Hepatic Tuberculosis

Hepatic tuberculosis is infection of the liver by Mycobacterium tuberculosis, either as part of miliary or disseminated disease (the commonest) or as an isolated local form with nodular or abscess lesions. It is a treatable cause of fever and cholestasis in endemic areas and in immunocompromised patients.

Hepatic involvement is found at autopsy in 50% to 80% of patients with miliary tuberculosis. Localised disease is rare. Risk groups are people with HIV (CD4 count under 200 cells/microlitre), alcohol misuse, diabetes and those on immunosuppression.

Pathophysiology.

Bacilli reach the liver by the hepatic artery or portal vein and form caseating or non-caseating granulomas in the portal tracts and parenchyma. Larger lesions form tuberculomas or abscesses, and biliary involvement causes strictures.

Fever, night sweats, weight loss, right upper quadrant pain, hepatomegaly, ascites and jaundice (uncommon). Pulmonary or other extrapulmonary disease is often present.

Red flags.

• Acute liver failure.
• Obstructive jaundice from nodal compression.
• Haemodynamic instability with miliary disease.
• Immunosuppression with cholestasis.

Alkaline phosphatase and gamma glutamyl transferase are raised out of proportion to bilirubin. Chest radiograph or CT shows miliary or other changes. Ultrasound or CT shows hypoechoic or hypodense lesions and calcification. Liver biopsy shows granulomas with caseation, with acid fast bacilli stain, culture and nucleic acid amplification (Xpert MTB/RIF). Test sputum, urine and other samples, and HIV status. Sputum or tissue culture with drug susceptibility testing guides treatment.

Differential diagnosis.

• Sarcoidosis.
• Primary biliary cholangitis.
• Hepatic abscess (pyogenic or amoebic).
• Lymphoma.
• Brucellosis and other granulomatous hepatitis.
• Metastases.

Give a 6-month regimen: 2 months of four drugs followed by 4 months of two drugs. Extend to 9 to 12 months for slow response. Monitor liver tests closely, because drugs are hepatotoxic.

• Isoniazid: 5 mg/kg orally once daily (maximum 300 mg daily) for 6 months; monitor liver tests every 2 weeks for the first 2 months, then monthly, and neuropathy; give pyridoxine 10 to 25 mg daily; stop if alanine aminotransferase is over 5 times the upper limit (or over 3 times with symptoms); adjust the dose in slow acetylators and reduce in cirrhosis.
• Rifampicin: 10 mg/kg orally once daily (maximum 600 mg daily) for 6 months; monitor liver tests and drug interactions; reduce the dose or avoid in decompensated cirrhosis.
• Pyrazinamide: 25 mg/kg orally once daily (maximum 2,000 mg daily) for the first 2 months; monitor liver tests and uric acid; avoid in severe liver disease and reduce frequency to three times weekly when creatinine clearance is under 30 mL/min.
• Ethambutol: 15 mg/kg orally once daily (maximum 1,200 mg daily) for the first 2 months; monitor visual acuity and colour vision; give 15 to 25 mg/kg three times weekly when creatinine clearance is under 30 mL/min.

In severe liver disease, use a regimen with fewer hepatotoxic drugs (rifampicin and ethambutol with a fluoroquinolone) under specialist care. Biliary stenting or drainage is used for obstruction. Start antiretroviral treatment within 2 to 8 weeks in HIV, taking care over drug interactions.

Monitoring. Liver tests every 2 weeks for 2 months then monthly; clinical response and weight at each visit; repeat imaging at 2 and 6 months.

Referral and escalation. Infectious disease, hepatology and a tuberculosis programme.

Special groups. Children need weight band dosing. Pregnancy: isoniazid, rifampicin and ethambutol are used, and pyrazinamide is used when benefit outweighs risk.