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Digestive Disease Week (DDW 2014)
Sofosbuvir-ribavirin treats hepatitis C virus genotypes 2, 3
CHICAGO – Oral sofosbuvir and ribavirin given for 12 weeks produced a sustained virologic response in 93% of 250 patients with hepatitis C virus genotype 2 and in 85% of patients with genotype 3 infection who were treated for 24 weeks.
The 77-center European study defined a sustained virologic response as a hepatitis C virus RNA level of less than 25 IU/mL, Dr. Stefan Zeuzem and his associates reported. More than half of the patients (58%) had undergone prior therapy with interferon-based regimens, with no response in 30%. Cirrhosis was present in 21% of patients.
The study began as a phase III trial randomizing patients to receive 12 weeks of once-daily oral sofosbuvir 400 mg and twice-daily oral ribavirin (administered according to body weight), or matching placebo. The investigators turned the trial into a descriptive study after a previous study reported that patients with genotype 3 infection might benefit from more than 12 weeks of sofosbuvir therapy (N. Engl. J. Med. 2013;368:1867-77).
Dr. Zeuzem and his associates unblinded the treatment arms, dropped placebo treatment, and extended treatment for patients with genotype 3 infection to 24 weeks. The findings were published online in the New England Journal of Medicine (N. Engl. J. Med. 2014 May 4 [doi: 1056/NEJMoa1316145]).
Among patients with genotype 3 infection, a sustained virologic response developed in 68% of those with cirrhosis and 91% without cirrhosis, reported Dr. Zeuzem, who is professor of medicine and chief of the department of medicine I at Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany.
Headache, fatigue, and pruritus were the most common adverse events. Approximately 1% of patients in both the genotype 3 and 4 groups discontinued treatment due to side effects.
Treatment history and the presence of cirrhosis affected response rates in patients with genotype 3 infection. In previously untreated patients, a sustained virologic response was seen in 92% of those with cirrhosis and in 95% without cirrhosis. Response rates were lower in previously treated patients with cirrhosis (62%) and without cirrhosis (87%). The reasons for these differences are unknown.
Four factors were independently associated with a sustained virologic response in patients with genotype 3 infection, a multivariate regression analysis found. A sustained response was four times as likely in those with a baseline hepatitis C virus RNA level of less than 6 log10 IU and three times as likely in women, patients without cirrhosis, or those under age 50, compared with patients without those characteristics. These predictive factors must be validated in further studies, Dr. Zeuzem said.
Three patients with genotype 3 infection had a virologic relapse. The response rate and relapse rate for patients with genotype 3 who were treated for 24 weeks were "substantially" better than rates reported in previous studies using the same regimen for 12 or 16 weeks, the investigators said. Extending the duration of treatment did not significantly increase adverse events or discontinuation of therapy.
The findings suggest that sofosbuvir-ribavirin can be an alternative therapy for patients with hepatitis C virus genotype 2 or 3 who have contraindications to peginterferon-based treatment, Dr. Zeuzem said.
Gilead Sciences, which markets sofosbuvir, funded the study. Dr. Zeuzem reported financial associations with Gilead and multiple other pharmaceutical companies, as did many of his coinvestigators.
On Twitter @sherryboschert
CHICAGO – Oral sofosbuvir and ribavirin given for 12 weeks produced a sustained virologic response in 93% of 250 patients with hepatitis C virus genotype 2 and in 85% of patients with genotype 3 infection who were treated for 24 weeks.
The 77-center European study defined a sustained virologic response as a hepatitis C virus RNA level of less than 25 IU/mL, Dr. Stefan Zeuzem and his associates reported. More than half of the patients (58%) had undergone prior therapy with interferon-based regimens, with no response in 30%. Cirrhosis was present in 21% of patients.
The study began as a phase III trial randomizing patients to receive 12 weeks of once-daily oral sofosbuvir 400 mg and twice-daily oral ribavirin (administered according to body weight), or matching placebo. The investigators turned the trial into a descriptive study after a previous study reported that patients with genotype 3 infection might benefit from more than 12 weeks of sofosbuvir therapy (N. Engl. J. Med. 2013;368:1867-77).
Dr. Zeuzem and his associates unblinded the treatment arms, dropped placebo treatment, and extended treatment for patients with genotype 3 infection to 24 weeks. The findings were published online in the New England Journal of Medicine (N. Engl. J. Med. 2014 May 4 [doi: 1056/NEJMoa1316145]).
Among patients with genotype 3 infection, a sustained virologic response developed in 68% of those with cirrhosis and 91% without cirrhosis, reported Dr. Zeuzem, who is professor of medicine and chief of the department of medicine I at Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany.
Headache, fatigue, and pruritus were the most common adverse events. Approximately 1% of patients in both the genotype 3 and 4 groups discontinued treatment due to side effects.
Treatment history and the presence of cirrhosis affected response rates in patients with genotype 3 infection. In previously untreated patients, a sustained virologic response was seen in 92% of those with cirrhosis and in 95% without cirrhosis. Response rates were lower in previously treated patients with cirrhosis (62%) and without cirrhosis (87%). The reasons for these differences are unknown.
Four factors were independently associated with a sustained virologic response in patients with genotype 3 infection, a multivariate regression analysis found. A sustained response was four times as likely in those with a baseline hepatitis C virus RNA level of less than 6 log10 IU and three times as likely in women, patients without cirrhosis, or those under age 50, compared with patients without those characteristics. These predictive factors must be validated in further studies, Dr. Zeuzem said.
Three patients with genotype 3 infection had a virologic relapse. The response rate and relapse rate for patients with genotype 3 who were treated for 24 weeks were "substantially" better than rates reported in previous studies using the same regimen for 12 or 16 weeks, the investigators said. Extending the duration of treatment did not significantly increase adverse events or discontinuation of therapy.
The findings suggest that sofosbuvir-ribavirin can be an alternative therapy for patients with hepatitis C virus genotype 2 or 3 who have contraindications to peginterferon-based treatment, Dr. Zeuzem said.
Gilead Sciences, which markets sofosbuvir, funded the study. Dr. Zeuzem reported financial associations with Gilead and multiple other pharmaceutical companies, as did many of his coinvestigators.
On Twitter @sherryboschert
CHICAGO – Oral sofosbuvir and ribavirin given for 12 weeks produced a sustained virologic response in 93% of 250 patients with hepatitis C virus genotype 2 and in 85% of patients with genotype 3 infection who were treated for 24 weeks.
The 77-center European study defined a sustained virologic response as a hepatitis C virus RNA level of less than 25 IU/mL, Dr. Stefan Zeuzem and his associates reported. More than half of the patients (58%) had undergone prior therapy with interferon-based regimens, with no response in 30%. Cirrhosis was present in 21% of patients.
The study began as a phase III trial randomizing patients to receive 12 weeks of once-daily oral sofosbuvir 400 mg and twice-daily oral ribavirin (administered according to body weight), or matching placebo. The investigators turned the trial into a descriptive study after a previous study reported that patients with genotype 3 infection might benefit from more than 12 weeks of sofosbuvir therapy (N. Engl. J. Med. 2013;368:1867-77).
Dr. Zeuzem and his associates unblinded the treatment arms, dropped placebo treatment, and extended treatment for patients with genotype 3 infection to 24 weeks. The findings were published online in the New England Journal of Medicine (N. Engl. J. Med. 2014 May 4 [doi: 1056/NEJMoa1316145]).
Among patients with genotype 3 infection, a sustained virologic response developed in 68% of those with cirrhosis and 91% without cirrhosis, reported Dr. Zeuzem, who is professor of medicine and chief of the department of medicine I at Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany.
Headache, fatigue, and pruritus were the most common adverse events. Approximately 1% of patients in both the genotype 3 and 4 groups discontinued treatment due to side effects.
Treatment history and the presence of cirrhosis affected response rates in patients with genotype 3 infection. In previously untreated patients, a sustained virologic response was seen in 92% of those with cirrhosis and in 95% without cirrhosis. Response rates were lower in previously treated patients with cirrhosis (62%) and without cirrhosis (87%). The reasons for these differences are unknown.
Four factors were independently associated with a sustained virologic response in patients with genotype 3 infection, a multivariate regression analysis found. A sustained response was four times as likely in those with a baseline hepatitis C virus RNA level of less than 6 log10 IU and three times as likely in women, patients without cirrhosis, or those under age 50, compared with patients without those characteristics. These predictive factors must be validated in further studies, Dr. Zeuzem said.
Three patients with genotype 3 infection had a virologic relapse. The response rate and relapse rate for patients with genotype 3 who were treated for 24 weeks were "substantially" better than rates reported in previous studies using the same regimen for 12 or 16 weeks, the investigators said. Extending the duration of treatment did not significantly increase adverse events or discontinuation of therapy.
The findings suggest that sofosbuvir-ribavirin can be an alternative therapy for patients with hepatitis C virus genotype 2 or 3 who have contraindications to peginterferon-based treatment, Dr. Zeuzem said.
Gilead Sciences, which markets sofosbuvir, funded the study. Dr. Zeuzem reported financial associations with Gilead and multiple other pharmaceutical companies, as did many of his coinvestigators.
On Twitter @sherryboschert
AT DDW 2014
Major finding: Sustained virologic response occurred in 93% after 12 weeks of treatment for genotype 2 and in 85% after 24 weeks of therapy for genotype 3.
Data source: A descriptive cohort study of 419 patients with hepatitis C genotypes 2 or 3 treated with sofosbuvir and ribavirin.
Disclosures: Gilead Sciences, which markets sofosbuvir, funded the study. Dr. Zeuzem reported financial associations with Gilead and multiple other pharmaceutical companies, as did many of his coinvestigators.
Initial dilation no help in eosinophilic esophagitis
CHICAGO – Esophageal dilation combined with standard medical management of eosinophilic esophagitis doesn’t provide added benefit over medication alone in terms of dysphagia relief, according to a randomized, blinded clinical trial.
"In our group of patients with moderate endoscopic findings and without severe stricturing disease, esophageal dilation does not appear to be a necessary additional treatment strategy," Dr. Robert T. Kavitt stated at the annual Digestive Disease Week.
The study involved 31 patients newly diagnosed with eosinophilic esophagitis and baseline moderate to severe difficulty in swallowing. They were randomized to dilation or no dilation at initial endoscopy. Then all patients received standard medical management with 440 mcg of swallowed fluticasone b.i.d. and dexlansoprazole at 60 mg/day for 2 months. Patients were blinded as to their dilation status, as were the physicians who rated their change in dysphagia scores during follow-up.
Both groups experienced robust albeit equal reductions in overall dysphagia scores upon assessment at 30 and 60 days after endoscopy. At baseline, dysphagia scores averaged 6-6.5 on a 0-9 scale, indicative of moderate to severe dysphagia. At follow-up, scores in both groups had dropped to an average of 3 or less, reported Dr. Kavitt of the University of Chicago.
Complete resolution of dysphagia, defined as a dysphagia score of 0, occurred in only 23% of the dilation group and 57% of the no-dilation controls, which was not a statistically significant difference. The looser standard of "significant improvement" – meaning a dysphagia score of 3 or less – was met by 92% of the dilation group and 86% of controls.
Two patients in the dilation group and one control reported odynophagia.
Patients in the dilation group were dilated to the endpoint of mucosal tear. Three-quarters of the patients were dilated to a maximum size of 50 French or larger.
Baseline endoscopic scores assessing strictures, fissures, rings, and other abnormalities were in the moderate range on a 0-13 severity scale, so the study finding of a lack of benefit for dilation as part of an initial treatment strategy in eosinophilic esophagitis may not extend to the minority of patients having truly severe stricturing disease, according to Dr. Kavitt.
He noted that, before this study, the role of dilation in the treatment of eosinophilic esophagitis was a matter of divergent expert opinion unsupported by randomized trial evidence. The 2013 American College of Gastroenterology guidelines state that "the role of dilation as a primary monotherapy of eosinophilic esophagitis is still controversial and should be individualized."
Later during the meeting, in his state-of-the-art lecture on changing therapeutic concepts in eosinophilic esophagitis, Dr. Ikuo Hirano cited Dr. Kavitt’s randomized trial in support of his argument against dilation as primary therapy.
"Dilation does nothing to address the underlying inflammatory response that’s causing strictures to form," noted Dr. Hirano, professor of medicine at Northwestern University, Chicago. "I believe that dilation is inappropriate therapy for children and adults with a predominantly inflammatory phenotype of disease."
Medication and diet therapies not only relieve the symptoms of eosinophilic esophagitis, he continued, they also improve the histopathology.
Dilation entails considerable pain as well as a risk of perforation. Recent reassuring safety data regarding dilation for eosinophilic esophagitis come from specialized esophageal centers with an unusual amount of experience with the procedure, the gastroenterologist said.
Dr. Kavitt reported having no financial conflicts of interest with regard to the randomized trial, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
This is the first prospective examination of the role of esophageal dilation in eosinophilic esophagitis (EoE). The symptom-based outcomes suggest that dilation is not necessary for the initial therapy of EoE. The improvement in dysphagia was equivalent in patients treated with dilation combined with medical therapy, compared with those treated with medical therapy alone.
 |
| Dr. Ikuo Hirano |
Moreover, while all patients randomized to dilation had dysphagia, not all had endoscopically identified esophageal strictures. One would not expect therapeutic gain for esophageal dilation in the absence of an identifiable stricture. Furthermore, randomized controlled trials of medical therapy for EoE have identified a surprisingly high placebo-response rate for the outcome of dysphagia that may have made demonstration of the benefits of dilation difficult to detect, especially in patients with mild disease severity. Symptom improvement in dysphagia may occur in response to modifications in eating habits such as meticulous mastication or avoidance of highly textured foods.
Finally, the inability to discern a difference in treatment groups may reflect the use of a nonvalidated dysphagia severity assessment instrument.
Despite these shortcomings, the results support current guideline recommendations that dilation should target aspects of esophageal remodeling in EoE that are not amenable to currently available medical or diet therapies.
The data, however, do not exclude an important therapeutic benefit of esophageal dilation in EoE. The study excluded patients with significant strictures that could not be traversed with a standard adult endoscope. The findings, therefore, would not apply to EoE patients with substantial fibrostenosis.
In this study, medical therapy was highly effective at relieving symptoms, but prior studies have shown that symptoms recur in almost all patients following cessation of medications.
Dilation, on the other hand, is generally safe and provides long-lasting relief of dysphagia in adults, even in the absence of medical or diet therapy. Additional prospective studies are needed to define the most appropriate patient subgroups that would benefit from dilation.
Dr. Ikuo Hirano is professor of medicine in the division of gastroenterology at Northwestern University's Feinberg School of Medicine in Chicago. He serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
This is the first prospective examination of the role of esophageal dilation in eosinophilic esophagitis (EoE). The symptom-based outcomes suggest that dilation is not necessary for the initial therapy of EoE. The improvement in dysphagia was equivalent in patients treated with dilation combined with medical therapy, compared with those treated with medical therapy alone.
|
| Dr. Ikuo Hirano |
Moreover, while all patients randomized to dilation had dysphagia, not all had endoscopically identified esophageal strictures. One would not expect therapeutic gain for esophageal dilation in the absence of an identifiable stricture. Furthermore, randomized controlled trials of medical therapy for EoE have identified a surprisingly high placebo-response rate for the outcome of dysphagia that may have made demonstration of the benefits of dilation difficult to detect, especially in patients with mild disease severity. Symptom improvement in dysphagia may occur in response to modifications in eating habits such as meticulous mastication or avoidance of highly textured foods.
Finally, the inability to discern a difference in treatment groups may reflect the use of a nonvalidated dysphagia severity assessment instrument.
Despite these shortcomings, the results support current guideline recommendations that dilation should target aspects of esophageal remodeling in EoE that are not amenable to currently available medical or diet therapies.
The data, however, do not exclude an important therapeutic benefit of esophageal dilation in EoE. The study excluded patients with significant strictures that could not be traversed with a standard adult endoscope. The findings, therefore, would not apply to EoE patients with substantial fibrostenosis.
In this study, medical therapy was highly effective at relieving symptoms, but prior studies have shown that symptoms recur in almost all patients following cessation of medications.
Dilation, on the other hand, is generally safe and provides long-lasting relief of dysphagia in adults, even in the absence of medical or diet therapy. Additional prospective studies are needed to define the most appropriate patient subgroups that would benefit from dilation.
Dr. Ikuo Hirano is professor of medicine in the division of gastroenterology at Northwestern University's Feinberg School of Medicine in Chicago. He serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
This is the first prospective examination of the role of esophageal dilation in eosinophilic esophagitis (EoE). The symptom-based outcomes suggest that dilation is not necessary for the initial therapy of EoE. The improvement in dysphagia was equivalent in patients treated with dilation combined with medical therapy, compared with those treated with medical therapy alone.
|
| Dr. Ikuo Hirano |
Moreover, while all patients randomized to dilation had dysphagia, not all had endoscopically identified esophageal strictures. One would not expect therapeutic gain for esophageal dilation in the absence of an identifiable stricture. Furthermore, randomized controlled trials of medical therapy for EoE have identified a surprisingly high placebo-response rate for the outcome of dysphagia that may have made demonstration of the benefits of dilation difficult to detect, especially in patients with mild disease severity. Symptom improvement in dysphagia may occur in response to modifications in eating habits such as meticulous mastication or avoidance of highly textured foods.
Finally, the inability to discern a difference in treatment groups may reflect the use of a nonvalidated dysphagia severity assessment instrument.
Despite these shortcomings, the results support current guideline recommendations that dilation should target aspects of esophageal remodeling in EoE that are not amenable to currently available medical or diet therapies.
The data, however, do not exclude an important therapeutic benefit of esophageal dilation in EoE. The study excluded patients with significant strictures that could not be traversed with a standard adult endoscope. The findings, therefore, would not apply to EoE patients with substantial fibrostenosis.
In this study, medical therapy was highly effective at relieving symptoms, but prior studies have shown that symptoms recur in almost all patients following cessation of medications.
Dilation, on the other hand, is generally safe and provides long-lasting relief of dysphagia in adults, even in the absence of medical or diet therapy. Additional prospective studies are needed to define the most appropriate patient subgroups that would benefit from dilation.
Dr. Ikuo Hirano is professor of medicine in the division of gastroenterology at Northwestern University's Feinberg School of Medicine in Chicago. He serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
CHICAGO – Esophageal dilation combined with standard medical management of eosinophilic esophagitis doesn’t provide added benefit over medication alone in terms of dysphagia relief, according to a randomized, blinded clinical trial.
"In our group of patients with moderate endoscopic findings and without severe stricturing disease, esophageal dilation does not appear to be a necessary additional treatment strategy," Dr. Robert T. Kavitt stated at the annual Digestive Disease Week.
The study involved 31 patients newly diagnosed with eosinophilic esophagitis and baseline moderate to severe difficulty in swallowing. They were randomized to dilation or no dilation at initial endoscopy. Then all patients received standard medical management with 440 mcg of swallowed fluticasone b.i.d. and dexlansoprazole at 60 mg/day for 2 months. Patients were blinded as to their dilation status, as were the physicians who rated their change in dysphagia scores during follow-up.
Both groups experienced robust albeit equal reductions in overall dysphagia scores upon assessment at 30 and 60 days after endoscopy. At baseline, dysphagia scores averaged 6-6.5 on a 0-9 scale, indicative of moderate to severe dysphagia. At follow-up, scores in both groups had dropped to an average of 3 or less, reported Dr. Kavitt of the University of Chicago.
Complete resolution of dysphagia, defined as a dysphagia score of 0, occurred in only 23% of the dilation group and 57% of the no-dilation controls, which was not a statistically significant difference. The looser standard of "significant improvement" – meaning a dysphagia score of 3 or less – was met by 92% of the dilation group and 86% of controls.
Two patients in the dilation group and one control reported odynophagia.
Patients in the dilation group were dilated to the endpoint of mucosal tear. Three-quarters of the patients were dilated to a maximum size of 50 French or larger.
Baseline endoscopic scores assessing strictures, fissures, rings, and other abnormalities were in the moderate range on a 0-13 severity scale, so the study finding of a lack of benefit for dilation as part of an initial treatment strategy in eosinophilic esophagitis may not extend to the minority of patients having truly severe stricturing disease, according to Dr. Kavitt.
He noted that, before this study, the role of dilation in the treatment of eosinophilic esophagitis was a matter of divergent expert opinion unsupported by randomized trial evidence. The 2013 American College of Gastroenterology guidelines state that "the role of dilation as a primary monotherapy of eosinophilic esophagitis is still controversial and should be individualized."
Later during the meeting, in his state-of-the-art lecture on changing therapeutic concepts in eosinophilic esophagitis, Dr. Ikuo Hirano cited Dr. Kavitt’s randomized trial in support of his argument against dilation as primary therapy.
"Dilation does nothing to address the underlying inflammatory response that’s causing strictures to form," noted Dr. Hirano, professor of medicine at Northwestern University, Chicago. "I believe that dilation is inappropriate therapy for children and adults with a predominantly inflammatory phenotype of disease."
Medication and diet therapies not only relieve the symptoms of eosinophilic esophagitis, he continued, they also improve the histopathology.
Dilation entails considerable pain as well as a risk of perforation. Recent reassuring safety data regarding dilation for eosinophilic esophagitis come from specialized esophageal centers with an unusual amount of experience with the procedure, the gastroenterologist said.
Dr. Kavitt reported having no financial conflicts of interest with regard to the randomized trial, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
CHICAGO – Esophageal dilation combined with standard medical management of eosinophilic esophagitis doesn’t provide added benefit over medication alone in terms of dysphagia relief, according to a randomized, blinded clinical trial.
"In our group of patients with moderate endoscopic findings and without severe stricturing disease, esophageal dilation does not appear to be a necessary additional treatment strategy," Dr. Robert T. Kavitt stated at the annual Digestive Disease Week.
The study involved 31 patients newly diagnosed with eosinophilic esophagitis and baseline moderate to severe difficulty in swallowing. They were randomized to dilation or no dilation at initial endoscopy. Then all patients received standard medical management with 440 mcg of swallowed fluticasone b.i.d. and dexlansoprazole at 60 mg/day for 2 months. Patients were blinded as to their dilation status, as were the physicians who rated their change in dysphagia scores during follow-up.
Both groups experienced robust albeit equal reductions in overall dysphagia scores upon assessment at 30 and 60 days after endoscopy. At baseline, dysphagia scores averaged 6-6.5 on a 0-9 scale, indicative of moderate to severe dysphagia. At follow-up, scores in both groups had dropped to an average of 3 or less, reported Dr. Kavitt of the University of Chicago.
Complete resolution of dysphagia, defined as a dysphagia score of 0, occurred in only 23% of the dilation group and 57% of the no-dilation controls, which was not a statistically significant difference. The looser standard of "significant improvement" – meaning a dysphagia score of 3 or less – was met by 92% of the dilation group and 86% of controls.
Two patients in the dilation group and one control reported odynophagia.
Patients in the dilation group were dilated to the endpoint of mucosal tear. Three-quarters of the patients were dilated to a maximum size of 50 French or larger.
Baseline endoscopic scores assessing strictures, fissures, rings, and other abnormalities were in the moderate range on a 0-13 severity scale, so the study finding of a lack of benefit for dilation as part of an initial treatment strategy in eosinophilic esophagitis may not extend to the minority of patients having truly severe stricturing disease, according to Dr. Kavitt.
He noted that, before this study, the role of dilation in the treatment of eosinophilic esophagitis was a matter of divergent expert opinion unsupported by randomized trial evidence. The 2013 American College of Gastroenterology guidelines state that "the role of dilation as a primary monotherapy of eosinophilic esophagitis is still controversial and should be individualized."
Later during the meeting, in his state-of-the-art lecture on changing therapeutic concepts in eosinophilic esophagitis, Dr. Ikuo Hirano cited Dr. Kavitt’s randomized trial in support of his argument against dilation as primary therapy.
"Dilation does nothing to address the underlying inflammatory response that’s causing strictures to form," noted Dr. Hirano, professor of medicine at Northwestern University, Chicago. "I believe that dilation is inappropriate therapy for children and adults with a predominantly inflammatory phenotype of disease."
Medication and diet therapies not only relieve the symptoms of eosinophilic esophagitis, he continued, they also improve the histopathology.
Dilation entails considerable pain as well as a risk of perforation. Recent reassuring safety data regarding dilation for eosinophilic esophagitis come from specialized esophageal centers with an unusual amount of experience with the procedure, the gastroenterologist said.
Dr. Kavitt reported having no financial conflicts of interest with regard to the randomized trial, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
AT DDW 2014
Key clinical point: Dilation offers no added benefit over medication alone in relieving dysphagia symptoms in eosinophilic esophagitis.
Major finding: Significant improvement in dysphagia symptoms was documented 30 and 60 days post endoscopy in 92% of eosinophilic esophagitis patients who underwent dilation plus medical therapy and in 86% who got medication alone.
Data source: This was a randomized trial involving 31 patients newly diagnosed with eosinophilic esophagitis who were assigned to dilation or no dilation at initial endoscopy, after which all participants received 2 months of medical therapy with a swallowed corticosteroid and a proton pump inhibitor. Patients as well as the physicians who rated their dysphagia symptoms 30 and 60 days post endoscopy were blinded as to dilation status.
Disclosures: Dr. Kavitt reported having no financial conflicts regarding this study, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
Bariatric surgery improved liver histopathology in NAFLD
CHICAGO – Grade 2 or 3 hepatic fibrosis in the setting of nonalcoholic fatty liver disease resolved or improved in 56% of affected patients following their bariatric surgery for severe obesity, according to a large blinded, paired-biopsy study.
Bariatric surgery in patients with nonalcoholic fatty liver disease (NAFLD) also achieved a high rate of resolution of steatosis and steatohepatitis, but it was the improvement in advanced fibrosis, including stage 3 or bridging fibrosis, that was particularly impressive. Traditionally, liver fibrosis was thought to be an irreversible finding, Dr. Andrew A. Taitano observed at the annual Digestive Disease Week.
"Our data provide strong evidence that bariatric surgery improves liver histology in NAFLD," he said. "We conclude that bariatric surgery should be considered one of the treatments for NAFLD in patients with severe obesity."
Dr. Taitano presented a retrospective, single-center study of 160 patients with NAFLD at the time they underwent bariatric surgery for weight loss, all of whom had follow-up liver biopsies when they underwent abdominal operations for any reason an average of 31 months later. Their mean body-mass index was 52 kg/m2 at bariatric surgery, with a 62% excess body weight loss at the time of their subsequent abdominal surgery.
At bariatric surgery, 65% of patients had hepatic fibrosis. At follow-up, two blinded pathologists reported that only 36% of patients had liver fibrosis. Fibrosis was resolved or improved by at least one grade in 56% of patients, worse in 16%, and unchanged in the rest, reported Dr. Taitano, a bariatric surgery fellow at the University of South Florida, Tampa.
Of 56 patients without baseline liver fibrosis, only 12 had developed fibrosis at follow-up.
Steatosis was present in 77% of patients at bariatric surgery and in 21% at follow-up. Steatosis was resolved in 86% of patients at follow-up, the same in 8%, and worse in 6%, he said.
Steatohepatitis was found on liver biopsies at bariatric surgery in 26% of patients but was present in only 3% at follow-up. This form of histopathology was resolved or improved at follow-up in 93% of affected patients; fibrosis was worse in none.
NAFLD is the most common liver disorder in Western countries. The rate has doubled in the last 20 years. Risk factors include type 2 diabetes, central obesity, and dyslipidemia – all features of the metabolic syndrome. NAFLD is a progressive disease. Previous studies indicate that up to half of patients with NAFLD develop fibrosis within 13 years, and it’s estimated that one in five patients with NAFLD with steatohepatitis will develop cirrhosis within 20 years.
Discussant Dr. Guilherme M. Campos, a surgeon at the University of Wisconsin, Madison, commented, "It’s important to underscore that the magnitude of histologic improvements observed here is far greater than seen with maximum nonoperative therapy."
Asked if the study data pointed to any particular type of bypass surgery or any patient characteristics that correlate with change in NAFLD histopathology, Dr. Taitano replied that gastric bypass was the predominant operation. Although the limited patient numbers didn’t permit meaningful comparisons, he said, "as an overall recommendation, I would advise a weight-loss procedure that has a metabolic effect, such as gastric bypass, because I think both the amount of weight loss and the operation’s metabolic effect are improving this disease."
He reported having no financial conflicts regarding this study, which was conducted using institutional funds.
CHICAGO – Grade 2 or 3 hepatic fibrosis in the setting of nonalcoholic fatty liver disease resolved or improved in 56% of affected patients following their bariatric surgery for severe obesity, according to a large blinded, paired-biopsy study.
Bariatric surgery in patients with nonalcoholic fatty liver disease (NAFLD) also achieved a high rate of resolution of steatosis and steatohepatitis, but it was the improvement in advanced fibrosis, including stage 3 or bridging fibrosis, that was particularly impressive. Traditionally, liver fibrosis was thought to be an irreversible finding, Dr. Andrew A. Taitano observed at the annual Digestive Disease Week.
"Our data provide strong evidence that bariatric surgery improves liver histology in NAFLD," he said. "We conclude that bariatric surgery should be considered one of the treatments for NAFLD in patients with severe obesity."
Dr. Taitano presented a retrospective, single-center study of 160 patients with NAFLD at the time they underwent bariatric surgery for weight loss, all of whom had follow-up liver biopsies when they underwent abdominal operations for any reason an average of 31 months later. Their mean body-mass index was 52 kg/m2 at bariatric surgery, with a 62% excess body weight loss at the time of their subsequent abdominal surgery.
At bariatric surgery, 65% of patients had hepatic fibrosis. At follow-up, two blinded pathologists reported that only 36% of patients had liver fibrosis. Fibrosis was resolved or improved by at least one grade in 56% of patients, worse in 16%, and unchanged in the rest, reported Dr. Taitano, a bariatric surgery fellow at the University of South Florida, Tampa.
Of 56 patients without baseline liver fibrosis, only 12 had developed fibrosis at follow-up.
Steatosis was present in 77% of patients at bariatric surgery and in 21% at follow-up. Steatosis was resolved in 86% of patients at follow-up, the same in 8%, and worse in 6%, he said.
Steatohepatitis was found on liver biopsies at bariatric surgery in 26% of patients but was present in only 3% at follow-up. This form of histopathology was resolved or improved at follow-up in 93% of affected patients; fibrosis was worse in none.
NAFLD is the most common liver disorder in Western countries. The rate has doubled in the last 20 years. Risk factors include type 2 diabetes, central obesity, and dyslipidemia – all features of the metabolic syndrome. NAFLD is a progressive disease. Previous studies indicate that up to half of patients with NAFLD develop fibrosis within 13 years, and it’s estimated that one in five patients with NAFLD with steatohepatitis will develop cirrhosis within 20 years.
Discussant Dr. Guilherme M. Campos, a surgeon at the University of Wisconsin, Madison, commented, "It’s important to underscore that the magnitude of histologic improvements observed here is far greater than seen with maximum nonoperative therapy."
Asked if the study data pointed to any particular type of bypass surgery or any patient characteristics that correlate with change in NAFLD histopathology, Dr. Taitano replied that gastric bypass was the predominant operation. Although the limited patient numbers didn’t permit meaningful comparisons, he said, "as an overall recommendation, I would advise a weight-loss procedure that has a metabolic effect, such as gastric bypass, because I think both the amount of weight loss and the operation’s metabolic effect are improving this disease."
He reported having no financial conflicts regarding this study, which was conducted using institutional funds.
CHICAGO – Grade 2 or 3 hepatic fibrosis in the setting of nonalcoholic fatty liver disease resolved or improved in 56% of affected patients following their bariatric surgery for severe obesity, according to a large blinded, paired-biopsy study.
Bariatric surgery in patients with nonalcoholic fatty liver disease (NAFLD) also achieved a high rate of resolution of steatosis and steatohepatitis, but it was the improvement in advanced fibrosis, including stage 3 or bridging fibrosis, that was particularly impressive. Traditionally, liver fibrosis was thought to be an irreversible finding, Dr. Andrew A. Taitano observed at the annual Digestive Disease Week.
"Our data provide strong evidence that bariatric surgery improves liver histology in NAFLD," he said. "We conclude that bariatric surgery should be considered one of the treatments for NAFLD in patients with severe obesity."
Dr. Taitano presented a retrospective, single-center study of 160 patients with NAFLD at the time they underwent bariatric surgery for weight loss, all of whom had follow-up liver biopsies when they underwent abdominal operations for any reason an average of 31 months later. Their mean body-mass index was 52 kg/m2 at bariatric surgery, with a 62% excess body weight loss at the time of their subsequent abdominal surgery.
At bariatric surgery, 65% of patients had hepatic fibrosis. At follow-up, two blinded pathologists reported that only 36% of patients had liver fibrosis. Fibrosis was resolved or improved by at least one grade in 56% of patients, worse in 16%, and unchanged in the rest, reported Dr. Taitano, a bariatric surgery fellow at the University of South Florida, Tampa.
Of 56 patients without baseline liver fibrosis, only 12 had developed fibrosis at follow-up.
Steatosis was present in 77% of patients at bariatric surgery and in 21% at follow-up. Steatosis was resolved in 86% of patients at follow-up, the same in 8%, and worse in 6%, he said.
Steatohepatitis was found on liver biopsies at bariatric surgery in 26% of patients but was present in only 3% at follow-up. This form of histopathology was resolved or improved at follow-up in 93% of affected patients; fibrosis was worse in none.
NAFLD is the most common liver disorder in Western countries. The rate has doubled in the last 20 years. Risk factors include type 2 diabetes, central obesity, and dyslipidemia – all features of the metabolic syndrome. NAFLD is a progressive disease. Previous studies indicate that up to half of patients with NAFLD develop fibrosis within 13 years, and it’s estimated that one in five patients with NAFLD with steatohepatitis will develop cirrhosis within 20 years.
Discussant Dr. Guilherme M. Campos, a surgeon at the University of Wisconsin, Madison, commented, "It’s important to underscore that the magnitude of histologic improvements observed here is far greater than seen with maximum nonoperative therapy."
Asked if the study data pointed to any particular type of bypass surgery or any patient characteristics that correlate with change in NAFLD histopathology, Dr. Taitano replied that gastric bypass was the predominant operation. Although the limited patient numbers didn’t permit meaningful comparisons, he said, "as an overall recommendation, I would advise a weight-loss procedure that has a metabolic effect, such as gastric bypass, because I think both the amount of weight loss and the operation’s metabolic effect are improving this disease."
He reported having no financial conflicts regarding this study, which was conducted using institutional funds.
AT DDW 2014
Key clinical point: Bariatric surgery should be considered one of the treatments for NAFLD in patients with severe obesity.
Major finding: Advanced liver fibrosis in patients with nonalcoholic fatty liver disease at the time of bariatric surgery for severe obesity was resolved or improved by at least one grade in nearly 60% of cases at follow-up biopsy.
Data source: A retrospective, blinded, paired-biopsy study involving 160 patients with NAFLD at the time they underwent bariatric surgery and who had follow-up liver biopsies when they later underwent abdominal surgery.
Disclosures: The presenter reported having no financial conflicts regarding this study, which was conducted using institutional funds.
Laparoscopic-assisted colonoscopic polypectomy means shorter hospital stays
Laparoscopic-assisted colonoscopic polypectomy works as well as standard laparoscopic hemicolectomy to remove difficult to reach polyps in the right colon, with fewer complications and shorter hospital stays, according to data from a recent trial.
Instead of taking out a section of the ascending colon to remove the polyp, a surgeon uses a laparoscope to mobilize and position the right colon during laparoscopic-assisted colonoscopic polypectomy (LACP) so that an endoscopist can reach, snare, and remove it.
The team randomized 14 patients to LACP and 14 to laparoscopic hemicolectomy (LHC). The LACP group had shorter mean operating times (95 vs. 179 min.), less blood loss (13 vs. 63 mL), and required less intravenous fluid (2.1 vs. 3.1 L). LACP patients were also quicker to pass flatus (1.44 vs. 2.88 days), resume solid food (1.69 vs. 3.94 days), and leave the hospital (2.63 vs. 4.94 days), all statistically significant differences.
One LACP patient required conversion to LHC, while four LHC patients required conversion to laparotomy. There were no significant between-group differences in postoperative complications, readmissions, or second operations.
"That ability to remove polyps with LACP was as effective and safe as the standard laparoscopic hemicolectomy ... and patients were discharged from the hospital earlier. We think this is a very exciting change in how we deal with these difficult to remove colon polyps," said Dr. Jonathan Buscaglia, director of advanced endoscopy at Stony Brook (N.Y.) University.
There are a few case series in the literature about the technique, but uptake seems to have been slow so far. "I think the biggest roadblock is the ability of a surgeon to coordinate with a gastroenterologist. You need good working relationships, and schedules able to accommodate [both]. That’s not always easy, depending on where one works," Dr. Buscaglia said at a teleconference in advance of the annual Digestive Disease Week.
The patients in the trial had benign polyps with lift signs and generally tubular or tubulovillous adenomas. The groups were evenly matched for age, sex, body mass index, American Society of Anesthesiologists physical status, and previous abdominal surgery, plus polyp morphology, location, size, and histology.
It’s too soon after the procedures for serial surveillance colonoscopies and to know if any of the patients went on to develop cancer after their operations.
The right side is technically an easier place for laparoscopic surgeons to operate; with the left colon, operators have to worry more about diverticulitis, scarring, and tight anatomy. Even so, LACP may still be useful. "We are looking forward to conducting" a larger, possibly multicenter study on its application to polyps "in all areas of the colon," Dr. Buscaglia said.
The investigators have no disclosures.
Laparoscopic-assisted colonoscopic polypectomy works as well as standard laparoscopic hemicolectomy to remove difficult to reach polyps in the right colon, with fewer complications and shorter hospital stays, according to data from a recent trial.
Instead of taking out a section of the ascending colon to remove the polyp, a surgeon uses a laparoscope to mobilize and position the right colon during laparoscopic-assisted colonoscopic polypectomy (LACP) so that an endoscopist can reach, snare, and remove it.
The team randomized 14 patients to LACP and 14 to laparoscopic hemicolectomy (LHC). The LACP group had shorter mean operating times (95 vs. 179 min.), less blood loss (13 vs. 63 mL), and required less intravenous fluid (2.1 vs. 3.1 L). LACP patients were also quicker to pass flatus (1.44 vs. 2.88 days), resume solid food (1.69 vs. 3.94 days), and leave the hospital (2.63 vs. 4.94 days), all statistically significant differences.
One LACP patient required conversion to LHC, while four LHC patients required conversion to laparotomy. There were no significant between-group differences in postoperative complications, readmissions, or second operations.
"That ability to remove polyps with LACP was as effective and safe as the standard laparoscopic hemicolectomy ... and patients were discharged from the hospital earlier. We think this is a very exciting change in how we deal with these difficult to remove colon polyps," said Dr. Jonathan Buscaglia, director of advanced endoscopy at Stony Brook (N.Y.) University.
There are a few case series in the literature about the technique, but uptake seems to have been slow so far. "I think the biggest roadblock is the ability of a surgeon to coordinate with a gastroenterologist. You need good working relationships, and schedules able to accommodate [both]. That’s not always easy, depending on where one works," Dr. Buscaglia said at a teleconference in advance of the annual Digestive Disease Week.
The patients in the trial had benign polyps with lift signs and generally tubular or tubulovillous adenomas. The groups were evenly matched for age, sex, body mass index, American Society of Anesthesiologists physical status, and previous abdominal surgery, plus polyp morphology, location, size, and histology.
It’s too soon after the procedures for serial surveillance colonoscopies and to know if any of the patients went on to develop cancer after their operations.
The right side is technically an easier place for laparoscopic surgeons to operate; with the left colon, operators have to worry more about diverticulitis, scarring, and tight anatomy. Even so, LACP may still be useful. "We are looking forward to conducting" a larger, possibly multicenter study on its application to polyps "in all areas of the colon," Dr. Buscaglia said.
The investigators have no disclosures.
Laparoscopic-assisted colonoscopic polypectomy works as well as standard laparoscopic hemicolectomy to remove difficult to reach polyps in the right colon, with fewer complications and shorter hospital stays, according to data from a recent trial.
Instead of taking out a section of the ascending colon to remove the polyp, a surgeon uses a laparoscope to mobilize and position the right colon during laparoscopic-assisted colonoscopic polypectomy (LACP) so that an endoscopist can reach, snare, and remove it.
The team randomized 14 patients to LACP and 14 to laparoscopic hemicolectomy (LHC). The LACP group had shorter mean operating times (95 vs. 179 min.), less blood loss (13 vs. 63 mL), and required less intravenous fluid (2.1 vs. 3.1 L). LACP patients were also quicker to pass flatus (1.44 vs. 2.88 days), resume solid food (1.69 vs. 3.94 days), and leave the hospital (2.63 vs. 4.94 days), all statistically significant differences.
One LACP patient required conversion to LHC, while four LHC patients required conversion to laparotomy. There were no significant between-group differences in postoperative complications, readmissions, or second operations.
"That ability to remove polyps with LACP was as effective and safe as the standard laparoscopic hemicolectomy ... and patients were discharged from the hospital earlier. We think this is a very exciting change in how we deal with these difficult to remove colon polyps," said Dr. Jonathan Buscaglia, director of advanced endoscopy at Stony Brook (N.Y.) University.
There are a few case series in the literature about the technique, but uptake seems to have been slow so far. "I think the biggest roadblock is the ability of a surgeon to coordinate with a gastroenterologist. You need good working relationships, and schedules able to accommodate [both]. That’s not always easy, depending on where one works," Dr. Buscaglia said at a teleconference in advance of the annual Digestive Disease Week.
The patients in the trial had benign polyps with lift signs and generally tubular or tubulovillous adenomas. The groups were evenly matched for age, sex, body mass index, American Society of Anesthesiologists physical status, and previous abdominal surgery, plus polyp morphology, location, size, and histology.
It’s too soon after the procedures for serial surveillance colonoscopies and to know if any of the patients went on to develop cancer after their operations.
The right side is technically an easier place for laparoscopic surgeons to operate; with the left colon, operators have to worry more about diverticulitis, scarring, and tight anatomy. Even so, LACP may still be useful. "We are looking forward to conducting" a larger, possibly multicenter study on its application to polyps "in all areas of the colon," Dr. Buscaglia said.
The investigators have no disclosures.
FROM DDW 2014
Major finding: Compared with those undergoing laparoscopic hemicolectomy, patients whose right-colon polyps are removed by laparoscopic-assisted colonoscopic polypectomy have shorter mean operating times (95 min. vs. 179 min.), lose less blood (13 vs. 63 mL), and require less intravenous fluid (2.1 vs. 3.1 L). LACP patients are also quicker to pass flatus (1.44 vs. 2.88 days), resume solid food (1.69 vs. 3.94 days), and leave the hospital (2.63 vs. 4.94 days).
Data source: Randomized, unblinded trial in 28 patients with benign right-colon polyps.
Disclosures: The investigators have no disclosures.
NAFLD Mortality Higher in Normal Weight Patients
Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.
Reviewing blood and other samples taken at the time of liver biopsy, the investigators found that the 125 (11.5%) patients with a body mass index (BMI) below 25 kg/m2 (average 23 kg/m2) had less insulin resistance and less advanced fibrosis than did the 965 (88.5%) who presented with higher BMIs (average 33 kg/m2).
But among the 483 patients biopsied before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
The cumulative survival was significantly shorter in lean patients, as well; only lean NAFLD (hazard ratio, 11.8; 95% confidence interval, 2.8-50.1; P = .001) and age (HR, 1.05; 95% CI, 1.008-1.1; P =.02) remained significant when the findings were adjusted for sex, degree of fibrosis, and other confounding factors.
Cardiovascular disease, malignancy, and liver problems were the main causes of death in both lean and overweight patients; there were no significant differences between the groups, and the reason is unclear. Perhaps lean patients have greater central fat distribution; the team plans to investigate the matter further.
"I thought patients with lean fatty liver would have lower mortality; it was exactly the opposite. The risk factors for fatty liver go beyond a person’s body weight, and signs of liver disease secondary to NAFLD in lean patients should be taken very seriously. We must not assume that patients of relatively healthy weight can’t have fatty liver disease," said senior investigator Dr. Paul Angulo, chief of hepatology at the University of Kentucky Medical Center in Lexington.
"We need to be more aggressive in patients with lean fatty liver in terms of biopsy to see how much liver injury they have, and really make a concerted effort to increase their physical activity and change their diet. They don’t need to lose weight, but they need less fat and carbohydrates and more exercise to increase insulin sensitivity, especially in the muscle mass and liver," he said at a teleconference in advance of the annual Digestive Disease Week.
Lean NAFLD patients were more likely to be men; nonwhite, especially Asian and Hispanic; and to have fewer chronic conditions, such as diabetes, hypertension, and dyslipidemia. They also had lower levels of alanine aminotransferase, fewer fatty liver deposits, and less advanced fibrosis, but more severe lobular inflammation. There was no significant difference between the two groups in age (average, 46 years), hepatocyte ballooning, or incidence of nonalcoholic steatohepatitis.
The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.
I have patients like this in my practice, and I am certainly going to pay attention to them now. In the past, I had assumed that the absence of risk factors was a good thing, but now I’ve learned it may not be. Pending study that demonstrates a benefit for specific interventions, I am going to follow Dr. Angulo’s advice and encourage these patients to exercise more robustly. We need to find out the optimal approach for them.
Dr. Lawrence Friedman is chair of the department of medicine at Newton-Wellesley (Mass.) Hospital. He moderated Dr. Angulo’s presentation but was not involved in the project.
I have patients like this in my practice, and I am certainly going to pay attention to them now. In the past, I had assumed that the absence of risk factors was a good thing, but now I’ve learned it may not be. Pending study that demonstrates a benefit for specific interventions, I am going to follow Dr. Angulo’s advice and encourage these patients to exercise more robustly. We need to find out the optimal approach for them.
Dr. Lawrence Friedman is chair of the department of medicine at Newton-Wellesley (Mass.) Hospital. He moderated Dr. Angulo’s presentation but was not involved in the project.
I have patients like this in my practice, and I am certainly going to pay attention to them now. In the past, I had assumed that the absence of risk factors was a good thing, but now I’ve learned it may not be. Pending study that demonstrates a benefit for specific interventions, I am going to follow Dr. Angulo’s advice and encourage these patients to exercise more robustly. We need to find out the optimal approach for them.
Dr. Lawrence Friedman is chair of the department of medicine at Newton-Wellesley (Mass.) Hospital. He moderated Dr. Angulo’s presentation but was not involved in the project.
Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.
Reviewing blood and other samples taken at the time of liver biopsy, the investigators found that the 125 (11.5%) patients with a body mass index (BMI) below 25 kg/m2 (average 23 kg/m2) had less insulin resistance and less advanced fibrosis than did the 965 (88.5%) who presented with higher BMIs (average 33 kg/m2).
But among the 483 patients biopsied before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
The cumulative survival was significantly shorter in lean patients, as well; only lean NAFLD (hazard ratio, 11.8; 95% confidence interval, 2.8-50.1; P = .001) and age (HR, 1.05; 95% CI, 1.008-1.1; P =.02) remained significant when the findings were adjusted for sex, degree of fibrosis, and other confounding factors.
Cardiovascular disease, malignancy, and liver problems were the main causes of death in both lean and overweight patients; there were no significant differences between the groups, and the reason is unclear. Perhaps lean patients have greater central fat distribution; the team plans to investigate the matter further.
"I thought patients with lean fatty liver would have lower mortality; it was exactly the opposite. The risk factors for fatty liver go beyond a person’s body weight, and signs of liver disease secondary to NAFLD in lean patients should be taken very seriously. We must not assume that patients of relatively healthy weight can’t have fatty liver disease," said senior investigator Dr. Paul Angulo, chief of hepatology at the University of Kentucky Medical Center in Lexington.
"We need to be more aggressive in patients with lean fatty liver in terms of biopsy to see how much liver injury they have, and really make a concerted effort to increase their physical activity and change their diet. They don’t need to lose weight, but they need less fat and carbohydrates and more exercise to increase insulin sensitivity, especially in the muscle mass and liver," he said at a teleconference in advance of the annual Digestive Disease Week.
Lean NAFLD patients were more likely to be men; nonwhite, especially Asian and Hispanic; and to have fewer chronic conditions, such as diabetes, hypertension, and dyslipidemia. They also had lower levels of alanine aminotransferase, fewer fatty liver deposits, and less advanced fibrosis, but more severe lobular inflammation. There was no significant difference between the two groups in age (average, 46 years), hepatocyte ballooning, or incidence of nonalcoholic steatohepatitis.
The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.
Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.
Reviewing blood and other samples taken at the time of liver biopsy, the investigators found that the 125 (11.5%) patients with a body mass index (BMI) below 25 kg/m2 (average 23 kg/m2) had less insulin resistance and less advanced fibrosis than did the 965 (88.5%) who presented with higher BMIs (average 33 kg/m2).
But among the 483 patients biopsied before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
The cumulative survival was significantly shorter in lean patients, as well; only lean NAFLD (hazard ratio, 11.8; 95% confidence interval, 2.8-50.1; P = .001) and age (HR, 1.05; 95% CI, 1.008-1.1; P =.02) remained significant when the findings were adjusted for sex, degree of fibrosis, and other confounding factors.
Cardiovascular disease, malignancy, and liver problems were the main causes of death in both lean and overweight patients; there were no significant differences between the groups, and the reason is unclear. Perhaps lean patients have greater central fat distribution; the team plans to investigate the matter further.
"I thought patients with lean fatty liver would have lower mortality; it was exactly the opposite. The risk factors for fatty liver go beyond a person’s body weight, and signs of liver disease secondary to NAFLD in lean patients should be taken very seriously. We must not assume that patients of relatively healthy weight can’t have fatty liver disease," said senior investigator Dr. Paul Angulo, chief of hepatology at the University of Kentucky Medical Center in Lexington.
"We need to be more aggressive in patients with lean fatty liver in terms of biopsy to see how much liver injury they have, and really make a concerted effort to increase their physical activity and change their diet. They don’t need to lose weight, but they need less fat and carbohydrates and more exercise to increase insulin sensitivity, especially in the muscle mass and liver," he said at a teleconference in advance of the annual Digestive Disease Week.
Lean NAFLD patients were more likely to be men; nonwhite, especially Asian and Hispanic; and to have fewer chronic conditions, such as diabetes, hypertension, and dyslipidemia. They also had lower levels of alanine aminotransferase, fewer fatty liver deposits, and less advanced fibrosis, but more severe lobular inflammation. There was no significant difference between the two groups in age (average, 46 years), hepatocyte ballooning, or incidence of nonalcoholic steatohepatitis.
The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.
FROM DDW 2014
NAFLD mortality higher in normal weight patients
Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.
Reviewing blood and other samples taken at the time of liver biopsy, the investigators found that the 125 (11.5%) patients with a body mass index (BMI) below 25 kg/m2 (average 23 kg/m2) had less insulin resistance and less advanced fibrosis than did the 965 (88.5%) who presented with higher BMIs (average 33 kg/m2).
But among the 483 patients biopsied before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
The cumulative survival was significantly shorter in lean patients, as well; only lean NAFLD (hazard ratio, 11.8; 95% confidence interval, 2.8-50.1; P = .001) and age (HR, 1.05; 95% CI, 1.008-1.1; P =.02) remained significant when the findings were adjusted for sex, degree of fibrosis, and other confounding factors.
Cardiovascular disease, malignancy, and liver problems were the main causes of death in both lean and overweight patients; there were no significant differences between the groups, and the reason is unclear. Perhaps lean patients have greater central fat distribution; the team plans to investigate the matter further.
"I thought patients with lean fatty liver would have lower mortality; it was exactly the opposite. The risk factors for fatty liver go beyond a person’s body weight, and signs of liver disease secondary to NAFLD in lean patients should be taken very seriously. We must not assume that patients of relatively healthy weight can’t have fatty liver disease," said senior investigator Dr. Paul Angulo, chief of hepatology at the University of Kentucky Medical Center in Lexington.
"We need to be more aggressive in patients with lean fatty liver in terms of biopsy to see how much liver injury they have, and really make a concerted effort to increase their physical activity and change their diet. They don’t need to lose weight, but they need less fat and carbohydrates and more exercise to increase insulin sensitivity, especially in the muscle mass and liver," he said at a teleconference in advance of the annual Digestive Disease Week.
Lean NAFLD patients were more likely to be men; nonwhite, especially Asian and Hispanic; and to have fewer chronic conditions, such as diabetes, hypertension, and dyslipidemia. They also had lower levels of alanine aminotransferase, fewer fatty liver deposits, and less advanced fibrosis, but more severe lobular inflammation. There was no significant difference between the two groups in age (average, 46 years), hepatocyte ballooning, or incidence of nonalcoholic steatohepatitis.
The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.
I have patients like this in my practice, and I am certainly going to pay attention to them now. In the past, I had assumed that the absence of risk factors was a good thing, but now I’ve learned it may not be. Pending study that demonstrates a benefit for specific interventions, I am going to follow Dr. Angulo’s advice and encourage these patients to exercise more robustly. We need to find out the optimal approach for them.
Dr. Lawrence Friedman is chair of the department of medicine at Newton-Wellesley (Mass.) Hospital. He moderated Dr. Angulo’s presentation but was not involved in the project.
I have patients like this in my practice, and I am certainly going to pay attention to them now. In the past, I had assumed that the absence of risk factors was a good thing, but now I’ve learned it may not be. Pending study that demonstrates a benefit for specific interventions, I am going to follow Dr. Angulo’s advice and encourage these patients to exercise more robustly. We need to find out the optimal approach for them.
Dr. Lawrence Friedman is chair of the department of medicine at Newton-Wellesley (Mass.) Hospital. He moderated Dr. Angulo’s presentation but was not involved in the project.
I have patients like this in my practice, and I am certainly going to pay attention to them now. In the past, I had assumed that the absence of risk factors was a good thing, but now I’ve learned it may not be. Pending study that demonstrates a benefit for specific interventions, I am going to follow Dr. Angulo’s advice and encourage these patients to exercise more robustly. We need to find out the optimal approach for them.
Dr. Lawrence Friedman is chair of the department of medicine at Newton-Wellesley (Mass.) Hospital. He moderated Dr. Angulo’s presentation but was not involved in the project.
Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.
Reviewing blood and other samples taken at the time of liver biopsy, the investigators found that the 125 (11.5%) patients with a body mass index (BMI) below 25 kg/m2 (average 23 kg/m2) had less insulin resistance and less advanced fibrosis than did the 965 (88.5%) who presented with higher BMIs (average 33 kg/m2).
But among the 483 patients biopsied before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
The cumulative survival was significantly shorter in lean patients, as well; only lean NAFLD (hazard ratio, 11.8; 95% confidence interval, 2.8-50.1; P = .001) and age (HR, 1.05; 95% CI, 1.008-1.1; P =.02) remained significant when the findings were adjusted for sex, degree of fibrosis, and other confounding factors.
Cardiovascular disease, malignancy, and liver problems were the main causes of death in both lean and overweight patients; there were no significant differences between the groups, and the reason is unclear. Perhaps lean patients have greater central fat distribution; the team plans to investigate the matter further.
"I thought patients with lean fatty liver would have lower mortality; it was exactly the opposite. The risk factors for fatty liver go beyond a person’s body weight, and signs of liver disease secondary to NAFLD in lean patients should be taken very seriously. We must not assume that patients of relatively healthy weight can’t have fatty liver disease," said senior investigator Dr. Paul Angulo, chief of hepatology at the University of Kentucky Medical Center in Lexington.
"We need to be more aggressive in patients with lean fatty liver in terms of biopsy to see how much liver injury they have, and really make a concerted effort to increase their physical activity and change their diet. They don’t need to lose weight, but they need less fat and carbohydrates and more exercise to increase insulin sensitivity, especially in the muscle mass and liver," he said at a teleconference in advance of the annual Digestive Disease Week.
Lean NAFLD patients were more likely to be men; nonwhite, especially Asian and Hispanic; and to have fewer chronic conditions, such as diabetes, hypertension, and dyslipidemia. They also had lower levels of alanine aminotransferase, fewer fatty liver deposits, and less advanced fibrosis, but more severe lobular inflammation. There was no significant difference between the two groups in age (average, 46 years), hepatocyte ballooning, or incidence of nonalcoholic steatohepatitis.
The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.
Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.
Reviewing blood and other samples taken at the time of liver biopsy, the investigators found that the 125 (11.5%) patients with a body mass index (BMI) below 25 kg/m2 (average 23 kg/m2) had less insulin resistance and less advanced fibrosis than did the 965 (88.5%) who presented with higher BMIs (average 33 kg/m2).
But among the 483 patients biopsied before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
The cumulative survival was significantly shorter in lean patients, as well; only lean NAFLD (hazard ratio, 11.8; 95% confidence interval, 2.8-50.1; P = .001) and age (HR, 1.05; 95% CI, 1.008-1.1; P =.02) remained significant when the findings were adjusted for sex, degree of fibrosis, and other confounding factors.
Cardiovascular disease, malignancy, and liver problems were the main causes of death in both lean and overweight patients; there were no significant differences between the groups, and the reason is unclear. Perhaps lean patients have greater central fat distribution; the team plans to investigate the matter further.
"I thought patients with lean fatty liver would have lower mortality; it was exactly the opposite. The risk factors for fatty liver go beyond a person’s body weight, and signs of liver disease secondary to NAFLD in lean patients should be taken very seriously. We must not assume that patients of relatively healthy weight can’t have fatty liver disease," said senior investigator Dr. Paul Angulo, chief of hepatology at the University of Kentucky Medical Center in Lexington.
"We need to be more aggressive in patients with lean fatty liver in terms of biopsy to see how much liver injury they have, and really make a concerted effort to increase their physical activity and change their diet. They don’t need to lose weight, but they need less fat and carbohydrates and more exercise to increase insulin sensitivity, especially in the muscle mass and liver," he said at a teleconference in advance of the annual Digestive Disease Week.
Lean NAFLD patients were more likely to be men; nonwhite, especially Asian and Hispanic; and to have fewer chronic conditions, such as diabetes, hypertension, and dyslipidemia. They also had lower levels of alanine aminotransferase, fewer fatty liver deposits, and less advanced fibrosis, but more severe lobular inflammation. There was no significant difference between the two groups in age (average, 46 years), hepatocyte ballooning, or incidence of nonalcoholic steatohepatitis.
The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.
FROM DDW 2014
Major finding: Among 483 patients with liver biopsies before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
Data source: Retrospective, international review of 1,090 NAFLD cases.
Disclosures: The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.