Approach

The treatment options for hepatitis D virus (HDV) infection are limited. Currently, no pharmacologic therapies are available for acute infection, while patients with chronic infection may be considered for antiviral treatment, including peginterferon alfa. Antiviral therapies specific for HDV infection are available in some countries, but not in the US as yet. Liver transplant is often required in patients with end-stage liver disease or acute liver failure.[12]

The goal of treatment should be to prevent disease progression and lead to biochemical and virologic resolution. In hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, control of virus replication and virus eradication, respectively, leads to improvement in liver function tests (LFTs) and a decrease in clinical endpoints such as cirrhosis, hepatocellular carcinoma, and death.[2][54] In HDV infection, sustained suppression of viral replication and seroconversion of HBV surface antigen (HBsAg) - loss of HBsAg and appearance of antibody to hepatitis B surface antigen (anti-HBs) - would be ideal but is rarely achievable with currently available therapy.

Given the limited efficacy of current treatment and issues with standardization of virologic assays, it is advisable to refer all patients with confirmed HDV infection to a specialized center for management.

This topic does not cover the management of special patient groups (e.g., pregnant women, children) as there are very limited data available on these patients.

Acute HDV infection

Manage patients with acute HDV infection with supportive care, according to their symptoms (e.g., encouraging the patient to remain hydrated and maintaining nutrition).

  • No antiviral drugs are approved for acute HDV infection.

Note that >95% of immunocompetent adults with simultaneous HDV/HBV coinfection will spontaneously clear the virus. However, evolution to chronic infection may occur in >90% of patients with superinfection (HDV infection in a person with chronic HBV infection).[34]

Monitor patients for any change in clinical status that indicates progression to a disease state that requires treatment.[2]

Evaluate patients with fulminant hepatitis for liver transplantation due to the high risk of mortality in this group of patients without transplant.[12] See Acute liver failure.

  • Transplantation in eligible patients is associated with an excellent outcome.[55]

Chronic HDV infection

Peginterferon alfa

Offer peginterferon alfa-2a in all eligible patients with chronic HDV infection with detectable HDV RNA (with or without associated compensated cirrhosis).[1] The preferred duration of treatment is 48 weeks.[1][56]

  • Note that the National Institute for Health and Care Excellence (NICE) in the UK recommends giving peginterferon alfa-2a to patients with chronic HDV infection only if there is evidence of significant fibrosis (METAVIR stage ≥F2 or Ishak stage ≥3) (see Criteria).[56]

  • Consider personalized treatment durations based on HDV RNA and HBsAg kinetics and treatment tolerability.[1]

  • Consider stopping treatment if there is no decrease in HDV RNA following 6 or more months of treatment.[56]

  • Stop treatment after HBsAg seroconversion.[56]

  • Treatment success is defined as undetectable HDV RNA 24 weeks after completing treatment (alongside normalization of alanine aminotransferase [ALT]).[2] One review of 13 studies including 1078 patients demonstrated that the overall virological response (defined as undetectable HDV RNA after 24 weeks following the end of treatment) was 31%.​[57]​ However, relapses of HDV RNA occur commonly in the post-treatment phase and have been reported even 5-10 years after the end of treatment.[58]

  • Peginterferon alfa is contraindicated in patients with decompensated cirrhosis.

Nucleoside/nucleotide analog therapy

Give a nucleoside/nucleotide analog (e.g., entecavir, tenofovir) in all patients with compensated cirrhosis and detectable HBV DNA, regardless of HBV DNA levels.[1] Also consider a nucleoside/nucleotide analog in patients with persistent HBV infection, especially if HBV DNA levels are close to or higher than 2000 IU/mL.[1][2] See Hepatitis B.

Give a nucleoside/nucleotide analog to patients with decompensated cirrhosis irrespective of the presence of detectable HBV DNA.[1]

Liver transplantation for decompensated cirrhosis

Evaluate patients with decompensated cirrhosis for liver transplantation.[1][2] This may include patients with end-stage liver disease as well as those with fulminant hepatitis.[12]

  • Transplantation in eligible patients is associated with an excellent outcome.[55]

  • If liver transplantation is not possible, a best-supportive-care strategy is recommended.[1] See Cirrhosis.

Give patients who have undergone liver transplantation for chronic HDV infection hepatitis B immune globulin combined with a high genetic barrier nucleoside/nucleotide analog after transplantation.[1]

Patients with hepatocellular carcinoma

Prioritize optimal treatment for hepatocellular carcinoma (including liver transplantation) in patients with chronic HDV infection and hepatocellular carcinoma.[1] Evaluate patients with hepatocellular carcinoma for antiviral treatment on an individual basis.[1] See Hepatocellular carcinoma.

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