A 34-year old Hispanic male presented with nausea, vomiting, abdominal pain, and dark urine. Testing revealed elevated transaminases and bilirubin; however, imaging failed to demonstrate cirrhosis or anatomic abnormality. Hepatitis work-up, including testing for viral hepatitis, hemochromatosis, Wilson’s disease, and autoimmune hepatitis, was unremarkable with exception of an elevated Ferritin level of 7089 mg/dL. Genetic testing for hemochromatosis was negative. Medical history was only positive for occasional social alcohol use, and drug toxicology testing was negative. He denied use of energy drinks, herbs, Chinese teas, or muscle milk. He was advised to discontinue alcohol use, which he did, and his symptoms initially seemed to abate.\nSix weeks later, the patient developed asterixis, jaundice, and confusion. Follow-up imaging was concerning for rapid onset of cirrhosis or infiltrative hepatocellular carcinoma. He was transferred to our center for further evaluation. On admission, transaminases were elevated with aspartate aminotransferase (AST) 624 U/L, alanine aminotransferase (ALT) 520 U/L and total bilirubin of 34.7 mg/dL. International normalized ratio (INR) remained elevated despite multiple infusions of fresh frozen plasma and vitamin K. Factor Vand VII activities were 18% and < 6%, respectively. Magnetic resonance imaging (MRI) with Eovist contrast demonstrated interval development of heterogeneous, enhancing nodularity with portal venous washout, unlikely to be an infiltrative tumor process.\nA full repeat hepatitis work-up was performed (Table ). No definitive cause of acute liver failure could be identified; however, some findings were equivocal. Autoantibody titers demonstrated a positive antinuclear antibody, but no other positive autoantibodies. Evaluation of Wilson’s disease demonstrated normal ceruloplasmin and copper levels; however, 24-h urine copper was elevated. Serum ferritin but not transferrin was elevated.\nLiver biopsy was performed and demonstrated submassive necrosis with collapse of the hepatic architecture involving about 70% of the liver parenchyma. Mild lymphocytic inflammatory infiltration and minimal canalicular cholestasis were seen. No viral inclusions or other infectious agents were identified by histology or immunohistochemistry. No evidence of granuloma, tumor, or features of cirrhosis were demonstrated. Periodic acid-Schiff (PAS) stain with diastase was negative for alpha-1 antitrypsin globules. Iron stain showed only mild iron deposition in Kupffer cells and hepatocytes. Quantitative tissue copper was within normal limits (Table ). Findings were felt to be potentially related to drug-induced liver injury.\nAfter extensive questioning, the patient divulged intake of Garcinia cambogia, purchased through the Internet retailor Swanson Vitamins. He imbibed two 80 mg capsules of “Garcinia Cambogia 5:1 Extract” three times daily before meals for five months preceding initial presentation. Since not advised against intake, he continued the supplement after initial presentation. He denied any other medications or supplements and reported no alcohol intake for two months.\nThe patient’s status declined and his mental status deteriorated. He was listed status 1A for liver transplantation. He received an orthotopic liver transplant from an ABO-identical brain dead donor and has recovered without incident. Histopathologic examination of the explanted liver demonstrated near total hepatic necrosis with massive hepatocellular dropout and mixed inflammatory cell infiltrates, consistent with severe drug-induced liver injury (Figure ).
A 57-year-old female with no previous history of liver disease presented with abdominal pain and vomiting for one day. The abdominal pain was described as 7/10 in severity, nonradiating, and diffuse, but most intense in the right upper quadrant. She denied previously experiencing any similar pain. She denied fever or chills but reported 3 episodes of nonbloody, nonbilious emesis after the pain started. There was a history of heart failure with preserved ejection fraction. She had been taking vitamins A and D and an herbal supplement for weight loss but she denied the use of any prescription weight loss medications. She denied using alcohol, acetaminophen, or any illicit drugs. Her vital signs were normal. Physical examination was significant for diffuse abdominal tenderness without any rigidity or guarding. There was no hepatosplenomegaly or scleral icterus. Laboratory evaluation revealed an alanine aminotransferase (ALT) of 738 U/L [normal: 7-55 U/L], aspartate aminotransferase (AST) of 856 U/L [normal: 8-48 U/L], and an alkaline phosphatase of 80 U/L [normal: 45-115 U/L]. Her total bilirubin was 2.4 mg/dL [normal: 0.1-1.2 mg/dL] and direct bilirubin was 1.4 mg/dL [normal: 0-0.4 mg/dL]. International normalized ratio (INR) was 1.19 [normal: 0.8-1.1] and prothrombin time (PT) was 12.7 seconds [normal 11-13.5 seconds]. Testing for hepatitis A, hepatitis B, hepatitis C, hepatitis E, Herpes-Simplex virus, Ebstein-Barr virus, Parvovirus, and Cytomegalovirus was negative. She had normal vitamins A and D levels ruling out hypervitaminosis as the cause of hepatitis. She tested negative for alcohol and acetaminophen. Anti-smooth muscle antibody, anti-mitochondrial antibody, antinuclear antibody, and anti-liver kidney microsomal antibody were negative. An iron profile was normal. Abdominal ultrasound showed a normal liver with normal echotexture and no biliary ductal dilatation. When the herbal supplement was scrutinized, it was found to be 100% pure GC fruit rind extract. She had consumed two capsules daily as recommended for about one month. Each capsule had 1400 mg of GC extract. She was asked to stop taking the supplement. Her liver enzymes decreased significantly with an ALT of 396 μ/L and AST of 138 μ/L within three days with resolution of her abdominal symptoms. Her total and direct bilirubin came down to 0.6 mg/dL and 0.4 mg/dL, respectively. Her INR and PT also normalized. She had a normal ALT of 25 and AST of 12 in the one-month follow-up visit. Six months later, patient was found to have an elevated ALT of 301 and AST of 69. On interrogation, it was found that she had started taking the same supplement again in the desperate need to lose weight. The CIOMS/RUCAM scale, a scoring system () that is used to establish the etiology of liver damage when drug induced liver damage is suspected, gave a score of 11 for our patient ()[, ]. The score classifies the drug as highly probable (score ≥ 9), probable (score 6-8), possible (score 3-5), unlikely (score 1-2), and excluded (score 0) as the cause of liver injury [, ]. This lead us to conclude that the etiology of the patient's hepatitis was GC extract.