From the Guidelines
The diagnostic criteria for Tuberculosis (TB) Drug-Induced Liver Injury (DILI) are met when the alanine aminotransferase (ALT) level is ≥3 times the upper limit of normal in the presence of hepatitis symptoms, or ≥5 times the upper limit of normal in the absence of symptoms, as indicated by 1. The diagnosis of TB DILI involves a combination of clinical evaluation and laboratory tests. Key considerations include:
- Elevated liver enzymes, specifically ALT levels, which are a critical marker for DILI
- Presence of symptoms such as nausea, vomiting, abdominal pain, and jaundice, which can indicate hepatitis
- Exclusion of other causes of liver injury, such as viral hepatitis, alcohol use, or other hepatotoxic medications
- Identification of risk factors, including older age, female gender, pre-existing liver disease, alcohol use, malnutrition, HIV co-infection, and genetic factors affecting drug metabolism The primary TB medications associated with DILI are isoniazid, rifampin, and pyrazinamide, with pyrazinamide carrying a notable risk, as suggested by 1. Regular monitoring of liver function tests is essential during TB treatment, with baseline testing recommended before starting therapy and follow-up testing at regular intervals, particularly for high-risk patients. Early detection is crucial as discontinuation of the offending drugs can prevent progression to severe liver damage or failure, highlighting the importance of vigilant monitoring and prompt action based on the criteria outlined in 1.
From the Research
Diagnostic Criteria for TB DILI
The diagnostic criteria for Tuberculosis (TB) Drug-Induced Liver Injury (DILI) involve a combination of clinical, laboratory, and histologic workup. According to 2, the American College of Gastroenterology (ACG) published guidelines to aid clinicians in diagnosing DILI, which includes:
- Temporal association between drug intake and liver injury
- Clinical-biochemical features
- Type of injury (hepatocellular and/or cholestatic)
- Extrahepatic features
- Likelihood that a given agent is the culprit based on its known manifestations with prior cases
Clinical Presentation of TB DILI
The clinical spectrum of TB DILI can range from asymptomatic elevation in liver tests to acute hepatitis and acute liver failure, as reported in 3. The presence of jaundice, hypoalbuminemia, ascites, encephalopathy, and high prothrombin time are poor prognostic markers.
Risk Factors for TB DILI
Several risk factors for TB DILI have been identified, including:
- Low patient weight
- HIV-1 co-infection
- Higher baseline ALP
- Alcohol intake, as reported in 4
- Pre-existing hepatitis, as reported in 5
Laboratory Monitoring
Laboratory monitoring is crucial in the early detection of TB DILI. According to 4, only a quarter of patients who developed DILI had British or American Thoracic Society defined criteria for pre-emptive liver test monitoring, suggesting that all patients on anti-tuberculous treatment should be considered for universal liver monitoring, particularly during the first 8 weeks of treatment.
Predictors of Acute Liver Failure
Several predictors of acute liver failure among inpatients with anti-TB DILI have been identified, including:
- Elevated total bilirubin
- Aspartate aminotransferase
- White blood cell count
- Pre-existing hepatitis
- Low platelet count, as reported in 5