RESEARCH PAPER
Markers of liver fibrosis and apoptosis in patients with HIV mono-infection and HIV/HCV co-infection
Submission date: 2018-06-18
Final revision date: 2018-12-11
Acceptance date: 2018-12-11
Publication date: 2019-03-28
HIV & AIDS Review 2019;18(1):33-39
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Human immunodeficiency virus (HIV)/hepatits C virus (HCV) co-infection has a significant impact on liver-related morbidity and mortality. Among many other pathogenic mechanisms leading to accelerated hepatic disease are liver fibrosis and hepatocyte apoptosis. Hence the objective of this investigator-initiated cross-sectional study was to analyse the plasma levels of hyaluronic acid, cytokeratin-18, and cytochrome c in order to assess their impact on progression of liver disease in patients with HIV/HCV co-infection comparing to those with HIV mono-infection.
Material and methods:
There were 80 patients with HIV infection included in the study. HCV co-infection was in 46 (57.5%) patients and HIV mono-infection in 34 patients. Blood levels of hyaluronic acid were tested using a Hyaluronic Acid test Kit, cytokeratin-18 neoepitope levels using M30-Apoptose ELISA test, and cytochrome c using human Cytochrome c ELISA test.
Results:
The levels of cytokeratin-18 and of hyaluronic acid were significantly higher in the group of patients with HIV/HCV co-infection. The differences in the level of cytochrome c were not significant. The analysis revealed that the main effect of HCV co-infection on the level of cytokeratine-18 is indirect. It is mediated by the level of hyaluronic acid.
Conclusions:
The progression of liver disease in patients with HIV/HCV co-infection is more pronounced compared to those with HIV mono-infection. It is shown by the higher plasma levels of hyaluronic acid, which is a relevant liver fibrosis marker and hepatocyte apoptosis marker cytokeratin-18 in patients with HIV/HCV co-infection. The hyaluronic acid level is important in assessing the impact of HCV co-infection on liver apoptosis.
Human immunodeficiency virus (HIV)/hepatits C virus (HCV) co-infection has a significant impact on liver-related morbidity and mortality. Among many other pathogenic mechanisms leading to accelerated hepatic disease are liver fibrosis and hepatocyte apoptosis. Hence the objective of this investigator-initiated cross-sectional study was to analyse the plasma levels of hyaluronic acid, cytokeratin-18, and cytochrome c in order to assess their impact on progression of liver disease in patients with HIV/HCV co-infection comparing to those with HIV mono-infection.
Material and methods:
There were 80 patients with HIV infection included in the study. HCV co-infection was in 46 (57.5%) patients and HIV mono-infection in 34 patients. Blood levels of hyaluronic acid were tested using a Hyaluronic Acid test Kit, cytokeratin-18 neoepitope levels using M30-Apoptose ELISA test, and cytochrome c using human Cytochrome c ELISA test.
Results:
The levels of cytokeratin-18 and of hyaluronic acid were significantly higher in the group of patients with HIV/HCV co-infection. The differences in the level of cytochrome c were not significant. The analysis revealed that the main effect of HCV co-infection on the level of cytokeratine-18 is indirect. It is mediated by the level of hyaluronic acid.
Conclusions:
The progression of liver disease in patients with HIV/HCV co-infection is more pronounced compared to those with HIV mono-infection. It is shown by the higher plasma levels of hyaluronic acid, which is a relevant liver fibrosis marker and hepatocyte apoptosis marker cytokeratin-18 in patients with HIV/HCV co-infection. The hyaluronic acid level is important in assessing the impact of HCV co-infection on liver apoptosis.
REFERENCES (40)
1.
Platt L, Easterbrook P, Gower E, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis 2016; 16: 797-808.
2.
Rao VB, Johari N, du Cros P, et al. Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Infect Dis 2015; 15: 819-824.
3.
Centre for Disease Prevention and Control in Latvia (in Latvian: SPKC – Slimību profilakses un kontroles centrs). Available online: https://www.spkc.gov.lv/lv/ statistika-un-petijumi/infekcijas-slimibas/datu-vizualizacija/hivaids (accessed: 3 April 2018).
4.
Centre for Disease Prevention and Control in Latvia. Letter to the authors (14.05.2018. Nr. 1-8.1.4/2611). Available on request.
5.
Mastroianni CM, Lichtner M, Mascia C, et al. Molecular mechanisms of liver fibrosis in HIV/HCV coinfection. Int J Mol Sci 2014; 15: 9184-9208.
6.
Sacchi P, Cima S, Corbella M, et al. Liver fibrosis, microbial translocation and immune activation markers in HIV and HCV infections and in HIV/HCV co-infection. Dig Liver Dis 2015; 47: 218-225.
7.
Allory Y, Charlotte F, Benhamou Y, et al. Impact of human immunodeficiency virus infection on the histological features of chronic hepatitis C: a case-control study. The MULTIVIRC group. Hum Pathol 2000; 31: 69-74.
8.
Duarte MI, Neto AN. Human immunodeficiency virus infection of the liver. In: Practical Hepatic Pathology: A Diagnostic Approach. 2nd ed. Saxena R (ed.). Elsevier, Inc. 2018; pp. 247-264.
9.
Kramer JR, Giordano TP, El-Serag HB. Effect of human immunodeficiency virus and antiretrovirals on outcomes of hepatitis C: a systematic review from an epidemiologic perspective. Clin Gastroenterol Hepatol 2007; 5: 1321-1328.e7.
10.
Deng L, Gui X, Xiong Y, et al. End-stage liver disease: Prevalence, risk factors and clinical characteristics in a cohort of HIV-HCV coinfected Han Chinese. Clin Res Hepatol Gastroenterol 2012; 36: 574-582.
11.
Bica I, McGovern B, Dhar R, et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001; 32: 492-497.
12.
Chen JY, Feeney ER, Chung RT. HCV and HIV co-infection: mechanisms and management. Nat Rev Gastroenterol Hepatol 2014; 11: 362-371.
13.
Cartón JA, Collazos J, de la Fuente B, et al. Course of liver fibrosis in HIV-hepatitis C virus-coinfected patients depending on the response to hepatitis C therapy. AIDS Res Hum Retroviruses 2013; 29: 215-222.
14.
Singh S, Facciorusso A, Loomba R, et al. Magnitude and Kinetics of Decrease in Liver Stiffness After Antiviral Therapy in Patients With Chronic Hepatitis C: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018; 16: 27-38.e4.
15.
Terrault NA, Roland ME, Schiano T, et al. Outcomes of Liver Transplantation in HCV-HIV Coinfected Recipients. Liver Transpl 2012; 18: 716-726.
16.
Cao YZ, Dieterich D, Thomas PA, et al. Identification and quantitation of HIV-1 in the liver of patients with AIDS. AIDS 1992; 6: 65-70.
17.
Jang JY, Shao RX, Lin W, et al. HIV infection increases HCV-induced hepatocyte apoptosis. J Hepatol 2011; 54: 612-620.
18.
Cho H, Ekikuchi M, Li Y, et al. Induction of multiple immune regulatory pathways with differential impact in HCV/HIV coinfection. Front Immunol 2014; 5: 265.
19.
Battaglia V, Compagnone A, Bandino A, et al. Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures. Int J Biochem Cell Biol 2009; 41: 586-594.
20.
Riedl SJ, Shi Y. Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 2004; 5: 897-907.
21.
Cao L, Quan XB, Zeng WJ, et al. Mechanism of hepatocyte apoptosis. J Cell Death 2016; 9: 19-29.
22.
Calabrese F, Pontisso P, Pettenazzo E, et al. Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV RNA levels. Hepatology 2000; 31: 1153-1159.
23.
Machida K, Tsukiyama-Kohara K, Seike E, et al. Inhibition of cytochrome c release in Fas-mediated signaling pathway in transgenic mice induced to express hepatitis C viral proteins. J Biol Chem 2001; 276: 12140-12146.
24.
Lee SH, Kim YK, Kim CS, et al. E2 of hepatitis C virus inhibits apoptosis. J Immunol 2005; 175: 8226-8235.
25.
Feuth T, Van Baarle D, Hoepelman AI, et al. Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV-HCV coinfected patients, irrespective of liver disease severity. Apoptosis 2014; 19: 1128-1135.
26.
Alimonti JB, Ball TB, Fowke KR. Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection and AIDS. J Gen Virol 2003; 84 (Pt 7): 1649-1661.
27.
Yamada H, Tada-Oikawa S, Uchida A, et al. TRAIL causes cleavage of bid by caspase-8 and loss of mitochondrial membrane potential resulting in apoptosis in BJAB cells. Biochem Biophys Res Commun 1999; 265: 130-133.
28.
Laskus T, Kibler KV, Chmielewski M, et al. Effect of hepatitis C infection on HIV-induced apoptosis. PLoS One 2013; 8: e75921.
29.
Tamimi TI, Elgouhari HM, Alkhouri N, et al. An apoptosis panel for nonalcoholic steatohepatitis diagnosis. J Hepatol 2011; 54: 1224-1229.
30.
Zampino R, Marrone A, Restivo L, et al. Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations. World J Hepatol 2013; 5: 528-540.
31.
Olubamwo OO, Aregbesola AO, Miettola J, et al. Hepatitis C and risk of coronary atherosclerosis – A systematic review. Public Health 2016; 138: 12-25.
32.
Rasmussen AL, Wang IM, Shuhart MC, et al. Chronic immune activation is a distinguishing feature of liver and PBMC gene signatures from HCV/HIV coinfected patients and may contribute to hepatic fibrogenesis. Virology 2012; 430: 43-52.
33.
Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 2004; 39: 273-278.
34.
Baranova A, Lal P, Birerdinc A, Younossi ZM. Non-invasive markers for hepatic fibrosis. BMC Gastroenterol 2011; 11: 91.
35.
Gressner OA, Weiskirchen R, Gressner AM. Biomarkers of liver fibrosis: clinical translation of molecular pathogenesis or based on liver dependent malfunction tests. Clin Chim Acta 2007; 381: 107-113.
36.
Bantel H, Lügering A, Poremba C, et al. Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infection. Hepatology 2001; 34: 758-767.
37.
Walsh MJ, Vanags DM, Clouston AD, et al. Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury. Hepatology 2004; 39: 1230-1238.
38.
IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.
39.
Rosseel Y. Iavaan: An R Package for Structural Equation Modeling. Journal of Statistical Software 2012; 48: 81291; DOI: 10.18637/jss.v048.i02.
40.
Satorra A, Bentler PM. Corrections to test statistics and standard errors in covariance structure analysis. In: Latent Variables Analysis: Applications for Developmental Research. von Eye A, Clogg CC (eds.). Sage Publications, Inc., Thousand Oaks 1994; 399-419.
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