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. HBV, 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. At this time, the only drug available to treat hepatitis D is pegIFN-α, and it is successful in only 20%–35% of patients (Durantel and Zoulim, 2016). A number of drugs are available for the treatment of hepatitis B and C. Indeed, the RdRp (NS5B), the NS5A replication complex, and the NS3 protease of HCV have been fruitful targets for drug development over the past decade. We now have a growing number of DAAs that inhibit HCV RdRp, the NS3 protease, and NS5A. These DAAs, often used in oral combination therapies, have revolutionized the treatment of HCV, have good safety profiles, and provide well-tolerated and very effective treatments for HCV infection. Available therapies for HBV include IFN and nucleoside and nucleotide analogues. Several agents are in various stages of clinical development for the treatment of HBV. 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 IFN, 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) and 69 (Ocular 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 histologic, 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 ...