Fig. 16.12 ). Hence, testing for HCV RNA must be done to confirm the diagnosis of chronic HCV infection. A characteristic clinical feature of chronic HCV infection is episodic elevations in serum aminotransferases separated by periods of normal or near-normal enzyme levels. However, even HCV-infected patients with normal transaminases are at high risk for developing permanent liver damage, and anyone with detectable serum HCV RNA needs treatment and long-term medical  follow-up.
Synthesis of anti-sense (–) RNA template RNA replication
Fig. 16.11 Life cycle of hepatitis C. Viral entry, replication, assembly, and budding are shown, emphasizing steps that can be effectively targeted with anti-viral drugs.
Fortunately, recent years have seen dramatic improvements in treatment of HCV infection that stem from development of drugs that specifically target the viral protease, RNA polymerase, and NS5A protein, all of which are required for production of virus (
Fig. 16.11 ). Combination therapy with these drugs (a strategy akin to triple drug therapy for HIV) has proven to be remarkably effective. The goal of current treatment is to eradicate HCV RNA, which is defined by the absence of detectable HCV RNA in the blood 6 months after treatment is stopped and is associated with a high probability of cure. Currently, over 95% of HCV infections are curable, and this can be expected to improve further as new anti-viral drugs become available. The major downside of these advances is their very high cost; a curative course of drug therapy costs over $100,000, and it is estimated that treatment of HCV infections in the United States alone may generate expenses of over $50 billion over the next 5 years.
Also called the delta agent, HDV is a unique RNA virus that is dependent for its life cycle on HBV. Infection with HDV arises in the following settings:
Coinfection by HDV and HBV. The HBV must become established first to provide the HBsAg, which is necessary for production of complete HDV virions. Coinfection with HBV and HDV is associated with higher rates of severe acute hepatitis and fulminant liver failure, particularly in intravenous drug abusers, and higher rates of progression to chronic infection, which is often complicated by emergence of liver cancer.
Superinfection of a chronic HBV carrier by HDV. The superinfection presents 30 to 50 days later as severe acute hepatitis in a previously unrecognized HBV carrier or as an exacerbation of preexisting chronic hepatitis B. Chronic HDV infection occurs in 80% to 90% of such patients. The superinfection may have two phases: an acute phase with active HDV replication and suppression of HBV with high ALT levels, followed by a chronic phase in which HDV replication decreases, HBV replication increases, ALT levels fluctuate, and the disease progresses to cirrhosis and hepatocellular cancer.
HDV infection occurs worldwide and affects an estimated 15 million individuals (about 5% of the 300 million individuals infected by HBV). Its prevalence varies, being highest in the Amazon basin, Africa, the Middle East, and Southern Italy, and lowest in Southeast Asia and China. In most western countries, it is largely restricted to intravenous drug abusers and those who have had multiple blood transfusions.