Hepatitis

Hepatitis refers to inflammation of the liver parenchyma and encompasses a wide spectrum of clinical presentations ranging from completely asymptomatic disease to fulminant liver failure. The condition may be acute, resolving within six months, or chronic when liver inflammation persists beyond this timeframe. Hepatitis remains a major global health concern, contributing significantly to morbidity, mortality and the long-term burden of liver-related complications.

Definitions and General Features

Hepatitis involves inflammatory injury to liver cells which may arise from infectious, metabolic, toxic, autoimmune or genetic causes. Some individuals show no symptoms, while others develop manifestations such as jaundice, anorexia, nausea, vomiting, fatigue, abdominal pain and diarrhoea. Acute hepatitis may resolve spontaneously or evolve into chronic hepatitis, whereas chronic disease can progress to cirrhosis, liver failure and hepatocellular carcinoma.
The major viral causes are hepatitis A, B, C, D and E viruses, but various other viruses, including cytomegalovirus, Epstein–Barr virus and yellow fever virus, may also cause liver inflammation. Important non-viral causes include excessive alcohol use, medications, toxins, autoimmune disease and non-alcoholic steatohepatitis.

Clinical Manifestations

The clinical spectrum ranges widely. Some individuals with mild or early-stage inflammation experience no noticeable symptoms, while others present with constitutional signs and liver-specific abnormalities.

Acute hepatitis

Acute viral hepatitis generally follows three characteristic phases:
• Prodromal phase: Marked by non-specific symptoms such as fatigue, nausea, vomiting, anorexia, joint pain and headaches. Fever may occur, particularly with hepatitis A and E. As the phase progresses, dark urine and pale stools may appear.
• Icteric phase: Jaundice typically emerges after one to two weeks of prodromal symptoms. Nonspecific symptoms usually improve, but hepatomegaly and right upper abdominal discomfort are common. Splenomegaly is seen in a minority of cases.
• Recovery phase: Clinical symptoms resolve gradually, although liver function tests may remain abnormal for some time. Hepatitis A and E generally resolve completely within months. Hepatitis B often follows a self-limiting course, whereas spontaneous clearance of hepatitis C is infrequent.
Acute disease may rarely progress to acute liver failure. Drug-induced and autoimmune hepatitis can closely resemble acute viral hepatitis, sometimes accompanied by rash, fever, eosinophilia or bone marrow suppression depending on the aetiology.

Fulminant hepatitis

Fulminant or massive hepatic necrosis is a severe and life-threatening form of acute hepatitis. It is most often associated with hepatitis B and D co-infection or with hepatitis E in pregnancy. Clinical features include coagulopathy, confusion, disorientation and rapid deterioration due to complications such as cerebral oedema, gastrointestinal bleeding, infection and multi-organ failure.

Chronic hepatitis

Chronic hepatitis persists beyond six months. Early disease is often silent and detected on routine laboratory examination. As inflammation advances, symptoms similar to acute hepatitis may appear, including fatigue, anorexia and joint discomfort. Jaundice tends to develop only in later stages.
Hormonal disturbances may arise because liver dysfunction affects endocrine processes, leading to acne, hirsutism and menstrual irregularities. Persistent inflammation and fibrosis eventually result in cirrhosis, characterised by jaundice, weight loss, ascites, coagulopathy and oedema. Cirrhosis predisposes individuals to severe complications such as hepatic encephalopathy, oesophageal varices, hepatorenal syndrome and primary liver cancer.

Causes and Modes of Transmission

Hepatitis arises from multiple categories of causative factors:

Infectious causes

• Hepatitis A and E: Spread mainly via contaminated food and water.• Hepatitis B: Transmitted sexually, through infected blood, or vertically during pregnancy and childbirth.• Hepatitis C: Spread primarily through infected blood, particularly via shared needles.• Hepatitis D: Occurs only in individuals already infected with hepatitis B.• Other viruses: Cytomegalovirus, Epstein–Barr virus and yellow fever virus may also cause hepatitis.

Non-infectious causes

• Alcohol-related liver disease from sustained excessive consumption.• Drug-induced and toxin-induced injury from a variety of medications and environmental exposures.• Autoimmune hepatitis resulting from aberrant immune responses.• Non-alcoholic steatohepatitis (NASH) associated with metabolic factors.• Ischaemic, metabolic and genetic disorders affecting hepatic function.

Epidemiology

Hepatitis has a substantial global impact. Hepatitis A affected over a hundred million individuals worldwide in 2015. Chronic hepatitis B and C together affected nearly half a billion people globally. In the United States, non-alcoholic steatohepatitis affects millions, and alcoholic hepatitis accounts for a significant additional burden. Hepatitis contributes to more than a million deaths annually, largely due to complications such as cirrhosis and liver cancer.
Hepatitis A remains comparatively rare in high-income countries but continues to cause severe outbreaks in areas with limited sanitation. Chronic viral hepatitis strongly influences global patterns of liver disease and is a major driver of transplant need.

Diagnostic and Laboratory Features

Diagnosis is based on a combination of clinical presentation, liver function tests, serology, imaging and, where necessary, liver biopsy. Elevated bilirubin, aminotransferases and alkaline phosphatase are common biochemical indicators of hepatic inflammation or dysfunction. Serological testing distinguishes viral types and identifies acute or chronic infections. Imaging may reveal hepatomegaly, cirrhosis or complications such as ascites.

Prevention and Management Approaches

Vaccines have markedly reduced the burden of several hepatitis viruses. Hepatitis A, B and D are preventable through immunisation strategies, with prevention of hepatitis D achieved via protection from hepatitis B infection. Measures such as adequate sanitation, safe sex practices and avoidance of contaminated needles reduce transmission.
Antiviral medications play an important role in managing chronic viral hepatitis, particularly hepatitis B and C. For NASH, lifestyle modifications including physical activity and dietary changes are central, while autoimmune hepatitis may be controlled with immunosuppressive therapies. Liver transplantation is a potential intervention for acute or chronic liver failure.

Broader Implications

Hepatitis continues to pose challenges to public health, clinical medicine and global disease control. Its varied causes and wide-ranging effects demand attention across prevention, monitoring and long-term management. Although medical advances have improved outcomes for many affected populations, the condition remains a significant contributor to chronic liver disease worldwide and a major focus of ongoing research and public health initiatives.