A 33 year old Newar housewife from Kathmandu, Nepal, with no known comorbidity, presented to Patan Hospital Emergency Department in November, 2019 with a history of cough with occasional sputum production over the previous 20 days and low grade fever for 10 days. There was no history of chest pain, difficulty breathing, headache, vomiting, altered mentation, abdominal pain, yellowish discoloration of eyes, burning urine, hair loss, photosensitivity, joint pain, or rash but she had decreased appetite and weight loss. There was no past history of tuberculosis or jaundice. She did not consume alcohol or any drugs including acetaminophen, aflatoxin or herbal products. Her father-in-law had been diagnosed with pulmonary tuberculosis five years earlier, but there was no family history of liver disease.
Initial examination showed temperature of 101 oF with pulse of 110 beats/minute and respiratory rate of 26 breaths/minute. There was diffuse fine crepitation on the left side on auscultation of the chest. There was no lymphadenopathy, icterus, peripheral edema or wheezes. Neck veins were not distended. Liver and spleen were not palpable, and abdomen examination was normal.
Laboratory parameters with normal ranges in parenthesis are as follow:
Complete blood count before transfusion: white cell count 7.8 (4-10) x 10 9/L; neutrophils 80%; lymphocytes 16%; monocytes 4%; red blood cells 3.6 (4.2-5.4) x 10 12/L; haemoglobin 10.6 (12-15) g/dL; platelets 410 (150-400) x 10 9/L.
Biochemistry: random blood sugar 126 (65-110) mg/dL; urea 39 (17-45) mg/dL; creatinine 1.1 (0.8-1.3) mg/dL; sodium 138 (135-145) mmol/L and potassium 4 (3.5-5) mmol/L.
Chest X-ray ( Figure 1) showed thick walled cavitating lesions in the left upper lobe and patchy infiltrates in left middle and lower zones. There were hyperinflated lung fields with blunting of left costophrenic angle. Sputum smear examination showed 3+ acid fast bacilli. Sputum Gene Xpert was positive for Rifampicin sensitive tubercle bacilli. A diagnosis of pulmonary tuberculosis was made, and planned for starting ATT.
Liver function test was performed as baseline workup before starting treatment which showed the following results (with normal ranges in parenthesis): bilirubin total 1.1 (0.1-1.2) mg/dL and direct 0.5 (0-0.4) mg/dL; alanine transaminase 308 (5-30) units/L; aspartate transaminase 605 (5-30) units/L; alkaline phosphatase 149 (50-100) IU/L; gamma-glutamyltranspeptidase66 (9-48) units/L. The raised transaminases led us to perform further workup for liver disease. There was no clinical evidence of chronic liver disease or portal hypertension. Liver synthetic functions were as following;albumin 3.5 (3.5-5) g/dL; total protein 6.5 (6-8.3) g/dL; prothrombin time 14 (11-13.5) s. Serologies for HIV, HBsAg, Hepatitis C virus (HCV), Hepatitis A virus (HAV) and Hepatitis E virus (HEV) were nonreactive. Testing for other hepatotropic viruses was not done because of unavailability of the tests. Neurological examinations and the slit lamp examination of eye were normal. Ultrasound of the abdomen showed a normal sized liver with smooth outline and echotexture. However fibroscan, upper gastrointestinal endoscopy, abdominal CT scan and liver biopsy were not done due to financial constraints of the patient.
She was admitted to the respiratory isolation unit. At first there was some hesitation in starting the full treatment for her pulmonary tuberculosis because of her liver function tests. But taking into consideration her presentation and laboratory findings, we opted for the full treatment rather than a modified TB regimen. We started standard four drugs ATT based on her weight as per national TB guidelines which included three tablets of HRZE given once daily with each tablet containing 75 mg isoniazid (H), 150 mg rifampicin (R), 400 mg pyrazinamide (Z) and 275 mg ethambutol (E). This led to improvement in her clinical status. She was closely observed for possible worsening of her liver disease due to the hepatotoxic antitubercular drugs. Providentially, at 1 week after starting treatment, she was afebrile and continuing to improve and her liver function test showed a total bilirubin of 0.7 mg/dl, aspartate transaminase of 40 IU/L and alanine transaminase of 62 IU/L.
She was discharged with advice to follow up in 1 month. At 1 month follow up she had no symptoms and therefore no further tests were done. At 2 months, she was still asymptomatic and her sputum smear was negative for acid fast bacilli. Her liver function test showed a total bilirubin of 0.6 mg/dl, aspartate transaminase of 30 IU/L and alanine transaminase of 35 IU/L. She was switched to3 tablets of HR to be taken for 4 months.