Revised Death Certificate Diagnosis Based on Laboratory Parameters
The most likely cause of death is drug-induced liver injury (DILI) from anti-tuberculosis medications, complicated by acute kidney injury and systemic inflammatory response, in a patient with active tuberculosis. 1
Primary Diagnosis: Anti-Tuberculosis Drug-Induced Hepatotoxicity
The laboratory parameters reveal severe hepatocellular injury with SGPT 285 U/L and SGOT 482.5 U/L, representing approximately 7-12 times the upper limit of normal (assuming normal upper limits of ~40 U/L). 1 This degree of transaminase elevation in a patient on anti-tuberculosis therapy strongly indicates drug-induced liver injury, as:
- Isoniazid and rifampin together produce hepatitis in 3-4% of patients, typically appearing within the first 2 weeks of treatment 1
- Pyrazinamide is the most common culprit for hepatotoxicity among anti-TB drugs 1
- The American Thoracic Society guidelines specify that treatment should be stopped when AST/ALT rises to ≥5 times the upper limit of normal 1, 2
The SGOT/SGPT ratio of approximately 1.7 suggests hepatocellular injury rather than pure cholestatic disease. 3
Contributing Factor: Acute Kidney Injury
Creatinine 4.79 mg/dL represents severe renal impairment (normal ~0.6-1.2 mg/dL). 1 This acute kidney injury likely resulted from:
- Rifampin-induced acute renal failure, which can occur particularly with intermittent administration or doses >600 mg daily 1
- Hepatorenal syndrome secondary to severe hepatic dysfunction 1
- The combination of elevated uric acid (9.7 mg/dL) suggests possible acute tubular injury 1
Ethambutol dosing should be reduced in renal impairment to prevent retrobulbar neuritis, but failure to adjust dosing may have contributed to toxicity. 1
Systemic Inflammatory Response
WBC 29.34 × 10³/μL (leukocytosis) and platelets 434 × 10³/μL (thrombocytosis) indicate:
- Severe systemic inflammatory response to either the underlying tuberculosis or drug-induced multi-organ injury 1
- The leukocytosis is markedly elevated and suggests either severe infection or a systemic inflammatory response syndrome 1
- Thrombocytosis can occur as an acute phase reactant, though rifampin can also cause thrombocytopenic purpura in some cases 1
Metabolic Derangement
FBS 205 mg/dL (hyperglycemia) likely represents:
- Stress hyperglycemia from critical illness 1
- Possible rifampin-induced reduction in oral hypoglycemic effectiveness if the patient was diabetic 1
- Metabolic decompensation from multi-organ failure
Critical Management Failures
The laboratory parameters suggest failure to implement guideline-recommended monitoring protocols:
- Liver function tests should be monitored weekly for 2 weeks, then biweekly when baseline AST/ALT is ≥2 times normal 1, 4, 2
- All hepatotoxic anti-TB drugs (isoniazid, rifampin, pyrazinamide) should have been stopped immediately when transaminases reached ≥5 times the upper limit of normal 1, 2
- Ethambutol dosing should have been adjusted for the elevated creatinine to prevent additional toxicity 1
Recommended Death Certificate Formulation
Immediate cause of death: Acute hepatorenal failure
Due to (or as a consequence of): Drug-induced liver injury from anti-tuberculosis medications (isoniazid, rifampin, pyrazinamide)
Underlying cause: Active pulmonary/extrapulmonary tuberculosis
Other significant conditions contributing to death: Acute kidney injury, systemic inflammatory response syndrome, hyperglycemia
This formulation reflects that the hepatotoxicity from anti-TB drugs was the proximate cause of death, while acknowledging that the underlying tuberculosis necessitated the treatment. 1 The constellation of multi-organ failure (hepatic, renal, metabolic) in the setting of anti-TB therapy represents a preventable adverse outcome that should have triggered treatment modification. 1, 2