SOC Post Liver Transplant

[mikesimon]

An extended treatment protocol with pegylated interferon and ribavirin for hepatitis C recurrence after liver liver transplantation

Nikroo Hashemi, Victor Araya, Kashif Tufail, Laxmi Thumma-lakunta, Eyob Feyssa, Ashaur Azhar, Mumtaz Niazi, Division of Hepatology, Center for Liver Disease and Transplantation, Albert Einstein Medical Center, Philadelphia, PA 19141, United States.


To evaluate the efficacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).
METHODS:

Between August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 fibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV undetectability.
RESULTS:

Extended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatment response and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not significant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not increased.
CONCLUSION:

Recurrent HCV after LT can be safely treated with extended virological response-guided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.

http://www.ncbi.nlm.nih.gov/pubmed/21866251

[HectorSF]

Here is a great talk from an AASLD "The Best of The Liver Meeting® 2010 Postgraduate Course" sessions regarding hepatitis B& C in 2010 that has audio and slides about the latest info on "Viral Hepatitis and Liver Transplantation" Paul Martin, MD
http://74.43.177.57/courses/2010/pg/martin/player.html

Lots of great info on all aspects of hepatitis C and liver disease.
http://www.aasld.org/education/bolm/Pages/pgcourse.aspx

Cheers!
Hector

[orphanedhawk]

Since I am gearing up to begin post transplant treatment, I thank you for sharing these articles.
As a genotype 2, my doctor is talking about 24 weeks of tx. I'm trying to stay upbeat, hoping for EVR. My suspicion is he is keeping me in a positive mind set.
OH

[HectorSF]

Hi all!

Whether a patient will treat post transplant depends upon how their HCV impacts the donor liver after transplant. This varies from patient to patient depending on a number of factors such as recipient, donor, and viral factors, and immunosuppressive treatment.

For an overview of post LT HCV treatment I would recommend the following paper...

"Management of Recurrent Hepatitis C Following Liver Transplantation"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978414/
Stevan A. Gonzalez, MD, MS. Stevan A. Gonzalez, Dr. Gonzalez is an Attending Physician in the Division of General and Transplant Hepatology at the Baylor Regional Transplant Institute at Baylor All Saints Medical Center in Fort Worth, Texas and Baylor University Medical Center in Dallas, Texas.

Some excerpts...

"Hepatitis C virus (HCV) is the most common indication for liver transplantation in the United States, and recurrent disease associated with HCV is a major cause of allograft loss and mortality. Up to 30% of transplant recipients with HCV will develop progressive fibrosis and cirrhosis within 5 years of transplantation....  Antiviral therapy with peginterferon alfa and ribavirin should be considered in select transplant recipients with recurrent HCV infection, as achievement of sustained virologic response is associated with increased allograft and patient survival; however, efficacy may be limited by poor tolerability, requirement for dose reductions, and treatment discontinuation. The use of emerging therapies such as direct-acting antiviral agents and steroid-sparing immunosuppression may play a major role in further advances associated with post-transplant management of recurrent HCV infection."

"...Annual liver biopsies are recommended in HCV liver transplant recipients in order to assess for progressive allograft fibrosis and potential candidacy for antiviral therapy, as combination peginterferon alfa (PegIFN) and ribavirin (RBV) should be considered in patients with histologic evidence of recurrent HCV and stage 2 fibrosis."

"The PHOENIX (Pegasys and Copegus Administered After Liver Transplantation for Hepatitis C) trial randomized patients after liver transplantation to receive 48 weeks of preemptive combination therapy or to undergo observation with the potential for treatment initiation once histologic evidence of recurrent HCV was established. A relatively low SVR was found in 22% of patients who received preemptive therapy, as well as discontinuation of therapy in over 40%, and increased reports of hematologic side effects.51 The PROTECT (Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy) study evaluated the treatment of established recurrent HCV following liver transplantation. Although the overall reported SVR was 29%, sustained response rates were over 50% in genotype 2 or 3 patients and in those who were able to complete a course of therapy. Similar to previous reports, hematologic side effects were prevalent; over 50% of patients required dose reductions; and up to 30% of patients discontinued therapy."

"Summary
Recurrent HCV is a major cause of allograft loss and mortality in liver transplant recipients with chronic HCV infection. The development of strategies designed to optimize patient and graft survival in this population is critical, as HCV is currently the most common indication for liver transplantation. A greater understanding of the risk factors for progressive disease and vigilant post-transplant monitoring through histologic assessment may guide management aimed toward reducing the potential for graft failure as well as helping identify candidates for antiviral therapy. As treatment with PegIFN and RBV may not be possible in many patients awaiting liver transplantation, post-transplant antiviral therapy is a consideration in select individuals; however, major limitations of both preemptive and recurrence-based therapy include poor tolerability and decreased efficacy. The emergence of DAA agents targeted specifically against HCV may ultimately have a major impact on the ability to achieve viral eradication both before and after transplantation. Likewise, increasing recognition and avoidance of post-transplant metabolic complications as well as the development of novel immunosuppression strategies, including the use of steroid-sparing agents, may potentially improve long-term outcomes in transplant recipients with chronic HCV."

Cheers!
Hector

[mikesimon]

The protocol was get undetectable and then do 48 more weeks - it's extended even if a patient does get UND at week 12 but I doubt most do respond that early.

I don't know what percentage of HCV transplant recipients treat. I'd take a wild guess that is is between 25% and 38% but I haven't any support for that estimation.  I do believe that the number, whatever it is, is going to increase soon and significantly once the new treatments are assimilated into the transplant population.

[frijole]

Mike
What do you think the percentage of transplant patients who treat is?  It seems like a lot of people don't treat after TP.  Is it hard to treat with all the other meds you have to take forever after TP?  Are they saying in this study that the patients treated for 3 years or was it the standard SOC?
frjole