Table 2 Genes and proteins involved in adult cholestasis

Recurrent Intrahepatic cholestasis (RIC)

ATP8B1/FIC1

ABCB11/BSEP

MyosinVB/MYO5B

Intermittent severe cholestasis (intervals weeks to years); hearing loss, pancreatitis, diarrhoea

High during attack

Low or normal

High

Normal or mild elevation

Centrilobular cholestasis,

no alteration of liver structure,

no BSEP tissue expression

Intrahepatic cholestasis of pregnancy (ICP)

ATP8B1/FIC1

ABCB11/BSEP

ABCB4/MDR3

TJP2/ZO-2

Transient cholestasis + itching during pregnancy; post-natal resolution; potentially serious fetal complications

High during pregnancy

Normal or mild elevation

Normal or mild elevation

Normal or mild elevation

Not performed

Drug-induced cholestasis (DIC)

ABCB11/BSEP

ABCB4/MDR3

Chronic liver injury; acute hepatitis; fulminant hepatic failure

Use of herbal remedies and naturopathic substances should be investigated

Onset < 1–12 months by drug administration

Normal or mild elevation

Variable

High

Moderate or severe

Loss of BSEP/MDR3 expression,

canalicular cholestasis,

hepatocellular inflammation

Low-Phospholipid Associated Cholelithiasis (LPAC)

ABCB4/MDR3

 < 40y cholelitiasis; intrahepatic microlithiasis; recurrence of biliary symptoms after cholecystectomy; previous episodes of ICP; familial history of gallstones

High during obstruction

High

Normal or high

Normal or mild elevation

Not required; imaging-based diagnosis

Adult Cryptogenetic Cholestasis (ACC)

ATP8B1/FIC1

ABCB4/MDR3

ABCB11/BSEP

TJP2/ZO-2

Itching for more than 6 months, lobular cholestasis

High

High

High

Normal

Lobular cholestasis (ductal hepatocyte metaplasia,

ductal proliferation and immunohistochemistry

for bile duct cytokeratin 7,

anti-BSEP, and anti-MDR3 antibodies)

Hepatobiliary Cancer (HBC)

ABCB11/BSEP

ABCB4/MDR3

TJP2/ZO-2

Hepatocellular carcinoma (HCC)

Cholangiocarcinoma (CCA)

Gallbladder and gallway cancer