Clarithromycin-Induced Acute Liver Failure (ALF)

Abstract

Clarithromycin is a macrolide antibiotic widely used to treat respiratory, skin, and soft tissue infections. Although elevated liver enzymes and cholestatic hepatitis have been infrequently reported, comprehensive literature review reveals only 6 cases of clarithromycin-induced ALF (fig 2). 60-year-old male with history of hypertension and hypothyroidism presented to the hospital with acute asthma exacerbation secondary to respiratory tract infection. Complete blood picture, and liver and kidney function tests were within normal limits. Clarithromycin, prednisone and albuterol inhaler were prescribed, and he was discharged. 10 days later, he represented and physical examination revealed stable vital data but soft, diffusely tender abdomen with hypoactive bowel sounds and no peritoneal signs. Laboratory analysis revealed WBC=12.2bil/L, hemoglobin(hb)=14.5 g/dL and platelets=129bil/L, lipase=33 U/L, lactic acid=0.6 mmol/L, ammonia=22 mcmol/L and normal coagulation profile. Figure 1 highlights the trend of liver function tests (LFTs) during hospitalization. CT of the abdomen with contrast, abdominal ultrasound with doppler and echocardiography were all normal. Viral hepatitis panel (anti-HAV, anti-HBs, anti-HBc, HBs antigen, anti-HCV, HCV-RNA, & anti-HEV), autoimmune hepatitis panel (ANA, AMA, smooth muscle antibody, liver-kidney microsomal antibody, and total immunoglobulin) and atypical viruses (HIV, CMV, and HSV) were insignificant. On third day, he developed altered mental status; Hb dropped to 5.5 g/dL, platelets dropped to 35 bil/L and LFTs worsened. Liver biopsy was canceled due to hemodynamic instability and coagulopathy. Massive transfusion was initiated, but despite aggressive resuscitation, the patient had cardiac arrest and expired. On autopsy, histopathologic analysis of the liver revealed diffuse hepatocellular necrosis with occasional sparing of periportal hepatocytes (fig 3) consistent with the prior reported cases and the pattern of idiosyncratic drug induced liver injury (DILI). There was no evident lobular or portal inflammation, fibrosis, viral cytopathic effect, thromboemboli, or malignancy.2304_A Figure 1. Trend of liver function testsProminent eosinophils in the portal tract or lobules can suggest a drug-induced hypersensitivity reaction but are rarely seen in cases of idiosyncratic drug reactions. There are no defined pathognomonic histopathologic findings of DILI and a high index of clinical suspicion in combination with histopathologic findings are needed for the diagnosis.2304_B Figure 2. Reported cases of acute liver failure from Clarithromycin2304_C Figure 3. A: Low power photomicrograph of H&E section of liver showing geographic areas of necrosis and marked sinusoidal congestion. B: High power photomicrograph of H&E stain of liver showing a central vein (*) with adjacent marked sinusoidal congestion and extensive hepatocyte necrosis.