Hepatitis overview, acute liver failure, hepatitis A and E

• "Hepatitis" means inflammation of the liver. It may be acute, settling within six months, or chronic, persisting longer than six months. ^[7]
• The five hepatotropic viruses (A, B, C, D and E) are the classic causes, but hepatitis also comes from other viruses, drugs and toxins, alcohol, autoimmune disease, poor blood flow, and metabolic disease. ^[8]
• Acute viral hepatitis runs through an incubation period, a prodrome of malaise, anorexia and arthralgia, an icteric phase, and convalescence. ^[7]
• Acute liver failure is a distinct emergency: an international normalised ratio (INR) of at least 1.5 and any degree of encephalopathy in a person without prior liver disease and with illness of under 26 weeks. ^{[1] [2]}
• Hepatitis A and E spread by the faecal-oral route and do not become chronic; hepatitis A never becomes chronic, while hepatitis E becomes chronic in immunosuppressed patients. ^{[3] [4]}

By the end of this page you should be able to:

1. Define acute and chronic hepatitis and list the common causes by group.
2. Describe the phases of acute viral hepatitis and explain the symptom pattern from the underlying mechanism.
3. Compare the five hepatitis viruses in a single table, including transmission, incubation, chronicity, distinctive features, vaccines and notes.
4. Recognise acute liver failure, list its complications, and outline ICU management, transplant listing (King's College criteria) and N-acetylcysteine use.
5. Manage a patient with hepatitis A, including diagnosis, supportive care, rare fulminant or relapsing or cholestatic courses, vaccination and post-exposure prophylaxis.
6. Diagnose and manage hepatitis E, including polymerase chain reaction (PCR) testing, ribavirin for chronic infection, pregnancy risk, vaccination and reporting.
7. Adapt care for drug-induced injury, alcoholic hepatitis, and low-resource epidemic settings.

Acute versus chronic. The line is drawn at six months. If hepatocellular injury lasts less than six months and the liver blood tests return to normal, the illness is acute hepatitis. If injury and inflammation persist beyond six months, it is chronic hepatitis. ^{[7] [8]}

This six-month rule is simple but arbitrary, and it is not a prognostic rule. A patient with hepatitis A who is still jaundiced at five months usually recovers; a patient with chronic hepatitis B may have normal tests for years. ^[7]

• Hepatitis A caused an estimated 35,569 deaths worldwide in 2023, about 2.6 percent of all viral-hepatitis mortality, and remains a disease of poor water and sanitation, childhood acquisition and cyclic outbreaks. ^[6]
• Hepatitis E causes an estimated 20 million infections and 3.3 million symptomatic illnesses each year, and caused an estimated 4,431 deaths in 2023. ^[5]
• In hyperendemic regions fewer than one adult in ten escapes hepatitis A: by age 10 years about 90 percent of children have been infected, usually without symptoms. High-income regions see disease mainly in adults in risk groups. ^[6]
• Viral hepatitis of all types is reported in every region. In low- and middle-income settings hepatitis A and E dominate the waterborne burden; hepatitis B and C dominate chronic liver disease and hepatocellular carcinoma. ^{[5] [8]}
• Reporting is the other half of epidemiology. In the United Kingdom every case of acute hepatitis A, B, C, D and E is notifiable to the local public-health body, and large outbreaks are reported to the World Health Organization. ^{[7] [5] [6]}

The book's list is long and worth learning in groups. Think of four families of cause: infection, toxins, immune injury, and the metabolic and vascular conditions that secondarily inflame hepatocytes.

Hepatitis A, B, C, D and E viruses. Hepatitis D is a defective RNA virus that can only replicate in a person who is also infected with hepatitis B virus, because it needs the hepatitis B surface antigen envelope. ^{[8] [7]}

Many viruses disturb the liver. Common examples:

• Cytomegalovirus, Epstein-Barr virus and herpes simplex virus, which are usually subclinical in the liver but can be severe, and are seen in immunosuppressed patients and in pregnancy. ^{[2] [8]}
• Yellow fever virus and the arboviruses, in endemic areas, where jaundice is a hallmark. ^[5]

• Drugs are a common cause, both predictable dose-dependent injury (for example acetaminophen) and idiosyncratic reaction. Antibiotics, antituberculosis drugs, anti-epileptics, non-steroidal anti-inflammatory drugs, statins, biologic agents and herbal or dietary supplements all feature in case series. ^{[1] [2]}
• Herbal products and over-the-counter supplements deserve a specific question in the history, because patients often do not report them as medicines. ^[2]
• Alcohol causes both fatty liver and alcoholic hepatitis; the alcoholic hepatitis syndrome is described briefly at the end of this page. ^[7]
• Food-borne toxins, in particular amatoxin-containing mushrooms (Amanita phalloides), cause a fulminant picture that is easy to miss unless the exposure history is sought. ^[2]

Autoimmune hepatitis, in which the immune system attacks hepatocytes. It can present with the biochemical pattern of acute or chronic hepatitis, and it is an important differential whenever tests do not settle. ^{[1] [2]}

Ischaemic or shock liver follows a sudden fall in liver perfusion: hypotension, sepsis, cardiac failure, or thrombosis of the hepatic or portal vein. Transaminases rise to the thousands within 24 to 48 hours, and the picture changes rapidly. ^[1]

Common important examples in this group are Budd-Chiari syndrome and veno-occlusive disease. ^{[1] [2]}

• Wilson disease (copper accumulation), classically a young person with haemolytic anaemia, high bilirubin, renal failure and a low alkaline phosphatase. ^[2]
• Haemochromatosis (iron overload).
• Alpha-1 antitrypsin deficiency, an important treatable cause of cryptogenic cirrhosis. ^{[8] [2]}
• Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease), now one of the commonest causes of raised transaminases in adults with obesity, diabetes, dyslipidaemia or hypertension. ^[8]

Biliary obstruction (gallstone, stricture, tumour) usually produces a cholestatic rather than hepatocellular pattern. Infiltrative disease such as sarcoidosis, lymphoma, amyloid, or metastatic disease can also raise alkaline phosphatase disproportionately. ^[8]

Acute viral hepatitis follows a characteristic shape, whatever the virus. Recognising the phases matters, because infectivity is highest before jaundice, and because the pattern of symptoms can be predicted. ^{[7] [3] [6]}

1. Incubation. Replication in liver cells, excretion in bile and stool. For hepatitis A the average is 28 days (range 15 to 50); for hepatitis B 30 to 180 days; for hepatitis C 14 to 180 days; for hepatitis E 2 to 10 weeks. ^{[3] [8] [5] [7]}
2. Prodrome. Non-specific symptoms begin a few days before jaundice: malaise, anorexia, nausea, vomiting, right upper quadrant discomfort, arthralgia, myalgia, and fever. Some patients experience a serum-sickness-like syndrome (rash and arthralgia) for 1 to 2 weeks, particularly in acute hepatitis B and C. ^{[7] [6]}
3. Icteric phase. Jaundice, dark urine and pale stools appear as hepatocellular injury limits excretion. For hepatitis A jaundice is seen in over 70 percent of infected adults and children over five, but in only about 10 percent of children under six. ^{[3] [6]}
4. Convalescence. Appetite returns, jaundice clears, and transaminases fall towards normal over 2 to 12 weeks. ^{[7] [6]}

Why these symptoms? The virus injures hepatocytes, but most of the illness is immunologically mediated. The immune response clears the infected cells; cytokines cause the malaise and fever, bile handling is disturbed, producing jaundice and dark urine, and cholestasis gives itch. ^{[8] [7]}

The timing of infectivity is what surprises students. For hepatitis A, the patient is most infectious during the two weeks before jaundice, when virus concentration in stool is highest. By the time jaundice has appeared, infectivity is falling, and most immunocompetent adults cease shedding about one week after jaundice onset. ^[3]

The crucial separator is hepatic encephalopathy. Acute liver injury (ALI) is coagulopathy without encephalopathy; it is the stage before ALF. ^[1] The syndrome is uncommon, 2,000 to 2,300 cases per year in the United States, and carries high mortality. ^[2]

ALF is not acute-on-chronic liver failure, and it is not alcoholic hepatitis presenting with jaundice, although these can look similar. Naming the syndrome correctly changes management. ^{[1] [2]}

• Hyperacute group (2 to 4 days): acetaminophen (paracetamol) toxicity and ischaemic injury; these are never subacute. ^[1]
• Subacute group (usually ill for at least two weeks): drug-induced liver injury, autoimmune hepatitis, viral hepatitis including hepatitis A, B, C, D and E, and Wilson disease. ^{[1] [2]}
• Pregnancy-related: acute fatty liver of pregnancy and HELLP syndrome. ^[2]
• Vascular: Budd-Chiari syndrome, usually with acute hepatic vein thrombosis. ^[2]

Aetiology varies by region. Acetaminophen dominates in North America and much of Europe; hepatitis B and E are more prominent in the Middle East, Asia, South America and Africa. ^[1] Alcohol-related injury and drug-induced injury account for roughly 12 percent of registered cases in the United States, with herbal and dietary supplement injury doubling over the past decade. ^[1]

In acute hepatitis B infection, only about 1 percent of patients progress to ALF, rising to about 20 percent with hepatitis D superinfection. 4 Out of 5 older patients and those with hepatitis C in acute hepatitis B have higher rates of ALF. ^[2]

Alert yourself to ALF whenever a patient has acute hepatitis with confusion, drowsiness, asterixis or any change in behaviour. Jaundice usually precedes encephalopathy. ^[2] The peak aminotransferase level does not predict liver failure; prolonged coagulation is the biochemical hallmark. ^[7]

ALF is a multi-organ syndrome. The expected complications are:

• Cerebral oedema and raised intracranial pressure, the classic and feared complication of ALF. ^{[1] [2]}
• Coagulopathy from failed synthesis of clotting factors. The INR rises but does not by itself predict bleeding risk; clinically significant bleeding is uncommon, about 5 percent of cases. ^{[1] [2]}
• Hypoglycaemia, which can be profound and continuous, requiring glucose infusion. ^[2]
• Infection, consistently the leading cause of death, fungal included. ^[2]
• Acute kidney injury and renal failure, common in acetaminophen toxicity. ^{[1] [2]}
• Cardiovascular collapse, with a hyperdynamic circulation and vasodilation. ^[1]
• Hypoxia, lactic acidosis and electrolyte disturbance. ^{[1] [2]}

1. Neurology and cerebral oedema. Allow spontaneous hyperventilation; do not warm a patient with spontaneous hypothermia; keep the head of the bed at 30 degrees; minimise stimulation; maintain serum sodium at 145 to 155 millimoles per litre. ^[1]
2. Established cerebral oedema: mannitol 0.5 to 1.0 gram per kilogram intravenously, hypertonic saline boluses, continued continuous venovenous haemofiltration; maintain cerebral perfusion pressure above 60 millimetres of mercury with norepinephrine; consider therapeutic plasma exchange and deeper sedation. ^{[1] [2]}
3. Vasopressors. Restore mean arterial pressure to above 65 millimetres of mercury; norepinephrine is preferred; add vasopressin or hydrocortisone if needed. ^{[1] [2]}
4. Renal replacement. Continuous renal replacement therapy is preferred, started early for oliguria, creatinine rise above 0.3 milligrams per decilitre, ammonia above 150 micromoles per litre, volume overload or intracranial hypertension; it lowers ammonia and may improve transplant-free survival. ^{[1] [2]}
5. Infection. Daily surveillance cultures are recommended; broad-spectrum antibiotics are used with infection, progression of encephalopathy or listing for transplant. ^{[1] [2]}
6. Glucose and nutrition. Treat glucose below 80 milligrams per decilitre with dextrose; begin enteral feeding early when possible. ^{[1] [2]}
7. Coagulopathy. Do not correct an elevated INR routinely in the absence of active bleeding or a high-risk procedure; the INR is not a reliable index of bleeding risk in ALF. ^[1]
8. Ventilation. Intubate for grade 3 or 4 encephalopathy; allow spontaneous hyperventilation and do not correct it. ^{[1] [2]}

N-acetylcysteine (NAC). NAC is the recognised antidote in acetaminophen poisoning, and intravenous NAC is recommended for all patients with ALF and grade 1 or 2 encephalopathy regardless of aetiology, because even non-acetaminophen ALF may improve. ^{[1] [2]} One 2010 review describes oral or 72-hour intravenous regimes. ^[2]

Intracranial pressure monitoring is controversial. It is used selectively in high-risk liver transplant candidates with clinical evidence of intracranial hypertension, because bleeding risk is real and no study has shown improved neurological outcome. ^[1]

King's College criteria remain the standard and divide patients by aetiology. ^[2]

Acetaminophen-induced ALF

• Arterial pH below 7.30 after fluid resuscitation, or all of the following in a 24-hour period: prothrombin time above 100 seconds (INR above 6.5), creatinine above 3.4 milligrams per decilitre, and grade 3 or 4 hepatic encephalopathy.

Non-acetaminophen ALF

• Prothrombin time above 100 seconds (INR above 6.5), regardless of grade of encephalopathy, or
• Any three of the following: an aetiology of non-A non-B viral hepatitis, drug-induced or indeterminate ALF; jaundice to encephalopathy interval above 7 days; age below 10 or above 40 years; prothrombin time above 50 seconds (INR above 3.5); or serum bilirubin above 17.4 milligrams per decilitre (about 300 micromoles per litre).

A United States status 1A (super-urgent) listing requires encephalopathy onset within 8 weeks of the first symptoms of liver disease, admission to an intensive care unit, and either INR above 2, intubation, or continuous renal replacement therapy. ^[1]

King's criteria provide reasonable but imperfect predictive accuracy; newer dynamic scores, including the United States Acute Liver Failure Study Group prognostic index and the updated King's dynamic model, try to capture deterioration over the first days. ^{[1] [2]}

Unassisted survival depends strongly on aetiology. In one large registry, 21-day transplant-free survival was about 65 percent for acetaminophen injury, 51 percent for hepatitis A, and about 19 percent for hepatitis B, with overall survival around 77 percent for hepatitis A and 53 percent for hepatitis B. ^[1] Even with aggressive care, ALF mortality is still 30 percent in Europe and North America, and it is higher where resources are scarce. ^[1]

Hepatitis A is an acute, self-limited infection that never becomes chronic. Clinical illness is age-dependent: around 70 percent of children under six are asymptomatic, while over 70 percent of older children and adults develop jaundice. ^{[3] [6]}

The usual incubation is 28 days (range 15 to 50). Jaundice appears in under 60 percent of patients overall in some series; dark urine and pale stools are typical; serum bilirubin and aminotransferases fall as recovery progresses, and recovery may take several weeks or months. ^[6]

Peak infectivity is in the two weeks before jaundice, and most immunocompetent adults stop shedding about one week after jaundice appears. Children and immunocompromised patients can shed for months. ^[3]

Rare variants matter clinically:

• Fulminant hepatitis A occurs in under 1 percent of cases, but more often in older adults and people with chronic liver disease; it is the reason ALF is listed as a complication. ^{[3] [6]}
• Prolonged or relapsing hepatitis is seen in 10 to 15 percent of symptomatic patients, with recurrent elevation of enzymes up to six months; recovery from relapse is universal and infectivity returns during relapses. ^[3]
• Cholestatic hepatitis A, with prolonged alkaline phosphatase and bilirubin elevation and itch. ^{[3] [6]}

ALF from hepatitis A is uncommon in healthy young adults: older patients develop ALF in about 0.2 to 0.4 percent of infections and hepatitis A accounted for 2.6 percent of United States ALF registry cases. ^[2]

Extrahepatic complications include arthritis, vasculitis, rash, and, rarely, pancreatitis. ^[3]

Clinical features alone cannot separate hepatitis A from other viral or drug-induced hepatitis. Diagnosis is the detection of immunoglobulin M (IgM) anti-hepatitis A virus (anti-HAV) in serum in a symptomatic patient. A total anti-HAV or IgG test shows prior infection or vaccination and confers lifelong protection. ^[3]

Biochemical markers follow the viral pattern: transaminases rise before symptoms and fall before enzymes normalise; viraemia is lower than stool levels. Polymerase chain reaction (PCR) for HAV RNA is reserved for unusual cases such as immunosuppressed patients or early infection. ^[3]

• Supportive care only: hydration, nutrition, rest, and avoidance of unnecessary hepatotoxins such as acetaminophen and alcohol. Recovery may take several weeks or months. ^[6]
• Hospital admission only is needed for severe disease or ALF. ^[6]
• Cholestatic variant is self-limited; treat pruritus with cholestyramine, and rifampicin or ursodeoxycholic acid as needed locally. ^[7]
• Fulminant hepatitis A is managed like any other ALF: ICU support, N-acetylcysteine has been described in children with hepatitis A-induced ALF, and liver transplantation when criteria are met. ^[2]

• Routine immunisation from 12 months of age, with catch-up for unvaccinated children and adolescents aged 2 to 18 years. ^[3]
• Single-antigen hepatitis A vaccines are given as two doses; the interval between doses is usually 6 to 18 months. The combined hepatitis A and hepatitis B vaccine is given as three doses at 0, 1 and 6 months in adults. ^[3]
• Adults at risk and those requesting protection should be offered vaccination: travellers to endemic areas, men who have sex with men, people who use injection or non-injection drugs, people experiencing homelessness, people with chronic liver disease, and people with HIV infection, including vaccination during pregnancy when risk is present. ^[3]
• Infants aged 6 to 11 months travelling to endemic areas may receive an early dose that does not count towards the routine series. ^[3]

Active or passive protection must be given within two weeks of exposure; after that it is no longer established to prevent infection. ^[3]

• Under 12 months: immune globulin 0.1 millilitres per kilogram intramuscularly, instead of vaccine. ^[3]
• Healthy people aged 12 months and over: one dose of single-antigen hepatitis A vaccine as soon as possible, with immune globulin co-administered to those aged over 40 years depending on the clinician's assessment. ^[3]
• Immunocompromised people or those with chronic liver disease: vaccine and immune globulin together in different limbs as soon as possible. ^[3]
• A second vaccine dose six months later gives long-term immunity; it is not needed for post-exposure protection. ^[3]

Water, sanitation, hygiene, and safe food (thorough cooking: heat above 85 degrees Celsius for one minute inactivates hepatitis A) and hand washing remain the backbone of prevention, with vaccination as the medical layer. ^{[3] [6]}

• Hepatitis E is the commonest cause of acute viral hepatitis worldwide. ^[4]
• Genotypes 1 and 2 infect humans and cause waterborne epidemics, mainly in South and Central Asia and Africa. Genotypes 3 and 4 are zoonotic, mainly genotypes of swine, and cause sporadic disease in high-income countries from undercooked pork, wild boar or deer. ^{[4] [5]}
• The incubation is 2 to 10 weeks, averaging 5 to 6 weeks. Most infections are mild or asymptomatic, with a self-limited icteric hepatitis resembling hepatitis A. HEV tends to cause more prolonged cholestasis. ^{[5] [4]}
• Less than 5 percent of acute HEV infections progress to ALF, more often in pregnant women, malnourished patients and those with chronic liver disease. ^[5]

Diagnosis combines serology and nucleic acid testing, as each compensates for the other's weakness. ^[4]

• Anti-HEV IgM appears roughly 4 weeks after infection and persists for 6 to 9 months; in immunocompetent patients sensitivity is about 80 to 90 percent and specificity at least 99.5 percent. ^[4]
• HEV RNA in blood or stool is the gold standard; it becomes positive about 2 weeks after infection and persists for 4 to 5 weeks. It is the essential test in immunosuppressed patients, in whom IgM may be falsely negative. ^[4]
• In immunosuppressed patients, HEV RNA must be detectable for 3 months or more to call the infection chronic; before declaring cure, RNA testing of both blood and stool is expected. ^{[4] [8]}

• Uncomplicated acute HEV is self-limited: supportive care, hydration and nutrition, avoiding hepatotoxins such as unnecessary paracetamol. ^{[4] [5]}
• Severe acute hepatitis or acute-on-chronic liver failure: oral ribavirin for three months is the drug of choice, based on accumulating evidence although mostly anecdotal in acute disease. ^[4]
• Chronic HEV in the immunosuppressed (transplant recipients, HIV, haematological malignancy): first try to reduce immunosuppression, which clears virus in about one third of patients; if that fails, or is unsafe, oral ribavirin (initially 3 months, median dose around 8 milligrams per kilogram per day; sustained virological response in about 78 percent) is the drug of choice. Interferon alpha works but risks transplant rejection. ^[4]
• Corticosteroids have been associated with biochemical recovery and may prevent progression of severe hepatitis to liver failure. ^[4]
• No licensed antiviral exists for HEV in pregnancy; sofosbuvir looks promising in laboratory and early clinical data but remains investigational. ^[4]

This is the headline clinical feature of hepatitis E. HEV genotypes 1 and 2 are responsible for most pregnancy morbidity. Maternal mortality is 15 to 25 percent with third-trimester infection, and up to 20 to 25 percent of pregnant women can die if they acquire HEV in the third trimester. ^{[4] [5]}

• Fulminant disease may include disseminated intravascular coagulation, encephalopathy and cerebral oedema in up to 70 percent of HEV-infected pregnant women. ^[4]
• Fetal loss is common: 15 to 50 percent of infants die in utero or within a week of birth in some series, and vertical transmission occurs. ^[4]
• Ribavirin and interferon are contraindicated in pregnancy (teratogenic and abortifacient), so management is supportive, intensive and multidisciplinary, with transfer to a transplant unit if liver failure develops. ^{[4] [5]}
• Genotypes 3 and 4 do not appear to carry the same maternal risk, but the evidence base is smaller. ^[5]

• Hepatitis E vaccine (HEV 239, Hecolin) is licensed in China for people aged 16 years and over at 0, 1 and 6 months; it is not yet licensed in most other countries, but the World Health Organization has recommended its use as an outbreak response measure, including in pregnant women during outbreaks. ^[5]
• Genotypes 1 and 2 protection depends on water, sanitation and hygiene: safe water, chlorination, safe disposal of faeces, and hand washing.
• For individual protection cook meat thoroughly at 70 degrees Celsius or above; avoid raw or undercooked pork, wild boar, deer and shellfish, especially in immunosuppressed people or those with chronic liver disease. ^[4]

Drug-induced liver injury (DILI) is the other common cause of the hepatocellular ALF group and a common cause of raised transaminases generally. It ranges from a brief ALT rise that resolves on stopping the drug to fatal failure. Key diagnostic clues: a temporal link to drug start (days to months, with drug-induced liver injury from isoniazid, amoxicillin-clavulanate, flucloxacillin, nitrofurantoin, alpha-methyldopa and many statins often appearing after weeks), exclusion of other causes, and improvement after withdrawal. ^{[1] [7]}

The R ratio classifier ((ALT divided by its upper limit of normal) divided by (alkaline phosphatase divided by its upper limit of normal)) separates hepatocellular (above 5), mixed (2 to 5) and cholestatic (below 2) patterns. ^[2]

Common culprits include antibiotics (amoxicillin-clavulanate is one of the leading causes in Western series), antituberculosis therapy (the commonest drug-induced cause of ALF in South Asia), anti-epileptics, non-steroidal anti-inflammatory drugs, herbal supplements, and acetaminophen. Hy's law (ALT above 3 times the upper limit of normal with bilirubin above 2 times the upper limit, without cholestasis) marks the high-risk picture. ^{[1] [2]}

See: hepatocellular carcinoma surveillance and management is outside this page; a separate MedGrasp page on drug-induced liver injury is planned.

Alcoholic hepatitis is an acute-on-chronic inflammatory syndrome on top of alcohol-related liver disease. Classically the AST is higher than ALT, often with an AST to ALT ratio of 2 to 1 or more, and the transaminases are rarely above 300 international units per litre; the bilirubin is raised and alkaline phosphatase modestly so. ^[7]

Patients are jaundiced, often with fever and a tender liver, and serious cases carry high short-term mortality. Abstinence is the cornerstone. Severe disease is stratified with scores (Maddrey's discriminant function, MELD, the Glasgow alcoholic hepatitis score, Lille model at day 7) and eligible severe cases may receive corticosteroids according to current guidelines, with the Lille model used to stop them at day 7 if there is no response. ^[1]

See: alcoholic liver disease and alcoholic hepatitis are covered on a separate MedGrasp page.

• Hepatitis A and E epidemics are water-borne and close-quarters diseases: refugee camps, conflict settings, institutional crowding and homelessness. Case numbers can be explosive, as in the 1988 Shanghai hepatitis A outbreak affecting about 300,000 people. ^[6]
• Prevention depends on safe water, sanitation, hand hygiene and food safety; in camps, the World Health Organization emphasises these measures, with HEV vaccine added as an outbreak-response tool where available. ^[5]
• Diagnostic capacity is limited. Hepatitis A IgM is widely available and cheap; IgM anti-HEV is not licensed in some countries, and HEV RNA requires a molecular laboratory. In endemic areas clinicians diagnose on epidemiological and clinical grounds, and confirm with IgM anti-HEV where possible. ^[4]
• Half of registered acute liver failure cases in rural communities in parts of Asia are classified indeterminate because serological testing is limited, and outcome is worse where liver transplantation is unavailable. ALF mortality is markedly higher in underdeveloped countries than in Europe and North America. ^[1]
• Antituberculosis drugs are the commonest drug-induced cause of ALF in South Asia, a point worth remembering in any jaundiced patient on TB treatment. ^[2]

• Hepatitis is liver inflammation; the acute versus chronic split is six months. ^[7]
• The four causes worth thinking of first are infection (viruses A to E plus others), drugs and toxins (including alcohol), autoimmune disease, and ischaemic injury. Add metabolic causes: Wilson disease, haemochromatosis, alpha-1 antitrypsin deficiency and MASLD. ^{[8] [1]}
• Acute viral hepatitis phases: incubation, prodrome (malaise, anorexia, arthralgia), icteric phase, convalescence; highest infectivity is before jaundice. ^{[7] [3]}
• Hepatitis A, D and E spread by the faecal-oral or body-fluid routes respectively: A and E faecal-oral; B, C and D bodily fluids; D needs B; A and E do not become chronic; E may become chronic in immunosuppressed people. ^[8]
• Hepatitis E is most severe in pregnancy (genotypes 1 and 2) and chronic in immunosuppressed patients; genotypes 1 and 2 are waterborne and epidemic, genotypes 3 zoonotic. ^{[4] [5]}
• Acute liver failure equals INR at least 1.5 plus any encephalopathy in a patient without prior liver disease and illness under 26 weeks. ^{[1] [2]}
• Complications of ALF include cerebral oedema, coagulopathy, hypoglycaemia, infection and renal failure. ^{[1] [2]}
• N-acetylcysteine benefits ALF generally, not just acetaminophen; acute liver failure is managed in an ICU with neuroprotection, renal replacement, infection surveillance and transplant planning. ^{[1] [2]}
• King's College criteria separate acetaminophen-induced and non-acetaminophen ALF and guide emergency liver transplantation. ^[2]
• Hepatitis A is self-limited with no chronic phase, diagnosed by IgM anti-HAV, managed with supportive care, and prevented by hygiene, vaccination from 12 months and immune globulin or vaccine within 14 days of exposure. ^[3]
• Hepatitis E is diagnosed by IgM anti-HEV plus HEV RNA, treated with ribavirin when severe, chronic or acute-on-chronic, and prevented by water, sanitation, hygiene, thorough cooking and (in licensed countries) HEV 239 vaccine. ^{[4] [5]}
• Hy's law and the R ratio are practical tools; reporting acute hepatitis to public health protects others. ^[7]