Liver-side of inflammatory bowel diseases: Hepatobiliary and drug-induced disorders

Table 1 Main features of hepatobiliary manifestations associated with inflammatory bowel diseases

Hepatobiliary manifestation	Main features
Immune-mediated
PSC	The most frequent (50%-80% of PSC patients have IBD, and 2%-8% of IBD patients have PSC)
	No medical treatment approved. Therapies directed towards PSC complications
	Increased risk of cholangiocarcinoma and colorectal cancer (surveillance needed)
Small duct PSC	Histological evidence of PSC, but normal cholangiogram
	More benign disease course than classic PSC (cholangiocarcinoma risk not increased)
PSC-AIH overlap syndrome	Coexistence of biochemical and histological features of AIH and PSC-associated biliary tract alterations
	Better response to steroids and immunosuppressants than PSC
IgG4-related sclerosing cholangitis	Part of the IgG4-related systemic disease
	Characterized by histological evidence of IgG4+ plasma cells infiltrate
	Good response to steroids
Granulomatous hepatitis	Rare, generally in Crohn’s disease
	Autoimmune or drug-induced pathogenesis
	Good response to steroids
Non-immune-mediated
Gallstone disease	Incidence increased in IBD, more in Crohn’s disease
	Bile salts malabsorption underlying the pathogenesis
NAFLD	Not strictly associated with IBD; similar risk factors in the general population
	Higher NAFLD prevalence in patients with severe IBD activity
Pyogenic liver abscess	Rare, mainly in Crohn’s disease
	Penetrating disease, steroid treatment and malnutrition are risk factors
Portal vein thrombosis	Increased risk in IBD, especially during severe disease flare and after surgery. Prophylactic treatment indicated in these settings
DILI
Aminosalicylates	Low risk of DILI
	LFT monitoring not necessary
Thiopurines	DILI quite frequent (prevalence of about 3%); both dose-independent and dose-dependent toxicities are possible
	Regular LFT monitoring indicated
Methotrexate	DILI quite frequent, with a prevalent dose-dependent mechanism
	Regular LFT monitoring indicated
	Folic acid supplementation indicated during treatment
Anti-tumour necrosis factor-α	Low risk of DILI, mainly with infliximab
	LFT monitoring not necessary
Anti-integrins	Low risk of DILI
	LFT monitoring not necessary
Anti-interleukin 12/23	Low risk of DILI
	LFT monitoring not necessary
Tofacitinib	Data in IBD still scarce
	Alanine aminotransferase elevation quite frequent in rheumatoid arthritis, but generally mild
Hepatitis B reactivation	A relevant concern
	Antiviral therapy indicated in HBsAg positive patients
	LFT monitoring indicated in HBsAg negative/anti-HBc positive patients
	Vaccination indicated in naïve patients
Hepatitis C reactivation	Not a relevant concern

IBD: Inflammatory bowel diseases; PSC: Primary sclerosing cholangitis; LFT: Liver function tests; HBsAg: Hepatitis B surface antigen; DILI: Drug-induced liver injury; NAFLD: Non-alcoholic fatty liver disease; AIH: Autoimmune hepatitis.

Table 2 Management of patients with inflammatory bowel disease undergoing immunosuppressive therapy according to hepatitis B status

Hepatitis B status	Indications
HBsAg positive/anti-HBc positive (chronic hepatitis B)	Antiviral treatment (start 3-4 wk before and continue at least 12 mo after the immunosuppressive treatment)
HBsAg negative/anti-HBc positive (occult hepatitis B)	Liver function tests monitoring every 2-3 mo
HBsAg negative/anti-HBc negative/anti-HBs negative (naïve for hepatitis B)	Vaccination (indicated at diagnosis)
HBsAg negative/anti-HBc negative/anti-HBs positive	Check previous hepatitis B vaccination. Dose hepatitis B virus-DNA if uncertainty

HBsAg: Hepatitis B surface antigen.