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Gastrointestinal & Hepatic System

Drug-Induced Liver Injury (DILI)

Liver damage caused by exposure to medications (prescription or over-the-counter), herbal remedies, or dietary supplements. Presentation ranges from asymptomatic LFT elevation to acute liver failure.

Also known as: DILI, Hepatotoxicity, Drug Hepatitis

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Referral and warning signs

When to refer

Refer to specialist (Gastroenterologist/Hepatologist) for: Significant LFT elevation (e.g., ALT >3-5x ULN, high Bilirubin). Signs of liver dysfunction (jaundice, coagulopathy - prolonged INR). Signs of hypersensitivity. Diagnostic uncertainty. Failure of LFTs to improve after stopping suspected agent. Any signs of acute liver failure (URGENT referral).

Red flags

  • Jaundice
  • Encephalopathy (confusion, drowsiness)
  • Prolonged INR / Easy bruising or bleeding
  • Ascites
  • High Bilirubin levels
  • Very high ALT/AST levels (>10-20x ULN)

Signs and symptoms

  • Often asymptomatic, detected by routine LFTs.
  • Non-specific symptoms: Fatigue, malaise, anorexia, nausea, vomiting, RUQ discomfort.
  • Jaundice, dark urine, pale stools (if significant cholestasis or hepatocellular injury).
  • Pruritus (itching - especially with cholestatic injury).
  • Fever, rash, eosinophilia (suggest hypersensitivity reaction).
  • Signs of acute liver failure (encephalopathy, coagulopathy) in severe cases.

Risk factors

  • Exposure to a known hepatotoxic agent.
  • Polypharmacy (multiple medications).
  • Older age.
  • Female gender (for some types).
  • Genetic predisposition.
  • Pre-existing liver disease.
  • Alcohol consumption.
  • Nutritional status (malnutrition).

Diagnosis

Clinical assessment

Diagnosis of exclusion. Requires high index of suspicion and careful medication/herb/supplement history (including timing relative to onset of injury). Rule out other causes of liver injury (viral hepatitis, autoimmune hepatitis, biliary obstruction, alcoholic liver disease, NAFLD, Wilson's, Haemochromatosis). Pattern of LFT abnormality helps classify injury: Hepatocellular (predominant ALT/AST elevation), Cholestatic (predominant ALP/GGT/Bilirubin elevation), or Mixed.

Investigations

  • Detailed History: ALL medications (Rx, OTC), herbals, supplements, alcohol use, timeline of exposure and symptom onset.
  • Liver Function Tests (LFTs): ALT, AST, ALP, GGT, Bilirubin, Albumin, INR/PT. Pattern helps classify injury.
  • Viral Hepatitis Serology (HAV IgM, HBsAg, Anti-HBc IgM, Anti-HCV): Rule out acute viral hepatitis.
  • Autoimmune markers (ANA, ASMA, IgG levels): Rule out autoimmune hepatitis.
  • Abdominal Ultrasound: Rule out biliary obstruction, assess liver parenchyma/vasculature.
  • Liver Biopsy: May be helpful in unclear cases to assess pattern/severity of injury and exclude other causes, but often not necessary if history strongly suggests DILI and agent is stopped.

Diagnostic criteria

Diagnosis based on exposure to potential hepatotoxin, exclusion of other liver diseases, and often temporal relationship between exposure and injury (including improvement after drug withdrawal). Causality assessment tools (e.g., RUCAM score) can aid diagnosis.

Management

Non-pharmacological management

  • Discontinue the Suspected Offending Agent(s): Primary management step.
  • Supportive care: Rest, hydration, nutrition.
  • Avoid alcohol and other potentially hepatotoxic agents.
  • Hospitalization if severe injury (significant jaundice, coagulopathy, encephalopathy).

Pharmacological treatment

  • No specific antidote for most DILI.
  • N-acetylcysteine (NAC): Specific antidote for Paracetamol (Acetaminophen) overdose/toxicity. May have role in some other non-paracetamol acute liver failure cases (specialist decision).
  • Ursodeoxycholic acid (UDCA): May be considered for cholestatic DILI (limited evidence).
  • Corticosteroids: May be considered for DILI with prominent hypersensitivity features (rash, fever, eosinophilia) or resembling autoimmune hepatitis (specialist decision).
  • Management of acute liver failure requires specialist/ICU care and potential liver transplant evaluation.

Monitoring

  • Monitor LFTs frequently after drug withdrawal until normalization or stabilization.
  • Monitor INR/PT and clinical signs for development/resolution of liver failure.
  • Monitor symptoms.

Complications

  • Acute Liver Failure
  • Chronic liver disease / Cirrhosis (rare, with prolonged/repeated exposure or specific drugs)
  • Vanishing bile duct syndrome (chronic cholestasis)

Prevention

  • Use medications only when necessary and at appropriate doses.
  • Awareness of potential hepatotoxicity of prescribed drugs.
  • Avoid hepatotoxic agents in patients with pre-existing liver disease if possible.
  • Patient education about risks of OTC/herbal/supplement use.
  • Regular LFT monitoring for patients on long-term potentially hepatotoxic drugs (e.g., some anti-TB drugs, methotrexate).

Patient education

  • Explain DILI and the suspected causative agent.
  • Emphasize the importance of stopping the offending drug/herb/supplement.
  • Advise avoiding alcohol and other potential liver toxins.
  • Need for follow-up LFT monitoring.
  • Importance of informing ALL future healthcare providers about the reaction.
  • Caution regarding future use of OTC/herbal products.

Uganda-specific notes

Common causes include anti-TB drugs (INH, Rifampicin, PZA), ARVs (esp. Nevirapine, Efavirenz historically), Fluconazole, Co-trimoxazole, Paracetamol overdose, and traditional herbal remedies. Careful history taking is crucial. Monitoring LFTs during TB/HIV treatment important.

References

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 6, Section 6.5.6

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 1, Section 1.3.5 (Paracetamol Poisoning)

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