Transplant, HIV and HCV Whats it Going to Be

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Transplant, HIV and HCVWhats it Going to Be?

• Katherine Jelinek, M.D., Fellow
• University of Illinois at Chicago
• Division of Gastroenterology and Hepatology

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HCV is Difficult to Manage After Liver
Transplantation

• Recurrence of HCV is universal
• Liver disease progresses more rapidly
• 10-30 develop cirrhosis in 5-7 years
• Anti-viral therapy
• Average response rate to IFN RBV is 20
• Dropout rates of 20-40 in carefully selected
  patients
• Firpi et al. Liver Transplantation 2002 8(11)
  1000-1006.
• Norris et al. Liver Transplantation 2004 10
  (10) 1271-1278.

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Influence of HIV on HCV Infection

• 300,000 people with HIV/HCV or HBV in the US
• HCV in the HIV population is approximately 23-33
  and up to 80 in HIV hemophiliacs
• Natural history of HCV is accelerated in pts with
  HIV
• More rapid progression to cirrhosis
• HCC at a younger age and shorter duration of HCV
  infection
• Increase in liver disease-related mortality
• HCV RNA levels are higher in patients with
  co-infection
• Karon et al. J Hepatology 1997 27 18-21
• Ragni et et al. J Infect Dis 2001 183
  1112-1115
• Benhamou et al. Hepatology 1999 30 1054-1058
• Darby et al. Lancet 1997 350 1425-31.
• Garcia et al. American J Gastroenterology 2001
  96 179-183.

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OLT in Patients with HIV Pre-HAART

• 38 liver transplants
• Poorly defined baseline characteristics (CD4
  counts, HIV RNA levels, OIs)
• 7-yr survival 36 compared to 70 HIV negative
  OLT during same period
• Rapidly progressive liver disease complicated HCV
  positive cases50 of hemophiliacs with HIV/HCV
  died
• Bouscarat et al. Clinical Infectious Dis 1994
  19 854-859
• Gordon et al. Gut 1998 42 744-749.

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OLT in Patients with HIVHAART Era

• Over 50 liver transplants done
• Early reports of HIV-HCV co-infection report more
  rapid progression of HCV infection
• Problems with data set HIV infection found at
  time of transplant for early cases
• Different transplant centers report different
  survival rates
• Prachalias, et al. Transplantation 2001 72
  1684-1688.

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Comparison of Pittsburgh Group to Kings College
Group

• Kings College Grp transplanted gt1000 pts between
  1995-2003, with 14 having HIV, and 7 having
  HIV/HCV co-infection.
• Poor outcomes of 7 pts, 57 alive at 12 months,
  but gt90 dead by 25 months
• 5 died due to recurrence of hep C and rejection
• Some developed cholestatic form of Hep C
  recurrence that lead to graft failure
• Prachalias et al. Transplantation 2001 72 (10),
  1684-88.
• Norris et al. Liver Transplantation Oct 2004 10
  (10), 1271-78.

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OLT in other CentersHIV and HCV

• Had pts from 5 different centers Univ.
  Pittsburgh, Univ. Miami, USCF and Kings College,
  London between 1997-2001
• Excluded if had OI, not affected if had previous
  OI or CD4 count
• Of 24, only 2 did not receive preoperative
  antiretroviral therapy
• 87 white (5 African American), 83 male, 62
  had Hep C (15 subjects)
• MELD score avg 15 (range 7-33)
• Platelets 73 (28-185)
• TB 3.2 (.7-27)
• INR 1.5 (.6-3.6)
• CD4 188 (76-973)
• HIV RNA PCR lt400 (lt400-179,000)
• Ragni et al. Survival of HIV-Infected Liver
  Transplant Recipients. Journal of Infectious
  Disease 2003 188 (15 Nov) 1412-1420.

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Results on Survival

• Median survival 18 months1 died within 1mo
• Results 6 died (25)83 of those from
  ESLD--60 due to drug hepatotoxicity, 60 had
  recurrent hep C infection, 40 with rejection
• Survival levels differ between study centers,
  better outcomes from University of Pittsburgh and
  worse outcomes from Kings College in the UK

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HIV/HCV OLT compared to HCV OLT in UNOS data
--Comparable survival until 18 months when
survival dropped to 56 in HIV/HCV group Ragni et
al. Journal Infectious Disease 2003 188
1412-20.
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Which HIV transplant pts did not survive (6/18)?

• 100 non-survivors had Hep C (p.03)
• 67 of non-survivors had post-OLT HAART
  intolerance (p.044)
• 60 had lower post-OLT CD4 count lt 200 (p.003)
• 33 of non-survivors had higher HIV RNA copies
  gt400 (p.016)
• Ragni et al. Journal Infectious Disease 188
  1412-20.

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Second Look at HIV and OLT University of
Pittsburgh Group

• Of 50 pts transplanted, HCV accounted for 68 of
  causes of liver disease
• Reports 80 alivewith varying periods of
  follow-up.
• Problems with paper
• 80 survival, but this group had 90 recurrence
  of HCV
• Largest Series from University of Pittsburgh with
  29 HIV/ESLD pts. since 1997, 89 with HCV, avg
  MELD 21, 80 white males
• 55 were taking HAART at time of transplant
• HCV VL not available, therefore
  Child-Turcotte-Pugh score was not available to
  assess survival
• Could not compare this group of highly selected
  pts to other groups
• Fung et al. Liver Transplantation, Vol 10, No
  10, Supp 2 (Oct) 2004 S39-S53.
• Norris et al. Liver Transplantation 10 (10),
  1271-1278

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Problems with HAART and Immunosuppression in HIV
OLT pts

• Problems with dosing medsadded hepatotoxicity of
  NRTI and altered pharmacokinetics of protease
  inhibitor metabolism
• Multiple different meds and constant adjustments
  to anti-retroviral and immunosuppressants (from
  drug interactions) make compliance a huge factor
• Mitochondrial toxicity reported with
  anti-retrovirals with hepatic steatosis
• Problems show the complexity of managing HAART
  for HIV in HCV-co-infected patients
• Antoniades et al. Liver Transplantation 2004
  Vol 10 (5) 699-702.

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Conclusions

• Multiple examples of drug-induced hepatotoxicity
  from HAART
• Increased risk of hepatic dysfunction due to HCV
  recurrence
• NO data for efficacy or tolerability of IFN in
  these patients
• Papers only mention that pts are treated, not how
  their response is
• Need studies to define patient selection for this
• Based on natural history of disease
• Based on use of anti-retroviral therapy

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Conclusions, cont.

• Potential to exposing patients to increased
  morbidity and mortality
• Increased organ usage
• Increased exposure to HIV and HCV (Surgeons, OR
  nurses, ICU nurses, respiratory therapists,
  hepatologists)
• Should base future decisions on clinical
  multi-center trials on variety of patients.

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Thank you.