Hepatitis and Liver Disease

TL;DR. The liver runs several hundred chemical processes, and it is the only major organ that can regrow itself. That regenerative power is also why liver disease is silent for so long: the liver keeps working while it is being destroyed, and by the time symptoms appear, much of it has been replaced by scar. Chronic hepatitis B and C viruses, alcohol, and fat accumulation all produce the same endpoint by different routes: cirrhosis, a shrunken, scarred, high-pressure liver that fails, bleeds, and becomes cancerous. Hepatitis B is preventable by a vaccine given at birth. Hepatitis C is curable in 8 to 12 weeks by tablets with almost no side effects. Both remain undiagnosed in most of the people who have them.

Key takeaways

• Roughly 254 million people live with chronic hepatitis B and about 50 million with hepatitis C. Viral hepatitis kills over a million people a year, mainly through cirrhosis and liver cancer.
• Hepatitis C is curable. Direct-acting antivirals achieve cure in over 95 percent of patients with a short oral course. Most people who have it do not know.
• The hepatitis B vaccine was the first vaccine shown to prevent a human cancer, and a birth dose blocks the mother-to-child transmission that causes most chronic infection.
• Cirrhosis is not one disease. Viruses, alcohol, and metabolic fatty liver converge on the same scarred organ.
• Metabolic dysfunction-associated steatotic liver disease (MASLD) now affects roughly a quarter to a third of adults worldwide and is becoming a leading cause of liver transplantation.
• The liver has no pain fibres in its substance, which is a large part of why liver disease is silent.

What the liver does

In short: Six jobs, and every symptom of liver failure is one of them stopping.

Understanding liver failure requires knowing what is lost.

All blood from the intestines passes through the liver before reaching the rest of the body, via the portal vein. That anatomy explains both the liver's job (screening everything absorbed from the gut) and the mechanics of cirrhosis, since a scarred liver obstructs that flow.

What it is

In short: Five lettered viruses plus alcohol and fatty liver, distinguished by route, whether they become chronic, and whether a vaccine exists.

Hepatitis means inflammation of the liver. It can be viral, alcoholic, autoimmune, metabolic, or drug-induced.

Non-viral liver disease now dominates in high-income countries: alcohol-related liver disease and MASLD, the fatty liver of insulin resistance and obesity (Chapter 19). When MASLD progresses to inflammation and cell injury, it is called MASH.

Don't be confused: the age at infection determines whether hepatitis B becomes chronic, and it works the opposite way to intuition. An infected newborn has roughly a 90 percent chance of chronic lifelong infection, because an immature immune system tolerates the virus rather than clearing it. An infected adult clears it more than 95 percent of the time, often after a nasty acute illness. This is why the birth-dose vaccine matters so much and why most of the world's chronic hepatitis B was acquired in infancy.

The history

In short: Hepatitis B gave the first vaccine ever shown to prevent a human cancer, and hepatitis C went from undetectable to curable in three decades.

Epidemic jaundice was described by Hippocrates and recurred through military history; "campaign jaundice" affected armies from the Napoleonic wars through the Second World War.

1965: Baruch Blumberg, studying blood protein variation, found an antigen in the serum of an Australian Aboriginal donor that reacted with antibodies from a haemophilia patient. The "Australia antigen" turned out to be the hepatitis B surface antigen. It gave a blood test in 1971, which allowed the blood supply to be screened, and a vaccine in 1981, the first from purified viral antigen and later the first made by recombinant DNA. Blumberg received the Nobel Prize in 1976.

1984: Taiwan began universal infant hepatitis B vaccination. Childhood liver cancer rates fell measurably over the following decades, making it the first demonstration that a vaccine prevents a human cancer.

Hepatitis C was the disease known throughout the 1970s and 1980s as "non-A, non-B hepatitis": clearly transmitted by transfusion, clearly not either known virus, and undetectable. Michael Houghton's team identified it by cloning viral genetic material directly from infected blood in 1989, without ever seeing the virus. Harvey Alter had defined the disease and Charles Rice later proved the cloned genome could cause infection. The three shared the 2020 Nobel Prize.

2013 to 2014: sofosbuvir and the other direct-acting antivirals arrived. A disease that had been treated with a year of interferon injections, with severe side effects and cure rates around 50 percent, became curable in 8 to 12 weeks of well-tolerated tablets with cure rates above 95 percent. The remaining obstacles have been price and diagnosis rather than biology.

What actually goes wrong

In short: Chronic injury of any cause activates the same scarring cells, so viruses, alcohol, and fat converge on an identical cirrhotic liver.

Viral hepatitis. Hepatitis B and C viruses are not directly very destructive to liver cells. Most damage is immune-mediated: cytotoxic T cells kill infected hepatocytes. In chronic infection, this continues at low intensity for decades. Hepatitis B additionally integrates fragments of its DNA into host chromosomes, which contributes directly to cancer risk and is why hepatitis B can cause liver cancer even without cirrhosis.

Fibrosis and cirrhosis. Chronic injury of any cause activates hepatic stellate cells, which normally store vitamin A and which transform into collagen-producing myofibroblasts. Collagen bands accumulate, dividing the liver into nodules of regenerating cells surrounded by scar. That is cirrhosis, and it produces two problems:

1. Loss of function: fewer working hepatocytes, so less albumin, fewer clotting factors, less detoxification.
2. Portal hypertension: blood from the gut cannot get through the scarred liver, so pressure rises in the portal vein and blood finds collateral routes through small veins that were never built for it, particularly in the oesophagus and stomach.

Early fibrosis is reversible if the cause is removed. Established cirrhosis is largely not, though removing the cause (curing hepatitis C, stopping alcohol) still substantially improves outcomes.

What it does to the body

In short: Silent for years, then fluid in the abdomen, bleeding veins in the oesophagus, confusion from toxins reaching the brain, and liver cancer.

Compensated cirrhosis can be entirely silent for years. Decompensated cirrhosis produces a characteristic set of failures:

• Ascites: litres of fluid accumulating in the abdomen, from low albumin and portal hypertension. It can become infected (spontaneous bacterial peritonitis), a medical emergency.
• Variceal bleeding: the collateral veins in the oesophagus are thin-walled and under high pressure. When one ruptures, the patient vomits large volumes of blood. Mortality from a first bleed remains substantial.
• Hepatic encephalopathy: ammonia and other gut-derived toxins bypass the liver and reach the brain, causing confusion, reversed sleep pattern, a characteristic flapping tremor, and eventually coma.
• Jaundice, itching, easy bruising and bleeding, muscle wasting, and in men, breast enlargement and testicular atrophy from disturbed hormone metabolism.
• Hepatorenal syndrome: kidney failure driven by the circulatory changes of advanced cirrhosis.
• Hepatocellular carcinoma: cirrhosis of any cause raises liver cancer risk substantially, which is why people with cirrhosis are offered six-monthly ultrasound surveillance.

Acute liver failure is a separate emergency: sudden loss of function in a previously healthy liver, most often from paracetamol/acetaminophen overdose, acute hepatitis, or certain drugs and toxins. It causes encephalopathy and coagulopathy within days and is a leading indication for emergency transplantation.

Is it deadly?

• Viral hepatitis causes over a million deaths a year, mostly from cirrhosis and liver cancer, a toll comparable to tuberculosis. Deaths from hepatitis B have been rising in absolute terms even as new infections fall, because of the large infected cohort ageing into complications.
• Cirrhosis of all causes accounts for roughly 2 million deaths a year worldwide.
• Liver cancer is among the leading causes of cancer death globally (Chapter 25).
• Alcohol-related liver disease mortality has risen sharply in several high-income countries, with a marked increase among younger adults and among women.
• Prognosis in cirrhosis is graded by scores (Child-Pugh, MELD) that combine bilirubin, albumin, clotting, and kidney function, and these determine transplant priority.

Is it contagious?

It depends entirely on which one.

• Hepatitis A and E: yes, by the faecal-oral route, through contaminated food and water and poor sanitation. Hepatitis A outbreaks occur in settings with poor hygiene and among people experiencing homelessness or using drugs; vaccination controls it.
• Hepatitis B: yes, through blood, sexual contact, and mother to child. It is roughly 50 to 100 times more infectious than HIV by the same routes and survives on surfaces for days. It does not spread by casual contact, food, or hugging.
• Hepatitis C: yes, through blood. Overwhelmingly through shared injecting equipment in high-income countries and through unsafe medical injections and unscreened blood in others. Sexual transmission is inefficient except in specific contexts.
• Hepatitis D: only in people who already have hepatitis B.
• Alcohol-related liver disease and MASLD: not contagious at all.

Who gets it

In short: 254 million with hepatitis B and 50 million with hepatitis C, most undiagnosed, plus a quarter to a third of all adults with fatty liver.

Hepatitis B is most prevalent in the Western Pacific and Africa, where most infections were acquired at birth or in early childhood. Universal infant vaccination has produced large falls in childhood prevalence in countries that adopted it early.

Hepatitis C prevalence is highest in parts of Central and East Asia, North Africa, and the Middle East. Egypt had the world's highest prevalence, a legacy of mass parenteral treatment campaigns against schistosomiasis in the mid-twentieth century using reused needles, and then ran the most successful elimination programme anywhere: mass screening and treatment of tens of millions of people, reducing prevalence dramatically within a decade. In high-income countries, hepatitis C is concentrated among people who inject drugs and among cohorts transfused before screening began in 1992.

MASLD follows obesity and type 2 diabetes: roughly a quarter to a third of adults worldwide, and over two thirds of people with type 2 diabetes. A genetic variant, PNPLA3, substantially increases risk and is more common in people of Hispanic ancestry, which contributes to higher rates in those populations.

Alcohol-related liver disease depends on quantity and duration, with substantial individual variation: women develop it at lower intakes than men, and genetic factors including PNPLA3 modify risk. Most heavy drinkers develop fatty liver, a minority develop hepatitis, and roughly 10 to 20 percent develop cirrhosis.

Treatment, and how it works

In short: Hepatitis B is suppressed, hepatitis C is cured in 8 to 12 weeks, and fatty liver and alcohol respond to weight loss and abstinence.

Hepatitis B

Treatment suppresses rather than cures, because the virus persists in liver cell nuclei as a stable form called cccDNA that current drugs cannot eliminate. Tenofovir and entecavir are nucleoside/nucleotide analogues that block the viral polymerase, driving viral load to undetectable and substantially reducing cirrhosis and liver cancer risk. Treatment is usually long-term or lifelong. Not everyone with chronic hepatitis B needs treatment; the decision rests on viral load, liver enzymes, and fibrosis.

Prevention is the main event: the vaccine is highly effective, and a birth dose within 24 hours plus antivirals for mothers with high viral load prevents nearly all mother-to-child transmission.

Hepatitis C

Direct-acting antivirals target three viral proteins: the NS3/4A protease, the NS5A protein, and the NS5B polymerase. Combinations such as sofosbuvir/velpatasvir or glecaprevir/pibrentasvir cure over 95 percent of patients in 8 to 12 weeks, across genotypes, with minimal side effects. Cure here means sustained virological response: no detectable virus 12 weeks after finishing, which is durable.

The obstacle has never been the drugs. It is finding people: most people with hepatitis C are unaware. Countries that have made progress did it with broad screening (for example, one-time testing of all adults, plus regular testing of people who inject drugs) plus treatment without restriction.

Fatty liver and alcohol

MASLD/MASH: weight loss is the established treatment, with roughly 7 to 10 percent body weight loss producing improvement in inflammation and fibrosis. GLP-1 based drugs and bariatric surgery achieve this reliably. Resmetirom, a thyroid hormone receptor beta agonist that increases fat metabolism in the liver, became the first drug approved specifically for MASH with fibrosis in 2024.

Alcohol-related liver disease: abstinence is the treatment, and it improves survival at every stage including in decompensated cirrhosis. Treatment of alcohol use disorder (Chapter 43) is therefore liver treatment, and integrating hepatology and addiction care is one of the clearest gaps in current services. Severe alcoholic hepatitis is treated with corticosteroids in selected patients.

Cirrhosis complications

Non-selective beta blockers and endoscopic band ligation to prevent variceal bleeding; diuretics, salt restriction, and drainage for ascites; lactulose (which acidifies the colon and traps ammonia) and rifaximin (a poorly absorbed antibiotic reducing ammonia-producing gut bacteria) for encephalopathy; TIPS, a stent creating a shunt through the liver to relieve portal pressure; and transplantation, which for many is the only definitive treatment.

What treatment costs

• Tenofovir: kidney and bone effects with long use. Stopping hepatitis B treatment abruptly can cause a dangerous flare, so it is not a drug to run out of.
• Direct-acting antivirals for hepatitis C: remarkably well tolerated (fatigue, headache). They can reactivate hepatitis B in co-infected patients, so screening for it first is required. Their price at launch, around 84,000 US dollars for a course, provoked a global argument about drug pricing; generic versions now cost a small fraction of that.
• Diuretics in cirrhosis: electrolyte disturbance and kidney injury.
• Lactulose: diarrhoea and bloating, and it is dosed to a target number of bowel movements per day, which patients are rarely told.
• Transplantation: lifelong immunosuppression, and recurrence of the original disease in the new liver if the cause is not addressed.

What the person can do

In short: Get tested, vaccinate, respect the paracetamol limit, be careful with supplements, and attend cancer surveillance if you have cirrhosis.

• Get tested. One-time hepatitis C testing for all adults is now recommended in several countries, and hepatitis B testing is recommended for anyone born in a high-prevalence region, anyone whose mother had it, and household or sexual contacts of an infected person. Both are silent, both are treatable, and neither is diagnosed by feeling unwell.
• Vaccinate: hepatitis B (universal in infancy in most countries, and available at any age), hepatitis A for travel and specific risk groups.
• Reduce alcohol. For someone with any liver disease, abstinence is the intervention with the largest effect size available.
• Lose weight if MASLD is present, and treat diabetes and lipids.
• Do not exceed paracetamol/acetaminophen dosing. It is the leading cause of acute liver failure in several countries, and the margin between the maximum dose and harm is narrower than most people assume, especially with alcohol or malnutrition, and especially with combination cold remedies that contain it without saying so prominently.
• Be careful with supplements. Herbal and dietary supplements, including green tea extract, anabolic steroids, and various weight-loss products, are a growing cause of drug-induced liver injury. "Natural" is not a pharmacological category.
• If you have cirrhosis, attend surveillance: six-monthly ultrasound for liver cancer, and endoscopy for varices. Both catch things while they are still treatable.

Living with it

Liver disease carries an unusual amount of moral judgement, because two of its leading causes (alcohol and obesity) are widely treated as personal failings, and a third (hepatitis C) is associated with drug use. That judgement has practical consequences: people delay presenting, clinicians under-refer, and transplant eligibility rules involving abstinence periods are debated on ethical as well as medical grounds. Hepatitis B carries heavy stigma in several high-prevalence countries, affecting employment and marriage prospects, despite being manageable and not casually transmissible.

What's next

• Hepatitis B functional cure: combinations of antivirals, RNA interference agents, capsid inhibitors, and immune-modulating approaches aimed at clearing surface antigen, which would allow treatment to stop.
• WHO's 2030 elimination targets for viral hepatitis (90 percent reduction in new infections, 65 percent in deaths). Most countries are not on track, and the gap is diagnosis and delivery, not science.
• MASH drug development, a crowded field following resmetirom, including GLP-1 based agents showing histological improvement.
• Non-invasive fibrosis assessment (elastography, blood-based scores) replacing biopsy, which is already largely accomplished and is what makes population-level screening practical.
• Machine perfusion of donor livers, keeping organs functioning outside the body so more marginal livers can be used and assessed before transplant.

Sources and notes

Prevalence figures are WHO's Global hepatitis report 2024: approximately 254 million people with chronic hepatitis B and 50 million with hepatitis C, and 1.3 million deaths from viral hepatitis in 2022. Australia antigen: Blumberg et al., 1965; Nobel Prize 1976. Taiwan hepatitis B vaccination and childhood liver cancer: Chang et al., NEJM, 1997. Hepatitis C discovery: Choo et al., Science, 1989; Nobel Prize 2020 to Alter, Houghton, and Rice. Direct-acting antiviral cure rates: pooled phase 3 data and real-world cohorts. Egypt's elimination programme: WHO reports, 2023. MASLD prevalence: Younossi et al., meta-analyses. Resmetirom: MAESTRO-NASH, NEJM, 2024. Cirrhosis mortality: Global Burden of Disease estimates.

Open questions. Whether hepatitis B functional cure is achievable with current approaches is unknown. Which patients with MASLD progress to fibrosis, and why most do not, is not resolved. The right abstinence requirements before liver transplantation for alcohol-related disease remain ethically contested.

Next: the diseases that used to kill children by the million, and the vaccines that stopped them. 👉