Case of persistent jaundice after bile duct stone clearance

Case presentation

A 67-year-old Caucasian man presented to our department with a 10-day history of painless jaundice and generalised pruritus. He reported no alcohol or drug intake, no history of travelling abroad and no significant personal or family medical history. Physical examination was normal except for excoriations.

Laboratory studies revealed cholestasis with markedly increased conjugated bilirubin (466.9 µmol/L) and an alkaline phosphatase (AP) level of 445 IU/mL. Transaminase, gamma-glutamyl transferase (GGT), serum albumin and prothrombin levels were within normal range. The extended viral hepatitis panel was negative as were the antimitochondrial and antinuclear antibodies. Abdominal ultrasound showed gallbladder stones and a 7 mm diameter common bile duct with no visible obstruction or intrahepatic biliary dilatations. The abdominal CT scan revealed choledocholithiasis with impaction at the level of the sphincter of Oddi and slight dilation of the bile ducts. Endoscopic retrograde cholangiopancreatography with extraction of the stone was performed, but the severe pruritus and malaise persisted while the bilirubin level continued to increase and reached a peak at 727 µmol/L. A short trial of corticosteroids was unsuccessful and ursodeoxycholic acid and cholestyramine were started with minimal improvement. Magnetic resonance cholangiopancreatography showed a normal biliary tree and liver biopsy was performed (figure 1).

Figure 1.

Liver biopsy specimen shows bland intracellular bile pigment deposits associated with minimal interface hepatitis and discrete areas of portal fibrosis. No signs of persistent biliary obstruction or sclerosing cholangitis are noted.

Question

What is the likely modification on liver histology?

Answer

The liver biopsy showed bland cholestasis with minimal interface hepatitis and portal fibrosis effectively ruling out small duct primary sclerosing cholangitis and infiltrative disorders. Extensive screening for autoimmune or metabolic liver disease and extrahepatic neoplasia was negative.

At the 2-week follow-up, the laboratory work showed increasing bilirubin levels and rifampicin was initiated (3 weeks). The bilirubin slowly reached normal levels after 14 weeks and a full clinical recovery was noted. Genetic testing for mutations in ATP8B1, ABCB11 and NR1H4 was negative.

Persistent hepatocellular secretory failure (PHSF) is a rare but potentially life-threatening disorder defined by non-remitting jaundice after removal of a hepatotoxic agent or short-term biliary obstruction.¹ Proposed diagnostic criteria include elevated bilirubin levels (proposed cut-off: 255 µmol/L) that persist at least 1 week after removal of the initial offender and the exclusion of ongoing obstruction or prior chronic liver disease.

A majority of patients have increased bilirubin and AP but normal GGT levels, a finding similar to progressive familiar intrahepatic cholestasis and benign recurrent intrahepatic cholestasis types 1 and 2. These are rare hereditary diseases caused by mutations in the genes (ATP8B1, ABCB11) coding for various hepatocellular membrane proteins involved in membrane stability and bile salt transport. PHSF can spontaneously resolve or lead to liver failure requiring transplant, and the only reported medical treatment is with rifampicin,² a potent pregnane-X-receptor agonist.

Ethics statements

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