Poster Presentation

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HCV and renal transplantationDr AC AnandNew
Delhi
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HCV and renal transplantation
Post Transplant problems
Renal Transplant
Renal Replacement Therapy
CRF
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Prevalence among HD patients (west)

• 10-50 of HD patients have chronic HCV infection
  (8-9 times more than CAPD patient)

Amer J Med 1999 107(6B) 90s-94s
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Risk factors for HCV infection in CRF

• Number of blood transfusions and injections
• Time on hemodialysis
• Contamination of equipment and environment with
  blood
• No separate machines
• Poor infection control practices
• 13 in those starting HD (1.3 general
  population)

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HCV in RT recipients
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Transplant patients

• Anti-HCV positivity 12.1 - 45.2
• HCV RNA positivity in renal transplant
  recipients 55.9

Indian J Med Res 1996, J Assoc Physicians India
1999 47(12) 1139-43 Indian J Med Res 2000 Jun
111204-11, Indian J Gastroenterol 2000
19(Suppl 3) C21
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Indian Armed Forces Hospital
Mean36.2
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Virological features

• Higher viral loads as compared to immunocompetent
  patients
• Same genotypes as found in geographical area

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Are biochemical parameters sensitive markers?

• ALT rise seen in only 20-70 patients with HCV
  infection.
• Transplantation 1996 62 699-700
• ALT rise reported in 10-16 of RT recipients
  without anti HCV by ELISA-2.
• Kidney International 1997 51 981-999
• Despite normal ALT levels, patients on HD more
  likely to have bridging hepatic fibrosis.
• Am J Gastroenterol 1999 94 3576

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Natural history

• Relative risk of death due to liver disease in
  HCV infected CRF patients is 2.39 (95 CI 1.28
  to 4.48)
• Kidney Int 1998 53 1374

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HCV related glomerulonephritis

• HCV may account for 10-20 GMN
• Commonest Membrano-proliferative
• 5th 6th decade of life
• More often in women
• Clinically asymptomatic, ALT mild rise, but
  biopsies show CAH or cirrhosis
• Amer J Med 1999 107(6B) 91s.

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HCV related glomerulonephritis

• Symptoms precede recognition of renal involvement
  by several years
• Weakness,arthralgias purpura
• Rarely Reynaud's phenomenon, leg ulcers severe
  vasculitis involving heart lungs
• 80 have hypertension at diagnosis
• Proteinuria common, 50 in nephrotic range
• Renal insufficiency variable but usually mild,
  renal failure needing dialysis only in 10-15
• Characteristic finding cryoglobulinaemia

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Can liver histology be predicted?

• Histological disease does not correlate with
  viral loads or biochemical parameters.
• Kidney Int 1997 52 843-61
• 90 (9/10) HCV RNA positive patients no
  histological change (Boletis et al 1995)
• 26 Anti HCV positive abnormal LFT normal liver
  histology
• Cirrhosis in first biopsy 4-23
• Transplant Proc 1993 25 1450-3

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Liver disease prevalence in RT recipients

• Liver disease found in 19-64 Anti HCV positive
  vs. 19- 30 anti HCV negative
• Pre transplant anti HCV positive Relative risk
  of post transplant liver disease was 5.0
• Pre transplant HCV RNA positive 1.8-30 fold
  rise in viral titers post transplant
• However no correlation between renal histology,
  and liver disease.

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Histological progression

• 15 Anti HCV renal transplant patients
• Chronic Hepatitis 13
• Early fibrosing cholestatic hepatitis 1
• Minimal hepatitis 1
• Follow up (17.14.9 months)
• Significant increase in fibrosis 13
• Full blown fibrosing cholestatic hepatitis 1
• Early fibrosing cholestatic hepatitis 1
• Kidney Int 1997 52 843-861

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Dialysis versus RT recipients

• Median follow up 73 months
• Presence of anti HCV 1.41 /2 .39 times increased
  risk of death on HD / Tx
• After Renal transplant relative risk of death
  greater than HD
• 0-3 months 4.74x ? in transplanted
• 4-6mths 1.76x ? in transplanted
• 7-48mths 0.31x ? in HD
• gt48 months 0.84x
• Liver disease as cause of death 3.3x
• Sepsis as cause of death 9x

New England Organ Bank (1986-1990) Kidney
International 1998 53 1374-81
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Factor affecting disease progression

• Acute HCV acquired at time of treatment (Max
  immunosuppression)
• 12/21 presented with jaundice, 6/21 presented
  with ascites and encephalopathy within 21 months
• Nephrol Dial Transplant 1998 13 3103-7
• 2/14 subfulminant hepatic failure, 6/14 died
• Kidney Int 1997 51 981-99

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Factor affecting disease progression

• HBV Co-infection 26 develop cirrhosis within 1
  year
• Type of immunosuppression
• Better with cyclosporin than with azathioprine
• Histological activity more severe with
  azathioprine
• FCH more common with azathioprine
• Am J Kid Dis 2001 38 919-34

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What effect does HCV have on patient and graft
survival?
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Graft and patient survival
LD Liver disease, GS Graft survival, Patient
survival
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Organs from HCV positive donor

• If recipient is HCV positive
• GS 100 versus 98
• PS 96 versus 93
• Favoured policy due to economic reasons
• Avoid for HCV negative recipients

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Treatment of HCV in CRF

• Patients on HD
• HCV related glomerulonephritis renal transplant
  recipients
• Interferon
• Ribavirin combination therapy
• Others

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Patients on HD

• Interferon Variable response
• fall in ALT (60-100) and HCV RNA clearance
  (66-77)
• Relapses common when treatment discontinued.
• Discontinuation of therapy 30-40 and reduction
  in dose in additional 26-67
• Pegylated interferons may be better, no dose
  modification
• J Infect Dis 1997 176 1614-7
• Nephrol Dial Transplant 1997 12 1414-9.

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Patients on HD

• No published trials of combination therapy
• Ribavirin is unsafe
• Ribavirin excreted in kidneys
• Not dialysed during routine dialysis
• Dose dependent hemolysis
• Contraindicated in CRF
• No treatment recommended unless transplantation
  is planned

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HCV related glomerulonephritis

• Rapidly progressive renal disease
  Corticosteroids, cyclophosphamide and
  plasmapheresis found effective
• Kidney International 1998 54 650-71
• Interferon
• 60 reduction in proteinuria, but serum
  creatinine did not change
• Reduced circulating cryoglobulins
• Blood 1994 84 3336-43
• N Engl J Med 1994 330 751-6

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Antiviral therapy for renal transplant recipients

• Reduce immunosuppression
• Interferon Rostaing et al (1996)
• 16 patients x 1 year
• 6 patients acute renal failure in 6-24 weeks
• 2 responded to steroids
• ALT normalized in 94, relapsed on stopping
  therapy in 47

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Antiviral therapy for renal transplant recipients

• Ribavirin monotherapy
• Decreased ALT seen but no effect on HCV RNA
  levels
• Drug combination with Amantidine being tried
• ? SNMC a ?-interferon inducer

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SNMC trial
SNMC Ribavirin
Ribavirin
5
4 5 9
13 - 5 8
6 mo therapy completed 7 13 ALT improvement
5(71) 4(31) HCV RNA negative 2(22) 0 With
drawn due to side effects 2 2
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Kidney biopsy intense mixed inflammatory cell
infiltrate in the glomeruli and interstitium
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Marked lymphomononuclear infiltrate in the
interstitium along with tubulitis
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Withdrawal of SNMC and high dose steroids results
in improvement
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Conclusions

• Hepatitis B C are not uncommon in CRF,
  increased morbidity, mortality in long term
• Treatment difficult, but best done before
  transplantation
• Can be transplanted with good short term results
• In post transplant setting no clear therapy
  exists, need for more clinical research in this
  group