Alcohol Consumption and Risk of Liver Fibrosis in People Living With HIV: A Systematic Review and Meta-Analysis

Lyu, Hang; Tang, Haotong; Liang, Yong; Huang, Shaoli; Wang, Yuyu; Huang, Wenyan; Zhou, Yi

doi:10.3389/fimmu.2022.841314

Cited by 12 publications

(8 citation statements)

References 56 publications

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“…Development of liver fibrosis is a significant clinically-relevant problem in HIV infection, and the risk of progression to end-stage liver disease in PLWH is more prominent in alcohol abusers [ 24 ]. As revealed from our previous studies, the combined treatment of RLW cells with AGS and HIV induced the highest rates of hepatic apoptotic cell death, and these data were confirmed on PHH exposed to HIV and ethanol [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol

New-Aaron

Koganti

Ganesan

et al. 2023

IJMS

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Liver disease is one of the leading comorbidities in HIV infection. The risk of liver fibrosis development is potentiated by alcohol abuse. In our previous studies, we reported that hepatocytes exposed to HIV and acetaldehyde undergo significant apoptosis, and the engulfment of apoptotic bodies (ABs) by hepatic stellate cells (HSC) potentiates their pro-fibrotic activation. However, in addition to hepatocytes, under the same conditions, ABs can be generated from liver-infiltrating immune cells. The goal of this study is to explore whether lymphocyte-derived ABs trigger HSC profibrotic activation as strongly as hepatocyte-derived ABs. ABs were generated from Huh7.5-CYP2E1 (RLW) cells and Jurkat cells treated with HIV+acetaldehyde and co-culture with HSC to induce their pro-fibrotic activation. ABs cargo was analyzed by proteomics. ABs generated from RLW, but not from Jurkat cells activated fibrogenic genes in HSC. This was driven by the expression of hepatocyte-specific proteins in ABs cargo. One of these proteins is Hepatocyte-Derived Growth Factor, for which suppression attenuates pro-fibrotic activation of HSC. In mice humanized with only immune cells but not human hepatocytes, infected with HIV and fed ethanol, liver fibrosis was not observed. We conclude that HIV+ABs of hepatocyte origin promote HSC activation, which potentially may lead to liver fibrosis progression.

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Section: Discussionmentioning

confidence: 99%

Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol

New-Aaron

Koganti

Ganesan

et al. 2023

IJMS

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“…A recent meta-analysis reported that PLWH drinking > 50 g (6.25 units) of alcohol daily were 3 times more likely to develop hepatic fibrosis. 38 In addition, alcohol use disorder is associated with a 3–7 fold higher risk of liver-related events and liver-related mortality in PLWH. 39,40 Our data suggest that alcohol is a major player contributing to CLD in PLWH and this needs to be addressed.…”

Section: Discussionmentioning

confidence: 99%

Nonviral Liver Disease Burden in People Living With HIV and Elevated Transaminases: A Cross-Sectional Study

Katarey,

Tan,

Mourad

et al. 2024

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Introduction: Due to improved life expectancy in people living with HIV (PLWH), liver disease is increasingly being recognised. We assessed non-viral chronic liver disease (CLD) burden in PLWH. Methods: The HeAL (HIV non-virAL liver disease) study (2014-2021) prospectively recruited PLWH with elevated serum alanine aminotransferase (ALT) levels and negative hepatitis serology. Clinically significant hepatic fibrosis (CSHF) was defined as liver stiffness measurement (LSM) of >7.1 kPa and hazardous alcohol use as AUDIT score > 8. Primary outcome was prevalence/predictors of CSHF. Results: Total recruited were n=274, 92% male, median age 52 (45-59) years, 96% having undetectable HIV viral load. Overall, n=97 (35%) had hazardous alcohol use, n=72 (26%) had metabolic syndrome (MS) and 17%-27% had exposure to hepatotoxic antiretrovirals (ARV). Prevalence of CSHF was 20% (n=54), prevalence of cirrhosis (LSM >12.5 kPa) being 7% (19/274). Risk factors for CSHF were hazardous alcohol use in 44% (n=24), MS in 46% (n=25) and hepatotoxic ARV in 56% (n=30), majority having more than one risk factor. Independent predictors of CSHF were serum HDL (OR 0.220; 95% CI 0.061-0.790, p=0.020) (inverse relationship); serum AST (OR 1.033, 95% CI 1.001-1.067, p=0.045) and didanosine use (OR 2.878, 95% CI 1.228-6.774, p=0.015). Moderate-severe hepatic steatosis was identified in 52%(n=142). Both FIB-4 and APRI performed poorly in predicting CSHF (PPV 27.3% and 30.6% respectively) and advanced fibrosis(>F3) (PPV 17.6% and 5.9% respectively). Conclusion: In this study, 20% of PLWH had CSHF associated with high prevalence of hazardous alcohol use/MS/potentially hepatotoxic ARV. These potentially modifiable risk factors need addressing.

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“…This suggests that in a subset of unhealthy alcohol consumption, there is decreased resiliency of intestinal barrier making the host more susceptible to increased intestinal permeability, gut-derived endotoxemia, and end-organ damage. This 2-hit hypothesis might explain why unhealthy alcohol consumption increases the risk of more severe liver disease in patients at risk of other forms of liver disease such as human immunodeficiency virus ( 59 ), viral hepatitis ( 60 ), and metabolic dysfunction–associated steatotic liver disease ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease

Swanson,

Garg,

Shaikh

et al. 2024

Clin Transl Gastroenterol

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Objectives: Only 20- 30% of individuals with Alcohol Use Disorder (AUD) develop Alcoholic Liver Disease (ALD). While the development of gut-derived endotoxemia is understood to be a required co-factor, increased intestinal permeability in ALD is not completely understood. Methods: We recruited 178 subjects – 58 healthy controls (HC), 32 with ALD, 53 with AUD but no liver disease (ALC), and 35 with nonalcoholic fatty liver disease (NAFLD). Intestinal permeability was assessed by a sugar cocktail as a percentage of oral dose. The permeability test was repeated after an aspirin challenge in a subset. Results: 5 hour urinary Lactulose/Mannitol (L/M) Ratio (primarily representing small intestinal permeability) was not statistically different in HC, ALC, ALD, and NAFLD (p=0.40). 24 hour urinary Sucralose (representing whole gut permeability) was increased in ALD (F= 5.3, p < 0.01) and distinguished ALD from ALC; 24 hour sucralose/lactulose (S/L) ratio (primarily representing colon permeability) separated the ALD group (F= 10.2, p<0.01) from NAFLD. After aspirin challenge, intestinal permeability increased in all groups and ALD had the largest increase. Conclusions: In a cohort of patients, we confirmed that (1) ALD has increased intestinal permeability compared to HC, ALC, or NAFLD. In addition, since small bowel permeability (L/M ratio) is normal, the disruption of intestinal barrier appears to be primarily in the large intestine.; (2) Decreased resiliency of intestinal barrier to injurious agents (like NSAID) might be the mechanism for gut leak in subset of AUD who develop ALD.

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Alcohol Consumption and Risk of Liver Fibrosis in People Living With HIV: A Systematic Review and Meta-Analysis

Cited by 12 publications

References 56 publications

Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol

Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol

Nonviral Liver Disease Burden in People Living With HIV and Elevated Transaminases: A Cross-Sectional Study

Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease

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