Thalha Abdul Malik, Mahadeva Sanjiv, Boon Tan Alexander Tong, Mun Kein Seong
Gastroenterology Unit, Department of Internal Medicine University Malaya Medical Centre Kuala Lumpur Malaysia.
Endocrinology Unit, Department of Internal Medicine University Malaya Medical Centre Kuala Lumpur Malaysia.
JGH Open. 2018 Oct 1;2(5):242-245. doi: 10.1002/jgh3.12083. eCollection 2018 Oct.
A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra-hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2-5:mixed-type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.
一名33岁男性因4周的高渗症状前来就诊。临床检查发现肝脏可触及肿大，无肝病体征。检查结果显示随机血糖16.6 mmol/L，糖化血红蛋白12.4%，甘油三酯6.2 mmol/L，肝功能正常，肝脏超声：回声增强。治疗措施包括转诊至营养师处，并开始服用二甲双胍500 mg，每日2次，达美康缓释片60 mg，每日1次，非诺贝特145 mg，每日1次。他不依从治疗，称服用口服降糖药后有“头部沉重感”，无低血糖症状。治疗改为使用捷诺达（西格列汀5 mg + 二甲双胍1000 mg）和恩格列净25 mg，每日1次。1周后，他出现全身瘙痒，谷丙转氨酶（ALT）307 IU/L，谷氨酰转肽酶（GGT）808 IU/L。此后，进行了经皮肝活检，结果显示脂肪性肝炎和明显的肝内胆汁淤积。停用捷诺达后，肝功能恢复至基线水平。肝损伤的表型根据R值进行分类，R值定义为ALT/正常上限（ULN）:ALP/ULN的比值。R值≥5为肝细胞损伤，≤2为胆汁淤积性损伤，2 - 5为混合型损伤。在此病例中，R值指向混合型（R = 3.203）。基于实验室参数，非酒精性脂肪性肝炎（NASH）患者的肝毒性难以诊断。肝脏组织学有助于发现除NASH之外的其他导致肝脏紊乱的变化。罗塞尔·乌克拉夫因果关系评估方法是一种确定药物性肝损伤可能性的评分方法。该病例的罗塞尔·乌克拉夫因果关系评估方法（RUCAM）评分为6分（可能的药物不良反应）。此前尚未报道过西格列汀导致的肝毒性。临床医生需要更加警惕，尤其是对于NASH患者。
