Drug-Induced Acute Cholestatic Liver Damage in a Patient with Mutation of UGT1A1

Igino Rigato*; Monica Cravatari; Claudio Avellini; Euro Ponte; Saveria Lory Crocè; Claudio Tiribelli

Disclosures

Nat Clin Pract Gastroenterol Hepatol. 2007;4(7):403-408. 

In This Article

Differential Diagnosis

The differential diagnosis of drug-related liver injury should include all the causes of acute hepatitis with jaundice (Figure 2).

Figure 2.

Factors influencing differential diagnoses of drug-related hepatitis in individuals with elevated levels of aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase and bilirubin (both conjugated and unconjugated). Abbreviations: ANA, anti-nuclear antibody; CDT, carbohydrate deficient transferrin; CMV, cytomegalovirus; EBV, Epstein–Barr virus; hBsAg, hepatitis B surface antigen; LKM, liver/kidney microsomal; MCV, mean corpuscular volume; SLA/LP, soluble liver antigen/liver pancreas antigen; SMA, smooth muscle antibody.

Viral Hepatitis

Acute hepatitis with jaundice can be the onset manifestation of acute viral hepatitis. The most common causative agents in developed countries are HBV and HAV and, less commonly, HCV, the acute clinical manifestation of which is usually without symptoms. Infection with other hepatotropic viruses (e.g. hepatitis E, Epstein-Barr virus and cytomegalovirus) should also be considered. The case patient tested negative for the serological markers of hepatotropic viruses that can cause acute hepatitis.

Autoimmune Hepatitis

Autoimmune hepatitis presents as acute hepatitis in 25% of cases. The clinical manifestation and histology pattern of autoimmune hepatitis are also typical of other diseases, and a diagnosis is therefore confirmed using a clinical score that considers multiple features of the case. Anti-nuclear antibody, anti-smooth muscle antibody, liver/kidney microsomal antibodies and/or autoantibodies against soluble liver antigen/liver pancreas antigen are typical serum markers of autoimmune hepatitis, and an increased level of serum globulins is usually observed.

In this case, autoimmune hepatitis was suspected because of the onset of the disease, a cholestatic acute hepatitis, and the age and gender of the patient; however, the complete absence of autoantibodies, the liver histology and the clinical outcome ruled out this possibility.

Hepatic Hemodynamic Diseases

Acute heart failure and shock syndrome can indicate an acute cholestatic liver failure. Thrombosis of the hepatic portal vein or acute occlusion of the hepatic artery can also result in acute hepatitis with jaundice. Ultrasonography with a color Doppler analysis allows the identification of portal vein obstruction. The patient did not present any abnormality of the hepatic vascular tract on color Doppler ultrasonographic analysis.

Alcoholic Hepatitis

A positive history of alcohol intake or abuse with alcohol detectable in the serum is the key factor in a diagnosis of alcoholic hepatitis. Aspartate aminotransferase (AST) levels are higher than alanine aminotransferase (ALT) levels and this is usually associated with an increase in GGT, especially if the alcohol addiction is long standing. The case patient claimed not to be an alcohol drinker and her AST/ALT ratio was below one. A carbohydrate-deficient transferrin test (a particularly sensitive indicator of alcohol abuse) was not performed as there was no suspicion of undeclared alcohol intake.

Biliary Tract Disorders

Any condition resulting in obstruction of the bile ducts can also result in acute hepatitis with jaundice. The clinical onset of an obstruction is usually characterized by pain in the upper right abdominal quadrant, nausea and/or vomiting, epigastric pain with tenderness during physical examination, guarding, rebound tenderness and Murphy's sign, all of which were absent in the case patient. Neoplastic obstruction of the bile ducts can also cause jaundice, although pain is frequently absent. Ultrasonography is the initial diagnosis test of choice for biliary tract disease. Ultrasonography and MRI-cholangiography in the case patient revealed no dilatation of the biliary tract ducts.

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