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Table 3. Established and putative risk factors for intra-and extrahepatic CC.

Intrahepatic CC			Extrahepatic CC
	Characteristics of the association			Characteristics of the association
Risk factor	Strength	Level of evidence	Risk factor	Strength	Level of evidence
Bile duct cysts ⁽⁴⁰⁾	+++	+++	Bile duct cysts ⁽⁴⁰⁾	+++	+++^a
PSC ⁽⁴⁰⁾	+++^a	+++^a	PSC ⁽⁴⁰⁾	+++^a	+++^a
Caroli's disease ⁽⁴¹⁾	+++^a	+++^a	Caroli's disease ⁽⁴¹⁾	+++^a	+++^a
Hepatolithiasis ⁽⁴⁰⁾	+++	+++	Choledocholitihasis ⁽⁴⁰⁾	+++	++
Choledocholitihasis ⁽⁴⁰⁾	+++	++	Cholangitis ⁽⁴⁰⁾	+++	++
Cholangitis ⁽⁴⁰⁾	+++	++	O. viverrini ⁽⁴⁰⁾	+++^a	+++^a
O. viverrini ⁽⁴⁰⁾	+++^a	+++^a	C. sinensis ⁽⁴⁰⁾	+++^a	+++^a
C. sinensis ⁽⁴⁰⁾	+++^a	+++^a	Cirrhosis ⁽⁴³⁾	++	++
Cirrhosis ⁽⁴³⁾	+++	+++	HBV ⁽⁴⁴⁾	+	+
HBV ⁽⁴⁴⁾	++	+++	HCV ⁽⁴²⁾	+	+
HCV ⁽⁴³⁾	++	+++	Cigarette smoking ⁽⁴³⁾	+	+
NASH ⁽⁵⁸⁾	+	+	Diabetes mellitus ⁽⁴³⁾	+	++
Hemochromatosis ⁽⁴⁵⁾	?	++	Thorotrast ⁽⁴⁰⁾	+++^a	+++^a
Wilson's disease ⁽⁴⁶⁾	?	++		+	+
Cigarette smoking ⁽⁴³⁾	+	+
Alcohol ⁽⁴³⁾	++	++
Obesity ⁽⁴³⁾	+	++
Diabetes mellitus ⁽⁴³⁾	+	++
Thorotrast ⁽⁴⁰⁾	+++^a	+++^a
Asbestos ⁽⁴⁷⁾	++	+

Abbreviations: HBV, hepatitis B virus; HCV hepatitis C virus; NASH, non-alcoholic steatohepatitis; PSC, primary sclerosing cholangitis.

Available studies did not distinguish between ICC and ECC

NB: + = weak association/weak evidence; ++ = moderate association/moderate evidence; +++ = strong association/strong evidence.