User login
BMI does not influence PPI effectiveness in GERD or erosive esophagitis
Proton pump inhibitors resolve symptoms of gastroesophageal reflux disease and promote healing of erosive esophagitis regardless of a patient’s body mass index, according to a new study.
However, research findings "suggest that obese or overweight patients may be at a greater risk of advanced grades of erosive esophagitis than patients with normal weight," reported Dr. Prateek Sharma of the University of Kansas, Kansas City, Mo., and his associates (J. Clin. Gastroenterol. 2013 Feb. 24 [doi: 10.1097/MCG.0b013e31827e46be]).
Other factors such as PPI treatment and older age may also influence the odds of symptom resolution in nonerosive reflux disease (NERD) and erosive esophagitis patients.
Investigators conducted two post hoc retrospective analyses of pooled data from randomized, double-blind, multicenter studies of patients with GERD treated with PPIs.
The first analysis consisted of two studies assessing 704 subjects with NERD who received esomeprazole 20 mg (n = 228), esomeprazole 40 mg (n = 238) or placebo (n = 238).
The second analysis pooled data from five studies of 11,027 patients with erosive esophagitis treated with esomeprazole 40 mg (n = 5,519), omeprazole 20 mg (n = 2,407), or lansoprazole 30 mg (n = 3,101).
Patients were analyzed in three groups: normal weight, overweight, and obese, defined as BMI <25 kg/m2, 25 to <35 kg/m2, and greater than or equal to 35 kg/m2, respectively.
Analysis 1 demonstrated that BMI had no effect on baseline heartburn in patients with NERD (P = .28). Specifically, 21.4% of overweight and obese individuals had no heartburn symptoms at baseline, while 35.9%, 32.5%, and 10.2% had mild, moderate, and severe symptoms, respectively. In comparison, 14.3% of patients at a normal weight had no heartburn, while 38.4%, 37.9%, and 9.4%, had mild, moderate, and severe symptoms, respectively.
In Analysis 2, however, 34.7% of patients who were overweight and 32% who were obese had Los Angeles (LA) grade C or D erosive esophagitis compared with 25.5% of normal weight subjects (P < .0001). At baseline, 34.2% of overweight or obese patients had LA grade C or D of the condition.
Heartburn resolution was similar in all NERD BMI subgroups. Symptoms were successfully treated in 36.5%, 36.7%, and 32.3% of normal weight, overweight, and obese individuals taking PPIs, respectively. Healing rates with PPIs were also similar across weight categories and within erosive esophagitis LA grade.
Further analysis with logistic regression models indicated that BMI did not influence resolution of heartburn (odds ratio [OR] =1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis healing (OR = 1.01; 95% CI, 1.00-1.02; P = .23).
However, the odds of heartburn resolution increased with esomeprazole 20 mg vs. placebo (OR = 4.26, 2.63-6.88, P < .0001), esomeprazole 40 mg vs. placebo (OR = 4.0, 2.48-6.44, P < .0001), older age (OR=1.0, 1.0-1.0, P = .0041), and in men vs. women (OR = 1.50, 1.04-2.14, P = .0284).
Additionally, the chance of erosive esophagitis healing increased with esomeprazole 40 mg vs. omeprazole 20 mg (OR = 1.70, 1.44-2.01, P < .0001), lansoprazole 30 mg vs. omeprazole 20 mg (OR = 1.30, 1.05-1.62, P = .0183), older age (OR = 1.02, 1.01-1.02, P < .0001), in black vs. white patients (OR = 0.67, 0.54-0.84, P = .0003), and hiatal hernia (OR = 1.21, 1.08-1.35, P = .0011).
The odds of erosive esophagitis healing were greater in patients with LA grade A vs. D (OR = 4.54, 3.71-5.55, P < .0001) than in patients with LA grade B vs. D (OR = 2.76, 2.30-3.32, P < .0001) or C vs. D (OR = 1.70, 1.42-2.03, P < .0001).
While this pooled analysis is limited because "data were obtained from post hoc analyses of clinical efficacy studies not designed to evaluate the effects of obesity on GERD symptom severity or treatment success," the research has "considerable statistical power" due to the large number of patients included, the investigators wrote.
The study was supported by AstraZeneca LP, in Wilmington, Del. Dr. Sharma receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda. His coauthors disclosed ties to various pharmaceutical companies, including AstraZeneca.
Proton pump inhibitors resolve symptoms of gastroesophageal reflux disease and promote healing of erosive esophagitis regardless of a patient’s body mass index, according to a new study.
However, research findings "suggest that obese or overweight patients may be at a greater risk of advanced grades of erosive esophagitis than patients with normal weight," reported Dr. Prateek Sharma of the University of Kansas, Kansas City, Mo., and his associates (J. Clin. Gastroenterol. 2013 Feb. 24 [doi: 10.1097/MCG.0b013e31827e46be]).
Other factors such as PPI treatment and older age may also influence the odds of symptom resolution in nonerosive reflux disease (NERD) and erosive esophagitis patients.
Investigators conducted two post hoc retrospective analyses of pooled data from randomized, double-blind, multicenter studies of patients with GERD treated with PPIs.
The first analysis consisted of two studies assessing 704 subjects with NERD who received esomeprazole 20 mg (n = 228), esomeprazole 40 mg (n = 238) or placebo (n = 238).
The second analysis pooled data from five studies of 11,027 patients with erosive esophagitis treated with esomeprazole 40 mg (n = 5,519), omeprazole 20 mg (n = 2,407), or lansoprazole 30 mg (n = 3,101).
Patients were analyzed in three groups: normal weight, overweight, and obese, defined as BMI <25 kg/m2, 25 to <35 kg/m2, and greater than or equal to 35 kg/m2, respectively.
Analysis 1 demonstrated that BMI had no effect on baseline heartburn in patients with NERD (P = .28). Specifically, 21.4% of overweight and obese individuals had no heartburn symptoms at baseline, while 35.9%, 32.5%, and 10.2% had mild, moderate, and severe symptoms, respectively. In comparison, 14.3% of patients at a normal weight had no heartburn, while 38.4%, 37.9%, and 9.4%, had mild, moderate, and severe symptoms, respectively.
In Analysis 2, however, 34.7% of patients who were overweight and 32% who were obese had Los Angeles (LA) grade C or D erosive esophagitis compared with 25.5% of normal weight subjects (P < .0001). At baseline, 34.2% of overweight or obese patients had LA grade C or D of the condition.
Heartburn resolution was similar in all NERD BMI subgroups. Symptoms were successfully treated in 36.5%, 36.7%, and 32.3% of normal weight, overweight, and obese individuals taking PPIs, respectively. Healing rates with PPIs were also similar across weight categories and within erosive esophagitis LA grade.
Further analysis with logistic regression models indicated that BMI did not influence resolution of heartburn (odds ratio [OR] =1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis healing (OR = 1.01; 95% CI, 1.00-1.02; P = .23).
However, the odds of heartburn resolution increased with esomeprazole 20 mg vs. placebo (OR = 4.26, 2.63-6.88, P < .0001), esomeprazole 40 mg vs. placebo (OR = 4.0, 2.48-6.44, P < .0001), older age (OR=1.0, 1.0-1.0, P = .0041), and in men vs. women (OR = 1.50, 1.04-2.14, P = .0284).
Additionally, the chance of erosive esophagitis healing increased with esomeprazole 40 mg vs. omeprazole 20 mg (OR = 1.70, 1.44-2.01, P < .0001), lansoprazole 30 mg vs. omeprazole 20 mg (OR = 1.30, 1.05-1.62, P = .0183), older age (OR = 1.02, 1.01-1.02, P < .0001), in black vs. white patients (OR = 0.67, 0.54-0.84, P = .0003), and hiatal hernia (OR = 1.21, 1.08-1.35, P = .0011).
The odds of erosive esophagitis healing were greater in patients with LA grade A vs. D (OR = 4.54, 3.71-5.55, P < .0001) than in patients with LA grade B vs. D (OR = 2.76, 2.30-3.32, P < .0001) or C vs. D (OR = 1.70, 1.42-2.03, P < .0001).
While this pooled analysis is limited because "data were obtained from post hoc analyses of clinical efficacy studies not designed to evaluate the effects of obesity on GERD symptom severity or treatment success," the research has "considerable statistical power" due to the large number of patients included, the investigators wrote.
The study was supported by AstraZeneca LP, in Wilmington, Del. Dr. Sharma receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda. His coauthors disclosed ties to various pharmaceutical companies, including AstraZeneca.
Proton pump inhibitors resolve symptoms of gastroesophageal reflux disease and promote healing of erosive esophagitis regardless of a patient’s body mass index, according to a new study.
However, research findings "suggest that obese or overweight patients may be at a greater risk of advanced grades of erosive esophagitis than patients with normal weight," reported Dr. Prateek Sharma of the University of Kansas, Kansas City, Mo., and his associates (J. Clin. Gastroenterol. 2013 Feb. 24 [doi: 10.1097/MCG.0b013e31827e46be]).
Other factors such as PPI treatment and older age may also influence the odds of symptom resolution in nonerosive reflux disease (NERD) and erosive esophagitis patients.
Investigators conducted two post hoc retrospective analyses of pooled data from randomized, double-blind, multicenter studies of patients with GERD treated with PPIs.
The first analysis consisted of two studies assessing 704 subjects with NERD who received esomeprazole 20 mg (n = 228), esomeprazole 40 mg (n = 238) or placebo (n = 238).
The second analysis pooled data from five studies of 11,027 patients with erosive esophagitis treated with esomeprazole 40 mg (n = 5,519), omeprazole 20 mg (n = 2,407), or lansoprazole 30 mg (n = 3,101).
Patients were analyzed in three groups: normal weight, overweight, and obese, defined as BMI <25 kg/m2, 25 to <35 kg/m2, and greater than or equal to 35 kg/m2, respectively.
Analysis 1 demonstrated that BMI had no effect on baseline heartburn in patients with NERD (P = .28). Specifically, 21.4% of overweight and obese individuals had no heartburn symptoms at baseline, while 35.9%, 32.5%, and 10.2% had mild, moderate, and severe symptoms, respectively. In comparison, 14.3% of patients at a normal weight had no heartburn, while 38.4%, 37.9%, and 9.4%, had mild, moderate, and severe symptoms, respectively.
In Analysis 2, however, 34.7% of patients who were overweight and 32% who were obese had Los Angeles (LA) grade C or D erosive esophagitis compared with 25.5% of normal weight subjects (P < .0001). At baseline, 34.2% of overweight or obese patients had LA grade C or D of the condition.
Heartburn resolution was similar in all NERD BMI subgroups. Symptoms were successfully treated in 36.5%, 36.7%, and 32.3% of normal weight, overweight, and obese individuals taking PPIs, respectively. Healing rates with PPIs were also similar across weight categories and within erosive esophagitis LA grade.
Further analysis with logistic regression models indicated that BMI did not influence resolution of heartburn (odds ratio [OR] =1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis healing (OR = 1.01; 95% CI, 1.00-1.02; P = .23).
However, the odds of heartburn resolution increased with esomeprazole 20 mg vs. placebo (OR = 4.26, 2.63-6.88, P < .0001), esomeprazole 40 mg vs. placebo (OR = 4.0, 2.48-6.44, P < .0001), older age (OR=1.0, 1.0-1.0, P = .0041), and in men vs. women (OR = 1.50, 1.04-2.14, P = .0284).
Additionally, the chance of erosive esophagitis healing increased with esomeprazole 40 mg vs. omeprazole 20 mg (OR = 1.70, 1.44-2.01, P < .0001), lansoprazole 30 mg vs. omeprazole 20 mg (OR = 1.30, 1.05-1.62, P = .0183), older age (OR = 1.02, 1.01-1.02, P < .0001), in black vs. white patients (OR = 0.67, 0.54-0.84, P = .0003), and hiatal hernia (OR = 1.21, 1.08-1.35, P = .0011).
The odds of erosive esophagitis healing were greater in patients with LA grade A vs. D (OR = 4.54, 3.71-5.55, P < .0001) than in patients with LA grade B vs. D (OR = 2.76, 2.30-3.32, P < .0001) or C vs. D (OR = 1.70, 1.42-2.03, P < .0001).
While this pooled analysis is limited because "data were obtained from post hoc analyses of clinical efficacy studies not designed to evaluate the effects of obesity on GERD symptom severity or treatment success," the research has "considerable statistical power" due to the large number of patients included, the investigators wrote.
The study was supported by AstraZeneca LP, in Wilmington, Del. Dr. Sharma receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda. His coauthors disclosed ties to various pharmaceutical companies, including AstraZeneca.
Major finding: BMI has no significant effect on resolving heartburn (OR = 1.00; 95% CI, 0.97-1.03, P = .99) or healing of erosive esophagitis (OR = 1.01; 95% CI, 1.00-1.02; P = .23).
Data source: Two retrospective analyses of pooled data from several PPI studies conducted in patients with GERD (N = 704) and erosive esophagitis (N = 11,027).
Disclosures: The study was supported by AstraZeneca LP. The lead author receives research funding from Barrx Medical, Mauna Kea Technologies, Olympus, and Takeda.
Genetics contribute to smoking habits of adolescents, adults
Genetic risk may contribute to the rapid progression of daily and heavy smoking during adolescence and subsequent problems with nicotine dependence and smoking cessation in adulthood, according to a recent study.
The research may have implications for the development of initiatives that deter smoking in adolescents, reported Daniel W. Belsky, Ph.D., of the University of North Carolina at Chapel Hill and Duke University Medical Center, Durham, N.C., and his associates. The 38-year longitudinal study included 1,037 men and women from the Dunedin Multidisciplinary Health and Development Study of New Zealand. Researchers assessed participants with a multilocus genetic risk score (GRS), originating from three meta-analyses of genome-wide association studies (GWAS) that used the number of cigarettes smoked daily as their phenotype. Dr. Belsky and his team focused their investigation on the single-nucleotide polymorphisms in 15q25.1 and19q13.2 (JAMA Psychiatry 2013 March 27 [doi:10.1001/jamapsychiatry.2013.736]).
Genotyping was possible in 880 Dunedin subjects. In addition to evaluating family history in these individuals, researchers gathered smoking information at eight assessments from the age 11-38 years.
The GRS was not associated with whether or when subjects started smoking. "In fact, daily smokers who did not progress to heavy use were at lower genetic risk than individuals who never smoked," the researchers wrote.
Among 627 ever-smokers in the cohort, those with a higher genetic risk were more likely to rapidly progress to heavy smoking, meaning 20 or more cigarettes daily (hazard ratio, 1.35; 95% confidence interval, 1.14-1.58).
Adolescents with high genetic risk had a greater chance of becoming daily smokers by age 15 (relative risk, 1.24; 95% CI, 1.06-1.45) and progressing to heavy smoking by age 18 (RR, 1.43; 95% CI, 1.10-1.86).
Over the course of the study, subjects with a high genetic risk accumulated more pack-years of smoking. As adults, 27% of ever-smokers became nicotine dependent and those at higher genetic risk had a greater chance of doing so (HR, 1.27; 95% CI, 1.09-1.47). Additionally, of 277 cohort members who smoked daily during their 30s, those with a higher genetic risk were more likely to use smoking to cope with stress.
Further analyses found that smoking cessation was also difficult in adults at high genetic risk. For example, in the cohort of 277 daily smokers, 53% quit smoking a month or longer across 72 months follow-up; however, relapse occurred in 62%. Quitters with a higher genetic risk had a greater chance of relapsing (HR, 1.22; 95% CI, 1.02-1.45).
Only 20% of daily smokers abstained from smoking for a year or more.
Associations detected between the GRS and smoking phenotypes were small, noted the study authors. "Children who our study would classify at high genetic risk are not guaranteed to become addicted if they try smoking, and, even more importantly, children we would classify at low genetic risk are not immune to addiction."
Finally, researchers found that that the GRS score did not correlate with family history. "The GRS contained different information about risk for developmental and mature phenotypes of smoking behavior, compared with family history," reported the study authors.
The authors said that their research "adds a genetic dimension to longstanding arguments" in favor of early cigarette prevention of cigarette consumption, including surtaxes and age restrictions on tobacco purchases.
Funding for this study was provided through grants from various organizations, including the U.S. National Institute on Aging, the U.S. National Institute on Mental Health, and the U.K. Medical Research Council. The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council.
Genetic risk may contribute to the rapid progression of daily and heavy smoking during adolescence and subsequent problems with nicotine dependence and smoking cessation in adulthood, according to a recent study.
The research may have implications for the development of initiatives that deter smoking in adolescents, reported Daniel W. Belsky, Ph.D., of the University of North Carolina at Chapel Hill and Duke University Medical Center, Durham, N.C., and his associates. The 38-year longitudinal study included 1,037 men and women from the Dunedin Multidisciplinary Health and Development Study of New Zealand. Researchers assessed participants with a multilocus genetic risk score (GRS), originating from three meta-analyses of genome-wide association studies (GWAS) that used the number of cigarettes smoked daily as their phenotype. Dr. Belsky and his team focused their investigation on the single-nucleotide polymorphisms in 15q25.1 and19q13.2 (JAMA Psychiatry 2013 March 27 [doi:10.1001/jamapsychiatry.2013.736]).
Genotyping was possible in 880 Dunedin subjects. In addition to evaluating family history in these individuals, researchers gathered smoking information at eight assessments from the age 11-38 years.
The GRS was not associated with whether or when subjects started smoking. "In fact, daily smokers who did not progress to heavy use were at lower genetic risk than individuals who never smoked," the researchers wrote.
Among 627 ever-smokers in the cohort, those with a higher genetic risk were more likely to rapidly progress to heavy smoking, meaning 20 or more cigarettes daily (hazard ratio, 1.35; 95% confidence interval, 1.14-1.58).
Adolescents with high genetic risk had a greater chance of becoming daily smokers by age 15 (relative risk, 1.24; 95% CI, 1.06-1.45) and progressing to heavy smoking by age 18 (RR, 1.43; 95% CI, 1.10-1.86).
Over the course of the study, subjects with a high genetic risk accumulated more pack-years of smoking. As adults, 27% of ever-smokers became nicotine dependent and those at higher genetic risk had a greater chance of doing so (HR, 1.27; 95% CI, 1.09-1.47). Additionally, of 277 cohort members who smoked daily during their 30s, those with a higher genetic risk were more likely to use smoking to cope with stress.
Further analyses found that smoking cessation was also difficult in adults at high genetic risk. For example, in the cohort of 277 daily smokers, 53% quit smoking a month or longer across 72 months follow-up; however, relapse occurred in 62%. Quitters with a higher genetic risk had a greater chance of relapsing (HR, 1.22; 95% CI, 1.02-1.45).
Only 20% of daily smokers abstained from smoking for a year or more.
Associations detected between the GRS and smoking phenotypes were small, noted the study authors. "Children who our study would classify at high genetic risk are not guaranteed to become addicted if they try smoking, and, even more importantly, children we would classify at low genetic risk are not immune to addiction."
Finally, researchers found that that the GRS score did not correlate with family history. "The GRS contained different information about risk for developmental and mature phenotypes of smoking behavior, compared with family history," reported the study authors.
The authors said that their research "adds a genetic dimension to longstanding arguments" in favor of early cigarette prevention of cigarette consumption, including surtaxes and age restrictions on tobacco purchases.
Funding for this study was provided through grants from various organizations, including the U.S. National Institute on Aging, the U.S. National Institute on Mental Health, and the U.K. Medical Research Council. The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council.
Genetic risk may contribute to the rapid progression of daily and heavy smoking during adolescence and subsequent problems with nicotine dependence and smoking cessation in adulthood, according to a recent study.
The research may have implications for the development of initiatives that deter smoking in adolescents, reported Daniel W. Belsky, Ph.D., of the University of North Carolina at Chapel Hill and Duke University Medical Center, Durham, N.C., and his associates. The 38-year longitudinal study included 1,037 men and women from the Dunedin Multidisciplinary Health and Development Study of New Zealand. Researchers assessed participants with a multilocus genetic risk score (GRS), originating from three meta-analyses of genome-wide association studies (GWAS) that used the number of cigarettes smoked daily as their phenotype. Dr. Belsky and his team focused their investigation on the single-nucleotide polymorphisms in 15q25.1 and19q13.2 (JAMA Psychiatry 2013 March 27 [doi:10.1001/jamapsychiatry.2013.736]).
Genotyping was possible in 880 Dunedin subjects. In addition to evaluating family history in these individuals, researchers gathered smoking information at eight assessments from the age 11-38 years.
The GRS was not associated with whether or when subjects started smoking. "In fact, daily smokers who did not progress to heavy use were at lower genetic risk than individuals who never smoked," the researchers wrote.
Among 627 ever-smokers in the cohort, those with a higher genetic risk were more likely to rapidly progress to heavy smoking, meaning 20 or more cigarettes daily (hazard ratio, 1.35; 95% confidence interval, 1.14-1.58).
Adolescents with high genetic risk had a greater chance of becoming daily smokers by age 15 (relative risk, 1.24; 95% CI, 1.06-1.45) and progressing to heavy smoking by age 18 (RR, 1.43; 95% CI, 1.10-1.86).
Over the course of the study, subjects with a high genetic risk accumulated more pack-years of smoking. As adults, 27% of ever-smokers became nicotine dependent and those at higher genetic risk had a greater chance of doing so (HR, 1.27; 95% CI, 1.09-1.47). Additionally, of 277 cohort members who smoked daily during their 30s, those with a higher genetic risk were more likely to use smoking to cope with stress.
Further analyses found that smoking cessation was also difficult in adults at high genetic risk. For example, in the cohort of 277 daily smokers, 53% quit smoking a month or longer across 72 months follow-up; however, relapse occurred in 62%. Quitters with a higher genetic risk had a greater chance of relapsing (HR, 1.22; 95% CI, 1.02-1.45).
Only 20% of daily smokers abstained from smoking for a year or more.
Associations detected between the GRS and smoking phenotypes were small, noted the study authors. "Children who our study would classify at high genetic risk are not guaranteed to become addicted if they try smoking, and, even more importantly, children we would classify at low genetic risk are not immune to addiction."
Finally, researchers found that that the GRS score did not correlate with family history. "The GRS contained different information about risk for developmental and mature phenotypes of smoking behavior, compared with family history," reported the study authors.
The authors said that their research "adds a genetic dimension to longstanding arguments" in favor of early cigarette prevention of cigarette consumption, including surtaxes and age restrictions on tobacco purchases.
Funding for this study was provided through grants from various organizations, including the U.S. National Institute on Aging, the U.S. National Institute on Mental Health, and the U.K. Medical Research Council. The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council.
FROM JAMA PSYCHIATRY
Major finding:Ever-smokers with a higher genetic risk were more likely to rapidly progress to heavy smoking, meaning 20 or more cigarettes daily (hazard ratio 1.35; 95% CI, 1.14-1.58).
Data source: A 38-year, prospective, longitudinal study of a birth cohort consisting of 1,037 subjects.
Disclosures: Funding for this study was provided through grants from various organizations, including the National Institute on Aging, the National Institute on Mental Health, and the U.K. Medical Research Council. The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council.
Analysis of exhaled volatile organic compounds may accurately detect NASH
The analysis of volatile organic compounds in exhaled breath may provide a noninvasive and accurate test for diagnosing nonalcoholic steatohepatitis, according to results from a pilot study published in March.
This test could reduce the number of unnecessary liver biopsies and missed diagnoses associated with assessing plasma transaminase levels, reported Dr. Froukje J. Verdam of Maastricht (the Netherlands) University Medical Center and her associates (J. Hepatol. 2013;58:543-8).
Researchers evaluated breath samples with gas chromatography–mass spectrometry from 65 consecutive overweight or obese patients before they underwent laparoscopic abdominal surgery, between October 2007 and May 2011. These results were compared with histologic analysis of liver biopsies taken intraoperatively and assessments of plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Overall, liver biopsies showed that 39 patients (60%) had nonalcoholic steatohepatitis (NASH), defined as "showing signs of steatosis and inflammation." Additionally, ALT and AST levels were significantly higher in patients with the disease than without. However, "parameters such as gender, age, BMI, and HbA1c did not differ significantly," reported the study authors.
The analysis of three volatile organic compounds (VOCs) – n-tridecane, 3-methylbutanonitrile, and 1-propanol – enabled investigators to distinguish between patients with and without NASH, with a sensitivity of 90%, a specificity of 69%, and an area under the receiver operating characteristic (ROC) curve of 0.77 plus or minus 0.07. The positive predictive value of using VOC analysis for NASH was 81%, while the negative predictive value was 82%.
In comparison, in 61 patients from whom plasma was available, the sensitivity of measuring ALT was 19%, while the specificity was 96%. The positive and negative predictive values of ALT were 88% and 43%, respectively.
Further evaluation of the AST/ALT ratio found that it was 32% sensitive and 79% specific, while positive and negative predictive values were 70% and 43%, respectively.
"It can be concluded that the diagnostic value of VOC is much higher than that of plasma transaminases, resulting in less misdiagnosed patients," wrote the study authors. Prediction of NASH using VOC, ALT, and the AST/ALT ratio did not reflect liver biopsy results in 18%, 51%, and 49% of subjects, respectively.
Using VOC evaluation rather than histologic testing has several other advantages, according to the researchers. "The analysis of exhaled breath can identify NASH presence at an early stage, and early identification in a mild stage is pivotal to enhance the chances of cure," they wrote. "Furthermore, whereas a small part of the liver is considered in the evaluation of biopsies, the breath test used in this study noninvasively reflects total liver function."
Funding for this pilot study was provided by grants from the Dutch SenterNovem Innovation Oriented Research Program on Genomics and the Transnational University Limburg, Belgium. The study authors reported no conflicts of interest.
Dr. Scott L. Friedman comments: The study findings are
"intriguing," and the performance metrics of the analysis of exhaled
VOCs "are promising but not exceptional," wrote Dr. Scott L. Friedman.
However, "they well exceed the predictive values of transaminases, so
that the technology has value and merits further refinement and
validation."
The investigators do "not indicate through what
metabolic pathways and in which cells these specific organic compounds
are generated, and why they might correlate with disease activity," he
added. "Without such insight, the test is a correlative marker rather
than a true biomarker since there is no mechanistic link to a
disease-related pathway, which is a key requirement for a biomarker."
Dr.
Friedman is professor of medicine, liver diseases, at the Mount Sinai
School of Medicine in New York. These remarks were adapted from his
editorial accompanying this article and another on fatty liver disease
and telomerase length (J. Hepatol. 2013;58:j407-8 ). He is a consultant
for Exalenz Biosciences, which produces the methacetin breath test.
Dr. Scott L. Friedman comments: The study findings are
"intriguing," and the performance metrics of the analysis of exhaled
VOCs "are promising but not exceptional," wrote Dr. Scott L. Friedman.
However, "they well exceed the predictive values of transaminases, so
that the technology has value and merits further refinement and
validation."
The investigators do "not indicate through what
metabolic pathways and in which cells these specific organic compounds
are generated, and why they might correlate with disease activity," he
added. "Without such insight, the test is a correlative marker rather
than a true biomarker since there is no mechanistic link to a
disease-related pathway, which is a key requirement for a biomarker."
Dr.
Friedman is professor of medicine, liver diseases, at the Mount Sinai
School of Medicine in New York. These remarks were adapted from his
editorial accompanying this article and another on fatty liver disease
and telomerase length (J. Hepatol. 2013;58:j407-8 ). He is a consultant
for Exalenz Biosciences, which produces the methacetin breath test.
Dr. Scott L. Friedman comments: The study findings are
"intriguing," and the performance metrics of the analysis of exhaled
VOCs "are promising but not exceptional," wrote Dr. Scott L. Friedman.
However, "they well exceed the predictive values of transaminases, so
that the technology has value and merits further refinement and
validation."
The investigators do "not indicate through what
metabolic pathways and in which cells these specific organic compounds
are generated, and why they might correlate with disease activity," he
added. "Without such insight, the test is a correlative marker rather
than a true biomarker since there is no mechanistic link to a
disease-related pathway, which is a key requirement for a biomarker."
Dr.
Friedman is professor of medicine, liver diseases, at the Mount Sinai
School of Medicine in New York. These remarks were adapted from his
editorial accompanying this article and another on fatty liver disease
and telomerase length (J. Hepatol. 2013;58:j407-8 ). He is a consultant
for Exalenz Biosciences, which produces the methacetin breath test.
The analysis of volatile organic compounds in exhaled breath may provide a noninvasive and accurate test for diagnosing nonalcoholic steatohepatitis, according to results from a pilot study published in March.
This test could reduce the number of unnecessary liver biopsies and missed diagnoses associated with assessing plasma transaminase levels, reported Dr. Froukje J. Verdam of Maastricht (the Netherlands) University Medical Center and her associates (J. Hepatol. 2013;58:543-8).
Researchers evaluated breath samples with gas chromatography–mass spectrometry from 65 consecutive overweight or obese patients before they underwent laparoscopic abdominal surgery, between October 2007 and May 2011. These results were compared with histologic analysis of liver biopsies taken intraoperatively and assessments of plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Overall, liver biopsies showed that 39 patients (60%) had nonalcoholic steatohepatitis (NASH), defined as "showing signs of steatosis and inflammation." Additionally, ALT and AST levels were significantly higher in patients with the disease than without. However, "parameters such as gender, age, BMI, and HbA1c did not differ significantly," reported the study authors.
The analysis of three volatile organic compounds (VOCs) – n-tridecane, 3-methylbutanonitrile, and 1-propanol – enabled investigators to distinguish between patients with and without NASH, with a sensitivity of 90%, a specificity of 69%, and an area under the receiver operating characteristic (ROC) curve of 0.77 plus or minus 0.07. The positive predictive value of using VOC analysis for NASH was 81%, while the negative predictive value was 82%.
In comparison, in 61 patients from whom plasma was available, the sensitivity of measuring ALT was 19%, while the specificity was 96%. The positive and negative predictive values of ALT were 88% and 43%, respectively.
Further evaluation of the AST/ALT ratio found that it was 32% sensitive and 79% specific, while positive and negative predictive values were 70% and 43%, respectively.
"It can be concluded that the diagnostic value of VOC is much higher than that of plasma transaminases, resulting in less misdiagnosed patients," wrote the study authors. Prediction of NASH using VOC, ALT, and the AST/ALT ratio did not reflect liver biopsy results in 18%, 51%, and 49% of subjects, respectively.
Using VOC evaluation rather than histologic testing has several other advantages, according to the researchers. "The analysis of exhaled breath can identify NASH presence at an early stage, and early identification in a mild stage is pivotal to enhance the chances of cure," they wrote. "Furthermore, whereas a small part of the liver is considered in the evaluation of biopsies, the breath test used in this study noninvasively reflects total liver function."
Funding for this pilot study was provided by grants from the Dutch SenterNovem Innovation Oriented Research Program on Genomics and the Transnational University Limburg, Belgium. The study authors reported no conflicts of interest.
The analysis of volatile organic compounds in exhaled breath may provide a noninvasive and accurate test for diagnosing nonalcoholic steatohepatitis, according to results from a pilot study published in March.
This test could reduce the number of unnecessary liver biopsies and missed diagnoses associated with assessing plasma transaminase levels, reported Dr. Froukje J. Verdam of Maastricht (the Netherlands) University Medical Center and her associates (J. Hepatol. 2013;58:543-8).
Researchers evaluated breath samples with gas chromatography–mass spectrometry from 65 consecutive overweight or obese patients before they underwent laparoscopic abdominal surgery, between October 2007 and May 2011. These results were compared with histologic analysis of liver biopsies taken intraoperatively and assessments of plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Overall, liver biopsies showed that 39 patients (60%) had nonalcoholic steatohepatitis (NASH), defined as "showing signs of steatosis and inflammation." Additionally, ALT and AST levels were significantly higher in patients with the disease than without. However, "parameters such as gender, age, BMI, and HbA1c did not differ significantly," reported the study authors.
The analysis of three volatile organic compounds (VOCs) – n-tridecane, 3-methylbutanonitrile, and 1-propanol – enabled investigators to distinguish between patients with and without NASH, with a sensitivity of 90%, a specificity of 69%, and an area under the receiver operating characteristic (ROC) curve of 0.77 plus or minus 0.07. The positive predictive value of using VOC analysis for NASH was 81%, while the negative predictive value was 82%.
In comparison, in 61 patients from whom plasma was available, the sensitivity of measuring ALT was 19%, while the specificity was 96%. The positive and negative predictive values of ALT were 88% and 43%, respectively.
Further evaluation of the AST/ALT ratio found that it was 32% sensitive and 79% specific, while positive and negative predictive values were 70% and 43%, respectively.
"It can be concluded that the diagnostic value of VOC is much higher than that of plasma transaminases, resulting in less misdiagnosed patients," wrote the study authors. Prediction of NASH using VOC, ALT, and the AST/ALT ratio did not reflect liver biopsy results in 18%, 51%, and 49% of subjects, respectively.
Using VOC evaluation rather than histologic testing has several other advantages, according to the researchers. "The analysis of exhaled breath can identify NASH presence at an early stage, and early identification in a mild stage is pivotal to enhance the chances of cure," they wrote. "Furthermore, whereas a small part of the liver is considered in the evaluation of biopsies, the breath test used in this study noninvasively reflects total liver function."
Funding for this pilot study was provided by grants from the Dutch SenterNovem Innovation Oriented Research Program on Genomics and the Transnational University Limburg, Belgium. The study authors reported no conflicts of interest.
Major finding: Analysis of volatile organic compounds (VOCs) in exhaled breath to diagnose NASH was 90% sensitive and 69% specific.
Data source: A pilot study of 65 consecutive patients comparing VOC analysis of exhaled breath with plasma transaminase levels and liver biopsy.
Disclosures: Funding for this pilot study was provided by grants from the Dutch SenterNovem Innovation Oriented Research Program on Genomics and the Transnational University Limburg, Belgium. The study authors reported no conflicts of interest.