Is naltrexone (opioid receptor antagonist) safe to use in a patient with hepatitis C, history of jaundice, elevated liver enzymes (alkaline phosphatase (ALP) elevation, mild transaminitis), and thrombocytosis, who consumes alcohol and uses methamphetamine?

Naltrexone Safety in This Patient with Hepatitis C and Liver Disease

Naltrexone should NOT be used in this patient due to active alcohol use, evidence of underlying liver disease (hepatitis C with prior jaundice and elevated ALP), and ongoing substance use that requires strict abstinence and alternative pharmacotherapy. 1, 2

Critical Contraindications Present

This patient has multiple red flags that make naltrexone inappropriate:

• Active alcohol consumption is an absolute contraindication - The American Association for the Study of Liver Diseases explicitly states that patients on naltrexone must avoid alcohol, as continued drinking leads to disease progression in alcohol-induced liver disease and reduces medication effectiveness 1

• Evidence of liver disease with hepatitis C - The patient has chronic hepatitis C, history of jaundice (indicating prior hepatic decompensation), and elevated alkaline phosphatase in the 300s (normal <120 U/L), suggesting cholestatic liver injury or advanced fibrosis 1, 2

• Hepatotoxicity risk is documented - The FDA label clearly warns that naltrexone causes hepatocellular injury, particularly at therapeutic doses, with cases of hepatitis and clinically significant liver dysfunction reported 2

Specific Laboratory Concerns

The elevated ALP (300s) is particularly concerning:

• While ALT (48) and AST (30) are near-normal, the markedly elevated alkaline phosphatase suggests cholestatic injury or advanced liver disease 2

• The FDA specifically notes that adequate studies in patients with severe hepatic impairment have not been conducted 2

• Thrombocytosis (platelets 492) is unusual and may indicate underlying inflammatory processes or myeloproliferative disorder, but does not mitigate liver concerns 2

Why Naltrexone is Specifically Contraindicated Here

The combination of active substance use and liver disease creates unacceptable risk:

• Naltrexone requires first-pass hepatic metabolism with only 5-40% oral bioavailability, placing significant metabolic burden on an already compromised liver 3, 2

• The drug is explicitly not recommended in patients with alcoholic liver disease due to toxic liver injury risk 1

• Continued alcohol and methamphetamine use will cause ongoing hepatic injury that naltrexone cannot prevent and may worsen 1, 2

Recommended Alternative Approach

Baclofen is the preferred medication for this patient:

• Baclofen (30-60 mg/day) is the only medication for alcohol use disorder tested in randomized controlled trials specifically in patients with cirrhosis, including decompensated disease 3

• The American Association for the Study of Liver Diseases recommends baclofen as a better alternative for patients with liver cirrhosis who need medication to maintain abstinence 1

• Baclofen has minimal hepatic metabolism and an acceptable safety profile in advanced liver disease 3

Acamprosate is another safer alternative:

• Acamprosate has no hepatic metabolism and no reported hepatotoxicity 3, 1

• It is renally excreted and does not place metabolic burden on the liver 3

• While not studied specifically in hepatitis C patients, it appears safe in liver disease 3

Essential Next Steps Before Any Pharmacotherapy

This patient requires comprehensive liver disease staging:

• Liver imaging (ultrasound or FibroScan) is mandatory - The patient has never had liver imaging despite hepatitis C, prior jaundice, and elevated ALP 3

• Calculate FIB-4 score to assess fibrosis stage: FIB-4 = (Age × AST) / (Platelets × √ALT). With these values, staging is essential before any hepatotoxic medication 3

• Screen for hepatocellular carcinoma - Patients with chronic hepatitis C and possible cirrhosis require ultrasound surveillance 3

• Assess for cirrhosis and decompensation - Prior jaundice suggests possible decompensation; Child-Pugh scoring is needed 3

Critical Management Priorities

Strict abstinence from alcohol must be the primary goal:

• For patients with evidence of alcohol-related liver disease, strict abstinence is mandatory as continued use is associated with disease progression 1

• Patients who attempt to cut back rather than stop completely have significant recidivism risk 3

• There is no safe amount of alcohol consumption after hepatic injury 3

Address hepatitis C treatment:

• This patient should be evaluated for direct-acting antiviral therapy for hepatitis C, which can prevent progression to cirrhosis and improve outcomes 3

• Active substance use is not a contraindication to hepatitis C treatment in current guidelines 3

Common Pitfalls to Avoid

Do not prescribe naltrexone based solely on "normal" transaminases:

• The elevated ALP is more concerning than the near-normal ALT/AST, as it suggests cholestatic injury or advanced disease 2

• Transaminases can be normal in cirrhosis, making them unreliable markers of hepatic reserve 3

Do not assume naltrexone is safe because recent studies show safety in cirrhosis:

• While a 2024 study showed no DILI in patients with cirrhosis on naltrexone, those patients were abstinent from alcohol 4

• This patient's active alcohol and methamphetamine use creates ongoing hepatotoxicity that fundamentally changes the risk-benefit calculation 1, 2

Monitor for hepatic encephalopathy with baclofen:

• If baclofen is chosen, monitor closely for worsening mental status or sedation, as it may impair mentation in advanced liver disease 3

• Patients with hepatic encephalopathy were excluded from baclofen trials 3