In high-resource countries, they have been supplanted by direct acting antiviral agents, which first appeared in 2011; these agents target proteins responsible for viral replication and include the following three classes:
NS3/4A protease inhibitors, including telaprevir, boceprevir, simeprevir, and others
NS5A inhibitors, including ledipasvir, daclatasvir, and others
NS5B polymerase inhibitors, including sofosbuvir, dasabuvir, and othersThese drugs are used in various combinations, sometimes combined with ribavirin, based on the patients genotype, delineated as genotypes 1–6. Genotype 1 (GT1), which is the most prevalent genotype in the United States and around the world, can now be cured with a direct acting antiviral regimen. First-line therapy for GT1 is a combination of sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks for most patients, including those with advanced fibrosis or cirrhosis. Certain patients with early disease need only 8 weeks of treatment while those with advanced fibrosis or cirrhosis who have not responded to prior treatment require 24 weeks. Cost remains a major factor limiting access to these drugs, particularly in low-resource nations; the cost of the 12-week GT1 regimen (SOF/LDV)  has been estimated at US$94,500. Hepatitis D
Hepatitis D is difficult to treat, and effective treatments are lacking. Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis. Hepatitis E
Similar to hepatitis A, treatment of hepatitis E is supportive and includes rest and ensuring adequate nutrition and hydration. Hospitalization may be required for particularly severe cases or for pregnant women. Alcoholic hepatitis
First-line treatment of alcoholic hepatitis is treatment of alcoholism.
Most chronic carriers of hepatitis C are unaware of their infection status. The most common mode of transmission of hepatitis C virus is exposure to blood products via blood transfusions (prior to 1992) and intravenous drug injection. A history of intravenous drug injection is the most important risk factor for chronic hepatitis C. Other susceptible populations include those engaged in high-risk sexual behavior, infants of infected mothers, and healthcare workers. Hepatitis D
The hepatitis D virus causes chronic and fulminant hepatitis in the context of co-infection with the hepatitis B virus. It is primarily transmitted via non-sexual contact and via needles. Susceptibility to hepatitis D differs by geographic region. In the United States and Northern Europe, populations at risk are intravenous drug users and people who receive multiple transfusions. In the Mediterranean, hepatitis D is predominant among hepatitis B virus co-infected people. Hepatitis E
Similar to Hepatitis A, hepatitis E manifests as large outbreaks and epidemics associated with fecal contamination of water sources. It accounts for more than 55,000 deaths annually with approximately 20 million people worldwide thought to be infected with the virus. It affects predominantly young adults, causing acute hepatitis. In infected pregnant women, Hepatitis E infection can lead to fulminant hepatitis with third trimester mortality rates as high as 30%. Those with weakened immune systems, such as organ transplant recipients, are also susceptible. Infection is rare in the United States but rates are high in the developing world (Africa, Asia, Central America, Middle East). Many genotypes exist and are differentially distributed around the world.