Helen S. Te

Epidemiology of Hepatitis B and C Viruses: A Global Overview

This article reviews the prevalence, disease burden, genotype distribution, and transmission patterns of hepatitis B virus (HBV) and hepatitis C virus in the 6 World Health Organization regions. The global epidemiology of hepatitis B and C demonstrates a predominantly declining prevalence of the diseases. Improvement in the control of hepatitis B has been largely achieved with implementation of a more universal HBV vaccine program, although a large gap still remains in the effort toward global prevention of hepatitis B. The transmission of hepatitis C has been greatly impacted by mandatory screening of blood donors in most countries in the world, although intravenous drug use continues to be a major source of infection. Public education regarding the risks of exposure to infected paraphernalia as well as household items such as razors is necessary in the continuing effort to curb this disease.

An Interferon-free Antiviral Regimen for HCV after Liver Transplantation

BACKGROUND Hepatitis C virus (HCV) infection is the leading indication for liver transplantation worldwide, and interferon-containing regimens are associated with low response rates owing to treatment-limiting toxic effects in immunosuppressed liver-transplant recipients. We evaluated the interferon-free regimen of the NS5A inhibitor ombitasvir coformulated with the ritonavir-boosted protease inhibitor ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and ribavirin in liver-transplant recipients with recurrent HCV genotype 1 infection. METHODS We enrolled 34 liver-transplant recipients with no fibrosis or mild fibrosis, who received ombitasvir-ABT-450/r (at a once-daily dose of 25 mg of ombitasvir, 150 mg of ABT-450, and 100 mg of ritonavir), dasabuvir (250 mg twice daily), and ribavirin for 24 weeks. Selection of the initial ribavirin dose and subsequent dose modifications for anemia were at the investigators discretion. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. RESULTS Of the 34 study participants, 33 had a sustained virologic response at post-treatment weeks 12 and 24, for a rate of 97% (95% confidence interval, 85 to 100). The most common adverse events were fatigue, headache, and cough. Five patients (15%) required erythropoietin; no patient required blood transfusion. One patient discontinued the study drugs owing to adverse events after week 18 but had a sustained virologic response. Blood levels of calcineurin inhibitors were monitored, and dosages were modified to maintain therapeutic levels; no episode of graft rejection was observed during the study. CONCLUSIONS Treatment with the multitargeted regimen of ombitasvir-ABT-450/r and dasabuvir with ribavirin was associated with a low rate of serious adverse events and a high rate of sustained virologic response among liver-transplant recipients with recurrent HCV genotype 1 infection, a historically difficult-to-treat population. (Funded by AbbVie; CORAL-I ClinicalTrials.gov number, NCT01782495.).

Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease

Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease

Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events

Nonalcoholic steatohepatitis (NASH) is an independent predictor of coronary artery disease (CAD). Our aim was to compare the incidence of cardiovascular (CV) events between patients transplanted for NASH and alcohol (ETOH)‐induced cirrhosis. This is a retrospective cohort study (August 1993 to March 2010) of 242 patients (115 NASH and 127 ETOH) with ≥12 months follow‐up after liver transplantation (LT). Those with hepatocellular carcinoma or coexisting liver diseases were excluded. Kaplan‐Meiers and Coxs proportional hazard analyses were conducted to compare survival. Logistic regression was used to calculate the likelihood of CV events, defined as death from any cardiac cause, myocardial infarction, acute heart failure, cardiac arrest, arrhythmia, complete heart block, and/or stroke requiring hospitalization <1 year after LT. Patients in the NASH group were older (58.4 versus 53.3 years) and were more likely to be female (45% versus 18%; P < 0.001). They were more likely to be morbidly obese (32% versus 9%), have dyslipidemia (25% versus 6%), or have hypertension (53% versus 38%; P < 0.01). On multivariate analysis, NASH patients were more likely to have a CV event <1 year after LT, compared to ETOH patients, even after controlling for recipient age, sex, smoking status, pretransplant diabetes, CV disease, and the presence of metabolic syndrome (26% versus 8%; odds ratio = 4.12; 95% confidence interval = 1.91‐8.90). The majority (70%) of events occurred in the perioperative period, and the occurrence of a CV event was associated with a 50% overall mortality. However, there were no differences in patient, graft, or CV mortality between groups. Conclusions: CV complications are common after LT, and NASH patients are at increased risk independent of traditional cardiac risk factors, though this did not affect overall mortality. (HEPATOLOGY 2012;56:1741–1750)

Autoimmune hepatitis associated with the use of black cohosh: a case study.

Herbal remedies generate more than

Current State of Combined Heart–Liver Transplantation in the United States

1.8 billion in annual sales in the United States. Herbal products have been associated with a wide spectrum of hepatic toxicities. With the recent Women’s Health Initiative Study demonstrating increased risk of breast cancer and cardiovascular events associated with hormone therapy, many women may resort to herbal remedies for persistent menopause symptoms. We report a case of autoimmune hepatitis likely triggered by the use of black cohosh (Actaea racemosa), an agent marketed to treat menopause symptoms. Given this case report, we recommend close monitoring of women using this herbal preparation.

Peginterferon α-2a Combination Therapies in Chronic Hepatitis C Patients Who Relapsed After or Had a Viral Breakthrough on Therapy with Standard Interferon α-2b Plus Ribavirin: A Pilot Study of Efficacy and Safety

BACKGROUND Combined heart-liver transplantation (CHLT) has been increasingly performed in the USA, but published data on overall patient and graft outcomes have been limited. METHODS This study aimed to review the indications, immunosuppression, complications and outcomes of CHLT in the USA. From October 1987 to December 2005, a total of 47 cases of combined heart-liver (n = 41) and heart-liver-kidney transplantation (n = 6) were reported to the United Network for Sharing (UNOS) database. One pediatric case was excluded from the analysis. The mean age of recipients was 46 years (range, 22 to 65 years) and included 31 (67%) men and 16 (33%) women. RESULTS The most common indication for both heart and liver transplantation was amyloidosis (30%). Patients were followed for a mean duration of 1,362 days or 3.7 years (range, 1 to 4,598 days or 0 to 12.6 years). Patient, heart and liver graft survival rates were 84.8%, 84.8% and 82.4% at 1 year, and 75.6%, 75.6% and 73.5% at 5 years, respectively. At the latest follow-up of patients who survived at least 6 months after transplantation (n = 39), 28.2% of patients were on a single immunosuppressive agent. CONCLUSIONS Combined heart-liver transplantation is a viable option for candidates who require the combined transplantation, with outcomes comparable to those of single-organ recipients.

Varicella Infection Following Varicella Vaccination in a Liver Transplant Recipient

There are no established therapeutic regimens for hepatitis C virus (HCV) patients who relapse following treatment with interferon α-2b and ribavirin or those who break through while on interferon α-2b and ribavirin. We therefore evaluated various combination therapies in HCV patients who relapsed or experienced a viral breakthrough. Patients (n = 124) were randomized to 48 weeks of treatment with once-weekly subcutaneous injections of 180 μg pegylated (peg-) interferon α-2a plus oral ribavirin (800–1000 mg/day), mycophenolate mofetil (2 g/day), amantadine (200 mg/day), or ribavirin and amantadine and followed for an additional 24 weeks. The sustained virologic response was higher in patients administered peginterferon α-2a plus ribavirin (38%) or ribavirin and amantadine (45%) than in those administered peginterferon α-2a plus mycophenolate mofetil (17%) or amantadine (10%). As in previous studies, patients with genotype non-1 and those with lower viral loads had better responses than those with genotype 1 and high viral loads, though the differences did not reach significance. The four treatment regimens had similar safety profiles, except that patients receiving ribavirin had greater maximal hemoglobin decreases. These findings suggest that the combination of peginterferon α-2a plus ribavirin or with ribavirin and amantadine is effective in some HCV patients who relapse after treatment with interferon α-2b plus ribavirin.

Results of steroid-based therapy for the hepatitis C-autoimmune hepatitis overlap syndrome.

Varicella infection may result in significant morbidity and mortality in patients who have received an orthotopic liver transplant (OLT). It is unclear if vaccinating these patients against varicella‐zoster virus (VZV) infection is safe or effective. We report on a liver transplant recipient with no prior history of VZV infection who was given the varicella vaccine after an indirect VZV exposure. The patient was subsequently hospitalized twice for treatment of cutaneous varicella infection. We will discuss VZV infection, particularly in relation to liver transplantation, and review the prophylaxis and management of VZV infection after OLT.

Fulminant hepatic failure secondary to malignant melanoma: case report and review of the literature.

OBJECTIVE:Overlap syndromes in which persons manifest clinical, histological, or immunological features of both hepatitis C infection and autoimmune hepatitis are well described. The discordant forms of treatment for hepatitis C and autoimmune hepatitis have made medical management of these patients difficult. We report our experience in using corticosteroids as first line therapy for the hepatitis C–autoimmune hepatitis overlap syndrome.METHODS:Seven patients with this overlap syndrome (diagnosis based on the presence of serum hepatitis C antibody by RIBA and serum hepatitis C RNA by polymerase chain reaction, and serum hypergammaglobulinemia, elevated ANA or ASMA titers, or histological findings consistent with autoimmune hepatitis) were treated with prednisone with or without azathioprine or cyclosporine, and followed for a median duration of 44.5 months.RESULTS:Five patients (71%) showed improvement of median serum ALT level from 162 U/L to 38 U/L (p = 0.04) and median serum γ-globulin from 2.1 g/dl to 1.4 g/dl (p = 0.04) by 6 months of therapy. The mean modified histological activity index score also decreased from 11.4 ± 2.5 to 6.6 ± 2.6 (p = 0.04) by at least 1 yr of therapy. One patient discontinued prednisone while taking azathioprine and experienced a rebound elevation of serum ALT that did not respond to retreatment with prednisone. Antiviral therapy was subsequently administered and resulted in biochemical and virologic response. Hepatitis C virus RNA remained detectable in all other patients.CONCLUSION:Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis C–autoimmune overlap syndrome, resulting in appreciable biochemical and histological response but without viral eradication.