Hepatitis E Treatment & Management

Updated: Mar 13, 2019
  • Author: Prospere Remy, MD; Chief Editor: BS Anand, MD  more...
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Medical Management


Management should be predominantly preventive, relying on clean drinking water, good sanitation, and proper personal hygiene. Travelers to endemic areas should avoid drinking water or other beverages that may be contaminated and should avoid eating uncooked shellfish. Heating pork to an internal temperature of 71°C for 20 minutes is necessary to completely inactivate the hepatitis E virus (HEV). [50] Care should be taken in the preparation of uncooked fruits or vegetables. Boiling water may prevent infection, but the effectiveness of chlorination is unknown.

Hepatitis E is preventable by vaccination. Studies in Nepal and China have shown 95% efficacy of a recombinant genotype 1 HEV vaccine in preventing infection and clinical disease. [11, 12] Not only did the vaccine prevent the genotype 1 (Hecolin) HEV infection, genotype 4 HEV was also prevented with the vaccination, indicating cross-protection against different HEV genotypes. At this time, the vaccine efficacy against HEV genotype 3 is not known. A vaccine developed from HEV genotype 1 HEV vaccine was approved in China in December 2011. A study showed long-term efficacy of this vaccine, as it induced a sustained level of antibodies and protection against hepatitis E for up to 4.5 years. [51]  

However, further evaluation of these vaccines is required to determine their efficacy in special risk groups, such as patients with end-stage liver disease or immunosuppressed individuals, to define the anti-HEV titers that can be considered protective, and to know the duration of their protective effect. [52]

Treatment of acute HEV infection

Acute hepatitis E in immunocompetent persons usually only requires symptomatic treatment, as almost all of them are able to clear the virus spontaneously. A report showed significant improvement of liver enzymes and functions in a patient with severe acute hepatitis E who was treated with ribavirin for 21 days. [53] Although ribavirin therapy is contraindicated in pregnancy owing to teratogenicity, the risks of untreated HEV to the mother and fetus are high, and trials of antiviral therapy might be worthwhile. [34]

Treatment of chronic HEV infection

In transplant recipients with chronic HEV infection, viral clearance is desirable. The first step is to reduce the immunosuppressive therapy, as reduction of immunosuppression results in viral clearance in 30% of patients. [54, 55] Calcineurin inhibitor (cyclosporine A, tacrolimus) and mTOR inhibitors (rapamycin, everolimus) have an in vitro effect of stimulation of HEV replication. [56] However, mycophenolic acid (including prodrug mycophenolate mofetil) inhibits the HEV replication in vitro. [57] Steroids were found not to influence HEV replication in vitro. [57]

Antiviral therapy should be considered for patients for whom immunosuppressive therapy cannot be reduced and for those who do not achieve viral clearance after reducing immunosuppression. Although data are limited, ribavirin monotherapy (600–1000 mg/day) for at least 3 months seems to be the first treatment option for patients with chronic hepatitis E who are not able to clear HEV after immunosuppression is reduced. [58] However, the presence of G1634 mutation in the RdRp domain of HEV ORF1 protein was reported to be associated with ribavirin treatment failure. [59, 60]  In this situation, pegylated interferon alfa may be used as an alternative treatment option if there is no contraindication. It appears that ribavirin causes HEV mutagenesis in treated patients, and distinct mutants within the viral population occur during ribavirin therapy. [60]

Treatment with pegylated interferon alfa for 3-12 months has led to sustained clearance of HEV RNA in patients with chronic hepatitis E who underwent liver transplantation. [61, 62] However, interferon therapy can cause significant adverse effects and organ rejection in transplant recipients, especially those who have undergone heart or kidney transplantation.

A study revealed that sofosbuvir, a nucleotide analogue, inhibits RNA replication of HEV genotype 3 in vitro. In addition, sofosbuvir has an additive antiviral effect when it is combined with ribavirin. [63] Although the data appear promising, more studies are needed to explore the antiviral potential of sofosbuvir in combination with ribavirin in chronic HEV infection, especially in patients in whom ribavirin monotherapy fails to achieve HEV elimination. [64]


Diet and Activity

The acute illness may result in anorexia, nausea, and vomiting, predisposing patients to dehydration. These symptoms tend to be worse in the afternoon or evening. Patients should attempt to ingest significant calories in the morning. As they improve, frequent small meals may be better tolerated. Hospitalization should be considered for patients with dehydration. Neither multivitamins nor specific dietary requirements are required.

Patients should be allowed to function at whatever activity levels they can tolerate. No evidence indicates that bed rest hastens recovery. It actually may retard recovery.