Ben-Yakov Gil, Alao Hawwa, Haydek John P, Fryzek Nancy, Cho Min Ho, Hemmati Mehdi, Samala Vikram, Shovlin Margaret, Dunleavy Kieron, Wilson Wyndham, Jones Elizabeth C, Rotman Yaron
Liver and Energy Metabolism Unit, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD.
Department of Gastroenterology Louis Stokes VA Medical Center Cleveland OH.
Hepatol Commun. 2018 Dec 28;3(2):220-226. doi: 10.1002/hep4.1304. eCollection 2019 Feb.
Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for steatosis during chemotherapy for non-Hodgkin lymphoma (NHL). In this retrospective case-control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R-CHOP) or R-CHOP + etoposide (EPOCH-R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3- to 6-month intervals and reviewed for steatosis. Patients with steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow-up 53 months), 25 (10%) developed steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m; = 0.014) and hyperlipidemia (12% versus 2%; = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls ( = 0.003). Etoposide-containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; < 0.001) despite similar baseline risk factors. The recovery period from NHL chemotherapy appears to be a "hot spot" for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.
非酒精性脂肪性肝病是发达国家最常见的肝脏疾病。尽管通常反映热量过载，但它也可能继发于药物毒性。我们旨在描述非霍奇金淋巴瘤（NHL）化疗期间脂肪变性的发生率和危险因素。在这项回顾性病例对照研究中，成年NHL患者接受利妥昔单抗、环磷酰胺、阿霉素、泼尼松和长春新碱（R-CHOP）或R-CHOP + 依托泊苷（EPOCH-R）治疗。排除患有肝病或脂肪变性的患者。在治疗前以及每隔3至6个月进行腹部计算机断层扫描，并检查是否存在脂肪变性。脂肪变性患者按年龄、性别和种族与对照组1:1匹配。在251例接受治疗的患者中（中位随访53个月），25例（10%）出现脂肪变性，绝大多数（25例中的23例；92%）在化疗后出现。其中, 14例（61%）在治疗后18个月内出现脂肪变性，20例（87%）在36个月内出现。病例组的基线体重指数（BMI；平均值±标准差，29.0±6.5与26.0±5.2kg/m²；P = 0.014）和高脂血症发生率（12%对2%；P = 0.035）更高。尽管化疗期间他们的体重没有变化，但病例组从治疗结束到出现脂肪变性时BMI增加了2.4±2kg/m²（平均值±标准差），而对照组为0.68±1.4（P = 0.003）。尽管基线危险因素相似，但含依托泊苷的方案与出现脂肪变性的时间较短相关（中位时间34周对154周；P < 0.001）。NHL化疗后的恢复期似乎是脂肪肝发生的一个“热点”，这是由治疗后早期体重增加驱动的，尤其是在有基线危险因素的患者中。
