Hepatic manifestations of non-steroidal inflammatory bowel disease therapy

Table 1 Risk of hepatitis B viral DNA associated with medication use and hepatitis B status

Risk group	Medication	Hepatitis B virus status
High risk (> 10%)	Corticosteroids > 4 wk (moderate-high dose)	HBsAg+/HBcAb+
Moderate risk (1%-10%)	TNF-α inhibitors	HBsAg+/HBcAb+ (1%-10%)
	Ustekinumab	HBsAg-/HBcAb+ (1%)
	Vedolizumab
	Natalizumab
	Corticosteroids > 4 wk	HBsAg+/HBcAb+ (1%-10%) (low dose)
		HBsAg-/HBcAb+ (1%) (moderate-high dose)
Low-risk (< 1%)	Azathioprine	HBsAg+/HBcAb+
	6-mercaptopurine	HBsAg-/HBcAb+
	Methotrexate

Adapted from American Gastroenterological Association Institute Technical Review on Prevention and Treatment of Hepatitis B Virus Reactivation During Immunosuppressive Drug Therapy[66]. Corticosteroids (prednisone equivalent): Low dose: < 10 mg; Moderate dose: 10-20 mg; High dose: > 20 mg. HBsAg: Hepatitis B surface antigen; HBcAb: Anti-hepatitis B core antibody; TNF-α: Tumor necrosis factor-alpha.

Table 2 Summary of medication side effects and management options

Medication	Prevalence of liver injury	Manifestation	Management1
Sulfasalazine	0.4%-2.9%	Mild liver test abnormalities
		Severe systemic hypersensitivity
		Granulomatous hepatitis
		DRESS syndrome
5-ASA	Approximately 2.6%	Mild liver test abnormalities
		Drug induced autoimmune hepatitis
		Systemic hypersensitivity reaction
AZA/6-MP	1.4%-7.1%	Hypersensitivity reaction	Slight liver test elevation →
		Cholestasis	Monitor
		Peliosis hepatitis
		Disse space fibrosis	Persistent elevation →
		Veno-occlussive disease	Consider stopping medication/reducing dose
		Nodular regenerative hyperplasia	Marked elevation →
		Hepatosplenic T-cell lymphoma	Stop medication
Methotrexate	Approximately 10.2%	Elevated liver tests
		Fibrosis
Anti-TNF-α agents	0.37%-6.7%	Hepatocellular injury
		Cholestasis
		Hepatosplenic T-cell lymphoma
		Autoimmune hepatitis
Anti-integrin therapy	< 5%	Hepatocellular injury
		Cholestasis
		Autoimmune hepatitis
		Liver failure
Ustekinumab	1.4%	Elevated liver tests
Cyclosporine	1%-4%	Increased bile acids
		Cholestasis
		Hepatocellular injury

¹For general management of elevated liver tests. For specific recommendations see text. ASA: Aminosalicylic acid; AZA: Azathioprine; 6-MP: 6-Mercaptopurine; TNF: Tumor necrosis factor; DRESS: Drug reaction with eosinophilia and systemic symptoms.