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Blood test could aid steroid decision in alcoholic hepatitis
AMSTERDAM – Determining the ratio of neutrophils to leukocytes in the blood could help identify patients with alcoholic hepatitis that would and would not benefit from steroid treatment.
Patients who had a neutrophil to lymphocyte ratio (NLR) of between 5 and 8 before being treated with the corticosteroid prednisolone appeared to obtain a benefit versus no-steroid treatment (P = .007) while those with higher and lower NLR values did not, in an analysis presented at the International Liver Congress.
This could potentially help clinicians avoid putting some patients through a futile trial of steroid therapy, study author Ewan H. Forrest, MD, explained in an interview at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL).
“The traditional approach would be to give steroids to patients with severe alcoholic hepatitis, wait 7 days, see if they are getting better, and if so, keep them on the steroids,” Dr. Forrest of the liver unit at Glasgow Royal Infirmary observed. Conversely, if patients are not doing better then steroids should be stopped.
“What we are increasingly aware of is that not only do some people not do well with steroids but also they actually do considerably more badly,” Dr. Forrest cautioned.
Usually, the response to steroid treatment in alcoholic hepatitis is measured by changes in serum bilirubin after a week of treatment, but this, of course, exposes patients to a “futile course of treatment with a risk of complication such as sepsis,” Dr. Forrest and his coauthors noted in a a late-breaking poster.
Determining the NLR has already been shown to help predict the prognosis of patients with several diseases with an underlying inflammatory component, such as cardiovascular diseases and several types of cancer. It also has proven useful in patients with liver disease, although not specifically in alcoholic hepatitis before this study, Dr. Forrest observed.
Data on patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial were used to see if the baseline NLR could help stratify patients who would benefit from steroid therapy.
STOPAH had compared the use of prednisolone or pentoxifylline for the treatment of alcoholic hepatitis but found no benefit for the latter, although there was a possible benefit of steroids for improving overall survival, at least in the short term (N Engl J Med. 2015 Apr;372:1619-28).
Dr. Forrest noted that measurement of the lymphocyte count was not part of the original study design, so data to calculate the NLR were obtained retrospectively. As there had been little or no response to pentoxifylline in the trial, patients who had taken this drug were regarded as having had no treatment in the analysis.
In all, baseline NLR values could be worked out for 630 patients from the STOPAH trial, but 113 were excluded from further analysis as they met the prespecified exclusion criteria of gastrointestinal bleeding or sepsis.
Overall, a NLR of 5 or less, indicating milder liver disease, was associated with significantly better survival at 3 months than if the NLR was 5 or more (85.5% vs. 67.3%; P less than .0001), study findings suggested.
Dr. Forest noted that 29% of patients fell into the “sweet spot” of the NLR of between 5 and 8, where patients did benefit from steroids, but that the 23% of study subjects who had an NLR ratio above 8 did not. These patients may have had disease too severe to benefit from the prednisolone, he suggested, and tended to have a worse prognosis regardless. A baseline NLR greater than 8 was associated with acute kidney infection but not sepsis, the team found.
There was also no great effect of the steroid in the 48% of patients who had an NLR ratio less than 5, suggesting that maybe they had disease that was too mild to warrant such treatment and did well regardless.
Of course, these findings still need further validation, but they are “not far off” from clinical application, Dr. Forrest offered. Calculating the ratio is simple, can be done during a routine whole-blood cell count, and is potentially cost saving because it reduces the standard practice in the United Kingdom of giving “all-comers” 7 days of corticosteroid therapy as a trial to see if they get better, he said.
Dr. Forrest had no conflicts of interest to disclose.
AMSTERDAM – Determining the ratio of neutrophils to leukocytes in the blood could help identify patients with alcoholic hepatitis that would and would not benefit from steroid treatment.
Patients who had a neutrophil to lymphocyte ratio (NLR) of between 5 and 8 before being treated with the corticosteroid prednisolone appeared to obtain a benefit versus no-steroid treatment (P = .007) while those with higher and lower NLR values did not, in an analysis presented at the International Liver Congress.
This could potentially help clinicians avoid putting some patients through a futile trial of steroid therapy, study author Ewan H. Forrest, MD, explained in an interview at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL).
“The traditional approach would be to give steroids to patients with severe alcoholic hepatitis, wait 7 days, see if they are getting better, and if so, keep them on the steroids,” Dr. Forrest of the liver unit at Glasgow Royal Infirmary observed. Conversely, if patients are not doing better then steroids should be stopped.
“What we are increasingly aware of is that not only do some people not do well with steroids but also they actually do considerably more badly,” Dr. Forrest cautioned.
Usually, the response to steroid treatment in alcoholic hepatitis is measured by changes in serum bilirubin after a week of treatment, but this, of course, exposes patients to a “futile course of treatment with a risk of complication such as sepsis,” Dr. Forrest and his coauthors noted in a a late-breaking poster.
Determining the NLR has already been shown to help predict the prognosis of patients with several diseases with an underlying inflammatory component, such as cardiovascular diseases and several types of cancer. It also has proven useful in patients with liver disease, although not specifically in alcoholic hepatitis before this study, Dr. Forrest observed.
Data on patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial were used to see if the baseline NLR could help stratify patients who would benefit from steroid therapy.
STOPAH had compared the use of prednisolone or pentoxifylline for the treatment of alcoholic hepatitis but found no benefit for the latter, although there was a possible benefit of steroids for improving overall survival, at least in the short term (N Engl J Med. 2015 Apr;372:1619-28).
Dr. Forrest noted that measurement of the lymphocyte count was not part of the original study design, so data to calculate the NLR were obtained retrospectively. As there had been little or no response to pentoxifylline in the trial, patients who had taken this drug were regarded as having had no treatment in the analysis.
In all, baseline NLR values could be worked out for 630 patients from the STOPAH trial, but 113 were excluded from further analysis as they met the prespecified exclusion criteria of gastrointestinal bleeding or sepsis.
Overall, a NLR of 5 or less, indicating milder liver disease, was associated with significantly better survival at 3 months than if the NLR was 5 or more (85.5% vs. 67.3%; P less than .0001), study findings suggested.
Dr. Forest noted that 29% of patients fell into the “sweet spot” of the NLR of between 5 and 8, where patients did benefit from steroids, but that the 23% of study subjects who had an NLR ratio above 8 did not. These patients may have had disease too severe to benefit from the prednisolone, he suggested, and tended to have a worse prognosis regardless. A baseline NLR greater than 8 was associated with acute kidney infection but not sepsis, the team found.
There was also no great effect of the steroid in the 48% of patients who had an NLR ratio less than 5, suggesting that maybe they had disease that was too mild to warrant such treatment and did well regardless.
Of course, these findings still need further validation, but they are “not far off” from clinical application, Dr. Forrest offered. Calculating the ratio is simple, can be done during a routine whole-blood cell count, and is potentially cost saving because it reduces the standard practice in the United Kingdom of giving “all-comers” 7 days of corticosteroid therapy as a trial to see if they get better, he said.
Dr. Forrest had no conflicts of interest to disclose.
AMSTERDAM – Determining the ratio of neutrophils to leukocytes in the blood could help identify patients with alcoholic hepatitis that would and would not benefit from steroid treatment.
Patients who had a neutrophil to lymphocyte ratio (NLR) of between 5 and 8 before being treated with the corticosteroid prednisolone appeared to obtain a benefit versus no-steroid treatment (P = .007) while those with higher and lower NLR values did not, in an analysis presented at the International Liver Congress.
This could potentially help clinicians avoid putting some patients through a futile trial of steroid therapy, study author Ewan H. Forrest, MD, explained in an interview at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL).
“The traditional approach would be to give steroids to patients with severe alcoholic hepatitis, wait 7 days, see if they are getting better, and if so, keep them on the steroids,” Dr. Forrest of the liver unit at Glasgow Royal Infirmary observed. Conversely, if patients are not doing better then steroids should be stopped.
“What we are increasingly aware of is that not only do some people not do well with steroids but also they actually do considerably more badly,” Dr. Forrest cautioned.
Usually, the response to steroid treatment in alcoholic hepatitis is measured by changes in serum bilirubin after a week of treatment, but this, of course, exposes patients to a “futile course of treatment with a risk of complication such as sepsis,” Dr. Forrest and his coauthors noted in a a late-breaking poster.
Determining the NLR has already been shown to help predict the prognosis of patients with several diseases with an underlying inflammatory component, such as cardiovascular diseases and several types of cancer. It also has proven useful in patients with liver disease, although not specifically in alcoholic hepatitis before this study, Dr. Forrest observed.
Data on patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial were used to see if the baseline NLR could help stratify patients who would benefit from steroid therapy.
STOPAH had compared the use of prednisolone or pentoxifylline for the treatment of alcoholic hepatitis but found no benefit for the latter, although there was a possible benefit of steroids for improving overall survival, at least in the short term (N Engl J Med. 2015 Apr;372:1619-28).
Dr. Forrest noted that measurement of the lymphocyte count was not part of the original study design, so data to calculate the NLR were obtained retrospectively. As there had been little or no response to pentoxifylline in the trial, patients who had taken this drug were regarded as having had no treatment in the analysis.
In all, baseline NLR values could be worked out for 630 patients from the STOPAH trial, but 113 were excluded from further analysis as they met the prespecified exclusion criteria of gastrointestinal bleeding or sepsis.
Overall, a NLR of 5 or less, indicating milder liver disease, was associated with significantly better survival at 3 months than if the NLR was 5 or more (85.5% vs. 67.3%; P less than .0001), study findings suggested.
Dr. Forest noted that 29% of patients fell into the “sweet spot” of the NLR of between 5 and 8, where patients did benefit from steroids, but that the 23% of study subjects who had an NLR ratio above 8 did not. These patients may have had disease too severe to benefit from the prednisolone, he suggested, and tended to have a worse prognosis regardless. A baseline NLR greater than 8 was associated with acute kidney infection but not sepsis, the team found.
There was also no great effect of the steroid in the 48% of patients who had an NLR ratio less than 5, suggesting that maybe they had disease that was too mild to warrant such treatment and did well regardless.
Of course, these findings still need further validation, but they are “not far off” from clinical application, Dr. Forrest offered. Calculating the ratio is simple, can be done during a routine whole-blood cell count, and is potentially cost saving because it reduces the standard practice in the United Kingdom of giving “all-comers” 7 days of corticosteroid therapy as a trial to see if they get better, he said.
Dr. Forrest had no conflicts of interest to disclose.
Key clinical point: Calculating the neutrophil to leukocyte ratio (NLR) could save some patients with alcoholic hepatitis from having steroid therapy.
Major finding: 90-day survival was 85.5% vs. 67.3%, (P less than .0001), comparing an NLR less than 5 with an NLR of 5 or greater in all patients.
Data source: 513 patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial.
Disclosures: Dr. Forrest had no conflicts of interest to disclose.
‘Rich pipeline’ of novel NASH treatments being studied
AMSTERDAM – There is a “very, very rich pipeline” of drugs being developed for the treatment of nonalcoholic steatohepatitis (NASH), Jean-François Dufour, MD, the head of hepatology and director of the University Clinic for Visceral Surgery and Medicine at the University of Berne (Switzerland) said at the International Liver Congress.
“We have many therapeutic options [under investigation],” Dr. Dufour noted at the Congress, which is sponsored by the European Association for the Study of the Liver (EASL). These include drugs that target metabolic homeostasis, insulin resistance, inflammation, oxidative stress, or fibrosis (Liver Int. 2017 May;37:634-47).
In fact, there is such a range of options that target different pathways, from fatty acid and bile acid synthesis to the early and late stages of fibrosis, that it is very likely that these drugs will be used in combination, Dr. Dufour observed as he gave an overview of the current trials that are underway in NASH.
There are currently five ongoing multicenter phase III trials being undertaken with four drugs. First, there is the REGENERATE trial with Intercept’s farnesoid X receptor obeticholic acid(Ocaliva). This is a placebo-controlled trial comparing two daily doses of obeticholic acid (10 and 25 mg) on top of the standard of care. The trial will recruit just over 2,000 patients with biopsy-proven stage 2-3 NASH fibrosis, and the primary endpoint is the resolution of NASH without fibrosis worsening or improvement in fibrosis without worsening of NASH at week 72.
Second there is the RESOLVE-IT trial with Genfit’s peroxisome proliferator-activated receptor alpha/delta agonist elafibranor. This randomized, double-blind trial hopes to recruit 2,000 patients with biopsy-proven NASH stage 1-3 fibrosis and will compare elafibranor 120 mg given once a day with placebo. The primary endpoint is the resolution of NASH without worsening of fibrosis at week 72.
Next, Tobira Therapeutics’ C-C chemokine receptor type 2 and 5 antagonist cenicriviroc is being studied in the AURORA trial. Again, recruiting around 2,000 patients is the target, but this time with stage 2-3 biopsy-proven NASH fibrosis. Cenicriviroc will be given daily at a dose of 150 mg and will be compared against placebo. The primary endpoint is the improvement of fibrosis by one or more stage with no worsening of steatohepatitis at 1 year.
Finally, there are the STELLA 3 and STELLA 4 trials with Gilead’s apoptosis signal-regulated kinase-1 inhibitor selonsertib. Target accrual in both studies is 800 patients with STELLA 3 recruiting patients with stage-3 NASH fibrosis and STELLA 4 recruiting those with compensated cirrhosis from NASH. Both trials will compared two daily doses of selonsertib (6 mg and 18 mg) versus placebo. The primary endpoints are the improvement of at least one or more fibrosis stage with no worsening of steatohepatitis at 48 weeks and event-free survival at week 240.
In addition, there are at least 20 phase 2b and 2a studies looking at a variety of other novel drugs with different therapeutic targets, Dr. Dufour said, and during separate presentations at the congress, results of several early trials with novel drugs being tested for NASH were given.
Eric J. Lawitz, MD, reported the promising results of a “proof of concept” open-label study in which the safety and efficacy of 12 weeks’ treatment with the oral acetyl-CoA carboxylase (ACC) inhibitor, GS-0976, was examined in 10 patients with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD).
“ACC catalyzes the rate-limiting step in de novo hepatic lipogenesis (DNL),” which is an underlying pathologic process in NASH, Dr. Lawitz, who is vice president of scientific and research development at the Texas Liver Institute, San Antonio, observed.
He reported that 12 weeks’ treatment with the ACC inhibitor GS-0976 suppressed DNL by 29%, compared with baseline (P = .022). There was also a 43% decrease in hepatic steatosis from baseline to 12 weeks (P = .006), as measured by the magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), and a nonsignificant 9% reduction in liver stiffness measured using magnetic resonance elastography (MRE).
Two markers of fibrosis and cell death (TIMP-1 and CK18) were also improved, he said, noting that overall, the drug was well tolerated, bar a trend to an increase in triglycerides and reduction in high-density lipoprotein cholesterol that needs further follow up.
“There is a placebo-controlled phase II trial of GS-0976 in patients with NASH that is ongoing,” Dr. Lawitz said. Results of two phase II studies presented during the late-breaking abstracts session at the meeting showed similar promising results could be achieved with drugs mimicking the activity of different fibroblast growth factors.
“Fibroblast growth factor 21 (FGF21) is a nonmitogenic hormone produced in the liver that is an important regulator of energy metabolism,” said Arun J. Sanyal, MD, who presented the findings of a study with the FGF21 inhibitor BMS-986036.
”From a NASH perspective, it improves insulin sensitivity and by doing that, decreases lipogenesis, and it also has been shown to have some antifibrotic effects,” Dr. Sanyal of Virginia Commonwealth University in Richmond, added.
FGF21 has a short half-life, however, and BMS-986036 is a recombinant human analog of this hormone that could potentially allow it to be given up to once weekly.
The study involved 74 patients with stage 1-3 biopsy-proven NASH fibrosis and a hepatic fat fraction of 10% or greater measured by MRI-PDFF. Patients were randomized to treatment with BMS-986036 at subcutaneously administered doses of 10 mg given once daily or 20 mg given once weekly or to placebo for 16 weeks.
A significant reduction in the hepatic fat fraction was seen in patients treated with both the once-daily and once-weekly regimen of the active treatment relative to placebo, with absolute changes from baseline of –6.8% (P = .008) and –5.2% (P = .0004), respectively, and just –1.3% for placebo.
“Results suggest that BMS-986036 had beneficial effects on steatosis, liver injury, and fibrosis in NASH,” said Dr. Sanyal, who also noted that there were no deaths and no signal that there could be any safety concerns.
NGM282 is another recombinant human analog mimicking the action of an FGF, this time FGF19, and early data also suggest that it also reduces hepatic steatosis and key biomarkers of NASH. Dr. Stephen Harrison, MD, the medical director of Pinnacle Clinical Research in Live Oak, reported data on 82 patients with stage 1-3 NASH fibrosis who had been treated with NGM-282 3 mg or 6 mg subcutaneously once a day or placebo for 12 weeks.
“The primary endpoint [decrease in absolute liver fat content greater than or equal to 5%] was met in 79% of NGM-282-treated subjects, with over one-third of subjects achieving normalization of liver fat content with 12 weeks of therapy,” Dr. Harrison reported.
“There were significant and rapid reductions in multiple markers that are relevant to the resolution of NASH and improvement in fibrosis,” Dr. Harrison added.
One serious adverse event of acute pancreatitis occurred in a patient treated with FGF19, which was possibly thought to be treatment related, but otherwise adverse events were generally mild and included gastrointestinal effects such as diarrhea and nausea, and injection site reactions.
“These data strongly support the continued development of NGM282 in NASH,” Dr. Harrison said.
During his presentation at a symposium session on current and future approaches to NAFLD and NASH, Dr. Dufour was keen to point out that a combination of diet and exercise remains central to managing patients with NASH.
“We should not forget, that the first line of discussion with these patients should be about changing their lifestyles.” Improving diet and exercise is something that everybody can do, he said, it is widely available and inexpensive, associated with few side effects and can produce good results.
However, convincing some patients can be difficult and those with a low acceptance to lifestyle changes often prefer to take medication. That is likely to come at a cost, not just in terms of money but there are likely to be some side effects, and, of course, efficacy in NASH is yet to be proven in many cases, Dr. Dufour said.
Dr. Dufour disclosed he had been part of a number of advisory committees or received speaking and teaching fees from a host of pharmaceutical companies, many of whom have an interest in the development of treatments for NASH.
Gilead Sciences supported the study reported by Dr. Lawitz and he disclosed receiving research grants or other support from the company, as well as several other pharmaceutical companies.
The study presented by Dr. Sanyal was financed by Bristol-Myers Squibb and he disclosed research funding was provided to his institution. Dr. Sanyal also disclosed receiving research support and consulting fees from multiple other pharmaceutical companies.
Dr. Harrison acknowledged receiving research funding from and acting as a consultant to NGM Bio, who sponsored the study he presented. He also disclosed acting as an adviser or speaker, and receiving grants from other pharmaceutical companies in the past 12 months.
AMSTERDAM – There is a “very, very rich pipeline” of drugs being developed for the treatment of nonalcoholic steatohepatitis (NASH), Jean-François Dufour, MD, the head of hepatology and director of the University Clinic for Visceral Surgery and Medicine at the University of Berne (Switzerland) said at the International Liver Congress.
“We have many therapeutic options [under investigation],” Dr. Dufour noted at the Congress, which is sponsored by the European Association for the Study of the Liver (EASL). These include drugs that target metabolic homeostasis, insulin resistance, inflammation, oxidative stress, or fibrosis (Liver Int. 2017 May;37:634-47).
In fact, there is such a range of options that target different pathways, from fatty acid and bile acid synthesis to the early and late stages of fibrosis, that it is very likely that these drugs will be used in combination, Dr. Dufour observed as he gave an overview of the current trials that are underway in NASH.
There are currently five ongoing multicenter phase III trials being undertaken with four drugs. First, there is the REGENERATE trial with Intercept’s farnesoid X receptor obeticholic acid(Ocaliva). This is a placebo-controlled trial comparing two daily doses of obeticholic acid (10 and 25 mg) on top of the standard of care. The trial will recruit just over 2,000 patients with biopsy-proven stage 2-3 NASH fibrosis, and the primary endpoint is the resolution of NASH without fibrosis worsening or improvement in fibrosis without worsening of NASH at week 72.
Second there is the RESOLVE-IT trial with Genfit’s peroxisome proliferator-activated receptor alpha/delta agonist elafibranor. This randomized, double-blind trial hopes to recruit 2,000 patients with biopsy-proven NASH stage 1-3 fibrosis and will compare elafibranor 120 mg given once a day with placebo. The primary endpoint is the resolution of NASH without worsening of fibrosis at week 72.
Next, Tobira Therapeutics’ C-C chemokine receptor type 2 and 5 antagonist cenicriviroc is being studied in the AURORA trial. Again, recruiting around 2,000 patients is the target, but this time with stage 2-3 biopsy-proven NASH fibrosis. Cenicriviroc will be given daily at a dose of 150 mg and will be compared against placebo. The primary endpoint is the improvement of fibrosis by one or more stage with no worsening of steatohepatitis at 1 year.
Finally, there are the STELLA 3 and STELLA 4 trials with Gilead’s apoptosis signal-regulated kinase-1 inhibitor selonsertib. Target accrual in both studies is 800 patients with STELLA 3 recruiting patients with stage-3 NASH fibrosis and STELLA 4 recruiting those with compensated cirrhosis from NASH. Both trials will compared two daily doses of selonsertib (6 mg and 18 mg) versus placebo. The primary endpoints are the improvement of at least one or more fibrosis stage with no worsening of steatohepatitis at 48 weeks and event-free survival at week 240.
In addition, there are at least 20 phase 2b and 2a studies looking at a variety of other novel drugs with different therapeutic targets, Dr. Dufour said, and during separate presentations at the congress, results of several early trials with novel drugs being tested for NASH were given.
Eric J. Lawitz, MD, reported the promising results of a “proof of concept” open-label study in which the safety and efficacy of 12 weeks’ treatment with the oral acetyl-CoA carboxylase (ACC) inhibitor, GS-0976, was examined in 10 patients with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD).
“ACC catalyzes the rate-limiting step in de novo hepatic lipogenesis (DNL),” which is an underlying pathologic process in NASH, Dr. Lawitz, who is vice president of scientific and research development at the Texas Liver Institute, San Antonio, observed.
He reported that 12 weeks’ treatment with the ACC inhibitor GS-0976 suppressed DNL by 29%, compared with baseline (P = .022). There was also a 43% decrease in hepatic steatosis from baseline to 12 weeks (P = .006), as measured by the magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), and a nonsignificant 9% reduction in liver stiffness measured using magnetic resonance elastography (MRE).
Two markers of fibrosis and cell death (TIMP-1 and CK18) were also improved, he said, noting that overall, the drug was well tolerated, bar a trend to an increase in triglycerides and reduction in high-density lipoprotein cholesterol that needs further follow up.
“There is a placebo-controlled phase II trial of GS-0976 in patients with NASH that is ongoing,” Dr. Lawitz said. Results of two phase II studies presented during the late-breaking abstracts session at the meeting showed similar promising results could be achieved with drugs mimicking the activity of different fibroblast growth factors.
“Fibroblast growth factor 21 (FGF21) is a nonmitogenic hormone produced in the liver that is an important regulator of energy metabolism,” said Arun J. Sanyal, MD, who presented the findings of a study with the FGF21 inhibitor BMS-986036.
”From a NASH perspective, it improves insulin sensitivity and by doing that, decreases lipogenesis, and it also has been shown to have some antifibrotic effects,” Dr. Sanyal of Virginia Commonwealth University in Richmond, added.
FGF21 has a short half-life, however, and BMS-986036 is a recombinant human analog of this hormone that could potentially allow it to be given up to once weekly.
The study involved 74 patients with stage 1-3 biopsy-proven NASH fibrosis and a hepatic fat fraction of 10% or greater measured by MRI-PDFF. Patients were randomized to treatment with BMS-986036 at subcutaneously administered doses of 10 mg given once daily or 20 mg given once weekly or to placebo for 16 weeks.
A significant reduction in the hepatic fat fraction was seen in patients treated with both the once-daily and once-weekly regimen of the active treatment relative to placebo, with absolute changes from baseline of –6.8% (P = .008) and –5.2% (P = .0004), respectively, and just –1.3% for placebo.
“Results suggest that BMS-986036 had beneficial effects on steatosis, liver injury, and fibrosis in NASH,” said Dr. Sanyal, who also noted that there were no deaths and no signal that there could be any safety concerns.
NGM282 is another recombinant human analog mimicking the action of an FGF, this time FGF19, and early data also suggest that it also reduces hepatic steatosis and key biomarkers of NASH. Dr. Stephen Harrison, MD, the medical director of Pinnacle Clinical Research in Live Oak, reported data on 82 patients with stage 1-3 NASH fibrosis who had been treated with NGM-282 3 mg or 6 mg subcutaneously once a day or placebo for 12 weeks.
“The primary endpoint [decrease in absolute liver fat content greater than or equal to 5%] was met in 79% of NGM-282-treated subjects, with over one-third of subjects achieving normalization of liver fat content with 12 weeks of therapy,” Dr. Harrison reported.
“There were significant and rapid reductions in multiple markers that are relevant to the resolution of NASH and improvement in fibrosis,” Dr. Harrison added.
One serious adverse event of acute pancreatitis occurred in a patient treated with FGF19, which was possibly thought to be treatment related, but otherwise adverse events were generally mild and included gastrointestinal effects such as diarrhea and nausea, and injection site reactions.
“These data strongly support the continued development of NGM282 in NASH,” Dr. Harrison said.
During his presentation at a symposium session on current and future approaches to NAFLD and NASH, Dr. Dufour was keen to point out that a combination of diet and exercise remains central to managing patients with NASH.
“We should not forget, that the first line of discussion with these patients should be about changing their lifestyles.” Improving diet and exercise is something that everybody can do, he said, it is widely available and inexpensive, associated with few side effects and can produce good results.
However, convincing some patients can be difficult and those with a low acceptance to lifestyle changes often prefer to take medication. That is likely to come at a cost, not just in terms of money but there are likely to be some side effects, and, of course, efficacy in NASH is yet to be proven in many cases, Dr. Dufour said.
Dr. Dufour disclosed he had been part of a number of advisory committees or received speaking and teaching fees from a host of pharmaceutical companies, many of whom have an interest in the development of treatments for NASH.
Gilead Sciences supported the study reported by Dr. Lawitz and he disclosed receiving research grants or other support from the company, as well as several other pharmaceutical companies.
The study presented by Dr. Sanyal was financed by Bristol-Myers Squibb and he disclosed research funding was provided to his institution. Dr. Sanyal also disclosed receiving research support and consulting fees from multiple other pharmaceutical companies.
Dr. Harrison acknowledged receiving research funding from and acting as a consultant to NGM Bio, who sponsored the study he presented. He also disclosed acting as an adviser or speaker, and receiving grants from other pharmaceutical companies in the past 12 months.
AMSTERDAM – There is a “very, very rich pipeline” of drugs being developed for the treatment of nonalcoholic steatohepatitis (NASH), Jean-François Dufour, MD, the head of hepatology and director of the University Clinic for Visceral Surgery and Medicine at the University of Berne (Switzerland) said at the International Liver Congress.
“We have many therapeutic options [under investigation],” Dr. Dufour noted at the Congress, which is sponsored by the European Association for the Study of the Liver (EASL). These include drugs that target metabolic homeostasis, insulin resistance, inflammation, oxidative stress, or fibrosis (Liver Int. 2017 May;37:634-47).
In fact, there is such a range of options that target different pathways, from fatty acid and bile acid synthesis to the early and late stages of fibrosis, that it is very likely that these drugs will be used in combination, Dr. Dufour observed as he gave an overview of the current trials that are underway in NASH.
There are currently five ongoing multicenter phase III trials being undertaken with four drugs. First, there is the REGENERATE trial with Intercept’s farnesoid X receptor obeticholic acid(Ocaliva). This is a placebo-controlled trial comparing two daily doses of obeticholic acid (10 and 25 mg) on top of the standard of care. The trial will recruit just over 2,000 patients with biopsy-proven stage 2-3 NASH fibrosis, and the primary endpoint is the resolution of NASH without fibrosis worsening or improvement in fibrosis without worsening of NASH at week 72.
Second there is the RESOLVE-IT trial with Genfit’s peroxisome proliferator-activated receptor alpha/delta agonist elafibranor. This randomized, double-blind trial hopes to recruit 2,000 patients with biopsy-proven NASH stage 1-3 fibrosis and will compare elafibranor 120 mg given once a day with placebo. The primary endpoint is the resolution of NASH without worsening of fibrosis at week 72.
Next, Tobira Therapeutics’ C-C chemokine receptor type 2 and 5 antagonist cenicriviroc is being studied in the AURORA trial. Again, recruiting around 2,000 patients is the target, but this time with stage 2-3 biopsy-proven NASH fibrosis. Cenicriviroc will be given daily at a dose of 150 mg and will be compared against placebo. The primary endpoint is the improvement of fibrosis by one or more stage with no worsening of steatohepatitis at 1 year.
Finally, there are the STELLA 3 and STELLA 4 trials with Gilead’s apoptosis signal-regulated kinase-1 inhibitor selonsertib. Target accrual in both studies is 800 patients with STELLA 3 recruiting patients with stage-3 NASH fibrosis and STELLA 4 recruiting those with compensated cirrhosis from NASH. Both trials will compared two daily doses of selonsertib (6 mg and 18 mg) versus placebo. The primary endpoints are the improvement of at least one or more fibrosis stage with no worsening of steatohepatitis at 48 weeks and event-free survival at week 240.
In addition, there are at least 20 phase 2b and 2a studies looking at a variety of other novel drugs with different therapeutic targets, Dr. Dufour said, and during separate presentations at the congress, results of several early trials with novel drugs being tested for NASH were given.
Eric J. Lawitz, MD, reported the promising results of a “proof of concept” open-label study in which the safety and efficacy of 12 weeks’ treatment with the oral acetyl-CoA carboxylase (ACC) inhibitor, GS-0976, was examined in 10 patients with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD).
“ACC catalyzes the rate-limiting step in de novo hepatic lipogenesis (DNL),” which is an underlying pathologic process in NASH, Dr. Lawitz, who is vice president of scientific and research development at the Texas Liver Institute, San Antonio, observed.
He reported that 12 weeks’ treatment with the ACC inhibitor GS-0976 suppressed DNL by 29%, compared with baseline (P = .022). There was also a 43% decrease in hepatic steatosis from baseline to 12 weeks (P = .006), as measured by the magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), and a nonsignificant 9% reduction in liver stiffness measured using magnetic resonance elastography (MRE).
Two markers of fibrosis and cell death (TIMP-1 and CK18) were also improved, he said, noting that overall, the drug was well tolerated, bar a trend to an increase in triglycerides and reduction in high-density lipoprotein cholesterol that needs further follow up.
“There is a placebo-controlled phase II trial of GS-0976 in patients with NASH that is ongoing,” Dr. Lawitz said. Results of two phase II studies presented during the late-breaking abstracts session at the meeting showed similar promising results could be achieved with drugs mimicking the activity of different fibroblast growth factors.
“Fibroblast growth factor 21 (FGF21) is a nonmitogenic hormone produced in the liver that is an important regulator of energy metabolism,” said Arun J. Sanyal, MD, who presented the findings of a study with the FGF21 inhibitor BMS-986036.
”From a NASH perspective, it improves insulin sensitivity and by doing that, decreases lipogenesis, and it also has been shown to have some antifibrotic effects,” Dr. Sanyal of Virginia Commonwealth University in Richmond, added.
FGF21 has a short half-life, however, and BMS-986036 is a recombinant human analog of this hormone that could potentially allow it to be given up to once weekly.
The study involved 74 patients with stage 1-3 biopsy-proven NASH fibrosis and a hepatic fat fraction of 10% or greater measured by MRI-PDFF. Patients were randomized to treatment with BMS-986036 at subcutaneously administered doses of 10 mg given once daily or 20 mg given once weekly or to placebo for 16 weeks.
A significant reduction in the hepatic fat fraction was seen in patients treated with both the once-daily and once-weekly regimen of the active treatment relative to placebo, with absolute changes from baseline of –6.8% (P = .008) and –5.2% (P = .0004), respectively, and just –1.3% for placebo.
“Results suggest that BMS-986036 had beneficial effects on steatosis, liver injury, and fibrosis in NASH,” said Dr. Sanyal, who also noted that there were no deaths and no signal that there could be any safety concerns.
NGM282 is another recombinant human analog mimicking the action of an FGF, this time FGF19, and early data also suggest that it also reduces hepatic steatosis and key biomarkers of NASH. Dr. Stephen Harrison, MD, the medical director of Pinnacle Clinical Research in Live Oak, reported data on 82 patients with stage 1-3 NASH fibrosis who had been treated with NGM-282 3 mg or 6 mg subcutaneously once a day or placebo for 12 weeks.
“The primary endpoint [decrease in absolute liver fat content greater than or equal to 5%] was met in 79% of NGM-282-treated subjects, with over one-third of subjects achieving normalization of liver fat content with 12 weeks of therapy,” Dr. Harrison reported.
“There were significant and rapid reductions in multiple markers that are relevant to the resolution of NASH and improvement in fibrosis,” Dr. Harrison added.
One serious adverse event of acute pancreatitis occurred in a patient treated with FGF19, which was possibly thought to be treatment related, but otherwise adverse events were generally mild and included gastrointestinal effects such as diarrhea and nausea, and injection site reactions.
“These data strongly support the continued development of NGM282 in NASH,” Dr. Harrison said.
During his presentation at a symposium session on current and future approaches to NAFLD and NASH, Dr. Dufour was keen to point out that a combination of diet and exercise remains central to managing patients with NASH.
“We should not forget, that the first line of discussion with these patients should be about changing their lifestyles.” Improving diet and exercise is something that everybody can do, he said, it is widely available and inexpensive, associated with few side effects and can produce good results.
However, convincing some patients can be difficult and those with a low acceptance to lifestyle changes often prefer to take medication. That is likely to come at a cost, not just in terms of money but there are likely to be some side effects, and, of course, efficacy in NASH is yet to be proven in many cases, Dr. Dufour said.
Dr. Dufour disclosed he had been part of a number of advisory committees or received speaking and teaching fees from a host of pharmaceutical companies, many of whom have an interest in the development of treatments for NASH.
Gilead Sciences supported the study reported by Dr. Lawitz and he disclosed receiving research grants or other support from the company, as well as several other pharmaceutical companies.
The study presented by Dr. Sanyal was financed by Bristol-Myers Squibb and he disclosed research funding was provided to his institution. Dr. Sanyal also disclosed receiving research support and consulting fees from multiple other pharmaceutical companies.
Dr. Harrison acknowledged receiving research funding from and acting as a consultant to NGM Bio, who sponsored the study he presented. He also disclosed acting as an adviser or speaker, and receiving grants from other pharmaceutical companies in the past 12 months.
Key clinical point: Lots of new approaches to treating nonalcoholic steatohepatitis are being investigated, some with phase III trials underway.
Major finding: Hepatic steatosis was significantly reduced by the GS-0976, BMS-986036, and NGM282.
Data source: An expert review and three early-phase studies testing of the safety and efficacy of novel NASH treatments.
Disclosures: Dr. Dufour disclosed he had been part of a number of advisory committees or received speaking and teaching fees from a host of pharmaceutical companies, many of whom have an interested in the development of treatments for NASH. Gilead Sciences supported the study reported by Dr. Lawitz and he disclosed receiving research grants or other support from the company, as well as several other pharmaceutical companies. The study presented by Dr. Sanyal was financed by Bristol-Myers Squibb and he disclosed research funding was provided to his institution. Dr. Sanyal also disclosed receiving research support and consulting fees from multiple other pharmaceutical companies. Dr. Harrison acknowledged receiving research funding from and acting as a consultant to NGM Bio, who sponsored the study he presented. He also disclosed acting as an adviser or speaker and receiving grants from other pharmaceutical companies in the past 12 months.
Radioembolization could be alternative to sorafenib in advanced liver cancer trial
AMSTERDAM – While there was no overall or progression-free survival benefit, results of the randomized, controlled phase III SARAH trial showed that the use of selective internal radioactive therapy (SIRT) was better tolerated than sorafenib for the treatment of patients with advanced liver cancer.
There was also early evidence that SIRT, using the radiopharmaceutical yttrium-90 (SIR-Spheres microspheres), reduced radiologic progression in the liver and improved tumor responses to a greater extent that did sorafenib.
“I feel [the results] will open a new door in the treatment of HCC [hepatocellular carcinoma],” study investigator Valérie Vilgrain, MD, of Hôpital Beaujon, Paris, said at the International Liver Congress, sponsored by the European Association for the Study of the Liver.
The standard treatment for advanced HCC at present is sorafenib, which is based on the SHARP trial findings that showed an overall survival of around 10.7 months, Dr. Vilgrain observed.
Transarterial chemoembolization (TACE) is the reference treatment for intermediate HCC, she said, and of the 467 patients included in the SARAH trial, just over 40% had failed to respond to two rounds of this therapy and had inoperable or advanced disease.
Dr. Frank Tacke, EASL vice secretary and professor of medicine in the department of gastroenterology, metabolic diseases, and intensive care medicine at University Hospital Aachen, Germany, said during a press briefing that the trial was “the first phase III, randomized controlled trial putting this intervention in perspective with current therapy.”
Dr. Tacke, who was not involved in the trial, added: “The overall survival is the same but there are so many patient-relevant parameters that are actually better in the one treatment [SIRT].”
The SARAH trial was conduced at 25 centers in France and there were 237 patients with a life expectancy of at least 3 months who were randomized to treatment with SIRT and 222 to treatment with sorafenib 800 mg daily.
The mean age of all randomized patients was 65 years, 90% were male, and 90% had cirrhosis. Cirrhosis was caused by alcoholic liver disease in 65%, hepatitis C virus infection in about one-quarter, and nonalcoholic steatohepatitis in roughly one-fifth of cases.
Comparing SIRT with sorafenib in all patients who were randomized, the median overall survival was 8.0 months versus 9.9 months (P = .018) and the median progression-free survival was a respective 4.1 months versus 3.7 months (P = .76). No differences in survival were observed when only patients who actually received the treatments were compared.
While there was no difference in radiologic progression seen overall – one of the secondary endpoints – when progression in the liver as the first site of progression was considered, there was a significant difference favoring the use of SIRT over sorafenib (P = .014), Dr. Vilgrain reported.
In addition, 26 (19%) of SIRT versus 23 (11.6%) of sorafenib-treated patients showed an objective response at 6 months, so there was “a strong signal” that SIRT could have an eventual edge over sorafenib but perhaps effects take longer to materialize (P = .042).
Fewer patients receiving SIRT than sorafenib experienced treatment-related adverse events (76.5% vs. 95%), with a median number of adverse events per patient of 5 and 10, respectively.
Adverse events of note that occurred less frequently in the SIRT than sorafenib arm were fatigue (20% vs. 41%), diarrhea (3% vs. 30%), abdominal pain (6% vs. 14%), hand-foot reaction (1% vs. 12%), infection (3% vs. 9%), weight loss (0% vs. 6%), and hypertension (0% vs. 5%).
Quality of life was significantly better in the SIRT group than in the sorafenib group over time, Dr. Vilgrain said. Quality of life was measured via the Global Health Status subscore of the EORTC QLQ-C30 scale.
Dr. Vilgrain noted during a press briefing that patients in the sorafenib group were able to start oral treatment 1 or 2 days after randomization, whereas there was a delay of 1-2 weeks before the patients randomized to SIRT could receive their treatment and just over one-quarter did not get SIRT as per the protocol, compared to 7% of those randomized to sorafenib.
Whether the lag time in patients getting their treatment might have affected the survival outcomes seen with the treatment is not known. Future studies look at reducing the time between randomization and SIRT, she said.
Dr. Vilgrain noted in an interview that SIRT was given as a single injection after an initial test injection. While it is possible to retreat patients, the study design was such that patients had to wait 6 months before they could be retreated and in theory a second treatment should not be needed.
The study was sponsored Assistance Publique – Hôpitaux de Paris (supported by grants from Sirtex Medical Limited. Dr. Vilgrain disclosed acting as a study investigator and receiving speaker fees from Guerbet and Sirtex, and speaker fees from SuperSonic Imagine and Toshiba.
AMSTERDAM – While there was no overall or progression-free survival benefit, results of the randomized, controlled phase III SARAH trial showed that the use of selective internal radioactive therapy (SIRT) was better tolerated than sorafenib for the treatment of patients with advanced liver cancer.
There was also early evidence that SIRT, using the radiopharmaceutical yttrium-90 (SIR-Spheres microspheres), reduced radiologic progression in the liver and improved tumor responses to a greater extent that did sorafenib.
“I feel [the results] will open a new door in the treatment of HCC [hepatocellular carcinoma],” study investigator Valérie Vilgrain, MD, of Hôpital Beaujon, Paris, said at the International Liver Congress, sponsored by the European Association for the Study of the Liver.
The standard treatment for advanced HCC at present is sorafenib, which is based on the SHARP trial findings that showed an overall survival of around 10.7 months, Dr. Vilgrain observed.
Transarterial chemoembolization (TACE) is the reference treatment for intermediate HCC, she said, and of the 467 patients included in the SARAH trial, just over 40% had failed to respond to two rounds of this therapy and had inoperable or advanced disease.
Dr. Frank Tacke, EASL vice secretary and professor of medicine in the department of gastroenterology, metabolic diseases, and intensive care medicine at University Hospital Aachen, Germany, said during a press briefing that the trial was “the first phase III, randomized controlled trial putting this intervention in perspective with current therapy.”
Dr. Tacke, who was not involved in the trial, added: “The overall survival is the same but there are so many patient-relevant parameters that are actually better in the one treatment [SIRT].”
The SARAH trial was conduced at 25 centers in France and there were 237 patients with a life expectancy of at least 3 months who were randomized to treatment with SIRT and 222 to treatment with sorafenib 800 mg daily.
The mean age of all randomized patients was 65 years, 90% were male, and 90% had cirrhosis. Cirrhosis was caused by alcoholic liver disease in 65%, hepatitis C virus infection in about one-quarter, and nonalcoholic steatohepatitis in roughly one-fifth of cases.
Comparing SIRT with sorafenib in all patients who were randomized, the median overall survival was 8.0 months versus 9.9 months (P = .018) and the median progression-free survival was a respective 4.1 months versus 3.7 months (P = .76). No differences in survival were observed when only patients who actually received the treatments were compared.
While there was no difference in radiologic progression seen overall – one of the secondary endpoints – when progression in the liver as the first site of progression was considered, there was a significant difference favoring the use of SIRT over sorafenib (P = .014), Dr. Vilgrain reported.
In addition, 26 (19%) of SIRT versus 23 (11.6%) of sorafenib-treated patients showed an objective response at 6 months, so there was “a strong signal” that SIRT could have an eventual edge over sorafenib but perhaps effects take longer to materialize (P = .042).
Fewer patients receiving SIRT than sorafenib experienced treatment-related adverse events (76.5% vs. 95%), with a median number of adverse events per patient of 5 and 10, respectively.
Adverse events of note that occurred less frequently in the SIRT than sorafenib arm were fatigue (20% vs. 41%), diarrhea (3% vs. 30%), abdominal pain (6% vs. 14%), hand-foot reaction (1% vs. 12%), infection (3% vs. 9%), weight loss (0% vs. 6%), and hypertension (0% vs. 5%).
Quality of life was significantly better in the SIRT group than in the sorafenib group over time, Dr. Vilgrain said. Quality of life was measured via the Global Health Status subscore of the EORTC QLQ-C30 scale.
Dr. Vilgrain noted during a press briefing that patients in the sorafenib group were able to start oral treatment 1 or 2 days after randomization, whereas there was a delay of 1-2 weeks before the patients randomized to SIRT could receive their treatment and just over one-quarter did not get SIRT as per the protocol, compared to 7% of those randomized to sorafenib.
Whether the lag time in patients getting their treatment might have affected the survival outcomes seen with the treatment is not known. Future studies look at reducing the time between randomization and SIRT, she said.
Dr. Vilgrain noted in an interview that SIRT was given as a single injection after an initial test injection. While it is possible to retreat patients, the study design was such that patients had to wait 6 months before they could be retreated and in theory a second treatment should not be needed.
The study was sponsored Assistance Publique – Hôpitaux de Paris (supported by grants from Sirtex Medical Limited. Dr. Vilgrain disclosed acting as a study investigator and receiving speaker fees from Guerbet and Sirtex, and speaker fees from SuperSonic Imagine and Toshiba.
AMSTERDAM – While there was no overall or progression-free survival benefit, results of the randomized, controlled phase III SARAH trial showed that the use of selective internal radioactive therapy (SIRT) was better tolerated than sorafenib for the treatment of patients with advanced liver cancer.
There was also early evidence that SIRT, using the radiopharmaceutical yttrium-90 (SIR-Spheres microspheres), reduced radiologic progression in the liver and improved tumor responses to a greater extent that did sorafenib.
“I feel [the results] will open a new door in the treatment of HCC [hepatocellular carcinoma],” study investigator Valérie Vilgrain, MD, of Hôpital Beaujon, Paris, said at the International Liver Congress, sponsored by the European Association for the Study of the Liver.
The standard treatment for advanced HCC at present is sorafenib, which is based on the SHARP trial findings that showed an overall survival of around 10.7 months, Dr. Vilgrain observed.
Transarterial chemoembolization (TACE) is the reference treatment for intermediate HCC, she said, and of the 467 patients included in the SARAH trial, just over 40% had failed to respond to two rounds of this therapy and had inoperable or advanced disease.
Dr. Frank Tacke, EASL vice secretary and professor of medicine in the department of gastroenterology, metabolic diseases, and intensive care medicine at University Hospital Aachen, Germany, said during a press briefing that the trial was “the first phase III, randomized controlled trial putting this intervention in perspective with current therapy.”
Dr. Tacke, who was not involved in the trial, added: “The overall survival is the same but there are so many patient-relevant parameters that are actually better in the one treatment [SIRT].”
The SARAH trial was conduced at 25 centers in France and there were 237 patients with a life expectancy of at least 3 months who were randomized to treatment with SIRT and 222 to treatment with sorafenib 800 mg daily.
The mean age of all randomized patients was 65 years, 90% were male, and 90% had cirrhosis. Cirrhosis was caused by alcoholic liver disease in 65%, hepatitis C virus infection in about one-quarter, and nonalcoholic steatohepatitis in roughly one-fifth of cases.
Comparing SIRT with sorafenib in all patients who were randomized, the median overall survival was 8.0 months versus 9.9 months (P = .018) and the median progression-free survival was a respective 4.1 months versus 3.7 months (P = .76). No differences in survival were observed when only patients who actually received the treatments were compared.
While there was no difference in radiologic progression seen overall – one of the secondary endpoints – when progression in the liver as the first site of progression was considered, there was a significant difference favoring the use of SIRT over sorafenib (P = .014), Dr. Vilgrain reported.
In addition, 26 (19%) of SIRT versus 23 (11.6%) of sorafenib-treated patients showed an objective response at 6 months, so there was “a strong signal” that SIRT could have an eventual edge over sorafenib but perhaps effects take longer to materialize (P = .042).
Fewer patients receiving SIRT than sorafenib experienced treatment-related adverse events (76.5% vs. 95%), with a median number of adverse events per patient of 5 and 10, respectively.
Adverse events of note that occurred less frequently in the SIRT than sorafenib arm were fatigue (20% vs. 41%), diarrhea (3% vs. 30%), abdominal pain (6% vs. 14%), hand-foot reaction (1% vs. 12%), infection (3% vs. 9%), weight loss (0% vs. 6%), and hypertension (0% vs. 5%).
Quality of life was significantly better in the SIRT group than in the sorafenib group over time, Dr. Vilgrain said. Quality of life was measured via the Global Health Status subscore of the EORTC QLQ-C30 scale.
Dr. Vilgrain noted during a press briefing that patients in the sorafenib group were able to start oral treatment 1 or 2 days after randomization, whereas there was a delay of 1-2 weeks before the patients randomized to SIRT could receive their treatment and just over one-quarter did not get SIRT as per the protocol, compared to 7% of those randomized to sorafenib.
Whether the lag time in patients getting their treatment might have affected the survival outcomes seen with the treatment is not known. Future studies look at reducing the time between randomization and SIRT, she said.
Dr. Vilgrain noted in an interview that SIRT was given as a single injection after an initial test injection. While it is possible to retreat patients, the study design was such that patients had to wait 6 months before they could be retreated and in theory a second treatment should not be needed.
The study was sponsored Assistance Publique – Hôpitaux de Paris (supported by grants from Sirtex Medical Limited. Dr. Vilgrain disclosed acting as a study investigator and receiving speaker fees from Guerbet and Sirtex, and speaker fees from SuperSonic Imagine and Toshiba.
AT ILC 2017
Key clinical point: Selective internal radiotherapy (SIRT) was found to be better tolerated than standard therapy but did not meet the primary endpoint of improved overall survival.
Major finding: Comparing SIRT with sorafenib in all patients who received it, the median overall survival was 8.0 months versus 9.9 months (P = .018).
Data source: SARAH, a prospective, randomized, open-label, multicenter, controlled phase III trial of radioembolization versus sorafenib for the treatment of 459 patients with advanced or inoperable hepatocellular carcinoma.
Disclosures: The study was sponsored Assistance Publique – Hôpitaux de Paris (supported by grants from Sirtex Medical Limited. Dr. Vilgrain disclosed acting as a study investigator and receiving speaker fees from Guerbet and Sirtex, and speaker fees from SuperSonic Imagine and Toshiba.
Fibrate could offer additional option for primary biliary cholangitis
AMSTERDAM – Patients with primary biliary cholangitis (PBC) who are not responding to first-line therapy with ursodeoxycholic acid (UDCA) may benefit from the addition of bezafibrate, randomized, double-blind, placebo-controlled study findings have suggested.
Almost one-third of the 50 patients who were treated with bezafibrate in addition to UDCA in the 2-year, phase III BEZURSO study met the primary endpoint for response, compared with none of the 50 patients in the control arm of the study.
The findings, presented as a late-breaking abstract at the International Liver Congress, sponsored by the European Association for the Study of the Liver (EASL), could be practice changing for a population of patients who have relatively few treatment options.
Although obeticholic acid was recently approved as a second-line treatment in combination with UDCA for PBC, one of the side effects of obeticholic acid is that it can cause pruritus, which is one of the symptoms of the condition as well. It can be tricky to explain to patients that there is a treatment but that this treatment might also increase their symptoms, Dr. Corpechot observed.
Between October 2012 and December 2014, mostly female patients (more than 92%), mean age 53 years, who were being treated with UDCA were recruited at 21 centers in France. For inclusion in the study, patients had to have an inadequate biochemical response to UDCA, which was defined by the Paris-2 criteria of an alkaline phosphatase (ALP) or an aspartate aminotransferase (AST) of more than 1.5 times the upper limit of normal (ULN), or a total bilirubin level of more than 17 micromol/L.
Patients were randomized to continue UDCA treatment (13-15 mg/kg per day) with or without the addition of bezafibrate, given as a 400-mg daily dose.
The primary endpoint was a complete biochemical response as defined by normal serum levels of total bilirubin, ALP, aminotransferases, albumin, and a normal prothrombin time at 2 years. The hypothesis was that 40% of the patients in the bezafibrate group and only 10% of patients in the UDCA group would reach this primary endpoint. The actual percentages were 30% and 10% (P less than .0001).
A significantly higher (67% vs. 0%) percentage of patients treated with the fibrate versus UDCA also achieved a normal serum ALP by 2 years, Dr. Corpechot reported, with a significant decrease seen by the third month of treatment.
The mean changes in all the biochemical parameters tested from baseline to the end of the study comparing the bezafibrate group with the control group were a respective –14% and +18% (P less than .0001) for total bilirubin, –60% and 0% for ALP (P less than .0001), –36% and 0% for alanine aminotransferase (P less than .0001), –8% and +8% for AST (P less than .05), –38% and +7% for gamma-glutamyl transferase (P less than .0001), 0% and –3% for albumin (P less than .05), and –16% and 0% for cholesterol (P less than .0001).
Other significant findings favoring the fibrate therapy were a significantly (–75% vs. 0%, P less than .01) decreased itch score (assessed with a visual analog scale) and a significantly lower (–10% vs. +10%, P less than .01) liver stiffness (assessed by transient elastography) at 2 years.
Importantly, the frequency of adverse events, including serious adverse events, did not differ significantly between the two groups.
Fibrates could thus offer a well tolerated and cheaper alternative, as they are already widely used in clinical practice, although they are not licensed for PBC treatment at the current time.
Dr. Tacke, professor of medicine in the department of gastroenterology, metabolic diseases and intensive care medicine at University Hospital Aachen, Germany, also noted that bezafibrate was a drug that “had been on the market for a very long time,” and was very inexpensive in comparison to obeticholic acid and, importantly, seemed to be very well tolerated in the study.
“One question the community will want to know is whether [bezafibrate] is as effective as obeticholic acid in the second-line treatment of PBC,” Dr. Tacke said. This is a question only a head-to-head study can answer and also it is not possible to say whether other fibrates may have the same benefit as bezafibrate as seen in this trial.
Although the study included only 100 patients, this was a relatively large study considering the disease area and that most patients given the primary treatment of UDCA will do well on it, Dr. Tacke acknowledged in an interview.
“What I like about this study is that they treated patients for 2 years and bezafibrate was given as an add-on treatment, so nobody was at risk for not receiving the UDCA, and they saw a very stable and solid improvement in the parameters studied,” Dr. Tacke said.
EASL launched new guidelines for the diagnosis and treatment of PBC to coincide with the meeting, which state that patients should be treated with UDCA for 1 year and then their biochemical response to treatment should assessed to see if they might need additional treatment. “Up to now, the second-line treatment recommended is obeticholic acid but off-label therapy is mentioned,” Dr. Tacke said.
He noted that there were small, nonrandomized studies with two fibrates – bezafibrate and fenofibrate – that have shown “very encouraging” results but that the current findings suggested that bezafibrate therapy may be an alternative, well-tolerated treatment option for patients failing to respond to standard UDCA therapy that could well be added into the guidelines when they are next revised.
The BEZURSO study was an investigator-led trial sponsored by the Assistance Publique – Hôpitaux de Paris. Dr. Corpechot disclosed financial relationships with Arrow Génériques, Intercept Pharma France, Mayoly-Spindler. Dr. Tacke had nothing to disclose.
AMSTERDAM – Patients with primary biliary cholangitis (PBC) who are not responding to first-line therapy with ursodeoxycholic acid (UDCA) may benefit from the addition of bezafibrate, randomized, double-blind, placebo-controlled study findings have suggested.
Almost one-third of the 50 patients who were treated with bezafibrate in addition to UDCA in the 2-year, phase III BEZURSO study met the primary endpoint for response, compared with none of the 50 patients in the control arm of the study.
The findings, presented as a late-breaking abstract at the International Liver Congress, sponsored by the European Association for the Study of the Liver (EASL), could be practice changing for a population of patients who have relatively few treatment options.
Although obeticholic acid was recently approved as a second-line treatment in combination with UDCA for PBC, one of the side effects of obeticholic acid is that it can cause pruritus, which is one of the symptoms of the condition as well. It can be tricky to explain to patients that there is a treatment but that this treatment might also increase their symptoms, Dr. Corpechot observed.
Between October 2012 and December 2014, mostly female patients (more than 92%), mean age 53 years, who were being treated with UDCA were recruited at 21 centers in France. For inclusion in the study, patients had to have an inadequate biochemical response to UDCA, which was defined by the Paris-2 criteria of an alkaline phosphatase (ALP) or an aspartate aminotransferase (AST) of more than 1.5 times the upper limit of normal (ULN), or a total bilirubin level of more than 17 micromol/L.
Patients were randomized to continue UDCA treatment (13-15 mg/kg per day) with or without the addition of bezafibrate, given as a 400-mg daily dose.
The primary endpoint was a complete biochemical response as defined by normal serum levels of total bilirubin, ALP, aminotransferases, albumin, and a normal prothrombin time at 2 years. The hypothesis was that 40% of the patients in the bezafibrate group and only 10% of patients in the UDCA group would reach this primary endpoint. The actual percentages were 30% and 10% (P less than .0001).
A significantly higher (67% vs. 0%) percentage of patients treated with the fibrate versus UDCA also achieved a normal serum ALP by 2 years, Dr. Corpechot reported, with a significant decrease seen by the third month of treatment.
The mean changes in all the biochemical parameters tested from baseline to the end of the study comparing the bezafibrate group with the control group were a respective –14% and +18% (P less than .0001) for total bilirubin, –60% and 0% for ALP (P less than .0001), –36% and 0% for alanine aminotransferase (P less than .0001), –8% and +8% for AST (P less than .05), –38% and +7% for gamma-glutamyl transferase (P less than .0001), 0% and –3% for albumin (P less than .05), and –16% and 0% for cholesterol (P less than .0001).
Other significant findings favoring the fibrate therapy were a significantly (–75% vs. 0%, P less than .01) decreased itch score (assessed with a visual analog scale) and a significantly lower (–10% vs. +10%, P less than .01) liver stiffness (assessed by transient elastography) at 2 years.
Importantly, the frequency of adverse events, including serious adverse events, did not differ significantly between the two groups.
Fibrates could thus offer a well tolerated and cheaper alternative, as they are already widely used in clinical practice, although they are not licensed for PBC treatment at the current time.
Dr. Tacke, professor of medicine in the department of gastroenterology, metabolic diseases and intensive care medicine at University Hospital Aachen, Germany, also noted that bezafibrate was a drug that “had been on the market for a very long time,” and was very inexpensive in comparison to obeticholic acid and, importantly, seemed to be very well tolerated in the study.
“One question the community will want to know is whether [bezafibrate] is as effective as obeticholic acid in the second-line treatment of PBC,” Dr. Tacke said. This is a question only a head-to-head study can answer and also it is not possible to say whether other fibrates may have the same benefit as bezafibrate as seen in this trial.
Although the study included only 100 patients, this was a relatively large study considering the disease area and that most patients given the primary treatment of UDCA will do well on it, Dr. Tacke acknowledged in an interview.
“What I like about this study is that they treated patients for 2 years and bezafibrate was given as an add-on treatment, so nobody was at risk for not receiving the UDCA, and they saw a very stable and solid improvement in the parameters studied,” Dr. Tacke said.
EASL launched new guidelines for the diagnosis and treatment of PBC to coincide with the meeting, which state that patients should be treated with UDCA for 1 year and then their biochemical response to treatment should assessed to see if they might need additional treatment. “Up to now, the second-line treatment recommended is obeticholic acid but off-label therapy is mentioned,” Dr. Tacke said.
He noted that there were small, nonrandomized studies with two fibrates – bezafibrate and fenofibrate – that have shown “very encouraging” results but that the current findings suggested that bezafibrate therapy may be an alternative, well-tolerated treatment option for patients failing to respond to standard UDCA therapy that could well be added into the guidelines when they are next revised.
The BEZURSO study was an investigator-led trial sponsored by the Assistance Publique – Hôpitaux de Paris. Dr. Corpechot disclosed financial relationships with Arrow Génériques, Intercept Pharma France, Mayoly-Spindler. Dr. Tacke had nothing to disclose.
AMSTERDAM – Patients with primary biliary cholangitis (PBC) who are not responding to first-line therapy with ursodeoxycholic acid (UDCA) may benefit from the addition of bezafibrate, randomized, double-blind, placebo-controlled study findings have suggested.
Almost one-third of the 50 patients who were treated with bezafibrate in addition to UDCA in the 2-year, phase III BEZURSO study met the primary endpoint for response, compared with none of the 50 patients in the control arm of the study.
The findings, presented as a late-breaking abstract at the International Liver Congress, sponsored by the European Association for the Study of the Liver (EASL), could be practice changing for a population of patients who have relatively few treatment options.
Although obeticholic acid was recently approved as a second-line treatment in combination with UDCA for PBC, one of the side effects of obeticholic acid is that it can cause pruritus, which is one of the symptoms of the condition as well. It can be tricky to explain to patients that there is a treatment but that this treatment might also increase their symptoms, Dr. Corpechot observed.
Between October 2012 and December 2014, mostly female patients (more than 92%), mean age 53 years, who were being treated with UDCA were recruited at 21 centers in France. For inclusion in the study, patients had to have an inadequate biochemical response to UDCA, which was defined by the Paris-2 criteria of an alkaline phosphatase (ALP) or an aspartate aminotransferase (AST) of more than 1.5 times the upper limit of normal (ULN), or a total bilirubin level of more than 17 micromol/L.
Patients were randomized to continue UDCA treatment (13-15 mg/kg per day) with or without the addition of bezafibrate, given as a 400-mg daily dose.
The primary endpoint was a complete biochemical response as defined by normal serum levels of total bilirubin, ALP, aminotransferases, albumin, and a normal prothrombin time at 2 years. The hypothesis was that 40% of the patients in the bezafibrate group and only 10% of patients in the UDCA group would reach this primary endpoint. The actual percentages were 30% and 10% (P less than .0001).
A significantly higher (67% vs. 0%) percentage of patients treated with the fibrate versus UDCA also achieved a normal serum ALP by 2 years, Dr. Corpechot reported, with a significant decrease seen by the third month of treatment.
The mean changes in all the biochemical parameters tested from baseline to the end of the study comparing the bezafibrate group with the control group were a respective –14% and +18% (P less than .0001) for total bilirubin, –60% and 0% for ALP (P less than .0001), –36% and 0% for alanine aminotransferase (P less than .0001), –8% and +8% for AST (P less than .05), –38% and +7% for gamma-glutamyl transferase (P less than .0001), 0% and –3% for albumin (P less than .05), and –16% and 0% for cholesterol (P less than .0001).
Other significant findings favoring the fibrate therapy were a significantly (–75% vs. 0%, P less than .01) decreased itch score (assessed with a visual analog scale) and a significantly lower (–10% vs. +10%, P less than .01) liver stiffness (assessed by transient elastography) at 2 years.
Importantly, the frequency of adverse events, including serious adverse events, did not differ significantly between the two groups.
Fibrates could thus offer a well tolerated and cheaper alternative, as they are already widely used in clinical practice, although they are not licensed for PBC treatment at the current time.
Dr. Tacke, professor of medicine in the department of gastroenterology, metabolic diseases and intensive care medicine at University Hospital Aachen, Germany, also noted that bezafibrate was a drug that “had been on the market for a very long time,” and was very inexpensive in comparison to obeticholic acid and, importantly, seemed to be very well tolerated in the study.
“One question the community will want to know is whether [bezafibrate] is as effective as obeticholic acid in the second-line treatment of PBC,” Dr. Tacke said. This is a question only a head-to-head study can answer and also it is not possible to say whether other fibrates may have the same benefit as bezafibrate as seen in this trial.
Although the study included only 100 patients, this was a relatively large study considering the disease area and that most patients given the primary treatment of UDCA will do well on it, Dr. Tacke acknowledged in an interview.
“What I like about this study is that they treated patients for 2 years and bezafibrate was given as an add-on treatment, so nobody was at risk for not receiving the UDCA, and they saw a very stable and solid improvement in the parameters studied,” Dr. Tacke said.
EASL launched new guidelines for the diagnosis and treatment of PBC to coincide with the meeting, which state that patients should be treated with UDCA for 1 year and then their biochemical response to treatment should assessed to see if they might need additional treatment. “Up to now, the second-line treatment recommended is obeticholic acid but off-label therapy is mentioned,” Dr. Tacke said.
He noted that there were small, nonrandomized studies with two fibrates – bezafibrate and fenofibrate – that have shown “very encouraging” results but that the current findings suggested that bezafibrate therapy may be an alternative, well-tolerated treatment option for patients failing to respond to standard UDCA therapy that could well be added into the guidelines when they are next revised.
The BEZURSO study was an investigator-led trial sponsored by the Assistance Publique – Hôpitaux de Paris. Dr. Corpechot disclosed financial relationships with Arrow Génériques, Intercept Pharma France, Mayoly-Spindler. Dr. Tacke had nothing to disclose.
AT ILC 2017
Key clinical point: Fibrates may offer another second-line treatment option for patients with primary biliary cholangitis (PBC), but their current use is off label.
Major finding: The primary endpoint of a complete biochemical response at 2 years was achieved by 30% and 0% of fibrate- and placebo-treated patients, respectively.
Data source: A multicenter, randomized, double-blind, placebo controlled phase III trial of bezafibrate added onto ursodeoxycholic acid (UDCA) versus UDCA in the treatment of 100 patients with PBC.
Disclosures: The BEZURSO study was an investigator-led trial sponsored by the Assistance Publique – Hôpitaux de Paris. Dr. Corpechot disclosed financial relationships with Arrow Génériques, Intercept Pharma France, Mayoly-Spindler. Dr. Tacke had nothing to disclose.
Norfloxacin improves short-term advanced cirrhosis survival
AMSTERDAM – Prolonged oral treatment with norfloxacin improved the survival of patients with Child-Pugh class C liver disease versus no antibiotic prophylaxis in a randomized, double-blind, placebo-controlled, phase III multicenter trial.
Fewer patients (15.3% vs. 24.5%) treated with norfloxacin for 6 months died by the 6-month mortality primary endpoint than did those treated with placebo, with a hazard ratio of 0.59 (95% confidence interval, 0.35-0.99; P = .047) favoring prolonged antibiotic treatment. Adjustments for the concomitant use of nonselective beta-blockers and corticosteroids did not greatly alter the significance of the findings (adjusted HR, 0.58; 95% CI, 0.34-0.98; P = .042).
“The results of this study provide evidence that 6 months of norfloxacin therapy reduces the risk of death in the short term, but not in the long term,” he observed in an official EASL press release.
The occurrence of infections at 6 months and 12 months were secondary outcomes of the study and showed that fewer infections overall (23.9% vs. 35.0%, P = .04) had occurred in the norfloxacin group versus the placebo group at 6 months, which was sustained at 12 months, suggesting an overhanging effect of the antibiotic treatment.
There was no difference between the groups in the incidence of other secondary endpoints including septic shock, systolic blood pressure, liver transplantation, kidney dysfunction, encephalopathy, and variceal bleeding at 6 months, Dr. Moreau reported on behalf of the NORFLOCIR study group.
Norfloxacin is a fluoroquinolone antibiotic and earlier data (Gastroenterology 2007;133:818-24) had suggested that its prolonged use could improve survival in patients with advanced cirrhosis significantly at 3 months and nonsignificantly at 12 months. This was a small study, however, and although several other small-sized trials followed, the long-term use of fluoroquinolone therapy to improve outcomes in patients cirrhosis remained debated,” Dr. Moreau said during his presentation of the study’s findings.
There was also the concern that such prolonged antibiotic use might up the risk for infection with gram-positive bacteria, he observed, but the current study’s finding showed that this was not the case. The cumulative incidence of gram-positive (3.4% vs. 8.1%, P = .08) infections was numerically although not significantly lower in the antibiotic-treated patients at 6 months while the cumulative incidence of gram-negative infections was significantly lowered (3.2% vs. 13.0%, P less than .005).
The study does have its limitations, Dr. Moreau conceded. Fewer patients were recruited than anticipated, 291 rather than a planned sample size of 392 patients, which was caused by a combination of factors – slow recruitment, termination of funding, and time expiry of the trial drug. Nevertheless, the study findings are strengthened by the fact it was conducted in 18 centers throughout France and that liver transplantation was taken into account as a potential competing risk.
During the trial, 144 patients with Child-Pugh class C cirrhosis were randomized to receive oral norfloxacin at a dose of 400 mg/day and 147 were randomized to a matching placebo daily for 6 months. Patients were followed for 6 additional months.
Just 3% of patients were lost to follow-up by the time of the primary endpoint assessment at 6 months, with just over half (55%) modifying their consent and almost half (46%) discontinuing the study because of death (15%), liver transplant (9%), elevated systolic blood pressure (9%), or patient decision (12%).
Patients included in the study were mostly middle-aged (55 years or older), male (more than 65%), and had alcoholic cirrhosis (greater than 74%) or alcoholic hepatitis (39%), with around 88% having ascites.
Dr. Moreau had nothing to disclose. The study was sponsored by the French government.
AMSTERDAM – Prolonged oral treatment with norfloxacin improved the survival of patients with Child-Pugh class C liver disease versus no antibiotic prophylaxis in a randomized, double-blind, placebo-controlled, phase III multicenter trial.
Fewer patients (15.3% vs. 24.5%) treated with norfloxacin for 6 months died by the 6-month mortality primary endpoint than did those treated with placebo, with a hazard ratio of 0.59 (95% confidence interval, 0.35-0.99; P = .047) favoring prolonged antibiotic treatment. Adjustments for the concomitant use of nonselective beta-blockers and corticosteroids did not greatly alter the significance of the findings (adjusted HR, 0.58; 95% CI, 0.34-0.98; P = .042).
“The results of this study provide evidence that 6 months of norfloxacin therapy reduces the risk of death in the short term, but not in the long term,” he observed in an official EASL press release.
The occurrence of infections at 6 months and 12 months were secondary outcomes of the study and showed that fewer infections overall (23.9% vs. 35.0%, P = .04) had occurred in the norfloxacin group versus the placebo group at 6 months, which was sustained at 12 months, suggesting an overhanging effect of the antibiotic treatment.
There was no difference between the groups in the incidence of other secondary endpoints including septic shock, systolic blood pressure, liver transplantation, kidney dysfunction, encephalopathy, and variceal bleeding at 6 months, Dr. Moreau reported on behalf of the NORFLOCIR study group.
Norfloxacin is a fluoroquinolone antibiotic and earlier data (Gastroenterology 2007;133:818-24) had suggested that its prolonged use could improve survival in patients with advanced cirrhosis significantly at 3 months and nonsignificantly at 12 months. This was a small study, however, and although several other small-sized trials followed, the long-term use of fluoroquinolone therapy to improve outcomes in patients cirrhosis remained debated,” Dr. Moreau said during his presentation of the study’s findings.
There was also the concern that such prolonged antibiotic use might up the risk for infection with gram-positive bacteria, he observed, but the current study’s finding showed that this was not the case. The cumulative incidence of gram-positive (3.4% vs. 8.1%, P = .08) infections was numerically although not significantly lower in the antibiotic-treated patients at 6 months while the cumulative incidence of gram-negative infections was significantly lowered (3.2% vs. 13.0%, P less than .005).
The study does have its limitations, Dr. Moreau conceded. Fewer patients were recruited than anticipated, 291 rather than a planned sample size of 392 patients, which was caused by a combination of factors – slow recruitment, termination of funding, and time expiry of the trial drug. Nevertheless, the study findings are strengthened by the fact it was conducted in 18 centers throughout France and that liver transplantation was taken into account as a potential competing risk.
During the trial, 144 patients with Child-Pugh class C cirrhosis were randomized to receive oral norfloxacin at a dose of 400 mg/day and 147 were randomized to a matching placebo daily for 6 months. Patients were followed for 6 additional months.
Just 3% of patients were lost to follow-up by the time of the primary endpoint assessment at 6 months, with just over half (55%) modifying their consent and almost half (46%) discontinuing the study because of death (15%), liver transplant (9%), elevated systolic blood pressure (9%), or patient decision (12%).
Patients included in the study were mostly middle-aged (55 years or older), male (more than 65%), and had alcoholic cirrhosis (greater than 74%) or alcoholic hepatitis (39%), with around 88% having ascites.
Dr. Moreau had nothing to disclose. The study was sponsored by the French government.
AMSTERDAM – Prolonged oral treatment with norfloxacin improved the survival of patients with Child-Pugh class C liver disease versus no antibiotic prophylaxis in a randomized, double-blind, placebo-controlled, phase III multicenter trial.
Fewer patients (15.3% vs. 24.5%) treated with norfloxacin for 6 months died by the 6-month mortality primary endpoint than did those treated with placebo, with a hazard ratio of 0.59 (95% confidence interval, 0.35-0.99; P = .047) favoring prolonged antibiotic treatment. Adjustments for the concomitant use of nonselective beta-blockers and corticosteroids did not greatly alter the significance of the findings (adjusted HR, 0.58; 95% CI, 0.34-0.98; P = .042).
“The results of this study provide evidence that 6 months of norfloxacin therapy reduces the risk of death in the short term, but not in the long term,” he observed in an official EASL press release.
The occurrence of infections at 6 months and 12 months were secondary outcomes of the study and showed that fewer infections overall (23.9% vs. 35.0%, P = .04) had occurred in the norfloxacin group versus the placebo group at 6 months, which was sustained at 12 months, suggesting an overhanging effect of the antibiotic treatment.
There was no difference between the groups in the incidence of other secondary endpoints including septic shock, systolic blood pressure, liver transplantation, kidney dysfunction, encephalopathy, and variceal bleeding at 6 months, Dr. Moreau reported on behalf of the NORFLOCIR study group.
Norfloxacin is a fluoroquinolone antibiotic and earlier data (Gastroenterology 2007;133:818-24) had suggested that its prolonged use could improve survival in patients with advanced cirrhosis significantly at 3 months and nonsignificantly at 12 months. This was a small study, however, and although several other small-sized trials followed, the long-term use of fluoroquinolone therapy to improve outcomes in patients cirrhosis remained debated,” Dr. Moreau said during his presentation of the study’s findings.
There was also the concern that such prolonged antibiotic use might up the risk for infection with gram-positive bacteria, he observed, but the current study’s finding showed that this was not the case. The cumulative incidence of gram-positive (3.4% vs. 8.1%, P = .08) infections was numerically although not significantly lower in the antibiotic-treated patients at 6 months while the cumulative incidence of gram-negative infections was significantly lowered (3.2% vs. 13.0%, P less than .005).
The study does have its limitations, Dr. Moreau conceded. Fewer patients were recruited than anticipated, 291 rather than a planned sample size of 392 patients, which was caused by a combination of factors – slow recruitment, termination of funding, and time expiry of the trial drug. Nevertheless, the study findings are strengthened by the fact it was conducted in 18 centers throughout France and that liver transplantation was taken into account as a potential competing risk.
During the trial, 144 patients with Child-Pugh class C cirrhosis were randomized to receive oral norfloxacin at a dose of 400 mg/day and 147 were randomized to a matching placebo daily for 6 months. Patients were followed for 6 additional months.
Just 3% of patients were lost to follow-up by the time of the primary endpoint assessment at 6 months, with just over half (55%) modifying their consent and almost half (46%) discontinuing the study because of death (15%), liver transplant (9%), elevated systolic blood pressure (9%), or patient decision (12%).
Patients included in the study were mostly middle-aged (55 years or older), male (more than 65%), and had alcoholic cirrhosis (greater than 74%) or alcoholic hepatitis (39%), with around 88% having ascites.
Dr. Moreau had nothing to disclose. The study was sponsored by the French government.
AT ILC 2017
Key clinical point: Prolonged antibiotic therapy proved beneficial in patients with advanced cirrhosis.
Major finding: Mortality at 6 months was significantly reduced with norfloxacin vs. placebo treatment (adjusted HR, 0.58; 95% CI, 0.34-0.98; P = .042).
Data source: A phase III, multicenter, randomized, double-blind, placebo-controlled trial of 291 patients with Child-Pugh class C cirrhosis who received either 400 mg of norfloxacin or placebo orally, once daily, for 6 months.
Disclosures: Dr. Moreau had nothing to disclose. The study was sponsored by the French government.
Long-term albumin shows survival benefit in decompensated cirrhosis
AMSTERDAM – Long-term treatment with human albumin improved the overall survival of patients with decompensated liver cirrhosis, compared with standard medical care, in a randomized, controlled trial presented at the International Liver Congress.
The final results of the ANSWER study showed that a 38% reduction in the risk of death could be achieved at 18 months’ follow-up by giving patients human albumin, with an overall survival of 78% vs. 66% in the two groups, respectively (hazard ratio, 0.62; 95% confidence interval, 0.40-0.95; P = .028).
“Long-term albumin administration to patients with decompensated cirrhosis may be seen as a disease-modifying treatment,” said the presenting study author, Mauro Bernardi, MD, professor in the department of medical and surgical sciences at the University of Bologna (Italy).
Not only was the overall survival improved, but there was improvement in the management of ascites, a reduction in the incidence of severe complications (such as spontaneous bacterial peritonitis, renal dysfunction, and hepatic encephalopathy), a reduction in the number of hospitalizations and duration of in-hospital treatment, and a signal for improved quality of life, he said.
“We know that it is good to give albumin as an infusion in many, many circumstances,” said Frank Tacke, MD, PhD, who was not involved in the study, during a press briefing at the meeting, sponsored by the European Association for the Study of the Liver (EASL).
“What we did not know before was if there was a role for giving albumin – which is unfortunately quite expensive – for a longer period of time in patients with liver cirrhosis,” said Dr. Tacke, who is the EASL vice-secretary and professor of medicine in the department of gastroenterology, metabolic diseases and intensive care medicine at University Hospital Aachen (Germany).
Although long-term treatment with human albumin is a relatively expensive treatment, particularly because it requires weekly infusion, Dr. Bernardi noted that a cost analysis was being performed, and potentially the cost of treatment could be offset by the reduction in paracentesis, duration of hospitalization, and reduced need for treating patients with complications, compared with standard medical care alone.
“The idea of supplying albumin to patients with advanced cirrhosis is quite an old one, and there is long debate. The point is that a reliable study that could resolve this was simply lacking up to now,” Dr. Bernard said at the briefing.
The results could mean that patients with decompensated cirrhosis now have a much-needed therapeutic option. These patients have “a very poor prognosis,” Dr. Bernardi said. The 1-year probability of survival is about 20%, and the only curative therapy at present is liver transplantation.
A total of 440 patients, mostly male with an average age of 61 years, with cirrhosis and uncomplicated ascites were randomized at 33 Italian centers to receive standard medical treatment alone (n = 213) or with human albumin (n = 218) given at an infused dose of 40 g twice a week for the first 2 weeks, then 40 g every week. The albumin used in the trial was provided by five different pharmaceutical companies and sent to a central location for generic relabeling and distribution out to the participating trial centers.
Significantly fewer patients who were given human albumin than those who were not (66% vs. 38%, P less than .001) needed at least one paracentesis. The incidence rate for the removal of peritoneal fluid in the standard medical treatment arm was 3.5/person per year. There was a 54% reduction in this rate by the addition of human albumin (HR = 0.46; 95% CI, 0.40-0.53; P less than .0001). There was also a significant 46% reduction in the incidence of refractory ascites (48% vs. 25%, P less than .0001).
Patients who received standard medical treatment plus albumin needed fewer hospitalizations and fewer days of in-hospital care per person per year than those in the standard care–only arm. The use of human albumin reduced the number of hospital stays by 35% (HR = 0.65; 95% CI, 0.55-0.77; P less than .0001) and the duration of days in hospital by 45% (HR = 0.55; 95% CI, 0.52-0.58; P less than .0001).
Although not statistically significant, a trend for greater improvements and fewer decreases in quality of life, as measured using the EQ-5D visual assessment scale, at 3, 6, and 12 months, was seen with the use of human albumin.
Four patients had adverse drug reactions: two were mild allergic reactions, and two were potentially life-threatening septic shock that needed intensive care treatment. One of the latter cases might have been caused by pneumonia, and the other required study interruption. But in all cases the patients recovered, Dr. Bernardi reported.
The study was funded by the Italian Drug Agency. Dr. Bernardi had acted as a speaker for and consultant to CLS Behring and Baxter Healthcare, and as a speaker to the Plasma Protein Therapeutics Association’s Europe division, Grifols, Gilead Sciences, and AbbVie Italia. Dr. Tacke had nothing to disclose.
AMSTERDAM – Long-term treatment with human albumin improved the overall survival of patients with decompensated liver cirrhosis, compared with standard medical care, in a randomized, controlled trial presented at the International Liver Congress.
The final results of the ANSWER study showed that a 38% reduction in the risk of death could be achieved at 18 months’ follow-up by giving patients human albumin, with an overall survival of 78% vs. 66% in the two groups, respectively (hazard ratio, 0.62; 95% confidence interval, 0.40-0.95; P = .028).
“Long-term albumin administration to patients with decompensated cirrhosis may be seen as a disease-modifying treatment,” said the presenting study author, Mauro Bernardi, MD, professor in the department of medical and surgical sciences at the University of Bologna (Italy).
Not only was the overall survival improved, but there was improvement in the management of ascites, a reduction in the incidence of severe complications (such as spontaneous bacterial peritonitis, renal dysfunction, and hepatic encephalopathy), a reduction in the number of hospitalizations and duration of in-hospital treatment, and a signal for improved quality of life, he said.
“We know that it is good to give albumin as an infusion in many, many circumstances,” said Frank Tacke, MD, PhD, who was not involved in the study, during a press briefing at the meeting, sponsored by the European Association for the Study of the Liver (EASL).
“What we did not know before was if there was a role for giving albumin – which is unfortunately quite expensive – for a longer period of time in patients with liver cirrhosis,” said Dr. Tacke, who is the EASL vice-secretary and professor of medicine in the department of gastroenterology, metabolic diseases and intensive care medicine at University Hospital Aachen (Germany).
Although long-term treatment with human albumin is a relatively expensive treatment, particularly because it requires weekly infusion, Dr. Bernardi noted that a cost analysis was being performed, and potentially the cost of treatment could be offset by the reduction in paracentesis, duration of hospitalization, and reduced need for treating patients with complications, compared with standard medical care alone.
“The idea of supplying albumin to patients with advanced cirrhosis is quite an old one, and there is long debate. The point is that a reliable study that could resolve this was simply lacking up to now,” Dr. Bernard said at the briefing.
The results could mean that patients with decompensated cirrhosis now have a much-needed therapeutic option. These patients have “a very poor prognosis,” Dr. Bernardi said. The 1-year probability of survival is about 20%, and the only curative therapy at present is liver transplantation.
A total of 440 patients, mostly male with an average age of 61 years, with cirrhosis and uncomplicated ascites were randomized at 33 Italian centers to receive standard medical treatment alone (n = 213) or with human albumin (n = 218) given at an infused dose of 40 g twice a week for the first 2 weeks, then 40 g every week. The albumin used in the trial was provided by five different pharmaceutical companies and sent to a central location for generic relabeling and distribution out to the participating trial centers.
Significantly fewer patients who were given human albumin than those who were not (66% vs. 38%, P less than .001) needed at least one paracentesis. The incidence rate for the removal of peritoneal fluid in the standard medical treatment arm was 3.5/person per year. There was a 54% reduction in this rate by the addition of human albumin (HR = 0.46; 95% CI, 0.40-0.53; P less than .0001). There was also a significant 46% reduction in the incidence of refractory ascites (48% vs. 25%, P less than .0001).
Patients who received standard medical treatment plus albumin needed fewer hospitalizations and fewer days of in-hospital care per person per year than those in the standard care–only arm. The use of human albumin reduced the number of hospital stays by 35% (HR = 0.65; 95% CI, 0.55-0.77; P less than .0001) and the duration of days in hospital by 45% (HR = 0.55; 95% CI, 0.52-0.58; P less than .0001).
Although not statistically significant, a trend for greater improvements and fewer decreases in quality of life, as measured using the EQ-5D visual assessment scale, at 3, 6, and 12 months, was seen with the use of human albumin.
Four patients had adverse drug reactions: two were mild allergic reactions, and two were potentially life-threatening septic shock that needed intensive care treatment. One of the latter cases might have been caused by pneumonia, and the other required study interruption. But in all cases the patients recovered, Dr. Bernardi reported.
The study was funded by the Italian Drug Agency. Dr. Bernardi had acted as a speaker for and consultant to CLS Behring and Baxter Healthcare, and as a speaker to the Plasma Protein Therapeutics Association’s Europe division, Grifols, Gilead Sciences, and AbbVie Italia. Dr. Tacke had nothing to disclose.
AMSTERDAM – Long-term treatment with human albumin improved the overall survival of patients with decompensated liver cirrhosis, compared with standard medical care, in a randomized, controlled trial presented at the International Liver Congress.
The final results of the ANSWER study showed that a 38% reduction in the risk of death could be achieved at 18 months’ follow-up by giving patients human albumin, with an overall survival of 78% vs. 66% in the two groups, respectively (hazard ratio, 0.62; 95% confidence interval, 0.40-0.95; P = .028).
“Long-term albumin administration to patients with decompensated cirrhosis may be seen as a disease-modifying treatment,” said the presenting study author, Mauro Bernardi, MD, professor in the department of medical and surgical sciences at the University of Bologna (Italy).
Not only was the overall survival improved, but there was improvement in the management of ascites, a reduction in the incidence of severe complications (such as spontaneous bacterial peritonitis, renal dysfunction, and hepatic encephalopathy), a reduction in the number of hospitalizations and duration of in-hospital treatment, and a signal for improved quality of life, he said.
“We know that it is good to give albumin as an infusion in many, many circumstances,” said Frank Tacke, MD, PhD, who was not involved in the study, during a press briefing at the meeting, sponsored by the European Association for the Study of the Liver (EASL).
“What we did not know before was if there was a role for giving albumin – which is unfortunately quite expensive – for a longer period of time in patients with liver cirrhosis,” said Dr. Tacke, who is the EASL vice-secretary and professor of medicine in the department of gastroenterology, metabolic diseases and intensive care medicine at University Hospital Aachen (Germany).
Although long-term treatment with human albumin is a relatively expensive treatment, particularly because it requires weekly infusion, Dr. Bernardi noted that a cost analysis was being performed, and potentially the cost of treatment could be offset by the reduction in paracentesis, duration of hospitalization, and reduced need for treating patients with complications, compared with standard medical care alone.
“The idea of supplying albumin to patients with advanced cirrhosis is quite an old one, and there is long debate. The point is that a reliable study that could resolve this was simply lacking up to now,” Dr. Bernard said at the briefing.
The results could mean that patients with decompensated cirrhosis now have a much-needed therapeutic option. These patients have “a very poor prognosis,” Dr. Bernardi said. The 1-year probability of survival is about 20%, and the only curative therapy at present is liver transplantation.
A total of 440 patients, mostly male with an average age of 61 years, with cirrhosis and uncomplicated ascites were randomized at 33 Italian centers to receive standard medical treatment alone (n = 213) or with human albumin (n = 218) given at an infused dose of 40 g twice a week for the first 2 weeks, then 40 g every week. The albumin used in the trial was provided by five different pharmaceutical companies and sent to a central location for generic relabeling and distribution out to the participating trial centers.
Significantly fewer patients who were given human albumin than those who were not (66% vs. 38%, P less than .001) needed at least one paracentesis. The incidence rate for the removal of peritoneal fluid in the standard medical treatment arm was 3.5/person per year. There was a 54% reduction in this rate by the addition of human albumin (HR = 0.46; 95% CI, 0.40-0.53; P less than .0001). There was also a significant 46% reduction in the incidence of refractory ascites (48% vs. 25%, P less than .0001).
Patients who received standard medical treatment plus albumin needed fewer hospitalizations and fewer days of in-hospital care per person per year than those in the standard care–only arm. The use of human albumin reduced the number of hospital stays by 35% (HR = 0.65; 95% CI, 0.55-0.77; P less than .0001) and the duration of days in hospital by 45% (HR = 0.55; 95% CI, 0.52-0.58; P less than .0001).
Although not statistically significant, a trend for greater improvements and fewer decreases in quality of life, as measured using the EQ-5D visual assessment scale, at 3, 6, and 12 months, was seen with the use of human albumin.
Four patients had adverse drug reactions: two were mild allergic reactions, and two were potentially life-threatening septic shock that needed intensive care treatment. One of the latter cases might have been caused by pneumonia, and the other required study interruption. But in all cases the patients recovered, Dr. Bernardi reported.
The study was funded by the Italian Drug Agency. Dr. Bernardi had acted as a speaker for and consultant to CLS Behring and Baxter Healthcare, and as a speaker to the Plasma Protein Therapeutics Association’s Europe division, Grifols, Gilead Sciences, and AbbVie Italia. Dr. Tacke had nothing to disclose.
AT ILC 2017
Key clinical point: A weekly infusion of human albumin has a beneficial effect in patients with decompensated cirrhosis.
Major finding: Overall survival was 78% vs. 66% for standard medical care with albumin vs. no albumin (HR, 0.62; 95% CI, 0.40-0.95; P = .028).
Data source: The ANSWER study, a multicenter, open-label, randomized clinical trial of 440 patients with decompensated cirrhosis.
Disclosures: The study was funded by the Italian Drug Agency. Dr. Bernardi had acted as a speaker for and consultant to CLS Behring and Baxter Healthcare, and as a speaker to the Plasma Protein Therapeutics Association’s Europe division, Grifols, Gilead Sciences, and AbbVie Italia. Dr. Tacke had nothing to disclose.
WHO report sets baseline for viral hepatitis elimination
AMSTERDAM – An estimated 328 million people worldwide were living with chronic hepatitis B or C virus infection in 2015 according to a new report issued by the World Health Organization and launched at the International Liver Congress sponsored by the European Association for the Study of the Liver (EASL).
The WHO Global Hepatitis Report gives the worldwide prevalence of chronic hepatitis B (HBV) infection as 257 million and that of chronic hepatitis C (HCV) infection as 71 million at this time point, reported Yvan Hutin, MD, medical officer at the WHO Department of HIV and Global Hepatitis Programme (HIV/GHP) in Geneva.
Dr. Hutin explained that the report was needed as it sets the baseline or “year zero” for tracking the success of WHO’s new global health sector strategy on viral hepatitis, which aims to eliminate viral hepatitis as a public health threat, reduce the number of new HBV and HCV infections by 90%, and reduce viral hepatitis mortality by 65% by 2030.
The report was “a very important statement for all of us who work in this field,” said EASL Vice-Secretary Tom Hemming Karslen, MD, during a press briefing. “This is a wonderful initiative helping all the activities that are now already ongoing and need to be strengthened to move in a coordinated manner.”
The launch of the report at the International Liver Congress was “win-win situation”, Gottfried Hirnschall, MD, director of the WHO Department of HIV/GHP, said at the press briefing.
“We are in the era of elimination. It is not only the commitment of the WHO, it is the commitment of the 194 member states who have signed up for elimination,” he said.
“An important message is that people are still dying of hepatitis, the numbers are still going up,” Dr. Hirnschall said. There were an estimated 1.34 million viral hepatitis deaths worldwide in 2015, most (95%) were due to the development of cirrhosis or hepatocellular carcinoma, according to the new report. “We have a public health issue that obviously still needs to be addressed.”
Three decades ago, little could be done to prevent or treat infection with HBV or HCV, Dr. Hutin said during the opening general scientific session. A lot has changed since then, prevention of hepatitis B started to become a reality with the availability of a vaccine and understanding of the importance of improved blood safety and injection practices. Since 2010, there have also been improvements in the drugs available to treat, and potentially eliminate, HCV, notably direct-acting antiviral agents.
“To reach elimination, we modeled that we needed to reach sufficient service coverage for five core interventions,” Dr. Hutin said. Specifically:
- At least 90% of the world’s eligible population receives the three-dose hepatitis B vaccine
- 100% of blood donations are screened appropriately
- Proper injection technique is employed in 90% of cases
- Clean needles made available where they are needed
- 90% of people infected are diagnosed and 80% are treated.
Vaccination against HBV has been one success in the past 20 years, Ana Maria Henao Restrepo, MD, medical officer at the WHO Department of Immunization Vaccination and Biologicals, said at the press briefing.
Vaccination against HBV started in 1982, she said, “when the first safe and effective vaccine became available, and now four out of five children receive this life-saving vaccine. We are very pleased with this achievement but we know that there is still more work to do.”
The WHO report estimates that the global incidence of chronic HBV infection in children under 5 years of age was reduced from 4.7% in the pre-vaccination era to 1.3% in 2015 because of immunization.
But while uptake of the three-dose hepatitis B vaccine has increased, with 85% coverage of the worlds population in 2015, the number of children receiving this vaccine at birth is just 39% overall, with lower rates in the African region.
“Unsafe health care injections and injection drug use continue to transmit HCV, particularly in the eastern Mediterranean region and the European region,” Dr. Hutin said.
The WHO has already set up a campaign to improve blood and injection safety called “Get the Point,” but there is still a long way to go. The target is to provide 300 needle and syringe sets per person per year to people who inject drugs; the current rate is around 27 sets.
Of the 257 people infected with hepatitis B in 2015, only 9% were diagnosed and 1.7 million received treatment. As for hepatitis C, 20% of 71 million were diagnosed and 1.1 million received treatment.
“We need a public health approach that delivers all the basic services to all, including to specific groups that may differ from the general population in terms of incidence, prevalence, vulnerability, or needs,” said Dr. Hutin. This includes health care workers, intravenous drug users, prisoners, migrants, blood donors, men who have sex with men, sex workers, and indigenous populations.
“We have all the tools we need to eliminate hepatitis,” he said, adding that improved point of care tests, a functional cure for HBV, and a vaccine against HCV would accelerate the process.
“A year ago, elimination by 2030 looked very ambitious, but not that we’ve carefully looked at the baseline, it seems that we have a start. It’s going to be a lot of work but the train has left the station and we should get there,” Dr. Hutin concluded.
The U.S. Centers for Disease Control and Prevention provided funding for the production of the report. All speakers had no conflicts of interest.
AMSTERDAM – An estimated 328 million people worldwide were living with chronic hepatitis B or C virus infection in 2015 according to a new report issued by the World Health Organization and launched at the International Liver Congress sponsored by the European Association for the Study of the Liver (EASL).
The WHO Global Hepatitis Report gives the worldwide prevalence of chronic hepatitis B (HBV) infection as 257 million and that of chronic hepatitis C (HCV) infection as 71 million at this time point, reported Yvan Hutin, MD, medical officer at the WHO Department of HIV and Global Hepatitis Programme (HIV/GHP) in Geneva.
Dr. Hutin explained that the report was needed as it sets the baseline or “year zero” for tracking the success of WHO’s new global health sector strategy on viral hepatitis, which aims to eliminate viral hepatitis as a public health threat, reduce the number of new HBV and HCV infections by 90%, and reduce viral hepatitis mortality by 65% by 2030.
The report was “a very important statement for all of us who work in this field,” said EASL Vice-Secretary Tom Hemming Karslen, MD, during a press briefing. “This is a wonderful initiative helping all the activities that are now already ongoing and need to be strengthened to move in a coordinated manner.”
The launch of the report at the International Liver Congress was “win-win situation”, Gottfried Hirnschall, MD, director of the WHO Department of HIV/GHP, said at the press briefing.
“We are in the era of elimination. It is not only the commitment of the WHO, it is the commitment of the 194 member states who have signed up for elimination,” he said.
“An important message is that people are still dying of hepatitis, the numbers are still going up,” Dr. Hirnschall said. There were an estimated 1.34 million viral hepatitis deaths worldwide in 2015, most (95%) were due to the development of cirrhosis or hepatocellular carcinoma, according to the new report. “We have a public health issue that obviously still needs to be addressed.”
Three decades ago, little could be done to prevent or treat infection with HBV or HCV, Dr. Hutin said during the opening general scientific session. A lot has changed since then, prevention of hepatitis B started to become a reality with the availability of a vaccine and understanding of the importance of improved blood safety and injection practices. Since 2010, there have also been improvements in the drugs available to treat, and potentially eliminate, HCV, notably direct-acting antiviral agents.
“To reach elimination, we modeled that we needed to reach sufficient service coverage for five core interventions,” Dr. Hutin said. Specifically:
- At least 90% of the world’s eligible population receives the three-dose hepatitis B vaccine
- 100% of blood donations are screened appropriately
- Proper injection technique is employed in 90% of cases
- Clean needles made available where they are needed
- 90% of people infected are diagnosed and 80% are treated.
Vaccination against HBV has been one success in the past 20 years, Ana Maria Henao Restrepo, MD, medical officer at the WHO Department of Immunization Vaccination and Biologicals, said at the press briefing.
Vaccination against HBV started in 1982, she said, “when the first safe and effective vaccine became available, and now four out of five children receive this life-saving vaccine. We are very pleased with this achievement but we know that there is still more work to do.”
The WHO report estimates that the global incidence of chronic HBV infection in children under 5 years of age was reduced from 4.7% in the pre-vaccination era to 1.3% in 2015 because of immunization.
But while uptake of the three-dose hepatitis B vaccine has increased, with 85% coverage of the worlds population in 2015, the number of children receiving this vaccine at birth is just 39% overall, with lower rates in the African region.
“Unsafe health care injections and injection drug use continue to transmit HCV, particularly in the eastern Mediterranean region and the European region,” Dr. Hutin said.
The WHO has already set up a campaign to improve blood and injection safety called “Get the Point,” but there is still a long way to go. The target is to provide 300 needle and syringe sets per person per year to people who inject drugs; the current rate is around 27 sets.
Of the 257 people infected with hepatitis B in 2015, only 9% were diagnosed and 1.7 million received treatment. As for hepatitis C, 20% of 71 million were diagnosed and 1.1 million received treatment.
“We need a public health approach that delivers all the basic services to all, including to specific groups that may differ from the general population in terms of incidence, prevalence, vulnerability, or needs,” said Dr. Hutin. This includes health care workers, intravenous drug users, prisoners, migrants, blood donors, men who have sex with men, sex workers, and indigenous populations.
“We have all the tools we need to eliminate hepatitis,” he said, adding that improved point of care tests, a functional cure for HBV, and a vaccine against HCV would accelerate the process.
“A year ago, elimination by 2030 looked very ambitious, but not that we’ve carefully looked at the baseline, it seems that we have a start. It’s going to be a lot of work but the train has left the station and we should get there,” Dr. Hutin concluded.
The U.S. Centers for Disease Control and Prevention provided funding for the production of the report. All speakers had no conflicts of interest.
AMSTERDAM – An estimated 328 million people worldwide were living with chronic hepatitis B or C virus infection in 2015 according to a new report issued by the World Health Organization and launched at the International Liver Congress sponsored by the European Association for the Study of the Liver (EASL).
The WHO Global Hepatitis Report gives the worldwide prevalence of chronic hepatitis B (HBV) infection as 257 million and that of chronic hepatitis C (HCV) infection as 71 million at this time point, reported Yvan Hutin, MD, medical officer at the WHO Department of HIV and Global Hepatitis Programme (HIV/GHP) in Geneva.
Dr. Hutin explained that the report was needed as it sets the baseline or “year zero” for tracking the success of WHO’s new global health sector strategy on viral hepatitis, which aims to eliminate viral hepatitis as a public health threat, reduce the number of new HBV and HCV infections by 90%, and reduce viral hepatitis mortality by 65% by 2030.
The report was “a very important statement for all of us who work in this field,” said EASL Vice-Secretary Tom Hemming Karslen, MD, during a press briefing. “This is a wonderful initiative helping all the activities that are now already ongoing and need to be strengthened to move in a coordinated manner.”
The launch of the report at the International Liver Congress was “win-win situation”, Gottfried Hirnschall, MD, director of the WHO Department of HIV/GHP, said at the press briefing.
“We are in the era of elimination. It is not only the commitment of the WHO, it is the commitment of the 194 member states who have signed up for elimination,” he said.
“An important message is that people are still dying of hepatitis, the numbers are still going up,” Dr. Hirnschall said. There were an estimated 1.34 million viral hepatitis deaths worldwide in 2015, most (95%) were due to the development of cirrhosis or hepatocellular carcinoma, according to the new report. “We have a public health issue that obviously still needs to be addressed.”
Three decades ago, little could be done to prevent or treat infection with HBV or HCV, Dr. Hutin said during the opening general scientific session. A lot has changed since then, prevention of hepatitis B started to become a reality with the availability of a vaccine and understanding of the importance of improved blood safety and injection practices. Since 2010, there have also been improvements in the drugs available to treat, and potentially eliminate, HCV, notably direct-acting antiviral agents.
“To reach elimination, we modeled that we needed to reach sufficient service coverage for five core interventions,” Dr. Hutin said. Specifically:
- At least 90% of the world’s eligible population receives the three-dose hepatitis B vaccine
- 100% of blood donations are screened appropriately
- Proper injection technique is employed in 90% of cases
- Clean needles made available where they are needed
- 90% of people infected are diagnosed and 80% are treated.
Vaccination against HBV has been one success in the past 20 years, Ana Maria Henao Restrepo, MD, medical officer at the WHO Department of Immunization Vaccination and Biologicals, said at the press briefing.
Vaccination against HBV started in 1982, she said, “when the first safe and effective vaccine became available, and now four out of five children receive this life-saving vaccine. We are very pleased with this achievement but we know that there is still more work to do.”
The WHO report estimates that the global incidence of chronic HBV infection in children under 5 years of age was reduced from 4.7% in the pre-vaccination era to 1.3% in 2015 because of immunization.
But while uptake of the three-dose hepatitis B vaccine has increased, with 85% coverage of the worlds population in 2015, the number of children receiving this vaccine at birth is just 39% overall, with lower rates in the African region.
“Unsafe health care injections and injection drug use continue to transmit HCV, particularly in the eastern Mediterranean region and the European region,” Dr. Hutin said.
The WHO has already set up a campaign to improve blood and injection safety called “Get the Point,” but there is still a long way to go. The target is to provide 300 needle and syringe sets per person per year to people who inject drugs; the current rate is around 27 sets.
Of the 257 people infected with hepatitis B in 2015, only 9% were diagnosed and 1.7 million received treatment. As for hepatitis C, 20% of 71 million were diagnosed and 1.1 million received treatment.
“We need a public health approach that delivers all the basic services to all, including to specific groups that may differ from the general population in terms of incidence, prevalence, vulnerability, or needs,” said Dr. Hutin. This includes health care workers, intravenous drug users, prisoners, migrants, blood donors, men who have sex with men, sex workers, and indigenous populations.
“We have all the tools we need to eliminate hepatitis,” he said, adding that improved point of care tests, a functional cure for HBV, and a vaccine against HCV would accelerate the process.
“A year ago, elimination by 2030 looked very ambitious, but not that we’ve carefully looked at the baseline, it seems that we have a start. It’s going to be a lot of work but the train has left the station and we should get there,” Dr. Hutin concluded.
The U.S. Centers for Disease Control and Prevention provided funding for the production of the report. All speakers had no conflicts of interest.
AT ILC 2017