Direct-acting antivirals for hepatitis C have not only led to a cure for the virus — they’ve also changed the paradigm in liver transplantation. This includes the transplantation of HCV-positive organs into HCV-negative recipients.
Treatment with transarterial chemoembolization and Nexavar improved progression-free survival compared with transarterial chemoembolization alone in patients withunresectable hepatocellular carcinoma, according to a study published inGut.
Masatoshi Kudo, MD, PhD, from the Kindai University Faculty of Medicine in Japan, and colleagues explained that because of the high tumor recurrence rate after TACE, the procedure is usually repeated many times, which can lead to deterioration of liver function.
To explore the safety and efficacy of combination therapy with Nexavar (sorafenib, Bayer), Kudo and colleagues randomly assigned patients with unresectable HCC to receive either TACE with sorafenib (n = 80) or TACE alone (n = 76).
The researchers defined progression as untreatable, or “unTACEable,” progression such as the inability for a patient to further receive or benefit from TACE for reasons including intrahepatic tumor progression, invasion or extrahepatic spread, transient deterioration of liver function to Child-Pugh C, or macrovascular invasion.
Median PFS was longer in the TACE plus sorafenib group than the TACE only group (25.2 vs. 13.5 months; HR = 0.59; 95% CI, 0.41-0.87).
Among TACE naive group, the researchers observed no difference between median PFS based on unTACEable progression in either group. However, among those with one to two previous treatments with TACE, median PFS was longer in the combination group that the TACE alone group (HR = 0.57; 95% CI, 0.33-0.99).
Kudo and colleagues noted that adverse events occurred more often in the combination group, likely due to treatment with sorafenib, but none of the events were unexpected and rates of grade 3 and grade 4 adverse events were relatively low.
“These findings differ markedly from those of previous trials testing the combination of TACE plus sorafenib in patients with HCC,” they wrote. “In contrast to [three previous] negative trials, the present trial assessed the efficacy of TACE plus sorafenib using an endpoint more suitable for a TACE combination trial, with this endpoint being consistent with those used in clinical practice.”
The researchers concluded that pre-treatment with sorafenib 2 weeks to 3 weeks before initial TACE enhanced the treatment effect of TACE through tumor vessel normalization leading to homogenous distribution of lipiodol mixed with anticancer drugs and gelatin sponge particle within the tumors. – by Talitha Bennett
Disclosures: Kudo reports honoraria from Bayer, Eisai, Merck Sharp & Dohme, and Ajinomoto; consulting or advisory roles with Kowa, Merck Sharp & Dohme, Bristol-Myers Squibb, Bayer, Chugai and Taiho; and has received funding from Chugai, Otuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, Merck Sharp & Dohme, Eisai, Bayer and AbbVie. Please see the full study for all other authors’ relevant financial disclosures.
Tig said
Dec 9, 2019
Hey Obs,
My bits, like Canuck’s are a bit crunchy, but will do in a pinch! It all depends on how badly they need the parts and pieces.
Observer said
Dec 8, 2019
Great to know Tig... I dont know if when I die my bits will be too old to be of use...but I sure will register to be a donor...
Tig said
Dec 7, 2019
This is an interesting article for those interested in organ donation and recent advances in pre-transplant, anti viral administration. The sad part of the article is where they are obtaining these organs and why. The stuff is bad, real bad...
Combination therapy prevents HCV infection in non-viremic organ recipients November 10, 2019
Jordan J. Feld, MD, MPH, FAASLD Jordan J. Feld BOSTON — Hepatitis C infection was prevented or rapidly cured in transplant recipients who received organs from donors infected with the virus following combined treatment with ezetimibe and direct-acting antiviral therapy, according to study results presented at The Liver Meeting 2019.
“Unfortunately, most of you know that the opioid epidemic continues and, with that, an overdose crisis,” Jordan J. Feld, MD, MPH, FAASLD, from the University of Toronto University Health Network, said during a press conference. “What has been observed is that among potential organ donors, particularly those who died of overdose, the prevalence of hepatitis C has increased dramatically.”
During the study period, transplant specialists considered donors infected with HCV for lung, heart, kidney or kidney-pancreas recipients.
To test the possibility of preventing HCV infection, recipients received Mavyret (glecaprevir/pibrentasvir, AbbVie) with ezetimibe 6 hours to 12 hours before transplantation and then daily for 1-week posttransplant.
“Ezetimibe is a cholesterol-lowering drug that is approved and quite safe, but also happens to be a ligand ... for one of the entry factors that hepatitis C uses to enter hepatocytes,” Feld explained.
Of the 13 recipients without HCV who received HCV-infected organs, four developed quantifiable viremia posttransplant with a maximum HCV RNA of 2.96 log 10 IU/mL. HCV RNA declined rapidly and was unquantifiable by day 4 after transplant in all patients.
Six other patients had detectable but unquantifiable HCV RNA at day 1 posttransplant which was undetectable by day 2 in five patients and by day 4 in one patient.
All four patients with quantifiable HCV RNA received kidney or kidney-pancreas transplants, but no other factors correlated with posttransplant viremia. Additionally, Feld reported no relapses to date with a median follow-up of 10.2 weeks (range, 1-12.1 weeks).
Medication was well-tolerated with no serious adverse events related to treatment.
“Despite the horrible tragedy of the opioid epidemic, there is some good to come from the epidemic by using these organs for others,” Feld said. “But we must also focus on what we can do about this epidemic.” – by Talitha Bennett
Disclosure: Feld reports receiving grant or research support, and serving as a consultant for Abbott, AbbVie, Enanta, Gilead, Janssen, Merck and Roche.
Direct-acting antivirals for hepatitis C have not only led to a cure for the virus — they’ve also changed the paradigm in liver transplantation. This includes the transplantation of HCV-positive organs into HCV-negative recipients.
DAA's Change HCV + Liver Transplant Use
TACE plus Nexavar for unresectable HCC improves progression-free survival
Kudo M, et al. Gut. 2019;doi:10.1136/gutjnl-2019-318934.
December 12, 2019
Treatment with transarterial chemoembolization and Nexavar improved progression-free survival compared with transarterial chemoembolization alone in patients with unresectable hepatocellular carcinoma, according to a study published in Gut.
Masatoshi Kudo, MD, PhD, from the Kindai University Faculty of Medicine in Japan, and colleagues explained that because of the high tumor recurrence rate after TACE, the procedure is usually repeated many times, which can lead to deterioration of liver function.
To explore the safety and efficacy of combination therapy with Nexavar (sorafenib, Bayer), Kudo and colleagues randomly assigned patients with unresectable HCC to receive either TACE with sorafenib (n = 80) or TACE alone (n = 76).
The researchers defined progression as untreatable, or “unTACEable,” progression such as the inability for a patient to further receive or benefit from TACE for reasons including intrahepatic tumor progression, invasion or extrahepatic spread, transient deterioration of liver function to Child-Pugh C, or macrovascular invasion.
Median PFS was longer in the TACE plus sorafenib group than the TACE only group (25.2 vs. 13.5 months; HR = 0.59; 95% CI, 0.41-0.87).
Among TACE naive group, the researchers observed no difference between median PFS based on unTACEable progression in either group. However, among those with one to two previous treatments with TACE, median PFS was longer in the combination group that the TACE alone group (HR = 0.57; 95% CI, 0.33-0.99).
Kudo and colleagues noted that adverse events occurred more often in the combination group, likely due to treatment with sorafenib, but none of the events were unexpected and rates of grade 3 and grade 4 adverse events were relatively low.
“These findings differ markedly from those of previous trials testing the combination of TACE plus sorafenib in patients with HCC,” they wrote. “In contrast to [three previous] negative trials, the present trial assessed the efficacy of TACE plus sorafenib using an endpoint more suitable for a TACE combination trial, with this endpoint being consistent with those used in clinical practice.”
The researchers concluded that pre-treatment with sorafenib 2 weeks to 3 weeks before initial TACE enhanced the treatment effect of TACE through tumor vessel normalization leading to homogenous distribution of lipiodol mixed with anticancer drugs and gelatin sponge particle within the tumors. – by Talitha Bennett
Disclosures: Kudo reports honoraria from Bayer, Eisai, Merck Sharp & Dohme, and Ajinomoto; consulting or advisory roles with Kowa, Merck Sharp & Dohme, Bristol-Myers Squibb, Bayer, Chugai and Taiho; and has received funding from Chugai, Otuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, Merck Sharp & Dohme, Eisai, Bayer and AbbVie. Please see the full study for all other authors’ relevant financial disclosures.
My bits, like Canuck’s are a bit crunchy, but will do in a pinch! It all depends on how badly they need the parts and pieces.
Combination therapy prevents HCV infection in non-viremic organ recipients
November 10, 2019
Jordan J. Feld, MD, MPH, FAASLD
Jordan J. Feld
BOSTON — Hepatitis C infection was prevented or rapidly cured in transplant recipients who received organs from donors infected with the virus following combined treatment with ezetimibe and direct-acting antiviral therapy, according to study results presented at The Liver Meeting 2019.
“Unfortunately, most of you know that the opioid epidemic continues and, with that, an overdose crisis,” Jordan J. Feld, MD, MPH, FAASLD, from the University of Toronto University Health Network, said during a press conference. “What has been observed is that among potential organ donors, particularly those who died of overdose, the prevalence of hepatitis C has increased dramatically.”
During the study period, transplant specialists considered donors infected with HCV for lung, heart, kidney or kidney-pancreas recipients.
To test the possibility of preventing HCV infection, recipients received Mavyret (glecaprevir/pibrentasvir, AbbVie) with ezetimibe 6 hours to 12 hours before transplantation and then daily for 1-week posttransplant.
“Ezetimibe is a cholesterol-lowering drug that is approved and quite safe, but also happens to be a ligand ... for one of the entry factors that hepatitis C uses to enter hepatocytes,” Feld explained.
Of the 13 recipients without HCV who received HCV-infected organs, four developed quantifiable viremia posttransplant with a maximum HCV RNA of 2.96 log 10 IU/mL. HCV RNA declined rapidly and was unquantifiable by day 4 after transplant in all patients.
Six other patients had detectable but unquantifiable HCV RNA at day 1 posttransplant which was undetectable by day 2 in five patients and by day 4 in one patient.
All four patients with quantifiable HCV RNA received kidney or kidney-pancreas transplants, but no other factors correlated with posttransplant viremia. Additionally, Feld reported no relapses to date with a median follow-up of 10.2 weeks (range, 1-12.1 weeks).
Medication was well-tolerated with no serious adverse events related to treatment.
“Despite the horrible tragedy of the opioid epidemic, there is some good to come from the epidemic by using these organs for others,” Feld said. “But we must also focus on what we can do about this epidemic.” – by Talitha Bennett
Reference: Feld JJ. Abstract 0038. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.
Disclosure: Feld reports receiving grant or research support, and serving as a consultant for Abbott, AbbVie, Enanta, Gilead, Janssen, Merck and Roche.