Hepatitis A and E

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Hepatitis A virus is a non-enveloped RNA virus transmitted in stool before and during early illness. Household contact, contaminated food or water, travel, outbreaks in closed settings and sexual practices involving faeco-oral exposure are important routes. Disease severity rises with age and pre-existing liver disease, but recovery produces immunity and chronic carriage does not occur.

Hepatitis E virus is also an RNA virus but has distinct epidemiology. Waterborne genotypes cause large outbreaks in areas with poor sanitation, whereas UK infections are frequently food-borne zoonoses associated with inadequately cooked pork products, offal, wild boar and venison. Blood products and transplanted organs are uncommon additional routes.

The key infectious-disease decisions are who has a transmissible acute infection, who is developing liver failure, which contacts need action and whether HEV has persisted in an immunosuppressed host. Detailed fibrosis staging, portal-hypertension care and long-term hepatocellular-carcinoma surveillance belong to the linked hepatology pathway.

Notification is based on the acute infectious hepatitis syndrome and jurisdictional rules, not on waiting for every reference result. Early discussion with health protection prevents secondary cases and avoids inappropriate blanket exclusion or prophylaxis.

Key points

HAV spreads mainly through faeco-oral exposure; HEV acquired in the UK is commonly zoonotic and linked to undercooked pork, offal, wild boar or game.
Both usually cause an acute hepatitic illness with malaise, nausea, anorexia, dark urine, pale stools, pruritus and jaundice, but infection may be asymptomatic.
HAV never becomes chronic; HEV can persist in transplant recipients and other immunosuppressed people and may cause rapid fibrosis.
First assess glucose, INR, cognition, renal function and haemodynamic state because liver failure management must not wait for pathogen confirmation.
Request HAV IgM for recent HAV; combine HEV IgM with HEV RNA when immune impairment, early disease or persistent infection makes antibody testing unreliable.
Most uncomplicated infections need supportive care, alcohol avoidance, medication review and planned biochemical reassessment rather than an antiviral prescription.
Acute infectious hepatitis is notifiable; contact the relevant health-protection team for exclusion, contact tracing, outbreak investigation and HAV post-exposure prophylaxis.
Use current UKHSA criteria for HAV vaccine or human normal immunoglobulin after exposure; no routinely available UK vaccine prevents HEV.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

HAV faeco-oral spread

Virus excreted in stool reaches susceptible people through close contact, contaminated hands, food, water or sexual practices involving faeco-oral exposure.

Waterborne HEV

HEV genotypes circulating in areas with poor sanitation cause large outbreaks through faecally contaminated drinking water and food chains.

Zoonotic HEV

UK acquisition commonly follows inadequately cooked pork, offal, wild boar or venison containing HEV able to cross from animal reservoirs.

Parenteral HEV

Infrequent transfusion and transplanted-organ transmission becomes important because recipients are often immunosuppressed and prone to persistent infection.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Hepatocyte immune injury
Viral replication triggers host cytotoxic immune responses against infected hepatocytes, producing aminotransferase release and the systemic inflammatory prodrome.
2
Conjugated jaundice
Inflamed hepatocytes cannot efficiently transport conjugated bilirubin into bile, causing dark urine, pale stool, pruritus and visible jaundice.
3
Synthetic collapse
Extensive hepatocyte loss reduces clotting-factor production, glucose homeostasis and toxin clearance, leading to coagulopathy, hypoglycaemia and encephalopathy.
4
HEV persistence
Weak cellular immune control permits continuing HEV replication in transplant and other immunosuppressed hosts, driving chronic inflammation and accelerated fibrosis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Prodromal viral illness

Fever, profound malaise, anorexia, nausea, vomiting, myalgia and right-upper-quadrant discomfort can precede jaundice by several days.

Cholestatic clues

Dark urine, pale stools, pruritus and scleral icterus accompany conjugated hyperbilirubinaemia and may outlast systemic symptoms.

Severe synthetic failureRed flag

New confusion, low glucose, bruising, rising INR, acidosis or renal dysfunction identifies acute liver failure rather than uncomplicated hepatitis.

UK HEV exposure

Undercooked pork, offal, processed pork products, wild boar or venison is relevant even without overseas travel.

Persistent HEV phenotype

Fluctuating aminotransferases or unexplained graft dysfunction in a transplant recipient should prompt HEV RNA testing despite absent jaundice.

Pregnancy vulnerabilityRed flag

Acute jaundice after travel or sanitation exposure during pregnancy needs urgent assessment because severe HEV can deteriorate rapidly.

Red flags requiring action

Confusion, drowsiness, asterixis or behavioural change with acute hepatitis is encephalopathy until proved otherwise and needs emergency liver-centre discussion.
INR prolongation, hypoglycaemia, metabolic acidosis, oliguria or lactate elevation marks severe hepatic dysfunction even when aminotransferases begin to fall.
Pregnancy with suspected hepatitis E requires urgent obstetric, infection and hepatology assessment because some imported HEV genotypes carry disproportionate maternal and fetal risk.
Immunosuppression with persistent HEV RNA can progress silently to fibrosis and cirrhosis, so apparent biochemical improvement does not prove clearance.
Intractable vomiting, dehydration, bleeding or inability to maintain intake warrants admission rather than routine community observation.
Jaundice in a food handler, care worker or outbreak setting requires prompt health-protection advice before occupational or contact decisions are made.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Immediate severity bundleFirst step
Why
Identify hepatic failure and complications before virological classification.
Interpretation and limitations
Check glucose, INR or prothrombin time, bilirubin, ALT, AST, ALP, albumin, FBC, urea, creatinine, electrolytes, venous gas and lactate; worsening INR or encephalopathy drives escalation.
02
HAV IgM antibody
Why
Support recent hepatitis A infection in a compatible acute syndrome.
Interpretation and limitations
Reactive HAV IgM usually indicates recent infection, but interpret unexpected low-pretest-probability results with timing, clinical findings and laboratory advice; total antibody alone reflects previous infection or vaccination.
03
HEV IgM and IgG
Why
Look for a recent humoral response to hepatitis E.
Interpretation and limitations
IgM supports recent infection but assay limitations and immune suppression cause false results; it cannot by itself establish viral clearance or chronicity.
04
HEV RNA PCR
Why
Confirm active viraemia and detect persistence when serology is unreliable.
Interpretation and limitations
Detectable RNA establishes current infection; repeat positivity over time in an immunosuppressed person requires specialist assessment for chronic HEV and fibrosis.
05
Broader acute-hepatitis screen
Why
Exclude concurrent or alternative causes of hepatocellular injury.
Interpretation and limitations
Select HBV, HCV, EBV, CMV and other infection tests plus paracetamol concentration, autoimmune markers and metabolic work-up from age, exposure and severity; a positive HAV or HEV test does not exclude dual pathology.
06
Ultrasound hepatobiliary imaging
Why
Assess obstruction, vascular disease and structural liver abnormalities when the presentation is not purely hepatitic.
Interpretation and limitations
Biliary dilatation redirects investigation toward obstruction; a normal scan does not exclude acute viral hepatitis or early liver failure.
07
Pregnancy and immune-status assessment
Why
Identify hosts needing modified testing, surveillance or escalation.
Interpretation and limitations
Document gestation, transplant status, immunosuppressive drugs, HIV status when relevant and underlying liver disease because these alter HEV severity and clearance.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Other viral hepatitis

Acute HBV, HCV, EBV and CMV can produce similar malaise, jaundice and hepatocellular enzyme elevation but require different virological markers.

Drug-induced liver injury

Paracetamol, antibiotics, antiepileptics, supplements and other agents produce hepatitic or cholestatic patterns linked to a medication timeline.

Autoimmune hepatitis

Autoantibodies, raised IgG and compatible histology support immune-mediated hepatitis, although infection can coexist or trigger misleading markers.

Biliary obstruction

Gallstones or malignant obstruction favour colicky pain, duct dilatation and a cholestatic profile, but early obstruction can briefly raise ALT markedly.

Ischaemic hepatitis

Shock, hypoxia or cardiac failure causes abrupt massive aminotransferase elevation with a clear physiological insult and rapid biochemical evolution.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01STABILISETriage acute jaundiceFirst stepA patient presents with jaundice, dark urine or a markedly hepatitic blood-test pattern.

1Assess ABCDE, cognition and hydration, then obtain bedside glucose, INR, renal function, acid-base status and a complete medication and toxin history.
2Treat hypoglycaemia immediately, stop non-essential hepatotoxic agents and provide cautious fluid, antiemetic and electrolyte support according to clinical state.
3Discuss encephalopathy, progressive coagulopathy, acidosis, renal injury or rapid deterioration urgently with critical care and a liver-transplant centre.
4Send pathogen tests and notify suspected acute infectious hepatitis in parallel; neither action should delay physiological stabilisation or referral.

02DIAGNOSESeparate HAV from HEV and mimicsThe patient is stable enough for cause-directed acute-hepatitis investigation.

1Build a dated exposure history covering travel, water, food, pork or game, household illness, sexual practices, occupational setting, transfusion, transplantation and medicines.
2Request HAV IgM and HEV serology, adding HEV RNA early when immunosuppression, pregnancy, early sampling or persistent biochemical abnormality raises concern.
3AlternativeTest for alternative viral, toxic, autoimmune, ischaemic and obstructive causes in proportion to severity rather than stopping after the first reactive result.
4Use the local laboratory or reference service to resolve discordant serology, define RNA follow-up and support outbreak typing when health protection requests it.

03SUPPORTManage uncomplicated acute infectionHAV or acute HEV is confirmed without liver failure, uncontrolled vomiting or a high-risk host feature.

1Encourage oral fluids and nutrition as tolerated, prescribe symptom relief cautiously and advise complete avoidance of alcohol until clinical and biochemical recovery.
2Review prescribed, over-the-counter and herbal products for hepatotoxicity; do not give routine antiviral therapy to an immunocompetent person with self-limiting disease.
3Arrange repeat clinical review, bilirubin, aminotransferases, INR and renal function at an interval matched to the initial abnormality and trajectory.
4Give explicit return instructions for confusion, bleeding, reduced urine, persistent vomiting, worsening jaundice or inability to maintain intake.

04CONTROLInterrupt faeco-oral transmissionAcute HAV or HEV is suspected or confirmed in a household, workplace, care setting or cluster.

1Notify promptly and let the health-protection team define the infectious period, significant contacts, high-risk occupations and any outbreak investigation.
2Reinforce soap-and-water handwashing after toileting and before food preparation, environmental cleaning and avoidance of food preparation for others while advised.
3Apply UKHSA exclusion advice to food handlers, healthcare or care workers and childcare attendance rather than inventing a universal interval.
4For HAV contacts, arrange vaccine and any indicated human normal immunoglobulin through the current Green Book risk-and-timing pathway.

05PERSISTENCEAddress prolonged HEV viraemiaHEV RNA remains detectable or liver tests remain unexplained in an immunosuppressed patient.

1Refer to transplant medicine or hepatology for serial RNA, fibrosis assessment and review of competing graft, drug and infection causes.
2Consider carefully supervised reduction of immunosuppression only when graft and disease risks permit; do not alter transplant therapy independently.
3If viraemia persists, let the specialist team decide whether off-label ribavirin is justified and define dose, duration and virological stopping rules.
4Use strict pregnancy prevention and haematological monitoring around ribavirin because teratogenicity and haemolytic anaemia are major hazards.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Active prophylaxis for eligible susceptible contacts and people with continuing exposure risk after health-protection assessment.

Hepatitis A vaccine for post-exposure prophylaxis

Give one age-appropriate intramuscular dose as soon as possible and within the current UKHSA contact window, then complete the product-specific course if ongoing protection is indicated.

Use the current Green Book product, age and immune-status schedule; pregnancy is not an automatic contraindication when exposure risk justifies vaccination, and HNIG may also be indicated for vulnerable contacts.

Provides immediate passive protection for defined contacts at higher risk of severe disease or with inadequate vaccine response.

Human normal immunoglobulin for selected HAV contacts

Arrange the exact intramuscular product dose through the health-protection and Green Book pathway as soon as possible; do not substitute a locally remembered volume.

Supply, timing and eligibility are nationally controlled; review bleeding risk, previous immunoglobulin reaction and interference with subsequent live vaccines.

Off-label option for persistent HEV when immune reduction is unsuccessful, unsafe or insufficient in an immunosuppressed host.

Ribavirin for persistent hepatitis E

Use only a transplant or hepatology specialist protocol with weight- and renal-adjusted oral dosing, commonly for an initial 12-week course with serial HEV RNA response assessment.

Highly teratogenic and causes haemolytic anaemia; exclude pregnancy, enforce contraception for all exposed reproductive partners, adjust for renal function and monitor FBC and liver tests.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Acute liver failure

Rapid loss of hepatic function causes encephalopathy, coagulopathy, hypoglycaemia, cerebral oedema, renal injury, infection and multiorgan failure.

Cholestatic hepatitis

Persistent bilirubin elevation and pruritus can prolong disability for weeks or months despite eventual clearance of the acute infection.

Relapsing HAV

A minority experience recurrent symptoms and enzyme elevation after initial improvement without developing chronic viral carriage.

Chronic HEV fibrosis

Persistent viraemia in immunosuppressed people can progress from mild biochemical abnormality to advanced fibrosis, cirrhosis and graft dysfunction.

Pregnancy loss

Severe maternal HEV, particularly from endemic genotypes, can cause fulminant hepatitis, fetal compromise, preterm birth or fetal death.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Reassess symptoms, intake, hydration and cognition alongside bilirubin, ALT, INR, glucose and renal function until a clear improving trajectory is established.
A falling ALT is not reassuring when INR, bilirubin, lactate or encephalopathy worsens because hepatocyte mass may be declining.
Follow occupational and contact restrictions supplied by health protection, documenting who will communicate clearance to the patient or employer.
In immunosuppressed HEV, use serial RNA rather than aminotransferases alone to demonstrate virological clearance and detect recurrence.
After ribavirin, monitor haemoglobin, renal function, adverse effects and specialist-defined HEV RNA endpoints throughout and after treatment.
Offer HAV vaccination for continuing indications such as chronic liver disease, relevant travel or sexual and occupational exposure under the current Green Book.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Jaundice follows infectivity

HAV shedding is substantial before jaundice, so contact assessment must reach back before the patient recognised liver disease.

Travel is not required

Autogenous UK HEV commonly follows food exposure, making an exclusively travel-based testing strategy unsafe and insensitive.

Antibody answers differ

HAV IgM addresses recent infection, whereas total HAV antibody mainly answers whether immunity from infection or vaccination is present.

RNA matters in immune suppression

An impaired antibody response can conceal active HEV, while RNA directly demonstrates viraemia and supports clearance decisions.

Public health is treatment

Timely notification, hygiene, contact risk assessment and prophylaxis can prevent more illness than any medicine given to the index case.

Scope boundary

Transmission control and acute infectious triage are emphasised here; detailed chronic-liver staging and surveillance are addressed in hepatology care.

11Common pitfallsFrequent interpretation and management errors.

01
Do not diagnose acute HAV from total antibody alone; vaccination and remote infection commonly make it reactive.
02
Do not exclude HEV because the patient has not travelled or because the first antibody test is negative during immunosuppression.
03
Do not delay transplant-centre discussion until the INR reaches an arbitrary extreme when encephalopathy or rapid deterioration is already present.
04
Do not prescribe a standard analgesic dose without considering active liver injury, co-ingestion, alcohol use and the cumulative paracetamol total.
05
Do not give HAV post-exposure prophylaxis from memory; eligibility, timing and the addition of HNIG depend on current UKHSA criteria.
06
Do not equate biochemical improvement with HEV eradication in a transplant recipient; confirm RNA clearance through specialist follow-up.