Severe hepatotoxicity associated with bromfenac sodium

Subacute hepatitis and liver failure occurred in a 40-yr-old woman following a 1-month course of treatment with the nonsteroidal anti-inflammatory drug bromfenac. Serologies for hepatitis A, B, and C were negative, as were antinuclear antibodies and ceruloplasmin. A transjugular liver biopsy demonstrated submassive hepatic necrosis. The clinical course was complicated by encephalopathy, fluid retention, and spontaneous bacterial peritonitis, prompting consideration for liver transplantation. With supportive measures, jaundice and fluid retention resolved over a 3-month period. We conclude that prolonged use of bromfenac was the etiological agent in this case, and that this drug can cause severe hepatotoxicity resulting in liver failure.     

Severe cholestatic jaundice associated with piroxicam

A 62-year-old man with rheumatoid arthritis developed jaundice while taking piroxicam. A full evaluation including ultrasound, computerized tomography, endoscopic cholangiography, and liver biopsy confirmed the diagnosis of intrahepatic cholestasis. The patient's jaundice and all other liver function abnormalities normalized 4 months after he discontinued taking piroxicam. This is the first case report in the United States of severe liver toxicity associated with piroxicam. The six cases in the English-language literature are reviewed, featuring the presentation, patterns of liver injury, and outcome in each. Piroxicam should be considered as a potential cause of cholestatic jaundice when other more common etiologies have been excluded.     

Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects

Human immunodeficiency virus (HIV)-infected South African patients (n=468) received blinded lamivudine or emtricitabine, stavudine, and either nevirapine or efavirenz (based on screening viral load). Baseline characteristics were analyzed in univariate and multivariate regression, to identify risk factors for hepatotoxicity (grade 3 or greater increase in serum aminotransferase levels). The occurrence of early hepatotoxicity was 17% in the nevirapine group and 0% in the efavirenz group and was balanced between the lamivudine and emtricitabine arms. Two subjects died of hepatic failure. Independent risk factors were body-mass index (BMI) <18.5, female sex, serum albumin level <35 g/L, mean corpuscular volume >85 fL, plasma HIV-1 RNA load <20,000 copies/mL, aspartate aminotransferase level <75 IU/L, and lactate dehydrogenase level <164 IU/L. The use of nevirapine in female patients with a low BMI should be discouraged.     

Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole

Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially – available combination of two antibiotics – spiramycin and metronidazole – commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.     

Severe jaundice following treatment with ezetimibe

Ezetimibe is a cholesterol-lowering agent that modulates intestinal absorption of sterols. It is well tolerated but hepatic toxicity has been reported when ezetimibe is used in conjunction with a statin medication. In this case report, we report severe isolated hyperbilirubinaemia occurring in a patient with occult cirrhosis, probably owing to nonalcoholic steatohepatitis, who was treated with ezetimibe alone. The adverse event started after ezetimibe therapy was initiated and resolved when the drug was stopped. We propose a mechanism for this reaction and believe that liver function should be monitored in patients with abnormal liver tests who are treated with ezetimibe, even if they are not on concomitant treatment with a statin.     

Marked hepatotoxicity associated with losartan treatment

Nygaard B, Strandgaard S. Marked hepatotoxicity associated with losartan treatment.

Losartan represent a novel approach in the treatment of hypertension. Clinical trials have reported a very low incidence of side effects. We describe two patients who developed increases in alanine/aspartate amino transferase of 8 and 15 times the upper normal limit, as well as thoracic pain, after a short time of treatment with losartan. The increase resolved after discontinuing losartan treatment.     

Cholestatic jaundice associated with D-penicillamine therapy

Cholestatic jaundice is a rare complication of penicillamine therapy. We report here a 35-year-old patient who developed fever, a rash and cholestatic jaundice 16 days after commencing treatment with penicillamine for cystinuria. The jaundice subsided slowly after discontinuation of the drug and with prolonged therapy with prednisone. The literature on penicillamine-induced liver injury is reviewed.     

Hepatorenal syndrome associated with obstructive jaundice

In almost all cases of acute renal failure associated with cholestatic jaundice, the occurrence of renal failure is preceded by episodes of shock, hypotension, sepsis, or surgical intervention. The pathologic finding is usually that of acute tubular necrosis. A patient with obstructive jaundice developed renal failure; the clinical and pathologic features were consistent with those found in the hepatorenal syndrome. No episodes of shock or sepsis preceded the onset of that renal failure. At autopsy, the findings were normal.