Acute hepatitis and acute liver failure

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

Acute hepatocellular injury ranges from an incidental ALT rise to rapidly progressive multiorgan failure. Jaundice, nausea and right upper-quadrant discomfort may precede coagulopathy, hypoglycaemia, kidney injury, lactic acidosis, infection susceptibility and cerebral oedema.

The central decision is whether synthetic function or cognition is deteriorating. Once encephalopathy accompanies coagulopathy, management belongs in a liver-capable critical-care network with parallel cause-specific treatment and transplant assessment.

Viral patterns depend on exposure and host. Hepatitis A and E are usually self-limiting but can be severe; acute hepatitis B can rarely fail rapidly; hepatitis C seldom causes fulminant failure. Herpes simplex hepatitis can be anicteric and devastating in pregnancy or immunosuppression, so exposure risk and specialist antiviral decisions matter.

Key points

Acute hepatitis is hepatocellular injury developing over days to weeks; causes include viral infection, medicines and toxins, autoimmunity, ischaemia, vascular obstruction, Wilson disease and pregnancy-related syndromes.
Aminotransferase height reflects hepatocyte injury, not remaining liver function. INR, glucose, lactate, pH, mental state, renal function and trajectory identify danger.
Acute liver failure requires acute liver injury with coagulopathy and hepatic encephalopathy in a person without pre-existing cirrhosis; diagnostic and transplant criteria are specialist protocol decisions.
Ask specifically about paracetamol in prescribed, combined cold-and-flu and over-the-counter products, deliberate or staggered ingestion, herbal products, recreational drugs, travel and viral exposures.
Send a paracetamol concentration even when ingestion is denied or timing is unclear, and follow current TOXBASE advice because treatment is most effective when started early.
Falling ALT is not always recovery: in massive hepatic necrosis it can fall while INR, bilirubin, lactate, creatinine and encephalopathy worsen.
Ultrasound with portal and hepatic-vein Doppler looks for biliary obstruction, Budd–Chiari syndrome and chronic liver morphology, but normal imaging does not exclude severe hepatitis.
Avoid sedatives and unnecessary correction of INR; frequent neurological, glucose and acid-base monitoring and early transplant-centre dialogue are more important than normalising laboratory numbers.

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

Viral infection

Acute hepatitis A, B or E and selected systemic viral infections cause hepatocellular injury; travel, food, blood, sexual and immune-status histories guide testing.

Medicines and toxins

Paracetamol, prescribed medicines, recreational substances and herbal or nutritional products can cause direct or idiosyncratic injury, sometimes after staggered or unrecognised exposure.

Immune, vascular and metabolic

Autoimmune hepatitis, ischaemia, hepatic venous obstruction, Wilson disease and pregnancy-associated liver syndromes are important non-infective causes, particularly when routine viral tests are negative.

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

1
Acute hepatocyte injury
Viral, toxic, immune or hypoxic damage causes hepatocyte death and release of aminotransferases, without enzyme height directly measuring remaining function.
2
Synthetic and metabolic failure
Extensive injury impairs clotting-factor synthesis, glucose regulation, bilirubin handling and toxin clearance, producing coagulopathy, hypoglycaemia and jaundice.
3
Encephalopathy and organ failure
Accumulated neurotoxins, inflammation and circulatory disturbance cause cerebral dysfunction while vasodilatation, infection and renal injury drive multiorgan deterioration.

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

Uncomplicated acute hepatitis

Malaise, anorexia, nausea, right upper-quadrant discomfort, dark urine, pale stool, pruritus and jaundice with a hepatocellular biochemical pattern occur while cognition, glucose and coagulation remain stable.

Acute liver failureRed flag

New confusion, altered sleep, asterixis, agitation, somnolence or coma with prolonged INR after acute injury signals failing synthetic and detoxification function and mandates transplant-centre contact.

Hyperacute paracetamol or ischaemic patternRed flag

Very high aminotransferases, early coagulopathy, metabolic acidosis, raised lactate and kidney injury with initially modest jaundice suggest paracetamol toxicity or hypoxic hepatitis; obtain the exposure and haemodynamic history urgently.

Autoimmune hepatitisRed flag

Acute jaundice can occur at any age and may have high IgG or autoimmune markers, but serology can be negative. Treatment and biopsy decisions require urgent hepatology input when severe.

Wilson acute failureRed flag

A young person with haemolysis, low alkaline phosphatase relative to bilirubin, renal dysfunction or neuropsychiatric clues may have Wilson disease; routine copper markers are imperfect during acute failure and specialist assessment is urgent.

Vascular or pregnancy-associated diseaseRed flag

Painful hepatomegaly, ascites and hepatic-vein obstruction suggest Budd–Chiari; hypertension, haemolysis, thrombocytopenia or late-pregnancy illness raises HELLP or acute fatty liver and needs immediate obstetric-hepatology coordination.

Infection or cerebral deteriorationRed flag

Fever, hypotension, rising vasopressor need, worsening acidosis, seizures, unequal pupils or decreasing consciousness in liver failure may reflect sepsis or intracranial hypertension and require critical-care intervention.

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
Liver panel, INR and albuminFirst step
Why
Define injury pattern and assess hepatic synthetic function.
Interpretation and limitations
Calculate whether ALT or ALP predominates against laboratory upper limits. INR trend carries more acute prognostic weight than ALT; albumin may remain normal early because of its long half-life.
02
Bedside glucose, blood gas and lactate
Why
Detect hypoglycaemia, acidosis and impaired lactate clearance promptly.
Interpretation and limitations
Recurrent low glucose, persistent acidosis or lactate despite resuscitation signals severe loss of hepatic reserve or shock. Repeat frequently in evolving failure rather than relying on admission values.
03
Paracetamol concentration and toxicology history
Why
Identify a common treatable cause even when history is incomplete.
Interpretation and limitations
Interpret timing only through the current TOXBASE pathway; a late or staggered overdose may have a low concentration despite toxicity. Begin acetylcysteine promptly when indicated rather than awaiting every result.
04
Viral hepatitis and infection screen
Why
Identify transmissible and cause-specific viral disease.
Interpretation and limitations
Select HAV IgM, HBV surface antigen and core IgM, HCV antibody with RNA, HEV testing and HIV according to context; seek specialist testing for HSV, CMV or EBV in pregnancy, immunosuppression or an atypical anicteric syndrome.
05
Autoimmune and immunoglobulin profile
Why
Assess autoimmune hepatitis and related inflammatory disease.
Interpretation and limitations
Request ANA, smooth-muscle, liver-kidney microsomal antibodies and IgG with specialist interpretation. Negative antibodies or normal IgG do not completely exclude acute severe autoimmune hepatitis.
06
Ultrasound liver with Doppler
Why
Assess biliary calibre, hepatic and portal flow, liver morphology and ascites.
Interpretation and limitations
Hepatic-vein thrombosis or reversed flow changes the pathway. A normal biliary tree supports hepatocellular rather than obstructive disease, but ultrasound cannot quantify viable hepatocyte mass.
07
Blood count, haemolysis and metabolic tests
Why
Identify sepsis, HELLP, Wilson disease and other mimics.
Interpretation and limitations
Review platelets, blood film, LDH, haptoglobin, reticulocytes, renal profile and, when appropriate, caeruloplasmin and copper studies. Interpret Wilson tests with a specialist because acute failure distorts standard markers.
08
Pregnancy test and obstetric assessment
Why
Detect pregnancy-specific disease and alter medicine or imaging choices.
Interpretation and limitations
In later pregnancy, hypertension, thrombocytopenia, haemolysis, hypoglycaemia and liver dysfunction require immediate maternity-led assessment for HELLP or acute fatty liver and timely delivery decisions.
09
Liver biopsy by specialist route
Why
Resolve selected uncertain diagnoses when the result will change urgent treatment.
Interpretation and limitations
Coagulopathy often makes percutaneous biopsy unsafe; a transjugular route may be considered by hepatology. Biopsy must not delay transplant referral or empiric treatment for a highly time-sensitive cause.

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

Ischaemic liver injury

Shock, hypoxaemia or cardiac failure with a marked, rapidly changing aminotransferase pattern favours hypoxic injury over primary viral hepatitis.

Acute biliary obstruction

Colicky pain, duct dilatation and an evolving cholestatic pattern suggest common-duct obstruction, though early obstruction can transiently raise aminotransferases substantially.

Decompensated chronic liver disease

Portal-hypertension signs, nodular imaging, thrombocytopenia or previous decompensation indicate acute-on-chronic disease rather than acute liver failure in a previously normal liver.

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

01TriageAcute hepatitis severity screenFirst stepNew marked liver-test abnormality, jaundice or a compatible systemic illness.

1Assess ABCDE, mental state and asterixis; check bedside glucose, INR, blood gas, lactate, renal function and urine output alongside the liver panel.
2Take a time-anchored exposure history covering every medicine, paracetamol-containing product, supplement, toxin, alcohol or drug use, travel, food, sexual, blood and pregnancy risk.
3Stop non-essential potentially hepatotoxic agents, send the structured aetiology screen and ultrasound with Doppler, and discuss severe injury early with hepatology.
4EscalationAdmit and escalate when INR is prolonged, glucose falls, renal function worsens, lactate or acidosis persists, mental state changes, vomiting prevents hydration or diagnostic uncertainty is high.

02FailureAcute liver failure stabilisationHepatic encephalopathy plus coagulopathy after an acute liver insult.

1Contact the regional liver transplant centre immediately with timing, suspected cause, observations, mental state, INR, pH, lactate, creatinine, bilirubin, glucose and available imaging; repeat contact as the trajectory changes.
2Manage in critical care, protect the airway when consciousness or seizures require it, elevate the head, avoid hypotension and hypoxaemia, and seek transplant-centre advice on neurological monitoring and sodium targets.
3Give cause-specific therapy such as acetylcysteine or specialist antiviral treatment without delay, monitor glucose continuously or very frequently, and use renal support for accepted metabolic and volume indications.
4Screen actively for infection and bleeding, use blood products for active bleeding or an essential procedure rather than routine INR cosmetic correction, and coordinate transfer before instability makes transport unsafe.

03CauseParallel aetiology treatmentA plausible reversible cause identified during acute injury.

1For paracetamol or uncertain toxic injury, follow TOXBASE and the local acetylcysteine protocol and continue treatment according to clinical and laboratory stopping criteria.
2For acute severe hepatitis B, suspected herpes hepatitis or autoimmune hepatitis, involve hepatology or infectious diseases urgently because antiviral, corticosteroid and biopsy decisions depend on severity and diagnostic confidence.
3For Budd–Chiari syndrome, obtain vascular imaging and specialist anticoagulation or interventional planning; for ischaemic hepatitis, restore perfusion and treat the cardiac, septic or respiratory driver.
4DefinitiveFor pregnancy-specific liver disease, transfer into coordinated obstetric, anaesthetic, neonatal and hepatology care because delivery and organ support may be definitive and time sensitive.

04RecoverySafe follow-up after acute hepatitisImproving synthetic function and no encephalopathy after observation or admission.

1Confirm INR, glucose, renal function, symptoms and aminotransferase trajectory are improving and that the cause-specific plan, public-health duties and pending results have an owner.
2Advise avoidance of alcohol and non-essential medicines or supplements during recovery, and provide exact guidance on future use of the suspected agent rather than a vague lifetime medicine ban.
3Arrange repeat bloods and clinical review at an interval matched to severity; new confusion, vomiting, bleeding, reduced urine, worsening jaundice or drowsiness requires immediate reassessment.
4Refer confirmed viral, autoimmune, Wilson, vascular or unexplained disease to the appropriate specialist and offer vaccination, contact testing or notification actions under current UK guidance.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Replenishes glutathione in paracetamol toxicity and may support selected non-paracetamol acute liver failure under specialist direction.

Intravenous acetylcysteine

Start and continue according to current TOXBASE, BNF and local weight-based protocol.

Do not delay for a late level or complete history when treatment is indicated. Infusion reactions and fluid volume require monitoring; a reaction does not automatically mean abandoning essential antidote therapy.

Prevents and treats hypoglycaemia caused by depleted hepatic glycogen and impaired gluconeogenesis.

Intravenous glucose

Titrate concentrated or maintenance glucose to frequent bedside measurements and critical-care targets.

Avoid wide glycaemic swings and fluid overload; monitor potassium, phosphate and sodium, and use a central route when the selected concentration requires it.

Treats selected severe acute hepatitis B or herpes-family infection when clinical context supports it.

Cause-specific antiviral therapy

Agent and regimen are selected urgently with hepatology or infectious-disease specialists.

Do not use empirically without specialist reasoning except when delay carries exceptional risk. Adjust for renal function, check interactions and obtain virology samples before treatment when this causes no delay.

Corrects concurrent vitamin-K deficiency but does not restore synthetic function in true liver failure.

Vitamin K

Use a short diagnostic or replacement course when deficiency or cholestasis is plausible.

A persistently prolonged INR after replacement remains a severity marker. Do not use vitamin K or plasma to conceal a worsening trend or delay transplant discussion.

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

Cerebral and metabolic injury

Progressive encephalopathy can accompany cerebral oedema, seizures and loss of airway protection; hypoglycaemia and acidosis further worsen neurological and cardiovascular instability.

Bleeding and infection

Coagulopathy reflects impaired synthesis, while immune dysfunction and invasive support increase infection risk; bleeding tendency cannot be inferred from INR alone.

Renal and multiorgan failure

Acute kidney injury, vasodilatory shock, respiratory failure and severe acidosis can develop rapidly and may remove the opportunity for safe transplant assessment.

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

Record neurological grade, pupils, asterixis, agitation and sedation exposure at frequent intervals; subtle sleep inversion or slowed responses can precede overt encephalopathy.
Trend INR, glucose, lactate, pH, bicarbonate, creatinine, sodium, phosphate, bilirubin and aminotransferases at a frequency agreed with critical care and the transplant centre.
Monitor urine output, fluid balance, haemodynamics and oxygenation, avoiding both hypoperfusion and inappropriate fluid loading that worsens cerebral or pulmonary oedema.
Screen repeatedly for infection using examination, cultures and imaging as indicated because fever and leukocytosis may be absent and prophylactic strategies vary between liver units.
Update the transplant centre with trajectory and organ-support needs, not just isolated results; follow its current super-urgent listing and transfer criteria exactly.

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

ALT can fall ominously

Recovery produces falling aminotransferases with improving INR and physiology. Massive necrosis produces the same enzyme direction while synthetic failure, acidosis and encephalopathy worsen.

INR is more than bleeding risk

In acute liver injury INR is a dynamic marker of synthesis and prognosis. Routine plasma can obscure that signal, cause volume harm and does not reliably normalise haemostasis.

Paracetamol histories are incomplete

Patients may not recognise combination products or may disclose self-harm later. A concentration and early toxicology advice are appropriate when severe unexplained hepatocellular injury is present.

Encephalopathy is a clinical diagnosis

Ammonia can support risk assessment in specialist care but does not replace repeated bedside cognition, and a normal or modest value cannot explain away clear neurological change.

Hepatitis E belongs on the list

Travel is not essential because infection can be acquired in the UK. Immunosuppressed patients may develop persistent infection and need specialist virological management.

Transfer before collapse

A patient can deteriorate rapidly through cerebral oedema, acidosis and vasoplegia. Early communication allows safe transfer and transplant evaluation while transport remains possible.

11Common pitfallsFrequent interpretation and management errors.

01
Using the peak ALT as the main measure of liver function or prognosis.
02
Waiting for overt coma before contacting a transplant centre.
03
Failing to ask about combined products and staggered paracetamol exposure.
04
Correcting INR routinely and thereby obscuring the severity trajectory.
05
Assuming normal ultrasound excludes dangerous hepatocellular injury.
06
Forgetting pregnancy-specific, vascular, Wilson or herpes causes in the appropriate context.