Painless Jaundice!

This morning we discussed an interesting case of a patient with painless jaundice after receiving multiple courses of antibiotics, including septra, for a presumed cellulitis.

Here is an approach to painless jaundice (not an exhaustive list):

1) Prehepatic causes:

• Hemolysis: i.e. AIHA, G6PD with offending drug
• Impaired hepatic bilirubin conjugation: Gilbert's, Crigler Najjar

2) Intra-hepatic causes:

• Inflammatory: Primary biliary cirrhosis, primary sclerosing cholangitis
• Malignant: Cholangiocarcinoma, hepatocellular carcinoma
• Infectious: Chlonorcus senensis (Chinese liver fluke), Ascaris lumbricoides, Viral: HBV, HCV, EBV, CMV (but usually produces more hepatocellular picture rather than a cholestatic picture), alcoholic hepatitis
• Drug induced liver injury
• Other: NASH, liver infiltration (amyloid, sarcoid, lymphoma)

3) Post-hepatic causes:

• Cholelithiasis: common bile duct obstruction, Mirizzi syndrome where distended gallbladder causes obstruction of extrahepatic bile duct
• Pancreatic neoplasm
• Stricture post instrumentation

A little more on Drug Induced Liver Injury (DILI)

1) Types of DILI:

• Can mimic all patterns observed in primary liver disease
• Acute hepatocellular injury: increased ALT/ALP ratio
• Cholestatic injury: Isolated increase in ALP, with decrease in ALT/ALP ratio
• Granulomatous hepatitis
• Steatohepatitis
• Can present as acute or chronic liver injury
• Acute hepatocellulary injury and fulminant liver failure:
• Examples of drugs that cause acute fulminant hepatitis include: acetaminophen, isoniazid, sulfonamides, cotrimoxazole, ketoconazole, anticonvulsants
• Acute Cholestatic injury:
• Presents clinically with jaundice, pruritis, dark urine and pale stools
• Liver enzymes reveal elevated ALP, GGT and Bili.
• Common culprit drugs include: anabolic steroids, oral contraceptives, prochlorperazine, and antibiotics (septra and erythromycin)
• See the following articles for more information:
• NEJM article on DILI
• Case report of Septra induced prolonged cholestasis: http://www.ncbi.nlm.nih.gov/pubmed/1587437