Skip to main content

Advertisement

Log in

The Prevalence and Risk Factors for Abnormal Liver Enzymes in HIV-Positive Patients without Hepatitis B or C Coinfections

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background Abnormal liver enzymes (LFTs) are frequently seen in HIV patients. Because HCV and HBV overshadow other possible variables, little is known about the prevalence and predictive factors of abnormal LFTs in the absence of viral hepatitis. Aims To determine the prevalence and factors associated with abnormal LFTs defined as >1.25 ULN. Methods A retrospective analysis of HIV clinic patients was performed. Variables were determined at the time of abnormal LFTs or by history and included diabetes mellitus (DM), hypertension (HTN), dyslipidemia, HCV and HBV status, metabolic syndrome (MS), and HAART use (NRTI, NNRTI, and PI). Results Patients without HCV/HBV (n = 679/1,208) were younger, Caucasian, had a BMI >30 and had dyslipidemia. The prevalences of elevated LFTs in those without HCV/HBV were AST 20%, ALT 15%, and ALP 43% compared to 64%, 46%, and 63% in those with HCV (all P < 0.0001), and 98% were mild-moderate (grade 1–2). While AST was highly correlated with ALT, neither was associated with increased ALP. In those without HCV/HBV, increased AST was associated with HTN, HIV RNA, and absence of PI use; increased ALT was associated with HTN, HIV RNA, CD4 < 200, MS, and absence of PI use, while increased ALP was associated with age, BMI, CD4%, DM, and NRTI use. Conclusions Mild-moderate increased liver enzymes are common in HIV patients without HCV/HBV and absence of PI use is independently associated with elevations in both AST and ALT, while features typical of hepatic steatosis (DM and BMI) are only associated with increased ALP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

LFTs:

Liver function tests

HIV:

Human immunodeficiency virus

HCV:

Hepatitis C virus

HBV:

Hepatitis B virus

ULN:

Upper limits of normal

DM:

Diabetes mellitus

IR:

Insulin resistance

HTN:

Hypertension

MS:

Metabolic syndrome

HAART:

Highly active antiretroviral therapy

NRTI:

Nucleoside/tide reverse transcriptase inhibitor

NNRTI:

Non-nucleoside reverse transcriptase inhibitor

PI:

Protease inhibitor

RNA:

Ribonucleic acid

BMI:

Body mass index

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

ALP:

Alkaline phosphatase

MLR:

Multivariate logistic regression

AZT:

Zidovudine

LAM:

Lamivudine

ddI:

Didanosine

d4T:

Stavudine

FTC:

Emtricitobine

ABAC:

Abacavir

EFV:

Efavirenz

NVP:

Nevirapine

LOP:

Lopinavir

NEL:

Nelfinavir

AMP:

Amprinavir

ATZ:

Atazanavir

RIT:

Ritonavir

IND:

Indinavir

References

  1. Lee LM, Karon JM, Selik R, Neal JJ, Fleming PL (2001) Survival after AIDS diagnosis in adolescents and adults during the treatment era, United States, 1984–1997. JAMA 285(10):1308–1315

    Article  PubMed  CAS  Google Scholar 

  2. Palella FJ Jr., Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA et al (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338(13):853–860

    Article  PubMed  Google Scholar 

  3. Pol S, Lebray P, Vallet-Pichard A (2004) HIV infection and hepatic enzyme abnormalities: intricacies of the pathogenic mechanisms. Clin Infect Dis 38(Suppl 2):S65–S72

    Article  PubMed  CAS  Google Scholar 

  4. Sabin CA (2004) Pitfalls of assessing hepatotoxicity in trials and observational cohorts. Clin Infect Dis 38(Suppl 2):S56–S64

    Article  PubMed  Google Scholar 

  5. Sulkowski MS, Mehta SH, Chaisson RE, Thomas DL, Moore RD (2004) Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir. AIDS 18(17):2277–2284

    Article  PubMed  CAS  Google Scholar 

  6. Meraviglia P, Schiavini M, Castagna A, Vigano P, Bini T, Landonio S et al (2004) Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation. HIV Med 5(5):334–343

    Article  PubMed  CAS  Google Scholar 

  7. Kottilil S, Polis MA, Kovacs JA (2004) HIV Infection, hepatitis C infection, and HAART: hard clinical choices. JAMA 292(2):243–250

    Article  PubMed  CAS  Google Scholar 

  8. Armstrong GL, Wasley A, Simard EP, McQuillan GM et al (2006) The prevalence of hepatitis C virus infection in the United States, 1999–2002. Ann Intern Med 144:705–714

    PubMed  Google Scholar 

  9. Rockstroh JK, Mocroft A, Soriano V, Tural C et al (2005) Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiviral therapy. J Infect Dis 192:992–1002

    Article  PubMed  Google Scholar 

  10. Maida I, Nunez M, Rios MJ, Martin-Carbonero L, Sotgiu G et al (2006) Severe liver disease associated with prolonged exposure to antiretroviral drugs. JAIDS 42:177–182

    PubMed  CAS  Google Scholar 

  11. Puoti M, Torti C, Ripamonti D, Castelli F, Zaltron S, Zanini B et al (2003) Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome. J Acquir Immune Defic Syndr 32(3):259–267

    Article  PubMed  Google Scholar 

  12. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD (2000) Elevated liver enzymes following initiation of antiretroviral therapy. JAMA 283(19):2526–2527

    Article  PubMed  Google Scholar 

  13. French AL, Benning L, Anastos K, Augenbraun M, Nowicki M, Sathasivam K et al (2004) Longitudinal effect of antiretroviral therapy on markers of hepatic toxicity: impact of hepatitis C coinfection. Clin Infect Dis 39(3):402–410

    Article  PubMed  CAS  Google Scholar 

  14. Maddrey WC (2005) Drug-induced hepatoxicity. J Clin Gastroenterol 39(Suppl 2):S83–S89

    Article  PubMed  Google Scholar 

  15. Neff GW, Jayawerra D, Sherman KE (2006) Drug-induced liver injury in HIV patients. Gastroenterol Hepatol 2:430–437

    Google Scholar 

  16. Pantsari MW, Harrison SA (2006) Nonalcoholic fatty liver disase presenting with an isolated elevated alkaline phosphatase. J Clin Gastroenterol 40:633–635

    Article  PubMed  CAS  Google Scholar 

  17. Bjornsson E, Olsson R (2005) Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 42:481–489

    Article  PubMed  CAS  Google Scholar 

  18. Andrade RJ, Lucena MI, Fernandez MC, Pelaez G, Pachkoria K, Garcia-Ruiz E, Garcia-Munoz B, Gonzalez-Grande R et al (2005) Drug-induced liver injury: An analysis of 461 incidences submitted to the Spanish Registry over a 10-year period. Gastroenterology 129:512–521

    PubMed  Google Scholar 

  19. Ioannou GN, Weiss NS, Boyko EJ, Kahn SE, Lee SP (2005) Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease. Gastroenterology 128:627–635

    Article  PubMed  CAS  Google Scholar 

  20. Rodriguez-Rosado R, Perez-Olmeda M, Garcia-Samaniego J, Soriano V (2001) Management of hepatitis C in HIV-infected persons. Antiviral Res 52(2):189–198

    Article  PubMed  CAS  Google Scholar 

  21. Carr A (2000) HIV protease inhibitor-related lipodystrophy syndrome. Clin Infect Dis 30(Suppl 2):S135–S142

    Article  PubMed  CAS  Google Scholar 

  22. Hui DY (2003) Effects of protease inhibitor therapy on lipid metabolism. Prog Lipid Res 42:81–92

    Article  PubMed  CAS  Google Scholar 

  23. Carr A, Samaras K, Thorisdottir A, Kaufmann GR et al (1999) Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidemia, and diabetes mellitus: a cohort study. Lancet 353:2093–2099

    Article  PubMed  CAS  Google Scholar 

  24. Stein JH (2003) Dyslipidemia in the era of HIV protease inhibitors. Prog Cardiovasc Dis 45:293–304

    PubMed  CAS  Google Scholar 

  25. Tsiodras S, Mantzoros C, Hammer S, Samore M (2000) Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy. Arch Intern Med 160:2050–2056

    Article  PubMed  CAS  Google Scholar 

  26. Mulligan K, Grundfeld C, Tai VW, Algren H et al (2000) Hyperlipidemia and insulin rsistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. JAIDS 23:35–43

    PubMed  CAS  Google Scholar 

  27. Nolan D, Mallal S (2001) Getting to the HAART of insulin resistance. AIDS 15(15):2037–2041

    Article  PubMed  CAS  Google Scholar 

  28. Sulkowski MS, Mehta SH, Torbenson M, Afdhal NH, Mirel L, Moore RD et al (2005) Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS 19(6):585–592

    Article  PubMed  Google Scholar 

  29. Bani-Sadr F, Carrat F, Bedossa P, Piroth L et al (2006) Hepatic steatosis in HIV-HCV coinfected patients: analysis of risk factors. AIDS 20:525–531

    Article  PubMed  Google Scholar 

  30. Kakuda TN (2000) Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther 22:685–708

    Article  PubMed  CAS  Google Scholar 

  31. Benhamou Y, Di MV, Bochet M, Colombet G, Thibault V, Liou A et al (2001) Factors affecting liver fibrosis in human immunodeficiency virus- and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy. Hepatology 34(2):283–287

    Article  PubMed  CAS  Google Scholar 

  32. Macias J, Castellano V, Merchante N, Palacios RB, Mira JA et al (2004) Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine. AIDS 18:767–774

    Article  PubMed  CAS  Google Scholar 

  33. Zhou H, Gurley EC, Jarujaron S, Ding H, Fang Y, Xu Z, Pandak WM, Hyleman PB (2006). HIV protease inhibitors activate the unfolded protein response, disrupt lipid metabolism in primary hepatocytes. Am J Physiol Gastrointest Liver Physiol. doi:10.1152/ajpgi.00182.2006

  34. Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ (2003) Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37:1286–1292

    Article  PubMed  Google Scholar 

  35. Sánchez-Conde M, Berenguer J, Miralles P, Alvarez F, Carlos Lopez J, Cosin J, Pilar C, Ramírez M, Gutierrez I, Alvarez E (2006) Liver biopsy findings for HIV-infected patients with chronic hepatitis c and persistently normal levels of alanine aminotransferase. Clin Infect Dis 43:640–644

    Article  PubMed  Google Scholar 

  36. Urial A, Moorehead L, Agarwal K et al (2005). Insulin resistance associated with poorer HCV virologic response in HCV/HIV coinfected patients. Program and abstracts of the 12th conference on retroviruses and opportunistic infections, Boston, MA, February 22–25, 2005, Abstract 925

  37. Monto A, Dove LM, Bostrom A, Kakar S, Tien PC, Wright TL (2005) Hepatic steatosis in HIV/hepatitis C coinfection: prevalence and significance compared with hepatitis C monoinfection. Hepatology 42(2):310–316

    Article  PubMed  Google Scholar 

  38. Marks KM, Petrovic LM, Talal AH, Murray MP et al (2005) Histologic findings and clinical characteristics associated with hepatic steatosis in patients coinfected with HIV and hepatitis C virus. J Infect Dis 192:1943–1949

    Article  PubMed  Google Scholar 

  39. Lapoile E, Vona G, Canioni D, Chaix M-L, Nalpas B, Fontaine C et al (2002). Factors participating in severe HCV-related liver disease in HIV/HCV coinfection. J Hepatol 36(Suppl 1):172 (Abstract 609)

    Google Scholar 

  40. Wanless IR, Lentz JS (1990) Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12(5):1106–1110

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant to RKS (K23 DK064578).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard K. Sterling.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sterling, R.K., Chiu, S., Snider, K. et al. The Prevalence and Risk Factors for Abnormal Liver Enzymes in HIV-Positive Patients without Hepatitis B or C Coinfections. Dig Dis Sci 53, 1375–1382 (2008). https://doi.org/10.1007/s10620-007-9999-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-007-9999-6

Keywords

Navigation