Antiviral therapy in chronic hepatitis E: a systematic review

Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon‐α can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and clinicaltrials.gov for articles and abstracts. The keywords ‘“Hepatitis E” or HEV’ AND ‘ribavirin or Rebetol or Copegus’ OR ‘pegylated interferon OR peginterferon′ were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty‐four studies matched our criteria, representing a total of 105 ribavirin‐treated and 8 pegylated interferon‐treated patients. The majority of patients had a solid organ transplant. Sixty‐four per cent of ribavirin‐treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon‐treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E.     

Adherence to treatment and quality of life during hepatitis C therapy: a prospective,real‐life,observational study

Background: Adherence is important for therapy of chronic diseases, but has still not been well studied in real life in chronic hepatitis C. Aims: To assess adherence to hepatitis C combination therapy in routine clinical practice and to identify factors associated with imperfect adherence. Methods: This cohort study included unselected chronic hepatitis C patients initiating peginterferon α‐2b plus ribavirin. 100% adherence was defined by taking all the prescribed doses of both drugs for the full initially intended duration, as declared by the patient or believed by the physician. Quality of life was assessed using the short‐form health survey (SF‐36) questionnaire. Results: 1860 patients were analysed, including 72% treatment‐naive, 36% genotype 2/3, 23% psychiatric, 44% drug addicts and 3% human immunodeficiency virus (HIV)‐positive patients. Early treatment discontinuation occurred in 30% of patients. Overall, 38% of patients reported 100% adherence. Patient‐ and physician‐reported adherences were discordant, with a 20–30% overestimation by physicians. HIV co‐infection [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.36–4.67], no drug use during follow‐up (2.37, 1.30–4.31), genotype 3 (1.55, 1.20–2.00) and treatment‐naive (1.32, 1.03–1.69) were associated with 100% adherence. Quality of life worsened during treatment but returned to baseline after the end of treatment. Conclusions: Imperfect adherence to combination therapy is common in routine patients. Adherence is markedly overestimated by physicians and is associated with some patient's baseline characteristics. Knowledge of these factors might help identify patients who are most in need of intervention and plan more frequent and accurate follow‐up.     

The effects of hepatitis C recurrence on health‐related quality of life in liver transplant recipients

Orthotopic liver transplantation (OLT) remains the definitive treatment for hepatitis C (HCV). Although HCV is the number one indication for OLT in the USA, health‐related quality of life (HRQOL) scores are consistently lower for HCV patients when compared with all OLT indications. HCV is unique in that 95% of transplanted patients experience virological recurrence of HCV hepatitis. Despite few physical manifestations of disease at the time of HCV recurrence, patients report an impaired quality of life and functional status compared with OLT recipients without recurrence. Studies show that patient knowledge of the diagnosis of recurrent HCV alone can negatively impact HRQOL. This suggests that patients perceive themselves as unwell and have significant changes in their mental and physical health despite the absence of disease‐related complications. Multiple studies show that patients with HCV recurrence report significantly higher scores for depression, anxiety and psychological distress. However, only a limited number of studies have investigated the influence of gender, HCV genotype, or HCV antiviral treatment on the HRQOL of OLT recipients with HCV recurrence. This review article describes what is currently known about the impact of recurrent HCV on HRQOL specifically after OLT. Understanding modifiable factors on HRQOL after HCV recurrence in OLT patients can greatly aid in tailoring multidimensional interventions to improve patient HRQOL.     

Acute hepatitis E virus infection causing acute liver failure requiring living‐donor liver transplantation in a non‐pregnant immunocompetent woman

We report a rare case of acute liver failure from acute hepatitis E virus (HEV) in a non‐pregnant woman without comorbidities who survived after liver transplantation. The source was likely consumption of partially cooked pig liver. HEV genotype 3 is the second most common genotype causing acute hepatitis E in developed countries. Fulminant hepatitis E rarely occurs without a risk factor, as in our patient. Vigilant monitoring for chronic hepatitis E in post‐transplant immunocompromised patients is needed.     

Hepatitis E virus: an underdiagnosed cause of chronic hepatitis in renal transplant recipients

Hepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients leading to rapidly progressive cirrhosis. Proper diagnosis is therefore important, as reducing immunosuppressive therapy can allow clearance of the virus. We report a case of chronic HEV infection in a renal transplant recipient that went undiagnosed for many years, discuss the therapeutic options, and review the current available literature.     

Hepatitis E infection in HIV‐infected liver and kidney transplant candidates

Hepatitis E virus (HEV) has been reported to cause acute and chronic hepatitis in those with HIV infection and among solid organ transplant recipients in Europe. Limited data indicate that HEV is endemic in the United States, but the prevalence and significance of HEV infection among those with HIV and awaiting solid organ transplantation is unknown. We evaluated anti‐HEV IgM and IgG antibodies and HEV RNA in 166 HIV‐infected solid organ transplant candidates enrolled in the NIH HIV‐Transplant Cohort. Overall prevalence of anti‐HEV IgG approached 20% in both liver and renal transplant candidates. Evidence of recent infection was present in approximately 2% of liver transplant candidates and none of the kidney transplant candidates. HEV RNA was not detected in any patient. We conclude that markers of HEV infection are frequent among candidates for transplantation, but active, ongoing viremia is not seen. Evidence of recent infection (acute on chronic) liver disease was present in liver but not kidney recipients.     

Types,causes, and therapies of hepatitis occurring in liver transplant recipients

Liver transplantation (OLTx) has become a common life-saving procedure for individuals with chronic advanced liver disease. It is also used in the clinical treatment of patients with fulminant hepatic failure and those with primary neoplastic disease of the liver. Despite its overall success in restoring meaningful life to those who undergo the procedure, the posttransplant life of a liver allograft recipient is not without hazard. A common problem following liver transplantation is the finding of abnormal liver injury tests reflecting a hepatitis that can not be ascribed to allograft rejection. The majority of such cases are a consequence of either a technically flawed operation, drug-induced liver injury, or one or another form of viral hepatitis. Each of these problems is discussed in the following clinical review.     

Prolonged treatment with pegylated interferon α 2b plus ribavirin improves sustained virological response in chronic hepatitis C genotype 1 patients with late response in a clinical real‐life setting in Japan

Aim: This study was conducted to clarify the factors related to sustained virological response (SVR) to pegylated interferon α 2b (PEG‐IFN) plus ribavirin (RBV) combination therapy administered for 48 weeks in patients with chronic hepatitis C virus (CHCV) and to evaluate the usefulness of prolonged treatment in patients with late virological response (LVR). Methods: Of 2257 patients registered at 68 institutions, those with genotype 1 and high viral load were selected to participate in two studies. Study 1 (standard 48‐week group, n = 1480) investigated SVR‐determining factors in patients who received the treatment for ≤52 weeks, whereas study 2 compared SVR rates between patients with LVR who received treatment for either 36–52 weeks (48‐week group, n = 223) or 60–76 weeks (72‐week group, n = 73). Results: In study 1, SVR rate was 44.9%; that in male subjects (50.4%) was significantly (P < 0.0001) higher than in female subjects (36.4%). SVR rate significantly (P < 0.0001) decreased with 10‐year age increments in both sexes. Multivariate logistic regression analysis revealed that age, F score, platelet count, and HCV load were SVR‐related factors. In study 2, SVR rate in the 72‐week group (67.1%) was significantly (P = 0.0020) higher than in the 48‐week group (46.2%). Conclusions: Patients with CHCV genotype 1 infection should be treated with PEG‐IFN plus ribavirin combination therapy as early as possible, and 72 weeks' treatment is recommended in patients with LVR regardless of age.     

Hepatitis E virus infection in the liver transplant recipients:Clinical presentation and management

Hepatitis E virus(HEV) is an emerging pathogen and an increasingly recognized cause of graft hepatitis, especially in the post-orthotopic liver transplantation immunocompromised population. The exact incidence and prevalence of HEV infection in this population remains unclear but is certainly greater than historical estimates. Identifying acute HEV infection in this population is imperative for choosing the right course of management as it is very difficult to distinguish histologically from acute rejection on liver biopsy. Current suggested approach to manage acute HEV involves modifying immunosuppression, especially discontinuing calcineurin inhibitors which are the preferred immunosuppressive agents post-orthotopic liver transplantation. The addition of ribavirin monotherapy has shown promising success rates in clearing HEV infection and is used commonly in reported cases.