1 / 38

HIV and Viral Hepatitis (B & C) H. Nina Kim, MD MSc University of Washington July 9, 2009

HIV and Viral Hepatitis (B & C) H. Nina Kim, MD MSc University of Washington July 9, 2009. 36 yo man to establish care. HIV infection: Risk factor: unprotected heterosexual sex. Dx 2004 with CD4 155, HIV RNA 222,000. No hx OIs. Started Combivir & Efavirenz 9/2004

zaza
Télécharger la présentation

HIV and Viral Hepatitis (B & C) H. Nina Kim, MD MSc University of Washington July 9, 2009

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. HIV and Viral Hepatitis (B & C) H. Nina Kim, MD MSc University of Washington July 9, 2009

  2. 36 yo man to establish care • HIV infection: Risk factor: unprotected heterosexual sex. Dx 2004 with CD4 155, HIV RNA 222,000. No hx OIs. • Started Combivir & Efavirenz 9/2004 • Switched to Atripla in Jan 2007 • Chronic hepatitis B • Started on adefovir Jan 2007 • Normal alpha-fetoprotein, abdominal ultrasound March 2007 • PMH otherwise notable for: • BRBPR – negative EGD/colonoscopy; attributed to hemorrhoids • Hypertriglyciridemia

  3. Additional Hx Medications • Truvada • Efavirenz • Omeprazole • Gemfibrozil Soc Hx Works as cleaner in Chinese restaurant. Born in Mexico; immigrated to US 15 yrs ago. Lives with several coworkers in hotel. Smokes 2 cigs per day. Used cocaine 1 mon ago. Rare EtOH.

  4. PEx & Labs T 36.3 C, 117/66, HR 84, RR 20 Wt 68.5 kg Well-appearing young Latino in NAD. Exam normal; no stigmata of cirrhosis; no palpable hepatosplenomegaly. Hep B surface Ag positive, HB surface Ab negative, HBV core Ab+, HAV Ab+, HBV Ab negative. CD4 375/28%, HIV RNA <30 copies/mL. HBV PCR 240,000 IU/mL – no prior values available. ALT 42, AST 30, alk phos 91. Normal total bilirubin & albumin.

  5. Questions • Does this patient need treatment for chronic hepatitis B? • How would you risk stratify this patient? • If tx, what agent(s) would you use? • What is natural hx in this HIV-HBV coinfected patient? • Special considerations esp re HAART • Does this patient need screening for HCC?

  6. Chronic Hepatitis B:Epidemiology • Definition: HBsAg+ for >6 months • US – Low endemic • Most infections occur in adolescents, young adults • Sexual transmission > percutaneous • Asia – High endemic • Perinatal transmission predominates • Genotypes B, C • Africa – Intermediate to High endemic • Childhood • Vertical transmission less important role (possibly b/c lower prevalence of HBeAg+ mothers)

  7. Chronic HBV: Worldwide prevalence www.cdc.gov

  8. www.hepwebstudy.com

  9. Chronic Hepatitis B:Stage the infection

  10. Chronic Hepatitis B & HIV:Epidemiology & Natural Hx • Prevalence 6-17% depending on population • Consequences of coinfection: • Higher risk of developing chronic hepatitis B when exposed (estimated 5X greater c/w HIV-unininfected) • Higher HBV viremia  higher risk of reactivation & transmission • Higher rates of disease progression w/ adverse outcomes, i.e. cirrhosis • Poorer response to standard therapies? • Increased risk of HAART-related hepatoxicity Colin JF, et al. Hepatology. 1999;29:1306-1310. Puoti M, et al. AIDS Rev. 2002;4:27-35. Hadler SC, et al. J Infect Dis. 1991;163:454-459.

  11. HBV DNA Associated With Increased Risk of HCC & Cirrhosis REVEAL: Long-term follow-up of untreated HBsAg+ individuals in Taiwan 50 Cumulative Incidence of HCC at Year 13 Follow-up[1] (N = 3653) Cumulative Incidence of Cirrhosis at Year 13 Follow-up[2] (N = 3582) 40 36.2 30 23.5 Patients (%) 20 14.9 12.2 9.8 10 5.9 4.5 3.6 1.4 1.3 0 < 300 < 300 100,000- 999,999 ≥ 1 million 300- 999 1000- 9999 10,000- 99,999 300- 9999 ≥ 100,000 10,000- 99,999 Baseline HBV DNA (copies/mL) 1. Chen CJ, et al. JAMA. 2006;295:65-73. 2. Iloeje UH, et al. Gastroenterology. 2006;130:678-686.

  12. Risk of Liver-related Mortality among MSM in MACS Cohort 14.2 1.7 0.8 Thio, et. al. Lancet 2002; 360: 1921-26.

  13. Treatment End-points for HIV-uninfected chronic Hep B • HBeAg seroconversion to anti-Hbe (if eAg+) • Spontaneous in HIV-negative pt: 8-12% per yr • Treatment-associated rate: 15-27% • HBV DNA suppression: ideally, complete (prior threshold goal <20,000 IU/mL) • ALT normalization • HBsAg loss & seroconversion These pts need to be monitored after tx discontinued: q6 mon ALT, annual HBV DNA. 30% over 10 years can reactivate viral replication. So what about HIV-infected?

  14. Treatment of HBV in HIV+ Patient • Interferon (standard or pegylated) • Pros: HBsAb loss, short duration, no drug resistance • Cons: SC, freq adverse effects, HBeAg seroconversion rate lower than in HIV-negative population (11.5% vs. 28%) • Lamivudine • Use in ESLD, pregnant women • High rate resistance (~20%/yr  approaches 100% x 5 yr if only anti-HBV drug) • Adefovir • Use in ESLD • Drug resistance: delayed, less common than 3TC • Entecavir • Potent • Drug resistance rare in nucleoside-naïve pt (<1% in 4 yrs), higher if treatment-experienced (14% at year 2) • Telbivudine • Drug resistance: intermediate (~22% at year 2). • Category B pregnancy • Tenofovir • Potent with high genetic barrier for HBV resistance

  15. Antiviral agents active against HBV • Lamivudine (3TC) or Emtricitabine (FTC) • Adefovir (ADF) • Entecavir (ETV) • Telbivudine (LDT) • Tenofovir (TDF) … & HIV

  16. Lamivudine (3TC) Resistance in HIV-HBV infected patients on 3TC monotherapy Matthews, AIDS 2006. 20:863-870.

  17. Treatment of HBV in HIV+ Patient

  18. Combination Therapy • Not yet the paradigm the way it is for HIV infection • Dual nucleos/tide analogues: more widely used in • Cirrhotic patients • HIV-coinfected patients • s/p OLT after HBV infection • Combination Peg-IFN & lamivudine – results disappointing • No additional efficacy c/w Peg-IFN alone

  19. HCC Screening for HBV+ Pts • Asian males >40 years • Asian females >50 years • All cirrhotic hepatitis B carriers (stage 3+ fibrosis) • Family history of HCC • Africans over age 20 • Other risks – severity of liver disease as measured by current & hx inflammation, esp +ongoing HBV viremia, ?coinfection HCV, alcohol AASLD Practice Guidelines 2005, Hepatology 42(5): 1208.

  20. Sensitivity of AFP >20 is 60% PPV = 41% Still see false positives with this cutoff Cutoff = 20 ng/ml Alpha-fetoprotein: Imperfect screening tool for HCC

  21. CONTEST: Most Interesting Dermatology Case • Submit a dermatology case by Friday, July 24 using the case referral form • Instructions will be sent in a follow-up email • Dr Roy Colven will be the judge and announce the winner during his session on July 30 • The winner will receive a 2 GB I-TECH thumb drive!

  22. 42 yo woman with remote hx IVDU • HIV Hx: • Dx 1996, nadir CD4 120 • Has been undetectable on Kaletra + Combivir x several years, most recent CD4 250 (25%) • Tested positive for HCV Ab • Hx of alcohol & heroin dependence • Hx depression with psychotic features • PEx: T 37 BP 104/80 HR 86 RR 12 • Well-appearing woman, alert & conversant • No stigmata of advanced liver disease (No spider telangiectasia, palmar erythema, scleral icterus, abd distension, no appreciable HSM

  23. Lab Data • ALT 35-45, AST 25-35 • Normal alk phos, total bilirubin, serum albumin • HCV RNA 2.8 million IU/mL • HCV genotype 1a • Hepatitis A & B immune • CBC: WBC 3.5, Hgb 11.0, Hct 35% with MCV 110, platelets 160K.

  24. Chronic Hep C & HIVEpidemiology • 1/4 to 1/3 of HIV-infected pts in US & Europe are coinfected with chronic hepatitis C • Much higher prevalence (75%) in high-risk groups with hx blood exposure: IVDU & hemophiliacs • HCV one of the major causes of morbidity & mortality in HIV-infected pts • More rapid disease progression • Higher risk of hepatotoxicity from HAART Rockstroh, J Infect Dis. 2005; 192:992-1002. Pol, Clin Infect Dis. 2008; 47: 94-101.

  25. Factors to ConsiderTo Treat or not Treat? • HIV-related • CD4 count • Antiretroviral therapy • Liver-related • HCV genotype • Liver enzymes? • Histology • Other • Neuropsychiatric history • Substance dependence & Alcohol consumption

  26. Normal ALTLess Predictive of Benign Histology in HIV-HCV Coinfected patients Percentage of patients with grade 3-4 necroinflammation Gonzalez, et. al. J Acquir Immune Defic Syndr. 2006; 41(5): 582-9.

  27. HCV Treatment & Risk of Mitochondrial Toxicity Odds Ratio (95%CI) • US FDA Adverse Event Reporting 2002 • 31 patients had 58 events c/w MT: • Pancreatitis • Lactic acidosis • Elevated LFTs • Hepatic steatosis • Elevated CK • Neuropathy Ribavirin + ddI ddI + d4T d4T ABC 3TC AZT 12.4 8.0 3.3 1.1 0.2 0.06 0.01 0.1 1.0 10 100 Fleischer, R. Clin Infect Dis. 2004; 38: e79-80.

  28. Anemia & HCV TreatmentRole of AZT • AZT use associated with higher incidence of anemia in 1st 12 wks • Not associated with lower rates of EVR or higher rates of tx discontinuation Alvarez, D. J Viral Hepat. 2006; 13(10):683-9.

  29. Current Standard Therapies for HIV-HCV coinfected pts • Peg-IFN + RBV more effective than standard IFN + RBV combination or peg-IFN alone • Genotype 1, 2, 3 or 4 • Peg-IFN + RBV 1000 mg/day if wt <75 kg or 1200 mg/day if wt >75 kg → 48 weeks • Goal of treatment is sustained virologic response (SVR) defined as • No detectable serum HCV RNA 24 weeks after the end of treatment • Tested using sensitive HCV RNA assay with lower limit of detection of 50 IU/mL

  30. Definitions of Virologic Response on HCV Treatment

  31. Percentage of HIV-HCV patients achieving treatment response

  32. Clinical Trials of HIV-HCV Coinfected

  33. Pegylated InterferonSide Effects

  34. Reality of Treating HIV-HCV Coinfected Pts: Few eligible Fleming, et. al. Clin Infect Dis 2003; 36:99-101.

  35. Questions?

  36. Next session: July 30, 2009 Dr. Roy Colven HIV Dermatology: Virtual Office Hours

  37. Next session: July 30, 2009 Listserv: itechdistlearning@u.washington.edu Email: DLinfo@u.washington.edu

More Related