Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1731-1743 |
| Number of pages | 13 |
| Journal | AIDS (London, England) |
| Volume | 30 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Jul 2016 |
Keywords
- (fos)amprenavir
- d-drugs
- end-stage liver disease
- hepatocellular carcinoma
- hepatotoxicity
- HIV
- tenofovir
- alpha fetoprotein
- didanosine
- emtricitabine
- fosamprenavir
- nevirapine
- stavudine
- antiretrovirus agent
- adult
- Article
- CD4 lymphocyte count
- cohort analysis
- drug exposure
- end stage liver disease
- esophagus varices bleeding
- female
- follow up
- hepatic encephalopathy
- hepatorenal syndrome
- highly active antiretroviral therapy
- human
- Human immunodeficiency virus infected patient
- Human immunodeficiency virus infection
- liver cell carcinoma
- liver histology
- liver transplantation
- major clinical study
- male
- mortality
- priority journal
- prognosis
- prospective study
- sensitivity analysis
- survival
- chemically induced
- complication
- liver tumor
- middle aged
- risk assessment
- Adult
- Anti-Retroviral Agents
- Carcinoma, Hepatocellular
- End Stage Liver Disease
- Female
- HIV Infections
- Humans
- Liver Neoplasms
- Male
- Middle Aged
- Prospective Studies
- Risk Assessment
Access to Document
Other files and links
Fingerprint
Dive into the research topics of 'Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons. / Ryom, L.; Lundgren, J.D.; De Wit, S. et al.
In: AIDS (London, England), Vol. 30, No. 11, 07.2016, p. 1731-1743.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons
AU - Ryom, L.
AU - Lundgren, J.D.
AU - De Wit, S.
AU - Kovari, H.
AU - Reiss, P.
AU - Law, M.
AU - El-Sadr, W.
AU - Monforte, A.D.
AU - Mocroft, A.
AU - Smith, C.
AU - Fontas, E.
AU - Dabis, F.
AU - Phillips, A.
AU - Sabin, C.
AU - Torres, Ferran
N1 - Cited By :42 Export Date: 17 February 2022 CODEN: AIDSE Correspondence Address: Ryom, L.; Department of Infectious Diseases, Blegdamsvej 9, Denmark; email: lene.ryom.nielsen@regionh.dk Chemicals/CAS: didanosine, 69655-05-6; emtricitabine, 137530-41-7, 143491-54-7, 143491-57-0; fosamprenavir, 226700-79-4, 226700-80-7, 226700-81-8; nevirapine, 129618-40-2; stavudine, 3056-17-5; tenofovir, 147127-19-3, 147127-20-6; Anti-Retroviral Agents References: Wit, F.W., Weverling, G.J., Weel, J., Jurriaans, S., Lange, J.M., Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy (2002) J Infect Dis, 186, pp. 23-31; Kovari, H., Weber, R., Influence of antiretroviral therapy on liver disease (2011) Curr Opin HIV AIDS, 6, pp. 272-277; Abrescia, N., D'Abbraccio, M., Figoni, M., Busto, A., Maddaloni, A., De Marco, M., Hepatotoxicity of antiretroviral drugs (2005) Curr Pharm des, 11, pp. 3697-3710; (2015) EACS Treatment Guidelines Version 8. 0, , http://www.eacsociety.org/guidelines/eacsguidelines/eacs-guidelines.html, European AIDS Clinical Society [Accessed 5 November 2015]; Maida, I., Nunez, M., Rios, M.J., Martin-Carbonero, L., Sotgiu, G., Toro, C., Severe liver disease associated with prolonged exposure to antiretroviral drugs (2006) J Acquir Immune Defic Syndr, 42, pp. 177-182; Kalyesubula, R., Kagimu, M., Opio, K.C., Kiguba, R., Semitala, C.F., Schlech, W.F., Hepatotoxicity from first line antiretroviral therapy: An experience from a resource limited setting (2011) Afr Health Sci, 11, pp. 16-23; Sulkowski, M.S., Thomas, D.L., Chaisson, R.E., Moore, R.D., Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection (2000) JAMA, 283, pp. 74-80; Lapadula, G., Costarelli, S., Chatenoud, L., Castelli, F., Astuti, N., Di Giambenedetto, S., Risk of liver enzyme elevation during treatment with ritonavir-boosted protease inhibitors among HIV-monoinfected and HIV/HCV coinfected patients (2015) J Acquir Immune Defic Syndr, 69, pp. 312-318; Kovari, H., Ledergerber, B., Battegay, M., Rauch, A., Hirschel, B., Foguena, A.K., Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus co-infection (2010) Clin Infect Dis, 50, pp. 502-511; Peters, L., Rockstroh, J.K., Biomarkers of fibrosis and impaired liver function in chronic hepatitis C: How well do they predict clinical outcomes? (2010) Curr Opin HIV AIDS, 5, pp. 517-523; Suarez-Zarracina, T., Valle-Garay, E., Collazos, J., Montes, A.H., Carcaba, V., Carton, J.A., Didanosine (ddI) associates with increased liver fibrosis in adult HIV-HCV coinfected patients (2012) J Viral Hepat, 19, pp. 685-693; Pinol, V., Bessa, X., Bruguera, M., Rodes, J., Steatosis and nonalcoholic steatohepatitis. A comparative analysis (2000) Gastroenterol Hepatol, 23, pp. 57-61; Loko, M.A., Bani-Sadr, F., Winnock, M., Lacombe, K., Carrieri, P., Neau, D., Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients (2011) J Viral Hepat, 18, pp. e307-e314; Blanco, F., Barreiro, P., Ryan, P., Vispo, E., Martin-Carbonero, L., Tuma, P., Risk factors for advanced liver fibrosis in HIVinfected individuals: Role of antiretroviral drugs and insulin resistance (2011) J Viral Hepat, 18, pp. 11-16; Macias, J., Berenguer, J., Japon, M., Cumulative exposure to ARV drugs leads to progressive hepatic steatosis among HIV/ HCV-co-infected patients [Abstract 781] (2012) 19th CROI, , Seattle, Washington, USA; 5-8 March; Bani-Sadr, F., Lapidus, N., Bedossa, P., De Boever, C.M., Perronne, C., Halfon, P., Progression of fibrosis in HIV and hepatitis C virus-coinfected patients treated with interferon plus ribavirinbased therapy: Analysis of risk factors (2008) Clin Infect Dis, 46, pp. 768-774; McGovern, B.H., Ditelberg, J.S., Taylor, L.E., Gandhi, R.T., Christopoulos, K.A., Chapman, S., Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients (2006) Clin Infect Dis, 43, pp. 365-372; Merchante, N., Perez-Camacho, I., Mira, J.A., Rivero, A., Macias, J., Camacho, A., Prevalence and risk factors for abnormal liver stiffness in HIV-infected patients without viral hepatitis coinfection: Role of didanosine (2010) Antivir Ther, 15, pp. 753-763; Borghi, V., Puoti, M., Mussini, C., Bellelli, S., Angeletti, C., Sabbatini, F., HIV coinfection and antiretroviral therapy enhances liver steatosis in patients with hepatitis C, but only in those infected by HCV genotype other than 3 (2008) Antivir Ther, 13, pp. 1057-1065; Kovari, H., Sabin, C.A., Ledergerber, B., Ryom, L., Worm, S.W., Smith, C., Antiretroviral drug-related liver mortality among HIV-positive persons in the absence of hepatitis B or C virus coinfection: The data collection on adverse events of anti-HIV drugs study (2013) Clin Infect Dis, 56, pp. 870-879; Mocroft, A., Soriano, V., Rockstroh, J., Reiss, P., Kirk, O., De Wit, S., Is there evidence for an increase in the death rate from liver-related disease in patients with HIV? (2005) AIDS, 19, pp. 2117-2125; Marine-Barjoan, E., Saint-Paul, M.C., Pradier, C., Chaillou, S., Anty, R., Michiels, J.F., Impact of antiretroviral treatment on progression of hepatic fibrosis in HIV/hepatitis C virus co-infected patients (2004) AIDS, 18, pp. 2163-2170; Benhamou, Y., Di Martino, V., Bochet, M., Colombet, G., Thibault, V., Liou, A., Factors affecting liver fibrosis in human immunodeficiency virus-and hepatitis C virus-coinfected patients: Impact of protease inhibitor therapy (2001) Hepatology, 34, pp. 283-287; Weber, R., Sabin, C.A., Friis-Moller, N., Reiss, P., El-Sadr, W.M., Kirk, O., Liver-related deaths in persons infected with the human immunodeficiency virus: The D:A:D study (2006) Arch Intern Med, 166, pp. 1632-1641; Qurishi, N., Kreuzberg, C., Luchters, G., Effenberger, W., Kupfer, B., Sauerbruch, T., Effect of antiretroviral therapy on liverrelated mortality in patients with HIV and hepatitis C virus coinfection (2003) Lancet, 362, pp. 1708-1713; Shubber, Z., Calmy, A., Andrieux-Meyer, I., Vitoria, M., Renaud-Thery, F., Shaffer, N., Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: A systematic review and meta-analysis (2013) AIDS, 27, pp. 1403-1412; Phan, V., Thai, S., Choun, K., Lynen, L., Van Griensven, J., Incidence of treatment-limiting toxicity with stavudine-based antiretroviral therapy in Cambodia: A retrospective cohort study (2012) PLoS One, 7, p. e30647; Pascual Pareja, J.F., Camino, A., Larrauri, J., Lopez-Dieguez, M., Montes, M.L., Gonzalez-Garcia, J., Factors associated with hepatic steatosis in human immunodeficiency virus and hepatits C virus coinfected patients (2009) Med Clin (Barc), 132, pp. 208-213; Miller, K.D., Cameron, M., Wood, L.V., Dalakas, M.C., Kovacs, J.A., Lactic acidosis and hepatic steatosis associated with use of stavudine: Report of four cases (2000) Ann Intern Med, 133, pp. 192-196; Bleeker-Rovers, C.P., Kadir, S.W., Van Leusen, R., Richter, C., Hepatic steatosis and lactic acidosis caused by stavudine in an HIVinfected patient (2000) Neth J Med, 57, pp. 190-193; Bekolo, C.E., Sonkoue, C., Djidjou, H., Bekoule, P.S., Kollo, B., Evaluating the utility of early laboratory monitoring of antiretroviral-induced haematological and hepatic toxicity in HIV-infected persons in Cameroon (2014) BMC Infect Dis, 14, p. 519; Kovari, H., Ledergerber, B., Peter, U., Flepp, M., Jost, J., Schmid, P., Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: A nested case-control study (2009) Clin Infect Dis, 49, pp. 626-635; Vispo, E., Moreno, A., Maida, I., Barreiro, P., Cuevas, A., Albertos, S., Noncirrhotic portal hypertension in HIV-infected patients: Unique clinical and pathological findings (2010) AIDS, 24, pp. 1171-1176; Scourfield, A., Jackson, A., Waters, L., Gazzard, B., Nelson, M., The value of screening HIV-infected individuals for didanosinerelated liver disease? (2011) Antivir Ther, 16, pp. 941-942; (2014) Recommendations for A Public Health Approach, , http://www.who.int/hiv/pub/guidelines/arv2013/arvs2013upplement_march2014/en/, WHO. March 2014 supplement to the 2013 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. [Accessed 14 September 2015]; Podlekareva, D., Grint, D., Karpov, I., Rakmanova, A., Mansinho, K., Chentsova, N., Changing utilization of Stavudine (D4T) in HIV-positive people in 2006-2013 in the EuroSIDA cohort (2015) HIV Med, 16, pp. 533-543; Macias, J., Neukam, K., Mallolas, J., Lopez-Cortes, L.F., Carton, J.A., Domingo, P., Liver toxicity of initial antiretroviral drug regimens including two nucleoside analogs plus one nonnucleoside analog or one ritonavir-boosted protease inhibitor in HIV/HCV-coinfected patients (2012) HIV Clin Trials, 13, pp. 61-69; Chu, K.M., Boulle, A.M., Ford, N., Goemaere, E., Asselman, V., Van Cutsem, G., Nevirapine-associated early hepatotoxicity: Incidence, risk factors, and associated mortality in a primary care ART programme in South Africa (2010) PLoS One, 5, p. e9183; Dieterich, D.T., Robinson, P.A., Love, J., Stern, J.O., Drug-induced liver injury associated with the use of nonnucleoside reversetranscriptase inhibitors (2004) Clin Infect Dis, 38, pp. S80-S89; Vogel, M., Rockstroh, J.K., Hepatotoxicity and liver disease in the context of HIV therapy (2007) Curr Opin HIV AIDS, 2, pp. 306-313; Mikl, J., Sulkowski, M.S., Benhamou, Y., Dieterich, D., Pol, S., Rockstroh, J., Hepatic profile analyses of tipranavir in Phase II and III clinical trials (2009) BMC Infect Dis, 9, p. 203; Spagnuolo, V., Gentilini, G., De Bona, A., Galli, L., Uberti-Foppa, C., Soldarini, A., Liver function parameters in HIV/HCV coinfected patients treated with amprenavir and ritonavir and correlation with plasma levels (2007) New Microbiol, 30, pp. 279-282; Kowalska, J.D., Friis-Moller, N., Kirk, O., Bannister, W., Mocroft, A., Sabin, C., The coding causes of death in HIV (CoDe) project: Initial results and evaluation of methodology (2011) Epidemiology, 22, pp. 516-523; Friis-Moller, N., Sabin, C.A., Weber, R., D'Arminio Monforte, A., El-Sadr, W.M., Reiss, P., Combination antiretroviral therapy and the risk of myocardial infarction (2003) N Engl J Med, 349, pp. 1993-2003; Lo Re, V., III, Kallan, M.J., Tate, J.P., Localio, A.R., Lim, J.K., Goetz, M.B., Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: A cohort study (2014) Ann Intern Med, 160, pp. 369-379; Lo, R.V., Kallan, M., Tate, J., Localio, R., Lim, J., Goetz, M., Determinants of hepatic decompensation in ARV-treated HIV/ hepatitis C virus co-infected patients: Atlanta, Georgia, USA (2013) CROI; Moyle, G., Toxicity of antiretroviral nucleoside and nucleotide analogues: Is mitochondrial toxicity the only mechanism? (2000) Drug Saf, 23, pp. 467-481; Walker, U.A., Bauerle, J., Laguno, M., Murillas, J., Mauss, S., Schmutz, G., Depletion of mitochondrial DNA in liver under antiretroviral therapy with didanosine, stavudine, or zalcitabine (2004) Hepatology, 39, pp. 311-317; Kosi, L., Reiberger, T., Payer, B.A., Grabmeier-Pfistershammer, K., Strassl, R., Rieger, A., Five-year on-treatment efficacy of lamivudine-, tenofovir-and tenofovir R emtricitabine-based HAART in HBV-HIV-coinfected patients (2012) J Viral Hepat, 19, pp. 801-810; Kovari, H., Sabin, C., Ledergerber, B., Ryom, L., Monforte, A., Law, M., Antiretroviral drugs associated with chronic ALT elevations in persons withouy HCV and HBV infection: Seattle, Washington, USA (2015) CROI; Qayyum, S., Dong, H., Kovacic, D., Sohail, S., Waters, B., Thornton, C., Combination therapy efavirenz/emtricitabine/tenofovir disoproxil fumarate associated with hepatic failure (2012) Curr Drug Saf, 7, pp. 391-393; Lattuada, E., Lanzafame, M., Carolo, G., Gottardi, M., Concia, E., Vento, S., Does tenofovir increase efavirenz hepatotoxicity? (2008) AIDS, 22, p. 995; Kohler, J.J., Hosseini, S.H., Hoying-Brandt, A., Green, E., Johnson, D.M., Russ, R., Tenofovir renal toxicity targets mitochondria of renal proximal tubules (2009) Lab Invest, 89, pp. 513-519; (2001) Drug Approval Package VIREAD (Tenofovir Disoproxil Fumarate) Tablets, , http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-356_Viread.cfm, FDA. [Accessed 14 September 2015]; Wood, R., Gathe, J.C., Givens, N., Sedani, S., Cheng, K., Sievers, J., Long-term safety study of fosamprenavir-containing regimens in HIV-1-infected patients (2013) HIV Clin Trials, 14, pp. 183-191; Summary of Product Characteristics, , http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000264/WC500022929.pdf, Amprenavir package leaflet. [Accessed 14 September 2015]; Esposito, V., Verdina, A., Manente, L., Spugnini, E.P., Viglietti, R., Parrella, R., Amprenavir inhibits the migration in human hepatocarcinoma cell and the growth of xenografts (2013) J Cell Physiol, 228, pp. 640-645; Seminari, E., De Bona, A., Gentilini, G., Galli, L., Schira, G., Gianotti, N., Amprenavir and ritonavir plasma concentrations in HIV-infected patients treated with fosamprenavir/ritonavir with various degrees of liver impairment (2007) J Antimicrob Chemother, 60, pp. 831-836
PY - 2016/7
Y1 - 2016/7
N2 - Objectives: Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. Design: Prospective cohort study. Methods: Data collection on adverse events of anti-HIV drugs study (D:A:D) participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or α-fetoprotein along with imaging), death, 6 months after last visit or 1 February 2014. Associations between ESLD/HCC and cumulative use of individual antiretrovirals were investigated using Poisson regression adjusting for potential confounders. Results: During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred [incidence 1.01/1000 person-years (95% confidence interval 0.90-1.12)] with a 1-year mortality rate of 62.6%. After adjustment, cumulative (per 5 years) exposure to d4T [relative rate 1.46 (95% confidence interval 1.20-1.77)], ddI [1.32 (1.07-1.63)], tenofovir [TDF, 1.46 (1.11-1.93)] and (fos)amprenavir [APV; 1.47 (1.01-2.15)] was associated with increased ESLD/HCC rates. Longer exposure to emtricitabine [0.51 (0.32-0.83)] and nevirapine [0.76 (0.58-0.98)] were associated with lower ESLD/HCC rates. The ddI/d4T-associated increased ESLD/HCC rate only started to decline 6 years after cessation. Conclusion: Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered among all individuals exposed for longer time periods. The use of d-drugs should furthermore be avoided, where there are alternatives available, and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis-independent, TDF association calls for further investigations. © Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
AB - Objectives: Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. Design: Prospective cohort study. Methods: Data collection on adverse events of anti-HIV drugs study (D:A:D) participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or α-fetoprotein along with imaging), death, 6 months after last visit or 1 February 2014. Associations between ESLD/HCC and cumulative use of individual antiretrovirals were investigated using Poisson regression adjusting for potential confounders. Results: During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred [incidence 1.01/1000 person-years (95% confidence interval 0.90-1.12)] with a 1-year mortality rate of 62.6%. After adjustment, cumulative (per 5 years) exposure to d4T [relative rate 1.46 (95% confidence interval 1.20-1.77)], ddI [1.32 (1.07-1.63)], tenofovir [TDF, 1.46 (1.11-1.93)] and (fos)amprenavir [APV; 1.47 (1.01-2.15)] was associated with increased ESLD/HCC rates. Longer exposure to emtricitabine [0.51 (0.32-0.83)] and nevirapine [0.76 (0.58-0.98)] were associated with lower ESLD/HCC rates. The ddI/d4T-associated increased ESLD/HCC rate only started to decline 6 years after cessation. Conclusion: Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered among all individuals exposed for longer time periods. The use of d-drugs should furthermore be avoided, where there are alternatives available, and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis-independent, TDF association calls for further investigations. © Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
KW - (fos)amprenavir
KW - d-drugs
KW - end-stage liver disease
KW - hepatocellular carcinoma
KW - hepatotoxicity
KW - HIV
KW - tenofovir
KW - alpha fetoprotein
KW - didanosine
KW - emtricitabine
KW - fosamprenavir
KW - nevirapine
KW - stavudine
KW - antiretrovirus agent
KW - adult
KW - Article
KW - CD4 lymphocyte count
KW - cohort analysis
KW - drug exposure
KW - end stage liver disease
KW - esophagus varices bleeding
KW - female
KW - follow up
KW - hepatic encephalopathy
KW - hepatorenal syndrome
KW - highly active antiretroviral therapy
KW - human
KW - Human immunodeficiency virus infected patient
KW - Human immunodeficiency virus infection
KW - liver cell carcinoma
KW - liver histology
KW - liver transplantation
KW - major clinical study
KW - male
KW - mortality
KW - priority journal
KW - prognosis
KW - prospective study
KW - sensitivity analysis
KW - survival
KW - chemically induced
KW - complication
KW - liver tumor
KW - middle aged
KW - risk assessment
KW - Adult
KW - Anti-Retroviral Agents
KW - Carcinoma, Hepatocellular
KW - End Stage Liver Disease
KW - Female
KW - HIV Infections
KW - Humans
KW - Liver Neoplasms
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - Risk Assessment
UR - http://www.ncbi.nlm.nih.gov/pubmed/26752282
U2 - 10.1097/QAD.0000000000001018
DO - 10.1097/QAD.0000000000001018
M3 - Article
C2 - 26752282
VL - 30
SP - 1731
EP - 1743
IS - 11
ER -