Insights Into the Pathophysiology of Liver Disease in HCV/HIV: Does It End With HCV Cure?

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2020 Nov 27

PMID 33245355

Citations 7

Authors

Andre J Jeyarajan

Raymond T Chung

Affiliations

Soon will be listed here.

Abstract

HCV-HIV coinfected patients exhibit rapid progression of liver damage relative to HCV monoinfected patients. The availability of new directly acting antiviral agents has dramatically improved outcomes for coinfected patients as sustained virologic response rates now exceed 95% and fibrosis-related parameters are improved. Nevertheless, coinfected patients still have a higher mortality risk and more severe hepatocellular carcinoma compared to HCV monoinfected patients, implying the existence of pathways unique to people living with HIV that continue to promote accelerated liver disease. In this article, we review the pathobiology of liver disease in HCV-HIV coinfected patients in the directly acting antiviral era and explore the mechanisms through which HIV itself induces liver damage. Since liver disease is one of the leading causes of non-AIDS-related mortality in HIV-positive patients, enhancing our understanding of HIV-associated fibrotic pathways will remain important for new diagnostic and therapeutic strategies to slow or reverse liver disease progression, even after HCV cure.

Citing Articles

Impact of Policy Changes Expanding Access to Direct-Acting Antivirals on Hepatitis C Virus-Related Hospitalizations in People With HIV: A Population-Based Study.

Antoniou T, Ledlie S, Wang T, Tadrous M, Gomes T Open Forum Infect Dis. 2025; 12(1):ofaf003.

PMID: 39877398 PMC: 11773189. DOI: 10.1093/ofid/ofaf003.

Chronic Hepatitis C Infection Treated with Direct-Acting Antiviral Agents and Occurrence/Recurrence of Hepatocellular Carcinoma: Does It Still Matter?.

Smirne C, Crobu M, Landi I, Vercellino N, Apostolo D, Pinato D Viruses. 2025; 16(12.

PMID: 39772206 PMC: 11680226. DOI: 10.3390/v16121899.

Role of hepatitis c virus in hepatocellular carcinoma and neurological disorders: an overview.

Suhail M, Sohrab S, Kamal M, Azhar E Front Oncol. 2022; 12:913231.

PMID: 35965577 PMC: 9372299. DOI: 10.3389/fonc.2022.913231.

LOXL-2 and TNC-C are markers of liver fibrogenesis in HCV/HIV-, HIV- and HCV-infected patients.

Altinbas A, Holmes J, Salloum S, Lidofsky A, Alatrakchi N, Somsouk M Biomark Med. 2022; 16(11):839-846.

PMID: 35786977 PMC: 9437769. DOI: 10.2217/bmm-2021-0596.

Circulating MicroRNAs as a Tool for Diagnosis of Liver Disease Progression in People Living with HIV-1.

Martinez M, Tural C, Franco S Viruses. 2022; 14(6).

PMID: 35746590 PMC: 9227922. DOI: 10.3390/v14061118.

References

Dominguez-Molina B, Ferrando-Martinez S, Tarancon-Diez L, Hernandez-Quero J, Genebat M, Vidal F . Immune Correlates of Natural HIV Elite Control and Simultaneous HCV Clearance-Supercontrollers. Front Immunol. 2019; 9:2897. PMC: 6295470. DOI: 10.3389/fimmu.2018.02897. View

Noor M, Parker R, OMara E, Grasela D, Currie A, Hodder S . The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults. AIDS. 2004; 18(16):2137-44. DOI: 10.1097/00002030-200411050-00005. View

Kandathil A, Sugawara S, Goyal A, Durand C, Quinn J, Sachithanandham J . No recovery of replication-competent HIV-1 from human liver macrophages. J Clin Invest. 2018; 128(10):4501-4509. PMC: 6159970. DOI: 10.1172/JCI121678. View

Salloum S, Holmes J, Jindal R, Bale S, Brisac C, Alatrakchi N . Exposure to human immunodeficiency virus/hepatitis C virus in hepatic and stellate cell lines reveals cooperative profibrotic transcriptional activation between viruses and cell types. Hepatology. 2016; 64(6):1951-1968. PMC: 5116014. DOI: 10.1002/hep.28766. View

Danta M, Semmo N, Fabris P, Brown D, Pybus O, Sabin C . Impact of HIV on host-virus interactions during early hepatitis C virus infection. J Infect Dis. 2008; 197(11):1558-66. DOI: 10.1086/587843. View

Sun H, Cheng P, Tseng C, Tsai W, Chiu Y, Young K . Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection. Gut. 2017; 67(7):1342-1350. DOI: 10.1136/gutjnl-2017-313832. View

Renga B, Francisci D, Carino A, Marchiano S, Cipriani S, Monti M . The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma. Sci Rep. 2015; 5:15403. PMC: 4606811. DOI: 10.1038/srep15403. View

Akil A, Endsley M, Shanmugam S, Saldarriaga O, Somasunderam A, Spratt H . Fibrogenic Gene Expression in Hepatic Stellate Cells Induced by HCV and HIV Replication in a Three Cell Co-Culture Model System. Sci Rep. 2019; 9(1):568. PMC: 6345841. DOI: 10.1038/s41598-018-37071-y. View

Macias J, Berenguer J, Japon M, Giron-Gonzalez J, Rivero A, Lopez-Cortes L . Hepatic steatosis and steatohepatitis in human immunodeficiency virus/hepatitis C virus-coinfected patients. Hepatology. 2012; 56(4):1261-70. DOI: 10.1002/hep.25791. View

10.

Agarwal N, Iyer D, Gabbi C, Saha P, Patel S, Mo Q . HIV-1 viral protein R (Vpr) induces fatty liver in mice via LXRα and PPARα dysregulation: implications for HIV-specific pathogenesis of NAFLD. Sci Rep. 2017; 7(1):13362. PMC: 5645472. DOI: 10.1038/s41598-017-13835-w. View

11.

Mederacke I, Hsu C, Troeger J, Huebener P, Mu X, Dapito D . Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun. 2013; 4:2823. PMC: 4059406. DOI: 10.1038/ncomms3823. View

12.

Gorin J, Malone D, Strunz B, Carlsson T, Aleman S, Bjorkstrom N . Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection. Sci Rep. 2020; 10(1):2081. PMC: 7005788. DOI: 10.1038/s41598-020-58768-z. View

13.

Mohammed S, Aghdassi E, Salit I, Avand G, Sherman M, Guindi M . HIV-positive patients with nonalcoholic fatty liver disease have a lower body mass index and are more physically active than HIV-negative patients. J Acquir Immune Defic Syndr. 2007; 45(4):432-8. DOI: 10.1097/QAI.0b013e318074efe3. View

14.

Rao R . Endotoxemia and gut barrier dysfunction in alcoholic liver disease. Hepatology. 2009; 50(2):638-44. PMC: 6209509. DOI: 10.1002/hep.23009. View

15.

Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm D . A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998; 12(7):F51-8. DOI: 10.1097/00002030-199807000-00003. View

16.

Lewis W, Day B, Copeland W . Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective. Nat Rev Drug Discov. 2003; 2(10):812-22. DOI: 10.1038/nrd1201. View

17.

Mueller Y, De Rosa S, Hutton J, Witek J, Roederer M, Altman J . Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells. Immunity. 2002; 15(6):871-82. DOI: 10.1016/s1074-7613(01)00246-1. View

18.

Junger W . Immune cell regulation by autocrine purinergic signalling. Nat Rev Immunol. 2011; 11(3):201-12. PMC: 4209705. DOI: 10.1038/nri2938. View

19.

Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, McGowan C . Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016; 16(7):797-808. DOI: 10.1016/S1473-3099(15)00485-5. View

20.

Ganesan M, New-Aaron M, Dagur R, Makarov E, Wang W, Kharbanda K . Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease. Biomolecules. 2019; 9(12). PMC: 6995634. DOI: 10.3390/biom9120851. View