Riche Daniel M, Fleming Joshua W, Malinowski Scott S, Black Catherine A, Miller Kristen H, Wofford Marion R
University of Mississippi, Jackson, MS, USA.
Ann Pharmacother. 2014 Jan;48(1):137-41. doi: 10.1177/1060028013507239. Epub 2013 Oct 9.
To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy.
A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient's ALT and AST serum concentrations had normalized. Repeat liver ultrasound demonstrated improvement in steatosis grading and reduction in liver size. These improvements occurred despite a 4.5-kg weight gain since starting rosuvastatin and pioglitazone.
Pharmacotherapy in NAFLD is not well validated, particularly combination therapy. Medications that target obesity-related consequences are commonly used, although evidence regarding biochemical and histological improvement is inconclusive. Consideration should be given to the use of combination of thiazolidinediones and statins for rapid biochemical improvement and long-term histological impact.
The improvement in this patient's biochemical and ultrasonographic markers of resistant, severe NAFLD was rapid and sustained with combination therapy. This case represents a potential solution for initiating or maintaining statin therapy in patients with NAFLD who are at high cardiovascular risk.
报告一例使用联合疗法使重度难治性非酒精性脂肪性肝病（NAFLD）患者持续升高的转氨酶恢复正常的病例。
一名47岁肥胖男性患者，有转氨酶升高病史且对多种他汀类药物不耐受。除糖尿病和血脂异常控制不佳外，确诊为重度NAFLD。开始使用瑞舒伐他汀，该药导致转氨酶短期升高，患者停药。随着时间推移，NAFLD的生化指标恶化。因此，同时开始每日服用20 mg瑞舒伐他汀和15 mg吡格列酮，以可能减轻瑞舒伐他汀引起的转氨酶早期升高。2周时，患者的丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）分别较基线水平下降了57%和56%。到9个月时，患者的ALT和AST血清浓度恢复正常。重复肝脏超声检查显示脂肪变性分级改善，肝脏大小减小。尽管自开始使用瑞舒伐他汀和吡格列酮以来体重增加了4.5 kg，但仍出现了这些改善。
NAFLD的药物治疗尚未得到充分验证，尤其是联合治疗。尽管关于生化和组织学改善的证据尚无定论，但常用于治疗与肥胖相关后果的药物。应考虑使用噻唑烷二酮类药物和他汀类药物联合治疗，以实现快速的生化改善和长期的组织学影响。
联合治疗使该患者重度难治性NAFLD的生化和超声指标快速且持续改善。该病例为心血管疾病高危的NAFLD患者启动或维持他汀类治疗提供了一种可能的解决方案。
