Hepatitis viruses cause inflammation and necrosis of the liver. Hepatitis A and E, which are transmitted via the fecal-oral route, are typically self-limiting, although a small percentage (1%–2%) of those infected will develop fulminant hepatic failure. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D viruses, however, are transmitted parenterally. Hepatitis B and C may or may not cause symptoms of acute infection, but both may progress to chronic infection. Individuals with chronic hepatitis B or C infection are at risk for cirrhosis, liver failure, and hepatocellular carcinoma. There are two notable differences between HBV and HCV. First, HBV is a vaccine-preventable illness, whereas there is no vaccine available to prevent HCV. Second, HCV can be cured with effective treatment, whereas the current treatments for HBV are not completely curative. The hepatitis D virus is defective and requires the presence of the HBV to propagate. Individuals coinfected with hepatitis B and D are at greater risk for cirrhosis and hepatocellular carcinoma compared with individuals with only hepatitis B infection, but fortunately, only about 5% of individuals with HBV are coinfected with hepatitis D.
There are no antiviral therapies available for the treatment of hepatitis A and E viruses. Limited options are available to treat hepatitis D, including pegylated interferon α (pegIFN-α), which is successful in only 20% to 35% of patients (Durantel and Zoulim, 2016) and bulevirtide, an agent recently approved in Europe (Kang and Syed, 2020). Multiple drugs are available for the treatment of hepatitis B and C. Available therapies for HBV include pegIFN-α and nucleoside and nucleotide analogues. Several investigational agents are in various stages of clinical development for the treatment of HBV (Soriano et al., 2020). Hepatitis C is treated with combinations of drugs that inhibit the RNA-dependent RNA polymerase (RdRp, NS5B), the NS5A replication complex, and the NS3 protease. Therapeutic strategies for these two chronic viral infections, hepatitis B and C, are very different and are described separately in this chapter.
Several agents employed against hepatitis viruses, including pegIFN-α, ribavirin, and the nucleoside/nucleotide analogues lamivudine, emtricitabine, and tenofovir, are also used to treat other conditions, described in Chapters 64 (Antiretroviral Agents and Treatment of HIV Infection), 74 (Ocular Pharmacology), and 75 (Dermatological Pharmacology).
Assessing the stage and severity of liver disease is an important aspect of treating individuals with chronic viral hepatitis. Individuals with cirrhosis require additional monitoring for potential complications (e.g., varices and hepatocellular carcinoma), and the approach to treatment differs in cirrhotics and decompensated cirrhotics compared to individuals without significant liver fibrosis. Cirrhosis can be diagnosed with histological, radiographic, or laboratory tests. However, decompensated cirrhosis (also known as end-stage liver disease) is a clinical diagnosis based on the presence of variceal hemorrhage, ascites, jaundice, or hepatic encephalopathy. Decompensated cirrhosis carries a high risk of mortality (median survival 2 years), and these ...