An Insight Into the Factors Affecting the Prevalence and Natural History of Hepatitis D

Abstract

Epidemiological studies and recent metanalyses addressing hepatitis D have reported a wide variation in the prevalence of the disease. Between 4.5% to 15% of all hepatitis B surface antigen (HBsAg) positive patients are thought to harbor the hepatitis D virus. The emergent variation in prevalence can be attributed to several factors. Unsurprisingly, published literature shows that the prevalence of the disease is higher in areas where aggregate viral hepatitis infections are endemic and amongst groups with high-risk practices facilitating the horizontal transfer. Meanwhile, the natural history of the disease is influenced by the genotype of the virus, the hepatitis D virus (HDV) RNA levels, HBV-HDV codominance, HBsAg titers, HBV genotype, nutritional status, HIV co-infection, and prior treatment. Together these factors contribute to the accelerated development of fibrosis and the increased risk of hepatocellular carcinoma. Superinfection with genotype 1 results in rapid progression to cirrhosis with lower rates of remission. Genotype 3 follows an aggressive course but shows a good response to interferon therapy. Other genotypes have better outcomes. The course of the disease leading to these outcomes can be tracked by HDV-specific models integrating clinical surrogate markers and epidemiological factors such as age, region, alanine aminotransferase (ALT), gamma-glutamyl transferase, albumin, platelets and cholinesterase, and liver stiffness.

Keywords: cirrhosis; genotypes; hepatitis d; natural history; prevalence; surrogate markers; transmission.

Figure 1. Hepatitis D virus (HDV) life cycle

HDV viral entry is facilitated by the Sodium taurocholate co-transporting polypeptide (NTCP) binding of the HBsAg. Replication of the HDV genome (HDV G) is nuclear and is mediated by RNA Pol I/II. HDV mRNA is used to make hepatitis D antigen (HDAg). The HDAg is prenylated and along with HDV G, is used to assemble the HDV ribonucleoprotein (RNP) in the endoplasmic reticulum (ER). The HDV RNP is enveloped in the Golgi by HBsAg. Expression of cccDNA and HBV integrated into the human genome may provide HBsAg. Other helper viruses may also provide envelope proteins. Superinfection increases the risk of cirrhosis and hepatocellular carcinoma compared to HBV monoinfection.