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Hepatitis C in HIV

Hepatitis C in HIV. Ronald D. Wilcox MD FAAP Program Director/PI, Delta AETC Asst Professor of Internal Medicine and Pediatrics, Section of Infectious Diseases Louisiana State University Health Sciences Center. www.deltaaetc.org. 504-903-0788. LPS Coordinator: Dana Gray. Create Unique ID.

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Hepatitis C in HIV

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  1. Hepatitis C in HIV Ronald D. Wilcox MD FAAP Program Director/PI, Delta AETC Asst Professor of Internal Medicine and Pediatrics, Section of Infectious Diseases Louisiana State University Health Sciences Center

  2. www.deltaaetc.org 504-903-0788 LPS Coordinator: Dana Gray

  3. Create Unique ID Please darken the circles completely No check marks, X’s, or other markings Employment Setting Zip code

  4. Disclosure • The speaker receives or has received research support from all companies that make HIV medications in the US now or in the past five years • The speaker is NOT on a speakers bureau for any pharmaceutical company

  5. Polling Question • Please choose which category best describes your profession: • 1. Nurse or Advanced Practice Nurse • 2. Physician or Physician Assistant • 3. Dental professional • 4. Pharmacist • 5. Case Manager / Social Worker • 6. Other medical professional or Administrator

  6. Polling Question • My current knowledge/experience of Hepatitis C in the setting of HIV most closely resembles which of the following: • 1. I know basically nothing about hepatitis C • 2. I know hepatitis C infects the liver but that is all • 3. I take care of many patients with hepatitis C for their HIV but do not do anything with their hepatitis C • 4. I have a good working knowledge of Hepatitis C and have treated some patients in the past • 5. I am an expert in this field and should actually be giving this talk

  7. Case • 37 y/o AA male diagnosed 12 years prior with HIV when his lover tested +. Lowest CD4 per pt had been 179. Placed on CombivirTM and abacavir. • Previous meds: indinavir, ddI, AZT, 3TC, nevirapine, and ritonavir. • PMH: syphilis, pneumonia, and + antibodies for hepatitis C and B (HBsAg neg). • SH: Denied IVDU or tobacco. Incarcerated x 12 years • Lab values: AST 131 ALT 147 AlkPO4 75 plts 92,000 HCV RNA PCR 115,000

  8. Case • Liver biopsy two months after presentation: mild piecemeal necrosis of the parenchyma as well as moderate portal inflammation and bridging fibrosis, compatible with moderate chronic active hepatitis. • 5 months later: acute left hand weakness x 2-3 weeks, facial droop, slurred speech, left foot weakness. MRI consistent with PML; JC virus PCR +. CD4 328, viral load 495.

  9. Case • HAART changed to d4T, ddI, Efavirenz, and Amprenavir. • Began cidofovir 2 doses one week apart then q3w w/ probenecid . • 6th dose: worsening renal and liver function: ALT 158 AST 207 AlkPO4 209 TB 5.0 Creat 1.5

  10. Case • Two months later, after 9 doses of cidofovir: AST 390 ALT 162 AlkPO4 193 TB 10.6 PT 14.9 • Pt reported anorexia, diarrhea, and pruritus. • Efavirenz held. • One month later pt died encephalopathic with ESLD 5 days before his parole hearing date. PT one week prior to death 40.9.

  11. Polling Question • Hepatitis C differs from HIV in all the following ways EXCEPT: • 1. Likelihood of chronicity • 2. Amount of virus production per day in an untreated patient • 3. Ability to integrate into host DNA • 4. Likelihood of cure with therapy • 5. Most common means of transmission when comparing parenteral versus sexual

  12. HIV versus Hepatitis C

  13. HIV/HCV Co-infection in the United States

  14. Risk of HIV, HCV, and HBV in IV Drug Users Garfein et al. Am J Public Health. 1996;86:655-61

  15. Influence of HIV on Sexual Transmission of HCV • Multi-center cross-sectional study to look at hepatitis C antibody positivity among female sexual partners of hemophiliac men • 3% in partners of co-infected men • 0% in partners of HIV negative men Eyster et al. Ann Inter Med. 1991; 115:764-8

  16. Perinatal Transmission • Increase risk factors • Maternal HIV • High maternal HCV viral load • Membrane rupture > 6 hours • Internal fetal monitoring • No increase in breast feeding • ? C-section role ? • Testing: Ab after 15 months

  17. Perinatal TransmissionRole of HCV/HIV Co-infection • HIV Co-infection HCV transmission • HCV only 5% (3-8%) • HIV/HCV 17% (7-36%) • HCV co-infection may HIV transmission • HIV only 16.3% • HIV/HCV 26.1% (RO 1.82) Zanetti et al. Lancet. 1995;345:289-91 Hershow et al. J Infect Dis. 1997;176:414-20

  18. Co-infection HIV Risk Factor Prevalence at Johns Hopkins HIV Clinic N=1742 Sulkowski et al. Hepatology. 2000;32:212A.

  19. Co-infection HIV Risk Factor Prevalence at the HOP clinic N = 402 Data abstracted from the ASD database by Kathleen Welch, PhD

  20. Polling Question • If someone has chronic hepatitis C, their chance of developing cirrhosis is approximately: • 1. 5% • 2. 20% • 3. 35% • 4. 50% • 5. 65%

  21. Effect of HCV/HIV Co-infection on Fibrosis Progression Rate HIV+, n=122 HIV– matched controls, n=122 Progression rate was increased in those persons with CD4 < 200 or Ongoing EtOH use Benhamou et al. Hepatology. 1999;1054-8.

  22. Wilcox’s Rules of 20 • Applies to mono-infected patients with Hep C • 15-20% - chronicity • 20% of those with chronic disease develop cirrhosis • Development of cirrhosis occurs in 20-40 years • Of those with cirrhosis, about 5% (1 in 20) develop hepatocellular carcinoma • Chance of perinatal transmission – 1 in 20 (5%)

  23. Causes of death in HIV+ patients Berggren R. 39th IDSA Conference 2001

  24. Cause of Death by CD4 count P<.0001 P=.025 Berggren R. 39th IDSA Conference 2001

  25. HCV and HAART • NNRTIs • 20% increase incidence of transaminase elevation • Increased levels of EFV seen with cirrhosis • Once daily nevirapine highest incidence of significant transaminase elevation in class in co-infected • NRTIs • Abacavir may influence chance of cure – mixed results from studies • AZT relatively contra-indicated secondary to anemia • ddI interacts with ribavirin so is absolutely contraindicated

  26. HCV and HAART • PIs • Full dose ritonavir probably worse choice • Tipranavir, darunavir have case reports of significant toxicity in co-infected patients • Nelfinavir, atazanavir, fos-amprenavir may be safest choices in co-infected patients • IIs • Case reports of liver toxicity when raltegravir added to a tipranavir-based regimen

  27. HAART and Mortality in HCV • SMART Study • “Interruption of antiretroviral therapy is particularly unsafe in persons with hepatitis virus coinfection. Although HCV- and/or HBV-coinfected participants constituted 17% of participants in the SMART study, almost one-half of all non-OD deaths occurred in this population. Viral hepatitis was an unlikely cause of this excess risk” Tedaldi E, Peters L, Neuhaus J et al. Opportunistic disease and mortality in patients coinfected with hepatitis B or C virus in the strategic management of antiretroviral therapy (SMART) study. Clin Infect Dis. 2008 Dec 1;47(11):1468-75

  28. Polling Question • If an HIV+ patient with + hepatitis C antibody has a normal ALT level, the chance of significant liver disease is the same as in the mono-infected HCV+ patient. • 1. True • 2. False

  29. ALT Levels in Chronic HCV • Co-infected patients • 7-9% have consistently normal liver enzymes • 25-40% have significant liver fibrosis on biopsy • 12-14% have cirrhosis • Mono-infected • 10-30% of those with normal enzymes have significant fibrosis • Genotype 3 shown to have faster progression to cirrhosis • Lower ALT • Women • Genotype 4

  30. ANA TSH Alpha-fetoprotein HCV genotype HCV Viral load ART / RPR Ferritin (plus transferrin if elevated) PT/ PTT CBC with plts Chemistry 7 LFTs Uric Acid ECG Stress Test, if indicated Lipid Profile Insulin Tests to Order Prior to the Liver Biopsy

  31. Liver Biopsy • Gold standard, especially in those with genotype 1 • Often by-passed for those with genotypes 2 or 3 • Predictive of outcome and prognosis • Low morbidity/mortality : risk of death 1 per 10-12,000 • GI vs. interventional radiology

  32. Stage 0 Stage 1 Stage 2 Few septa No Fibrosis Portal Fibrosis Stage 3 Stage 4 Numerous septa Cirrhosis Histologic Staging

  33. Progression of Fibrosis on Biopsy Stage 4: Fibrous expansion of portal areas with marked bridging (portal to portal and portal to central) No Fibrosis Stage 1: Fibrous expansion of some portal areas Stage 5,6: Cirrhosis, probable or defined Stage 3: Fibrous expansion of most portal areas with occasional portal to portal bridging Cirrhotic liver: Gross anatomy of cadaver Courtesy of Gregory Everson, MD.

  34. Non-invasive Procedures to Assess Liver Fibrosis • Elastrometry (ie FibroScan) • Serum Biochemical markers (ie Fibrotest, APRI, SHASTA, FIB-4, Forn’s Index, etc.) • Less accurate in co-infected pts • Good for lack of fibrosis versus advanced disease but less accurate for intermediate stages

  35. Fig. 1. Main variables to assess in patients considered as candidates for hepatitis C (HCV) therapy. *Low viral load defined as HCV RNA < 500 000–800 000 IU/ml. Ab, antibody. From:   Soriano: AIDS, Volume 21(9).May 31, 2007.1073–1089

  36. Polling Question • When patients have chronic hepatitis, they should be advised to limit acetaminophen use to: • 1. none at all • 2. less than 500 mg per day • 3. less than 1000 mg per day • 4. less than 2000 mg per day • 5. less than 4000 mg per day

  37. Prevention Practices • Hepatic Diet - balanced • Avoid Alcohol • Immunizations – hepatitis A & B, Pneumovax, Influenza • Limit acetaminophen (Tylenol) < 2 gm/day • Avoid raw seafood, esp from the Gulf

  38. Nutrition with Hep C • Avoid alcohol • Avoid crash diets and / or binges • Educate self about food pyramid • Eat a variety of foods • Drink plenty of water • If have cirrhosis, need to decrease protein, salt, and iron in diet

  39. Alcohol Use in HCV • More rapid fibrosis progression • Higher viral loads • 2 schools of thought • No use acceptable • Minimal or special occasion use accepted

  40. Baseline Screenings Ophthalmologic exam in patients with HTN/DM Alcohol and Depression screen Consider anti-depressant prophylaxis

  41. Polling Question • The standard therapy for treatment of hepatitis C in HIV is: • 1. Herbal medications • 2. Interferon-alpha plus ritonavir • 3. Pegylated-interferon-alpha plus ribavirin • 4. Lamivudine plus entacavir • 5. Tenofovir plus emtricitabine

  42. Treatment for Hepatitis C co-infection • Modalities : -- pharmacotherapy : Peg-Interferon alpha (2 choices of formulation) weekly + Ribavirin weight based (usually 1 gm to 1.2 gm daily) -- transplant: referral for MELD score above 25 & end-stage liver disease

  43. MELD Score • Three blood tests: • Bilirubin • Prothrombin time (PT) - measured as international normalized ratio (INR) • Creatinine (a measure of kidney function) • 3.8 x log (e) (bilirubin mg/dL) + 11.2 x log (e) (INR) + 9.6 log (e) (creatinine mg/dL) • There are many internet websites that have automatic calculators.  All you have to do is to plug in your bilirubin, INR, and creatinine. One such website is the UNOS website- www.unos.org. • Scores range from 6-40

  44. Flu-like illness Fatigue Alopecia Weight loss Emotional lability Neutropenia Depression Thrombocytopenia Insomnia Thyroid dysfunction Anorexia Retinopathy Neuropathy Diarrhea Hearing loss Rash Side Effects of Interferon

  45. Interferon + RBV in HIV/HCV • Special Toxicity Concerns • Ribavirin • Dose-dependent hemolytic anemia (aggrevated in HIV) • Potential antagonism between AZT, d4T, ddC • Enhancement of ddI levels • Lactic acidosis? • Teratogenicity

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