-transfusional and sporadic chronic hepatitis.

    PubMed

    Porchon, C; Kremsdorf, D; Pol, S; Lunel-Fabianni, F; Driss, F; Opolon, P; Berthelot, P; Bréchot, C

    1992-09-01

    The sera of 36 French patients with post-transfusional and sporadic non-A, non-B chronic hepatitis were investigated, for HBV and HCV infections using a combination of serological and polymerase chain reaction (PCR) assays. Anti-HCV was detected in 75% (27/36) of the patients by ELISA1 and/or RIBA2 tests. HCV-RNA sequences were found in 75% (27/36) of the sera by a single step PCR, using a set of primers located in the 5' non-coding region. Altogether, 89% (32/36) of the patients were found positive with serological and/or molecular tests. Among the positive patients, 68% (22/32) were found positive for both anti-HCV and HCV-RNA, 16% (5/32) and 16% (5/32) were found positive for either anti-HCV or HCV-RNA, respectively. HBV-DNA sequences were detected in two patients associated to the HCV viraemia. This study confirms the extremely high prevalence of HCV infection in NANB chronic hepatitis in France. It also shows possible co-infection by HCV and HBV in hepatitis.

  8. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.

    PubMed

    Liaw, Yun-Fan; Kao, Jia-Horng; Piratvisuth, Teerha; Chan, Henry Lik Yuen; Chien, Rong-Nan; Liu, Chun-Jen; Gane, Ed; Locarnini, Stephen; Lim, Seng-Gee; Han, Kwang-Hyub; Amarapurkar, Deepak; Cooksley, Graham; Jafri, Wasim; Mohamed, Rosmawati; Hou, Jin-Lin; Chuang, Wan-Long; Lesmana, Laurentius A; Sollano, Jose D; Suh, Dong-Jin; Omata, Masao

    2012-06-01

    Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier "Asian-Pacific consensus statement on the management of chronic hepatitis B" was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.

  9. Post-transfusional vs. sporadic non-A, non-B chronic hepatitis. A clinico-pathological and evolutive study.

    PubMed

    Jové, J; Sánchez-Tapias, J M; Bruguera, M; Mas, A; Costa, J; Barrera, J M; Rodés, J

    1988-02-01

    The clinical, morphological and evolutive features of 60 patients with chronic hepatitis, presumably caused by non-A, non-B virus infection, have been retrospectively analyzed. In all the cases the disease began as an acute episode of viral hepatitis that was followed by persistently abnormal liver function tests. No patient had evidence of current or past hepatitis B virus infection and other known causes of chronic liver disease were excluded. Thirty patients had received blood transfusions in the recent past, five were drug addicts and the source of the infection was not identified in the remaining 25, in whom the disease was considered to be sporadic. Clinical or biochemical differences between patients with post-transfusional and sporadic non-A, non-B chronic hepatitis were not observed, but liver histology showed a higher proportion of patients with chronic persistent hepatitis in the sporadic (72%) than in the transfusional group (53%). On follow-up, sustained normalization of liver function tests was observed in 46% of the cases with sporadic hepatitis but only in 13% of the cases with post-transfusion hepatitis. These observations suggest that non-A, non-B chronic hepatitis is more severe in patients with transfusion-related infection than in sporadic cases.

  10. [Characterization of Serial Passage of 1b/2a Chimera Hepatitis C Virus Cell Culture System Carrying Envelope E1E2 Coding Gene from Hebei Strain of China].

    PubMed

    Lu, Sha; Zhang, Ling; Tao, Gesi; Cai, Min; Bao Lili; LI, Lian; Deng, Yao; Shen, Xiaoling; Tan, Wenjie

    2015-11-01

    To character a novel chimera(1b/2a) hepatitis C virus cell culture (HCVcc) system carrying envelope E1E2 coding gene from Hebei strain of China, chimera HCVcc (cHCVcc) was developed from Huh7.5-CD81 cells after transfection with in vitro transcribed full-length 1b/2a chimera RNA, which carrying envelope E1E2 coding gene from Hebei strain of China. Then the replication, expression and infectious titer of serial passage HCVcc were assessed by Real Time RT-PCR, indirect immunofluorescence assay (IFA) and Western blotting (WB). In addition, chimeric envelope gene from HCVcc was sequenced after serial passage. We found that the number of HCV positive focus increased gradually in cell post-transfection with chimera HCVcc (1b/2a) RNA and reach a peak platform (80% to 90%) at 41 days post-transfection; the expression of HCV protein was also confirmed by WAB during serial passage. At meantime, HCV RNA copy number in the supernatant peaked at 10(4)-10(7) copies/mL and the highest infectious titer of this 1b/2a cHCVcc reinfection were tested as 10(4) ffu/mL. Sequence analysis indicated 6 of adaptive amino acid substitutes occur among chimeric envelope E1E2 during serial passages. We con:luded that a novel 1b/2a chimera HCVcc carrying envelope E1E2 coding gene from Hebei strain of China was developed and its infectious titer increased after serial passage of HCVcc. This novel cHCVcc will be an effective tool for further evaluation of anti-virus drugs and immune effects against the major genotype from Chinese.

  11. Chronic hepatitis C in Austria, 1992-2006: genotype distribution and demographic factors.

    PubMed

    Maieron, A; Metz-Gercek, S; Hackl, F; Luger, C; Ziachehabi, A; Strauss, R; Schöfl, R; Mittermayer, H

    2010-02-25

    Chronic hepatitis C is a leading cause of end-stage liver disease and, with a worldwide prevalence of up to 3%, is a pandemic infectious disease. Austria, like most western European countries can be considered as a low prevalence country. This analysis aimed to assess the distribution of hepatitis C virus (HCV) genotypes in patients with chronic HCV infection in Upper Austria. Between September 1992 and December 2006, we identified 1,318 consecutive patients who tested positive for HCV RNA. Genotyping was routinely performed in 1,239 of the 1,318 patients, and in a subgroup of 617 patients data on the source of transmission were collected. Additionally we obtained data on liver histology and body mass index in a subsample of 273 of the 617 patients. Hepatitis C genotypes 1, 2, 3, 4, 6 and co-infections were found in 80.4%, 4.5%, 12.3%, 2.7%, 0.1% and 0.2% of the patients, respectively. There was a highly significant age difference in relation to gender at the time of diagnosis of chronic hepatitis C, with women being older than men (men: 45.0 years; women: 49.3 years; p<0.0001). The number of new cases of chronic hepatitis C decreased substantially over the last decade, but although risk factors for obtaining HCV are well established, we did not find a decrease in the age of first diagnosis. Besides consistent screening in defined risk groups it is important to raise awareness for risk factors for HCV acquisition and liver disease progression.

  12. Chronic hepatitis C--assessment in civil law: a case study.

    PubMed

    Santos, Bruno Miguel; Sousa, Paula; Mena, Filomena; Costa, Graça Santos; Corte-Real, Francisco; Vieira, Duarte Nuno

    2010-02-01

    This article describes the case of a 58-year-old man who asked for an assessment of physical damage of a civil nature, having been diagnosed with chronic hepatitis C for which he blamed a blood transfusion, supposedly contaminated with hepatitis C virus (HCV). After studying the documentary information, a number of presuppositions were drawn up with a view to determining the causal nexus, but this could not be proved. The assessment of situations like this is not common in civil law. This article is intended to add to the body of information on the forensic assessment of similar cases.

  13. Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury

    PubMed Central

    Liu, Yanlong; Zhao, Cuiqing; Xiao, Jian; Liu, Liming; Zhang, Min; Wang, Cuiling; Wu, Guicheng; Zheng, Ming-Hua; Xu, Lan-Man; Chen, Yong-Ping; Mohammadi, Moosa; Chen, Shao-Yu; Cave, Matthew; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid β-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis. PMID:27498701

  14. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality?

    PubMed

    Vanni, Ester; Bugianesi, Elisabetta; Saracco, Giorgio

    2016-02-01

    Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.

  15. Colitis during new direct-acting antiviral agents (DAAs) therapy with sofosbuvir, simeprevir and ribavirin for genotype 1b hepatitis C.

    PubMed

    Izzo, Ilaria; Zanotti, Paola; Chirico, Claudia; Casari, Salvatore; Villanacci, Vincenzo; Salemme, Marianna; Biasi, Luciano; Festa, Elena; Castelli, Francesco

    2016-12-01

    Since 2014 several direct-acting antivirals (DAAs) have been made available, allowing interferon-free antiviral treatments with high sustained virological response rates. Side effects are, however, a real challenge during treatment. Sarkar et al. recently published a case of colitis following initiation of sofosbuvir and simeprevir for genotype 1 hepatitis C. We report the case of a patient with no prior history of inflammatory bowel disease, who developed significant bloody diarrhea within 3 weeks of sofosbuvir/simeprevir/ribavirin initiation. Colonoscopy and biopsy suggested a drug-induced colitis.

  16. Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

    PubMed

    Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M

    2014-09-01

    MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed.

  17. Chlorogenic acid from honeysuckle improves hepatic lipid dysregulation and modulates hepatic fatty acid composition in rats with chronic endotoxin infusion.

    PubMed

    Zhou, Yan; Ruan, Zheng; Wen, Yanmei; Yang, Yuhui; Mi, Shumei; Zhou, Lili; Wu, Xin; Ding, Sheng; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong

    2016-03-01

    Chlorogenic acid as a natural hydroxycinnamic acid has protective effect for liver. Endotoxin induced metabolic disorder, such as lipid dysregulation and hyperlipidemia. In this study, we investigated the effect of chlorogenic acid in rats with chronic endotoxin infusion. The Sprague-Dawley rats with lipid metabolic disorder (LD group) were intraperitoneally injected endotoxin. And the rats of chlorogenic acid-LD group were daily received chlorogenic acid by intragastric administration. In chlorogenic acid-LD group, the area of visceral adipocyte was decreased and liver injury was ameliorated, as compared to LD group. In chlorogenic acid-LD group, serum triglycerides, free fatty acids, hepatic triglycerides and cholesterol were decreased, the proportion of C20:1, C24:1 and C18:3n-6, Δ9-18 and Δ6-desaturase activity index in the liver were decreased, and the proportion of C18:3n-3 acid was increased, compared to the LD group. Moreover, levels of phosphorylated AMP-activated protein kinase, carnitine palmitoyltransferase-I, and fatty acid β-oxidation were increased in chlorogenic acid-LD group compared to LD rats, whereas levels of fatty acid synthase and acetyl-CoA carboxylase were decreased. These findings demonstrate that chlorogenic acid effectively improves hepatic lipid dysregulation in rats by regulating fatty acid metabolism enzymes, stimulating AMP-activated protein kinase activation, and modulating levels of hepatic fatty acids.

  18. Hepatitis

    MedlinePlus

    ... A if they've been vaccinated against it. Hepatitis B Hepatitis B is a more serious infection. It may lead ... of which cause severe illness and even death. Hepatitis B virus (HBV) is transmitted from person to person ...

  19. Hepatitis

    MedlinePlus

    ... Issues Listen Español Text Size Email Print Share Hepatitis Page Content Article Body Hepatitis means “inflammation of ... it has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool ...

  20. ["Epidemiological profile of chronic hepatitis C virus patients and his early virological response to pegylated interferon plus ribavirin therapy. Gastroenterology Service, HNCASE EsSALUD Arequipa"].

    PubMed

    Chirinos de Rivero, Luis Fernando; Campos Nizama, Juan; Castro Valdivia, Raúl; Valdez Herrera, Jesús

    2007-01-01

    The present descriptive, retrospective and longitudinal study was designed to determine the epidemic profile of patients infected by hepatitis C virus and chronic hepatitis, as well as to describe the eligibility criteria for treatment with pegilated interferon plus ribavirina and its early virological answer to the treatment. We studied 20 patients treated at Gastroenterology Service of Carlos Seguín Escobedo Hospital of EsSalud between 2004 and 2006. The diagnosis of HVC infection was confirmed by detection of viral RNA with PCR, and the viral load by counting number of RNA copies. The eligibility criteria for antiviral treatment were determined, and also the METAVIR score to determine hepatic fibrosis. After 12 weeks of treatment the patients with eligibility criteria and received treatment were evaluated, and the effectivity of treatment was evaluated with a new determination of viral load. There were more female (15; 75%) than male patients (5; 25%), with ages between 50 and 59 years. The more frequent risk antecedent was blood transfusion (45%), surgery (35%), and traffic accident (10%). The hematological, hepatic, renal and hormonal parameters were in normal range; and the viral load at the moment of diagnosis was of 580 thousand copies mean (between 4100 to 2 millions copies). The most frequent viral genotypes were 1a and 1b. Up to 40% of patients did not fulfilled eligibility criteria for treatment. Nine of 12 patients with eligibility criteria received treatment (75%), 6 of them were evaluated for early virologic response and of them 100,0% had an early virologic response with decrease of post-therapeutic viral load in all but one cases until non-detectable levels. In conclusion our study described the profile of patients infected by HCV with chronic hepatitis in gastroenterology ward of our hospital, and it has been determined that is suggestive that antiviral treatment is highly effective in patients with eligibility criteria for treatment, related to

  1. Treatment of Chronic Hepatitis C in Special Populations.

    PubMed

    Bunchorntavakul, Chalermrat; Tanwandee, Tawesak

    2015-12-01

    The management of hepatitis C virus (HCV) infection in special populations is challenging. The efficacy and safety data of the currently approved all-oral direct-acting antiviral combinations, including sofosbuvir, ledipasvir, daclatasvir, paritaprevir/ritonavir/ombitasvir plus dasabuvir (3D), and ribavirin, is compelling for use in special HCV populations, as has recently been recommended by expert guidelines. The treatment regimens and sustained virological response rates for special populations are nearly similar to those of the general HCV population. Sofosbuvir is not recommended in patients with severe renal impairment, and simeprevir and 3D regimen are not recommended for those with decompensated liver disease.

  2. The role of chemokines in acute and chronic hepatitis C infection.

    PubMed

    Fahey, Stephen; Dempsey, Eugene; Long, Aideen

    2014-01-01

    Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.

  3. Chronically infected wild boar can transmit genotype 3 hepatitis E virus to domestic pigs.

    PubMed

    Schlosser, Josephine; Vina-Rodriguez, Ariel; Fast, Christine; Groschup, Martin H; Eiden, Martin

    2015-10-22

    Hepatitis E virus (HEV) causes acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialized nations. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with the consumption of raw and undercooked products from domestic pig and wild boar. As shown recently, naturally acquired HEV gt3 replicates efficiently in experimentally infected wild boar and is transmissible from a wild boar to domestic pigs. Generally, following an acute infection swine suffer from a transient febrile illness and viremia in connection with fecal virus shedding. However, little is known about sub-acute or chronic HEV infections in swine, and how and where HEV survives the immune response. In this paper, we describe the incidental finding of a chronic HEVgt3 infection in two naturally infected European wild boar which were raised and housed at FLI over years. The wild boar displayed fecal HEV RNA excretion and viremia over nearly the whole observation period of more than five months. The animal had mounted a substantial antibody response, yet without initial clearance of the virus by the immune system. Further analysis indicated a subclinical course of HEV with no evidence of chronic hepatitis. Additionally, we could demonstrate that this chronic wild boar infection was still transmissible to domestic pigs, which were housed together with this animal. Sentinel pigs developed fecal virus shedding accompanied by seroconversion. Wild boar should therefore be considered as an important reservoir for transmission of HEV gt3 in Europe.

  4. Prevalence of rheumatologic manifestations of chronic hepatitis C virus infection among Egyptians.

    PubMed

    Mohammed, Reem Hamdy Abdellatif; ElMakhzangy, Hesham Ibrahim; Gamal, Amira; Mekky, Fatma; El Kassas, Mohammed; Mohammed, Nabil; Abdel Hamid, Mohammed; Esmat, Gamal

    2010-12-01

    Chronic hepatitis C virus (HCV) viremia has been known to provoke a plethora of autoimmune syndromes referred to as extrahepatic manifestations of chronic HCV infection. Aim of the current study was to assess the prevalence of rheumatologic manifestations among Egyptians with hepatitis C infection and its' association with cryoglobulin profile. The current research represents a cross-sectional study where patients with chronic HCV infection attending the outpatient clinic of the National Hepatology and Tropical Medicine Research Institute over a period of 1 year were interviewed. Patients with decompensated liver disease, on interferon therapy, having end-stage renal disease or coexisting viral infection like hepatitis B surface antibody positive patients were all excluded from the research. Laboratory investigations as well as serological assay including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed. Three hundred and six patients having chronic HCV infection were interviewed in this research. The overall estimated prevalence of rheumatologic manifestations in the current research was 16.39%, chronic fatigue syndrome 9.5%, sicca symptoms 8.8%, arthralgia 6.5%, fibromyalgia 1.9%, myalgia 1.3%, arthritis 0.7%, cryoglobulinemic vasculitis 0.7%, autoimmune hemolytic anemia 0.7%, thrombocytopenia 0.7%. Xerophthalmia was significantly present in male population (p = 0.04), whereas fibromyalgia, cryoglobulinemic vasculitis, arthritis, and autoimmune hemolytic anemia were significantly present in female population under study (p < 0.05). In chronic HCV genotype 4 infection, the prevalence of rheumatologic manifestations was 16.3% with chronic fatigue syndrome and sicca symptoms being the most common with no significant correlation to the degree of elevation of liver disease or viral load.

  5. Impact of sustained virus elimination on natural anticoagulant activity in patients with chronic viral hepatitis C.

    PubMed

    Saray, Aida; Mesihović, Rusmir; Vukobrat-Bijedić, Zora; Gornjaković, Srđan; Vanis, Nenad; Mehmedović, Amila; Papović, Vedad; Glavaš, Sanjin

    2013-05-01

    Previous studies have reported reduced synthesis of various hemostatic factors in patients with chronic liver disease. Whether changes in plasma levels of these proteins reflect recovered liver synthetic function following virological eradication therapy has not been approved yet. The aim of the study was to determine the impact of sustained viral suppression achieved with pegylated interferon alpha and ribavirin on hemostatic parameters including natural anticoagulants in patients with chronic hepatitis C. The following coagulation screening tests were obtained in thirty patients with chronic viral hepatitis C before and after completion of antiviral treatment: activated partial thromboplastin time, prothrombin time, plasma fibrinogen and natural anticoagulant proteins antithrombin III, protein C (PC) and total protein S (PS) activity. Only patients who achieved durable virus suppression were included. The mean PC and PS levels were significantly lower in patients with chronic viral hepatitis C before antiviral therapy than in healthy controls (79.04 ± 16.19 % vs. 109.92 ± 21.33% and 54.04 ± 16.11% vs. 87.60 ± 8.15%, respectively; (p<0.001). Mean levels of PC exhibited a significant increase by 14.69 % after the completion of antiviral treatment (93.73 ± 14.18%, p<0.001) as well as PS levels, which significantly increased by 21.46% (75.50 ± 15.43, p<0.001) when compared with pre-treatment values. No remarkable fluctuations in other hemostatic parameters were noted. Protein C and protein S are sensitive markers of hepatocyte synthetic impairment and are valuable markers in monitoring the efficacy of antiviral treatment in chronic hepatitis C patients. Larger studies are needed to confirm our results.

  6. Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

    PubMed Central

    Udoh, Uduak S.; Swain, Telisha M.; Filiano, Ashley N.; Gamble, Karen L.; Young, Martin E.

    2015-01-01

    Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease. PMID:25857999

  7. Hepatitis C virus infection in Argentina: Burden of chronic disease

    PubMed Central

    Ridruejo, Ezequiel; Bessone, Fernando; Daruich, Jorge R; Estes, Chris; Gadano, Adrián C; Razavi, Homie; Villamil, Federico G; Silva, Marcelo O

    2016-01-01

    AIM: To estimate the progression of the hepatitis C virus (HCV) epidemic and measure the burden of HCV-related morbidity and mortality. METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed: (1) increased sustained virologic response (SVR); and (2) increased SVR and treatment. RESULTS: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liver-related deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030. CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina. PMID:27239258

  8. Travelers' Health: Hepatitis B

    MedlinePlus

    ... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B is ... their exposures. Map 3-04. Prevalence of chronic hepatitis B virus infection among adults PDF Version (printable) ...

  9. Oropharyngeal pemphigus in a patient with chronic hepatitis C during interferon alpha-2a therapy.

    PubMed

    Marinho, R T; Johnson, N W; Fatela, N M; Serejo, F S; Glória, H; Raimundo, M O; Velosa, J F; Ramalho, F J; Moura, M C

    2001-07-01

    There are a few reports in the literature concerning pemphigus induced by interferon given for hepatitis C. We present the case of a 28-year-old woman with post-transfusional chronic hepatitis C who developed ulcers and vesicles on her tongue, cheeks, posterior oropharynx and vocal cords 5 months after beginning treatment with recombinant interferon alpha-2a. The direct and indirect immunofluorescence was diagnostic of pemphigus vulgaris. The drug was promptly withdrawn; the patient was medicated with prednisolone and azathioprine and recovered only 3 months later. Although there are several publications describing the occurrence of other autoimmune diseases in patients receiving interferon alpha therapy, this is the first report of a pemphigus induced by interferon in hepatitis C patients involving oropharyngeal and laryngeal mucosae without cutaneous involvement.

  10. Loss of discoidin domain receptor 2 promotes hepatic fibrosis after chronic carbon tetrachloride through altered paracrine interactions between hepatic stellate cells and liver-associated macrophages.

    PubMed

    Olaso, Elvira; Arteta, Beatriz; Benedicto, Aitor; Crende, Olatz; Friedman, Scott L

    2011-12-01

    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl(4)) to DDR2(+/+) and DDR2(-/-) mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after chronic CCl(4) administration, DDR2(-/-) livers had increased collagen deposition, gelatinolytic activity, and HSC density. Increased basal gene expression of osteopontin, transforming growth factor-β1, monocyte chemoattractant protein-1, and IL-10 and reduced basal gene expression of matrix metalloproteinase-2, matrix metalloproteinase-13, and collagen type I in quiescent DDR2(-/-) HSCs were amplified further after chronic CCl(4). In concordance, DDR2(-/-) HSCs isolated from chronically injured livers had enhanced in vitro migration and proliferation, but less extracellular matrix degradative activity. Macrophages from chronic CCl(4)-treated DDR2(-/-) livers showed stronger chemoattractive activity toward DDR2(-/-) HSCs than DDR2(+/+) macrophages, increased extracellular matrix degradation, and higher cytokine mRNA expression. In conclusion, loss of DDR2 promotes chronic liver fibrosis after CCl(4) injury. The fibrogenic sinusoidal milieu generated in chronic DDR2(-/-) livers recruits more HSCs to injured regions, which enhances fibrosis. Together, these findings suggest that DDR2 normally orchestrates gene programs and paracrine interactions between HSCs and macrophages that together attenuate chronic hepatic fibrosis.

  11. Interferon lambda genotype and low serum LDL cholesterol levels in patients with chronic hepatitis C infection

    PubMed Central

    Li, Josephine H.; Lao, Xiang Qian; Tillmann, Hans L.; Rowell, Jennifer; Patel, Keyur; Thompson, Alexander; Suchindran, Sunil; Muir, Andrew J.; Guyton, John R.; Gardner, Stephen D.; McHutchison, John G.; McCarthy, Jeanette J.

    2010-01-01

    Background Recently, genetic polymorphisms occurring in the interferon lambda gene region were associated with response to interferon-based treatment of hepatitis C infection. Both infection with the hepatitis C virus and interferon therapy are associated with decreased serum cholesterol and high cholesterol has been associated with increased likelihood to respond to interferon. We sought to determine if the interferon lambda gene variant was also associated with serum lipid levels in chronic hepatitis C patients. We compared genotypes of the rs12979860 polymorphism, located proximal to the IL28 gene, with serum lipid and apolipoprotein levels in 746 subjects with chronic HCV infection, not currently undergoing treatment, using multivariable analysis of variance. Results Levels of total cholesterol (p=6.0×10-4), apolipoprotein B (p=1.3×10-6) and low density lipoprotein (LDL) cholesterol (p=8.9×10-10) were significantly higher in subjects carrying the rs12979860 CC ‘responder’ genotype compared to those with the CT or TT genotype. Levels of triglycerides (p=0.03), apolipoprotein A-I (p=0.06) and apolipoprotein E (p=0.01) were slightly lower in the rs12979860 CC genotype group, while levels of high density lipoprotein cholesterol (p=0.78) and apolipoprotein C-III (p=0.74) did not vary by rs12979860 genotype. Conclusions Our results suggest that low levels of LDL cholesterol in chronic hepatitis C patients may be a marker of host endogenous interferon response to hepatitis C and that subjects with the rs12979860 CC ‘responder’ genotype may have a lower endogenous interferon response to the virus. PMID:20235331

  12. Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective

    PubMed Central

    Nkuize, Marcel; Sersté, Thomas; Buset, Michel; Mulkay, Jean-Pierre

    2016-01-01

    Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A) and sofosbuvir 400 mg (anti-NS5B), has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-naïve, treatment-experienced, and with advanced liver disease or posttransplant) patients and HIV–hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection. PMID:27350749

  13. Specific Inhibition of the Distribution of Lobeglitazone to the Liver by Atorvastatin in Rats: Evidence for a Rat Organic Anion Transporting Polypeptide 1B2-Mediated Interaction in Hepatic Transport.

    PubMed

    Yim, Chang-Soon; Jeong, Yoo-Seong; Lee, Song-Yi; Pyeon, Wonji; Ryu, Heon-Min; Lee, Jong-Hwa; Lee, Kyeong-Ryoon; Maeng, Han-Joo; Chung, Suk-Jae

    2017-03-01

    Cytochrome P450 enzymes and human organic anion transporting polypeptide (OATP) 1B1 are reported to be involved in the pharmacokinetics of lobeglitazone (LB), a new peroxisome proliferator-activated receptor γ agonist. Atorvastatin (ATV), a substrate for CYP3A and human OATP1B1, is likely to be coadministered with LB in patients with the metabolic syndrome. We report herein on a study of potential interactions between LB and ATV in rats. When LB was administered intravenously with ATV, the systemic clearance and volume of distribution at steady state for LB remained unchanged (2.67 ± 0.63 ml/min per kg and 289 ± 20 ml/kg, respectively), compared with that of LB without ATV (2.34 ± 0.37 ml/min per kg and 271 ± 20 ml/kg, respectively). Although the tissue-to-plasma partition coefficient (Kp) of LB was not affected by ATV in most major tissues, the liver Kp for LB was decreased by ATV coadministration. Steady-state liver Kp values for three levels of LB were significantly decreased as a result of ATV coadministration. LB uptake was inhibited by ATV in rat OATP1B2-overexpressing Madin-Darby canine kidney cells and in isolated rat hepatocytes in vitro. After incorporating the kinetic parameters for the in vitro studies into a physiologically based pharmacokinetics model, the characteristics of LB distribution to the liver were consistent with the findings of the in vivo study. It thus appears that the distribution of LB to the liver is mediated by the hepatic uptake of transporters such as rat OATP1B2, and carrier-mediated transport is involved in the liver-specific drug-drug interaction between LB and ATV in vivo.

  14. Comparative Molecular Dynamics Simulation of Hepatitis C Virus NS3/4A Protease (Genotypes 1b, 3a and 4a) Predicts Conformational Instability of the Catalytic Triad in Drug Resistant Strains

    PubMed Central

    Kramer, Mitchell; Halleran, Daniel; Rahman, Moazur; Iqbal, Mazhar; Anwar, Muhammad Ikram; Sabet, Salwa; Ackad, Edward; Yousef, Mohammad

    2014-01-01

    The protease domain of the Hepatitis C Virus (HCV) nonstructural protein 3 (NS3) has been targeted for inhibition by several direct-acting antiviral drugs. This approach has had marked success to treat infections caused by HCV genotype 1 predominant in the USA, Europe, and Japan. However, genotypes 3 and 4, dominant in developing countries, are resistant to a number of these drugs and little progress has been made towards understanding the structural basis of their drug resistivity. We have previously developed a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active sites of the NS3 proteases of HCV-1b and 4a in relation to their catalytic activity and drug susceptibility. Here, we improved the methodology, extended the analysis to include genotype 3a (predominant in South Asia including Pakistan), and compared the results of the three genotypes (1b, 3a and 4a). The 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) indicate conformational instability of the catalytic site in HCV-3a and 4a compared to that of HCV-1b NS3 protease. The divergence is gradual and genotype-dependent, with HCV-1b being the most stable, HCV-4a being the most unstable and HCV-3a representing an intermediate state. These results suggest that the structural dynamics behavior, more than the rigid structure, could be related to the altered catalytic activity and drug susceptibility seen in NS3 proteases of HCV-3a and 4a. PMID:25111232

  15. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin

    PubMed Central

    Jain, K; Lam, W; Waheeb, S; Thai, Q; Heathcote, J

    2001-01-01

    AIM—To assess the ocular effect of interferon alfa 2b prescribed with ribavirin in patients undergoing therapy for chronic hepatitis C.
METHODS—19 patients with chronic hepatitis C who satisfied the follow up criteria were assessed for ocular complications using slit lamp biomicroscopy and indirect ophthalmoscopy before, during, and after the treatment at regular intervals.
RESULTS—8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.
CONCLUSION—Retinopathy was more common in interferon monotherapy non-responders than relapsers when treated with interferon alfa 2b with the addition of ribavirin. The changes were transient, disappearing while the patients were still being treated.

 PMID:11567959

  16. Observational descriptive study of cutaneous manifestations in patients from Mato Grosso with viral chronic hepatitis*

    PubMed Central

    Rostey, Renato Roberto Liberato; Souto, Francisco José Dutra

    2015-01-01

    BACKGROUND Extrahepatic manifestations are seen in association with chronic infection by hepatitis B or C virus including cutaneous disorders. The frequency of these findings seems to vary among different places and reports. There is a lack of information about this issue in Brazil. OBJECTIVES To estimate the prevalence of cutaneous findings affecting HBV or HCV carriers from a reference outpatient unit in Mato Grosso. METHODS A cross-sectional observational study. RESULTS 108 patients were studied. 88.9% presented some cutaneous findings but must of them were nonrelated to chronic viral infection. Four patients had cutaneous or autoimmune syndromes that may be HBV or HCV related. CONCLUSION In our study we found no statistical association between viral hepatitis and skin diseases. PMID:26734863

  17. Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for the diagnosis of rheumatic diseases.

    PubMed

    Palazzi, Carlo; Buskila, Dan; D'Angelo, Salvatore; D'Amico, Emilio; Olivieri, Ignazio

    2012-07-01

    Hepatitis C virus infection (HCV) is one of the best mimes in medicine. About 40-70% of patients suffering from this disorder develop at least one extra-hepatic disorder that can have a rheumatic nature (arthralgias, arthritis, vasculitis and sicca syndrome) and must be differentiated from the primitive rheumatic diseases. In addition, HCV infection can also alter the laboratory tests. Several alterations of first line laboratory tests can be usually found in both chronic HCV infection and chronic inflammatory rheumatic disorders. In the present review we analyze the interference of HCV in tests more specifically used in rheumatology: rheumatoid factor and other autoantibodies (ANA, anti-ENA, ANCA, anti-DNA, antiphospholipid, anti-CCP). In patients suffering from HCV infection, the diagnosis of connective tissue diseases (CTD) or rheumatoid arthritis (RA) should be made only when the detected symptoms or laboratory data are not inducible by HCV, otherwise only a diagnosis of "possible CTD" or "possible RA" should be considered.

  18. Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

    PubMed

    Kage, M; Fujisawa, T; Shiraki, K; Tanaka, T; Fujisawa, T; Kimura, A; Shimamatsu, K; Nakashima, E; Kojiro, M; Koike, M; Tazawa, Y; Abukawa, D; Okaniwa, M; Takita, H; Matsui, A; Hayashi, T; Etou, T; Terasawa, S; Sugiyama, K; Tajiri, H; Yoden, A; Kajiwara, Y; Sata, M; Uchimura, Y

    1997-09-01

    Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

  19. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    PubMed

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C.

  20. LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

    PubMed Central

    CORAL, Gabriela P.; ANTUNES, Aline Dal Pozzo; SERAFINI, Ana Paula Almeida; ARAUJO, Fernanda B.; de MATTOS, Angelo Alves

    2016-01-01

    Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts. PMID:26910447

  1. CD133(+) human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis.

    PubMed

    Elkhafif, Nagwa; El Baz, Hanan; Hammam, Olfat; Hassan, Salwa; Salah, Faten; Mansour, Wafaa; Mansy, Soheir; Yehia, Hoda; Zaki, Ahmed; Magdy, Ranya

    2011-01-01

    The in vivo angiogenic potential of transplanted human umbilical cord blood (UCB) CD133(+) stem cells in experimental chronic hepatic fibrosis induced by murine schistosomiasis was studied. Enriched cord blood-derived CD133(+) cells were cultured in primary medium for 3 weeks. Twenty-two weeks post-Schistosomiasis infection in mice, after reaching the chronic hepatic fibrotic stage, transplantation of stem cells was performed and mice were sacrificed 3 weeks later. Histopathology and electron microscopy showed an increase in newly formed blood vessels and a decrease in the fibrosis known for this stage of the disease. By immunohistochemical analysis the newly formed blood vessels showed positive expression of the human-specific angiogenic markers CD31, CD34 and von Willebrand factor. Few hepatocyte-like polygonal cells showed positive expression of human vascular endothelial growth factor and inducible nitric oxide synthase. The transplanted CD133(+) human stem cells primarily enhanced hepatic angiogenesis and neovascularization and contributed to repair in a paracrine manner by creating a permissive environment that enabled proliferation and survival of damaged cells rather than by direct differentiation to hepatocytes. A dual advantage of CD133(+) cell therapy in hepatic disease is suggested based on its capability of hematopoietic and endothelial differentiation.

  2. Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B.

    PubMed Central

    Boni, C; Bertoletti, A; Penna, A; Cavalli, A; Pilli, M; Urbani, S; Scognamiglio, P; Boehme, R; Panebianco, R; Fiaccadori, F; Ferrari, C

    1998-01-01

    High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This effect was dramatic and persistent in 10 patients but undetectable in 2. It occurred concomitant with a rapid and marked reduction of viremia. Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells. In conclusion, an efficient antiviral T cell response can be restored by lamivudine treatment in patients with chronic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimulate the T cell response may represent an effective strategy to induce eradication of chronic HBV infection. PMID:9727065

  3. Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection.

    PubMed

    Deng, Y-R; Yoshida, K; Jin, Q L; Murata, M; Yamaguchi, T; Tsuneyama, K; Moritoki, Y; Niu, J Q; Matsuzaki, K; Lian, Z-X

    2014-04-01

    Transforming growth factor (TGF)-β, type I receptor (TβRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1-4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients.

  4. Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection

    PubMed Central

    Deng, Y-R; Yoshida, K; Jin, Q L; Murata, M; Yamaguchi, T; Tsuneyama, K; Moritoki, Y; Niu, J Q; Matsuzaki, K; Lian, Z-X

    2014-01-01

    Transforming growth factor (TGF)-β, type I receptor (TβRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1–4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients. PMID:24372395

  5. [Salivary glands and oral mucous membrane status in patients with chronic hepatitis].

    PubMed

    Afanas'ev, V V; Muromtsev, A V; Derkach, N V

    2008-01-01

    The status of salivary glands and oral mucous membrane was investigated in 50 patients with chronic active hepatitis against the background of chronic alcoholism. The check up disclosed sialadenosis in 38% of patients and in 54% of patients - such diseases of oral mucous membrane as stomatitis, candidosis and geographic tonque. Besides there were disclosed such disturbances as big and small salivary glands secretion reduction, mixed saliva viscosity increase, increase of protein, P, K, Na and catalase content in it, glycogen hyperaccumulation in gingival tissues. The received data indicated the necessity of dispensary supervision of such patients and their treatment in stomatologist.

  6. Peripheral blood dendritic cells are phenotypically and functionally intact in chronic hepatitis B virus (HBV) infection

    PubMed Central

    Tavakoli, S; Mederacke, I; Herzog-Hauff, S; Glebe, D; Grün, S; Strand, D; Urban, S; Gehring, A; Galle, P R; Böcher, W O

    2008-01-01

    Persistence of hepatitis B virus (HBV) infection is associated with reduced anti-viral T cell responses. Impaired dendritic cell (DC) function was suggested as the cause of reduced T cell stimulation in chronic HBV carriers. Thus, we compared myeloid (mDC) and plasmacytoid DC (pDC) from chronic HBV carriers and controls. Frequency and phenotype of isolated DC were analysed by fluorescence activated cell sorter staining, DC function by mixed lymphocyte reaction, cytokine bead array, intracellular cytokine staining, enzyme-linked immunosorbent assay and enzyme-linked immunospot. Expression of HBV DNA and mRNA was studied by polymerase chain reaction (PCR). Circulating total DC, mDC or pDC were not reduced in chronic HBV carriers. Isolated mDC and pDC from chronic HBV carriers exhibited similar expression of co-stimulatory molecules and alloreactive T helper cell stimulation as control DC, whether tested directly ex vivo or after in vitro maturation. Secretion of pro- and anti-inflammatory cytokines by CD40 or Toll-like receptor ligand-stimulated patient DC was intact, as was human leucocyte antigen A2-restricted HBV-specific cytotoxic lymphocyte stimulation. Although both DC populations contained viral DNA, viral mRNA was undetectable by reverse transcription–PCR, arguing against viral replication in DC. We found no quantitative, phenotypic or functional impairment of mDC or pDC in chronic hepatitis B, whether studied ex vivo or after in vitro maturation. PMID:18031557

  7. Evaluation of Helicobacter pylori Infection in Patients with Chronic Hepatic Disease

    PubMed Central

    Huang, Ju; Cui, Jun

    2017-01-01

    Background: The 13C urea breath test (13C-UBT) is the gold standard for detecting Helicobacter pylori infection. H. pylori pathogenesis in patients with hepatitis B virus (HBV) and related diseases remains obscure. We used 13C-UBT to detect H. pylori infection in patients with chronic HBV infection, HBV-related cirrhosis, HBV-related hepatic carcinoma, and other chronic hepatic diseases. Methods: A total of 131 patients with chronic hepatitis B (HB), 179 with HBV-related cirrhosis, 103 with HBV-related hepatic carcinoma, 45 with HBV-negative hepatic carcinoma, and 150 controls were tested for H. pylori infection using 13C-UBT. We compared H. pylori infection rate, liver function, complications of chronic hepatic disease, serum HBV-DNA, serum alpha-fetoprotein (AFP), and portal hypertensive gastropathy (PHG) incidence among groups. Results: HBV-related cirrhosis was associated with the highest H. pylori infection rate (79.3%). H. pylori infection rate in chronic HB was significantly higher than in the HBV-negative hepatic carcinoma and control groups (P < 0.001). H. pylori infection rate in patients with HBV-DNA ≥103 copies/ml was significantly higher than in those with HBV-DNA <103 copies/ml (76.8% vs. 52.4%, P < 0.001). Prothrombin time (21.3 ± 3.5 s vs. 18.8 ± 4.3 s), total bilirubin (47.3±12.3 μmol/L vs. 26.6 ±7.9 μmol/L), aspartate aminotransferase (184.5 ± 37.6 U/L vs. 98.4 ± 23.5 U/L), blood ammonia (93.4 ± 43.6 μmol/L vs. 35.5 ± 11.7 μmol/L), and AFP (203.4 ± 62.6 μg/L vs. 113.2 ± 45.8 μg/L) in the 13C-UBT-positive group were significantly higher than in the 13C-UBT-negative group (P < 0.01). The incidence rates of esophageal fundus variceal bleeding (25.4% vs. 16.0%), ascites (28.9% vs. 17.8%), and hepatic encephalopathy (24.8% vs. 13.4%) in the 13C-UBT-positive group were significantly higher than in the 13C-UBT-negative group (P < 0.01). The percentages of patients with liver function in Child-Pugh Grade C (29.6% vs. 8.1%) and PHG (43

  8. Chronic hepatitis C in the aged: much ado about nothing or nothing to do?

    PubMed

    Malnick, Stephen; Maor, Yaakov; Melzer, Ehud; Tal, Sari

    2014-05-01

    Hepatitis C is a common infection worldwide. It is a major cause of cirrhosis and its complications, including hepatocellular carcinoma and liver transplantation. Treatment of hepatitis C has dramatically improved since its discovery. Current treatment includes pegylated interferon and ribavirin, and the addition of the protease inhibitors telaprevir, boceprevir, or simeprevir, or the polymerase inhibitor sofosbuvir. The rate of sustained viral response, considered a cure, now approaches 80 %. These treatments are complex, with multiple morbidities and drug interactions. The majority of patients with chronic hepatitis C are from the birth cohort of the 'baby boomer' years (1945-1965) with the oldest already 68 years old. In spite of this, most hepatitis C patients in clinical trials have been much younger and this is still the case in the ongoing studies. Thus, the group of patients most likely to require treatment in the future will have decisions made with a relative lack of evidence-based medicine. It is the purpose of this article to review the epidemiology, clinical manifestations, and treatment of hepatitis C with the data available in the aged population.

  9. [Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus].

    PubMed

    Gonzalez-Huezo, María Sarai; Gallegos-Orozco, Juan Fernando

    2003-01-01

    The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited.

  10. Clinical analysis of patients suffering from chronic hepatitis B superinfected with other hepadnaviruses.

    PubMed

    Fu, Jia; Guo, Dan; Gao, Dandan; Huang, Wenxiang; Li, Ziqiong; Jia, Bei

    2016-06-01

    To compare the clinical manifestations, laboratory examinations, and prognoses of patients with chronic hepatitis B (CHB) who were superinfected with hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV). Two hundred and eleven patients with confirmed CHB in our hospital, a tertiary teaching hospital in China, between 2005 and 2014 were analyzed retrospectively. Among 211 patients with CHB, 35 were superinfected with HAV, 31 were superinfected with HCV, 22 were superinfected with HDV, and 53 were superinfected with HEV. We analyzed and compared the clinical features of the five groups. The tested biochemical indices and markers of liver function included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), prothrombin activity (PTA), serum albumin (Alb), and the serum levels of HBV DNA. The peak values of ALT, AST, and TBil were significantly higher in all of the superinfected groups. Lower peak Alb concentration and PTA were also observed in the superinfected patients, with the exception of patients in the CHB + HAV group. The CHB + HCV, and CHB + HEV groups had higher death rates than the CHB monoinfected group, and the difference was statistically significant. Further analysis of the liver failure groups showed that the level of HBV DNA was not correlated with prognosis. The comparison of clinical outcomes revealed that CHB patients superinfected with HCV, HDV, and HEV compared with CHB monoinfection had statistically greater incidences of exacerbation of the condition and poor prognosis, whereas the patients superinfected with HAV generally had better outcomes.

  11. Hepatitis B: progress in understanding chronicity, the innate immune response, and cccDNA protection

    PubMed Central

    Shimazaki, Tomoe; Takeda, Rei; Izumi, Takaaki; Umumura, Machiko; Sakamoto, Naoya

    2016-01-01

    Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus. While HBV infection exhibits a variety of clinical presentations, even asymptomatic carriers can develop HCC without liver fibrosis. Current therapeutic options against HBV include pegylated interferon (Peg-IFN) and nucleos(t)ide reverse transcriptase inhibitors (NRTIs), with clinical studies showing a significant association between loss of HBV DNA and a decrease in cancer risk. However, the ultimate goal of HBV therapy is a complete cure of HBV—including the elimination of covalently closed circular DNA (cccDNA)—in order to further decrease the risk of developing HCC. The development of hepatitis B is associated with the host immune response to virus-infected hepatocytes, as HBV is understood to lack direct cytotoxicity. While HBV-specific CD8+ T cells are thus involved in hepatitis development, they also play an important role in eliminating HBV infection. Indeed, the innate immune response during the initial phase of HBV infection is essential to the induction of acquired immunity. However, the innate immune response to HBV infection, including the roles of specific immunocompetent cells and associated molecules, is not well understood. In this review, we focus on the current understanding of the mechanisms underlying hepatitis development by HBV infection. We also address the mechanisms by which HBV protects cccDNA. PMID:27761441

  12. Changes in the balance between Treg and Th17 cells in patients with chronic hepatitis B.

    PubMed

    Su, Zhi-Jun; Yu, Xue-Ping; Guo, Ru-Yi; Ming, De-Song; Huang, Lv-Ye; Su, Mi-Long; Deng, Yong; Lin, Zhen-Zhong

    2013-08-01

    The purpose of this study was to explore the role of Treg cells, Th17 cells and cytokines associated with Treg/Th17 differentiation in the occurrence, development and outcome of chronic hepatitis B (CHB). To do so, we detected populations of Treg and Th17 cells and their associated cytokines in the peripheral blood of CHB patients. The populations of Treg cells (CD4(+)CD25(high)CD127(low) T cells) and Th17 cells (CD3(+)CD8(-)IL-17(+) T cells) were analyzed in 46 patients with low to moderate chronic hepatitis B (CHB-LM), 24 patients with severe chronic hepatitis B (CHB-S) and 20 healthy controls (HC) using flow cytometry. The levels of cytokines associated with Treg/Th17 differentiation, including IL-10, TGF-β1, IL-17 and IL-23, were measured by enzyme-linked immunosorbent assay (ELISA). Our study showed that the imbalance of Treg and Th17 cells might play an important role in the occurrence, development and outcome of CHB.

  13. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    PubMed

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  14. Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

    PubMed Central

    Lee, Hye Won; Ahn, Sang Hoon

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B (CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-naïve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM (Individual Prediction Model), CU-HCC (Chinese University-HCC), GAG-HCC (Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC (Nomogram-HCC), REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM (Liver Stiffness Measurement)-based model, LSM-HCC, and mREACH-B (modified REACH-B). PMID:27729738

  15. Chronic hepatitis B with type I diabetes mellitus and autoimmune thyroiditis development during interferon alpha therapy.

    PubMed

    Kose, Sukran; Gozaydin, Ayhan; Akkoclu, Gulgun; Ece, Gulfem

    2012-04-13

    Interferon alpha is a molecule frequently used in the treatment of chronic hepatitis B, C, and D, with immunomodulatory and antiviral activity. It is also used in some cancer types. It has been widely claimed that interferon alpha triggers autoimmunity, with its broad adverse effect profile. Here we present the case of a 29-year-old male patient with chronic hepatitis B diagnosis who developed type 1 diabetes mellitus and autoimmune thyroiditis during treatment with interferon alfa-2b. Within four months of initiation of treatment with interferon alfa-2b, the patient presented to our clinic with dry mouth, urinary frequency (8 to 10 times per day), drinking plenty of water, night time urination, and tiredness. He was admitted to the clinic when his fasting blood glucose level was detected to be high. After examinations, the patient was diagnosed with type 1 diabetes and autoimmune thyroiditis and began to receive treatment with insulin and propranolol. Fasting blood glucose levels were controlled and thyroid hormones decreased to normal levels within one month after the treatments began. For patients who will receive treatment with interferon alpha, especially those individuals with chronic hepatitis, pancreatic autoantibodies should be checked and close monitoring should be performed as there may be glucose tolerance impairment in patients with high titers. In addition, follow-up with thyroid function tests should be performed prior to and during the treatment.

  16. On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B

    PubMed Central

    Gao, Yu-Hua; Meng, Qing-Hua; Zhang, Zhan-Qing; Zhao, Ping; Shang, Qing-Hua; Yuan, Quan; Li, Yao; Deng, Juan; Li, Tong; Liu, Xue-En; Zhuang, Hui

    2016-01-01

    AIM To investigate potential predictors for treatment response to nucleos(t)ide analogues (NAs) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS Seventy-six HBeAg-positive CHB patients received 96-wk NAs optimized therapy (lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeAg, hepatitis B core antibody, hepatitis B virus (HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves (AUROC) of the independent predictors were calculated. RESULTS Forty-three CHB patients (56.6%) achieved virological response (VR: HBV DNA ≤ 300 copies/mL) and 15 patients (19.7%) developed HBeAg seroconversion (SC) after the 96-wk NAs treatment. The HBeAg level (OR = 0.45, P = 0.003) as well as its declined value (OR = 2.03, P = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBeAg titer < 1.3 lg PEIU/mL and its decreased value > 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeAg level (OR = 0.37, P = 0.013) as well as its declined value (OR = 2.02, P = 0.012) at 24-wk also independently predicted HBeAg SC, with the AUROC of 0.828 and 0.814, respectively. The HBeAg titer < -0.5 lg PEIU/mL combined with its declined value > 2.2 lg PEIU/mL at 24-wk predicted HBeAg SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928. CONCLUSION The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy. PMID:28008342

  17. Trace element analysis by PIXE in liver samples from dogs with chronic active hepatitis and liver cirrhosis

    NASA Astrophysics Data System (ADS)

    Andersson, Marianne; Ekholm, Ann-Kristin; Sevelius, Ewa

    1990-04-01

    Trace element levels of liver samples obtained from necropsied dogs suffering from hepatitis and/or liver cirrhosis were determined by PIXE. Two different techniques for preparation of the samples were compared: the pellet press method and wet digestion. Both methods gave similar results, but the pellet press method was chosen for the subsequent routine analyses because of its simplicity due to few preparation steps and little risk of contamination. Preliminary results indicate elevated levels of Cu in chronic hepatitis and cirrhosis. In hereditary copper-induced hepatitis (Bedlington hepatitis) Fe and Br levels were increased as well.

  18. Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe.

    PubMed

    Ozaras, R; Corti, G; Ruta, S; Lacombe, K; Mondelli, M U; Irwing, W L; Puoti, M; Khalighi, A; Santos, M L; Harxhi, A; Lazarevic, I; Soriano, V; Gervain, J; Leblebicioglu, H; Salmon, D; Arends, J E

    2015-11-01

    The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

  19. Tumour promotion versus tumour suppression in chronic hepatic iron overload.

    PubMed

    Bloomer, Steven A; Brown, Kyle E

    2015-06-01

    Although iron-catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague-Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β-catenin, CHOP, C/EBPα and Yes-associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β-catenin levels compared with control livers. Countering these factors, the iron-loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes-associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour-promoting mechanisms in rodent liver.

  20. Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles.

    PubMed

    Pham, T N Q; Mercer, S E; Michalak, T I

    2009-08-01

    Hepatitis C virus (HCV) replicates in immune cells in both chronic hepatitis C (CHC) and occult HCV infection, but the extent of virus replication in this compartment in these opposing infection forms varies greatly. It was unknown whether this could be linked to HCV genotype or to differences in host gene expression shaping the immune response, and whether HCV replication in immune cells is sensitive to endogenous antiviral cytokines. In this study, we uncovered that significantly greater HCV load in peripheral blood mononuclear cells (PBMC), but not in plasma, coincided with HCV genotypes 2 and 3 in CHC, but with genotype 1 in residual occult infection after clinical resolution of hepatitis C. Moreover, PBMC from individuals with occult infection transcribed significantly greater levels of IFN-alpha, IFN-gamma and TNF-alpha, but less interleukin (IL)-10 than those from CHC. In CHC, PBMC with low HCV load expressed significantly more IFN-gamma but less IL-12 than did cells with high virus content. In occult infection, HCV RNA detection in PBMC was associated with much lower IFN-alpha and IL-12 expression. Further, HCV replication in T lymphocytes could be completely eliminated by activation of endogenous IFN-gamma in CHC, but of IFN-alpha in occult infection. In conclusion, CHC and persistent occult HCV infection are characterized by clearly different profiles of antiviral cytokine response in circulating immune cells which are also different from those of healthy individuals. Higher expression of IL-10, combined with lower transcription of IFN-alpha, IFN-gamma and TNF-alpha, is associated with a more robust HCV replication in immune cells.

  1. Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B

    PubMed Central

    Peng, Cheng-Yuan; Lai, Hsueh-Chou; Su, Wen-Pang; Lin, Chia-Hsin; Chuang, Po-Heng; Chen, Sheng-Hung; Chen, Ching-Hsiang

    2017-01-01

    Early declines in serum hepatitis B surface (HBsAg) levels, their optimal cutoffs, and association with therapeutic endpoints in chronic hepatitis B (CHB) patients receiving entecavir treatment remain unclear. We prospectively enrolled 529 patients (195 hepatitis B e antigen [HBeAg]-positive and 334 HBeAg-negative) with a median treatment duration of 49.2 months. Median HBsAg levels declined significantly in both groups at Month 3, but only at Months 6–12 in the HBeAg-negative group. Both groups exhibited a significant HBsAg decline with each successive year of treatment. An HBsAg decline of ≥75% from baseline, assessed at Months 3 and 12 of treatment in the HBeAg-positive and -negative patients, respectively, independently predicted a virological response and HBeAg seroconversion in the HBeAg-positive patients, an HBsAg level of <100 IU/mL in the HBeAg-negative patients, and HBsAg loss in all the patients during treatment. HBsAg levels of <3,000 IU/mL at baseline combined with an HBsAg decline of ≥75% from baseline provided a predictive algorithm for HBsAg loss (positive and negative predictive values: 70% and 100%, respectively) during 5 years of treatment. The proposed cutoffs for defining an HBsAg decline may assist clinicians in early assessments of treatment responses in genotype B-infected or C-infected CHB patients receiving entecavir therapy. PMID:28220833

  2. Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis

    PubMed Central

    Mata-Santos, Hílton Antônio; Dutra, Fabianno Ferreira; Rocha, Carolina Carneiro; Lino, Fabiana Gonçalves; Xavier, Fabiola Ramos; Chinalia, Leandro Andrade; Hossy, Bryan Hudson; Castelo-Branco, Morgana Teixeira Lima; Teodoro, Anderson Junger; Paiva, Claudia N.

    2014-01-01

    In chronic schistosomiasis, hepatic fibrosis is linked to the portal hypertension that causes morbidity in Schistosoma mansoni infection. Silymarin (SIL) is a hepatoprotective and antioxidant medicament largely prescribed against liver diseases that has previously been shown to prevent fibrosis during acute murine schistosomiasis. Here we employed silymarin to try to reverse established hepatic fibrosis in chronic schistosomiasis. Silymarin or vehicle was administered to BALB/c mice every 48 h, starting on the 40th (80 days of treatment), 70th (50 days), or 110th (10 days) day postinfection (dpi). All mice were sacrificed and analyzed at 120 dpi. Treatment with silymarin reduced liver weight and granuloma sizes, reduced the increase in alanine aminotransferase and aspartate aminotransferase levels, and reduced the established hepatic fibrosis (assessed by hydroxyproline contents and picrosirius staining). Treatment with silymarin also reduced the levels of interleukin-13 (IL-13) in serum and increased the gamma interferon (IFN-γ)/IL-13 ratio. There was a linear correlation between IL-13 levels in serum and hydroxyproline hepatic content in both infected untreated and SIL-treated mice, with decreased IL-13 levels corresponding to decreased hydroxyproline hepatic contents. Treatment with either SIL or N-acetylcysteine reduced both proliferation of fibroblast cell lines and basal/IL-13-induced production of collagen I, indicating that besides inhibiting IL-13 production during infection, SIL antioxidant properties most likely contribute to inhibition of collagen production downstream of IL-13. These results show that silymarin interferes with fibrogenic cytokines, reduces established fibrosis, and inhibits downstream effects of IL-13 on fibrogenesis, indicating the drug as a safe and cheap treatment to liver fibrotic disease in schistosomiasis. PMID:24449779

  3. [New drugs in the treatment of chronic hepatitis C].

    PubMed

    Jimenez Galan, R; Albacete Ramirez, A; Monje Agudo, P; Borrego Izquierdo, Y; Morillo Verdugo, R

    2014-05-01

    Objetivos: Analizar la eficacia y seguridad de los nuevos agentesantivirales directos (AAD) que formaran parte del arsenal terapéuticopara el tratamiento de la hepatitis C.Método: Se realizó una búsqueda en la base de datos electrónicaPubMed, de artículos publicados Febrero de 2014 quecumplieran los siguientes criterios: ensayos clínicos (EC) en faseII o III y cuyos objetivos fueran evaluar la eficacia y seguridad denuevas generaciones de inhibidores de la proteasa (IP) frente alVHC, excluyendo con boceprevir y telaprevir.Resultados: Se incluyeron de 24 EC que incluyen asociacionesde AAD con ribavirina (RBV) y con o sin peginterferon (PegINF)y asociaciones de varios AAD. Los resultados de daclatasvircon PegINF y RBV no han sido muy satisfactorios. Por el contrario,sofosbuvir es activo en todos los genotipos virales y permiteser administrado en regímenes libres de PegINF. Alrededordel 90% de los pacientes naïve alcanzan respuesta viralsostenida (RVS) , y no llegan al 80% en pretratados. En cuantoa la segunda generación de IP NS3/4A, destacar a simeprevir,con respuestas próximas al 90% en pacientes naïve y cercanasal 80% en pretratados. Entre las combinaciones de AAD evaluadas,sofosbuvir y daclatasvir y sofosbuvir y ledipasvir alcanzanel 100% de respuesta en no respondedores a triple terapiacon boceprevir y telaprevir.Conclusiones: Las nuevas generaciones de AAD frente al VHCvan a suponer un aumento de las tasas de curación en todoslos subtipos de pacientes, a través de regímenes más sencillosy mejor tolerados.

  4. Hepatitis C virus infection among chronic dialysis patients in the south of France: a collaborative study.

    PubMed

    Dussol, B; Berthezène, P; Brunet, P; Roubicek, C; Berland, Y

    1995-03-01

    During the last quarter of 1992, 984 patients from 13 dialysis centers in the Provence-Alpes-Côte-d'Azur region in France participated in a multicenter cross-sectional study to determine the prevalence, the risk factors, and the clinical consequences of infection by the hepatitis C virus (HCV). Serum samples were tested for anti-HCV antibodies using second-generation enzyme-linked immunosorbent assay (ELISA). In the case of a positive result, a combination test was performed using second-generation recombinant immunoblot (RIBA) or direct detection of HCV-RNA by nested polymerase chain reaction (PCR). Collected data included the patient's age, gender, cause of the kidney disease, type of dialysis treatment, number of years on dialysis, weekly dialysis time, drug addiction, co-infection with hepatitis B virus and human immunodeficiency virus (HIV), number of kidney transplants, number of blood transfusions, and history of acute or chronic hepatitis. Chronic HCV infection was detected in 232 (23.6%) patients, whereas only 71 (7.2%) were infected by HBV. Logistic-regression analysis showed that HCV infection was associated with dialysis over a long period, numerous blood transfusions, female gender, kidney grafts, HBV infection, hemodialysis, and acute as well as chronic hepatitis. Multiple-correspondence analysis confirmed that the contamination was both transfusional and nosocomial. These results underscore the need for a strict compliance with "universal precautions" (Centers for Disease Control [CDC], Atlanta) in dialysis units and raise the question as to whether anti-HCV-positive patients should be isolated.

  5. The expression of thymosin β4 in chronic hepatitis B combined nonalcoholic fatty liver disease

    PubMed Central

    Liang, Jing; Cai, Wenjuan; Han, Tao; Jing, Li; Ma, Zhe; Gao, Yingtang

    2016-01-01

    Abstract The aim of the study was to detect the expression level of thymosin β4 (Tβ4) in serum and tissues of patients with chronic hepatitis B (CHB) combined nonalcoholic fatty liver disease (NAFLD). The effects of Tβ4 in hepatic steatosis, chronic inflammation, and fibrosis development in CHB combined NAFLD patients were also discussed. The study included 46 patients in the case group with CHB and NAFLD and 42 patients in the control group with CHB. ELISA was applied to detect serum Tβ4 and TNF-α level. Furthermore, the correlation analysis of Tβ4 levels with biochemical index, pathological index, and TNF-α level was performed. The Tβ4 immunohistochemical levels of different inflammation fibrosis levels were compared, and the correlation analysis with TNF expression was performed. The Tβ4 levels in patients with CHB combined NAFLD showed no statistical difference when compared to the control group. In patients with CHB combined NAFLD group, the Tβ4 level had no correlation with ALT, AST, TG, FGP, hepatitis B virus (HBV)-DNA levels, and fat grading, but had negative correlation with inflammation score and fibrosis score (P <0.01). The immunohistochemical results of hepatic tissues showed that the expression intensity of severe inflammation fibrosis group had statistical significance compared with that of slight group, and the Tβ4 expression both in serum and in liver tissue negatively correlated with TNF-α expression. Tβ4 could be involved in the regulation of chronic inflammation and fibrosis and plays a defense role in the disease progression of CHB combined NAFLD patients. PMID:28033294

  6. Clinical significance of the changes of platelet counts and serum thrombopoietin levels in chronic hepatitis C patients treated with different doses of consensus interferon.

    PubMed

    Chu, Chen Wei; Hwang, Shinn Jang; Lu, Rei Hwa; Lai, Chiung Ru; Luo, Jiing Chyuan; Wang, Yuan Jen; Chang, Full Young; Lee, Shou Dong

    2002-11-01

    Thrombocytopenia is commonly seen in patients with cirrhosis. Both splenomegaly and inadequate thrombopoietin (TPO) production by the cirrhotic liver are responsible for thrombocytopenia. In addition, thrombocytopenia is frequently observed in chronic hepatitis patients who received interferon therapy, and may even lead to the discontinuation of treatment. The aim of this study is to evaluate the clinical significance of the changes of platelet counts and serum TPO levels in chronic hepatitis C patients treated with different doses of consensus interferon (CIFN). Data from 75 chronic hepatitis C patients who received subcutaneous injection of either CIFN 9 (25 patients) or 3 &mgr;g (26 patients) or placebo (24 patients), three times a week for 24 weeks, were analyzed from a randomized controlled study. All patients received a 24-week observation period after the end of the treatment. The results showed a significantly higher degree of decrease in platelet counts and elevated serum TPO in patients receiving CIFN 9 or 3 &mgr;g as compared with placebo at week 12 and week 24 of treatment, respectively. These changes were more obvious in patients receiving CIFN 9 &mgr;g than in patients receiving CIFN 3 &mgr;g. However, both the decrease of platelet counts and elevated serum TPO levels returned to the baseline values after stopping CIFN therapy. Lower hepatic fibrosis score, lower pretreatment serum HCV RNA level, genotype non-1b infection and patients with sustained response to CIFN were manifested with higher degree of serum TPO elevation in response to the CIFN-induced thrombocytopenia. Multivariate logistic regression analysis showed that an age of less than 45 years and a serum TPO level elevation greater than 50% of baseline level at week 12 of CIFN treatment were significantly independent predictors associated with the sustained response to the CIFN treatment. In conclusion, the changes of platelet counts and serum TPO levels in chronic hepatitis C patients

  7. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

    PubMed Central

    2012-01-01

    Background Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. Results Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228) weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. Conclusions Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance. PMID:22913805

  8. Hepatitis B Virus Genotype C Prevails Among Chronic Carriers of the Virus in Korea

    PubMed Central

    Bae, Si Hyun; Yoon, Seung Kew; Jang, Jeong Won; Kim, Chang Wook; Nam, Soon Woo; Choi, Jong Young; Kim, Boo Sung; Park, Young Min; Suzuki, Seiji; Sugauchi, Fuminaka

    2005-01-01

    Hepatitis B virus (HBV) is one of the major causative agents of chronic liver diseases in Korea. HBV has been classified into 8 genotypes by a divergence of >8% in the entire genomic sequence, and have distinct geographic distributions. There are limited data on the relevance between HBV genotypes and clinical outcomes in Korea. To investigate the clinical feature relating to HBV genotype in Korea, a total 120 serum samples with HBsAg (65 from Seoul and 55 from the other city in Korea) were obtained from each 30 chronic HBV carriers with asymptomatic carrier (ASC), chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HBV genotype was determined by either enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies against genotype-specific epitopes in the preS2-region or the direct sequencing of small S gene. HBV genotypes were determined in 105 (87.5%) of 120 samples. HBV genotype C was identified in all HBV carriers with ASC, CH, LC, and HCC. Genotypes A, B, D, E, F and G were not detected in any of them. Genotype C HBV prevails predominantly among chronic carriers of the virus in Korea, irrespective of their clinical stages of liver disease and geographic origin. PMID:16224156

  9. Increasing LAG-3 expression suppresses T-cell function in chronic hepatitis B

    PubMed Central

    Ye, Bo; Li, Xuefen; Dong, Yuejiao; Wang, Yiyin; Tian, Li; Lin, Sha; Liu, Xia; Kong, Haishen; Chen, Yu

    2017-01-01

    Abstract Weak or absent virus-specific CD8+ T-cell responses to hepatitis B virus (HBV) infection are thought to be responsible for persistent HBV infection. Previous studies have indicated that multiple inhibitory receptors, including lymphocyte activation gene-3 (LAG-3), can suppress the CD8+ T-cell response in chronic viral infection. This study aimed to detect LAG-3 expression and to investigate the manner in which the immune response is regulated to balance the strength of the response with the extent of liver injury in chronic HBV infection. The results showed that LAG-3 expression levels were significantly higher in CD8+ T cells from chronic hepatitis B patients in the immune-active phase compared with chronic asymptomatic HBV carriers and healthy controls. CD8+ T-cell function was suppressed in cells with high LAG-3 expression, and these cells exhibited reduced interferon-γ (IFN-γ) secretion. Furthermore, IFN-γ secretion was restored in CD8+ T cells that were treated with a specific antibody to LAG-3. Taken together, liver injury was prominent in the immune-active phase, but suppressing T-cell function could mitigate this damage. Importantly, the inhibitory function of LAG-3 can be blocked using a LAG-3-specific antibody, and this can restore the activity of non-functional T cells. PMID:28072682

  10. Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene

    SciTech Connect

    Wakui, Shin . E-mail: wakui@azabu-u.ac.jp; Yokoo, Kiyofumi; Takahashi, Hiroyuki; Muto, Tomoko; Suzuki, Yoshihiko; Kanai, Yoshikatsu; Hano, Hiroshi; Furusato, Masakuni; Endou, Hitoshi

    2006-02-01

    We previously reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 {mu}g of PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 {mu}g group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunohistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.

  11. Primary lymphoma of the liver in a patient with acquired immune deficiency syndrome and chronic hepatitis B.

    PubMed

    Lisker-Melman, M; Pittaluga, S; Pluda, J M; Kleiner, D E; Thompson, P; Martin, P; Yarchoan, R; Di Bisceglie, A M

    1989-11-01

    We describe the case of a homosexual man with asymptomatic infection with human immunodeficiency virus and hepatitis B virus who developed primary hepatic lymphoma. The lymphoma presented with rapid enlargement of the liver, and ultrasound examination revealed multiple hypoechoic lesions within the liver. Histological examination of the liver showed massive replacement by lymphomatous tissue, as well as changes of chronic active hepatitis B. Immunohistochemical stains for hepatitis B surface and core antigens were strongly positive in almost all hepatocytes, but not in tumor tissue. Whereas the occurrence of lymphoma probably is related to HIV infection, possible interactions between hepatitis B virus and HIV infection are discussed. Thus, the presence of mass lesions within the liver in a patient with HIV infection should raise the possibility of hepatic lymphoma even if there is no evidence of generalized lymphadenopathy.

  12. Associated Factors for Metabolic Syndrome in the Older Adults with Chronic Virus Hepatitis in the Community

    PubMed Central

    Kuo, Yuan-Hung; Tsai, Ming-Chao; Kee, Kwong-Ming; Chang, Kuo-Chin; Wang, Jing-Houng; Lin, Chun-Yin; Lin, Sheng-Che; Lu, Sheng-Nan

    2016-01-01

    This study was to evaluate the association between metabolic syndrome (MetS) and chronic virus hepatitis elders in the community. Those subjects with positive hepatitis B surface antigen (HBsAg) and/or anti-hepatitis C virus (anti-HCV) screened in the community before were invited to this study and 451 responded. All participants underwent anthropometric measurements, blood tests, ultrasound and fibroscan examinations. The cut-off of liver stiffness measurement-liver cirrhosis (LSM-LC) was 10 kPa for chronic hepatitis B (CHB) patients and 12 kPa for chronic hepatitis C (CHC) patients, respectively. Among 451 responders, 56 were excluded due to negative HBsAg or anti-HCV. Three hundreds and ninety-five subjects included 228 CHB patients, 156 CHC patients and 11 dual hepatitis patients, had a mean age of 62±12.6 years. Fifty-four (23.7%) CHB patients coexisted with MetS whereas 40 (25.6%) CHC patients also had MetS. Those patients with MetS had more LSM-LC cases than those without (20.4% vs 9.8%, p = 0.04 in CHB patients; 28.2% vs 13.5%, p = 0.037 in CHC patients, respectively). In multivariate logistic analysis, detectable viremia was reversely associated with MetS in CHB patients after adjustment for age, gender and body mass index (odds ratio (OR): 0.42; 95% confidence interval (CI): 0.18–0.99; p = 0.047). Regarding CHC patients, higher LSM level was the only factor contributed to MetS (OR: 1.1; 95% CI: 1.02–1.19; p = 0.012). In conclusion, elder CHB patients coexisted with MetS might experience an inactive virus replication but have an advanced liver fibrosis. In elder CHC patients, only higher LSM level was associated with MetS. PMID:27177024

  13. Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis

    PubMed Central

    Zhao, Xin; Deng, Bo; Xu, Xue-Yan; Yang, Shi-Jun; Zhang, Tao; Song, Yi-Jun; Liu, Xiao-Ting; Wang, Yue-Qi; Cai, Da-Yong

    2013-01-01

    AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage

  14. Increased prevalence of coronary artery disease risk markers in patients with chronic hepatitis C – a cross-sectional study

    PubMed Central

    Roed, Torsten; Kristoffersen, Ulrik Sloth; Knudsen, Andreas; Wiinberg, Niels; Lebech, Anne-Mette; Almdal, Thomas; Thomsen, Reimar W; Kjær, Andreas; Weis, Nina

    2014-01-01

    Objective Chronic hepatitis C is a global health problem and has been associated with coronary artery disease. Our aim was to examine the prevalence of coronary artery disease risk markers including endothelial biomarkers in patients with chronic hepatitis C and matched comparisons without manifest cardiovascular disease or diabetes in a cross-sectional design. Methods Sixty patients with chronic hepatitis C (mean age 51 years) were recruited from the Department of Infectious Diseases at Copenhagen University Hospital, and compared with 60 age-matched non-hepatitis C virus-infected individuals from a general population survey. We examined traditional coronary artery disease risk factors, metabolic syndrome, carotid intima media thickness, and a range of endothelial biomarkers. Results Patients with chronic hepatitis C had more hypertension (40% versus 25%, prevalence ratio [PR] 1.6; 95% confidence interval [CI] 0.9–2.7) and smoked more (53% versus 38%, PR 1.4; 95% CI 0.9–2.1). The two groups had similar body mass index (mean 25.0 versus 25.7 kg/m2), whereas those with chronic hepatitis C had less dyslipidemia (including significantly lower low-density lipoprotein and cholesterol/high-density lipoprotein ratio), higher glycosylated hemoglobin level (mean 6.2 versus 5.7, difference of means 0.5; 95% CI 0.3–0.8), and a higher prevalence of metabolic syndrome (28% versus 18%, PR 1.6; 95% CI 0.8–3.0). Increased carotid intima media thickness above the standard 75th percentile was seen more frequently in chronic hepatitis C (9% versus 3%, PR 1.7; 95% CI 0.4–6.7), though difference of means was only 0.04 mm (95% CI 0.00–0.10). Patients with chronic hepatitis C had increased hsCRP (high-sensitivity C-reactive protein), sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and soluble E-selectin, but lower levels of tPAI-1 (tissue-type plasminogen activator inhibitor-1), MMP9 (matrix metallopeptidase 9), and

  15. Telbivudine vs tenofovir in hepatitis B e antigen-negative chronic hepatitis B patients: OPTIMA roadmap study

    PubMed Central

    Krastev, Zahari; Petrova, Diana; Kotzev, Iskren; Celen, Mustafa Kemal; Mendelson, Meryl; Chandra, Richa; Pandey, Priti; Hamed, Kamal

    2016-01-01

    AIM To make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. METHODS This was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period (i.e., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA < 300 copies/mL at week 52. Secondary efficacy endpoints included the rates of HBV DNA < 300 and < 169 copies/mL, HBV DNA change from baseline, alanine aminotransferase normalisation, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, VB, and emergence of resistance at various timepoints throughout the study. Safety and estimated glomerular filtration rate (eGFR) were also analysed. RESULTS A total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (± 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level < 300 copies/mL. Both arms were similar in terms of key secondary efficacy variables at weeks 104 and 156. The percentage of patients achieving HBV DNA < 300 copies/mL remained high and was similar in the telbivudine and tenofovir arms at both weeks 104 and 156. Over 82% of patients in both arms achieved alanine aminotransferase normalisation at week 52, and this percentage remained high at weeks 104 and 156. Telbivudine treatment progressively reduced serum HBsAg levels from baseline while no change was reported in quantitative HBsAg during therapy with tenofovir

  16. Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice.

    PubMed

    Santos Rocha, Sura Wanessa; Silva, Bruna Santos; Gomes, Fabiana Oliveira dos Santos; Soares e Silva, Amanda Karolina; Raposo, Catarina; Barbosa, Karla Patrícia Sousa; Torres, Dilênia de Oliveira Cipriano; dos Santos, Ana Célia Oliveira; Peixoto, Christina Alves

    2012-08-15

    Some pharmacological studies showed that diethylcarbamazine (DEC) interferes with the arachidonic acid metabolism, acting as an anti-inflammatory drug. The chronic alcohol consumption activates the hepatic inflammatory response associated to T-cell activation and overproduction of pro-inflammatory cytokines. The present work analyzed the anti-inflammatory effect of DEC on hepatic cells of alcoholic mice. Thirty-two male C57BL/6 mice were equally divided in the following groups: (a) control group (C), which received only water, (b) DEC-treated group, which received 50 mg/kg for 12 day (DEC50), (c) the alcoholic group (EtOH), submitted to only alcohol and (d) the alcohol-DEC treated group (EtOH50), submitted to alcohol plus DEC treatment after the induction of chronic alcoholism for 5 weeks. Biochemical analyses were performed and liver fragments were processed for light microscopy, transmission electron microscopy, immunohistochemical and western blot. The level of AST increased significantly in alcoholic group whereas a significant reduction of serum AST was detected in the EtOH50 group. Histological and ultrastructural analysis of alcoholic group showed evident hepatocellular damage, which was strikingly reduced in the alcoholic DEC-treated group. Immunohistochemistry results revealed highly expression of inflammatory markers as MDA, NF-κB, TNF-α, IL-6, VCAM and ICAM by the hepatic cells of the EtOH group; however no immunoreactivity for any of these cytokines was detected after DEC treatment. Western blot analyses showed increased MCP-1 and iNOS expression in EtOH group, which was significantly inhibited by DEC treatment. According to the present results, DEC can be a potential drug for the treatment of chronic inflammation induced by chronic alcoholism.

  17. EXCESS MORTALITY IN PATIENTS WITH ADVANCED CHRONIC HEPATITIS C TREATED WITH LONG-TERM PEGINTERFERON

    PubMed Central

    Di Bisceglie, Adrian M.; Stoddard, Anne M.; Dienstag, Jules L.; Shiffman, Mitchell L.; Seeff, Leonard B.; Bonkovsky, Herbert L.; Morishima, Chihiro; Wright, Elizabeth C.; Snow, Kristin K.; Lee, William M.; Fontana, Robert J.; Morgan, Timothy R.; Ghany, Marc G.

    2011-01-01

    Background/Aims Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The HALT-C Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who had failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis was to describe the frequency and causes of death among this cohort of patients. Methods Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or non-liver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Results Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%) of which 76 were considered liver-related (62%) and 46 non-liver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years, the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, p=0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, p=0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to non-liver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality, and only one death was suspected to be a direct complication of peginterferon. Conclusions Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to non-liver-related causes among patients with bridging fibrosis. PMID:21480316

  18. Preliminary trial of recombinant fibroblast interferon in chronic hepatitis B virus infection.

    PubMed Central

    Eisenberg, M; Rosno, S; Garcia, G; Konrad, M W; Gregory, P B; Robinson, W S; Merigan, T C

    1986-01-01

    Five patients with chronic hepatitis B were treated with 8-day courses of leukocyte (alpha) interferon (5 X 10(6) U/day) and with 8-day courses of recombinant fibroblast (betaser) interferon at dosages of 5 X 10(6), 35 X 10(6), and 105 X 10(6) U/day. Inhibition of hepatitis B virus replication as evidenced by a decrease in DNA polymerase (DNAP) activity was seen during all treatment courses. Equivalent reduction in DNAP was seen from the low-dose alpha and beta ser regimens, but beta ser interferon at 35 X 10(6) U/day achieved a significantly greater decrease in DNAP activity than did the low-dose regimens. In no patient, however, was permanent loss of DNAP noted. Because of dose-limiting toxicity, only two patients were escalated to the 105 X 10(6)-U/day dosage level. Transient proteinuria was noted in two patients while they were receiving interferon. This has not been noted in other patients receiving this preparation and could not be explained by the development of anti-interferon antibodies. This study has defined an appropriate dosage for future longer-term trials of this agent alone and in combination with other antivirals for the treatment of chronic hepatitis B. PMID:3524420

  19. [Good virological response to pegylated interferon alfa monotherapy of chronic hepatitis C infection in hemodialysis patient].

    PubMed

    Caro, P; Núñez, A; Delgado, R; Dapena, F; Amann, R

    2007-01-01

    Liver disease caused by hepatitis C virus infection is associated to significant morbidity and mortality among patient with end stage renal disease on maintenance hemodialysis (HD). Therapy in these patients consists of Interferon, preferably pegylated Interferon (pIFN), thus Ribavirin (RBV) is not recommended for patients with impaired renal function, outside its use in controlled trials. We report a case of 35 years young woman on HD treatment, renal transplantation candidate with chronic hepatitis C virus infection, HCV RNA positive (by PCR), genotype 3a, moderate viral load, light increase of aminotransferases. Pegylated Interferon alfa-2a (135 mcg/weekly/SC) was initiated. She achieved HVC RNA negative within 12 weeks, following with pINF as monotherapy to complete 24 weeks (6 months). Sustained virologic response persisted to 24 and 48 weeks. Most important side effects were light detriment of anemia, moderate neutropenia and thombocytopenia, transitory elevation of transaminases and "flu-like" syndrome. Adverse events were well tolerated with total compliance with pIFN dose, no requiring reduce or stop the treatment. These findings confirm that hemodialysis patients with chronic hepatitis C respond well to pegylated IFN monotherapy and a long-term sustained virologic response is achieved, appears to be better tolerated with less side effects, so combination therapy with pINF plus ribavirin is not necessary in all cases.

  20. Chronic Schistosoma japonicum Infection Reduces Immune Response to Vaccine against Hepatitis B in Mice

    PubMed Central

    Chen, Lin; Liu, Wen-qi; Lei, Jia-hui; Guan, Fei; Li, Man-jun; Song, Wen-jian; Li, Yong-long; Wang, Ting

    2012-01-01

    Background Hepatitis B and schistosomiasis are most prevalent in Africa and Asia, and co-infections of both are frequent in these areas. The immunomodulation reported to be induced by schistosome infections might restrict immune control of hepatitis B virus (HBV) leading to more severe viral infection. Vaccination is the most effective measure to control and prevent HBV infection, but there is evidence for a reduced immune response to the vaccine in patients with chronic schistosomiasis japonica. Methodology/Principal Findings In this paper, we demonstrate in a mouse model that a chronic Schistosoma japonicum infection can inhibit the immune response to hepatitis B vaccine (HBV vaccine) and lead to lower production of anti-HBs antibodies, interferon-γ (IFN-γ) and interleukin-2 (IL-2). After deworming with Praziquantel (PZQ), the level of anti-HBs antibodies gradually increased and the Th2-biased profile slowly tapered. At 16 weeks after deworming, the levels of anti-HBs antibodies and Th1/Th2 cytokines returned to the normal levels. Conclusions/Significance The results suggest that the preexisting Th2-dominated immune profile in the host infected with the parasite may down–regulate levels of anti-HBs antibodies and Th1 cytokines. To improve the efficacy of HBV vaccination in schistosome infected humans it may be valuable to treat them with praziquantel (PZQ) some time prior to HBV vaccination. PMID:23272112

  1. Natural history of chronic hepatitis B in Euro-Mediterranean and African countries.

    PubMed

    Hadziyannis, Stephanos J

    2011-07-01

    Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic infection. Perinatal HBV infection is rare while the vast majority of chronic infections originate from horizontal HBV transmission to infants and children. HBeAg loss and seroconversion to anti-HBe occur in a few years time, usually during the second decade of life. HBeAg-negative/anti-HBe-positive chronic hepatitis B (CHB), predominates in these countries being 7-9 times more frequent than HBeAg-positive CHB. The predominance of HBeAg-negative CHB is largely linked to the molecular characteristics of HBV genotype D prevailing in European and African countries of the Mediterranean basin and of genotype E and subgenotype A1 that prevail in the other parts of Africa. The molecular characteristics of the African subgenotype A1 differ from those of European subgenotype A2 explaining the fact that patients infected subgenotype A1 demonstrate an earlier loss of HBeAg and seroconversion to anti-HBe during the natural course of HBV infection compared to those infected with subgenotype A2. It is proposed that the molecular characteristics of HBV genotypes and subgenotypes prevailing in Euro-Mediterranean and African countries acting in concert with host and environmental factors largely determine the natural history of chronic HBV infection and its significant differences from countries of HBV genotype C and B and of subgenotype Ae predominance. The knowledge of the natural history of chronic HBV infection in Euro-Mediterranean and African countries combined with wide screening programs for prompt recognition and treatment of chronic HBV infection both in its HBeAg-positive and -negative immune reactive phases can be expected to increase the efficacy of current

  2. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis

    PubMed Central

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  3. Effect of Oral Administration of Emtricitabine on Woodchuck Hepatitis Virus Replication in Chronically Infected Woodchucks

    PubMed Central

    Korba, Brent E.; Schinazi, R. F.; Cote, Paul; Tennant, Bud C.; Gerin, John L.

    2000-01-01

    Emtricitabine [(−)FTC] [(−)-β-2′,3′-dideoxy-5-fluoro-3′-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (−)FTC against WHV replication in chronically infected woodchucks, an established and predictive model for antiviral therapy against HBV, was examined in a placebo-controlled study. (−)FTC significantly reduced viremia and intrahepatic WHV replication in a dose-dependent manner that was comparable to the antiviral activity of lamivudine observed in previous studies conducted by our laboratories. No effect on the levels of hepatic WHV RNA or the levels of woodchuck hepatitis surface antigen or anti-woodchuck hepatitis surface and core antibodies in the serum of the treated animals was observed. No evidence of drug-related toxicity was observed in any of the animals treated. PMID:10817750

  4. Nationwide Experience of Treatment with Protease Inhibitors in Chronic Hepatitis C Patients in Denmark: Identification of Viral Resistance Mutations

    PubMed Central

    Sølund, Christina; Krarup, Henrik; Ramirez, Santseharay; Thielsen, Peter; Røge, Birgit T.; Lunding, Suzanne; Barfod, Toke S.; Madsen, Lone G.; Tarp, Britta; Christensen, Peer B.; Gerstoft, Jan; Laursen, Alex L.; Bukh, Jens; Weis, Nina

    2014-01-01

    Background and Aims The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. Methods 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. Results 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. Conclusions The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response. PMID:25438153

  5. Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada

    PubMed Central

    Osiowy, Carla; Giles, Elizabeth; Trubnikov, Max; Choudhri, Yogesh; Andonov, Anton

    2015-01-01

    Objective The prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk. Methods HBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV. Results Nine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections. Conclusion Chronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection. PMID:26406309

  6. Ribavirin induced hemolysis: a novel mechanism of action against chronic hepatitis C virus infection.

    PubMed

    Soota, Kaartik; Maliakkal, Benedict

    2014-11-21

    Hepatitis C virus (HCV) is not usually cleared by our immune system, leading to the development of chronic hepatitis C infection. Chronic HCV induces the production of various cytokines, predominantly by Kupffer cells (KCs), and creates a pro-inflammatory state in the liver. The chronic dysregulated production of interferon (IFN) and other cytokines by KCs also promotes innate immune tolerance. Ribavirin (RBV) monotherapy has been shown to decrease inflammation in liver of patients with chronic hepatitis C. Sustained virological response (SVR) is significantly higher when IFN is combined with RBV in chronic HCV (cHCV) infection. However, the mechanism of their synergy remains unclear. Previous theories have attempted to explain the anti-HCV effect based on direct action of RBV alone on the virus or on the immune system; however, these theories have serious shortcomings. We propose that hemolysis, which universally occurs with RBV therapy and which is considered a limiting side effect, is precisely the mechanism by which the anti-HCV effect is exerted. Passive hemolysis results in anti-inflammatory/antiviral actions within the liver that disrupt the innate immune tolerance, leading to the synergy of RBV with IFN-α. Ribavirin-induced hemolysis floods the hepatocytes and KCs with heme, which is metabolized and detoxified by heme oxygenase-1 (HMOX1) to carbon monoxide (CO), biliverdin and free iron (which induces ferritin). These metabolites of heme possess anti-inflammatory and antioxidant properties. Thus, HMOX1 plays an extremely important anti-oxidant, anti-inflammatory and cytoprotective role, particularly in KCs and hepatocytes. HMOX1 has been noted to have anti-viral effects in hepatitis C infected cell lines. Additionally, it has been shown to enhance the response to IFN-α by restoring interferon-stimulated genes (ISGs). This mechanism can be clinically corroborated by the following observations that have been found in patients undergoing RBV/IFN combination

  7. Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

    PubMed Central

    Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

    2015-01-01

    Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their

  8. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance.

    PubMed

    Tarantino, Giovanni; Savastano, Silvia; Colao, Annamaria

    2010-10-14

    Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infiltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acid-induced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.

  9. Randomised controlled trial of lymphoblastoid interferon for chronic active hepatitis B.

    PubMed Central

    Anderson, M G; Harrison, T J; Alexander, G; Zuckerman, A J; Murray-Lyon, I M

    1987-01-01

    Thirty male patients (27 homosexual) with biopsy proven chronic active hepatitis B were randomised to receive lymphoblastoid interferon (Wellferon) or no treatment. All patients were HBeAg positive and had continuing viral replication. Patients receiving treatment were given a single daily intramuscular injection of interferon for 28 days at a starting dose of 2.5 MU/m2 increasing to a maximum of 7.5 MU/m2/day. Transient side effects of malaise and influenza like symptoms occurred in all patients and resolved rapidly after treatment. Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy. After one year there was no appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly, three month regimes recently reported from other centres. PMID:3297940

  10. Tenofovir-induced Fanconi syndrome in chronic hepatitis B monoinfected patients that reverted after tenofovir withdrawal.

    PubMed

    Viganò, Mauro; Brocchieri, Alessandra; Spinetti, Angiola; Zaltron, Serena; Mangia, Giampaolo; Facchetti, Floriana; Fugazza, Alessandro; Castelli, Francesco; Colombo, Massimo; Lampertico, Pietro

    2014-12-01

    Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor widely used to treat patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi syndrome have been reported among HIV patients exposed to TDF. In the HBV monoinfection scenario, only two cases of TDF-associated Fanconi syndrome have been reported thus far. Here, we describe two additional patients with chronic hepatitis B (CHB) who developed a TDF-induced Fanconi syndrome that reverted after TDF withdrawal and had viral replication fully suppressed upon switching to entecavir (ETV). Though the overall risk of TDF associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular function should be monitored in patients exposed to TDF, especially when other renal risk factors or a history of previous exposure to adefovir dipivoxil (ADV) are present.

  11. Does RNA interference provide new hope for control of chronic hepatitis B infection?

    PubMed

    Wilson, Rachel; Purcell, Damian; Netter, Hans J; Revill, Peter A

    2009-01-01

    Hepatitis B virus (HBV) infection is a global human health problem, with an estimated 350 million people having chronic hepatitis B (CHB) infection worldwide. The majority of infections acquired during adulthood are resolved without intervention; however, infections acquired at birth or during early childhood have a 90% chance of progressing to CHB, leading to a host of adverse effects on the liver, including cirrhosis and cancer. CHB is currently treated with a combination of cytokines and/or nucleoside/nucleotide analogues; however, adverse side effects to cytokine therapy and the selection of resistance mutations to nucleoside analogues often abrogate the efficacy of treatment. The recent discovery that small interfering RNA and microRNA are active in mammalian cells suggests it might be possible to supplement existing HBV therapies with small RNA-based therapeutic(s).

  12. Antibodies to liver membrane antigens in chronic active hepatitis (CAH). II. Specificity for autoimmune CAH.

    PubMed Central

    Frazer, I H; Kronborg, I J; Mackay, I R

    1983-01-01

    An immunoradiometric assay for IgG class autoantibody to liver membrane antigens, based on serum binding to glutaraldehyde treated monkey hepatocytes, was used to examine sera from patients with chronic active hepatitis (CAH) and other acute and chronic liver diseases. All sera from normals and patients showed binding, up to a titre of 1/2,048. For comparison of assays, results were normalized by selecting two reference sera, one with a high degree of binding, and one from a healthy subject with a low degree of binding: at a dilution of 1/2,048, these sera were given binding values of 100% and 0%. The values for the binding of unknown sera at the same dilution were calculated from these two reference values. For 26 patients with autoimmune CAH, the mean (+/- s.d.) percentage binding value (70 +/- 33%) was significantly higher than the mean value for 26 healthy subjects (10 +/- 15%), and high binding values were significantly associated with biochemically active hepatitis. The mean percentage binding value was moderately increased for eight patients with HBsAg associated CAH (42 +/- 12%), 13 patients with alcoholic hepatitis with cirrhosis (37 +/- 25%) and 45 patients with acute viral hepatitis A (40 +/- 27%) or B (52 +/- 37%). At a cut-off binding value of 65%, the assay as a single diagnostic procedure was shown to have a 70% sensitivity and a 95% specificity for the diagnosis of autoimmune CAH. Better understanding of the pathogenetic significance of antibodies to liver membrane antigens in CAH and other liver diseases will depend upon biochemical analysis of the presumably multiple antigenic determinants on the hepatocyte membrane. PMID:6616969

  13. Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection.

    PubMed

    Valva, P; Gismondi, M I; Casciato, P C; Galoppo, M; Lezama, C; Galdame, O; Gadano, A; Galoppo, M C; Mullen, E; De Matteo, E N; Preciado, M V

    2014-12-01

    Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3(+) and TUNEL(+) hepatocytes, as well as total, CD4(+), CD8(+), Foxp3(+) and CD20(+) lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3(+) r = 0.74, p < 0.0001; TUNEL(+) r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3(+) cell count was increased in severe hepatitis (p = 0.009). Total, CD4(+), CD8(+) and Foxp3(+) lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8(+) cells correlated with infected (r = 0.495, p 0.04) and TUNEL(+) hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3(+) hepatocytes (r = 0.387, p 0.04). In adults, CD8(+) was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8(+) r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

  14. Occult hepatitis B virus infection among chronic hemodialysis patients in Alexandria, Egypt.

    PubMed

    Helaly, Ghada F; El Ghazzawi, Ebtisam F; Shawky, Sherine M; Farag, Farag M

    2015-01-01

    The prevalence of end-stage renal disease has increased dramatically in developing countries. Hepatitis B virus (HBV) infection is a global health problem that represents a significant co-morbidity event that has led to outbreaks of hepatitis B. There are inadequate data concerning occult HBV infection among Egyptian chronic hemodialysis patients. This study aimed to detect occult HBV infection among chronic hemodialysis patients in Alexandria, Egypt. A cross-sectional study was performed on 100 patients with end-stage renal disease that received maintenance hemodialysis and had tested negative for HBV surface antigen. Blood samples were collected before the initiation of hemodialysis. Sera were tested for hepatitis C virus (HCV) and hepatitis B core (HBc) antibodies using ELISA, and HBV DNA was detected by SYBR Green real-time PCR using specific primers for the s and c genes and by nested PCR using pol gene-specific primers. The serum activity of alanine and aspartate aminotransferase (ALT and AST) were also measured. Anti-HCV and anti-HBc antibodies were detected in 34% and 48% of patients, respectively, and 70.6% of anti-HCV positive patients were also positive for anti-HBc antibodies. This association was statistically significant (p=0.001). HBV DNA was detected in 32% of the hemodialysis patients. A significant association was determined between the presence of HBV DNA and anti-HCV positivity (p=0.021). Aminotransferases were elevated in 21% of the studied patients, more often in patients with positive anti-HCV profiles than in patients negative for anti-HCV (p<0.05). In conclusion, the serological markers of HBV infection should be verified with molecular tests to investigate possible occult infections, especially among anti-HBc-positive hemodialysis patients, to improve our understanding of their clinical, laboratory, and epidemiological characteristics.

  15. Treating chronic hepatitis B virus: Chinese physicians’ awareness of the 2010 guidelines

    PubMed Central

    Wei, Lai; Jia, Ji-Dong; Weng, Xin-Hua; Dou, Xiao-Guang; Jiang, Jia-Ji; Tang, Hong; Ning, Qin; Dai, Qing-Qing; Li, Run-Qin; Liu, Jie

    2016-01-01

    AIM: To investigate Chinese physicians’ awareness of the 2010 guidelines on the treatment of chronic hepatitis B virus (HBV) infection. METHODS: This was a quantitative survey that investigated the characteristics and practices of physicians who were treating patients with hepatitis B, the profile of their patients and physician practices regarding the diagnosis and treatment of HBV at the time of the survey. Participants were randomly selected from available databases of Chinese physicians and requested to complete either an online or paper-based survey. Data from the survey responses were analysed. For data validation and interpretation, qualitative indepth interviews were conducted with 39 of the respondents. RESULTS: Five-hundred completed surveys, from 663 physicians were available for analysis. A mean of 175 chronic hepatitis B (CHB) patients was seen by each physician every month, of whom 85 (49%) were treated in line with therapeutic indications stated in the 2010 guidelines. A total of 444 (89%) physicians often (> 60% of the time) adhered to the guidelines. Most physicians used antiviral medications as recommended. For patients with compensated and decompensated cirrhosis, 342 (68%) and 336 (67%) of physicians, respectively, often followed the recommendation to use potent nucleos(t)ide analogues with a high genetic barrier to resistance, using the appropriate treatment more than 60% of the time. Physicians from infectious disease or liver disease departments were better informed than those from gastrointestinal or other departments. CONCLUSION: The majority of Chinese physicians often adhere to Chinese 2010 CHB guidelines and are well-informed about the use of antiviral medications for hepatitis B. PMID:27366303

  16. Clinical Monitoring of Chronic Hepatitis C Based on its Natural History and Therapy

    PubMed Central

    Nguyen, Douglas L.; Hu, Ke-Qin

    2014-01-01

    Hepatitis C virus (HCV) infection is a major public health problem and a leading cause of chronic liver disease. Chronic HCV infection often follows a progressive course over years and can result in cirrhosis, hepatocellular carcinoma, and need for liver transplantation. In the United States alone, the estimated prevalence of HCV infection is up to 5.1 million persons. The optimal approach to detecting HCV infection is to screen persons for possible history of risks of exposure to virus and to test those selected individuals with risk factors. Both host and viral factors may be important contributors to the natural history of HCV. Currently, effective pharmacologic therapy are available to induce sustained virologic response (SVR) or virologic “cure,” which results in improved morbidity and mortality. Patient education before treatment is essential and should include a full discussion of potential side effects. It is important to work collaboratively and closely with patients to ensure early recognition of adverse events and to effectively manage them in order to ensure treatment compliance. This paper provides a thorough overview on screening for the diagnosis, clinical management, and treatment indications and contraindications for chronic hepatitis C. PMID:25580186

  17. Cyclooxygenase-2 Inhibitor Reduces Hepatic Stiffness in Pediatric Chronic Liver Disease Patients Following Kasai Portoenterostomy

    PubMed Central

    Chang, Hye Kyung; Chang, Eun Young; Ryu, Seonae

    2016-01-01

    Purpose The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. Materials and Methods From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. Results Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. Conclusion COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia. PMID:27189282

  18. Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection

    PubMed Central

    Parikh, Pathik; Ryan, John D.

    2017-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepatocellular carcinoma (HCC), without intervention. Due to the complex natural history of HBV infection, patients require an expert assessment to interpret biochemistry, viral serology and appropriately stage the disease, and to initiate monitoring and/or therapy where indicated. The detection and quantification of liver fibrosis is a key factor for disease management and prognostication for an individual with HBV. The reliance on invasive liver biopsy to stage disease is diminishing with the advent of robust non-invasive blood- and imaging-based algorithms which can reliably stage disease in many cases. These tests are now incorporated into International guidelines for HBV management and relied upon daily to inform clinical judgement. Both blood- and imaging-based approaches have advantages over liver biopsy, including minimal risks, lower cost, better patient acceptance and speed of results, while disadvantages include lower diagnostic accuracy in intermediate disease stages and variability with co-existing hepatic inflammation or steatosis. This review outlines the methods of fibrosis assessment in chronic HBV infection and focuses on the most commonly used blood- and imaging-based non-invasive tests, reviewing their diagnostic performance and applicability to patient care. PMID:28251119

  19. Chronic hepatitis C virus infection and neurological and psychiatric disorders: An overview

    PubMed Central

    Adinolfi, Luigi Elio; Nevola, Riccardo; Lus, Giacomo; Restivo, Luciano; Guerrera, Barbara; Romano, Ciro; Zampino, Rosa; Rinaldi, Luca; Sellitto, Ausilia; Giordano, Mauro; Marrone, Aldo

    2015-01-01

    Hepatitis C virus (HCV) infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease. Among the extrahepatic manifestations, neuropsychiatric disorders have been reported in up to 50% of chronic HCV infected patients. Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations. Main HCV-associated neurological conditions include cerebrovascular events, encephalopathy, myelitis, encephalomyelitis, and cognitive impairment, whereas “brain fog”, depression, anxiety, and fatigue are at the top of the list of psychiatric disorders. Moreover, HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia, and has also been recently recognized as an independent risk factor for stroke. These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy. The brain is a suitable site for HCV replication, where the virus may directly exert neurotoxicity; other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells, alterations in neurotransmitter circuits, autoimmune disorders, and cerebral or systemic inflammation. A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment; however, further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders. PMID:25741133

  20. Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

    PubMed Central

    Ghamari, Shiva; Alavian, Seyed Moayed; Rizzetto, Mario; Olivero, Antonella; Smedile, Antonina; Khedive, Abulfazl; Alavian, Seyed Ehsan; Zolfaghari, Mohammad Reza; Jazayeri, Seyed Mohammad

    2013-01-01

    Background Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone. Objectives The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates. Patients and Methods 81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations. Results 12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients. Conclusions HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group. PMID:24098308

  1. Development and Validation of an Online Program for Promoting Self-Management among Korean Patients with Chronic Hepatitis B.

    PubMed

    Yang, Jinhyang

    2013-01-01

    The hepatitis B virus is second only to tobacco as a known human carcinogen. However, chronic hepatitis B usually does not produce symptoms and people feel healthy even in the early stages of live cancer. Therefore, chronically infected people should perceive it as a serious health problem and move on to appropriate health behaviour. The purpose of this paper is to develop and validate an online program for promoting self-management among Korean patients with chronic hepatitis B. The online program was developed using a prototyping approach and system developing life cycle method, evaluated by users for their satisfaction with the website and experts for the quality of the site. To evaluate the application of the online program, knowledge and self-management compliance of the subjects were measured and compared before and after the application of the online program. There were statistically significant increases in knowledge and self-management compliance in the user group. An online program with high accessibility and applicability including information, motivation, and behavior skill factors can promote self-management of the patient with chronic hepatitis B. Findings from this study allow Korean patients with chronic hepatitis B to engage in proactive and effective health management in the community or clinical practice.

  2. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

    SciTech Connect

    Sorrell, M.F.; Nauss, J.M.; Donohue, T.M. Jr.; Tuma, D.J.

    1983-03-01

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate (/sup 14/C)glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring (/sup 14/C)leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, (/sup 14/C)fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration.

  3. Chronic Low Dose Fructose infusion Does Not Reverse Glucagon-Mediated Decrease in Hepatic Glucose Utilization

    PubMed Central

    Johnson, Paulette M.; Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E; Lacy, D. Brooks; McGuinness, Owen P.

    2013-01-01

    Objective An adaptation to chronic total parenteral nutrition (TPN; 75% of non protein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if chronic fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Material/methods Studies were performed in conscious insulin-treated chronically catheterized pancreatectomized dogs that adapted to TPN for 33 h. They were then assigned to one of 4 groups: TPN (C), TPN + fructose (4.4 μmol·kg−1·min−1, F), TPN+ glucagon (0.2 pmol·kg−1·min−1, GGN), or a TPN + fructose and glucagon (F+GGN) for an additional 63h (33–96h). Insulin, fructose and glucagon were infused into the portal vein. During that period all animals received a fixed insulin infusion 0.4mU· kg−1·min−1 (33–96h) and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mM). Results Chronic fructose infusion was unable to further enhance net hepatic glucose uptake (NHGU; μmol·kg−1·min−1) (31.1±2.8 vs. 36.1±5.0; C vs. F) nor was it able to overcome glucagon-mediated decrease in NHGU (10.0±4.4 vs. 12.2±3.9; GGN vs. F+GGN). Conclusion In summary, chronic fructose infusion cannot augment liver glucose uptake during TPN nor can it overcome the inhibitory effects of glucagon. PMID:20940071

  4. Long-term prognosis of chronic hepatitis B virus infection in the childhood

    PubMed Central

    Akbulut, Ulaş Emre; Çakır, Murat

    2014-01-01

    Aim: It was aimed to investigate the modes of transmisson and long-term prognosis of the disease in patients who were followed up with a diagnosis of chronic hepatitis B infection. Material and Methods: The files of the patients who presented to our outpatient clinic between January 2002 and May 2013 and were being followed up with a diagnosis of chronic hepatitis B virus infection were examined retrospectively and the information related with the age, gender, age at the time of diagnosis, mode of transmission, follow-up period, transaminase levels, the amount of hepatitis B virus-deoxyribonucleic acid and treatment and responses to the treatment given were recorded. Results: The age at the time of diagnosis of 150 patients (97 males, 64%) included in the study was 14.95±2.94 years. 59 (39.3%) of the patients were inactive carriers, 61 (40.7%) were in the immunotolerant stage and 30 (20%) were in the immunoreactive stage. Vertical transmission was present in 86 (57.3%) patients, horizontal transmission was present in 41 patients (27.3%) and the mode of transmission was not known in 23 patients (15.3%). Response to treatment was obtained in 26 (72.2%) of 36 patients who received treatment. Lamivudine (4 mg/kg/day) was given to 29 of the patients who were given treatment, interferon-α (IFN-α) (6 MU/m2, three days a week) was given to 3 patients at the same dose and both IFN-α and lamivudine were given to 4 patients. The time to give response to treatment was 24.23±15.23 months (6–50 months). Spontaneous anti-HBe seroconversion occured in four (7.2%) of 55 immuntolerant children who were followed up without treatment. The time to development of seroconversion in these children was 2.50±1.91 years (1–5 years). Conclusions: Chronic hepatitis B virus infection has a more benign prognosis in children compared to adults, though it may lead to development of hepatic failure, cirrhosis and hepatocellular cancer. In addition, a decrease in the frequency of infection

  5. Screening and evaluation of chronic and occult Hepatitis B in chemo – radiotherapy patients with cancer

    PubMed Central

    Meidani, Mohsen; Rostami, Mojtaba; Hemmati, Simin; Ashrafi, Farzaneh; Gholamnezhad, Mohammad; Emadi, Maryam; Ghasemian, Rasoul; Ahmadian, Mehdi

    2016-01-01

    Background: Hepatitis B virus infection (HBV) and its complications is one of the most serious problems of the health system in many parts of the world. In the present study, we will assess chronic and occult HBV and isolated anti-Hepatitis B core antigen whose screening and evaluation is not routine in different populations. Materials and Methods: This descriptive analytical study was conducted on 213 patients undergoing chemotherapy - radiotherapy referred to the hematology - oncology clinics of Isfahan, Iran in 2012. In order to determine the serum levels of hepatitis B surface antigen (HbSAg), Hepatitis B Antigen and Antibody (HBCAb), aspartate aminotransferase (AST), alanine transaminase (ALT) and Alkaline phosphatase (ALK.P), venous blood samples were obtained. If the HBCAb sample was positive, another sample of the serum was sent to the laboratory to perform polymerase chain reaction and to determine viral load. Results: The mean age of the patients was 47.7 ± 9 years, with an age range of 27 -73 years; 98 (46%) and 115 (54%) cases were male and female, respectively, with mean age of 51.9 ± 8.3 and 44.1 ± 8.1 years, and there was no significant difference (P < 0.001). The mean level of liver enzymes including AST, ALT and ALK.P were 34.2 ± 36.02, 38.9 ± 47.1 and 252.1 ± 234.7, respectively. Two cases were HbSAg positive (0.9%) and six cases were HBCAb positive (2.8%) and HbSAg negative. Three cases had a high viral load at the rate of starting treatment among positive anti-HBC patients. Conclusion: Because occult hepatitis is investigated less commonly in routine studies, it seems that screening and evaluating its prevalence is useful in the management of patients. PMID:27274500

  6. Antibodies to hepatitis A virus in Italian patients with chronic liver disease.

    PubMed

    Sagnelli, E; Rossi, G; Coppola, N; Scolastico, C; Onofrio, M; Filippini, P; Chiaramonte, M; Pizzigall, E; Aceti, A; Spadaro, A; Raimondo, G; Piccinino, F

    2001-10-01

    To improve our knowledge for future hepatitis A virus (HAV) vaccination strategies we carried out a multicentre study on naturally acquired immunological protection against HAV in patients with chronic hepatitis in Italy. We enrolled 830 consecutive patients with chronic hepatitis on their first observation at one of the six Italian liver units participating in the study. Six hundred and fifty-eight patients (79.3%) were positive for total anti-HAV and 172 (20.7%) were negative. The anti-HAV negative patients were younger (median age 33, range 11-78) than the anti-HAV positive (median age 56, 18-87). There was a higher prevalence of cases with circulating anti-HAV among the 508 patients residing in southern Italy than in the 322 residing in northern Italy (88.8% vs. 64%, P < 0.001). No significant difference in the anti-HAV prevalence was observed between patients from northern Italy and those from southern Italy aged 0-30 years or in those over 60 years, while in those 31-60 years old there was a higher prevalence of anti-HAV positive patients from southern Italy (90.2% vs. 65.8%, P < 0.0001). Of the patients with liver cirrhosis in this study, only 3 of the 26 (11.5%) from northern Italy and 8 of the 228 (3.5%) from southern Italy had no immunological protection against HAV infection. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV is substantial in Italy, particularly in the north of the country, and that new vaccination strategies are needed.

  7. Chronic hepatitis C: treatment, complications, and long-term outcomes in a population of Latino veterans

    PubMed Central

    Santiago-Rolon, Amarilys; Purcell, Dagmary; Grigg, Nicole; Toro, Doris H.

    2016-01-01

    Objectives Chronic hepatitis C (CHC) is a major public health problem in Puerto Rico. It is the most common cause of chronic liver disease and the most frequent indication for liver transplantation in the United States." Our main objectives were to estimate the seroprevalence of CHC infection, to describe the demographic and histological parameters of the infection in our sample population, and to evaluate the treatment outcomes in Puerto Rican veterans. Methods To determine overall seroprevalence, we reviewed all the hepatitis C cases (encompassing from January 1, 2002, to December 31, 2009) of the VA Caribbean Healthcare System, Department of Veterans Affairs. The records of only those individuals who received treatment with pegylated interferon and ribavirin were reviewed to determine risks factors for infection, response rates, adverse events, and outcomes. Results During the study period, there were a total of 1,496 patients identified as being infected with HCV, for an estimated seroprevalence of 2.3%. Of these, approximately 10% (137) were treated with combination therapy and were included in this study. The mean age was 58 (±6.4); 96.4% were men. The most common genotype was type 1. The responses to treatment were generally poor, with only 48.4% of the patients achieving Ssustained virological response. Discussion Though the seroprevalence of chronic hepatitis C in the Latino veteran population of Puerto Rico is high, relatively few patients have received treatment, most probably because of the contraindications of the medications used. Combination therapy with pegylated interferon plus weight-based ribavirin was inefficient and plagued with side effects; as a whole, this therapy was not found to be overly beneficial to our patients. New emerging and approved therapies will change this paradigm, allowing the treatment of a larger population without the side effects of the studied therapy. PMID:26932282

  8. PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease

    PubMed Central

    Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

    2016-01-01

    AIM To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. RESULTS Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients. PMID:28050240

  9. Drug therapies for chronic hepatitis C infection: a cost-effectiveness analysis

    PubMed Central

    Wong, William W. L.; Lee, Karen M.; Singh, Sumeet; Wells, George; Feld, Jordan J.; Krahn, Murray

    2017-01-01

    Background: Before 2011, pegylated interferon plus ribavirin was the standard therapy for chronic hepatitis C. Interferon-free direct-acting antiviral agents were then approved. Although these treatments appear to be more effective, they are substantially more expensive. In anticipation of the need for information regarding the comparative cost-effectiveness of new regimens in a recent therapeutic review, we conducted the analysis to inform listing decision in Canada. Methods: A state-transition model was developed in the form of a cost-utility analysis. Regimens included in the analysis were comprehensive. The cohort under consideration had a mean age of 50 years. The cohort was defined by treatment status and cirrhosis status. Inputs for the model were derived from published sources and validated by clinical experts. Results: For each genotype 1 population, at least 1 of the interferon-free agents appeared to be economically attractive compared with pegylated interferon-ribavirin, at a willingness-to-pay of $50 000 per quality-adjusted life-year. The drug that was the most cost-effective varied by population. For genotype 2-4 population, the direct-acting antiviral therapies appeared not to be economically attractive compared with pegylated interferon-ribavirin for the treatment-naive; however, there were direct-acting antiviral therapies that appeared to be attractive when compared with no treatment for the treatment-experienced. Interpretation: Public health policy should be informed by consideration of health benefit, social and ethical values, feasibility and cost-effectiveness. Our analysis assists the development of reimbursements and policies for interferon-free direct-acting antiviral agent regimens for chronic hepatitis C infection by informing the last criterion. Considering the rapid development of treatments for chronic hepatitis C, further update and expanded reviews will be necessary.

  10. Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients

    PubMed Central

    Wu, Tao; Zheng, Xiaojiao; Yang, Ming; Zhao, Aihua; Li, Meng; Chen, Tianlu; Panee, Jun; Jia, Wei; Ji, Guang

    2017-01-01

    The incidences of chronic hepatitis B (CHB), Hepatitis B virus (HBV)-associated cirrhosis and HBV-associated carcinoma are high and increasing. This study was designed to evaluate serum lipid metabolite changes that are associated with the progression from CHB to HBV-associated cirrhosis and ultimately to HBV-associated HCC. A targeted metabolomic assay was performed in fasting sera from 136 CHB patients, 104 HBV-associated cirrhosis, and 95 HBV-associated HCC using ultra-performance liquid chromatography triple quadrupole mass spectrometry. A total of 140 metabolites were identified. Clear separations between each two groups were obtained using the partial least squares discriminate analysis of 9 lipid metabolites. Progressively lower levels of long-chain lysophosphatidylcholines (lysoPC a C18:2, lysoPC a C20:3, lysoPC a C20:4) were observed from CHB to cirrhosis to carcinoma; lower levels of lysoPC a C20:4 were found in patients with higher model for end-stage liver disease in the same disease group; and lysoPC a C20:3 levels were lower in Child-Pugh Class C than in Class A and Class B in HBV-associated cirrhosis and HBV-associated HCC groups. The octadecadienyl carnitine level was higher in HBV-associated cirrhosis group than in other two groups. Serum levels of selected long-chain lysoPCs are promising markers for the progression of HBV-associated liver diseases. PMID:28198443

  11. MicroRNA-196A-2 polymorphisms and hepatocellular carcinoma in patients with chronic hepatitis B.

    PubMed

    Kim, Hwi Young; Yoon, Jung-Hwan; Lee, Hyo-Suk; Cheong, Jae Youn; Cho, Sung Won; Shin, Hyoung Doo; Kim, Yoon Jun

    2014-03-01

    Single nucleotide polymorphisms (SNPs) in microRNA (miR)-196a-2 have been suggested to contribute to susceptibility to various human cancers. The aim of this study was to determine whether polymorphisms of miRNA-196a-2 affect the clinical outcomes of hepatitis B virus (HBV) infection in Korean patients. Genotyping was performed for 1,439 Korean patients with either past or present HBV infection, including 404 control subjects who underwent spontaneous recovery and 1,035 subjects with chronic HBV (313 cases of chronic hepatitis B, 305 cases of cirrhosis of the liver, and 417 cases of hepatocellular carcinoma [HCC]). Genotyping results revealed that the polymorphism rs12304647A>C, which lies in the pri-miRNA region of miR-196a-2, has a significant minor allele frequency (0.210). Logistic analysis revealed that the rs12304647A>C SNP was associated with a significant protective effect against HCC in patients with chronic hepatitis (odds ratio [OR] = 0.70, P = 0.005 in a codominant model; OR = 0.73, P = 0.03 in a dominant model; OR = 0.31, P = 0.004 in a recessive model), and in the patients with cirrhosis (OR = 0.63, P = 0.0009 in a codominant model; OR = 0.66, P = 0.01 in a dominant model; OR = 0.25, P = 0.001 in a recessive model). A Cox relative hazards model with adjustments for age, gender, HBeAg status, and cirrhosis revealed that rs12304647A>C retained its association with HCC in a codominant model (relative hazards [RH] = 1.14, P = 0.05) and in a recessive model (RH = 1.44, P = 0.03). However, the miR-196a-2 rs12304647A>C SNP had no association with HBV clearance. In conclusion, the miR-196a-2 rs12304647 CC genotype had a protective effect against development of HCC in comparison to the AA or AC genotypes in patients with chronic hepatitis and cirrhosis.

  12. [Expert recommendations for the diagnosis and treatment of chronic hepatitis C infection in the prison setting].

    PubMed

    Saiz de la Hoya-Zamácola, Pablo; Marco-Mouriño, Andrés; Clemente-Ricote, Gerardo; Portilla-Sogorb, Joaquín; Boix-Martínez, Vicente; Núñez-Martínez, Oscar; Reus-Bañuls, Sergio; Teixidó i Pérez, Nuria

    2006-11-01

    The prevalence of HCV infection in Spanish prisons is very high (38.5%). The characteristics of the infected patients, particularly the high rate of HIV coinfection, makes it very likely that the morbidity and mortality produced by serious liver disease secondary to this infection will increase considerably in the coming years. A group of Spanish experts with experience in patients who are inmates has been invited to establish a series of recommendations for the diagnosis and treatment of chronic hepatitis C infection in Spanish prisons.

  13. Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients

    PubMed Central

    Wang, Xiao-Ling; Ren, Jian-Ping; Wang, Xue-Qing; Wang, Xiao-Hong; Yang, Shao-Fang; Xiong, Yi

    2016-01-01

    AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes. METHODS: One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed. RESULTS: Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ2 = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ2 = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively

  14. Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

    PubMed

    Ghosh, S; Nandi, M; Pal, S; Mukhopadhyay, D; Chakraborty, B C; Khatun, M; Bhowmick, D; Mondal, R K; Das, S; Das, K; Ghosh, R; Banerjee, S; Santra, A; Chatterjee, M; Chowdhury, A; Datta, S

    2016-08-01

    Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and

  15. Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

    PubMed Central

    Li, Ming-Hui; Zhang, Lu; Qu, Xiao-Jing; Lu, Yao; Shen, Ge; Wu, Shu-Ling; Chang, Min; Liu, Ru-Yu; Hu, Lei-Ping; Li, Zhen-Zhen; Hua, Wen-Hao; Song, Shu-Jing; Xie, Yao

    2017-01-01

    Background: Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a. Methods: A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1–3 months. Results: Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72–96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions: Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss. PMID:28229987

  16. Interleukin-28B Polymorphisms and Response of Chronic Hepatitis C Patients from Indonesia to Pegylated Interferon/Ribavirin Treatment

    PubMed Central

    Juniastuti; Wibowo, Bogi P.; Wibawa, I D. N.; Utsumi, Takako; Mustika, Syifa; Amin, Mochamad; Wahyuni, Rury M.; Kurniawan, Hendra; Hendrayana, Agus; Setiawan, Poernomo B.; Yamani, Laura N.; Soetjipto; Yano, Yoshihiko; Hotta, Hak; Hayashi, Yoshitake

    2014-01-01

    This study demonstrated that Indonesian patients with chronic hepatitis C (mostly ethnic Java people) mostly were infected with hepatitis C virus (HCV) genotype 1; however, they carried mainly the major genotypes of interleukin 28B (IL-28B) single nucleotide polymorphisms (SNPs) (rs12979860 CC, rs11881222 TT, rs8103142 AA, and rs8099917 TT), and they mostly achieved sustained virological responses to pegylated interferon/ribavirin treatment. PMID:24696021

  17. TES Level 1B

    Atmospheric Science Data Center

    2014-12-08

    TES Level 1B data files contain radiometric calibrated spectral radiances and their ... and some engineering data are also provided. A Level 1B data file contains data from a single TES orbit for one focal ... as the Aura orbit number at the time of the South Pole apex crossing. version id represents the version identification number, ...

  18. Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Gómez-Ambrosi, Javier; Frago, Laura M; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

    2015-11-05

    Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia.

  19. Hepatic and Mesenteric Vasculitis as Presenting Manifestation of Mixed Cryoglobulinemia Related to Chronic Hepatitis C Virus Infection in a Female Patient.

    PubMed

    Calle Toro, Juan S; Davalos, Diana M; Charry, Jose D; Arrunategi, Ana M; Tobon, Gabriel

    2016-06-01

    Approximately 80% of patients with hepatitis C virus infection develop chronic liver disease as cirrhosis, and 40% develop autoimmune complications as mixed cryoglobulinemia (MC). Gastrointestinal involvement in MC is rare, and even more so is hepatic involvement. We report a case of an 87-year-old woman with a 10-year history of blood transfusion-acquired hepatitis C virus infection, without treatment. She consulted the emergency department for diffuse abdominal pain, associated with vomiting. After 2 weeks of hospitalization in the intensive care unit, a diagnosis of MC was made; cirrhosis and secondary mesenteric and hepatic vasculitis were confirmed by a diagnostic laparoscopy. Unfortunately the condition of the patient worsened with sepsis and resulted in death in the fourth week from admission. This case highlights the importance of having in mind gastrointestinal tract vasculitis as a medical cause of abdominal pain in patients with chronic hepatitis C virus infection and using data laboratory tests, images, and histopathologic studies to aid with the diagnosis.

  20. [Screening, diagnosis and treatment of chronic hepatitis C in clinical practice].

    PubMed

    Ridruejo, Ezequiel; Fainboim, Hugo; Villamil, Alejandra

    2016-01-01

    Chronic hepatitis C (HCV) is a global health problem. Worldwide, 170 million people are chronically infected. In Latin America its prevalence is estimated between 1.0 and 2.3%, and in Argentina between 1.0 and 1.5%. Treatment efficacy has considerably improved in the last 2 or 3 years. Sustained virological response (SVR) rates around 90-95% can be achieved with the new direct acting antiviral agents (DAAs) currently available, with few side effects. It is necessary to increase the number of diagnosed patients, linking them to adequate management and treatment. Raising treatment rates will increase the percentage of cured patients, reducing the burden of disease. Primary care physicians' role is essential to achieve this goal. They must identify persons at risk, diagnose them and work with specialists to continue their medical care. Team working of generalists and specialists will permit that more HCV infected people can access to adequate care and treatment.

  1. Chronic Hepatitis C Virus Infection: A Review of Current Direct-Acting Antiviral Treatment Strategies

    PubMed Central

    Zhang, Johnathan; Nguyen, Douglas; Hu, Ke-Qin

    2016-01-01

    Chronic Hepatitis C virus (HCV) infection carries a significant clinical burden in the United States, affecting more than 4.6 million Americans. Untreated chronic HCV infection can result in cirrhosis, portal hypertension, and hepatocellular carcinoma. Previous interferon based treatment carried low rates of success and significant adverse effects. The advent of new generation oral antiviral therapy has led to major improvements in efficacy and tolerability but has also resulted in an explosion of data with increased treatment choice complexity. Treatment guidelines are constantly evolving due to emerging regimens and real world treatment data. There also still remain subpopulations for whom current treatments are lacking or unclearly defined. Thus, the race for development of HCV treatment regimens still continues. This review of the current literature will discuss the current recommended treatment strategies and briefly overview next generation agents. PMID:27293521

  2. Search for a cure for chronic hepatitis B infection: How close are we?

    PubMed Central

    Phyo, Wah Wah; Soh, Alex Yu Sen; Lim, Seng Gee; Lee, Guan Huei

    2015-01-01

    Chronic hepatitis B (CHB) remains a significant unmet medical need, with 240 million chronically infected persons worldwide. It can be controlled effectively with either nucleoside/nucleotide-based or interferon-based therapies. However, most patients receiving these therapies will relapse after treatment withdrawal. During recent years, the advances in molecular biology and immunology have enabled a better understanding of the viral-host interaction and inspired new treatment approaches to achieve either elimination of the virus from the liver or durable immune control of the infection. This review aims to provide a brief overview on the potential new therapies that may overcome the challenge of persistent CHB infection in the near future. PMID:26019743

  3. Cryptococcal meningitis in a patient with chronic hepatitis C treated with pegylated-interferon and ribavirin.

    PubMed

    Lee, Tae-Hee; Lee, Kee-Ook; Kim, Yong-Seok; Kim, Sun-Moon; Huh, Kyu-Chan; Choi, Young-Woo; Kang, Young-Woo

    2014-05-01

    Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-α and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm(3), 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-α and ribavirin.

  4. Altered hepatic vasopressin and alpha 1-adrenergic receptors after chronic endotoxin infusion

    SciTech Connect

    Roth, B.L.; Spitzer, J.A.

    1987-05-01

    Sepsis and septic shock are complicated by a number of hemodynamic and metabolic aberrations. These include catecholamine refractoriness and altered glucose metabolism. Recently, a nonshock rat model of continuous endotoxin infusion via an implanted osmotic pump was developed that reproduces some of the metabolic and cardiovascular findings of human sepsis. By using this model, we have found a decreased number of hepatic plasma membrane alpha 1-adrenergic and (Arg8)vasopressin receptors in rats continuously infused with endotoxin. There was a significant decrease in (/sup 3/H)prazosin (35 +/- 7%) and (/sup 3/H) (Arg8)vasopressin (43 +/- 8%) receptors after 30 h of continuous endotoxin infusion with no change in affinity. The ability of norepinephrine to form the high-affinity complex with alpha 1-adrenergic receptors was not altered after chronic endotoxin infusion. The results are consistent with the concept that alterations in receptor number might underlie certain of the metabolic consequences of chronic sepsis.

  5. DNA vaccine therapy for chronic hepatitis C virus (HCV) infection: immune control of a moving target.

    PubMed

    Sällberg, Matti; Frelin, Lars; Weiland, Ola

    2009-07-01

    The use of DNA plasmids for DNA vaccination was first described in the early 1990 s. DNA vaccinations were successful in small animal models but in larger animals and humans problems appeared. One major obstacle, effective delivery, has been partly overcome by new delivery techniques, such as transdermal delivery with the gene gun, and in vivo electroporation. We are entering a new era of DNA vaccination, where such techniques can be tested in humans. DNA vaccination may be a useful therapy for chronic hepatitis C virus (HCV) infections. Patients with these infections have a reduced T cell response to the invading virus. The genetic variability of HCV, its immunomodulatory properties and high replication rate contribute to chronicity. By providing the correct stimulus T cells may be activated to clear the infection. The vaccination is intended to induce a coordinated immune-based attack on the continuously moving HCV target. If effective, this should help in clearing the infection.

  6. Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus.

    PubMed

    Wiersma, Steven T; McMahon, Brian; Pawlotsky, Jean-Michel; Thio, Chloe L; Thursz, Mark; Lim, Seng Gee; Ocama, Ponsiano; Esmat, Gamal; Mendy, Maimuna; Maimuna, Mendy; Bell, David; Vitoria, Marco; Eramova, Irina; Lavanchy, Daniel; Dusheiko, Geoff

    2011-07-01

    Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings.

  7. A chronic high-cholesterol diet paradoxically suppresses hepatic CYP7A1 expression in FVB/NJ mice.

    PubMed

    Henkel, Anne S; Anderson, Kristy A; Dewey, Amanda M; Kavesh, Mark H; Green, Richard M

    2011-02-01

    Cholesterol 7α-hydroxylase (CYP7A1) encodes for the rate-limiting step in the conversion of cholesterol to bile acids in the liver. In response to acute cholesterol feeding, mice upregulate CYP7A1 via stimulation of the liver X receptor (LXR) α. However, the effect of a chronic high-cholesterol diet on hepatic CYP7A1 expression in mice is unknown. We demonstrate that chronic cholesterol feeding (0.2% or 1.25% w/w cholesterol for 12 weeks) in FVB/NJ mice results in a >60% suppression of hepatic CYP7A1 expression associated with a >2-fold increase in hepatic cholesterol content. In contrast, acute cholesterol feeding induces a >3-fold upregulation of hepatic CYP7A1 expression. We show that chronic, but not acute, cholesterol feeding increases the expression of hepatic inflammatory cytokines, tumor necrosis factor (TNF)α, and interleukin (IL)-1β, which are known to suppress hepatic CYP7A1 expression. Chronic cholesterol feeding also results in activation of the mitogen activated protein (MAP) kinases, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, we demonstrate in vitro that suppression of CYP7A1 by TNFα and IL-1β is dependent on JNK and ERK signaling. We conclude that chronic high-cholesterol feeding suppresses CYP7A1 expression in mice. We propose that chronic cholesterol feeding induces inflammatory cytokine activation and liver damage, which leads to suppression of CYP7A1 via activation of JNK and ERK signaling pathways.

  8. Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation.

    PubMed Central

    Majano, P L; García-Monzón, C; López-Cabrera, M; Lara-Pezzi, E; Fernández-Ruiz, E; García-Iglesias, C; Borque, M J; Moreno-Otero, R

    1998-01-01

    Increased nitric oxide (NO) production may contribute to the pathological changes featuring in some inflammatory diseases, but the role of NO in chronic viral hepatitis is still unknown. We compared the inducible NO synthase (NOS2) expression in the liver of patients with chronic viral hepatitis with that of both nonviral liver disease and histologically normal liver. NOS2 expression was assessed by immunohistochemical and in situ hybridization studies of liver biopsy sections. An intense hepatocellular NOS2 reactivity was detected in chronic viral hepatitis, whereas it was weakly or not observed in nonviral liver disease or normal liver, respectively. In addition, we determined whether the hepatitis B virus (HBV) might regulate the synthesis of this enzyme. NOS2 mRNA and protein levels as well as enzyme activity were assessed in cytokine-stimulated HBV-transfected and untransfected hepatoma cells. Transfection with either HBV genome or HBV X gene resulted in induction of NOS2 mRNA expression, and the maximal induction of this transcript and NO production was observed in cytokine-stimulated HBV-transfected cells. These results indicate that hepatotropic viral infections are able to upregulate the NOS2 gene expression in human hepatocytes, suggesting that NO may mediate important pathogenic events in the course of chronic viral hepatitis. PMID:9525976

  9. Analysis of T cell repertoire in the liver of patients with chronic hepatitis C

    PubMed Central

    Umemura, T; Yoshizawa, K; Ota, M; Katsuyama, Y; Inada, H; Tanaka, E; Kiyosawa, K

    2000-01-01

    Many T cells infiltrate into the liver of patients with chronic hepatitis C (CH-C). They are believed to play a crucial role in the immunopathogenesis of hepatic inflammation, but their clonality and specificity are unknown. The aim of this study was to clarify the characteristics of these T cells. We analysed the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) β-chains by size spectratyping, and determined the sequences of Vβ CDR3 after subcloning Vβ-specific polymerase chain reaction products. Spectratyping showed clonal expansions in all liver specimens, most of which showed more than two T cell clones. Moreover, many non-clonal T cells also accumulated in the liver. Clonality of the T cells suspected by spectratyping was confirmed by CDR3 sequencing. Although the sequences revealed no whole CDR3-shared clones among different patients, some common motif sequences were observed. Our data suggest that T cells are stimulated by several hepatitis C virus (HCV) epitopes, then accumulate in the liver of CH-C patients. Shared motifs of expanded T cell clones suggest that they might recognize the same regions of HCV peptides, but have differences due to HCV peptide mutational changes. These clones might also interact with non-clonal T cells and play a crucial role in the immunopathogenesis of CH-C. PMID:10886248

  10. Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response

    PubMed Central

    Katrinli, Seyma; Enc, Feruze Yilmaz; Ozdil, Kamil; Ozturk, Oguzhan; Tuncer, Ilyas; Doganay, Gizem Dinler; Doganay, Levent

    2016-01-01

    OBJECTIVE: Chronic hepatitis B (CHB) is a major health problem. The outcome of hepatitis B virus (HBV) infection is associated with variations in HLA-DPA1 alleles. The aim of this study was to investigate possible associations of HLA-DPA1 alleles with treatment response and with hepatitis B virus e antigen (HBeAg) seroconversion. METHODS: Eight different HLA-DPA1 alleles from 246 CHB patients were genotyped by polymerase chain reaction with sequence-specific primers at high resolution to investigate the association of HLA-DPA1 alleles with treatment response, development of cirrhosis, HBeAg seroconversion, and disease reoccurrence upon HBeAg loss. RESULTS: There was no significant association between HLA-DPA1 alleles and treatment response, development of cirrhosis, or HBeAg seroconversion. However, HLA-DPA1*04:01 allele was significantly more frequently found in patients who redeveloped disease upon HBeAg seroconversion (100% vs 36.8%: p=0.037; Fisher’s exact test). CONCLUSION: HLA-DPA1*04:01 allele may be a risk factor for reoccurrence of CHB after HBeAg seroconversion. PMID:28275747

  11. Therapy of Chronic Hepatitis C in the Era of Nanotechnology: Drug Delivery Systems and Liver Targeting.

    PubMed

    Cuestas, Maria Lujan

    2017-01-01

    Since the British scientist Michael Houghton along with George Kuo, Qui-Lim Choo (Chiron Corporation Emeryville), and Daniel W. Bradley (Centers for Disease Control and Prevention) codiscovered the causative agent of hepatitis C in 1989, so much progress has been made for the screening of blood donors and management of this chronic liver disease. In this regard, direct-acting antiviral agents (DAAs) have emerged as the potential "cure" of this slowly progressing and devastating disease. However, improvements are still clearly required since the anti-hepatitis C drugs currently available in the market are so extremely expensive (i.e. $94,500 for a 12-week course of treatment), that many patients will have a denied access to such drugs by their insurers.

    In the last few years, nanotechnology has emerged as a new platform for drug development, contributing significantly to the improvement of the administration and delivery of many drugs. Additionally, nanotechnologies can provide unique solutions even in poorer societies.

    This manuscript reviews the current knowledges on the available anti-hepatitis C drugs and the new drug candidates being investigated as well, and introduces the recent advances in nanocarrier-based delivery systems. Finally, the challenges in the development of drug delivery systems for the targeting of antiviral drugs to the liver are also discussed.

  12. Paraproteins with antibody activity in acute viral hepatitis and chronic autoimmune liver diseases

    PubMed Central

    Roux, Maria E. B.; Florin-Christensen, A.; Arana, R. M.; Doniach, Deborah

    1974-01-01

    Of 27 patients with liver disease and cryoglobulinaemia 18 proved to have paraproteins. Six of these monoclonal immunoglobulins were shown to have antibody activity, directed to human gamma globulin, alpha1-fetoprotein, smooth muscle, and mitochondria. Eight of the patients suffered from acute viral hepatitis, five of whom were HB Ag positive; in all these cases the monoclonal spikes were transient and their antibody activities were directed against IgG in two cases and alpha1-fetoprotein in one. Seven of the patients had active chronic hepatitis and in these the paraproteinaemia persisted, though remaining quantitatively unchanged over several years. One of them had a cryoprecipitable monoclonal smooth muscle antibody. Three patients had primary biliary cirrhosis and in two of them monoclonal IgM mitochondrial antibodies were demonstrated. In three out of the 18 cases there was a double M-component. Since these monoclonal antibodies are directed to autoantigens not unlike the polyclonal ones usually seen in autoimmune hepatic diseases, it is suggested that the factor which triggers the uncontrolled plasma cell proliferation to produce paraproteins must meet cells from an already expanding clone. PMID:18668850

  13. A Retrospective Study on the Significance of Liver Biopsy and Hepatitis B Surface Antigen in Chronic Hepatitis B Infection

    PubMed Central

    Zeng, Da-Wu; Zhang, Jie-Min; Liu, Yu-Rui; Dong, Jing; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-01-01

    Abstract To investigate changes in the HBV replication level along with the natural course of chronic HBV infection and to examine the accuracy of the immune tolerant phase defined by the serological profile. A total of 390 chronic HBV-infected patients were retrospectively recruited for this study. They were classified into immune-tolerance (IT), immune-clearance (IC), low-replicative (LR), and HBeAg-negative hepatitis (ENH) phases according to serological profiles (single-standard, SS) or dual-standard (DS) with the inclusion of liver histology. Serum HBV DNA and HBsAg were quantitatively measured, and liver histology was quantitatively analyzed. The accuracy of the SS-defined IT phase was low, and active pathological changes were detected in 56 of 112 SS-defined IT patients. DS-defined IT patients had higher HBsAg levels (P = 0.0002) than the SS-defined patients. The quantitative HBsAg level can help identify SS-defined IT patients with potential liver injury. The area under the received operating characteristic curve for predicting the DS-defined IT phase was 0.831 (HBsAg 4.398 log IU/mL; sensitivity 87.5%; specificity 73.2%). HBV DNA was reduced by 4 logs, whereas HBsAg was only decreased by 2 logs with HBeAg positive to negative phase conversion. Approximately half of IT patients defined by SS may have medium or severe liver injury. Quantitative measurement of the HBsAg level can help identify SS-defined IT patients with potential liver injury. PMID:26937895

  14. Comparison of collagen proportionate areas in liver fibrosis quantification between chronic hepatitis B and C

    PubMed Central

    Chen, Sheng-Hung; Peng, Cheng-Yuan; Chiang, I-Ping; Lai, Hsueh-Chou; Lee, Chiung-Ju; Su, Wen-Pang; Kao, Jung-Ta; Chuang, Po-Heng

    2016-01-01

    Abstract Few studies have compared the distinct hepatic collagen morphometrics of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). This study compared the discrepancies between CHB and CHC in liver fibrosis (F) quantification by using the collagen proportionate area (CPA) and liver stiffness (LS) measured with shear wave velocity (SWV). This study enrolled 274 eligible consecutive patients diagnosed with CHB (n = 137) or CHC (n = 137). Their ages ranged from 20 to 80 years (median = 50). In total, 154 patients (56.2%) were male. Participant LS was measured by using acoustic radiation force impulse elastography preceding an immediate percutaneous liver biopsy. The total proportion of the collagen stained with picrosirius red to the total tissue area was expressed as the CPA percentage, which was stratified into portal–bridging (PB) and perisinusoidal (PS) proportionate areas (PAs). Based on the METAVIR F staging system, 36 (26.3%), 36 (26.3%), 28 (20.4%), and 37 (27.0%) participants in the CHB group and 34 (24.8%), 45 (32.9%), 34 (24.8%), and 24 (17.5%) participants in the CHC group were staged as F1, F2, F3, and F4, respectively. Both the total CPAs and PBPAs were significantly (P < 0.05) higher in the CHC group than in the CHB group within all F-stratified subgroups. The SWVs were significantly (P < 0.05) higher in the CHC group than in the CHB group only within the F2, F3, and F4 subgroups. However, the PSPAs did not differ significantly between the CHC and CHB groups within all subgroups. Multiple regression analysis revealed that viral hepatitis etiology (P < 0.001), METAVIR F stages (P < 0.001), and platelet count (P = 0.007) were independent factors correlated with the CPA (R2 = 0.543, P < 0.001). In conclusion, both the F stage-stratified CPAs and SWVs tended to be higher in cases of CHC than in those of CHB. The type of viral hepatitis significantly affected both the CPA and SWV values. The PBPAs were more

  15. Comparative performance evaluation of hepatitis C virus genotyping based on the 5' untranslated region versus partial sequencing of the NS5B region of brazilian patients with chronic hepatitis C

    PubMed Central

    2011-01-01

    Background Genotyping of hepatitis C virus (HCV) has become an essential tool for prognosis and prediction of treatment duration. The aim of this study was to compare two HCV genotyping methods: reverse hybridization line probe assay (LiPA v.1) and partial sequencing of the NS5B region. Methods Plasma of 171 patients with chronic hepatitis C were screened using both a commercial method (LiPA HCV Versant, Siemens, Tarrytown, NY, USA) and different primers targeting the NS5B region for PCR amplification and sequencing analysis. Results Comparison of the HCV genotyping methods showed no difference in the classification at the genotype level. However, a total of 82/171 samples (47.9%) including misclassification, non-subtypable, discrepant and inconclusive results were not classified by LiPA at the subtype level but could be discriminated by NS5B sequencing. Of these samples, 34 samples of genotype 1a and 6 samples of genotype 1b were classified at the subtype level using sequencing of NS5B. Conclusions Sequence analysis of NS5B for genotyping HCV provides precise genotype and subtype identification and an accurate epidemiological representation of circulating viral strains. PMID:21967749

  16. Hepatitis C virus (HCV) and hepatitis B virus (HBV) can coinfect the same hepatocyte in the liver of patients with chronic HCV and occult HBV infection.

    PubMed

    Rodríguez-Iñigo, E; Bartolomé, J; Ortiz-Movilla, N; Platero, C; López-Alcorocho, J M; Pardo, M; Castillo, I; Carreño, V

    2005-12-01

    In this work, we have shown that hepatitis C virus (HCV) and hepatitis B virus (HBV) can coexist in the same hepatocyte using double fluorescent in situ hybridization in liver biopsy samples from patients with chronic HCV infection with occult HBV infection. Digital image analysis of hybridization signals showed that the HBV DNA levels in coinfected hepatocytes were lower than those in cells infected only with HBV. This finding supports the hypothesis of inhibition of HBV replication by HCV. Furthermore, HCV RNA levels were lower in coinfected cells than in cells infected only with HCV, suggesting that HBV may also inhibit HCV replication.

  17. Parallel expression profiling of hepatic and serum microRNA-122 associated with clinical features and treatment responses in chronic hepatitis C patients.

    PubMed

    Butt, Azeem Mehmood; Raja, Arsalan Jamil; Siddique, Shafiqa; Khan, Jahangir Sarwar; Shahid, Muhammad; Tayyab, Ghias-Un-Nabi; Minhas, Zahid; Umar, Muhammad; Idrees, Muhammad; Tong, Yigang

    2016-02-22

    MicroRNAs (miRNAs) are small, non-coding RNAs that regulate a variety of biological processes. Recently, human liver-specific miRNA miR-122 has been reported to facilitate hepatitis C virus (HCV) replication in liver cells. HCV is one of the leading causes of liver diseases worldwide. In Pakistan, the estimated prevalence is up to 10%. Here, we report hepatic and serum miR-122 expression profiling from paired liver and serum samples from treatment-naive chronic hepatitis C (CHC) patients and controls. We aimed to elucidate the biomarker potential of serum miR-122 for monitoring disease progression and predicting end treatment response (ETR). Hepatic miR-122 levels were significantly down-regulated in CHC patients. A significant inverse correlation was observed between hepatic and serum miR-122 levels, indicating that serum miR-122 levels reflect HCV-associated disease progression. Both hepatic and serum miR-122 were significantly correlated (P < 0.05) with several clinicopathological features of CHC. Receiver operator curve analysis showed that serum miR-122 had superior discriminatory ability even in patients with normal alanine transaminase levels. Multivariate logistic regression analysis highlighted pre-treatment serum miR-122 levels as independent predictors of ETR. In conclusion, serum miR-122 holds the potential to serve as a promising biomarker of disease progression and ETR in CHC patients.

  18. Evaluation of Hepatic Tissue Blood Flow Using Xenon Computed Tomography with Fibrosis Progression in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis C

    PubMed Central

    Shigefuku, Ryuta; Takahashi, Hideaki; Kato, Masaki; Yoshida, Yoshihito; Suetani, Keigo; Noguchi, Yohei; Hatsugai, Moriaki; Nakahara, Kazunari; Ikeda, Hiroki; Kobayashi, Minoru; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Okuse, Chiaki; Itoh, Fumio; Maeyama, Shiro; Sase, Shigeru; Suzuki, Michihiro

    2014-01-01

    Aims The present study evaluated the utility of xenon computed tomography (Xe-CT) as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF) in patients with nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (CH-C). Methods Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. Results In group 1, portal venous TBF (PVTBF), hepatic arterial (HATBF), and total hepatic TBF (THTBF) were significantly lower in patients with in nonalcoholic steatohepatitis (NASH) than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively). In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively). In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. Conclusions PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage. PMID:24424317

  19. Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B

    PubMed Central

    Liu, Ping; Hu, Yi-Yang; Liu, Cheng; Zhu, Da-Yuan; Xue, Hui-Ming; Xu, Zhi-Qiang; Xu, Lie- Ming; Liu, Cheng-Hai; Gu, Hong-Tu; Zhang, Zhi-Qing

    2002-01-01

    AIM: To evaluate the clinical efficacy of salvianolic acid B (SA-B) on liver fibrosis in chronic hepatitis B. METHODS: Sixty patients with definite diagnosis of liver fibrosis with hepatitis B were included in the trial. Interferon-γ (IFN-γ) was used as control drug. The patients took orally SA-B tablets or received muscular injection of IFN-γ in the double blind randomized test. The complete course lasted 6 mo. The histological changes of liver biopsy specimen before and after the treatment were the main evidence in evaluation, in combination with the results of contents of serum HA, LN, IV-C, P-III-P, liver ultrasound imaging, and symptoms and signs. RESULTS: Reverse rate of fibrotic stage was 36.67% in SA-B group and 30.0% in IFN-γ group. Inflammatory alleviating rate was 40.0% in SA-B group and 36.67% in IFN-γ group. The average content of HA and IV-C was significantly lower than that before treatment. The abnormal rate also decreased remarkably. Overall analysis of 4 serological fibrotic markers showed significant improvement in SA-B group as compared with the IFN-γ group. Score of liver ultrasound imaging was lower in SA-B group than in IFN-γ group (HA 36.7% vs 80%, IV-C 3.3% vs 23.2%). Before the treatment, ALT AST activity and total bilirubin content of patients who had regression of fibrosis after oral administration of SA-B, were significantly lower than those of patients who had aggravation of fibrosis after oral administration of SA-B. IFN-γ showed certain side effects (fever and transient decrease of leukocytes, occurrence rates were 50% and 3.23%), but SA-B showed no side effects. CONCLUSION: SA-B could effectively reverse liver fibrosis in chronic hepatitis B. SA-B was better than IFN-γ in reduction of serum HA content, overall decrease of 4 serum fibrotic markers, and decrease of ultrasound imaging score. Liver fibrosis in chronic hepatitis B with slight liver injury was more suitable to SA-B in anti-fibrotic treatment. SA-B showed no

  20. Enhanced Liver Fibrosis (ELF) test accurately identifies liver fibrosis in patients with chronic hepatitis C.

    PubMed

    Parkes, J; Guha, I N; Roderick, P; Harris, S; Cross, R; Manos, M M; Irving, W; Zaitoun, A; Wheatley, M; Ryder, S; Rosenberg, W

    2011-01-01

    Assessment of liver fibrosis is important in determining prognosis and evaluating interventions. Due to limitations of accuracy and patient hazard of liver biopsy, non-invasive methods have been sought to provide information on liver fibrosis, including the European liver fibrosis (ELF) test, shown to have good diagnostic accuracy for the detection of moderate and severe fibrosis. Access to independent cohorts of patients has provided an opportunity to explore if this test could be simplified. This paper reports the simplification of the ELF test and its ability to identity severity of liver fibrosis in external validation studies in patients with chronic hepatitis C (CHC). Paired biopsy and serum samples from 347 naïve patients with CHC in three independent cohorts were analysed. Diagnostic performance characteristics were derived (AUROC, sensitivity and specificity, predictive values), and clinical utility modelling performed to determine the proportion of biopsies that could have been avoided if ELF test was used in this patient group. It was possible to simplify the original ELF test without loss of performance and the new algorithm is reported. The simplified ELF test was able to predict severe fibrosis [pooled AUROC of 0.85 (95% CI 0.81-0.89)] and using clinical utility modelling to predict severe fibrosis (Ishak stages 4-6; METAVIR stages 3 and 4) 81% of biopsies could have been avoided (65% correctly). Issues of spectrum effect in diagnostic test evaluations are discussed. In chronic hepatitis C a simplified ELF test can detect severe liver fibrosis with good accuracy.

  1. Bell's palsy during interferon therapy for chronic hepatitis C infection in patients with haemorrhagic disorders.

    PubMed

    Ogundipe, O; Smith, M

    2000-03-01

    Two adult patients with life-long severe haemorrhagic disorders commenced on interferon-alpha2b therapy for chronic hepatitis C infection. Both developed Bell's palsy several weeks after commencing therapy, They were started on steroids and, in addition, the first patient discontinued interferon-alpha2b therapy while the second patient elected to continue with therapy. In both cases facial paralysis improved over the ensuing weeks. Bell's palsy is often idiopathic but has been reported. in association with herpesviruses. It is not a recognised complication of chronic hepatitis B or C infection, or interferon-alpha2b therapy. However, the interferons are associated with numerous adverse reactions including various neuropsychiatric manifestations and neurological syndromes. There are several reports of nerve palsies, including optic tract neuropathy, occurring during interferon therapy, and immune-based mechanisms are thought to play a role in the aetiopathogenesis. No reports of Bell's palsy in association with interferon therapy were identified in our literature search, although one possible case has been reported to the Committee of Safety in Medicine. Although Bell's palsy in our patients may have occurred by chance, a neuropathic effect of interferon-alpha2b on the facial nerve cannot be excluded and we urge physicians using interferons to be aware of this potential side-effect.

  2. Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis

    PubMed Central

    Milkiewicz, Malgorzata; Klak, Marta; Kempinska-Podhorodecka, Agnieszka; Wiechowska-Kozlowska, Anna; Urasinska, Elzbieta; Blatkiewicz, Malgorzata; Wunsch, Ewa; Elias, Elwyn; Milkiewicz, Piotr

    2016-01-01

    Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression. This was associated with increased OSTβ protein levels in each part of analyzed gut. An intestinal fibroblast growth factor (FGF19) protein expression was significantly enhanced in ascending colon. Despite increased hepatic nuclear receptors (FXR, CAR, SHP), and FGF19, neither CYP7A1 suppression nor CYP3A4 induction were observed. The lack of negative regulation of BA synthesis may be accountable for lower levels of cholesterol observed in PSC in comparison to primary biliary cholangitis (PBC). In conclusion, chronic cholestasis in PSC induces adaptive changes in expression of BA transporters and FXR in the intestine. However hepatic impairment of expected in chronic cholestasis downregulation of CYP7A1 and upregulation of CYP3A4 may promote BA-induced liver injury in PSC. PMID:28008998

  3. Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection

    PubMed Central

    Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

    2016-01-01

    Abstract Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. Clinical findings: We report a case of acute-onset CIDP that was initially diagnosed as GBS. Diagnoses: A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. Interventions: After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. Outcomes: A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Conclusion: Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered. PMID:27930572

  4. Knowledge and fears among Asian Americans chronically infected with hepatitis B.

    PubMed

    Carabez, Rebecca M; Swanner, J Anthony; Yoo, Grace J; Ho, Minh

    2014-09-01

    Asian Americans are disproportionately affected by hepatitis B (HBV) infection. In the USA, one in ten Asian Americans is infected with HBV. The purpose of the study was to explore knowledge, fears and follow-up care among Asian Americans chronically infected with hepatitis B. A sample of 154 completed an online survey which included demographic information, follow-up treatment information, and HBV knowledge and fears/concerns. Our findings indicate that there are differences by ethnicity and birthplace among Asian Americans in terms of follow-up care and treatment. In addition, our study indicates that there were substantial knowledge gaps regarding contracting HBV, transmission, and prevention. We found that HBV-infected respondents had many fears about their infection. Three primary concerns were identified: (a) concerns related to liver cancer and overall health, (b) transmission to loved ones, and (c) stigma. Our findings indicate that Asian Americans chronically infected with HBV need more education to manage HBV including information on the importance of follow-up treatment and care and education on preventing transmission, risk for liver cancer, and HBV impact on overall health.

  5. Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C

    PubMed Central

    Martini, Andrea; Gallotta, Andrea; Pontisso, Patrizia; Fassina, Giorgio

    2015-01-01

    Hepatitis C virus (HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide - fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M (SCCA-IgM), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-IgM may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology. PMID:26689503

  6. Controlled trial of a thymic hormone extract (Thymostimulin) in 'autoimmune' chronic active hepatitis.

    PubMed Central

    Hegarty, J E; Nouri Aria, K T; Eddleston, A L; Williams, R

    1984-01-01

    A randomised controlled trial of thymic hormone extracts (Thymostimulin) (1 mg/kg/day for seven days; 1 mg/kg/weekly thereafter) was undertaken in 30 patients (21 women, nine men) with treated, apparently inactive 'autoimmune' chronic active hepatitis during withdrawal of maintenance corticosteroid and azathioprine therapy. Reactivation of disease occurred in 26 patients (86%) during or after treatment withdrawal and was as frequent in the Thymostimulin treated (11 of 13; 84%) and untreated (15 of 17; 88%; p greater than 0.05) groups. Reactivation of disease was accompanied by a severe defect in concanavalin A induced suppressor cell activity, the magnitude of which was similar in the Thymostimulin treated and untreated groups (mean % suppression = 16.4 and 3.2 respectively; p greater than 0.05 vs 84.4 in control subjects). Further studies assessing the optimal dose, duration of treatment, and mode of administration are required to establish a therapeutic role for thymic hormone extracts in 'autoimmune' chronic active hepatitis. PMID:6230296

  7. Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey.

    PubMed

    Suzuki, Saori; Mori, Ken-Ichi; Higashino, Atsunori; Iwasaki, Yuki; Yasutomi, Yasuhiro; Maki, Noboru; Akari, Hirofumi

    2016-01-01

    The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (<200 copies/mL), the viral RNA loads in plasma were detectable intermittently during the observation period. Of note, the chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.

  8. Assessment of indicators of vitamin A status in non-cirrhotic chronic hepatitis C patients.

    PubMed

    Santana, R C; Machado, A A; Martinelli, A L C; Jordão, A A; Ramalho, L N Z; Vannucchi, H

    2016-01-01

    Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.

  9. Relationship between nephrotoxicity and long-term adefovir dipivoxil therapy for chronic hepatitis B

    PubMed Central

    Luo, Qing; Deng, Yong; Cheng, Feifei; Kang, Juan; Zhong, Shan; Zhang, Dazhi; Zeng, Weiqiong

    2016-01-01

    Abstract Background: To assess the relationship between adefovir dipivoxil and renal function after anti-hepatitis B virus therapy and elucidate the risk factors involved. Methods: Based on the requirements of the Cochrane systematic review methodology, 21 observational articles on adefovir dipivoxil-associated renal dysfunction were obtained by searching various databases, between January 1, 1995 and July 1, 2016. The Newcastle Ottawa Scale was used to evaluate risk bias. Parameters for 4276 chronic hepatitis B patients were analyzed by Review Manager and R software, and glomerular filtration rate, creatinine clearance, and serum creatinine values were extracted to evaluate renal function. Results: Renal dysfunction was more likely to occur in patients receiving the adefovir dipivoxil therapy (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.40–2.80) than the none-adefovir dipivoxil group. Subgroup analysis showed that renal function predictive value is higher for glomerular filtration rate (OR 2.42, 95% CI 1.34–3.14), compared with serum creatinine levels (OR 1.51, 95% CI 0.75–3.04). The rate of adefovir dipivoxil-associated renal dysfunction was 12% (95% CI 0.08–0.16). Older patients and patients with renal insufficiency, hypertension, and diabetes mellitus were more prone to developing adefovir dipivoxil-associated renal dysfunction; however, integrated raw data were insufficient for further detailed analysis. Conclusion: Long-term adefovir dipivoxil therapy is connected to renal dysfunction in chronic hepatitis B, necessitating the monitoring of kidney function. PMID:27977591

  10. Assessment of indicators of vitamin A status in non-cirrhotic chronic hepatitis C patients

    PubMed Central

    Santana, R.C.; Machado, A.A.; Martinelli, A.L.C.; Jordão, A.A.; Ramalho, L.N.Z.; Vannucchi, H.

    2015-01-01

    Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels. PMID:26577844

  11. Fibrosis Progression in Chronic Hepatitis C: Morphometric Image Analysis in the HALT-C Trial

    PubMed Central

    Goodman, Zachary D.; Stoddard, Anne M.; Bonkovsky, Herbert L.; Fontana, Robert J.; Ghany, Marc G.; Morgan, Timothy R.; Wright, Elizabeth C.; Brunt, Elizabeth M.; Kleiner, David E.; Shiffman, Mitchell L.; Everson, Gregory T.; Lindsay, Karen L.; Dienstag, Jules L.; Morishima, Chihiro

    2013-01-01

    Computer-assisted morphometry can provide precise measurement of hepatic fibrosis on a continuous scale. Previous morphometric studies of large cohorts of patients with treatment refractory chronic hepatitis C showed a mean increase in fibrosis of 30% to 58% in one year. The aim of the present study was to quantify fibrosis progression in biopsies obtained over 1.5 to 5 years from three groups of patients with baseline bridging fibrosis or cirrhosis (Ishak stages 3-6) enrolled in the HALT-C Trial. Results The main group of 346 lead-in nonresponders (viremic after 24 weeks of peginterferon-ribavirin therapy) had a mean fibrosis increase of 61% over pretreatment baseline after 2 years and 80% after 4 years. In contrast, the 78 “breakthrough/relapse” patients (undetectable serum HCV RNA after 24 weeks of peginterferon-ribavirin and receiving antiviral therapy for 48 weeks) showed a mean increase in fibrosis of 48% when biopsied 36 months from pretreatment baseline but no further increase at 60 months. Finally, the 111 “express” patients with baseline biopsies following unsuccessful peginterferon-ribavirin outside the trial, had significantly more baseline fibrosis than the others but an increase of only 21% after 21 months and a slight decrease at 45 months. Maintenance therapy with low-dose peginterferon had no effect on fibrosis changes in any of the groups. Conclusion Morphometry demonstrated complex, nonlinear changes in fibrosis over time in this heterogeneous cohort of patients with interferon-refractory chronic hepatitis C. PMID:19824074

  12. [Changes of humoral and cellular immunity in chronic hepatitis C patients of different staging].

    PubMed

    Masalova, O V; Abdulmedzhidova, A G; Morgunov, K V; Grishchenko, S V; Shkurko, T V; Lakina, E I; Kelli, E I; L'vov, D K; Kushch, A A

    2003-01-01

    The purpose of the present study was to investigate the influence produced by viral proteins in the hepatic cells and RNA of hepatitis C virus (HCV) on the indices of T- and B-cell response in 52 patients with chronic hepatitis C (CHC). A relative count of peripheral-blood lymphocytes (PBL), expressing antigens CD3+, CD4+, CD8+, CD16+, CD20+ and CD95+ was estimated. The repertoire of antibodies to HCV proteins was specified. The thus obtained data were compared with an activity and a disease stage by using the histological diagnosis and alanine-amino-transferase (ALT) level as well as with the presence of HCV RNA in the serum and viral protein of the liver. Such comparison of data and the use of the correlation analysis made it possible to establish that the antibodies to NS5 protein were detected reliably more often in patients with a more pronounced hepatic fibrosis, with a higher ALT activity and with expression of HCV proteins in the liver. At the same time, the presence of proteins in the liver and of RNA in the serum were accompanied by a more active humoral response to the non-structure proteins of NS4 and NS5 as well as by more profound discrepancies of the immunity T-cell chain (a lowered ratio of CD4+/CD8+ and a smaller content of CD95+). There were no differences between PBL of the studied populations in patients with various activities and an HCV stage. A relatively bigger quantity of CD95(+)--positive PBL was found to be reliably higher in patients with viremia but lower in those cases, in which HCV proteins were detected in the liver. This confirms the inhibiting ability of HCV proteins to the Fas-mediated apoptose of PBL in CHC patient.

  13. Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C

    PubMed Central

    Svegliati-Baroni, Gianluca; Faraci, Graziella; Fabris, Luca; Saccomanno, Stefania; Cadamuro, Massimiliano; Pierantonelli, Irene; Trozzi, Luciano; Bugianesi, Elisabetta; Guido, Maria; Strazzabosco, Mario; Benedetti, Antonio; Marchesini, Giulio

    2013-01-01

    Objective To study the mechanism(s) linking insulin resistance (IR) to hepatic fibrosis and the role of the epithelial component in tissue repair and fibrosis in chronic hepatitis C (CHC). Design Prospective observational study. Setting Tertiary care academic centre. Patients 78 consecutive patients with CHC. Main outcome measures IR, calculated by the oral glucose insulin sensitivity during oral glucose tolerance test; necroinflammatory activity and fibrosis, defined according to Ishak’s score; steatosis, graded as 0 (<5% of hepatocytes), 1 (5–33%), 2 (33–66%) and 3 (>66%). To evaluate the role of the epithelial component in tissue repair and fibrosis, the expansion of the ductular reaction (DR) was calculated by keratin-7 (CK7) morphometry. Nuclear expression of Snail, downregulation of E-cadherin and expression of fibroblast specific protein-1 (FSP1) and vimentin by CK7-positive cells were used as markers of epithelial-mesenchymal transition in DR elements. Results IR, the degree of necroinflammation and expansion of the DR (stratified as reactive ductular cells (RDCs), hepatic progenitor cells and intermediate hepatobiliary cells according to morphological criteria) were all associated with the stage of fibrosis. Nuclear Snail expression, E-cadherin downregulation and vimentin upregulation were observed in RDCs. By dual immunofluorescence for CK7 and FSP1, the number of RDCs undergoing epithelial-mesenchymal transition progressively increased together with the necroinflammatory score. By multivariate analysis, total inflammation and insulin resistance were the only factors significantly predicting the presence of advanced fibrosis (Ishak score ≥3) and the expansion of RDCs. Conclusion This study indicates that IR is associated with the degree of necroinflammatory injury in CHC and contributes to hepatic fibrosis by stimulating the expansion of RDCs that express epithelial-mesenchymal transition markers. PMID:20966027

  14. Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C

    PubMed Central

    Yamagiwa, Satoshi; Ishikawa, Toru; Waguri, Nobuo; Sugitani, Soichi; Wakabayashi, Hiroto; Ohkoshi, Shogo; Tsukishiro, Takashi; Takahashi, Toru; Watanabe, Toshiaki; Terai, Shuji

    2017-01-01

    AIM To evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. METHODS The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment. RESULTS Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P < 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups (91.6% vs 81

  15. Regulatory and activated effector T cells in chronic hepatitis C virus: Relation to autoimmunity

    PubMed Central

    Fouad, Hanan; El Raziky, Maissa; Hassan, Eman Medhat; Aziz, Ghada Mahmoud Abdel; Darweesh, Samar K; Sayed, Ahmed Reda

    2016-01-01

    AIM To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTS Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSION Elevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response. PMID:27843539

  16. Hepatitis B e Antigen Status and Hepatitis B DNA Levels in Women of Childbearing Age with Chronic Hepatitis B Infection Screening for Clinical Trials

    PubMed Central

    Tran, Tram T.; Gordon, Stuart C.; Fung, Scott; Dinh, Phillip; Yee, Leland; Martins, Eduardo Bruno; Buti, Maria; Marcellin, Patrick

    2015-01-01

    Background Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load. Aim To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials. Methods Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18–69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive. Results Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load. Conclusions Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load. PMID:25789483

  17. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  18. Detection of Clonally Expanded Hepatocytes in Chimpanzees with Chronic Hepatitis B Virus Infection ▿ †

    PubMed Central

    Mason, William S.; Low, Huey-Chi; Xu, Chunxiao; Aldrich, Carol E.; Scougall, Catherine A.; Grosse, Arend; Clouston, Andrew; Chavez, Deborah; Litwin, Samuel; Peri, Suraj; Jilbert, Allison R.; Lanford, Robert E.

    2009-01-01

    During a hepadnavirus infection, viral DNA integrates at a low rate into random sites in the host DNA, producing unique virus-cell junctions detectable by inverse nested PCR (invPCR). These junctions serve as genetic markers of individual hepatocytes, providing a means to detect their subsequent proliferation into clones of two or more hepatocytes. A previous study suggested that the livers of 2.4-year-old woodchucks (Marmota monax) chronically infected with woodchuck hepatitis virus contained at least 100,000 clones of >1,000 hepatocytes (W. S. Mason, A. R. Jilbert, and J. Summers, Proc. Natl. Acad. Sci. USA 102:1139-1144, 2005). However, possible correlations between sites of viral-DNA integration and clonal expansion could not be explored because the woodchuck genome has not yet been sequenced. In order to further investigate this issue, we looked for similar clonal expansion of hepatocytes in the livers of chimpanzees chronically infected with hepatitis B virus (HBV). Liver samples for invPCR were collected from eight chimpanzees chronically infected with HBV for at least 20 years. Fifty clones ranging in size from ∼35 to 10,000 hepatocytes were detected using invPCR in 32 liver biopsy fragments (∼1 mg) containing, in total, ∼3 × 107 liver cells. Based on searching the analogous human genome, integration sites were found on all chromosomes except Y, ∼30% in known or predicted genes. However, no obvious association between the extent of clonal expansion and the integration site was apparent. This suggests that the integration site per se is not responsible for the outgrowth of large clones of hepatocytes. PMID:19535448

  19. The Effect of Chronic Hepatitis B Virus Infection on BDCA3+ Dendritic Cell Frequency and Function

    PubMed Central

    van der Aa, Evelyn; Buschow, Sonja I.; Biesta, Paula J.; Janssen, Harry L. A.; Woltman, Andrea M.

    2016-01-01

    Chronic hepatitis B virus (HBV) infection results from inadequate HBV-specific immunity. BDCA3+ dendritic cells (DCs) are professional antigen presenting cells considered to be important for antiviral responses because of specific characteristics, including high interferon-λ production. BDCA3+ DCs may thus also have a role in the immune response against HBV, and immunotherapeutic strategies aiming to activate DCs, including BDCA3+ DCs, in patient livers may represent an interesting treatment option for chronic HBV. However, neither the effect of chronic hepatitis B (CHB) infection on the frequency and function of BDCA3+ DCs in liver and blood, nor the effect of the viral surface protein (HBsAg) that is abundantly present in blood of infected individuals are known. Here, we provide an overview of BDCA3+ DC frequency and functional capacity in CHB patients. We find that intrahepatic BDCA3+ DC numbers are increased in CHB patients. BDCA3+ DCs from patient blood are not more mature at steady state, but display an impaired capacity to mature and to produce interferon-λ upon polyI:C stimulation. Furthermore, in vitro experiments exposing blood and intrahepatic BDCA3+ DCs to the viral envelope protein HBsAg demonstrate that HBsAg does not directly induce phenotypical maturation of BDCA3+ DCs, but may reduce IFN-λ production via an indirect unknown mechanism. These results suggest that BDCA3+ DCs are available in the blood and on site in HBV infected livers, but measures may need to be taken to revive their function for DC-targeted therapy. PMID:27529176

  20. Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection

    PubMed Central

    ZHANG, QINGQING; XU, MINGYI; QU, YING; LI, ZHENGHONG; ZHANG, QIDI; CAI, XIAOBO; LU, LUNGEN

    2015-01-01

    Considering the limitations of liver biopsy, reliable non-invasive serum biomarkers of liver fibrosis are required for early diagnosis. The present study analyzed the expression profile of circulating micro (mi)RNAs during the development and progression of hepatic fibrosis in patients with chronic hepatitis B virus (HBV) infection, aiming to identify novel earlier diagnostic biomarkers. Fresh plasma samples were collected from 50 patients diagnosed with chronic HBV infection and hepatic fibrosis. These patients were classified into five groups (S0, S1, S2, S3 and S4; n=10 per group) based on Scheuer's staging criteria. The differential expression of the circulating miRNAs was determined by performing miRNA microarray hybridization. Finally, the target genes of the miRNAs were predicted and classified using gene ontology analysis. A total of 140 miRNAs were detected in the S1–S4 patient groups, and their expression levels were >2-fold higher compared with those in the S0 group. The numbers of miRNAs differentially expressed in the S1–S4 patient groups were 48, 97, 84 and 56, respectively, with 12 miRNAs differentially expressed at all stages, 10 of which were upregulated and two of which were downregulated. The target genes of the miRNAs identified were found to be involved in 100 signal transduction pathways, the majority of which affected hepatic fibrosis via the TGF-/Smad, Wnt, MAPK, Jak/STAT and VEGF pathways. The differential expression levels of miRNAs were closely associated with the staging of hepatic fibrosis. The results of the present study provide evidence to facilitate the development and application of non-invasive biomarkers for earlier diagnosis of hepatic fibrosis. PMID:26299203

  1. Aflatoxin levels in chronic hepatitis B patients with cirrhosis or hepatocellular carcinoma in Balıkesir, Turkey.

    PubMed

    Aydın, M; Aydın, S; Bacanlı, M; Başaran, N

    2015-11-01

    Aflatoxins, the secondary metabolites produced by species of naturally occurring Aspergilli, are commonly found in food such as cereals, dried fruits and juice, wine, beer and spices. They are hepatotoxic and are well known human carcinogens based on evidence from human studies. Aflatoxins are an environmental risk factor for the development of hepatocellular carcinoma (HCC). Chronic hepatitis B-infected patients are at increased risk of cirrhosis, hepatic failure and liver cancer. This study was designed to determine the serum aflatoxin B1 (AFB1 ), aflatoxin B2 (AFB2 ), aflatoxin G1 (AFG1 ) and aflatoxin G2 (AFG2 ) concentrations using high-pressure liquid chromatography (HPLC) in hepatitis B-infected patients with or without cirrhosis and liver cancer, alongside healthy controls in Balıkesir, Turkey. The mean AFB1 and total AF levels in patients without liver cancer and cirrhosis were significantly higher than healthy controls. The mean AFB1 and total AF levels in patients with chronic hepatitis B and HCC were significantly higher than infected patients with or without cirrhosis. These results suggest that patients with chronic hepatitis B who are exposed to AFs are at increased risk for developing HCC, which might be prevented by reducing consumption of contaminated foods.

  2. AIC649 Induces a Bi-Phasic Treatment Response in the Woodchuck Model of Chronic Hepatitis B

    PubMed Central

    Paulsen, Daniela; Weber, Olaf; Ruebsamen-Schaeff, Helga; Tennant, Bud C.; Menne, Stephan

    2015-01-01

    AIC649 has been shown to directly address the antigen presenting cell arm of the host immune defense leading to a regulated cytokine release and activation of T cell responses. In the present study we analyzed the antiviral efficacy of AIC649 as well as its potential to induce functional cure in animal models for chronic hepatitis B. Hepatitis B virus transgenic mice and chronically woodchuck hepatitis virus (WHV) infected woodchucks were treated with AIC649, respectively. In the mouse system AIC649 decreased the hepatitis B virus titer as effective as the “gold standard”, Tenofovir. Interestingly, AIC649-treated chronically WHV infected woodchucks displayed a bi-phasic pattern of response: The marker for functional cure—hepatitis surface antigen—first increased but subsequently decreased even after cessation of treatment to significantly reduced levels. We hypothesize that the observed bi-phasic response pattern to AIC649 treatment reflects a physiologically “concerted”, reconstituted immune response against WHV and therefore may indicate a potential for inducing functional cure in HBV-infected patients. PMID:26656974

  3. Effect of chronic ethanol on hepatic apolipoprotein (Apo)E glycosylation

    SciTech Connect

    Ghosh, P.; Okoh, C.; Chirtel, S.J.; Liu, Q.H.; Lakshman, M.R. George Washington Univ., Washington, DC )

    1991-03-15

    The authors have previously shown that chronic ethanol feeding significantly inhibits the secretion of ApoE in rats. Since many carbohydrate precursors are essential for the synthesis of mature ApoE before it is secreted, the authors have investigated the effects of chronic ethanol on the incorporation of these precursors into ApoE. Male Wistar rats were divided into groups and were pair-fed with Control and Ethanol liquid diets for a period of 8 weeks. At the end, hepatocytes were isolated from each group and {approximately}400 mg cells were incubated in 8 ml final volume of Krebs bicarbonate buffer, pH 7.4 for 30 min. at 37C with the following labeled precursors individually: (2-{sup 3}H)mannose, (6-{sup 3}H)N-acetyl mannosamine, (4,5-{sup 3}H)galactose, (5,6-{sup 3}H)fucose, and (4,5-{sup 3}H)leucine. The incorporation of each precursor into immunoprecipitable ApoE was measured in cell homogenate, microsome and the Golgi fractions. The results showed that chronic ethanol treatment did not significantly inhibit the incorporation of leucine, fucose and galactose into ApoE at any of the subcellular levels. In contrast, chronic ethanol inhibited the incorporation of: (a) mannose into ApoE by 38% both at whole cell and at microsomal level and (b) N-acetyl mannosamine by 26% at the whole cell level and at the Golgi level. Based on these results, it is concluded that chronic ethanol feeding impairs the mannosylation and sialylation of ApoE in rat liver probably by altering the structure and functions of hepatic microsome and Golgi.

  4. Abbott RealTime Hepatitis C Virus (HCV) and Roche Cobas AmpliPrep/Cobas TaqMan HCV Assays for Prediction of Sustained Virological Response to Pegylated Interferon and Ribavirin in Chronic Hepatitis C Patients ▿

    PubMed Central

    Matsuura, Kentaro; Tanaka, Yasuhito; Hasegawa, Izumi; Ohno, Tomoyoshi; Tokuda, Hiroshi; Kurbanov, Fuat; Sugauchi, Fuminaka; Nojiri, Shunsuke; Joh, Takashi; Mizokami, Masashi

    2009-01-01

    Two commercial real-time PCR assays are currently available for sensitive hepatitis C virus (HCV) RNA quantification: the Abbott RealTime HCV assay (ART) and Roche Cobas AmpliPrep/Cobas TaqMan HCV assay (CAP/CTM). We assessed whether the two real-time PCR assays were more effective than Roche Cobas Amplicor HCV Monitor test, v.2.0 (CAM) for prediction of the sustained virological response (SVR) to pegylated interferon (PEG-IFN) plus ribavirin (RBV) in chronic hepatitis C. Sixty patients chronically infected with HCV genotype 1b (37 males and 23 females, 53 ± 12 years of age) were treated with PEG-IFNα2b plus RBV for 48 weeks. Stored specimens at nine time points for each patient (at baseline, on treatment, and 24 weeks after treatment) were tested by the two real-time PCR assays and CAM. Twenty-six (43.3%) patients reached SVR. The positive predictive values (PPVs) for SVR of undetectable HCV RNA at week 12 by CAM, ART, and CAP/CTM were 74.3%, 88.0%, and 95.2%, respectively. An undetectable HCV RNA level by CAM, ART, and CAP/CTM correctly predicted SVR at week 4 in 100%, 100%, and 100% of patients, at weeks 5 to 8 in 91.7%, 100%, and 100% of patients, at weeks 9 to 12 in 55.6%, 75%, and 87.5% of patients, and at weeks 13 to 24 in 0%, 26.7%, and 40% of patients, respectively. Of 16 patients who relapsed after treatment, HCV RNA was detectable in 2 patients at the end of treatment by CAP/CTM but undetectable by ART and CAM. HCV RNA tests using ART and CAP/CTM are considered to be more effective at predicting SVR than CAM, and the PPV for SVR was slightly higher in CAP/CTM than in ART. PMID:19091819

  5. Myeloid-derived suppressor cells are associated with viral persistence and downregulation of TCR ζ chain expression on CD8(+) T cells in chronic hepatitis C patients.

    PubMed

    Zeng, Qing-Lei; Yang, Bin; Sun, Hong-Qi; Feng, Guo-Hua; Jin, Lei; Zou, Zheng-Sheng; Zhang, Zheng; Zhang, Ji-Yuan; Wang, Fu-Sheng

    2014-01-01

    Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-α/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ζ expression on CD8(+) T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-1(+) cells were closely associated with the histological activity index in CHC. The TCR ζ chain was significantly downregulated on hepatic CD8(+) T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ζ chain expression in CD8(+) T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ζ chain expression.

  6. Chronic hepatitis B. Impact of hepatitis D virus superinfection and the hepatitis B e-system on histological outcome, and correlation of the hepatitis B e-system to HBV-DNA in serum.

    PubMed

    Lindh, G

    1986-01-01

    Chronic evolution after acute hepatitis B virus infection. During a 13 months period 1977-1978 a total of 129 cases of acute viral hepatitis type B occurred among patients who were admitted with hepatitis to Roslagstull, Hospital, Stockholm, Sweden. Less than 1% progressed to chronicity. Prevalence of Delta superinfection was studied among 60 patients with chronic hepatitis B. Nineteen (32%) were anti-delta positive. The majority of the positive patients were either non-European immigrants or addicts, both 9/19 (47%). Infections with the delta agent was found to have occurred in Stockholm already in the early 1970s. Rate of HBeAg clearance during chronic HBV was studied among 36 HBeAg positive patients. Seroconversion to anti-HBe was noted in 17 patients (47%), whereas HBeAg persisted in 19 during a mean follow-up period of 53 months. The spontaneous annual HBeAg seroconversion rate was 11%. HBeAg clearance occurred as frequently among homosexual men as among patients in other categories. However, 12/14 homosexual men were HBeAg positive after 2 years follow-up, compared with 1/13 drug addicts. Thus, homosexual men seemed to require a longer time for HBeAg seroconversion than i.v. drug addicts. HBV-DNA in serum, a strong indicator of viral particles and infectivity was analysed among patients with HBeAg seroconversion, initial HBeAg negativity and/or delta superinfection. HBV-DNA was found in 75-80% of our HBeAg positive patients. A correlation between chronic liver disease and presence of HBV-DNA in serum was also found. Thus, HBV DNA was found in 63% of patients with CAH or CAH/CI as compared with only 39% of patients with CPH. Delta infected patients had HBV-DNA more often than those without hepatitis D infection. Seven delta infected, anti-HBe positive, patients were still HBV-DNA positive five to eight years later. Therefore delta infected anti-HBe positive patients can be infectious for prolonged periods. Histological outcome. 63% (12/19) anti-delta positive

  7. [Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C].

    PubMed

    Rammeh, Soumaya; Khadra, Hajer Ben; Znaidi, Nadia Sabbegh; Romdhane, Neila Attia; Najjar, Taoufik; Bouzaidi, Slim; Zermani, Rachida

    2014-01-01

    Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

  8. Chronic alcohol intake up-regulates hepatic expressions of carotenoid cleavage enzymes and peroxisomal proliferator-activated receptors in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism.Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15’-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9910’-monooxygenase 2 (CMO2)...

  9. Lower Viral Response to Pegylated Interferon Alpha 2a Treatment of Chronic Hepatitis B in Roma People in Eastern Slovakia

    PubMed Central

    Drazilova, Sylvia; Janicko, Martin; Kristian, Pavol; Schreter, Ivan; Kucinsky, Branislav; Kozlej, Marek; Hockickova, Ivana; Jarcuska, Peter

    2016-01-01

    Aim. To evaluate the compliance and virological response to pegylated interferon alpha 2a treatment of chronic hepatitis B in Roma population compared to majority Caucasian population in Slovakia. Methods. Retrospective evaluation of a cohort of all Roma patients treated with pegylated interferon alpha 2a from 2007 to 2013 in 3 centers for treatment of chronic viral hepatitis B. The Study included 43 Roma patients with chronic viral hepatitis B and randomly selected control group. Treatment duration was 48 weeks. Viral response was evaluated after 24 weeks, at the end of treatment, and 24 weeks after the end of treatment. Results. Complete treatment course was finished by 79.1% of Roma patients compared to all patients from the control group (p = 0.0009). There was a tendency toward lower viral response rate in Roma at all time points; however significant difference was only at end of treatment viral response (51.2% Roma versus 81.4% majority, p = 0.003). We also did not find significant difference at the rate of HBsAg loss. Conclusion. Roma patients with chronic hepatitis B have significantly worse compliance to treatment with pegylated interferon and they have significantly lower rate of end of treatment viral response. PMID:26858755

  10. Interferon alpha in the treatment of chronic hepatitis C in children: a meta-analysis [correction of metanalysis].

    PubMed

    Di Ciommo, V; Russo, P; Ravà, L; Caprino, L

    2003-05-01

    Children with chronic hepatitis C may be ideal candidates for treatment with interferon alpha (IFNalpha) as they have liver disease at an early stage. However, adverse drug reactions need to be considered. The aim of this study was to conduct a systematic review of literature on interferon therapy of chronic hepatitis C in children, and to perform a meta-analysis of pooled data. A computerized search gave 18 articles on IFNalpha therapy in children with chronic hepatitis C; after exclusion of uncontrolled trials and of trials including patients with comorbidities, data from two studies could be pooled (48 patients). The outcomes assessed were biochemical, defined as normalization of alanine transaminase, and virologic, defined as HCV-RNA loss, both sustained at 24 months after enrollment. Results of the studies were homogenous. Risk difference was 37% (95%CI: 12.9-61) in favour of IFNalpha treated children for sustained biochemical response, and 36.8% (95%CI: 14.3-59.3) in favour of treated children for sustained HCV clearance, respectively. The differences were highly significant (P = 0.007 and P = 0.004, respectively). The histological end-point, as well as side-effects, could not be analysed, due to lack of data. This review identifies the poor methodology of the majority of the published trials. The study provides support for the efficacy of IFNalpha in improving both biochemical and virologic outcomes in chronic hepatitis C in children, but evidence is confined to these surrogate end-points.

  11. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    PubMed Central

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  12. Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients.

    PubMed

    Riva, E; Maggi, F; Abbruzzese, F; Bellomi, F; Giannelli, G; Picardi, A; Scagnolari, C; Folgori, A; Spada, E; Piccolella, E; Dianzani, F; Antonelli, G

    2009-02-01

    In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

  13. Chronic Liver Disease: Noninvasive Subharmonic Aided Pressure Estimation of Hepatic Venous Pressure Gradient

    PubMed Central

    Eisenbrey, John R.; Dave, Jaydev K.; Halldorsdottir, Valgerdur G.; Merton, Daniel A.; Miller, Cynthia; Gonzalez, José M.; Machado, Priscilla; Park, Suhyun; Dianis, Scott; Chalek, Carl L.; Kim, Christopher E.; Baliff, Jeffrey P.; Thomenius, Kai E.; Brown, Daniel B.; Navarro, Victor

    2013-01-01

    Purpose: To compare subharmonic aided pressure estimation (SHAPE) with pressure catheter–based measurements in human patients with chronic liver disease undergoing transjugular liver biopsy. Materials and Methods: This HIPAA-compliant study had U.S. Food and Drug Administration and institutional review board approval, and written informed consent was obtained from all participants. Forty-five patients completed this study between December 2010 and December 2011. A clinical ultrasonography (US) scanner was modified to obtain SHAPE data. After transjugular liver biopsy with pressure measurements as part of the standard of care, 45 patients received an infusion of a microbubble US contrast agent and saline. During infusion, SHAPE data were collected from a portal and hepatic vein and were compared with invasive measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. Results:- The 45 study patients included 27 men and 18 women (age range, 19–71 years; average age, 55.8 years). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the hepatic venous pressure gradient (HVPG) (R = 0.82). Patients at increased risk for variceal hemorrhage (HVPG ≥ 12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (1.93 dB ± 0.61 [standard deviation] vs −1.47 dB ± 0.29, P < .001), with a sensitivity of 100% and a specificity of 81%, indicating that SHAPE may be a useful tool for the diagnosis of clinically important portal hypertension. Conclusion: Preliminary results show SHAPE to be an accurate noninvasive technique for estimating portal hypertension. © RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121769/-/DC1 PMID:23525208

  14. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver.

    PubMed

    Savransky, Vladimir; Bevans, Shannon; Nanayakkara, Ashika; Li, Jianguo; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

    2007-10-01

    Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P < 0.01) and AST (637 +/- 37 U/l vs. 175 +/- 13 U/l in the control group; P < 0.001), whereas alkaline phosphatase and total bilirubin levels were unchanged. Histology revealed hepatic steatosis in both groups, with mild accentuation of fat staining in the zone 3 hepatocytes in mice exposed to CIH. Animals exposed to CIH exhibited lobular inflammation and fibrosis in the liver, which were not evident in control mice. CIH caused significant increases in lipid peroxidation in serum and liver tissue; significant increases in hepatic levels of myeloperoxidase and proinflammatory cytokines IL-1beta, IL-6, and CXC chemokine MIP-2; a trend toward an increase in TNF-alpha; and an increase in alpha1(I)-collagen mRNA. We conclude that CIH induces lipid peroxidation and inflammation in the livers of mice on a high-fat, high-cholesterol diet.

  15. Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response

    PubMed Central

    Welsch, Christoph; Efinger, Mira; von Wagner, Michael; Herrmann, Eva; Zeuzem, Stefan

    2017-01-01

    Background Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts. Methods This post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493). Results We observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens. Conclusion This is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR. PMID:28196130

  16. Role of fibrogenic markers in chronic hepatitis C and associated hepatocellular carcinoma.

    PubMed

    El-Bassiouni, N E; Nosseir, M M F; Madkour, M E; Zoheiry, M M K; Bekheit, I W; Ibrahim, R A; Ibrahim, I M; El Bassiouny, A E

    2012-06-01

    Detection and follow up of fibrogenesis in chronic hepatitis C (CHC) is mandatory for early treatment and risk stratification. The current study included 120 patients with CHC, of whom 30 had liver cirrhosis (LC) and 30 had hepatocellular carcinoma (HCC). 15 wedge liver biopsies, taken during laparoscopic cholecystectomy, were included as normal controls. Cases were subjected to laboratory investigations, serologic markers for viral hepatitis and assessment of circulating levels of hyaluronic acid (HA) and platelet-derived growth factor (PDGF). Immunohistochemical expression of connective tissue growth factor (CTGF), PDGF and transforming growth factor-β1 (TGF-β1) was also carried out. A significant increase (p < 0.01) in serum HA was noticed in CHC, LC and HCC compared to controls. Although, a significant decrease in serum PDGF was detected in CHC and LC compared to controls, HCC values were comparable. A significant up-regulation of CTGF was detected in CHC, LC and HCC (p < 0.01) in contrast to its limited mild expression in normal livers. Intense PDGF positive staining was noticed in CHC, LC and HCC compared to scattered faint expression in controls. The significant expression and marked intensity of PDGF staining matched the progress to tumorigenesis. A positive TGF-β1 immunostaining was also noticed in CHC, LC and HCC. An intense and extensive cytoplasmic expression of TGF-β1 was encountered in patients with LC revealing that CTGF, PDGF and TGF-β1 act synergistically in LC. Data revealed that HA and CTGF may be implicated as important diagnostic parameters for assessment of hepatic fibrosis and PDGF for monitoring malignant transformation in CHC.

  17. Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients with Chronic Hepatitis C.

    PubMed

    Qin, Lei; Zhou, Yan-Cai; Wu, Hong-Jie; Zhuo, Ya; Wang, Yan-Ping; Si, Chang-Yun; Qin, Yong-Mei

    2017-04-01

    The imbalance of regulatory T cells (Tregs) and T helper 17 (Th17) cells contributes to the persistent hepatitis C virus (HCV) infection. However, modulatory factors associated with Tregs-Th17 balance were not fully elucidated. A recent study demonstrated an immunoregulatory strategy by inactivation of Notch signaling to reverse the disequilibrium of Tregs-Th17 cells in immune thrombocytopenia. Thus, the aim of this study was to assess the effect of Notch signaling in regulating the functions of Tregs and Th17 cells in chronic hepatitis C. A total of 46 patients with chronic hepatitis C and 17 normal controls (NCs) were enrolled. mRNA expressions of Notch1 and Notch2 were semiquantified by real-time reserve polymerase chain reaction. Percentages of Tregs-Th17, levels of key transcriptional factors, and cytokine productions were measured in response to treatment by DAPT, a γ-secretase inhibitor to suppress Notch signaling. We found that Notch1 and Notch2 mRNAs were significantly elevated in peripheral blood mononuclear cells from chronic hepatitis C patients compared with those from NCs. DAPT treatment reduced Th17 response by downregulation of RORγt expression and interleukin (IL)-17/IL-22 secretion. Tregs proportion, FoxP3 expression, and IL-10 production did not change significantly with DAPT treatment in chronic hepatitis C; however, blockage of Notch signaling inhibited the suppressive function of Tregs. Moreover, effective anti-HCV therapy not only reduced Notch1 and Notch2 expression but also decreased Tregs and Th17 proportions. The current data provided a novel mechanism underlying the modulation of Treg-Th17 balance. The link between Notch signaling and Th cells might lead to a new intervention for breaking immunotolerance of chronic HCV infection.

  18. Recent successes and noteworthy future prospects in the treatment of chronic hepatitis C.

    PubMed

    Fox, Alyson N; Jacobson, Ira M

    2012-07-01

    Within the last year, the landscape of therapy for genotype 1 chronic hepatitis C virus (HCV) has changed dramatically as 2 much-anticipated protease inhibitors became available for use. These agents, telaprevir and boceprevir, when used in combination with pegylated interferon and ribavirin, offer patients an improved chance of cure and the opportunity for a shorter duration of therapy. Although these medications represent a significant achievement in the battle against HCV, they do not represent the final phase in the evolution of HCV therapy. Many other direct-acting antiviral agents representing several classes, as well as agents that act via host-mediated pathways, are in development. Recent proof of concept studies demonstrating the capacity to eradicate HCV without interferon signal the potential for yet another quantum leap in the field.

  19. Studies on the Pathogenesis of Experimental Chronic Active Hepatitis in Rabbits

    PubMed Central

    Hopf, U.; Meyer zum Büschenfelde, K.-H.

    1974-01-01

    Isolated hepatocytes of rabbits with experimentally induced chronic active hepatitis (CAH) in different stages and liver cirrhosis, respectively, and of animals without liver lesions were studied by immunofluorescence with regard to surface bound immunoglobulin. In 8 of 9 animals with CAH immunoglobulin could be demonstrated on the membranes of the hepatocytes. One animal with liver cirrhosis did not show fixed gammaglobulin; 8 animals without liver lesions which had been immunized with xenogeneic (human) together with allogeneic liver specific proteins (RLP) had no immunoglobulin bound to their hepatocytes, with one exception. The antibody titres in the serum of these animals against liver specific proteins (passive haemagglutination and gel diffusion) were not different from those in animals with liver lesions. The skin test reactivity with RLP as antigen corresponded largely to the development of liver lesions. The pathogenic importance of an antibody mediated lymphocytic cytotoxicity for the induction of CAH is discussed. ImagesFig. PMID:4217635

  20. Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection

    PubMed Central

    FakhriRavari, Alireza; Malakouti, Mazyar; Brady, Rebecca

    2016-01-01

    Abstract Hepatitis C virus (HCV) infection affects as many as 185 million people globally, many of whom are chronically infected and progress over time to cirrhosis, decompensated liver disease, hepatocellular carcinoma, and eventually death without a liver transplant. In the United States, HCV genotype 1 constitutes about 75% of all infections. While interferon and ribavirin therapy was the cornerstone of treatment for many years, interferon-free treatments have become the standard of care with the emergence of new direct-acting agents, resulting in more effective treatment, shorter duration of therapy, better tolerability, lower pill burden, and ultimately better adherence. This review will summarize the evidence for the currently available combination therapies as well as emerging therapies in phase 3 trials for treatment of HCV genotype 1. PMID:27350940

  1. Virological and serological tools to optimize the management of patients with chronic hepatitis B.

    PubMed

    Martinot-Peignoux, Michelle; Marcellin, Patrick

    2016-01-01

    Molecular biology techniques are routinely used to diagnose and monitor treatment in patients with chronic hepatitis B (CHB). These tools can detect and quantify viral genomes and analyse their sequences to determine genotype. The increasing use of these tools to monitor patients has greatly improved the management of CHB infection by maximizing the potential for individualized treatment. HBV genotyping has become increasingly important and provides additional information to predict a response to therapy. More sensitive methods to determine HBV DNA levels are now available and the units of measurements have been standardized. HBsAg levels in serum have been shown to reflect active intrahepatic covalently closed circular DNA (cccDNA) and to have additional value in treatment decisions, especially as an on-treatment marker.

  2. Hepatitis A and B screening and vaccination rates among patients with chronic liver disease.

    PubMed

    Ramirez, Jonathan C; Ackerman, Kimberly; Strain, Sasha C; Ahmed, Syed T; de Los Santos, Mario J; Sears, Dawn

    2016-01-01

    Vaccinations against hepatitis A virus (HAV) and hepatitis B virus (HBV) are recommended for patients with chronic liver disease (CLD), yet implementation of these recommendations is lacking. This study reviewed HAV and HBV antibody testing and vaccination status of patients with CLD. In 2008, we began using pre-printed liver order sets, which included vaccination options. We compared Scott & White liver clinic CLD patient records from 2005 (238) with patient records from 2008 (792). Screening rates for immunity and vaccination rates of those lacking immunity were calculated. In 2005, 66% of CLD patients were screened for HAV immunity. In 2008, 56% of CLD patients were screened. The HAV vaccination completion rate was 37% in 2005, while in 2008, the rate was 46%. In 2005, 66% of CLD patients were screened for HBV immunity; in 2008, 56 % CLD patients were screened. The HBV vaccination completion rate was 26% in 2005 compared with 36% in 2008. Although there was a lower percentage of screening in 2008, the overall number of patients tripled between 2005 and 2008. There was a significant increase in the total number of patients screened and vaccinated in 2008. Some physicians may have vaccinated their patients without checking for immunity. In January 2008, we implemented pre-printed order sets with checkboxes to help remind providers to order labs to screen for immunity against HAV and HBV and to order vaccinations for those who lacked immunity. The use of these sets may have aided in the increase of vaccination completion rates.

  3. Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression

    PubMed Central

    Jia, Hong-mei; Li, Qi; Zhou, Chao; Yu, Meng; Yang, Yong; Zhang, Hong-wu; Ding, Gang; Shang, Hai; Zou, Zhong-mei

    2016-01-01

    Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury. PMID:27006086

  4. alpha-Interferon treatment of chronic hepatitis C: a controlled, multicentre, prospective study.

    PubMed

    Angelini, G; Sgarbi, D; Colombari, R; Bezzi, A; Castagnini, A; de Berardinis, F; Conti, A; di Piramo, D; Dolci, L; Falezza, G

    1995-01-01

    This prospective, controlled study was designed in order to evaluate the response rate to alpha-interferon (IFN) versus no treatment in 63 patients affected by chronic hepatitis C. Fifty-two patients were randomly chosen to receive no treatment of IFN alfa-2b (6 MU 3 times weekly for the first month and 3 MU for the next 11 months). Eleven additional patients were crossed to active treatment after a 1-year control period without any change of serum pattern and were therefore enrolled both as controls and cases. Four patients had to be withdrawn from the active treatment for adverse effects. Sixteen out of the remaining 23 had normal alanine aminotransferase (ALT) values at the end of the treatment, and 14 were still normal 12 months later. A liver biopsy, taken 6 months after the end of the treatment, showed improvement in 12 patients and normalization in 1. Only 1 out of the 25 controls had transaminase normalization and 5 a decrease. One of them showed also a histological improvement. Eight of the 11 case/control patients showed ALT normalization after IFN administration, 5 of them histological improvement and 2 liver normalization. Hepatitis C virus (HCV) RNA became negative in 13 of 17 cases in whom the assay was carried out. Therefore this study confirms that the longterm administration of alpha-IFN induced a prolonged remission of disease activity in over 50% of the patients and the clearance of HCV RNA in the majority of the responders.

  5. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    PubMed Central

    Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

    2010-01-01

    AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

  6. Current role of transient elastography in the management of chronic hepatitis B patients

    PubMed Central

    2017-01-01

    Liver fibrosis is an important prognostic factor for chronic hepatitis B (CHB), and accurate evaluation of the stage of liver fibrosis is crucial in establishing management strategies. While liver biopsy is still considered the gold standard for staging liver fibrosis or cirrhosis, transient elastography (TE), a noninvasive means of assessing liver fibrosis, has come to play an increasing role in this process. After extensive validation, TE is now regarded as a reliable surrogate maker for grading the severity of liver fibrosis in CHB patients. It can detect the extent of fibrosis in a patient and can also be used to evaluate longitudinal changes in liver fibrosis over time with or without interventional management, such as antiviral therapy. However, several confounders hinder the effective assessment of liver fibrosis using TE, such as extensive liver necroinflammation, hepatic congestion, and cholestasis. TE has limited use in obese patients or patients with ascites. Although TE has several limitations, due to its accessibility and safety, it is a valuable tool for the initial evaluation and follow-up in patients with CHB. PMID:27956732

  7. Liver p53 expression in patients with HCV-related chronic hepatitis.

    PubMed

    Loguercio, C; Cuomo, A; Tuccillo, C; Gazzerro, P; Cioffi, M; Molinari, A M; Del Vecchio Blanco, C

    2003-07-01

    Mutated p53 acts as a dominant oncogene and alterations in the p53 gene are described in a large number of patients with hepatocellular carcinoma (HCC). It has been demonstrated that hepatitis C virus (HCV)-core protein regulates transcriptionally cellular genes, as well as cell growth and apoptosis. This study was undertaken to evaluate whether p53 may be expressed also in a precocious stage of HCV-related liver damage. We studied p53 expression by immunoluminometric assay on liver samples from 40 patients (M/F 18/ 22, median age 44 years, range 13-64 years) with biopsy-proven HCV-related chronic hepatitis. We considered the following factors: degree of liver damage, liver iron content and HCV-RNA titre. We also evaluated as possible co-factors alcohol and food intake in the last 3 years. p53 was over-expressed in seven of 40 (17.5%) patients. Liver histology documented the presence of unexpected cirrhosis in two patients among the p53 positive subjects. The p53 positive group had a daily ethanol intake significantly higher in respect to that of the p53 negative group (P < 0.05). Alimentary history documented that patients with a p53 over-expression had a lower intake of total calories, monounsaturated fatty acids, vitamin C and riboflavin. Data indicate that p53 over-expression can occur even in initial stages of HCV-related liver disease.

  8. Female gender lost protective effect against disease progression in elderly patients with chronic hepatitis B

    PubMed Central

    You, Hong; Kong, Yuanyuan; Hou, Jinlin; Wei, Lai; Zhang, Yuexin; Niu, Junqi; Han, Tao; Ou, Xiaojuan; Dou, Xiaoguang; Shang, Jia; Tang, Hong; Xie, Qing; Ding, Huiguo; Ren, Hong; Xu, Xiaoyuan; Xie, Wen; Liu, Xiaoqing; Xu, Youqing; Li, Yujie; Li, Jie; Chow, Shein-Chung; Zhuang, Hui; Jia, Jidong

    2016-01-01

    Female gender and younger age are protective factors against disease progression in chronic hepatitis B (CHB). However, it is not clear whether the disease progression still remains slow in elderly females. This study investigated the interaction of female gender and older age on the development of cirrhosis in patients recorded in China Registry of Hepatitis B. A total of 17,809 CHB patients were enrolled in this multi-center cross-sectional study. The prevalence of cirrhosis in female CHB patients increased faster than that in male CHB patients over 50 years old. Multivariate analysis showed that the increase of adjusted ORs for developing cirrhosis in females started to accelerate after 50 years old: 11.19 (95% CI: 5.93–21.11) in women versus 14.75 (95% CI: 8.35–26.07) in men at ages of 50–59 years, 21.67 (95% CI: 11.05–42.47) versus 24.4 (95% CI: 13.00–45.80) at ages 60–69 years, and 18.78 (95% CI: 6.61–53.36) versus 12.09 (95% CI: 4.35–33.61) in those over 70 years. In conclusion, the protective effect of female gender against cirrhosis gradually lost with increasing age, therefore disease progression should be monitored more closely in elderly women with CHB. PMID:27892487

  9. A review of psychosocial issues in patients with chronic hepatitis B.

    PubMed

    Modabbernia, Amirhossein; Ashrafi, Mandana; Malekzadeh, Reza; Poustchi, Hossein

    2013-02-01

    Psychosocial issues and health-related quality of life (HRQOL) are important components of care in patients diagnosed with chronic hepatitis B (CHBV). In this review, we searched Medline, ISI Web of Knowledge, Google Scholar and the American Association for the Study of Liver Diseases (AASLD) website (until January 2012) using relevant terms and we categorized the retrieved content into three areas: HRQOL, mental health, and psychosocial issues such as stigma and coping.  Increasing severity of CHBV leads to a decline in HRQOL. Cirrhosis worsens HRQOL, whereas treatment and psycho-education improves it. Frequency of mood disorders seems to be increased in patients with CHBV, although not all studies have shown this trend. Some factors such as alcohol consumption and low social support negatively impact patients' mental health. Those with CHBV generally have better HRQOL and mental health than their hepatitis C (HCV) counterparts. Patients with psychiatric disorders, particularly those with prolonged institutionalization, have a generally higher risk of acquiring CHBV infection compared to the general population. Robust studies regarding the stigma in patients with CHBV are lacking, although some studies have suggested a higher degree of perceived stigma in these patients.   HRQOL and mental health are significantly affected in CHBV patients, particularly in those with more severe forms of the disease. There are few studies that addressed the effects of intervention in CHBV patients with psychosocial problems. Other subjects necessitating additional research include stigma, coping mechanisms, and other less common, yet important psychosomatic disorders.

  10. MicroRNAs may solve the mystery of chronic hepatitis B virus infection.

    PubMed

    Wei, Ying-Feng; Cui, Guang-Ying; Ye, Ping; Chen, Jia-Ning; Diao, Hong-Yan

    2013-08-14

    Hepatitis B virus (HBV) infection is a global public health problem that causes persistent liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. A large amount of people die annually from HBV infection. However, the pathogenesises of the HBV-related diseases are ill defined and the therapeutic strategies for the diseases are less than optimum. The recently discovered microRNAs (miRNAs) are tiny noncoding RNAs that regulate gene expression primarily at the post-transcriptional level by binding to mRNAs. miRNAs contribute to a variety of physiological and pathological processes. A number of miRNAs have been found to play a pivotal role in the host-virus interaction including host-HBV interaction. Numerous studies have indicated that HBV infection could change the cellular miRNA expression patterns and different stages of HBV associated disease have displayed distinctive miRNA profiles. Furthermore, the differential expressed miRNAs have been found involved in the progression of HBV-related diseases, for instance some miRNAs are involved in liver tumorigenesis and tumor metastasis. Studies have also shown that the circulating miRNA in serum or plasma might be a very useful biomarker for the diagnosis and prognosis of HBV-related diseases. In addition, miRNA-based therapy strategies have attracted increasing attention, indicating a promising future in the treatment of HBV-related diseases.

  11. Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression.

    PubMed

    Jia, Hong-Mei; Li, Qi; Zhou, Chao; Yu, Meng; Yang, Yong; Zhang, Hong-Wu; Ding, Gang; Shang, Hai; Zou, Zhong-Mei

    2016-03-23

    Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury.

  12. Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; España Contreras, Pilar; Pinazo Martínez, Isabel; de la Cruz Lombardo, Jesús; Olmedo Martín, Raúl

    2016-01-01

    The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined. PMID:27547001

  13. Embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy

    SciTech Connect

    Sakurabayashi, Shin; Sezai, Shuichi; Yamamoto, Yoshihiro; Hirano, Masanori; Oka, Hiroshi

    1997-03-15

    Purpose. To evaluate the efficacy of embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). Methods. Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4 women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1 had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein shunt. Shunt embolization was performed using stainless steel coils, with a percutaneous transhepatic portal vein approach in 4 patients and a transrenal vein approach in 3 patients. Results. After embolization, the shunt disappeared in 4 patients on either ultrasound pulsed Doppler monitoring or portography. Complications observed in the 7 patients were fever, transient pleural effusion, ascites, and mild esophageal varices. For 3-6 months after embolization, the 4 patients whose shunts disappeared showed minimal or no reappearance of a shunt, and had no recurrence of encephalopathy. The serum ammonia levels decreased and electroencephalograms also improved. One of the 4 patients, who developed mild esophageal varices, required no treatment. Treatment was effective in 3 of the 4 patients (75%) who underwent embolization via a transhepatic portal vein. Conclusion. Transvascular embolization of shunts improved the outcome in 4 of 7 patients. The most effective embolization was achieved via the percutaneous transhepatic portal vein approach.

  14. ANTIGEN-SPECIFIC T LYMPHOCYTE PROLIFERATION DECREASES OVER TIME IN ADVANCED CHRONIC HEPATITIS C

    PubMed Central

    Morishima, Chihiro; Di Bisceglie, Adrian M.; Rothman, Alan L.; Bonkovsky, Herbert L.; Lindsay, Karen L.; Lee, William M.; Koziel, Margaret James; Fontana, Robert J.; Kim, Hae-Young; Wright, Elizabeth C.

    2011-01-01

    To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial. Peripheral blood responses to HCV, tetanus and Candida protein antigens were measured at baseline, Month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose PEG-IFN only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5–6) were less likely to have positive lymphoproliferative responses to HCV at baseline than patients with fibrosis (15% vs 29%, p=0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (p=0.11, p=0.05, p=0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive lymphoproliferative responses to HCV, tetanus and Candida antigens declined over time (p<0.003) and the slope of this decline was greater in the PEG-IFN treatment group than the observation group (p < 0.02). Lower levels of tetanus lymphoproliferative responses were associated with fibrosis progression and clinical outcomes (p=0.009). Poorer CD4+ T cell proliferative function is associated with more advanced liver disease in chronic hepatitis C, and may be further affected by long-term PEG-IFN treatment. PMID:22571902

  15. Intelligent MONitoring System for antiviral pharmacotherapy in patients with chronic hepatitis C (SiMON-VC).

    PubMed

    Margusino-Framiñán, Luis; Cid-Silva, Purificación; Mena-de-Cea, Álvaro; Sanclaudio-Luhía, Ana Isabel; Castro-Castro, José Antonio; Vázquez-González, Guillermo; Martín-Herranz, Isabel

    2017-01-01

    Two out of six strategic axes of pharmaceutical care in our hospital are quality and safety of care, and the incorporation of information technologies. Based on this, an information system was developed in the outpatient setting for pharmaceutical care of patients with chronic hepatitis C, SiMON-VC, which would improve the quality and safety of their pharmacotherapy. The objective of this paper is to describe requirements, structure and features of Si- MON-VC. Requirements demanded were that the information system would enter automatically all critical data from electronic clinical records at each of the visits to the Outpatient Pharmacy Unit, allowing the generation of events and alerts, documenting the pharmaceutical care provided, and allowing the use of data for research purposes. In order to meet these requirements, 5 sections were structured for each patient in SiMON-VC: Main Record, Events, Notes, Monitoring Graphs and Tables, and Follow-up. Each section presents a number of tabs with those coded data needed to monitor patients in the outpatient unit. The system automatically generates alerts for assisted prescription validation, efficacy and safety of using antivirals for the treatment of this disease. It features a completely versatile Indicator Control Panel, where temporary monitoring standards and alerts can be set. It allows the generation of reports, and their export to the electronic clinical record. It also allows data to be exported to the usual operating systems, through Big Data and Business Intelligence. Summing up, we can state that SiMON-VC improves the quality of pharmaceutical care provided in the outpatient pharmacy unit to patients with chronic hepatitis C, increasing the safety of antiviral therapy.

  16. Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

    PubMed Central

    Kekilli, Murat; Tanoglu, Alpaslan; Sakin, Yusuf Serdar; Kurt, Mevlut; Ocal, Serkan; Bagci, Sait

    2015-01-01

    AIM: To determine the association between the neutrophil to lymphocyte (N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B (CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the “no/minimal liver fibrosis” group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the “advanced liver fibrosis” group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant. RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the “no/minimal fibrosis” group included 79 individuals, while the “advanced fibrosis” group included 50 individuals. Mean (N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis. CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB. PMID:25987782

  17. Circulating visfatin level is associated with hepatocellular carcinoma in chronic hepatitis B or C virus infection.

    PubMed

    Tsai, I-Ting; Wang, Chao-Ping; Yu, Teng-Hung; Lu, Yung-Chuan; Lin, Chih-Wen; Lu, Li-Fen; Wu, Cheng-Ching; Chung, Fu-Mei; Lee, Yau-Jiunn; Hung, Wei-Chin; Hsu, Chia-Chang

    2017-02-01

    Adipocytokines play an important role in adipose tissue homeostasis, especially in obesity-associated disorders such as non-alcoholic fatty liver and their complications including hepatocellular carcinoma (HCC). Although visfatin is an adipocytokine highly expressed in visceral fat that has been demonstrated to play a critical role in the progression of human malignancies, little is known about the role of visfatin in HCC associated with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. In this study, we investigated whether plasma visfatin levels were altered in patients with HCC and the association between plasma visfatin levels and pretreatment hematologic profiles. Plasma visfatin levels were measured by enzyme-linked immunosorbent assays in 193 patients with different stages of HBV or HCV infection, and 92 healthy control subjects. The patients with HCC and chronic HCV or HBV infection had higher levels of visfatin than patients with HBV, HCV, and cirrhosis. In multivariate logistic regression analysis, levels of alpha-fetoprotein (AFP) (OR: 1.13, p=0.003), and plasma visfatin (OR: 1.17, p=0.046) were independently associated with HCC. Multiple stepwise regression analysis showed that plasma visfatin level was positively associated with age, aspartate aminotransferase to platelet ratio index (APRI), and AFP. Trend analyses confirmed that plasma visfatin concentration was associated with AFP>8ng/mL, cirrhosis, HCC, tumor size>5cm, and Barcelona Clinic Liver Cancer-C stage. These results suggested that the plasma visfatin level is associated with the presence of HCC, and that a higher plasma visfatin level may be important in the pathogenesis of HCC. Visfatin may act as both a protective and pro-inflammatory factor. Plasma visfatin concentration may serve as an additional tool to identify patients with more advanced necroinflammation.

  18. New aspects on the natural history of chronic hepatitis B infection: implication for therapy.

    PubMed

    Gjørup, Ida E; Skinhøj, Peter

    2003-01-01

    The incidence and sequelae of chronic hepatitis B (HBV) infection appear to have been overestimated previously, especially in areas outside Asia where neonatal infection predominates. A high rate of spontaneous HBeAg seroconversion is found in children as well as adults, and 40 to 50 y of replicative infection seems to be the most important risk factor for cirrhosis and hepatocellular carcinoma necessitating a cautious attitude towards antiviral treatment. Of concern, however, HBeAg seroconversion, which usually predicts a good outcome, is not always an irreversible event. Low grade replication of HBV may continue in anti-HBe positive individuals and shift in HBe status does occur in up to 10% of viral carriers with evidence of an increased risk of complications. Viral replication (HBV DNA positivity) is also found in HBeAg negative mutant infection and is an important parameter to note. To date, the data do not suggest any different prognosis for patients with this kind of infection. Also the various viral genotypes might have different prognoses partly due to the association with precore mutations, but the present knowledge does not allow different therapeutic management as in the case of hepatitis C. Treatment is available with a number of safe antiviral agents. However, all of them are mainly suppressive with low cure rates after 1 y. Initiation of therapy should therefore mainly be considered in symptomatic chronic infection and in cases with high risk of complications i.e. patients with ongoing viral replication and age above 40 y or bridging necroses verified by liver biopsy.

  19. Drug Induced Pneumonitis Secondary to Treatment with Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir (VIEKIRA PAK®) for Chronic Hepatitis C: Case Report of an Unexpected Life-Threatening Adverse Reaction

    PubMed Central

    Faire, Bridget; Gane, Edward

    2017-01-01

    VIEKIRA PAK (ritonavir-boosted paritaprevir/ombitasvir and dasabuvir) is an approved treatment for compensated patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection. This oral regimen has minimal adverse effects and is well tolerated. Cure rates are 97% in patients infected with HCV GT 1a and 99% in those with HCV GT 1b. We report the first case of life-threatening allergic pneumonitis associated with VIEKIRA PAK. This unexpected serious adverse event occurred in a 68-year-old Chinese female with genotype 1b chronic hepatitis C and Child-Pugh A cirrhosis. One week into treatment with VIEKIRA PAK without ribavirin, she was admitted to hospital with respiratory distress and acute kidney injury requiring intensive care input. She was initially diagnosed with community acquired pneumonia and improved promptly with intravenous antibiotics and supported care. No bacterial or viral pathogens were cultured. Following complete recovery, she recommenced VIEKIRA PAK but represented 5 days later with more rapidly progressive respiratory failure, requiring intubation and ventilation, inotropic support, and haemodialysis. The final diagnosis was drug induced pneumonitis.

  20. Tongue hyperpigmentation resulting from peginterferon alfa-2b and ribavirin treatment in a patient with chronic hepatitis C.

    PubMed

    Ghosh, Souvik; Duseja, Ajay; Dhiman, Radha Krishan; Chawla, Yogesh Kumar

    2012-03-01

    Hepatitis C virus (HCV) infection has been associated with several cutaneous diseases such as lichen planus, porphyria cutanea tarda, chronic pruritus, and cutaneous necrotizing vasculitis (Doutre, Arch Dermatol 135:1401-1403, 1999). The antiviral treatment for chronic HCV with interferon alfa (INF) or peginterferon alfa (PEG-INF) combined with rivabirin also leads to many skin side effects including injection site reaction, generalized skin rashes, pruritus, dry skin, alopecia, and exacerbation of autoimmune processes, particularly psoriasis, lichen planus or vitiligo (Dalekos et al., Eur J Gastroenterol Hepatol 10:933-939, 1998; Sookoian et al., Arch Dermatol 135:1000-1000, 1999). There are case reports of tongue hyperpigmentation during combination therapy of PEG IFN and RBV in chronic hepatitis C both in dark-skined as well as Caucasian. We report the first case of tongue hyperpigmentation associated with PEG-INF-2b plus ribavirin administration in a non-Caucasian patient with genotype 4.

  1. Detection of Hepatitis B Virus Covalently Closed Circular DNA in the Plasma of Iranian HBeAg-Negative Patients With Chronic Hepatitis B

    PubMed Central

    Tajik, Zahra; Keyvani, Hossein; Bokharaei-Salim, Farah; Zolfaghari, Mohammad Reza; Fakhim, Shahin; Keshvari, Maryam; Alavian, Seyed Moayed

    2015-01-01

    Background: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a marker of HBV replication in the liver of patients infected with HBV. Objectives: This study aimed to investigate the association between the presence of cccDNA in the plasma samples of Iranian treatment-naive patients with chronic hepatitis B infection and HBV viral load and HBsAg levels. Patients and Methods: From April 2012 to May 2015, 106 treatment-naive patients with chronic hepatitis B infection were enrolled in this cross-sectional study. The HBsAg titer was measured by the Roche HBsAg II assay on the Cobas e411 system, and HBV DNA quantitation was performed using the COBAS TaqMan 48 kit. Real-time polymerase chain reaction was performed for the detection of HBV cccDNA. Results: The mean (SD) age of the patients was 41.1 ± 12.4 years (range, 20 - 62 years). From a total of 106 study participants, 67 (63.2%) were males. The HBV cccDNA was detected in plasma specimens in 19 (17.9%) out of the total 106 patients, and a significant relationship was found between the presence of cccDNA in plasma sample of males (23.9%) and females (7.7%) (P = 0.039). Also, a significant correlation was found between the presence of cccDNA in plasma sample of the patients and HBV viral load level (P < 0.0001) and HBsAg titer (P = 0.0043). Conclusions: This study showed that cccDNA can be detected in the plasma specimen of 17.9% of Iranian treatment-naive patients with chronic hepatitis B infection. Therefore, designing prospective studies focusing on the detection of cccDNA in these patients would provide more information. PMID:26504471

  2. Genotype, viral load and age as independent predictors of treatment outcome of interferon-alpha 2a treatment in patients with chronic hepatitis C. Construct group.

    PubMed

    Bell, H; Hellum, K; Harthug, S; Maeland, A; Ritland, S; Myrvang, B; von der Lippe, B; Raknerud, N; Skaug, K; Gutigard, B G; Skjaerven, R; Prescott, L E; Simmonds, P

    1997-01-01

    Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p < 0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

  3. Intrahepatic CD4 T-Cell apoptosis is related to METAVIR score in patients with chronic hepatitis C virus.

    PubMed

    Roger, P-M; Chaillou, S; Breittmayer, J-P; Dahman, M; St Paul, M-C; Chevallier, P; Benzaken, S; Ticchioni, M; Bernard, A; Dellamonica, P; Tran, A

    2005-08-01

    Hepatitis C virus (HCV) infection leads to liver injury, which is thought to be immune-mediated. Apoptosis of hepatic T cells could influence histological damage. We quantified peripheral and intrahepatic T-cell apoptosis in 28 patients with chronic hepatitis C by using cytofluorometric techniques. METAVIR score and HCV plasma viral load were determined. Six liver biopsies, obtained from controls without chronic hepatitis during hepatobiliary surgery, served as controls. In patients, liver T-cell apoptosis was upregulated compared to peripheral T cells: 35 versus 7% for CD4+ and 56 versus 13% for CD8+ T cells (P < 0.001). Liver T-cell apoptosis levels from patients were increased compared to controls for both CD4+ (P = 0.041) and CD8+ T cells (P = 0.007). Nine patients exhibiting METAVIR scores A and F < or = 1 showed higher intrahepatic CD4+ T-cell apoptosis compared to the 19 patients with a higher METAVIR score (P = 0.001) and both histological activity and fibrosis were related to apoptosis level. There was also an inverse relationship between the level of intrahepatic CD8+ T-cell apoptosis and serum transaminase activity (P = 0.023). Our study shows immune compartmentalization, suggesting that the study of peripheral blood lymphocytes may not be fully relevant to the pathophysiology of HCV hepatitis, and that the severity of liver injury is inversely correlated with intrahepatic CD4+ T-cell apoptosis.

  4. Risk Factors for Renal Functional Decline in Chronic Hepatitis B Patients Receiving Oral Antiviral Agents.

    PubMed

    Shin, Jung-Ho; Kwon, Hee Jin; Jang, Hye Ryoun; Lee, Jung Eun; Gwak, Geum-Youn; Huh, Wooseong; Jung, Sin-Ho; Lee, Joon Hyeok; Kim, Yoon-Goo; Kim, Dae Joong; Oh, Ha Young

    2016-01-01

    Renal functional decline that is frequently seen during chronic hepatitis B (CHB) treatment can exert adverse effects on overall prognosis. It, however, is difficult to distinguish vulnerable patients who may experience renal dysfunction because most previous CHB studies were conducted in relatively healthy individuals. In this retrospective observational study, renal functional decline in CHB patients receiving oral antiviral agents for more than 6 months was analyzed and risk factors of chronic kidney disease (CKD) progression were determined. Renal functional decline was defined when the estimated glomerular filtration rate (eGFR) decreased by more than 25% from baseline and rapid CKD progression was defined as eGFR decreased by more than 5 mL/min/1.73 m2/y among patients who experienced renal functional decline. A total of 4178 patients were followed up for a median 23 months. Antiviral agents included lamivudine (17.0%), adefovir (3.7%), entecavir (70.4%), telbivudine (0.6%), tenofovir (4.0%), or clevudine (4.3%). Renal functional decline occurred in 706 (16.9%) patients. Based on multivariate Cox regression analysis, age, hypertension, diabetes, history of liver or kidney transplantation, underlying underlying CKD, and simultaneous administration of diuretics increased the hazard ratio for renal functional decline; however, clevudine reduced risk. The eGFR significantly increased over time in patients receiving telbivudine or clevudine compared with lamivudine. Among the 3175 patients followed up for more than 1 year, 407 (12.8%) patients experienced rapid CKD progression. Patients with rapid CKD progression showed lower serum albumin, higher total bilirubin, and prolonged prothrombin time compared with patients with stable renal function, but hepatitis B envelope antigen positivity and hepatitis B virus deoxyribonucleic acid level did not differ between the control and rapid CKD progression groups. Age, diabetes, kidney transplantation, underlying CKD, and

  5. Outcome of Sustained Virological Responders with Histologically Advanced Chronic Hepatitis C

    PubMed Central

    Morgan, Timothy R.; Ghany, Marc G.; Kim, Hae-Young; Snow, Kristin K.; Shiffman, Mitchell L.; De Santo, Jennifer L.; Lee, William M.; Di Bisceglie, Adrian M.; Bonkovsky, Herbert L.; Dienstag, Jules L.; Morishima, Chihiro; Lindsay, Karen L.; Lok, Anna S.F.

    2010-01-01

    Background & Aims Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR) and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C Trial. Methods Laboratory and/or clinical outcome data were available for 140 of the 180 SVR patients. Nonresponders (n=309) or BT/R (N=77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Results Median follow-up for SVR, BT/R, and NR patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that in NR (21.3% and 27.2%, p<0.001 for both) but not the BT/R (4.4% and 8.7%). The adjusted hazard ratio [HR] for time to death/liver transplantation (HR=0.17, 95% CI: 0.06–0.46), or development of liver-related morbidity/mortality (HR=0.15, 95% CI: 0.06–0.38) or HCC (HR=0.19, 95% CI: 0.04–0.80) was significant for SVR compared to NR. Laboratory tests related to liver-disease severity improved following SVR. Conclusions Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC. PMID:20564351

  6. Serum Basal Paraoxonase 1 Activity as an Additional Liver Function Test for the Evaluation of Patients with Chronic Hepatitis

    PubMed Central

    Halappa, Chandrakanth K; Pyati, Sudharani A; Nagaraj; Wali, Vinod

    2015-01-01

    Background The diagnostic accuracy of currently available standard panel of liver function tests is not satisfactory for the reliable diagnosis of chronic liver disorders. Earlier studies have reported that serum basal paraoxonase 1 (PON1) activity measurement may add a significant contribution to the liver function tests. Aim To assess whether the measurement of serum basal paraoxonase 1 (PON1) activity would be useful as an index of liver function status in chronic hepatitis patients. Materials and Methods The study included 50 chronic hepatitis patients and 50 apparently healthy controls based on inclusion & exclusion criteria. In all the subjects, standard liver function tests were analysed by using standard methods. Basal PON1 activity was estimated using spectrophotometric method by the hydrolysis of p-nitrophenylacetate. Student t-test, Pearson’s correlation coefficient, diagnostic validity tests and ROC curve analysis were the methods used for the statistical analysis of the data. Results The serum basal PON1 activity was significantly decreased in chronic hepatitis cases when compared to controls (p< 0.001). Also basal PON1 activity was positively correlated with serum total protein and albumin, and negatively correlated with serum total bilirubin, alanine amino transferase (ALT), and alkaline phosphatase (ALP) (p< 0.001) in chronic hepatitis cases but not in healthy controls. Diagnostic validity tests showed, basal PON1 activity was a better discriminator of chronic hepatitis than total protein, albumin and ALP with sensitivity of 68%, specificity of 100%, positive predictive value of 100% and negative predictive value of 75%. ROC curve analysis demonstrated highest diagnostic accuracy for ALT (AUC = 0.999) followed by PON1 (AUC = 0.990), total bilirubin (AUC = 0.977), ALP (AUC = 0.904), total protein (AUC = 0.790) and albumin (AUC = 0.595). Conclusion Diagnostic accuracy of serum PON1 activity is better than total bilirubin, total protein, albumin and

  7. Increased hepatocellular carcinoma risk in chronic hepatitis B patients with persistently elevated serum total bile acid: a retrospective cohort study

    PubMed Central

    Wang, Haoliang; Shang, Xiaoyun; Wan, Xing; Xiang, Xiaomei; Mao, Qing; Deng, Guohong; Wu, Yuzhang

    2016-01-01

    To investigate the association between long-term changes of serum total bile acid and hepatocellular carcinoma in chronic hepatitis B patients, we did a retrospective cohort study of 2262 chronic hepatitis B patients with regular antiviral treatment using data from the Hepatitis Biobank at Southwest Hospital Program from 2004 to 2014. Patients in the study were classified into 3 groups according to persistence of elevated serum total bile acid during follow-up: none-low, medium, and high persistence of elevated serum total bile acid. The association between persistence of elevated serum total bile acid and hepatocellular carcinoma was estimated using Cox proportional hazard models and Kaplan-Meier analysis including information about patients’ demographic and clinical characteristics. There were 62 hepatocellular carcinoma cases during a total follow-up of 14756.5 person-years in the retrospective study. Compared to patients with none-low persistence of elevated total bile acid, the multivariate adjusted hazard ratios (95% confidence interval) were 2.37 (1.16–4.84), and 2.57 (1.28–5.16) for patients with medium, and high persistence of elevated total bile acid. Our findings identified persistence of elevated serum total bile acid as an independent risk factor of hepatocellular carcinoma in chronic hepatitis B patients. PMID:27905528

  8. Off-treatment efficacy of 3-year nucleos(t)ide analogues in chronic hepatitis B patients.

    PubMed

    Lin, Ching-Chung; Bair, Ming-Jong; Chen, Chih-Jen; Lee, Keng-Han; Chen, Ming-Jen; Liu, Chia-Yuan; Chang, Chen-Wang; Hu, Kuang-Chun; Liou, Tai-Cherng; Lin, Shee-Chan; Wang, Horng-Yuan; Chu, Cheng-Hsin; Shih, Shou-Chuan; Wang, Tsang-En

    2016-01-01

    Lamivudine, telbivudine, and entecavir are the first-line drugs covered by the Taiwan National Health Insurance as 3-year treatments for patients with chronic hepatitis B virus (HBV), but the optimal treatment duration of each remains unclear. We aimed to detect HBV treatment-cessation durability, and compare the predictors in patients with and without clinical relapse. In this retrospective cohort study, 210 patients with chronic HBV who tested hepatitis B e-antigen positive or hepatitis B e-antigen negative were treated for 3 years with a nucleos(t)ide analogue. Of these, 102 patients continued therapy after 3 years, while 88 patients stopped treatment and were followed for 1 year due to financial difficulties. Efficacy was assessed in terms of alanine aminotransferase (ALT) level normalization, HBV DNA clearance, virus breakthrough, clinical relapse, and liver decompensation. The durability predictors were evaluated by host factors, HBV DNA, and drug differences. Eighty patients (14 on lamivudine, 19 on telbivudine, and 47 on entecavir) were recruited. There was no difference in clinical-relapse rate among lamivudine, telbivudine, and entecavir (35.7% vs. 36.8% vs. 31.9%, respectively; p = 0.916), and liver decompensated hepatitis was absent. In baseline clinical characteristics, there were no differences between the clinical-relapse and nonrelapse groups in age, sex, cirrhosis, prior treatment, HBV DNA, pretreatment ALT, or hepatitis B e-antigen (HBeAg). The mean 3(rd) year serum ALT level differed significantly between clinical-relapse and nonrelapse patients (37.5 U/L vs. 27.7 U/L, respectively; p = 0.044). The 3-year nucleos(t)ide analogue off-treatment in patients with chronic HBV delivered according to the Taiwan National Health Insurance guidelines had an overall 33.8% 1-year clinical-relapse rate without any decompensated hepatitis flare-ups.

  9. Multicenter clinical study on Fuzhenghuayu capsule against liver fibrosis due to chronic hepatitis B

    PubMed Central

    Liu, Ping; Hu, Yi-Yang; Liu, Cheng; Xu, Lie-Ming; Liu, Cheng-Hai; Sun, Ke-Wei; Hu, De-Chang; Yin, You-Kuan; Zhou, Xia-Qiu; Wan, Mo-Bin; Cai, Xiong; Zhang, Zhi-Qing; Ye, Jun; Zhou, Ren-Xing; He, Jia; Tang, Bao-Zhang

    2005-01-01

    AIM: To study the efficacy and safety of Fuzhenghuayu capsule (FZHY capsule, a capsule for strengthening body resistance to remove blood stasis) against liver fibrosis due to chronic hepatitis B. METHODS: Multicenter, randomized, double blinded and parallel control experiment was conducted in patients (aged from 18 to 65 years) with liver fibrosis due to chronic hepatitis B. Hepatic histologic changes and HBV markers were examined at wk 0 and 24 during treatment. Serologic parameters (HA, LM, P-III-P, IV-C) were determined and B ultrasound examination of the spleen and liver was performed at wk 0, 12 and 24. Liver function (liver function and serologic parameters for liver fibrosis) was observed at wk 0, 6, 12, 18 and 24. Blood and urine routine test, renal function and ECG were examined before and after treatment. RESULTS: There was no significant difference between experimental group (110 cases) and control group (106 cases) in demographic features, vital signs, course of illness, history for drug anaphylaxis and previous therapy, liver function, serologic parameters for liver fibrosis, liver histologic examination (99 cases in experimental group, 96 cases in control group), HBV markers, and renal function. According to the criteria for liver fibrosis staging, mean score of fibrotic stage(s) in experimental group after treatment (1.80) decreased significantly compared to the previous treatment (2.33, P<0.05), but there was no significant difference in mean score of fibrotic stage(s) (2.11 and 2.14 respectively). There was a significant difference in reverse rate between experimental group (52%) and control group (23.3%) in liver biopsy. With marked effect on decreasing the mean value of inflammatory activity and score of inflammation (P<0.05), Fuzhenghuayu capsule had rather good effects on inhibiting inflammatory activity and was superior to that of Heluoshugan capsule. Compared to that of pretreatment, there was a significant decrease in HA, LM, P-III-P and IV

  10. Chronic Hepatitis with Liver Granulomas in a Patient with Granuloma Annulare: A Case Report and Review of the Literature

    PubMed Central

    AlJasser, Mohammed I.; Kalia, Sunil; Yang, H. M.; Ramji, Alnoor

    2017-01-01

    Granuloma annulare (GA) is a benign granulomatous skin disorder of unknown etiology. GA is rarely associated with liver diseases. We report a unique case of chronic hepatitis with liver granulomas in a patient with GA. Despite an extensive workup, no clear etiology for the hepatitis was found. Based on the possible immune pathophysiology of GA and the presence of liver granulomas, the patient was treated with prednisone and azathioprine which resulted in complete normalization of the liver enzymes and concurrent improvement of GA. The association between liver diseases and GA is reviewed. PMID:28326206

  11. Fatal hepatic failure associated with graft rejection following reduced-intensity stem-cell transplantation for chronic idiopathic myelofibrosis (CIMF).

    PubMed

    Miyakoshi, Shigesaburo; Kami, Masahiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Kusumi, Eiji; Matsumura, Tomoko; Onishi, Yasushi; Kobayashi, Kazuhiko; Kim, Sung-Won; Hamaki, Tamae; Takaue, Yoichi; Taniguchi, Shuichi

    2004-12-01

    A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.

  12. Hepatocyte-targeted RNAi therapeutics for the treatment of chronic hepatitis B virus infection.

    PubMed

    Wooddell, Christine I; Rozema, David B; Hossbach, Markus; John, Matthias; Hamilton, Holly L; Chu, Qili; Hegge, Julia O; Klein, Jason J; Wakefield, Darren H; Oropeza, Claudia E; Deckert, Jochen; Roehl, Ingo; Jahn-Hofmann, Kerstin; Hadwiger, Philipp; Vornlocher, Hans-Peter; McLachlan, Alan; Lewis, David L