Vatsalya Vatsalya, Cave Matthew C, Kumar Rajarshi, Srivastava Shweta, Khanal Sujita, Jenson Alfred B, Schwandt Melanie L, Barve Shirish S, Ramchandani Vijay A, McClain Craig J
1 Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky.
2 Section on Human Psychopharmacology, DICBR/NIAAA, National Institutes of Health, Bethesda, Maryland.
AIDS Res Hum Retroviruses. 2019 Jan;35(1):92-99. doi: 10.1089/AID.2018.0124. Epub 2018 Dec 11.
Heavy alcohol drinking causes alterations in the metabolism of fatty acids and zinc that participate in inflammation and liver injury. HIV infection has been reported to cause dysregulated polyunsaturated fatty acid (PUFA) and zinc metabolism. In this pilot study, we examined the role of dysregulated PUFA metabolism and zinc deficiency in the liver injury occurring in heavy drinkers with early-stage HIV diagnosis. Fourteen heavy drinking alcohol-dependent (AD) patients [seven with treatment-naive HIV diagnosis (AD+HIV) and seven without HIV infection (AD)] participated in this study. Liver injury, serum zinc, PUFAs, viral load, CD4 count, and drinking measures using lifetime drinking history (LTDH), and timeline follow-back past 90 days (TLFB90) were evaluated. Liver injury was also assessed in seven age- and gender-matched socially drinking HIV treatment-naive patients who served as disease controls. HIV viral load by itself did not show any correlation with liver injury. Liver enzymes were significantly elevated in both AD+HIV and AD patients, and AD+HIV patients had significantly higher alanine aminotransferase (ALT) levels than did AD patients, even with lower drinking. Serum zinc was significantly lower in AD+HIV patients. Only AD+HIV patients showed a significant elevation in linoleic acid (LA) and alpha-linoleic acid (ALA) levels. Serum zinc and ALT, LA and ALT, and ALA and ALT were significantly associated only in AD+HIV patients. The association between LA and ALT showed a higher effect than did the ALA and ALT association in the AD+HIV patients. Interestingly, AD+HIV subjects (who drank less), nevertheless, showed more liver injury compared with AD patients, who reported heavier drinking. We speculate that the underlying proinflammatory response resulting from zinc deficiency and an elevation in serum LA likely contributed to liver injury in AD+HIV patients, even with a comparatively lower degree of heavy drinking.
大量饮酒会导致参与炎症和肝损伤的脂肪酸和锌代谢发生改变。据报道,HIV感染会导致多不饱和脂肪酸(PUFA)和锌代谢失调。在这项初步研究中,我们研究了PUFA代谢失调和锌缺乏在早期HIV诊断的重度饮酒者肝损伤中所起的作用。14名重度酒精依赖(AD)患者[7名初诊HIV感染者(AD+HIV)和7名未感染HIV者(AD)]参与了本研究。评估了肝损伤、血清锌、PUFA、病毒载量、CD4细胞计数以及使用终生饮酒史(LTDH)和过去90天的时间线随访(TLFB90)的饮酒量。还对7名年龄和性别匹配、社会饮酒的初诊HIV感染者进行了肝损伤评估,这些患者作为疾病对照。HIV病毒载量本身与肝损伤无任何相关性。AD+HIV和AD患者的肝酶均显著升高,即使饮酒量较低,AD+HIV患者的丙氨酸转氨酶(ALT)水平也显著高于AD患者。AD+HIV患者的血清锌显著降低。只有AD+HIV患者的亚油酸(LA)和α-亚麻酸(ALA)水平显著升高。血清锌与ALT、LA与ALT、ALA与ALT仅在AD+HIV患者中显著相关。在AD+HIV患者中,LA与ALT的关联比ALA与ALT的关联显示出更高的效应。有趣的是,与报告饮酒量更大的AD患者相比,AD+HIV受试者(饮酒较少)却表现出更严重的肝损伤。我们推测,锌缺乏和血清LA升高所引发的潜在促炎反应可能是导致AD+HIV患者肝损伤的原因,即便其重度饮酒程度相对较低。