Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity.
OBJECTIVE
Antituberculosis (anti-TB) drug induced hepatotoxicity (DIH) is the most common side effect leading to interruption of therapy. Wide variations have been found in the reported incidence of hepatotoxicity during short-course chemotherapy. Several risk factors for hepatotoxicity have been suggested in previous studies. We undertook a prospective case-control study to assess the role of these putative risk factors in the development of DIH in patients receiving anti-TB treatment.


METHODS
One hundred and seventy five consecutive cases with a diagnosis of anti-TB DIH were compared with 428 consecutive controls who took anti-TB drugs for the full duration of chemotherapy without clinical or biochemical evidence of hepatitis. Cases positive for markers of acute viral hepatitis were carefully excluded. Cases and controls were compared with respect to age, sex, site of tuberculosis, radiological extent of disease on chest radiograph, body mass index (BMI), mid-arm circumference (MAC) and liver function at baseline which included serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum total protein and serum albumin.


RESULTS
Univariate logistic regression revealed that the risk of developing DIH was greater in older patients. Significantly greater percentage of cases had extrapulmonary tuberculosis (TB) (P<0.01). Also, a significantly higher percentage of cases had moderate to far advanced disease severity on chest radiograph (P<0.01). On multivariate logistic regression, the adjusted odds were significant (P<0.01) for age>35 yr, MAC<20 cm and hypoalbuminaemia (albumin<3.5 g/dl).


CONCLUSIONS
Older age, poor nutritional status including baseline hypoalbuminaemia were independent predictors of occurrence of anti-TB DIH. Clinicians should be vigilant for occurrence of hepatotoxicity in this high risk group.
Singla
Rohit
R
Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
Sharma
Surendra K
SK
Mohan
Alladi
A
Makharia
Govind
G
Sreenivas
V
V
Jha
Brajesh
B
Kumar
Sanjeev
S
Sarda
Pawan
P
Singh
Sarman
S
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001798:Blood Proteins / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D005260:Female; D006801:Humans; D007194:India; D008099:Liver / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013902:Radiography, Thoracic; D012307:Risk Factors; D012709:Serum Albumin; D012737:Sex Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000473:pathology
D000995:Antitubercular Agents; D001798:Blood Proteins; D012709:Serum Albumin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin