Impact of genetic polymorphisms associated with nonalcoholic fatty liver disease on HIV-infected individuals

Macı́as, Juan; Rivero‐Juárez, Antonio; Neukam, Karin; Téllez, Francisco Ayuga; Merino, Dolores; Frías, Mario; Merchante, Nicolás; Rivero, Antonio; Pineda, Juan A.; Real, Luis Miguel

doi:10.1097/qad.0000000000000799

Cited by 23 publications

(19 citation statements)

References 35 publications

(66 reference statements)

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“…More studies are warranted to elucidate this issue. By contrast, the other SNPs evaluated here, linked to SAMM50 and LPPR4 genes, which were previously associated with FLD in the HIV-infected population [14], have not shown any association with cirrhosis or significant LSP in our study. Taking into account the sample size analyzed, the case-control ratio and the minor allele frequency of those genetic markers in our population, our study had a 75% and 80% power to detect OR = 2 for the study of association of SAMM50 rs738491 and LPPR4 rs12743824 polymorphisms with cirrhosis, respectively.…”

Section: Discussioncontrasting

confidence: 99%

“…We previously reported a lack of association between the PNPLA3 rs738409 variant and FLD in HIV/HCV-coinfected individuals [14]. Although Signelli et al found a relation of this SNP with steatosis in a small population [10], our finding has been replicated by others [8, 9].…”

Section: Discussionsupporting

confidence: 68%

“…This single nucleotide polymorphism (SNP) has been consistently associated with fatty liver disease (FLD) in both HCV-uninfected and HCV-infected individuals [12, 13]. Similarly, other SNPs that have been recently associated with FLD in the HIV-infected population [14] could also have an impact on the faster liver fibrosis progression observed in the HIV/HCV-coinfected population, but this has not been explored so far.…”

Section: Introductionmentioning

confidence: 99%

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The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients

et al. 2016

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Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12–3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23–6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01–11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients

et al. 2016

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“…There are no specific studies linking microbiome dysfunction to the development of NASH in HIV-infected patients. Furthermore, there is strong evidence on the impact of hereditary component with polymorphisms for hepatic lipid regulation and insulin signalling pathways, in both the HIV-infected and general populations [57,58].…”

Section: Pathogenesismentioning

confidence: 99%

A Review of Non-Alcoholic Fatty Liver Disease in HIV-Infected Patients: The Next Big Thing?

et al. 2019

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The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. Especially, the impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. The pathogenesis of NAFLD and the reasons for progression to non-alcoholic steatohepatitis (NASH) are still not fully elucidated, but insulin resistance, mitochondrial dysfunction and dyslipidemia seem to be the main drivers. Both HIV-infection itself and combination antiretroviral therapy (cART) can contribute to the development of NAFLD/NASH in various ways. As ongoing HIV-related immune activation is associated with insulin resistance, early initiation of cART is needed to limit its duration. In addition, the use of early-generation nucleoside reverse transcriptase inhibitors and protease inhibitors is also associated with the development of NAFLD/NASH. Patients at risk should therefore receive antiretroviral drugs with a more favorable metabolic profile. Only weight reduction is considered to be an effective therapy for all patients with NAFLD/NASH, although certain drugs are available for specific subgroups. Since patients with NASH are at risk of developing liver cirrhosis and hepatocellular carcinoma, several non-antifibrotic and antifibrotic drugs are under investigation in clinical trials to broaden the therapeutic options. The epidemiology and etiology of NAFLD/NASH in HIV-positive patients is likely to change in the near future. Current guidelines recommend early initiation of cART that is less likely to induce insulin resistance, mitochondrial dysfunction and dyslipidemia. In contrast, as a result of increasing life expectancy in good health, this population will adopt the more traditional risk factors for NAFLD/NASH. HIV-treating physicians should be aware of the etiology, pathogenesis and treatment of NAFLD/NASH in order to identify and treat the patients at risk.

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“…This may be due to the presence of multiple risk factors including high alcohol consumption, metabolic disorders driven by HIV, viral replication, and use of cART [22–25]. Studies have also shown that non-alcoholic fatty liver disease (NAFLD) and fibrosis is associated with duration of HIV, persistent HIV viral replication, cART use, as well as genetic variants [26–29]. As with CVD and respiratory comorbidity, these results suggest contributory effects of HIV-related factors.…”

Section: Introductionmentioning

confidence: 99%

Copenhagen comorbidity in HIV infection (COCOMO) study: a study protocol for a longitudinal, non-interventional assessment of non-AIDS comorbidity in HIV infection in Denmark

et al. 2016

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BackgroundModern combination antiretroviral therapy (cART) has improved survival for people living with HIV (PLWHIV). Non-AIDS comorbidities have replaced opportunistic infections as leading causes of mortality and morbidity, and are becoming a key health concern as this population continues to age. The aim of this study is to estimate the prevalence and incidence of non-AIDS comorbidity among PLWHIV in Denmark in the cART era and to determine risk factors contributing to the pathogenesis. The study primarily targets cardiovascular, respiratory, and hepatic non-AIDS comorbidity.Methods/designThe Copenhagen comorbidity in HIV-infection (COCOMO) study is an observational, longitudinal cohort study. The study was initiated in 2015 and recruitment is ongoing with the aim of including 1500 PLWHIV from the Copenhagen area. Follow-up examinations after 2 and 10 years are planned. Uninfected controls are derived from the Copenhagen General Population Study (CGPS), a cohort study including 100,000 uninfected participants from the same geographical region. Physiological and biological measures including blood pressure, ankle-brachial index, electrocardiogram, spirometry, exhaled nitric oxide, transient elastography of the liver, computed tomography (CT) angiography of the heart, unenhanced CT of the chest and upper abdomen, and a number of routine biochemical analysis are uniformly collected in participants from the COCOMO study and the CGPS. Plasma, serum, buffy coat, peripheral blood mononuclear cells (PBMC), urine, and stool samples are collected in a biobank for future studies. Data will be updated through periodical linking to national databases.DiscussionAs life expectancy for PLWHIV improves, it is essential to study long-term impact of HIV and cART. We anticipate that findings from this cohort study will increase knowledge on non-AIDS comorbidity in PLWHIV and identify targets for future interventional trials. Recognizing the demographic, clinical and pathophysiological characteristics of comorbidity in PLWHIV may help inform development of new guidelines and enable us to move forward to a more personalized HIV care.Trial registrationClinicalTrials.gov: NCT02382822.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2026-9) contains supplementary material, which is available to authorized users.

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Impact of genetic polymorphisms associated with nonalcoholic fatty liver disease on HIV-infected individuals

Abstract: LPPR4 and SAMM50 allelic variants are independent risk factors for FLD and steatohepatitis development, respectively, in HIV-infected individuals.

Cited by 23 publications

References 35 publications

The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients

The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients

A Review of Non-Alcoholic Fatty Liver Disease in HIV-Infected Patients: The Next Big Thing?

Copenhagen comorbidity in HIV infection (COCOMO) study: a study protocol for a longitudinal, non-interventional assessment of non-AIDS comorbidity in HIV infection in Denmark

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