17.10 — Hepatitis A to E

Five viruses share a name because they share a target, and they are otherwise unrelated — different families, different routes, different outcomes.

The name means "inflammation of the liver", and it is a description rather than a diagnosis.

And one of them has produced the most dramatic therapeutic improvement in modern medicine: hepatitis C went from an incurable progressive disease to a cure rate above 95 percent, with 8 to 12 weeks of well-tolerated tablets, within about a decade.

The five, compared

	A	B	C	D	E
Route	Faecal–oral	Blood, sexual, vertical	Blood	Needs B	Faecal–oral
Chronic?	Never	Sometimes	Usually	Yes	Rarely
Vaccine?	Yes	Yes	No	Via B	In some countries
Cure?	Self-limiting	Suppressed	Yes	Difficult	Self-limiting

The pattern worth holding: A and E come from contaminated food and water and do not become chronic. B, C and D come from blood and can.

Hepatitis A

Faecal–oral, from contaminated food or water, and from person to person.

Fever, nausea, abdominal pain, then jaundice with dark urine and pale stools (Chapter 9.4).

And its severity rises with age, which is the opposite of intuition. In young children it is usually asymptomatic; in adults it can be a substantial illness lasting weeks.

Which is why improved sanitation has had a paradoxical effect: fewer children are infected, so more adults reach exposure without immunity, and outbreaks are more symptomatic.

It never becomes chronic, and it confers lifelong immunity.

Rarely — around 0.1 to 0.5 percent — it causes fulminant liver failure, more often in older adults and in those with existing liver disease.

Vaccine: highly effective, two doses, protection for decades. Recommended for travel to endemic areas, for people with chronic liver disease, and for several risk groups.

Post-exposure vaccination within 2 weeks prevents disease in contacts.

Hepatitis B

Transmitted by blood, sexually, and vertically from mother to child.

And the age at infection determines everything.

Infected as a newborn: around 90 percent become chronic carriers.Infected as a young child: around 30 percent.Infected as an adult: around 5 percent.

The reason is immunological. A mature immune system mounts a vigorous response that clears the virus — and that response is what causes the symptoms. A newborn's immune system tolerates it, so there is no illness and no clearance.

Which is why the illness is milder and the outcome worse when infection occurs early, and why vertical transmission is the priority for prevention worldwide.

Chronic infection — around 250 million people. Leads to cirrhosis and liver cancer in a substantial minority over decades.

And hepatitis B causes liver cancer directly as well as through cirrhosis, by integrating into the host genome — which is why cancer can occur without cirrhosis, unlike most liver disease.

Prevention is where this is a success story.

The vaccine is highly effective and is given at birth in most countries.

And it was the first vaccine shown to prevent a cancer. Taiwan's universal infant vaccination programme, begun in 1984, reduced childhood liver cancer by around 70 percent — a direct demonstration that preventing an infection prevents a malignancy.

Preventing mother-to-child transmission: vaccine plus immunoglobulin to the newborn within 12 hours of birth, plus antiviral treatment for the mother if her viral load is high. This reduces transmission from around 90 percent to under 5 percent.

Treatment — antivirals suppress the virus and prevent progression. They do not eliminate it, because the viral DNA persists in liver cell nuclei, so treatment is generally long-term.

Which is the current research target: a cure for hepatitis B, and several approaches are in trials.

Hepatitis C

And this is the one with the transformation.

Blood-borne. Historically transmitted by transfusion before screening began in 1990, by unsafe injections, and now predominantly by sharing injecting equipment.

Around 50 million people chronically infected.

Acute infection is usually silent — most people have no symptoms at all, which is why the majority are diagnosed decades later or not at all.

Around 75 percent become chronic, and over 20 to 30 years a proportion develop cirrhosis and liver cancer.

The old treatment — interferon plus ribavirin — required weekly injections for 6 to 12 months, produced a flu-like illness throughout (Chapter 13.1), caused depression and anaemia, and cured around 40 to 50 percent.

Many patients could not tolerate it, and many were never offered it.

Direct-acting antivirals, from 2014, changed everything.

They target specific viral proteins — the protease, the polymerase, and a protein called NS5A — and are given in combination.

8 to 12 weeks of oral tablets. Cure rates above 95 percent. Side effects mild.

Cure means sustained virological response — no detectable virus 12 weeks after finishing — and it is a genuine cure, unlike HIV or hepatitis B.

And the WHO has set an elimination target for 2030, with several countries — Egypt notably, which had the highest prevalence in the world from historic unsafe injection campaigns — running mass screening and treatment programmes with substantial success.

The obstacles are cost, diagnosis and reaching the populations most affected, particularly people who inject drugs, prisoners, and people in low-income countries. The science is done.

There is no vaccine, largely because the virus is highly variable and natural infection does not produce lasting immunity — so reinfection is possible after cure.

Hepatitis D

A defective virus that cannot replicate on its own — it requires hepatitis B's surface protein to form a particle.

So it only infects people who have hepatitis B, either simultaneously or as a superinfection.

And it makes the disease considerably worse — faster progression to cirrhosis and higher cancer risk.

Which means hepatitis B vaccination prevents hepatitis D as well, by preventing the infection it depends on.

Treatment is difficult, and a new drug blocking viral entry has recently become available in some countries.

Hepatitis E

Faecal–oral, from contaminated water, and — increasingly recognised in high-income countries — from undercooked pork and game.

Usually a self-limiting illness like hepatitis A.

With two important exceptions.

In pregnancy, particularly the third trimester, mortality reaches 20 to 25 percent — a strikingly high figure that is not fully explained.

And in immunosuppressed people it can become chronic and cause rapid cirrhosis, which was only recognised in the 2000s.

A vaccine exists and is licensed in China.

Other causes of hepatitis

Because "hepatitis" is a description.

Alcohol — the commonest cause of liver disease in many countries.

Drugs — paracetamol overdose is the leading cause of acute liver failure in several countries (Chapter 23.6). Also antibiotics, anti-tuberculous drugs, and many herbal products.

Non-alcoholic fatty liver disease — now the commonest liver disease overall (Chapter 9.4), and largely reversible with weight loss.

Autoimmune hepatitis — responds well to immunosuppression.

Other viruses — Epstein–Barr, cytomegalovirus.

Inherited — haemochromatosis (iron overload) and Wilson's disease (copper overload), both of which are treatable and both of which are frequently diagnosed late.

What to do about it

Vaccination — hepatitis A and B. Hepatitis B is in the routine infant schedule in most countries, and adults who missed it can be vaccinated at any age.

Testing. Hepatitis C testing is recommended once in adulthood in several countries, precisely because it is silent and curable. Testing is offered routinely in pregnancy for hepatitis B.

Safe injecting equipment and needle exchange — which reduce transmission substantially and remain politically contested in some places despite consistent evidence.

Blood screening — which has made transfusion-transmitted hepatitis extremely rare (Chapter 13.7).

Safe tattooing and piercing.

Food and water precautions when travelling.

And avoiding alcohol excess and maintaining a healthy weight, which addresses the two commonest causes of liver disease overall.

The encouraging summary

Hepatitis A: vaccine-preventable.Hepatitis B: vaccine-preventable, and the vaccine prevents a cancer.Hepatitis C: curable in 8 to 12 weeks with tablets.Hepatitis D: prevented by preventing B.Hepatitis E: usually self-limiting, and vaccine-preventable in principle.

Within a single generation, a group of diseases that reliably progressed to cirrhosis and liver cancer became preventable or curable. The remaining problem is finding the people who have them.

What the next page fixes

Chapter 17.11 covers what happens when the response to infection becomes the disease — sepsis, which kills around 11 million people a year and where every hour of delay costs lives.