背景:慢性丙型肝炎(CHC)和合并2型糖尿病(DM)的患者表现出较高的发展为肝细胞癌(HCC)的风险。成功的抗病毒治疗降低了治疗后HCC的发生率,但即使在治愈的患者中,DM的存在仍然是不利的预测因素.二甲双胍(MET)被推荐作为DM的一线治疗,并且它的使用与不同病因的慢性肝病糖尿病患者中HCC的显着减少有关,但很少有研究专门针对CHC患者的这一问题。
目的:本综述的目的是评估使用MET是否会导致糖尿病合并CHC患者的HCC显着减少,治疗或未经治疗的抗病毒治疗。
方法:搜索PubMed,Medline,WebofSciences和Embase进行了出版物评估MET在降低DM和CHC患者HCC风险中的作用。到2023年6月30日没有语言和学习类型限制。仅考虑满足以下纳入标准的研究:(1)仅在CHC糖尿病患者的随访中有关HCC发生率的数据;(2)随访≥24个月;(3)足够的数据以确定使用二甲双胍或其他抗糖尿病药物治疗的CHC糖尿病患者的比率;(4)抗病毒治疗类型和临床结果的数据。
结果:三项研究符合纳入标准。一项前瞻性队列研究仅考虑DM和未经治疗的晚期CHC患者,或干扰素(IFN)治疗的无应答者,显示MET的使用与HCC发病率的显着降低有关,肝脏相关死亡和肝移植。最近的一项回顾性研究集中在台湾全国范围内成功接受IFN治疗的CHC患者的大规模队列研究,将患者分为3组:非MET使用者,MET使用者和非糖尿病患者,肝癌的5年累积率为10.9%,2.6%和3.0%,分别,与MET使用者和非糖尿病患者相比,非MET使用者的HCC风险显着升高,而MET使用者和非糖尿病患者之间无显著差异.在最近的意大利队列研究集中在7007例CHC患者治疗和治愈的直接作用抗病毒药物(DAAs),发现了DM和MET治疗的联合效果,与没有服用MET的糖尿病患者和没有服用MET的糖尿病患者相比,没有服用MET的糖尿病患者的HCC发生率更高。
结论:根据目前的证据,应鼓励糖尿病CHC患者使用MET,以降低HCC的风险;然而,需要一个精心设计的随机对照试验来确定MET在这一特定亚组患者中的有益作用的普遍性.
Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC.
the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy.
A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome.
Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET.
according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.