Pam Harrison

October 23, 2014

PHILADELPHIA — The so-called 3D + RBV regimen, an interferon-free oral treatment, improves early measures of liver function at 12 weeks in hepatitis C patients with cirrhosis, a new analysis of the TURQUOISE-II data shows.

"These results were really quite spectacular," Gregory Everson, MD, from the University of Colorado in Aurora, said here at the American College of Gastroenterology 2014 Annual Scientific Meeting. "And because of these very high sustained virologic responses, we had an opportunity to look at the impact of this treatment regimen on the liver."

In the TURQUOISE-II trial, investigators achieved sustained virologic responses of 91.8% after 12 weeks of treatment and 96.5% after 24 weeks of treatment in hepatitis C patients with cirrhosis treated with the combination of ABT-450, a protease inhibitor boosted with ritonavir (ABT-450r), the NS5A inhibitor ombitasvir, and the non-nucleoside polymerase inhibitor dasabuvir plus ribavirin (N Engl J Med. 2014;370:1973-1982).

To assess liver injury in this new analysis, investigators compared baseline levels of three liver enzymes: alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transferase.

"For both aminotransferases, there were highly significant improvements from baseline at 12 weeks post-treatment in both arms, and the same held true for glutamyl transferase levels," Dr. Everson reported.

In patients who had elevated transaminase levels at baseline, levels had normalized after 12 weeks of treatment in 70% to 90% of patients.

Table 1. Changes in Liver Injury

Enzyme Baseline After Treatment
12-week group    
   Alanine aminotransferase (U/L) 99 32
   Aspartate aminotransferase (U/L) 88 33
   Gamma glutamyl transferase (U/L) 94 33
24-week group    
   Alanine aminotransferase (U/L) 100 28
   Aspartate aminotransferase (U/L) 92 29
   Gamma glutamyl transferase (U/L) 100 31


To assess the impact of the 3D + RBV regimen on liver function, investigators compared levels of conjugated bilirubin, albumin levels, and prothrombin time.

"Again, we showed a highly significant improvement in conjugated bilirubin and albumin in both arms," Dr. Everson said. "And about 90% of patients who had abnormalities in conjugated bilirubin prior to treatment normalized in the post-treatment period, as did 80% to 90% of those with abnormal albumin levels at the start of treatment."

Changes in prothrombin were significant in the 12-week group, but they did not reach significance in the 24-week group. Approximately 60% of those with abnormal prothrombin at baseline were normal at follow-up, Dr. Everson explained.

Table 2. Changes in Liver Function

Variable Baseline After Treatment
12-week group    
   Conjugated bilirubin (mg/dL) 0.30 0.19
   Albumin (g/dL) 3.90 4.10
   Prothrombin time (seconds) 11.50 11.30
24-week group    
   Conjugated bilirubin (mg/dL) 0.31 0.17
   Albumin (g/dL) 3.90 4.20
   Prothrombin time (seconds) 11.30 11.20


To assess the impact of 3D + RBV on portal hypertension, Dr. Everson and his team used the surrogate of platelet count, and they saw a trend toward an increase in platelet counts in the 12-week group.

An increase in the platelet count might reflect a reduction in splenic sequestration and serve as a surrogate for improvement in portal hypertension, but longer follow-up is likely needed to see a significant increase.

"In the era of interferon, we all noticed that hepatitis C patients with advanced fibrosis and cirrhosis experienced a reduction in liver-related death, all-cause mortality, liver cancer, and risk for liver decompensation when they achieved a sustained virologic response," Dr. Everson pointed out.

"But interferon was not well tolerated in this population, and response rates were low. Now we have an interferon-free treatment. Hopefully, we can have an impact on this condition in a greater number of patients," he said.

The specialty is now moving into an era where we are seeing very high cure rates, even in cirrhosis, said Paul Kwo, MD, from Wayne State University in Indiana.

Rapid Improvements

"This is just the first glimpse of what I think is going to be a large number of studies that will follow patients with cirrhosis," Dr. Kwo said. "The hope is that with normalization of liver tests, we can expect that there will be continued gradual improvement in hepatitis C cirrhosis."

He pointed out that earlier studies of interferon and ribavirin showed that early cirrhosis in hepatitis C patients could be reversed in those who responded to treatment. "There is no reason to think we won't see similar patterns in patients who are treated with this regimen," Dr. Kwo said.

"The difference here is that we will be curing much larger numbers of patients with cirrhosis than ever before," said David Bernstein, MD, from North Shore University Hospital in Manhasset, New York. He said he is hopeful that the number of patients who develop cancer and decompensated cirrhosis will decrease, as will the need for transplantation.

"We're going to have to wait and see," Dr. Bernstein said. "These types of studies give us hope that we will see this, because if you can improve liver function after 12 or 24 weeks of therapy, hopefully we'll begin to see the liver repair itself, once the viral stimulus is gone, and patients will do much better in the long term. For me, that is the excitement of this study — that we're showing improvements in liver function in such a short period of time."

Both physicians emphasized, however, that even though these novel regimens are capable of clearing the virus in almost all patients, people still have liver disease and they still need to be monitored for potential complications that might arise as a result of the underlying disease.

This study was supported by a grant from AbbVie. Dr. Everson reports financial relationships with AbbVie, Vertex, BMS, Merck, Roche, Genentech, Gilead, Pharmasset, GSK, Novartis, Tibotec, Janssen, Vertex, Esai, Biotest, and HepQuant. Dr. Kwo and Dr. Bernstein have disclosed no relevant financial relationships.

American College of Gastroenterology (ACG) 2014 Annual Scientific Meeting: Abstract 5. Presented October 20, 2014.


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