Can Crohn's disease affect the liver?

Can Crohn's Disease Affect the Liver?

Yes, Crohn's disease can affect the liver through multiple mechanisms, including disease-specific hepatobiliary manifestations, drug-induced liver injury from IBD medications, and metabolic complications, with non-alcoholic fatty liver disease being the most common (prevalence 1.5-39.5%) and primary sclerosing cholangitis being the most specific hepatobiliary complication. 1

Direct Disease-Related Hepatic Manifestations

Crohn's disease causes several distinct liver and biliary complications that occur independently of intestinal disease activity:

Primary Sclerosing Cholangitis (PSC)

• PSC is less common in Crohn's disease compared to ulcerative colitis, but remains a significant hepatobiliary manifestation 1
• When PSC occurs with IBD, surveillance colonoscopy is required every 1-2 years due to 4-fold increased colorectal cancer risk 1
• Annual ultrasonography to detect gallbladder mass lesions is recommended, as these carry up to 56% malignancy risk in PSC patients 1

Non-Alcoholic Fatty Liver Disease (NAFLD)

• NAFLD is the most common hepatic manifestation, occurring in 1.5-39.5% of Crohn's disease patients (overall mean prevalence 23%) 1
• Risk factors include both metabolic syndrome components and Crohn's-specific factors: intra-abdominal abscesses, fistulizing disease, colitis severity, malnutrition, protein loss, and corticosteroid use 1

Other Hepatobiliary Complications

According to the European Crohn's and Colitis Organisation (ECCO), patients with Crohn's disease can develop 1:

• Granulomatous hepatitis - a rare manifestation that can mimic hepatic sarcoidosis and requires careful diagnostic workup to exclude infectious etiologies 2
• Portal vein thrombosis - more frequent in the postoperative setting, requiring thromboembolism prophylaxis during hospitalizations 1
• Hepatic abscess - reported as a serious infection requiring hospitalization 1
• Liver amyloidosis - rare complication (0.9% in Crohn's disease) from longstanding active inflammation 1
• Cholelithiasis 1

Drug-Induced Liver Injury (DILI)

Laboratory monitoring of liver tests every 1-3 months is required for many IBD medications, as DILI affects a substantial proportion of Crohn's disease patients. 1

Thiopurines (Azathioprine/6-Mercaptopurine)

• Hepatotoxicity incidence varies from 3-15% across studies, with 4% reported in a large Spanish database of nearly 4000 patients 1
• Most cases occur within the first few months of treatment and are dose-dependent 1
• Baseline and ongoing 12-weekly blood monitoring is mandatory, with bloods repeated 2 weeks after all dose increases 1
• Thiopurines can cause vascular endothelial damage leading to veno-occlusive disease, peliosis hepatis, and nodular regenerative hyperplasia - suspect these with elevated gamma-GT and thrombocytopenia 1
• Up to 81% of patients with azathioprine-induced liver toxicity tolerate switching to 6-mercaptopurine 1

Methotrexate

• Increased aminotransferase levels occur in approximately 10% of IBD patients, but withdrawal due to hepatotoxicity is unusual (only 5%) 1
• Risk of cirrhosis is much lower than previously thought, and routine liver biopsy after prolonged use is not necessary 1
• In a study of 518 patients (24% with Crohn's disease), only 4% had FibroScan results suggesting severe liver fibrosis 1
• Patients with BMI >28 kg/m² and alcohol intake >14 drinks per week should be screened using transient elastography 1
• Methotrexate should be stopped if transaminases exceed twice the upper limit of normal 1
• Folic acid (1 mg daily or 5 mg weekly) reduces gastrointestinal and liver toxicity 1

Anti-TNF Agents (Infliximab, Adalimumab)

• Hepatotoxicity is rare but has been reported, most frequently with infliximab 1, 3, 4
• Several cases of anti-TNF-induced autoimmune hepatitis and cholestatic liver disease have been documented 1
• In pediatric Crohn's disease trials, ALT elevations up to 3 times ULN occurred in 18% of patients, with 4% having elevations ≥3× ULN 5

5-Aminosalicylic Acid (5-ASA)

• DILI is uncommon and usually mild, though chronic hepatitis has been described 1

Antibiotics

• Ciprofloxacin, commonly used in Crohn's disease, can cause delayed and prolonged cholestatic hepatitis with ductopenia after long-term use 6

Clinical Approach and Monitoring

When Crohn's disease patients present with abnormal liver tests, clinicians must systematically evaluate whether abnormalities are disease-related, drug-induced, or from unrelated causes:

• Abnormal liver biochemical tests occur in up to 30% of IBD patients 4, 7
• The spectrum of hepatic manifestations varies according to disease type and activity 7
• Management typically requires collaboration between gastroenterologists and hepatologists due to diagnostic complexity 4, 7

Key Monitoring Recommendations

• Baseline liver function tests before initiating thiopurines or methotrexate 1
• Every 1-3 months monitoring during treatment with hepatotoxic medications 1
• Consider transient elastography for patients on methotrexate with additional risk factors (obesity, alcohol use) 1
• Liver biopsy when vascular complications suspected (elevated gamma-GT with thrombocytopenia) 1

Important Caveats

• Hepatitis B reactivation during immunosuppressive therapy is a major concern - screening and vaccination recommended for seronegative patients 4
• HBsAg-positive patients require prophylaxis with entecavir or tenofovir for 6-12 months after immunosuppressive therapy ends 4
• Immunosuppressive therapy does not appear to promote hepatitis C reactivation 4
• Early diagnosis of drug-induced liver injury is critical as it affects future clinical management 7