2型糖尿病和血脂异常通常是与非酒精性脂肪性肝病（NAFLD）患者的心血管和肝脏相关死亡相关的已知危险因子。2013年欧洲肝病学会（European Association for the Study of the Liver,EASL）主办的国际肝病大会（the International Liver Congress,ILC）上的一项研究发现，2型糖尿病患者，尤其是相关高脂血症的患者，比单纯高脂血症患者晚期肝纤维化和脂肪变性的比例更高，总死亡和肝脏相关的死亡率也更高。
这项研究评估了非侵入性标记物，FibroTest和SteatoTest，对糖尿病和/或血脂异常且无已知肝病患者的总生存期（OS）、肝脏相关死亡（LRD）和心血管疾病相关死亡（CVD）10年预后价值。研究人员对一组糖尿病和/或血脂异常且无已知肝病的患者进行12年的前瞻性随访（1999年~2012年），搜集死亡率数据。肝脏疾病的验证生物标志物：晚期肝纤维化（AF-METAVIR≥2，FibroTest≥0.48），晚期肝脂肪变性（＞32%，SteatoTest>0.69）。对3个子集按危险因素进行分析：糖尿病（D），高脂血症（H）和糖尿病合并高脂血症患者（DH）。
共纳入2322例患者，在12年的中位随访中，183例（7.8%）死亡[35例发生心血管疾病相关死亡CVD；6例发生肝脏相关死亡LRD（4例肝细胞癌，2胆管癌）]。H组的OS和无CVD生存显著高于D组或DH组(%Kaplan–Meier, 95% CI): OS 96 (95–97) vs 93 (91–96, Logrank P < 0.001 vs H) vs 88 (85–92, P<0.0001 vs H)。无CVD生存：99（98–99）vs 98（96–99，P=0.02 vs H）和97（96–99，P＜0.001 vs H）。Steatotest显示有进展性脂肪变性（AS）的H组患者较无AS者的无CVD生存较低：97（94-99）vs 99（98-99，P=0.004）。在多变量分析（Cox模型）中发现：FibroTest在糖尿病组[风险比（RR）=136.9（95%CI:11.6～1610，P<0.0001）和糖尿病合并高脂血症组[RR= 7.1（95%CI：2.1～24，P<0.0001）中对OS仍具有显著的预测价值。
研究还发现，在糖尿病患者中，无论是否有高脂血症，FibroTest对估测总生存和无肝病死亡生存具显著的10年预后价值。SteatoTest也是高脂血症患者CV相关死亡的预测因子。
论文摘要：
论文摘要：
10-years prognostic value of fibrotest and steatotest for liver-related and cardiovascular death in patients with type-2 diabetes and/or hyperlipidemia
Background: Cardiovascular and liver-related deaths have been described in nonalcoholic fatty liver disease (NAFLD) that is usually associated with risk factors, as type-2 diabetes and dyslipidemia.
Aims: To evaluate the 10-year prognostic value of non-invasive markers (FibroTest-SteatoTest) for the overall survival (OS) and survivals without liver-(LRD) and cardiovascular-related death
(CVD).
Methods: A cohort of patients with diabetes and/or dyslipidemia without known liver disease was prospectively followed[1999–2012]. Mortality data, according to the International Classification of Diseases, was collected in the French National Registry. Liver diseases were presumed by validated biomarkers: Advanced liver fibrosis (AF-METAVIR≥2, FibroTest≥0.48) and advanced steatosis (>32%-AS, SteatoTest>0.69). Three sub-populations were analyzed according to the risk factors: diabetics (D), hyperlipidemia (H) and diabetics with hyperlipidemia (DH).
Results: 2322 patients[52%males, age=52yrs, BMI 26 (15–64)Kg/m2, 61%H; 11%D and 28%DH] were included. The prevalence of presumed AF were H 2.5%, D 6.5% and DH 9% (P < 0.0001). AS was presumed in H 11%, D 23% and DH 39% (P < 0.0001). During a median follow-up of 12yrs, 183 (7.8%) patients died[35 CVD; 6 LRD (4 hepatocellular-carcinoma and 2 cholangio-carcinoma)]. Both OS and survival without-CVD were significantly higher in H than in D or DH (%Kaplan–Meier, 95% CI): OS 96 (95–97) vs 93 (91–96, Logrank P < 0.001 vs H) vs 88 (85–92, P < 0.0001 vs H), respectively. Survival without CVD: 99 (98–99) vs 98 (96–99, P = 0.02 vs H) vs 97 (96–99, P < 0.001 vs H), with no LRD in H-group. OS and survival without-LDR in AF vs non-AF presumed by FT were: D-group 81 (62–99) vs 94 (91–97, P = 0.04) and 94 (82–99) vs 100 (99–100, P < 0.01); DH-group 72 (55–88) vs 89 (86–93, P = 0.04) and 90 (81–99) vs 100 (99–100, P < 0.0001), respectively. H-group
with AS presumed by Steatotest had lower survival without-CVD, compared to non-AS: 97 (94–99) vs 99 (98–99, P = 0.004). In multivariate analysis (Cox model): Fibrotest remained significant for the prediction of OS in D-group[risk ratio (RR)=136.9 (95% CI 11.6–1610; P < 0.0001)] and in DH-group [RR=7.1 (95% CI 2.1–24; P < 0.0001)].
Conclusion: Patients with type-2 diabetes especially those with associated hyperlipidemia presented higher rates of advanced fibrosis and steatosis and also higher overall and liver-related mortalities than those with isolated hyperlipidemia. In diabetics, regardless associated hyperlipemia, FibroTest had a significant 10-years prognostic value for the overall and without liver-related death survivals. SteatoTest was predictive of cardiovascular-related death in hyperlipidemia patients.
