Tag Archives: Liver Transplant

Large Cure Rate for Patients with Hepatitis C May Have a Significant Impact on the Transplant Wait List

Posted on by December 1, 2015

SAN FRANCISCO, Nov. 16, 2015 /PRNewswire/ — The direct acting antivirals that have been used to treat many patients with hepatitis C virus and cure almost all treated in the past two years has led to many questions for the healthcare system including the impact on the transplant wait list. Researchers at Hahnemann University Hospital Drexel College of Medicine presented data at the Annual Meeting of the American Association for the Study of Liver Diseases on the specific topic of curing patients with decompensated hepatitis C cirrhosis similar to those patients who are on the waitlist for transplantation.

Viral hepatitis is a frequent cause of decompensated cirrhosis, which starts as compensated cirrhosis in which there are no symptoms of the scarring of the liver (cirrhosis). The symptoms of progression to decompensated cirrhosis, which is life-threatening unless a liver transplant is performed, are bleeding varices, ascites, encephalopathy, and jaundice.

Patients with decompensated HCV cirrhosis comprise 30 percent of adults on the transplant list waiting for a liver. Treating these patients successfully with antiviral therapy will change their Model End-Stage Liver Disease (MELD) scores. MELD scores control patient priority on the waiting list. Patients with a MELD score of 15 or lower are less likely to benefit from transplantation.

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SNAPSHOTS —Alan Franciscus, Editor-in-Chief

Posted on by December 1, 2015

This month’s (October 2015) column features a variety of studies, including treatment of people with advanced liver disease, treating people who have not achieved a cure with direct acting antiviral therapy, including people who had developed RAVs.

Article:  Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease—M Charlton et al. 
Source:  Gastroenterology. 2015 Sep;149(3):649-59. doi: 10.1053/j.gastro.2015.05.010. Epub 2015 May 15.
Results and Conclusions
This was a phase 2 study of 337 patients with decompensated cirrhosis with genotype 1 (332 patients) and genotype 4 (5 patients) who received 12 or 24 weeks of Harvoni plus ribavirin twice daily.  None of the patients previously treated developed resistance to sofosbuvir.  People who had been previously treated with an NS5A inhibitor were excluded from the study. 
There were two groups in the study:
  •  Group A, who had NOT had a liver transplant: 59 patients with Child-Pugh class B cirrhosis and 49 patients with Child-Pugh class C  cirrhosis*
  •  Group B who HAD undergone liver transplantation:  111 patients without cirrhosis, 51 patients with Child-Pugh class A cirrhosis, 52 with Child-Pugh class B cirrhosis, 9 with Child-Pugh class C cirrhosis, and 6 with fibrosing cholestatic hepatitis*

 *Child-Pugh cirrhosis scoring is a system that uses various types of blood markers and liver disease progression such as ascites to evaluate a patient to establish the severity of cirrhosis and long-term patient survival.  The classes are A, B and C with A as the less severe and C as the most severe.  Cholestatic hepatitis is bile duct blockage with fibrosis.
Group A and B had 12- and 24-week treatment arms, but cure rates were similar regardless of treatment duration.
     
 The Bottom Line
In group A (those who had not received a liver transplant), the cure rate was 86% to 89%.  In group B (transplant group) the people who did not have cirrhosis or Class A cirrhosis—the cure rate was 96% to 98%.  Furthermore, in group B with class B cirrhosis (compensated) the cure rate was 85% to 88%, and those with class C cirrhosis (moderate impairment) achieved 60% to 75% cure rates. The people who had fibrosing cholestatic hepatitis achieved 100% cure rates.  There were 13 patients (4%) who discontinued treatment.  Ten patients died in the trial.  The deaths were mainly attributed to complications from hepatic decompensation or end-stage liver disease.
Editorial Comment
In the past, people with these types of severe disease progression have been very difficult to cure or even treat, but now with these ‘miracle’ drugs many people now have a second chance at life.  Now if we could just get these drugs to everyone with hepatitis C before this stage, we would eliminate the need to treat at these stages of disease severity. 
___________
Article:  Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent—X Forns et al.
Source:  J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.
Results and Conclusions
There were 79 HCV genotype 1 patients in the study. 
  • Sixty-six patients who had been previously treated patients with an NS3/4A protease inhibitor but had not been cured. 
  • Of the 13 remaining patients, 12 had discontinued treatment due to side-effect(s). 
  • Thirty-four patients had NS3 resistance-associated variants (RAVs), and eight patients had NS5A RAVs. 
  • Eight patients treated with the combination of grazoprevir and elbasvir plus ribavirin twice daily.

 The Bottom Line
The overall cure rates were 96% (76 of 79 patients)—this included 93% (63 of 66 patients) of the genotype 1a, one hundred percent of the patients (43 of 43 patients) who DID NOT have RAVs achieved a cure.  Ninety-one percent of those who DID have NS3 RAV’s were cured and 75% (6 of 8 patients) of those who had NS5A RAVs were cured.  Of those with cirrhosis 94% were cured with this combination. 
Editorial Comment
The addition of ribavirin to grazoprevir and elbasvir works to help cure resistance-associated variants in people who have been previously treated but who have not been cured.  It is also good strategy to treat other negative predictors to current  medications.
____________________
Article:  Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens—D Wyles et al.  
Source:  Hepatology. 2015 Jun;61(6):1793-7. doi: 10.1002/hep.27814. Epub 2015 Apr 27.
Results and Conclusions
There were 51 genotype 1 patients enrolled in the study (Note: one patient was incorrectly typed as genotype 1, but was subsequently correctly genotyped as genotype 3).  All of the patients in this trial were previously treated with a sofosbuvir containing regimes in Gilead’s phase 1 or phase 2 studies.  The treatment duration in this study was 12 weeks. 
Breaking it down by type of prior type of non-response:
  • 25 pts (49%) had previously received sofosbuvir plus pegylated interferon plus ribavirin
  • 20 pts (39%) had previously received sofosbuvir plus ribavirin
  • 5 pts (10%) received sofosbuvir (sugar pill/placebo) plus pegylated interferon and ribavirin
  • 1 pt (2%) received GS-0938 only fourteen patients (27%) had compensated cirrhosis.

 The Bottom Line
The total number of patients who achieved a cure was 98% (50 of 51 patients).  Among those who had received a prior course of sofosbuvir 98% (44 of 45) were cured.  The only patient who did not achieve a cure was the patient who was originally misdiagnosed as a genotype 1. 
The most common side effects were fatigue, headache and diarrhea.  The patients in this trial are considered some the most difficult to treat—those who have not achieved a cure with a previous course of a direct acting antiviral medication, those with cirrhosis, and people with resistant antiviral variants (RAVs). 
Editorial Comment
The addition of ledipasvir and ribavirin to sofosbuvir increased the cure rates to 100% for genotype 1.  Excellent results!  This is a good strategy with another type of direct acting antiviral to stop the virus from replicating and escaping.
Gilead, Merck, AbbVie, Janssen, and Achillion are working on other HCV drugs that have a higher barrier to resistance to avoid the development of resistance and to work for people who are not responding to the current medications.
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SNAPSHOTS —Alan Franciscus, Editor-in-Chief

Posted on by December 13, 2015

This month’s (October 2015) column features a variety of studies, including treatment of people with advanced liver disease, treating people who have not achieved a cure with direct acting antiviral therapy, including people who had developed RAVs.

Article:  Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease—M Charlton et al. 
Source:  Gastroenterology. 2015 Sep;149(3):649-59. doi: 10.1053/j.gastro.2015.05.010. Epub 2015 May 15.
Results and Conclusions
This was a phase 2 study of 337 patients with decompensated cirrhosis with genotype 1 (332 patients) and genotype 4 (5 patients) who received 12 or 24 weeks of Harvoni plus ribavirin twice daily.  None of the patients previously treated developed resistance to sofosbuvir.  People who had been previously treated with an NS5A inhibitor were excluded from the study. 
There were two groups in the study:
  •  Group A, who had NOT had a liver transplant: 59 patients with Child-Pugh class B cirrhosis and 49 patients with Child-Pugh class C  cirrhosis*
  •  Group B who HAD undergone liver transplantation:  111 patients without cirrhosis, 51 patients with Child-Pugh class A cirrhosis, 52 with Child-Pugh class B cirrhosis, 9 with Child-Pugh class C cirrhosis, and 6 with fibrosing cholestatic hepatitis*

 *Child-Pugh cirrhosis scoring is a system that uses various types of blood markers and liver disease progression such as ascites to evaluate a patient to establish the severity of cirrhosis and long-term patient survival.  The classes are A, B and C with A as the less severe and C as the most severe.  Cholestatic hepatitis is bile duct blockage with fibrosis.
Group A and B had 12- and 24-week treatment arms, but cure rates were similar regardless of treatment duration.
     
 The Bottom Line
In group A (those who had not received a liver transplant), the cure rate was 86% to 89%.  In group B (transplant group) the people who did not have cirrhosis or Class A cirrhosis—the cure rate was 96% to 98%.  Furthermore, in group B with class B cirrhosis (compensated) the cure rate was 85% to 88%, and those with class C cirrhosis (moderate impairment) achieved 60% to 75% cure rates. The people who had fibrosing cholestatic hepatitis achieved 100% cure rates.  There were 13 patients (4%) who discontinued treatment.  Ten patients died in the trial.  The deaths were mainly attributed to complications from hepatic decompensation or end-stage liver disease.
Editorial Comment
In the past, people with these types of severe disease progression have been very difficult to cure or even treat, but now with these ‘miracle’ drugs many people now have a second chance at life.  Now if we could just get these drugs to everyone with hepatitis C before this stage, we would eliminate the need to treat at these stages of disease severity. 
___________
Article:  Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent—X Forns et al.
Source:  J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.
Results and Conclusions
There were 79 HCV genotype 1 patients in the study. 
  • Sixty-six patients who had been previously treated patients with an NS3/4A protease inhibitor but had not been cured. 
  • Of the 13 remaining patients, 12 had discontinued treatment due to side-effect(s). 
  • Thirty-four patients had NS3 resistance-associated variants (RAVs), and eight patients had NS5A RAVs. 
  • Eight patients treated with the combination of grazoprevir and elbasvir plus ribavirin twice daily.

 The Bottom Line
The overall cure rates were 96% (76 of 79 patients)—this included 93% (63 of 66 patients) of the genotype 1a, one hundred percent of the patients (43 of 43 patients) who DID NOT have RAVs achieved a cure.  Ninety-one percent of those who DID have NS3 RAV’s were cured and 75% (6 of 8 patients) of those who had NS5A RAVs were cured.  Of those with cirrhosis 94% were cured with this combination. 
Editorial Comment
The addition of ribavirin to grazoprevir and elbasvir works to help cure resistance-associated variants in people who have been previously treated but who have not been cured.  It is also good strategy to treat other negative predictors to current  medications.
____________________
Article:  Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens—D Wyles et al.  
Source:  Hepatology. 2015 Jun;61(6):1793-7. doi: 10.1002/hep.27814. Epub 2015 Apr 27.
Results and Conclusions
There were 51 genotype 1 patients enrolled in the study (Note: one patient was incorrectly typed as genotype 1, but was subsequently correctly genotyped as genotype 3).  All of the patients in this trial were previously treated with a sofosbuvir containing regimes in Gilead’s phase 1 or phase 2 studies.  The treatment duration in this study was 12 weeks. 
Breaking it down by type of prior type of non-response:
  • 25 pts (49%) had previously received sofosbuvir plus pegylated interferon plus ribavirin
  • 20 pts (39%) had previously received sofosbuvir plus ribavirin
  • 5 pts (10%) received sofosbuvir (sugar pill/placebo) plus pegylated interferon and ribavirin
  • 1 pt (2%) received GS-0938 only fourteen patients (27%) had compensated cirrhosis.

 The Bottom Line
The total number of patients who achieved a cure was 98% (50 of 51 patients).  Among those who had received a prior course of sofosbuvir 98% (44 of 45) were cured.  The only patient who did not achieve a cure was the patient who was originally misdiagnosed as a genotype 1. 
The most common side effects were fatigue, headache and diarrhea.  The patients in this trial are considered some the most difficult to treat—those who have not achieved a cure with a previous course of a direct acting antiviral medication, those with cirrhosis, and people with resistant antiviral variants (RAVs). 
Editorial Comment
The addition of ledipasvir and ribavirin to sofosbuvir increased the cure rates to 100% for genotype 1.  Excellent results!  This is a good strategy with another type of direct acting antiviral to stop the virus from replicating and escaping.
Gilead, Merck, AbbVie, Janssen, and Achillion are working on other HCV drugs that have a higher barrier to resistance to avoid the development of resistance and to work for people who are not responding to the current medications.
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Study’s Findings Could Help Expand the Donor Pool for Liver Transplantation

Posted on by December 13, 2015

Organ donation after circulatory death (DCD), in which transplant organs are taken from donors after ay period of no blood circulation or oxygenation, is often considered inferior to donation after brain death, in which circulation and oxygenation are maintained until organs are removed for transplantation. Currently, the use of livers from DCD donors remains controversial, particularly with donors with advanced age.

A new study of DCD liver transplantations conducted at the Cleveland Clinic from 2005 to 2014 found no significant correlation between donor age and organ survival, however. The results suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation.

“Aged DCD organs are generally underutilized by many transplant surgeons because of the higher risk of transplant organ failure; however, by eliminating other risk factors, aged DCD organs can greatly help expand the donor pool for life-saving liver transplantation,” said Dr. Koji Hashimoto, co-author of the Liver Transplantation study.

Source:  http://ca.wiley.com/WileyCDA/PressRelease/pressReleaseId-120486.html

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Study’s Findings Could Help Expand the Donor Pool for Liver Transplantation

Posted on by December 1, 2015

Organ donation after circulatory death (DCD), in which transplant
organs are taken from donors after ay period of no blood circulation or
oxygenation, is often considered inferior to donation after brain death,
in which circulation and oxygenation are maintained until organs are
removed for transplantation. Currently, the use of livers from DCD
donors remains controversial, particularly with donors with advanced
age.

A new study of DCD liver transplantations conducted at the Cleveland
Clinic from 2005 to 2014 found no significant correlation between donor
age and organ survival, however. The results suggest that stringent
donor and recipient selection may ameliorate the negative impact of
donor age in DCD liver transplantation.

“Aged DCD organs are generally underutilized by many transplant
surgeons because of the higher risk of transplant organ failure;
however, by eliminating other risk factors, aged DCD organs can greatly
help expand the donor pool for life-saving liver transplantation,” said
Dr. Koji Hashimoto, co-author of the Liver Transplantation study.

Source:  http://ca.wiley.com/WileyCDA/PressRelease/pressReleaseId-120486.html

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Liver transplants in HIV/HCV co-infection: study underlines importance of hepatitis C treatment

Posted on by December 13, 2015

People with HIV and hepatitis C co-infection were significantly more likely to experience organ rejection than people with hepatitis C alone or HIV alone after undergoing a liver transplant, according to a review of 11 years’ experience of liver transplantation in people with HIV and with hepatitis C virus (HCV) in the United States, published in advance online in the journal Clinical Infectious Diseases.

The study investigators say that their findings underline the importance of treating hepatitis C either before or immediately after liver transplantation in order to improve outcomes, rather than assuming that people with co-infection will have poorer outcomes based on historical data.

Liver transplantation remains a relatively rare procedure among people living with HIV, due in part to concerns about poorer survival and higher rates of organ rejection in people with HIV. Although a study carried out by the United States National Institutes of Health (NIH) showed a somewhat lower rate of survival three years after transplantation and a higher rate of organ rejection in people with HIV and hepatitis C co-infection compared to people with hepatitis C alone (mono-infection), the majority of transplants in each group was successful. The success of transplantation in people with HIV who are not do not have hepatitis C co-infection has been unclear. Furthermore, data are lacking outside the clinical trial setting regarding the outcomes of transplants in people with co-infection, particularly at transplant centres which did not take part in the NIH trial.

Reference

Sawinski D et al. Beyond the NIH Multicenter HIV Transplant Trial experience: outcomes of HIV+ liver transplant recipients compared to HCV+ or HIV+/HCV+ co-infected recipients in the United States. Clin Infect Dis, advance online publication, 16 June 2015.

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Liver transplants in HIV/HCV co-infection: study underlines importance of hepatitis C treatment

Posted on by December 1, 2015

People with HIV and hepatitis C co-infection were
significantly more likely to experience organ rejection than people with
hepatitis
C alone or HIV alone after undergoing a liver transplant, according to a
review
of 11 years’ experience of liver transplantation in people with HIV and
with hepatitis C virus (HCV) in the United States, published in advance
online in the journal Clinical Infectious Diseases.

The study investigators say that their findings underline
the importance of treating hepatitis C either before or immediately after liver
transplantation in order to improve outcomes, rather than assuming that
people with co-infection will have poorer outcomes based on historical data.

Liver transplantation remains a relatively rare procedure
among people living with HIV, due in part to concerns about poorer
survival and
higher rates of organ rejection in people with HIV. Although a study
carried
out by the United States National Institutes of Health (NIH) showed a
somewhat
lower rate of survival three years after transplantation and a higher
rate of
organ rejection in people with HIV and hepatitis C co-infection compared
to people with hepatitis C alone (mono-infection), the majority of
transplants in each group was successful.
The success of transplantation in people with HIV who are not do not
have hepatitis C co-infection has been unclear. Furthermore, data are
lacking outside the clinical trial
setting regarding the outcomes of transplants in people with
co-infection, particularly
at transplant centres which did not take part in the NIH trial.

Reference

Sawinski D et al. Beyond
the NIH Multicenter HIV Transplant Trial experience: outcomes of HIV+ liver
transplant recipients compared to HCV+ or HIV+/HCV+ co-infected recipients in
the United States. Clin Infect Dis, advance online publication, 16 June
2015.

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Potential Liver Recipients May Have New Option

Posted on by December 13, 2015
Organs harvested after cardiac death appear safe, effective, study says

FRIDAY, June 5, 2015 (HealthDay News) — Livers from donors who suffered cardiac death can be safely and effectively transplanted into patients dying of liver cancer, a new study suggests.

A liver transplant can cure many liver cancer patients, but many die waiting for a liver because most transplant centers use only livers from brain-dead donors. This study tested livers from both brain-dead donors and donors after cardiac death.

Cardiac death does not mean death from heart attack. Because of damaging oxygen loss, someone who dies from a heart attack is not considered a viable donor of organs for transplantation, the researchers said. Instead, cardiac death is controlled in a patient who will donate organs, they explained.

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