Anti-Tuberculosis Drug Induced Liver Injury and Ursodeoxycholic Acid

Susanne M Lang,Emad Al-Nemnem,Helmut Schiffl

doi:10.4236/jtr.2020.82007

Abstract

Hepatotoxicity induced by standard anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide) can result in significant morbidity and, rarely, even mortality. This major adverse side-effect of anti-tuberculosis treatment has a negative impact on patient adherence and patient outcomes as well as on tuberculosis control. Early recognition and prompt withdrawal of the offending drugs are the most critical interventions in the management of anti-tuberculosis drug-induced liver injury. No drug or herbal extract has been shown until recently to prevent or reverse anti-tuberculosis drug-induced hepatotoxicity. Ursodeoxycholic acid is the only FDA approved drug for the treatment of primary biliary cholangitis and has also been successfully used in various cholestatic liver diseases. Although still experimental, recent controlled clinical studies suggested that oral administration of ursodeoxycholic acid may prevent the onset of anti-tuberculosis drug-induced liver injury and accelerate the recovery of liver injury. These clinical data are supported by experimental models of anti-tuberculosis drug-induced hepatotoxicity. There is an urgent need for further randomized clinical trials to document the promising hepatoprotective properties of ursodeoxycholic acid.

Highlights

Hepatotoxicity is a frequent and potentially serious adverse effect of standard first line anti-tuberculosis drug (ATD) regimens containing the hepatotoxic compounds isoniazid, rifampicin, and pyrazinamide
Hepatotoxicity induced by standard anti-tuberculosis drugs can result in significant morbidity and, rarely, even mortality
Recent controlled clinical studies suggested that oral administration of ursodeoxycholic acid may prevent the onset of anti-tuberculosis drug-induced liver injury and accelerate the recovery of liver injury

Summary

Introduction

Hepatotoxicity is a frequent and potentially serious adverse effect of standard first line anti-tuberculosis drug (ATD) regimens containing the hepatotoxic compounds isoniazid, rifampicin, and pyrazinamide. This may be attributable to patient characteristics, the drug regimen involved, or the threshold of liver function tests used to define hepatoxicity. The usefulness of UDCA as a novel hepatoprotective agent for drug-induced hepatotoxicity was largely demonstrated by case reports and observational studies [13]-[21]. This narrative review describes the available experience with this drug in TB patients receiving standard first line treatment

UDCA and ATD-Induced Liver Injury

Mechanisms of Action of UDCA

Findings

Conclusion