1 / 17

1 Kaiser Permanente Southern California, Los Angeles, CA, USA 2 Kaiser Permanente Southern California, Pasadena, CA, U

Fatal and Non-fatal Hepatic Failure in HIV-infected versus HIV-uninfected Persons Enrolled in Kaiser Permanente California (KP), a Large Managed Care Organization.

edric
Download Presentation

1 Kaiser Permanente Southern California, Los Angeles, CA, USA 2 Kaiser Permanente Southern California, Pasadena, CA, U

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Fatal and Non-fatal Hepatic Failure in HIV-infected versus HIV-uninfected Persons Enrolled in KaiserPermanente California (KP), a Large Managed Care Organization William J. Towner1, Lanfang Xu2, Michael J. Silverberg3, Wendy A. Leyden3, Chun R. Chao2, Beth Tang2, Daniel Klein4, Leo Hurley3, Charles P. Quesenberry, Jr.3, , Michael A. Horberg3. 1 Kaiser Permanente Southern California, Los Angeles, CA, USA 2 Kaiser Permanente Southern California, Pasadena, CA, USA 3 Kaiser Permanente Northern California, Oakland, CA, USA 4 Kaiser Permanente Nothern California, Hayward, CA, USA Towner et al. Abstract # TUAB0102

  2. Background • Hepatic toxicity is commonly described in HIV infected persons. • Possible mechanisms: chronic viral hepatitis, alcohol or other drug abuse, opportunistic infections, antiretroviral therapy, or other liver diseases • Toxicity commonly defined as elevated transaminases which may not accurately prognosticate subsequent hepatic failure • Less data exists on fulminate hepatic failure (HF), either fatal or nonfatal, when comparing HIV+ persons to HIV- persons. Castellares et al. J Viral Hepat. 2008 Mar;15(3):165-72. Pol et al. Clin Infect Dis. 2004 Mar 1;38 Suppl 2:S65-72.

  3. Study Objectives • Assess whether HIV status is independently associated with increased risk of hepatic failure or hepatic related death • Assess difference in risk by recent CD4 levels • Assess difference in risk by use of antiretroviral therapy • Determine if other factors contribute to hepatic failure or hepatic related death

  4. Methods • Setting • Kaiser Permanente (KP), large integrated healthcare system in California, USA • Design • Cohort study, 1996 - 2007 • Study population • Adult HIV+ and HIV- matched 1:10 by age, sex, year, medical center, index year • Data sources • KP HIV registries, clinical databases, state/national death files

  5. Analysis • Fatal HF: primary or secondary liver related cause of death, or deaths preceded by a recent diagnosis of hepatic failure • Nonfatal HF: hepatic failure, hepatic encephalopathy, or bleeding esophageal varicies OR 2/3 lab elevations: ammonia (≥ ULN), INR (≥ 1.2, not on warfarin) & AST/ALT (≥ 5x ULN). • Followed until hepatic failure (fatal or nonfatal), death, lost KP membership, or end of study period • Cox regression modeling

  6. Study Population

  7. Study Population (2)

  8. Study Population (3)

  9. Fatal and Nonfatal HFHIV+ vs. HIV-

  10. Fatal and Nonfatal HFRecent CD4 0.33 0.51 Hazard Ratios adjusted for age, sex, race, smoking, alcohol/drug abuse, hepatitis B/C, hypertension, diabetes, lipid lowering medications Hazard ratio *p < 0.001 **p < 0.05

  11. Fatal and Nonfatal HFMedication Class p = Not Significant for both Fatal and Nonfatal HF

  12. Fatal and Nonfatal HFDuration ART Use (unadjusted incidence rates)† †Cases per 100,000 person-years Includes data through 31DEC2008

  13. Fatal and Nonfatal HFAdjusted Hazard Ratios for Selected Risk Factors in HIV+ (All combined data for Fatal + Nonfatal)† †Includes data through 31DEC2008. Factors not associated with elevated risk: sex, race/ethnicity, hypertension, obesity, and lipid lowering drug use.

  14. Discussion • Hepatic Failure: • Association with recent CD4 suggests hepatic failure risk is at least partially immune related • Earlier treatment with antiretrovirals may reduce risk by preventing CD4 decline • Antiretrovirals: • Antiretrovirals did not increase hepatic failure or hepatic related death rate • No antiretroviral class or duration effect was noted

  15. Strengths and Limitations • Strengths • HIV+ and HIV- from same health system • Large and population-based • Comprehensive HIV registries • Adjustment for hepatic failure risk factors • Limitations • Imperfect measurement of risk factors • No information on pathologic diagnosis for hepatic failure/death • Newer HIV medication classes (integrase inhibitors, CCR5 antagonists) not studied

  16. Conclusions • Hepatic Failure: • Adjusted risk for both hepatic failure and death increased in HIV+ vs. HIV– persons • No significant gender differences were noted • Risk lower in the more recent ART era • Increase risks In HIV+ include: • low CD4 cell count (recent and nadir), • high HIV RNA, • alcohol/drug abuse, • hepatitis B/C co-infection • diabetes • Antiretroviral therapy not associated with risk

  17. Acknowledgements • Kaiser Permanente Southern California Lanfang Xu, Chun Chao, Beth Tang, Hai Linh Kerrigan, Wansu Chen • Kaiser Permanente Northern California Wendy Leyden, Michael Silverberg, Michael Horberg, Leo Hurley, Charles Quesenberry, Jr., Amanda Charbonneau, Daniel Klein • Funding sources: Pfizer • Kaiser Permanente patients and providers

More Related