A Case Report of Living Donor Liver Transplantation for Fulminant Hepatitis Related to Hepatitis E Virus Infection.

Hepatitis E virus (HEV) infection which may become fulminant, especially in elderly people is more common than previously recognized in develop countries. Here we report successful living-donor liver transplantation (LDLT) in a case of acute liver failure due to HEV. A 63-year-old Japanese man with no previous history of liver disease was admitted for severe acute hepatitis. Detection of anti-HEV immunoglobulin A established a diagnosis of this virus-related liver failure. The patient suffered from hepatic encephalopathy 10 days after symptom onset and underwent LDLT. The patient had an uneventful course. The HEV RNA showed spontaneous negative conversion 10 weeks after LDLT. LDLT led to a successful outcome in a patient with acute liver failure due to HEV infection and regular testing for HEV RNA should be performed until HEV RNA is undetectable.

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.

Chronic hepatitis E in liver transplant recipients: a significant clinical problem?

Hepatitis E is an inflammatory liver disease caused by infection with the hepatitis E virus (HEV). Five different HEV genotypes have been described. While HEV genotypes 1 and 2 primarily infect man, genotypes 3 and 4 have been detected both in humans and several animal species including pigs. HEV genotype 1 and 2 infections are frequent in Southern Asia and Africa. However, Hepatitis E is more and more considered as an re-emerging zoonotic disease also in industrialized countries as HEV genotype 3 infections seem to increase in Western Europe and North America. Acute hepatitis E usually takes an acute self limited course but may take a fulminant course in particular in pregnant women and patients with pre-existing chronic liver disease. Several cases of persistent HEV-infection have been reported in immunosuppressed patients during the last three years being associated with progressive liver disease in some patients. Thus, screening for HEV RNA should be part of the diagnostic work-up of elevated liver transaminases in organ transplantation recipients or HIV-infected individuals. In this review we summarize the recent data on hepatitis E with a particular focus on the importance of persistent HEV infections in liver transplant recipients.

An Early Viral Response Predicts the Virological Response to Ribavirin in Hepatitis E Virus Organ Transplant Patients.

BACKGROUND: Ribavirin is efficient at treating chronic hepatitis E virus infection in solid-organ transplant patients. However, the early kinetics of viral replication under therapy and the impact of immunosuppressant regimens on viral replication are unknown: thus, determining the aim of our study. METHODS: Thirty-five patients with a solid-organ transplant and chronic hepatitis E virus infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA concentrations were determined before treatment, at days 7, 15, and 21 and at months 1, 2, and 3 during therapy and after ribavirin cessation. RESULTS: A sustained virological response (SVR) occurred in 63%. Decreased viral concentration within the first week post-ribavirin therapy was an independent predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL or greater had an 88% positive predictive value. No correlation between ribavirin trough level on day 7 or at month 2 with a virological response or an SVR was observed. Before therapy, HEV RNA concentration was significantly greater in patients receiving mechanistic target of rapamycin inhibitor-based immunosuppression compared to patients given calcineurin inhibitors. The use of mycophenolic acid did not impact on the response to ribavirin. CONCLUSION: An early response to ribavirin can be used to define the optimal duration of therapy in the setting of HEV infection.

Management of viral hepatitis in liver transplant recipients.

Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.

Hepatitis E seroprevalence and associated factors in rural settlers in Central Brazil

Abstract INTRODUCTION: Prevalence of hepatitis E virus (HEV) infection and associated factors were investigated in rural settlements in Central Brazil. METHODS: A total of 464 settlers were interviewed, and serum samples were tested for anti-HEV IgG/IgM. Positive samples were tested for HEV RNA. RESULTS: Sixteen participants (3.4%; 95% CI 2.0-5.7) were positive for anti-HEV IgG. None was positive for anti-HEV IgM. HEV RNA was not detected. Dwelling in a rural settlement for >5 years was associated with HEV seropositivity. CONCLUSIONS: The results revealed the absence of acute infection and a low prevalence of previous exposure to HEV.

Influence of immunosuppressive therapy on the natural history of genotype 3 hepatitis-E virus infection after organ transplantation.

BACKGROUND: Hepatitis-E virus (HEV) infection can be responsible for chronic hepatitis in solid-organ transplant patients. METHODS: We identified 33 cases of autochthonous acute HEV infection in solid-organ transplant patients. RESULTS: Among 27 HEV-positive patients, who had a follow-up of more than 6 months, 16 (59.25%) evolved to chronic HEV infection, defined by persisting elevated liver-enzyme levels and positive serum HEV RNA 6 months after diagnosis. Serial liver biopsies showed progression in liver activity and liver fibrosis. Three patients developed liver cirrhosis. The proportion of patients receiving tacrolimus compared with cyclosporine A was significantly higher in patients who evolved to chronic disease. Immunosuppressive therapy was reduced in patients with chronic hepatitis; however, those who had a dramatic decrease in tacrolimus trough levels were more likely to clear the virus. Four chronic liver transplant patients were cleared off the virus at 14, 16, 22, and 23 months after diagnosis. At last follow-up, their tacrolimus trough levels and daily steroid doses were significantly lower than those who remained viremic. These four patients had lower liver-enzyme levels and lower activity scores on liver biopsies, and their peripheral blood CD3- and CD4-positive cell counts were also significantly higher. CONCLUSIONS: The rate of chronic HEV-related hepatitis is approximately 60% in solid-organ transplant patients. When possible, the reduction of immunosuppressive drugs targeting T cells should be considered as a first-line therapeutic option.