Secondary Biliary Cirrhosis

Secondary biliary cirrhosis is cirrhosis resulting from prolonged extrahepatic (or large duct) biliary obstruction or chronic cholangitis, in contrast to primary biliary cholangitis.

It develops after months to years of obstruction, depending on severity and recurrent cholangitis. Causes include benign biliary strictures (postoperative, after cholecystectomy or liver transplant), chronic pancreatitis, choledocholithiasis, Mirizzi syndrome, biliary atresia, choledochal cysts, cystic fibrosis, primary sclerosing cholangitis (usually classed separately), chronic cholangitis and biliary tumours.

Cirrhosis can be reversed or arrested if obstruction is relieved early.

Pathophysiology.

Bile stasis causes retention of toxic bile acids, ductular proliferation, portal inflammation and periportal fibrosis. Bile infarcts and recurrent cholangitis lead to biliary fibrosis and eventually cirrhosis with portal hypertension.

Jaundice, pruritus, dark urine and pale stools, recurrent cholangitis (fever, rigors, pain), steatorrhoea, weight loss, fat soluble vitamin deficiency (night blindness, bruising, bone pain), osteoporosis, xanthelasma and, in cirrhosis, portal hypertension features (varices, ascites, splenomegaly).

Red flags.

• Fever with jaundice (cholangitis).
• Variceal bleeding.
• Encephalopathy or ascites.
• Weight loss and a stricture suggesting malignancy.

Cholestatic liver tests (alkaline phosphatase and gamma glutamyl transferase raised more than bilirubin early), with raised bilirubin later. Ultrasound shows dilated ducts. Magnetic resonance cholangiopancreatography defines strictures, stones and the level of obstruction. Endoscopic retrograde cholangiopancreatography or endoscopic ultrasound allows brushings and therapy. Liver biopsy shows ductular reaction, bile infarcts and fibrosis; elastography stages fibrosis. Check INR, vitamin A, D, E and K status, bone density and for varices.

Differential diagnosis.

• Primary biliary cholangitis.
• Primary sclerosing cholangitis.
• Cholangiocarcinoma.
• Vanishing bile duct syndrome.
• Drug induced cholestasis.
• Cystic fibrosis liver disease.

Relieve the obstruction: endoscopic or percutaneous stone clearance, stricture dilation and stenting, or surgical hepaticojejunostomy. Treat cholangitis promptly.

• Piperacillin-tazobactam (acute cholangitis): 4.5 g IV every 6 hours for 4 to 7 days after drainage; maximum 18 g daily; monitor renal function and blood counts; reduce for creatinine clearance under 40 mL/min.

Treat pruritus:

• Colestyramine: 4 g orally once daily, increased to 4 g two to four times daily; long term; maximum 16 g daily in this use; monitor bowel function and vitamin levels; take 4 hours before or 1 to 2 hours after other drugs; avoid in complete biliary obstruction.
• Rifampicin: 150 mg orally once daily, increased every 1 to 2 weeks to 300 to 600 mg daily; maximum 600 mg daily; monitor liver enzymes and blood counts every 2 to 4 weeks; avoid in decompensated cirrhosis; reduce in hepatic impairment; many drug interactions.
• Naltrexone: 12.5 mg orally once daily, increased to 50 mg daily; maximum 50 mg daily; monitor for opioid withdrawal like symptoms and liver function; avoid with opioid use.

Replace fat soluble vitamins: vitamin K (phytomenadione) 10 mg orally or IV once daily for 3 days when INR is raised, maximum 10 mg daily, monitor INR; vitamin D and calcium as needed. Treat osteoporosis. Manage portal hypertension and refer for liver transplant assessment for decompensated disease.

Monitoring. Liver tests and INR every 3 months, ultrasound every 6 months and varices screening; bone density every 2 years.

Referral and escalation. Hepatology, biliary endoscopy and hepatobiliary surgery; transplant centre for decompensation.