Causes and outcomes of hepatic fibrosis in persons living with HIV

Abstract

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.

Diagnostic Ability of Simple Noninvasive Blood Tests to Predict Increased Liver Stiffness in People Living With HIV and Steatotic Liver Disease

“…This small percentage may be a false positive in PWH to be accounted for in future studies. Alternatively, it may reflect true underlying liver disease from underreported alcohol use, other medications including ART, HIV itself, or other unrecognized inherited liver disease (12,50,51).…”

Bystander Effects and Profibrotic Interactions in Hepatic Stellate Cells during HIV and HCV Coinfection

“…Due to a common transmission route involving infected human blood, coinfections of the HCV and human immunodeficiency virus (HIV) are relatively prevalent, with an estimated 2.3 million individuals globally living with HCV/HIV coinfection [ 1 ]. Numerous studies have evidenced that HIV infection expedites the progression of HCV infection-induced hepatic fibrosis [ 2 , 3 ]. The underlying pathogenesis of accelerated hepatic fibrosis in individuals coinfected with HIV and HCV remains unclear but is likely intricate, potentially involving multiple factors such as direct viral effects, immune/cytokine dysregulation, and heightened oxidative stress [ 4 ].…”

No gender differences in the 24 month decline of non-invasive liver fibrosis markers in HCV-mono and HCV/HIV coinfection after direct-acting antiviral therapy

“…Different behaviors of men and women including the abuse of alcohol, tobacco or intravenous drugs, more prevalent among male patients, might enhance their HCV-induced LF. HIV infection could contribute to increasing LF in HCV/HIVcoinfected individuals [12][13][14][15][16][17]. However HCV/HIV coinfected women have lower degrees of LF compared to men with independence of their alcohol consumption [18].…”

“…Direct-acting antiviral agents (DAA) are extremely effective in combination and even in monotherapy to treat HCV infection with > 90% e cacy [19]. The dynamics of LF at long term after DAA are not well understood due to the lack of extended follow-up studies and the different tools used for LF assessment [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. It seems that LF decreases quickly after starting DAA therapy and then a slow decline or even a plateau in the LF curve is reached.…”