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PA24.3 | Viral & Toxic Hepatitis — SDL Guide (Part 3)

Distinguishing Viral vs Toxic vs Autoimmune Hepatitis

Three side-by-side panels compare viral, drug/toxic, and autoimmune hepatitis using exposure history, onset, liver injury pattern, laboratory clues, and diagnostic takeaway boxes. — **Panel A:** Viral hepatitis: travel and shellfish exposure, sexual/blood exposure, HAV/HEV and HBV/HCV clues, inflamed liver, ALT/AST 100-2000 U/L, viral serology markers.. **Panel B:** Drug/toxic hepatitis: paracetamol bottle, medicine blister pack, herbal supplement, abrupt onset timeline, severe hepatocyte injury, ALT/AST potentially >10,000 U/L in paracetamol toxicity, critical drug history.. **Panel C:** Autoimmune hepatitis: young/middle-aged woman silhouette, no clear exposure, immune cells and autoantibodies attacking hepatocytes, chronic inflammatory pattern, ANA, SMA, high IgG, moderate-high ALT/AST..

At the bedside and in the lab, differentiating the causes of hepatitis requires integrating history, serology, and biochemistry into a framework:

Feature	Viral Hepatitis	Drug/Toxic DILI	Autoimmune Hepatitis
Onset	Acute prodrome; chronic insidious	Often abrupt after dose threshold or new drug	Insidious; may mimic chronic hepatitis
Age/sex	Any; HAV/HEV epidemic pattern	Any	Young/middle-aged women (type 1)
Exposure history	Travel, shellfish (HAV/HEV); sexual/blood exposure (B/C)	Drug history CRITICAL (incl. OTC, herbal)	No clear exposure
Transaminases	Moderate–high (100–2000 U/L)	Very high in paracetamol (can exceed 10,000 U/L); variable in idiosyncratic	Moderate–high
ALP/GGT	Mildly elevated	Elevated (cholestatic DILI) or mildly elevated (hepatocellular)	Mildly elevated
Serology	HBsAg, anti-HAV IgM, anti-HCV, HCV RNA, anti-HDV, anti-HEV IgM	All viral serologies NEGATIVE	ANA, anti-SMA (anti-smooth muscle Ab), anti-LKM1; IgG elevated
Eosinophilia	Absent	Present in immune idiosyncratic DILI (allergic)	Absent
Biopsy	Viral cytopathic changes; ground-glass (HBV)	Centrilobular necrosis (paracetamol); eosinophils (idiosyncratic)	Plasma cell infiltrate; rosette formation; interface hepatitis
Resolution	Spontaneous (A, E); antiviral therapy (B, C)	Drug withdrawal ± NAC	Steroids + azathioprine

Key differentiating clues in practice:
- Paracetamol overdose: AST/ALT can exceed 10,000 U/L (a massive spike not seen in viral hepatitis). Ask about tablets taken.
- HAV/HEV: cluster/outbreak pattern; faeco-oral history; no HBsAg/HCV.
- Autoimmune hepatitis: female, associated autoimmunity, responds to steroids, relapses on withdrawal.
- Drug reaction: temporal relationship to starting/stopping drug; eosinophilia; rash.

A colour-coded three-column infographic compares viral, drug-induced, and autoimmune hepatitis by trigger, serology, biopsy findings, and first-line management, with a clinical self-check highlighting autoimmune hepatitis. — **Panel A:** Three colour-coded columns: Viral Hepatitis, Drug-Induced Liver Injury, Autoimmune Hepatitis; rows for transmission or trigger, serology or immune markers, biopsy hallmarks, and first-line management.. **Panel B:** Clinical self-check vignette showing jaundice, ALT 800 U/L, negative viral serology, ANA 1:640, raised IgG, plasma cell-rich interface hepatitis, and treatment with prednisolone +/- azathioprine..

SELF-CHECK

A 28-year-old woman has jaundice, markedly elevated ALT (800 U/L), and fatigue for 3 months. She has no significant drug exposure and denies risk factors for viral hepatitis. Serology shows negative HBsAg, negative anti-HCV, negative anti-HAV/HEV IgM. ANA titre is 1:640, IgG is 24 g/L (raised). Liver biopsy shows interface hepatitis with a plasma cell-rich infiltrate. What is the most likely diagnosis and first-line treatment?

A. Chronic hepatitis B — treat with tenofovir

B. Autoimmune hepatitis — treat with prednisolone ± azathioprine

C. Drug-induced liver injury — withdraw the offending agent

D. Primary biliary cholangitis — treat with ursodeoxycholic acid

Reveal Answer

Answer: B. Autoimmune hepatitis — treat with prednisolone ± azathioprine

The combination of young woman, negative viral serology, elevated IgG, positive ANA (1:640), and plasma cell-rich interface hepatitis on biopsy is the classic presentation of autoimmune hepatitis (AIH) type 1. First-line treatment is immunosuppression: prednisolone (to induce remission) plus azathioprine (to maintain remission and allow steroid tapering). Note: AIH can mimic every form of hepatitis — the critical diagnostic steps are ruling out viral causes and checking autoantibodies + IgG in any unexplained hepatitis.

Fulminant Hepatic Failure — The Critical Complication

A four-panel medical diagram explains fulminant hepatic failure through gross liver changes, Indian causes, massive hepatic necrosis histology, and the clinical cascade leading to transplant consideration. — **Panel A:** Normal liver; shrunken yellow-green liver; acute yellow atrophy; jaundice onset; hepatic encephalopathy; INR > 1.5; within 8 weeks; absence of prior liver disease. **Panel B:** Viral hepatitis; HAV in children; HEV in pregnant women; HBV reactivation; paracetamol overdose; isoniazid; anti-epileptics; Wilson disease acute presentation. **Panel C:** Panacinar necrosis; ghost hepatocyte outlines; collapsed reticulin framework; haemorrhagic sinusoids; surviving portal tract structures; sparse periportal hepatocytes; Kupffer cells engulfing debris; minimal regenerative activity. **Panel D:** Massive hepatic necrosis; coagulopathy; loss of clotting factor synthesis; bleeding; hyperammonaemia; cerebral oedema; hepatic encephalopathy grades 1–4; hypoglycaemia; loss of gluconeogenesis; bacterial infections; impaired Kupffer cell clearance; multi-organ failure; mortality approaches 80%; King's College Criteria.

Fulminant hepatic failure (FHF) — also called acute liver failure — is defined as hepatic encephalopathy and coagulopathy (INR >1.5) developing within 8 weeks of onset of jaundice in the absence of prior liver disease.

Causes in India:
1. Viral hepatitis — HAV (in children), HEV (in pregnant women), HBV reactivation
2. Paracetamol overdose
3. Other drugs (isoniazid, anti-epileptics)
4. Wilson disease (acute presentation)

Morphology — massive hepatic necrosis:
- Macroscopically: liver shrunken, soft, yellow-green ('acute yellow atrophy')
- Microscopically: panacinar necrosis — hepatocytes ghost outlines, collapsed reticulin framework, haemorrhagic sinusoids; only portal tract structures and sparse periportal hepatocytes may survive
- Kupffer cells engulf debris; minimal regenerative activity (too rapid)

Clinical cascade:
- Coagulopathy (loss of clotting factor synthesis) → bleeding
- Hyperammonaemia → cerebral oedema → hepatic encephalopathy (grades 1–4)
- Hypoglycaemia (loss of gluconeogenesis)
- Bacterial infections (loss of Kupffer cell-mediated clearance)
- Multi-organ failure

Prognosis: Without liver transplantation, mortality approaches 80%. The King's College Criteria (paracetamol vs non-paracetamol categories) guide transplant listing.