Metformin-induced mixed hepatocellular and cholestatic hepatic injury: case report and literature review
A 78-year-old Jewish male patient was hospitalized in our department with a 10-day history of fatigue, nausea, vomiting, diarrhea, anorexia, and abdominal pain. He had also had pruritus and jaundice for 8 days. DM-2 had been recently diagnosed and metformin 850 mg/day had been initiated 2 weeks before presentation to the hospital. The patient reported no alcohol use, smoking, previous liver disease, family history of liver diseases, blood transfusion, exposure to toxins, or cholelithiasis. One month before initiation of metformin treatment, the patient had been given a 13-day amoxicillin-clavulanate (Augmentin) treatment for acute parotitis. His past medical history was significant for hypertension, gout, hyperlipidemia, and diverticulosis. His other medications included aspirin (75 mg/day), pravastatin (20 mg/day), amlodipine (5 mg/day), atenolol (100 mg/day), candesartan (16 mg/day), and hydrochlorothiazide (12.5 mg/day).\nOn physical examination, the patient was alert, with prominent jaundice. No stigmata of chronic liver disease were present. There was no pedal edema or ascites. His weight was 82 kg, his height 172 cm, and his body mass index 27.7 kg/m2. The laboratory findings are summarized in . The level of lactic acid was normal. Creatinine, urea, and electrolytes were normal. The levels of glucose during hospitalization were between 120–180 mg/dL. Results of serologic tests were negative for the following: hepatitis B surface antigen; anti-hepatitis B core Immunoglobolin M (IgM); anti-hepatitis A virus IgM; anti-hepatitis C virus antibody; anti-Cytomegalovirus IgM; anti-Epstein–Barr virus IgM; anti-nuclear antibodies; anti-smooth-muscle antibodies; anti-mitochondrial antibodies; and anti-neutrophil cytoplasmic antibodies. Serum ferritin and ceruloplasmin levels were also normal. C-reactive protein level was 9.97 mg/L (normal range: 0–5 mg/L). Complete blood count was normal. An ultrasound and a computerized tomography (CT) scan of the abdomen revealed no abnormalities.\nOn admission, metformin and pravastatin were discontinued immediately. After 1 week, the patient described significant subjective improvement and the level of bilirubin, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALKP), and γ-glutamyl transpeptidase (GGT) began to decline gradually. After 9 days of hospitalization, the patient’s laboratory results were as follows: total bilirubin, 16.9 mg/dL; direct bilirubin, 12.4 mg/dL; ALT, 308 U/L; AST, 77 U/L; ALKP, 809 U/L; and GGT, 876 U/L. The patient was discharged for outpatient follow-up. Two months following discharge, all hepatobiliary laboratory abnormalities resolved. Thereafter, pravastatin therapy was readministered, and no changes in bilirubin, ALT, AST, ALKP, or GGT levels were observed.