Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease

Stanley, Takara L.; Fourman, Lindsay T; Wong, Lai Ping; Sadreyev, Ruslan I.; Billingsley, James M.; Feldpausch, Meghan N.; Zheng, Isabel; Pan, Chelsea S; Boutin, Autumn; Lee, Hang; Corey, Kathleen E.; Torriani, Martin; Kleiner, David E.; Chung, Raymond T.; Hadigan, Colleen; Grinspoon, Steven

doi:10.1093/cid/ciab019

Cited by 7 publications

(3 citation statements)

References 44 publications

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“…Correspondingly, it has been shown to reduce liver fat content and prevent fibrosis progression [96]. Long-term treatment with tesamorelin also notably decreased markers of T-cell and monocyte/macrophage activity, suggesting reduction in immune activation and systemic inflammation in patients with HIV and NAFLD [97 ▪▪ ]. Other classes of agents for NAFLD/NASH or reduction of hepatic fibrosis are under active evaluation (e.g., FXR agonists, thyroid hormone receptor agonists) in non-HIV infected populations and also show promising results, but studies in PLWH are lacking.…”

Section: Therapeutic Interventions For Hepatic Fibrosismentioning

confidence: 99%

Causes and outcomes of hepatic fibrosis in persons living with HIV

Yen

Sherman

2022

Current Opinion in HIV and AIDS

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Purpose of reviewThe epidemiology of liver disease in people living with HIV has evolved since the arrival of effective hepatitis C virus (HCV) treatment. Nonalcoholic fatty liver disease (NAFLD) in HIV patients is highly prevalent while hepatitis D, hepatitis E, and occult hepatitis B remain underappreciated. We discuss mechanisms of fibrosis in HIV and review clinical outcomes of HIV-associated liver diseases. Recent findingsHIV-HCV co-infection is receding as a cause of progressive liver disease, but fibrosis biomarkers after HCV treatment remain elevated. Antiretroviral therapy (ART) with anti-hepatitis B virus (HBV) activity promotes stable liver disease, but oversimplifying ART regimens in unrecognized suppressed HBV may lead to activation of HBV. A high prevalence of fibrosis and rapid progression of fibrosis are seen in HIVassociated NAFLD, with visceral fat as a major risk factor. Newer ART such as integrase strand inhibitors may have limited intrinsic hepatoxicity but do increase weight, which may secondarily lead to hepatic steatosis. Promising therapies for HIV-associated NAFLD include tesamorelin and CCR5 blockade agents. SummaryOur understanding of the natural history and pathogenesis of liver diseases in HIV has advanced and adapted to the changing landscape of liver disease in this population. Future research should evaluate long-term clinical and histological outcomes, prevention strategies, and treatment options to improve morbidity and mortality in HIV-related liver diseases.

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Section: Therapeutic Interventions For Hepatic Fibrosismentioning

confidence: 99%

Causes and outcomes of hepatic fibrosis in persons living with HIV

Yen

Sherman

2022

Current Opinion in HIV and AIDS

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“…In a multicenter AIDS cohort study (MACS) conducted from 1984 to 2009, CCL13 was found to be higher in the group of SUP (exposed to HARRT with HIV RNA suppressed to less than 50 copies/ml plasma) compared to the HAART-naive (NAI) group, on the timeline, CCL13 increased significantly in the first year of viral suppression, followed by a uniformly flat trajectory, HIV suppression appeared to increase the levels of the M2-associated chemokines ( 117 ). In addition, the growth hormone-releasing hormone (GHRH) analog tesamorelin significantly reduced CCL13 expression in HIV populations with metabolic dysregulation, and systemic and end-organ inflammation, suggesting that enhancement of the GH axis may improve immune activation in this population ( 21 ).…”

Section: Ccl13 and Aidsmentioning

confidence: 99%

CCL13 and human diseases

Dai

Wang

et al. 2023

Front. Immunol.

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CCL13/MCP-4 belongs to the CC chemokine family, which induces chemotaxis in many immune cells. Despite extensive research into its function in numerous disorders, a thorough analysis of CCL13 is not yet accessible. The role of CCL13 in human disorders and existing CCL13-focused therapies are outlined in this study. The function of CCL13 in rheumatic diseases, skin conditions, and cancer is comparatively well-established, and some studies also suggest that it may be involved in ocular disorders, orthopedic conditions, nasal polyps, and obesity. We also give an overview of research that found very little evidence of CCL13 in HIV, nephritis, and multiple sclerosis. Even though CCL13-mediated inflammation is frequently linked to disease pathogenesis, it’s fascinating to note that in some conditions, like primary biliary cholangitis (PBC) and suicide, it might even act as a preventative measure.

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“…Secondary mechanistic studies among this cohort have demonstrated that tesamorelin upregulated gene pathways in the liver related to oxidative phosphorylation and downregulated pathways related to inflammation [ 30 ] . Further, tesamorelin reduced circulating proteins related to cytotoxic T-cell and monocyte activation in conjunction with downregulation of hepatic gene pathways related to immune activation [ 88 ] . An ongoing study is investigating the effects of tesamorelin in individuals with NAFLD who do not have HIV-infection.…”

Section: Modulating the Gh Axis To Treat Nafldmentioning

confidence: 99%

Growth hormone and nonalcoholic fatty liver disease

Ingrid

Stanley

2023

Immunometabolism

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Nonalcoholic fatty liver disease (NAFLD) is a prevalent cause of liver disease and metabolic comorbidities. Obesity is strongly associated with NAFLD and is also a state of relative deficiency of growth hormone (GH). Evidence supports a role of reduced GH and insulin-like growth factor-1 (IGF-1) in NAFLD pathogenesis. Physiological actions of GH in the liver include suppression of de novo lipogenesis (DNL) and promotion of lipid beta-oxidation, and GH also appears to have anti-inflammatory actions. Physiologic actions of IGF-1 include suppression of inflammatory and fibrogenic pathways important in the evolution from steatosis to steatohepatitis and fibrosis. Rodent models of impaired hepatic GH signaling show the development of steatosis, sometimes accompanied by inflammation, hepatocellular damage, and fibrosis, and these changes are ameliorated by treatment with GH and/or IGF-1. In humans, individuals with GH deficiency and GH resistance demonstrate an increased prevalence of NAFLD compared to controls, with improvement in hepatic lipid, steatohepatitis, and fibrosis following GH replacement. As a corollary, individuals with GH excess demonstrate lower hepatic lipid compared to controls along with increased hepatic lipid following treatment to normalize GH levels. Clinical trials demonstrate that augmentation of GH reduces hepatic lipid content in individuals with NAFLD and may also ameliorate steatohepatitis and fibrosis. Taken together, evidence supports an important role for perturbations in the GH/IGF-1 axis as one of the pathogenic mechanisms of NAFLD and suggests that further study is needed to assess whether augmentation of GH and/or IGF-1 may be a safe and effective therapeutic strategy for NAFLD.

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Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease

Cited by 7 publications

References 44 publications

Causes and outcomes of hepatic fibrosis in persons living with HIV

Causes and outcomes of hepatic fibrosis in persons living with HIV

CCL13 and human diseases

Growth hormone and nonalcoholic fatty liver disease

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