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Liver fibrosis and accelerated immune dysfunction (immunosenescence) among HIV-infected Russians with heavy alcohol consumption - an observational cross-sectional study.

ABSTRACT: BACKGROUND:The multifactorial mechanisms driving negative health outcomes among risky drinkers with HIV may include immunosenescence. Immunosenescence, aging of the immune system, may be accentuated in HIV and leads to poor outcomes. The liver regulates innate immunity and adaptive immune tolerance. HIV-infected people have high prevalence of liver-related comorbidities. We hypothesize that advanced liver fibrosis/cirrhosis is associated with alterations in T-cell subsets consistent with immunosenescence. METHODS:ART-naïve people with HIV with a recent history of heavy drinking were recruited into a clinical trial of zinc supplementation. Flow cytometry was used to characterize T-cell subsets. The two primary dependent variables were CD8+ and CD4+ T-cells expressing CD28-CD57+ (senescent cell phenotype). Secondary dependent variables were CD8+ and CD4+ T-cells expressing CD45RO?+?CD45RA- (memory phenotype), CD45RO-CD45RA+ (naïve phenotype), and the naïve phenotype to memory phenotype T-cell ratio (lower ratios associated with immunosenescence). Advanced liver fibrosis/cirrhosis was defined as FIB-4?>?3.25, APRI?1.5, or Fibroscan measurement ?10.5?kPa. Analyses were conducted using multiple linear regression adjusted for potential confounders. RESULTS:Mean age was 34?years; 25% female; 88% hepatitis C. Those with advanced liver fibrosis/cirrhosis (N =?25) had higher HIV-1 RNA and more hepatitis C. Advanced liver fibrosis/cirrhosis was not significantly associated with primary or secondary outcomes in adjusted analyses. CONCLUSIONS:Advanced liver fibrosis/cirrhosis was not significantly associated with these senescent T-cell phenotypes in this exploratory study of recent drinkers with HIV. Future studies should assess whether liver fibrosis among those with HIV viral suppression and more advanced, longstanding liver disease is associated with changes in these and other potentially senescent T-cell subsets.

SUBMITTER: So-Armah K

PROVIDER: S-EPMC6938606 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Liver fibrosis and accelerated immune dysfunction (immunosenescence) among HIV-infected Russians with heavy alcohol consumption - an observational cross-sectional study.

So-Armah Kaku K Freiberg Matthew M Cheng Debbie D Lim Joseph K JK Gnatienko Natalia N Patts Gregory G Doyle Margaret M Fuster Daniel D Lioznov Dmitry D Krupitsky Evgeny E Samet Jeffrey J

BMC gastroenterology 20191231 1

<h4>Background</h4>The multifactorial mechanisms driving negative health outcomes among risky drinkers with HIV may include immunosenescence. Immunosenescence, aging of the immune system, may be accentuated in HIV and leads to poor outcomes. The liver regulates innate immunity and adaptive immune tolerance. HIV-infected people have high prevalence of liver-related comorbidities. We hypothesize that advanced liver fibrosis/cirrhosis is associated with alterations in T-cell subsets consistent with ...[more]

PMID: 31892306

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Project description:High average daily consumption of alcohol has been associated with elevated mortality risk, but more moderate consumption, relative to abstinence, has been associated with reduced mortality risk. However, average daily consumption can be complicated to assess, limiting its usefulness in both research and clinical practice. There are also concerns that average consumption fails to capture the risk associated with certain drinking patterns, such as heavy episodic drinking. This study assessed mortality associated with drinking pattern, operationalized as the frequency of both heavy and nonheavy drinking occasions.Data from the 1997 to 2001 administrations of the National Health Interview Survey (NHIS; n = 111,511) were paired with the current release of the NHIS Linked Mortality Files, which provided mortality follow-up data through the end of 2006. We estimated the impact of drinking pattern on all-cause mortality, operationalized as the frequency of heavy (5+ drinks) and nonheavy (<5 drinks) drinking occasions. Other covariates in the model included survey wave, sex, age, race/ethnicity, ratio of family income to poverty threshold, educational attainment, body mass index, and smoking status.Over a third of past-year drinkers reported heavy drinking. Mortality risk increased steadily as heavy drinking frequency increased; daily heavy drinkers exhibited an almost 2-fold risk of death compared with abstainers (p < 0.001). Regular nonheavy drinking was associated with decreased mortality, similar to the "J-shaped curve" highlighted in past research on alcohol mortality; this potential protective effect peaked around 2 nonheavy occasions per week.Any heavy drinking likely elevates mortality risk, and substantial health benefits could be realized by reducing heavy drinking occasions or limiting overall drinking. Heavy and nonheavy drinking frequencies are valid targets for clinical screening and could be helpful in assessing risk and promoting less harmful drinking behavior.

Dataset Information

Liver fibrosis and accelerated immune dysfunction (immunosenescence) among HIV-infected Russians with heavy alcohol consumption - an observational cross-sectional study.

Publications

Liver fibrosis and accelerated immune dysfunction (immunosenescence) among HIV-infected Russians with heavy alcohol consumption - an observational cross-sectional study.

Similar Datasets

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