Hepatitis A, B, C: Three Viruses, Three Stories

What is Hepatitis?

Hepatitis simply means inflammation of the liver. Many things can cause it (alcohol, drugs, autoimmune disease), but the term usually refers to viral hepatitis. Five main viruses cause hepatitis (A through E), but A, B, and C are the most significant globally.

Despite the alphabetical naming, these are completely unrelated viruses that happen to target the liver. They differ in transmission, chronicity, treatment, and outcomes.

Hepatitis A: The Waterborne Outbreak Virus

Discovery

Outbreaks of jaundice following contaminated food or water have been recognized for centuries. The term "infectious hepatitis" distinguished it from "serum hepatitis" (hepatitis B) in the mid-20th century.

In 1973, Stephen Feinstone at the NIH used electron microscopy to visualize the hepatitis A virus (HAV) in stool samples, finally identifying the agent. HAV is a small, non-enveloped picornavirus.

Transmission and Disease

HAV spreads through the fecal-oral route: contaminated water, shellfish from polluted waters, or food handlers with poor hygiene. It causes acute illness only and never becomes chronic.

Symptoms include jaundice, fatigue, abdominal pain, and nausea. Most people recover completely within weeks to months. Severity increases with age; children often have mild or no symptoms, while adults can become quite ill. Rarely, HAV causes fulminant hepatic failure.

Prevention

The hepatitis A vaccine, available since 1995, is highly effective and provides long-lasting immunity. It's recommended for travelers to endemic areas, men who have sex with men, people who use drugs, and those with chronic liver disease.

Hepatitis B: The Blood-Borne Vaccine Success

Discovery

In 1965, Baruch Blumberg, while studying inherited blood proteins in different populations, discovered a peculiar antigen in the blood of an Australian aboriginal patient. He called it the "Australia antigen."[2]

Initially puzzled by its meaning, Blumberg eventually connected Australia antigen to hepatitis: it was the hepatitis B surface antigen (HBsAg), part of the viral coat. This discovery enabled blood screening, dramatically reducing transfusion-transmitted hepatitis. Blumberg received the 1976 Nobel Prize.

The Virus

Hepatitis B virus (HBV) is a DNA virus with a complex lifecycle involving reverse transcription. It's 50-100 times more infectious than HIV, transmitting through:

• Mother-to-child transmission at birth
• Unprotected sexual contact
• Sharing needles
• Needlestick injuries
• Blood transfusion (now rare with screening)

Acute vs. Chronic

The age at infection determines outcomes dramatically:

• Perinatal infection: 90% become chronic carriers
• Childhood infection: 25-50% become chronic
• Adult infection: 5-10% become chronic

Chronic hepatitis B affects approximately 296 million people worldwide, causing cirrhosis and hepatocellular carcinoma (liver cancer).[1] HBV causes about 820,000 deaths annually.

Treatment and Prevention

The hepatitis B vaccine, developed by Blumberg and colleagues and first licensed in 1981, was the first vaccine to prevent cancer. Universal infant vaccination has dramatically reduced HBV prevalence in vaccinated generations.

Chronic hepatitis B is treated with antivirals (tenofovir, entecavir) that suppress the virus but rarely cure it, as HBV DNA persists in liver cells. Lifelong treatment is often needed.

Hepatitis C: From Mystery to Cure

The "Non-A, Non-B" Enigma

After hepatitis A and B were identified, physicians realized that many cases of post-transfusion hepatitis were caused by neither virus. This "non-A, non-B hepatitis" remained mysterious for over a decade.

In the 1980s, researchers at Chiron Corporation, led by Michael Houghton, embarked on an ambitious molecular search. Working with the CDC's Harvey Alter, who had characterized the clinical disease, they used novel molecular cloning techniques to fish the viral genome out of infected blood.

In 1989, they published the discovery of hepatitis C virus (HCV), the first time a virus was identified by molecular cloning without ever being seen or grown in culture.[3] Charles Rice later proved that HCV alone could cause hepatitis.

Alter, Houghton, and Rice received the 2020 Nobel Prize in Physiology or Medicine for their discovery.[4]

The Silent Epidemic

HCV is an RNA virus that spreads primarily through blood: shared needles, contaminated medical equipment, and historically, blood transfusions before screening began in 1992.

Unlike hepatitis B, most HCV infections become chronic (75-85%). The infection is often silent for decades, slowly damaging the liver. By the time symptoms appear, significant scarring (cirrhosis) may have developed. HCV is a leading cause of liver transplantation.

Approximately 58 million people have chronic HCV infection globally, with 290,000 deaths annually from cirrhosis and liver cancer.

The Cure

Early HCV treatment used interferon and ribavirin, harsh drugs with severe side effects and modest cure rates (~50%). The breakthrough came with direct-acting antivirals (DAAs).

In 2014, sofosbuvir (Sovaldi) was approved, heralding a new era. Modern DAA combinations cure HCV in over 95% of patients with just 8-12 weeks of oral therapy and minimal side effects.[5]

"In my career, I never imagined we'd be able to cure viral hepatitis. It's one of the great achievements of modern medicine."

The challenge now is finding the millions of people who don't know they're infected. In the US, the CDC recommends one-time HCV screening for all adults.

The Path to Elimination

WHO has set a goal of eliminating viral hepatitis as a public health threat by 2030, reducing new infections by 90% and deaths by 65%. Progress requires:

• Hepatitis B vaccination: Already successful; needs sustained coverage
• HCV treatment access: DAAs remain expensive in many countries
• Harm reduction: Needle exchange, safe injection sites
• Screening and linkage to care: Finding the undiagnosed

Several countries, including Egypt and Georgia, have made remarkable progress toward HCV elimination through mass screening and treatment campaigns.