Hepatitis is caused by processes that injure or inflame liver tissue. The five major viral causes are hepatitis A, B, C, D and E, but viruses are only one category. Other causes include prolonged or excessive alcohol exposure, medicines, recreational or toxic substances, autoimmune disease and metabolic liver conditions. The same clinical finding of elevated liver enzymes can therefore arise from very different mechanisms. Establishing the cause requires consideration of symptoms, exposure history, alcohol intake, medication and supplement use, underlying diseases and appropriate laboratory tests rather than assuming that hepatitis is viral.
Hepatitis A virus and hepatitis E virus primarily cause infection through the faecal-oral route. A person becomes infected by ingesting virus particles, often through contaminated food or water, inadequate sanitation or close contact with an infected person. Hepatitis A is especially associated with contaminated food, water and close-contact transmission, while hepatitis E epidemiology varies according to viral genotype and geographic setting. These viruses generally cause acute rather than persistent infection, although hepatitis E can persist in some immunosuppressed people. Hygiene, sanitation, food safety and vaccination against hepatitis A where indicated are important preventive measures.
Hepatitis B is transmitted through infected blood and body fluids. Important routes include sexual exposure, sharing contaminated injecting equipment, accidental occupational exposure to infected blood and transmission from an infected mother to her infant around the time of birth. The virus can establish chronic infection, particularly when infection occurs early in life. Chronic hepatitis B can produce continuing immune-mediated liver injury and fibrosis and can increase the risk of cirrhosis and liver cancer. Vaccination is a major method of prevention because it provides immunity before exposure to the virus.
Hepatitis C is predominantly a blood-borne infection. Transmission occurs when infected blood enters another person's bloodstream, including through sharing needles or other injecting equipment, inadequately sterilised medical or cosmetic equipment, needlestick injuries and some historical transfusion practices before reliable screening was established. Sexual transmission is less efficient than blood exposure but can occur in particular circumstances. Many acute infections produce few symptoms, allowing chronic infection to remain unnoticed for years. Persistent hepatitis C can cause fibrosis, cirrhosis and liver cancer, but antiviral treatment can eliminate the virus in most treated people.
Hepatitis D occurs only in association with hepatitis B. A person can acquire both viruses simultaneously, known as coinfection, or acquire hepatitis D after already having chronic hepatitis B, known as superinfection. Because hepatitis D depends on hepatitis B for part of its replication cycle, preventing hepatitis B also prevents new hepatitis D infections in people who are susceptible. Hepatitis D can intensify liver inflammation and accelerate progression to cirrhosis compared with hepatitis B infection alone. It is therefore a distinct cause of viral hepatitis but cannot be understood independently of hepatitis B biology.
Alcohol is a major non-viral cause of liver inflammation. Repeated heavy alcohol exposure can produce a spectrum ranging from hepatic steatosis to alcohol-associated hepatitis, fibrosis and cirrhosis. Alcohol metabolism generates acetaldehyde and oxidative stress and alters lipid metabolism, immune signalling and mitochondrial function. Alcohol-associated hepatitis may cause jaundice, abdominal symptoms, fever and systemic illness and can be severe. The amount of alcohol associated with risk varies between individuals, and additional factors such as sex, genetics, nutrition, obesity and coexisting liver disease can influence susceptibility.
Medicines, supplements and toxins can cause drug-induced liver injury, which may resemble viral or autoimmune hepatitis clinically and biochemically. NHS information specifically notes that some medicines, including statins and non-steroidal anti-inflammatory drugs, can be associated with hepatitis in some circumstances, while numerous other medicines can produce liver injury depending on the substance and individual susceptibility. Toxic exposures can similarly damage hepatocytes or interfere with bile flow. A suspected medicine should not automatically be stopped without medical advice when it is essential, because clinicians must balance the probability of drug-induced injury against the risks of discontinuing treatment.
Autoimmune hepatitis occurs when immune mechanisms inappropriately target liver tissue. It is not caused by an infectious organism and cannot be transmitted between people. The precise initiating cause is not completely understood, but genetic susceptibility and environmental triggers may contribute. Other non-infectious conditions, including metabolic fatty liver disease and haemochromatosis, can also produce liver inflammation or injury that may be described clinically in terms of hepatitis. Consequently, determining the cause requires targeted investigation, which may include viral serology, autoimmune markers, immunoglobulins, metabolic tests, imaging and sometimes biopsy. Different causes have fundamentally different treatments, so identifying the underlying mechanism is central to care.
