Hepatitis D

Abstract

ImportanceHepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV causes more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C virus.ObservationsHDV requires HBV to enter hepatocytes and to assemble and secrete new virions. Acute HDV-HBV coinfection is followed by clearance of both viruses in approximately 95% of people, whereas HDV superinfection in an HBV-infected person results in chronic HDV-HBV infection in more than 90% of infected patients. Chronic hepatitis D causes more rapidly progressive liver disease than HBV alone. Approximately 30% to 70% of patients with chronic hepatitis D have cirrhosis at diagnosis and more than 50% die of liver disease within 10 years of diagnosis. However, recent studies suggested that progression is variable and that more than 50% of people may have an indolent course. Only approximately 20% to 50% of people infected by hepatitis D have been diagnosed due to lack of awareness and limited access to reliable diagnostic tests for the HDV antibody and HDV RNA. The HBV vaccine prevents HDV infection by preventing HBV infection, but no vaccines are available to protect those with established HBV infection against HDV. Interferon alfa inhibits HDV replication and reduces the incidence of liver-related events such as liver decompensation, hepatocellular carcinoma, liver transplant, or mortality from 8.5% per year to 3.3% per year. Adverse effects from interferon alfa such as fatigue, depression, and bone marrow suppression are common. HBV nucleos(t)ide analogues, such as entecavir or tenofovir, are ineffective against HDV. Phase 3 randomized clinical trials of bulevirtide, which blocks entry of HDV into hepatocytes, and lonafarnib, which interferes with HDV assembly, showed that compared with placebo or observation, these therapies attained virological and biochemical response in up to 56% of patients after 96 weeks of bulevirtide monotherapy and 19% after 48 weeks of lonafarnib, ritonavir, and pegylated interferon alfa treatment.Conclusions and RelevanceHDV infection affects approximately 12 million to 72 million people worldwide and is associated with more rapid progression to cirrhosis and liver failure and higher rates of hepatocellular carcinoma than infection with HBV alone. Bulevirtide was recently approved for HDV in Europe, whereas pegylated interferon alfa is the only treatment available in most countries.

HDV screening in chronic HBV: An unmet need of growing importance

“…Gish and others now advocate for universal screening of HDV coinfection among all patients with chronic HBV in the United States. [1,2] However, it is important to remember that detection of HDV infection requires accurate, reliable, and standardized diagnostic tests before universal screening can be implemented. Currently, there is significant variability in the performance of anti-HDV antibody tests and none are Food and Drug Administration (FDA) approved for diagnostic testing.…”

“…Patients with acute HDV-HBV coinfection typically have anti-HDV IgM detectable for 1-3 months after exposure in the serum and HDV-RNA. [2,10] In contrast, a detectable anti-HDV IgG serological test is evidence of either past or current infection, and active HDV infection is defined by detectable HDV-RNA in the blood (Figure 1). If one assumes that up to 4% of the 1.5 million Americans with chronic HBV are anti-HDV IgG positive, there may be as many as 50,000-60,000 individuals with active HDV-HBV coinfection that could benefit from treatment.…”

“…HDV infection is an aggressive form of viral hepatitis associated with accelerated morbidity and mortality in patients with chronic HBV infection. [1,2] HDV is a singlestranded, defective circular RNA virus whose replication inhibits HBV replication but enhances hepatic fibrosis progression and cancer risk. HDV requires the HBsAg envelope protein to enter hepatocytes through the sodium taurocholate co-transporting polypeptide receptor.…”

“…HDV requires the HBsAg envelope protein to enter hepatocytes through the sodium taurocholate co-transporting polypeptide receptor. [2] Exposure to HDV can be determined by the detection of anti-HDV IgG or IgM antibodies, while active infection is defined by the presence of detectable HDV-RNA in the blood. HDV, like HBV, can be parenterally or sexually transmitted and may clinically present as acute coinfection with HBV that is usually self-limited in most patients (95%).…”

“…In contrast, HDV superinfection in a patient with established chronic HBV leads to chronic HDV infection in 80%-90% of patients. [2] HDV is considered a rare or "orphan disease" in the United States (ie, <200,000 patients) but screening for HDV among patients with chronic HBV remains woefully low at 5%-10% due to lack of physician education, awareness, and reliable diagnostic assays.…”