Impaired CD4+ T cell stimulation of NK cell anti-fibrotic activity may contribute to accelerated liver fibrosis progression in HIV/HCV patients

Glässner, A; Eisenhardt, M; Kokordelis, P; Krämer, Benjamin; Wolter, F; Nischalke, Hans Dieter; Boesecke, Christoph; Sauerbruch, Tilman; Rockstroh, Jürgen K.; Spengler, Ulrich; Nattermann, Jacob

doi:10.1016/j.jhep.2013.04.029

Cited by 68 publications

(57 citation statements)

References 37 publications

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“…[60] Supernatants from CD4 + T cells from individuals co-infected with HIV and HCV (as compared to HCV monoinfected or healthy controls) have been shown to have a reduced ability to stimulate NK cells to induce an apoptotic response in HSCs in vitro . [61] These findings suggest that both quantitative and qualitative immune dysfunction contributes to accelerated fibrosis in HIV/HCV co-infection.…”

Section: Mechanisms Of Accelerated Fibrosismentioning

confidence: 96%

HCV and HIV co-infection: mechanisms and management

Chen

Feeney

Chung

2014

Nat Rev Gastroenterol Hepatol

168

135

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HCV and HIV co-infection is associated with accelerated hepatic fibrosis progression and higher rates of liver decompensation and death compared to HCV monoinfection, and liver disease is a leading cause of non-AIDS related mortality among HIV-infected patients. New insights have revealed multiple mechanisms by which HCV and HIV lead to accelerated disease progression, specifically that HIV infection increases HCV replication, augments HCV-induced hepatic inflammation, increases hepatocyte apoptosis, increases microbial translocation from the gut, and leads to an impairment of HCV-specific immune responses. Treatment of HIV with antiretroviral therapy and treatment of HCV have independently been shown to delay the progression of fibrosis and reduce complications from end-stage liver disease among co-infected patients. However, rates of sustained virologic response with PEG-IFN and ribavirin have been significantly inferior among co-infected patients compared to HCV monoinfected patients, and treatment uptake has remained low given the limited efficacy and tolerability of current HCV regimens. With multiple direct acting antivirals in development to treat HCV, a unique opportunity exists to redefine the treatment paradigm for co-infected patients, which incorporates data on fibrosis stage as well as potential drug interactions with antiretroviral therapy.

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Section: Mechanisms Of Accelerated Fibrosismentioning

confidence: 96%

HCV and HIV co-infection: mechanisms and management

Chen

Feeney

Chung

2014

Nat Rev Gastroenterol Hepatol

168

135

View full text Add to dashboard Cite

show abstract

“…Several lines of evidence indicate that HIV-induced CD4 depletion is independently associated with the severity of liver fibrosis in chronic HCV infection. In particular, a recent study has demonstrated that both HIV-induced loss of CD4 + T cells and dysregulated CD4 + T cell function lead to a reduction in the anti-fibrotic activity of NK cells, which plausibly results in the accelerated progression of liver fibrosis seen in patients with HIV/HCV co-infection [105]. In addition, a marked intrahepatic CD4 T-cell depletion, associated to an increase in apoptotic lymphocytes in the liver lobule, has been demonstrated in HIV/HCV coinfected patients.…”

Section: Accelerated Liver Fibrosis In Human Immunodeficiency Virumentioning

confidence: 99%

Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

Mastroianni

Lichtner

Mascia

et al. 2014

IJMS

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Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

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“…Immunomodulation patterns to helpful immune reaction in order to clearance of HCV infection or detrimental role of immune system in liver injury and fibrosis have not clear completely so far [28,34,35]. According to literature [16], NKG2D may also function as a costimulatory receptor on CD4? regulatory T cells, suggesting that NKG2D signaling may induce dual tolerogenic and immunogenic response in hepatitis C infection.…”

Section: Nkg2d Polymorphism Effects On Peginterferon Alfa-2a/ribavirimentioning

confidence: 99%

Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174 GC polymorphism

et al. 2016

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Natural killer group 2D (NKG2D), as an activating receptor, plays pivotal role in viral infectious diseases. Several single nucleotide polymorphisms (SNPs) in the NKG2D gene have characterized that the rs1049174G/ C SNP of NKG2D is in the spotlight of notice because of its role in activating of human T cells. This study aimed to investigate rs1049174G/C genetic polymorphism in Chronic Hepatitis C (CHC) patients. The study compromised 107 CHC patients with genotype 1a and 1b. All recruited patients were under treatment with Peginterferon Alfa-2a/Ribavirin according to standard protocol. After completing treatment, 67 patients showed sustained virologic response (SVR) and the rest of patients did not respond to the treatment and considered as non-responder (NR). Genotyping of NKG2D rs1049174G/C SNP was performed using PCR-RFLP method in SVR and NR patients. The NKG2D rs1049174 genotypes frequency for GG, GC and CC were 45, 41 and 14 % respectively. Genotypes distribution were significantly different between SVR and NR groups (p = 0.005). So that the patients with the homozygous GG genotype demonstrated a higher response to Peginterferon Alfa-2a/Ribavirin therapy against HCV infection (OR = 6.0, 95 %CI 1.71-21.08, p = 0.005). In conclusion, the rs1049174 GG genotype of NKG2D receptor is an effective factor in successfully treatment of CHC patients by Peginterferon Alfa-2a/ Ribavirin.

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Impaired CD4+ T cell stimulation of NK cell anti-fibrotic activity may contribute to accelerated liver fibrosis progression in HIV/HCV patients

Cited by 68 publications

References 37 publications

HCV and HIV co-infection: mechanisms and management

HCV and HIV co-infection: mechanisms and management

Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174 GC polymorphism

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