Medico

7/10/2012

Management of HCV Infection Following Liver Transplantation
Kimmy Quach Jackson Memorial Hospital Transplant Rotation July 9, 2012

Hepatitis C Virus
• Small, RNA virus covered with envelop • After acute exposure:
– Some individuals will clear the virus within 6 months – 75% or more will progress to chronic infection

• Chronic infection:
– Cirrhosis (15-20%) – Hepatocellularcarcinoma (2-8%)

• At least 6 known genotypes:
– Genotype 1: most common in US, 75% of infected patients, and least response to antiviral therapy – Genotype 2 & 3: account ~20%, most response to antiviral therapy – Other: ~5%

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Background
• Hepatitis C virus (HCV) associated liver disease continues to be the most common indication for liver transplantation • Recurrence ofHCV is the most frequent cause of death and graft failure in HCV-infected recipients • Histological features of hepatitis develop in approximately 75% of recipients in the first 6 months post transplantation • 30% have progressed to cirrhosis by the 5th year post-op
– Once cirrhosis occurs, 40% decompensate within 1 year – 1 and 4-year survival: 66% and 33% respectively

• 4-7% develop anaccelerated course of liver injury with subsequent rapid allograft failure
– Poor outcomes with retransplantation for HCV induced graft loss

Risk factors for HCV Recurrence after Liver Transplantation
• Acute rejection therapy: – IV steroids:
• Associated with increasing HCV RNA level, mortality, and graft loss • Slow taper is preferred than rapid taper

– Calcineurin inhibitors:
• Patientsand graft survival benefit associated with tacrolimus as maintenance therapy • Cyclosporin is preferred during interferon-based antiviral therapy

– Mycophenolate mofetil:
• Potent inosine monophosphate inhibitor-antiviral properties • Neutral or beneficial to long-term outcomes on recurrence HCV recipients

– T-cell depleting:
• Alemtuzumab (campath): exacerbate recurrence of HCV •Thymoglobulin: use with caution in liver transplant recipients with HCV infection

– Interleukin 2 receptor inhibitor:
• Neutral impact on liver transplant recipients with HCV infection outcomes

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Risk factors for HCV Recurrence after Liver Transplantation
• Age:
– Associated with more rapid progression fibrosis and graft loss – Donor age: >65 years – Recipient age: >50 years

•CMV infection:
– Associated with increase severity of HCV recurrence – Prophylaxis might reduce the impact of CMV infection on HCV infected liver transplant recipients

Risk factors for HCV Recurrence after Liver Transplantation

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Transmission of HCV Infection
• Percutaneous (through the skin):
– – – – Use of clotting factor before 1987 Blood transfusion or organtransplant before 1992 Injection drug use (now) Occupational exposure (needlestick)

• Permucosal:
– Perinatal (mother to child) – Sexual contact

Diagnosis
• Liver function test:
– Commonly abnormal in HCV+ recipients – Unreliable to differentiate HCV recurrence

• Liver biopsy:
– Inaccurately differentiate other causes of early graft dysfunction from HCV recurrence – Inaccurately stage thedegree of fibrosis

• Hepatic venous pressure gradient (HVPG):
– Direct correlation between HVPG level and fibrosis

• Liver stiffness measurement with transient elastography:
– Higher sensitivity and positive predictive value for advanced fibrosis in HCV+ recipients

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Prevention/Prophylaxis
• Prophylaxis:
– Interferon with or without ribavirin immediate post-op:
• Lowsustain viral response • High incidence of complications (cytopenia, infection, rejection) • Poorly tolerated

– Hepatitis C immunoglobulin:
• Shown to lower HCV RNA • Not eliminate HCV viremia or the risk of recurrece

• Preemtive therapy:
– Unclear in delaying the onset of recurrence – Not currently recommended in clinical practice

Treatment
• Pre-transplant:
– Delay the need for liver...