Background Nearly 50% of cases of acute liver failure in the USA are due to drug-induced liver injury (DILI).1 The list of associated drugs and toxins has significantly expanded with the recognition of dietary and herbal supplements as offending agents. Unfortunately, an increasing number of Americans consume herbal supplements and energy drinks on a daily basis, with the misconception that their ‘natural ingredients’ must render them harmless.2 It has been estimated that ∼23 000 emergency department visits each year are due to adverse events related to dietary supplements.2 As the energy drink market continues to rapidly expand, consumers should be aware of the potential risks of their various ingredients. Vitamins and nutrients, such as niacin, are present in quantities that greatly exceed the recommended daily intake, lending to their high risk for harmful accumulation and toxicity.3 To the best of our knowledge, only one other case report has previously been published in the literature describing acute hepatitis related to energy drinks;3 herein, we report the second case. Appreciation of this under-recognised phenomenon in clinical practice will decrease prevalence and potentially fatal delays in discontinuation of the offending agent.

Case presentation A previously healthy man aged 50 years presented to the emergency department with a 2-week history of malaise, anorexia and worsening abdominal pain, which progressed to nausea, vomiting and scleral icterus. He initially attributed his symptoms to an influenza-like syndrome; however, he became alarmed when he developed dark urine and generalised jaundice. The patient had no known personal or family history of liver disease. He had not seen a primary care provider in years and was on no medications (prescription or over-the-counter) prior to admission. He denied any changes in his diet or use of alcohol, tobacco or illicit drugs, but endorsed drinking 4–5 energy drinks daily for 3 weeks prior to presentation. As a construction worker, he used the supplemental energy drinks to help get through his labour-intensive workday. He did get a tattoo in his 20s, but denied any transfusions of blood products or high-risk sexual behaviour. On physical examination, the patient had normal vital signs, scleral icterus and jaundice. Abdominal examination was remarkable for right upper quadrant (RUQ) tenderness, but there was no ascites, asterixis, spider angiomata or other signs of chronic liver disease.

Investigations Laboratory studies revealed normal renal function, elevated aminotransferases and direct hyperbilirubinaemia (table 1). Serum folate and vitamin B 12 levels exceeded quantifiable limits. Table 1 Laboratory results on admission Acetaminophen level was undetectable and urine and plasma toxicology screens were negative. Investigations for infectious aetiology, including hepatitis A, B, C, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus, only revealed a positive hepatitis C (HCV) antibody with HCV RNA PCR of 59 592 238 IU/mL. Autoimmune workup revealed a negative serum antinuclear antibody, antimitochondrial antibody, antismooth muscle antibody and anti-liver-kidney microsomal antibody (anti-LKM-1). Serum ceruloplasmin and α-1-antitrypsin levels were normal. Haemochromatosis DNA mutation testing was negative. RUQ ultrasound scan demonstrated an echogenic liver without cirrhosis, common bile duct obstruction or gallstones. There was also diffuse gallbladder wall thickening thought to be related to underlying hepatitis. The patient underwent a liver biopsy which revealed severe acute hepatitis with bridging necrosis and marked cholestasis.

Differential diagnosis While the serum aminotransferases and alkaline phosphatase were elevated on presentation, we were able to narrow our differential diagnosis to various possible aetiologies of hepatitis based on the predominant hepatocellular pattern of laboratory abnormalities. We then further narrowed our differential to the hepatocellular diseases associated with elevated bilirubin and jaundice, including viral infections (eg, hepatitis A, B, C, D and E, EBV, CMV), toxic (eg, alcohol, drugs, environmental), autoimmune, Wilson disease, ischaemia and congestive hepatopathy. Though the patient was found to have HCV infection, we did not think HCV was responsible for his acute hepatitis. HCV antibody production has a window period, with serum antibodies undetectable by assay until ∼10 weeks after the initial exposure.4 Being that our patient's symptoms only began 2 weeks prior, his positive serology was not compatible with an acute HCV infection, but was deemed more likely a chronic infection. In the absence of clinical signs of haemodynamic instability, we thought ischaemic hepatic injury to be less likely. Furthermore, ischaemic hepatitis is often accompanied by evidence of other end-organ hypoperfusion, such as renal acute tubular necrosis.5 Therefore, our patient's normal renal function on presentation did not favour the diagnosis of ischaemic hepatitis. History and examination also made aetiologies such as alcohol, prescribed medications, illicit drugs, environmental causes and congestive hepatopathy less likely. We excluded other viral causes of hepatitis, autoimmune aetiology and Wilson disease based on laboratory results. Biopsy findings in this case were non-specific and can be seen in drug-induced or toxin-induced hepatitis, and in hepatic injury related to other causes, such as autoimmune hepatitis, Wilson disease, coeliac disease and acute viral hepatitis. Having carefully excluded the alternative processes with similar pathological findings, the diagnosis of acute hepatitis secondary to consumption of energy drinks was rendered. Incidentally, the patient's high levels of serum folate and vitamin B 12 were also consistent with supplemental intake, likely from energy drink usage as he denied any alternative supplementation. The diagnosis was further supported by consideration of chronological and clinical data. His liver injury was directly subsequent to excessive consumption of energy drinks, and resolved on discontinuation of the product.

Treatment Our patient was seen in consultation by hepatology during his hospitalisation. He was treated supportively, and the offending agent was withdrawn. Daily liver functions tests (LFTs) and INR were obtained to ensure that the patient did not develop liver failure (table 2). Table 2 Laboratory results throughout hospitalisation

Outcome and follow-up The patient's symptoms resolved by the third day of hospitalisation, though his LFTs continued to uptrend until peaking on hospital day 4 (table 2). He was discharged home on hospital day 6. At the time of discharge, the patient was tolerating a regular diet without malaise, anorexia, abdominal pain, nausea or vomiting. Follow-up with hepatology was arranged for new diagnosis of chronic HCV infection. His transaminitis had completely resolved at 2-week follow-up (table 1).