重新审视 HIV/HCV 合并感染患者的肝病进展：维生素 D、胰岛素抵抗、免疫状态、IL28B 和 PNPLA3 的影响。
Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3.
机构信息
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna HIV & Liver Study Group, Vienna, Austria.
出版信息
Liver Int. 2015 Mar;35(3):876-85. doi: 10.1111/liv.12615. Epub 2014 Jun 26.
BACKGROUND & AIMS: To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients.
PATIENTS & METHODS: 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × μl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group.
RESULTS
Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels.
CONCLUSIONS
Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.
背景与目的
在一个有详细记录的 HIV/丙型肝炎病毒（HCV）合并感染患者队列中，全面研究肝纤维化进展的独立调节剂和门脉压的决定因素，考虑免疫状态、胰岛素抵抗（IR）、血清 25-羟维生素 D（25（OH）D）水平、载脂蛋白 L3（PNPLA3）和白细胞介素 28B（IL28B）的遗传变异。
方法
定义 25（OH）D 缺乏（25（OH）DDEF）、IR 和低 CD4（+）T 淋巴细胞最低点（lowCD4NAD）为 25（OH）D <20ng×ml（-1）、HOMA-IR >2 和 CD4nadir <200cells×μl（-1）。肝纤维化进展率（FPR）定义为 HCV 感染后每年 METAVIR F 单位的分数。FPR >中位数 FPR 的患者被分配到 highFPR 组。
结果
在 86 例 HIV/HCV 中，中位 FPR 为 0.167 单位×年（-1）。虽然 highFPR 患者中先前的酒精滥用、lowCD4NAD 和 25（OH）DDEF 的发生率较高，但 IR 的发生率相似。在 METAVIR 分期 F0/F1/F2 的患者亚组中，25（OH）D 水平不受肝病严重程度的影响，证实了 25（OH）DDEF 与 FPR 之间的关联。IL28B C/C 和 PNPLA3 非-C/C 的分布相似，而 PNPLA3 G/G 仅见于 highFPR 患者。lowCD4NAD（OR：2.95；95%CI：1.05-8.24；P = 0.039）和 25（OH）DDEF（OR：5.62；95%CI：2.05-15.38；P = 0.001）与 highFPR 独立相关，且具有相加效应。门脉压与先前的酒精滥用、HCV 基因型 3、CD4（+）最低点和 25（OH）D 水平相关。
结论
两个潜在的可调节因素，CD4（+）最低点和 25（OH）D 水平，都是肝纤维化进展的独立调节剂和门脉压的决定因素。需要进一步研究以评估 PNPLA3 在 HIV/HCV 中的 FPR 相关性。
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