Viral hepatitis: Past, present, and future

Table 1 Overview of epidemiology, symptoms, natural history and clinical management of viral hepatitis infections

Virus	Estimated number of infections worldwide	Mode of transmission	Typical clinical signs/symptoms	Natural history	Diagnosis	Treatment	Prevention
Hepatitis A	1.4 million annually	Fecal-oral route	Many asymptomatic. Most with non-specific symptoms of fatigue, nausea, vomiting, anorexia, jaundice	Asymptomatic, self-limited illness, prolonged cholestasis, relapsing, fulminant hepatitis (very rare)	Hepatitis A IgM	Supportive care, post-exposure vaccination and HAV immunoglobulin	Sanitation efforts, vaccination
Hepatitis B	257million chronic HBV infections (WHO 2017 Global Hepatitis Report)	Vertical transmission (common for chonic HBV); IVDU, blood product transfusions, sexual contact (common for acute HBV)	Acute: non-specific symptoms (fatigue, nausea, vomiting, anorexia, jaundice); chronic: often asymptomatic, can progress to cirrhosis and HCC	Infection at birth: chronic HBV infection (immune tolerance, immune clearance, inactive carrier, reactivation). Eventual progression to cirrhosis and HCC; infection in adulthood: > 95% clearance	Past infection-HBsAg negative, HBsAb positive, HBcAb positive, HBeAb +/-; current infection-HBsAg positive, HBsAb negative, HBcAb positive, HBeAb +/-	Nucleot(s)ide reverse transcriptase inhibitors (entecavir, tenofovir); interferon	HBV vaccine (universal vaccination recommended at birth); HBIG in select cases
Hepatitis C	71 million (WHO 2017 Global Hepatitis Report)	Direct blood stream inoculation (IVDU, unregulated tattoos/piercings, blood transfusion and organ transplants)	Typically asymptomatic until cirrhosis develops	Spontaneous clearance: 10%-25%; chronic Infection: 75%-90%, can progress to cirrhosis and HCC	HCV antibody, HCV RNA viral load	Direct acting antivirals	Widespread screening efforts
Hepatitis D	12 million cases annually, 4.5% of HBV-infected individuals	Similar to Hepatitis B (IVDU, blood product transfusions, sexual contact)	Non-specific symptoms of fatigue, nausea, vomiting, anorexia, jaundice	Simultaneous coinfection of HDV and HBV: rare fulminant hepatitis, usually complete recovery; superinfection on chronic HBV: accellerated progression of chronic HBV	HDV IgM (acute), HDV IgG (chronic)	Hepatitis B treatment	Hepatitis B vaccination
Hepatitis E	20 million acute infections (The Global Burden of Hepatitis E Virus Genotypes 1 and 2 in 2005)	Genotypes 1 and 2: Fecal-oral route; genotypes 3 and 4: Zoonotic, contaminated meat	Commonly asymptomatic; prodromal flu-like symptoms, nausea, vomiting, anorexia, fatigue followed by jaundice	Acute self-limited in majority of cases, severe in pregnant women; chronic hepatitis in immunocompromised hosts	HEV IgM (acute), HEV IgG (chronic)	Chronic infection: decrease immunosuppression, ribavirin	Genotypes 1 and 2: Sanitation efforts, vaccine available in China
Hepatitis G	4.8% worldwide	Direct blood stream inoculation (IVDU, unregulated tattoos/piercings, blood transfusion and organ transplants)	Not well-described, likely asymptomatic	Not well-described. Unlikely to cause clinically significant hepatitis in humans.	Hepatitis G RNA; not currently used clinically	None	None

HAV: Hepatitis A virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HDV: Hepatitis D virus; HEV: Hepatitis E virus; HGV: Hepatitis G virus; WHO: World Health Organization; IVDU: Intravenous drug use; HCC: Hepatocellular carcinoma; HBIG Hepatitis B immunoglobulin; HBsAb: Hepatitis B surface antibody; HBsAg: Hepatitis B surface antigen; IgG: Immunoglobulin G; IgM: Immunoglobulin M.