In the JournalsPerspective

DAA therapy may reduce number of LT candidates

Patients with hepatitis C virus, but without hepatocellular carcinoma treated with direct-acting antiviral agents saw lower MELD scores and improved liver function, enabling some of them to be removed from the liver transplant list.

“This study shows for the first time that DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of five,” Luca S. Belli, MD, of the department of gastroenterology and hepatology at the Niguarda Hospital in Milan, Italy, and colleagues wrote in the Journal of Hepatology.

Luca S. Belli

In this retrospective study, researchers studied 103 patients listed consecutively for LT in 11 European locations between February 2014 and February 2015. Through a competing risk analysis of inactivated and delisted patients, researchers discovered the collective frequency was 15.5% and 0% at 24 weeks, 27.6% and 10.3% at 48 weeks and 33.3% and 19.2% at 60 weeks. MELD score improved by 3.4 points in the patients (n = 34) who were inactivated and 62% of those (n = 21) were delisted after further improvement, according to Belli and colleagues.

The researchers stratified study participants according to baseline MELD: those less than 16, those between 16 and 20, and those greater than 20. Those in the lowest baseline MELD group inactivated at a rate of 27.3% with less than a 2-point change in MELD but 100% with a greater than 4-point change. But only two patients who entered the study with a MELD greater than 20 were delisted despite achieving a greater than 4-point change in MELD.

In a related editorial, Gregory T. Everson, MD, FACP, director of the hepatology section, University of Colorado School of Medicine, addressed this.

Gregory T. Everson, MD

Gregory T. Everson

“The rate of inactivation and delisting in the Belli study may not be translatable to all transplant centers,” Everson wrote. “In fact, many U.S. centers don’t currently list liver candidates until MELD [greater than] 20. If the Belli study is correct, and MELD [greater than] 20 is too sick to inactivate or delist, then the newly listed U.S. candidates for liver transplantation will not be activated or delisted after [sustained virologic response].”
Belli’s group noted patients taking DAA may not continue to see health improvements for the rest of their lives.

“We suggest designing long-term multinational observational studies on patients who have been listed for decompensated [HCV] cirrhosis and subsequently delisted because of clinical improvement,” Belli and researchers wrote. – by Janel Miller

Disclosure: Belli reports receiving grant/research support from Gilead, AbbVie and BMS as well as contributing to the Gilead consulting/advisory board. Please see the full study for a list of all other authors’ relevant financial disclosures. 

Patients with hepatitis C virus, but without hepatocellular carcinoma treated with direct-acting antiviral agents saw lower MELD scores and improved liver function, enabling some of them to be removed from the liver transplant list.

“This study shows for the first time that DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of five,” Luca S. Belli, MD, of the department of gastroenterology and hepatology at the Niguarda Hospital in Milan, Italy, and colleagues wrote in the Journal of Hepatology.

Luca S. Belli

In this retrospective study, researchers studied 103 patients listed consecutively for LT in 11 European locations between February 2014 and February 2015. Through a competing risk analysis of inactivated and delisted patients, researchers discovered the collective frequency was 15.5% and 0% at 24 weeks, 27.6% and 10.3% at 48 weeks and 33.3% and 19.2% at 60 weeks. MELD score improved by 3.4 points in the patients (n = 34) who were inactivated and 62% of those (n = 21) were delisted after further improvement, according to Belli and colleagues.

The researchers stratified study participants according to baseline MELD: those less than 16, those between 16 and 20, and those greater than 20. Those in the lowest baseline MELD group inactivated at a rate of 27.3% with less than a 2-point change in MELD but 100% with a greater than 4-point change. But only two patients who entered the study with a MELD greater than 20 were delisted despite achieving a greater than 4-point change in MELD.

In a related editorial, Gregory T. Everson, MD, FACP, director of the hepatology section, University of Colorado School of Medicine, addressed this.

Gregory T. Everson, MD

Gregory T. Everson

“The rate of inactivation and delisting in the Belli study may not be translatable to all transplant centers,” Everson wrote. “In fact, many U.S. centers don’t currently list liver candidates until MELD [greater than] 20. If the Belli study is correct, and MELD [greater than] 20 is too sick to inactivate or delist, then the newly listed U.S. candidates for liver transplantation will not be activated or delisted after [sustained virologic response].”
Belli’s group noted patients taking DAA may not continue to see health improvements for the rest of their lives.

“We suggest designing long-term multinational observational studies on patients who have been listed for decompensated [HCV] cirrhosis and subsequently delisted because of clinical improvement,” Belli and researchers wrote. – by Janel Miller

Disclosure: Belli reports receiving grant/research support from Gilead, AbbVie and BMS as well as contributing to the Gilead consulting/advisory board. Please see the full study for a list of all other authors’ relevant financial disclosures. 

    Perspective
     Raymond T. Chung

    Raymond T. Chung

    Belli and colleagues confirm, in very practical terms, some of the findings that were suggested by clinical trials of direct-acting antiviral agents in decompensated patients. A recent trial of direct acting antivirals in patients who had Child class B and class C cirrhosis demonstrated a majority of patients saw improved or stabilized MELD scores.  Here the authors demonstrate that a clear subset of patients on the transplant list with decompensated cirrhosis can be successfully removed or inactivated from the list with successful clearance of HCV. These patients tended to have less advanced MELD scores.

    This is wonderful news for our patients on the transplant list, many of whom are facing the prospect of waiting years for a donor organ.  The prospect of permanently removing even some portion of patients with lower MELD scores from the transplant list stands to produce net societal health benefit. One of the most interesting unanswered questions is whether this delisting represents a permanent obviation of transplantation. It is quite possible that we will witness continued clinical improvement over time in many of these patients.  However, some may stabilize but eventually still progress.  For others who have relatively low MELD, their scores may improve with successful HCV clearance, but they may still require transplantation because of factors not reflected in the score itself.  These include patients with intractable encephalopathy or ascites, which occasionally don’t track well with MELD.  In these cases, their problems may be ameliorated only by replacing their dysfunctional organ.

    The decision to treat HCV in these patients should be made carefully with consideration of the possible adverse consequences of reduction in MELD score, in terms of reducing their priority and increasing wait time for a curative but necessary transplant. While studies like that of Belli offer helpful guidance, the ultimate decision to treat a patient on the transplant list should remain individualized rather than algorithmized.

    • Raymond T. Chung, MD
    • HCV Next Editorial Board Member Massachusetts General Hospital Boston, Mass.

    Disclosures: Chung reports receiving grant support to Massachusetts General Hospital from Gilead, Abbvie, Merck and BMS.