Special Issue "Anti-HIV Therapy and the Development of Chronic Liver Diseases"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (31 March 2021).

Special Issue Editor

Prof. Nadezda Apostolova
E-Mail Website
Guest Editor
Department of Pharmacology, University of Valencia, avda. Blasco Ibañez n.15, 46010 Valencia, Spain
Interests: antiretroviral therapy; hepatic diseases; liver fibrosis; mitochondria; autophagy

Special Issue Information

Dear Colleagues, 

Since the introduction of combined antiretroviral therapy (cART) in the mid-1990s, HIV infection has become a manageable chronic disease. As HIV-infected patients now live significantly longer, non-AIDS illnesses have become a major cause of morbidity and mortality in this population. In particular, liver-related diseases which are becoming increasingly prominent in HIV-infected individuals are considered one of the leading causes of non-AIDS-related death accounting for 13–18% of all-cause mortality in these patients. 

Patients with controlled HIV infection (suppressed HIV RNA and restored CD4 counts) under long-term treatment develop liver diseases from a variety of causes, including alcohol consumption, NAFLD, and viral hepatitis, in addition to more HIV-specific processes such as cART-related toxicity and direct injury to the liver caused by the HIV virus itself. Intense research over the recent years has shown that the pathogenesis of these conditions involves increased levels of local and systemic inflammation, hepatic fibrogenesis that results in various degrees of liver fibrosis, and altered immunity. The mechanisms that have been described to underlie these processes involve but are not limited to oxidative stress, mitochondrial dysfunction, lipotoxicity, immune-mediated injury, direct cytotoxicity and toxic metabolite accumulation, gut microbial translocation, and senescence. Nevertheless, how these processes are interconnected and what their exact pathophysiological contribution is are still not clear. Moreover, the specificity of the therapeutic and prophylactic approaches for liver diseases in the context of HIV infection needs to be studied in greater detail. With this in mind, a broad understanding of the pathogenesis of liver injury, and in particular linking of these mechanisms to the different forms and outcomes of liver pathologies in HIV patients, would be of great utility to clinicians caring for HIV-infected patients. 

The aim of this Special Issue is to assemble cutting-edge basic and clinical research which elucidates the processes involved in the development/progression of chronic liver diseases in HIV-infected patients under treatment. The suggested topics of interest may include:

  • Pathophysiological changes in the liver of HIV patients;
  • Intercellular communication in the liver;
  • Gut–liver axis;
  • Liver-derived extracellular vesicles;
  • Antiretroviral drug-specific specific liver toxicity;
  • Altered liver metabolism in HIV patients;
  • Altered immunity and development of chronic liver disease.

Prof. Nadezda Apostolova
Guest Editor

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Keywords

  • HIV
  • Antiretroviral drugs
  • Liver
  • Toxicity
  • Chronic hepatic disease

Published Papers (4 papers)

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Research

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Communication
Psoriasis and Liver Damage in HIV-Infected Patients
Cells 2021, 10(5), 1099; https://doi.org/10.3390/cells10051099 - 04 May 2021
Viewed by 540
Abstract
Background/objectives: Psoriasis is the most frequent skin disease in HIV-infected patients. Nonalcohol fatty liver disease (NAFLD) is more prevalent in patients with psoriasis. We report the prevalence of psoriasis and NAFLD and investigate risk factors of liver damage in HIV-infected patients with [...] Read more.
Background/objectives: Psoriasis is the most frequent skin disease in HIV-infected patients. Nonalcohol fatty liver disease (NAFLD) is more prevalent in patients with psoriasis. We report the prevalence of psoriasis and NAFLD and investigate risk factors of liver damage in HIV-infected patients with psoriasis. Methods: We performed a retrospective observational study. Steatosis was defined as indicative abdominal ultrasound findings, CAP (controlled attenuated parameter by transient elastography) > 238 dB/m, and/or triglyceride and glucose index (TyG) > 8.38. Significant (fibrosis ≥ 2) and advanced liver fibrosis (fibrosis ≤ F3) were studied by transient elastography (TE) and/or FIB-4 using standard cutoff points. FIB-4 (Fibrosis 4 score) results were adjusted for hepatitis C (HCV)-coinfected patients. Results: We identified 80 patients with psoriasis (prevalence, 1.5%; 95% CI, 1.1–1.8). Psoriasis was severe (PASI > 10 and/or psoriatic arthritis) in 27.5% of cases. The prevalence of steatosis was 72.5% (95% CI, 65–85). Severe psoriasis was an independent risk factor for steatosis (OR, 12; 95% CI, 1.2–120; p = 0.03). Significant liver fibrosis (p < 0.05) was associated with HCV coinfection (OR 3.4; 95% CI, 1.1–10.6), total CD4 (OR 0.99; 95% CI, 0.99–1), and time of efavirenz exposure (OR 1.2; 95% CI, 1.0–1.3). Conclusions: The prevalence of psoriasis in HIV-infected patients was similar to that of the general population. Steatosis is highly prevalent, and severe psoriasis is an independent risk factor for steatosis in HIV-infected patients. Full article
(This article belongs to the Special Issue Anti-HIV Therapy and the Development of Chronic Liver Diseases)

Review

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Review
NNRTI and Liver Damage: Evidence of Their Association and the Mechanisms Involved
Cells 2021, 10(7), 1687; https://doi.org/10.3390/cells10071687 - 04 Jul 2021
Viewed by 707
Abstract
Due to the improved effectiveness and safety of combined antiretroviral therapy, human immunodeficiency virus (HIV) infection has become a manageable, chronic condition rather than a mortal disease. However, HIV patients are at increased risk of experiencing non-AIDS-defining illnesses, with liver-related injury standing out [...] Read more.
Due to the improved effectiveness and safety of combined antiretroviral therapy, human immunodeficiency virus (HIV) infection has become a manageable, chronic condition rather than a mortal disease. However, HIV patients are at increased risk of experiencing non-AIDS-defining illnesses, with liver-related injury standing out as one of the leading causes of death among these patients. In addition to more HIV-specific processes, such as antiretroviral drug-related toxicity and direct injury to the liver by the virus itself, its pathogenesis is related to conditions that are also common in the general population, such as alcoholic and non-alcoholic fatty liver disease, viral hepatitis, and ageing. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of combined anti-HIV treatment due to their unique antiviral activity, high specificity, and acceptable toxicity. While first-generation NNRTIs (nevirapine and efavirenz) have been related largely to liver toxicity, those belonging to the second generation (etravirine, rilpivirine and doravirine) seem to be generally safe for the liver. Indeed, there is preclinical evidence of rilpivirine being hepatoprotective in different models of liver injury, independently of the presence of HIV. The present study aims to review the mechanisms by which currently available anti-HIV drugs belonging to the NNRTI family may participate in the development of liver disease. Full article
(This article belongs to the Special Issue Anti-HIV Therapy and the Development of Chronic Liver Diseases)
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Review
Hepatotoxicity of Contemporary Antiretroviral Drugs: A Review and Evaluation of Published Clinical Data
Cells 2021, 10(5), 1263; https://doi.org/10.3390/cells10051263 - 20 May 2021
Cited by 2 | Viewed by 798
Abstract
Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. [...] Read more.
Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. We have segregated the antiretroviral agents used in contemporary practice into class groupings based on their mechanism of antiviral activity (non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and entry inhibitors) while providing a review and discussion of the hepatoxicity seen in the most relevant clinical literature published to date. Clinical literature for individual agents is discussed and agent comparisons afforded within each group in tabular format. Our review will provide a summative overview of the incidence and medications associated with hepatic adverse reactions linked to the use of contemporary antiretroviral drugs. Full article
(This article belongs to the Special Issue Anti-HIV Therapy and the Development of Chronic Liver Diseases)
Review
Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?
Cells 2021, 10(5), 1212; https://doi.org/10.3390/cells10051212 - 15 May 2021
Viewed by 661
Abstract
After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. [...] Read more.
After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. HIV itself may lead to liver damage and subsequent liver fibrosis (LF) through multiple pathways. Apart from HIV, viral hepatitis, alcoholic and especially non-alcoholic liver diseases have been implicated in liver involvement among PLWH. Another well known cause of hepatotoxicity is ART, raising clinically significant concerns about LF in long-term treatment. In this review we present the existing data and analyze the association of LF with all ART drug classes. Published data derived from many studies are to some extent controversial and therefore remain inconclusive. Among all the antiretroviral drugs, nucleoside reverse transcriptase inhibitors, especially didanosine and zidovudine, seem to carry the greatest risk for LF, with integrase strand transfer inhibitors and entry inhibitors having minimal risk. Surprisingly, even though protease inhibitors often lead to insulin resistance, they do not seem to be associated with a significant risk of LF. In conclusion, most ART drugs are safe in long-term treatment and seldom lead to severe LF when no liver-related co-morbidities exist. Full article
(This article belongs to the Special Issue Anti-HIV Therapy and the Development of Chronic Liver Diseases)
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