Drug-induced liver injury: Is chronic liver disease a risk factor and a clinical issue?

ABSTRACT

Introduction: Clinicians and practitioners caring for patients with chronic liver disease are often unsure whether drug therapy is a hazard that increases their patient’s risk for drug-induced liver injury (DILI).

Areas covered: We searched for reports of drug induced liver injury, both idiosyncratic and intrinsic, in patients with chronic liver disease including non-alcoholic and alcoholic liver disease, and cirrhosis. Reports we analyzed include statin treatment in patients with fatty liver, acetaminophen use in alcoholic fatty liver, antituberculous drugs in patients with tuberculosis and viral hepatitis, antiviral medications in hepatitis and antiretroviral medications in HIV/AIDS. The most challenging cases we found are drug therapy in patients with decompensated liver cirrhosis.

Expert opinion: We identified many case reports and case series discussing a potential increased risk of DILI in patients with pre-existing liver disease. However, most of these reports were retrospective and ambiguous. With few exceptions, we conclude that drugs seem to be well tolerated by the majority of patients with pre-existing, non-cirrhotic chronic liver diseases. Special care is needed for some therapies, however, including antiviral therapy in chronic hepatitis B and C and in decompensated liver cirrhosis with impaired drug metabolism. Prospective studies are warranted to valid our conclusions.

KEYWORDS:

• Drug-induced liver injury (DILI)
• Roussel Uclaf Causality Assessment Method (RUCAM)
• drug therapy
• chronic liver disease
• nonalcoholic fatty liver disease (NAFLD)
• alcoholic liver disease
• hepatitis B
• hepatitis C
• hepatitis E
• antituberculous drugs
• antiviral drugs
• statins
• liver cirrhosis

Article highlights

• Chronic liver disease is a common public health burden throughout the world. Western countries are plagued by nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD); most other countries by chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.

• Compared to these chronic liver diseases, drug-induced liver injury (DILI) is much less prevalent.

• Abnormal liver tests (LTs) are thus much more likely due to flares of chronic liver disease than to DILI.

• With few exceptions, most drugs do not appear to increase the risk of DILI in the majority of patients with preexisting non-cirrhotic chronic liver diseases. The exceptions included halogenated anesthetics, acetaminophen, antivirals, and antituberculous medications. Special care is needed for these drugs and in decompensated liver cirrhosis with antivirals that require close monitoring.

• Statins do not appear to increase the risk of DILI in patients with chronic liver disease.

• DILI is best diagnosed by a liver specific causality assessment method such as RUCAM.

• For patients with chronic HBV or HCV infection under antiviral therapy, hepatitis flares are validly recognized by quantitative virus load using HBV DNA or HCV RNA.

• The authors conclude that the use of most drugs in the majority of chronic, compensated liver diseases is not associated with an increased risk of DILI, but a few drugs such as antiviral drugs in decompensated HCV cirrhosis require special attention.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.