Liver Disease

Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.

Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.

To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).

Among their findings:

• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.

• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.

• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.

• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).

• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.

The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.

 

Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.

Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.

To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).

Among their findings:

• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.

• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.

• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.

• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).

• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.

The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.

 

Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.

Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.

To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).

Among their findings:

• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.

• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.

• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.

• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).

• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.

The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.

 

Nonalcoholic fatty liver disease (NAFLD) is estimated to affect over 64 million people each year in the United States, leading to medical costs of more than $100 billion, according to a new analysis.

Using a steady-state prevalence model, Zobair M. Younossi, MD, MPH, from the Center for Liver Diseases at Inova Fairfax (Va.) Hospital, and his coauthors, sought to estimate the prevalence and economic burden of NAFLD in the United States, Germany, France, Italy, and the United Kingdom.

Copyright sndr/istockphoto

Nonalcoholic fatty liver disease (NAFLD) is estimated to affect over 64 million people each year in the United States, leading to medical costs of more than $100 billion, according to a new analysis.

Using a steady-state prevalence model, Zobair M. Younossi, MD, MPH, from the Center for Liver Diseases at Inova Fairfax (Va.) Hospital, and his coauthors, sought to estimate the prevalence and economic burden of NAFLD in the United States, Germany, France, Italy, and the United Kingdom.

Copyright sndr/istockphoto

Nonalcoholic fatty liver disease (NAFLD) is estimated to affect over 64 million people each year in the United States, leading to medical costs of more than $100 billion, according to a new analysis.

Using a steady-state prevalence model, Zobair M. Younossi, MD, MPH, from the Center for Liver Diseases at Inova Fairfax (Va.) Hospital, and his coauthors, sought to estimate the prevalence and economic burden of NAFLD in the United States, Germany, France, Italy, and the United Kingdom.

Copyright sndr/istockphoto

Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.

Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.

Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new

Copyright s-c-s/Thinkstock

With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.

DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.

Access to these therapies, however, remains at issue.

“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”

Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.

There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.

Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.

Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
 

[email protected]

On Twitter @whitneymcknight

Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.

Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.

Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new

Copyright s-c-s/Thinkstock

With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.

DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.

Access to these therapies, however, remains at issue.

“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”

Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.

There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.

Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.

Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
 

[email protected]

On Twitter @whitneymcknight

Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.

Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.

Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new

Copyright s-c-s/Thinkstock

With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.

DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.

Access to these therapies, however, remains at issue.

“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”

Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.

There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.

Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.

Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
 

[email protected]

On Twitter @whitneymcknight

Regular physical exercise significantly improved measures of nonalcoholic fatty liver disease independently of dietary changes, according to a meta-analysis of randomized controlled* trials published in the October issue of Clinical Gastroenterology and Hepatology.

“On the basis of the current findings, physical activity should be recommended not only in combination with dietary changes but also independently as an effective approach to manage NAFLD,” wrote Lorenzo Orci, MD, and his associates at the University of Geneva. “We propose that the level of evidence surrounding the specific role of physical activity in the management of NAFLD is now sufficient to be awarded a grade of Ia.”

Nonalcoholic fatty liver disease, “the hepatic manifestation of metabolic syndrome,” affects at least one in four U.S. adults and 15%-35% of individuals in Europe, the Middle East, China, and Japan, the researchers noted. Dietary changes are the cornerstone of NAFLD management, and there is less evidence for how physical exercise affects liver fat content. Therefore, the researchers searched MEDLINE, Embase, and the Cochrane databases from inception through October 2015 to find randomized trials of the impact of physical activity on markers of liver steatosis and liver inflammation in patients diagnosed with NAFLD, obesity, type 2 diabetes, or metabolic syndrome. This approach yielded 28 trials with data from more than 1,600 patients. Only two trials were multicenter, 13 required participants to have an NAFLD diagnosis, four focused on type 2 diabetes, and most of the rest included sedentary obese patients without requiring a diagnosis of NAFLD, the researchers said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.036).

After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001). “Because effect sizes such as standard mean difference [SMD] are difficult to interpret, the translation of such a statistical measure into a clinically relevant notion has been the focus of research for more than a decade,” the investigators added. “A commonly used interpretation was proposed by Cohen, who suggested that SMDs of 0.2, 0.5, and 0.8 correspond to small, moderate, and large effect sizes, respectively. By using this rule of thumb, our results indicate that physical activity exerts a moderate-to-large impact on the reduction of intrahepatic lipid content.”

Exercise reduced liver fat content even more in pediatric patients (SMD, –0.75; 95% CI, –0.1 to –0.5; P less than .0001) and in patients who had been specifically diagnosed with NAFLD (SMD, –0.86; 95% CI, –1.26 to –0.46; P less than .0001). Patients with the highest baseline body mass index also seemed to benefit more than patients with lower baseline BMI (P = .04). Indeed, exercise reduced BMI itself by a weighted mean difference of 0.8 (95% CI, –1.22 to 0.38; P less than .001), the researchers noted. Exercise intensity did not seem to affect the likelihood of benefit. There was a trend toward a greater effect of aerobic over resistance training (P = .06), and few studies examined the effects of combining both types of exercise.

The multivariable analysis also linked physical activity to an average 3.30 IU/L drop in alanine aminotransferase levels (95% CI, –5.57 to –1.04) and to a 4.9 IU/L decrease in aspartate aminotransferase levels (95% CI, –8.68 to –1.02). The investigators were unable to assess the long-term effects of physical exercise, nor its effects on hepatic fibrosis or inflammation, they noted. Nonetheless, the moderate to large effect size “provides strong evidence for the recommendation of physical activity as an effective intervention in the treatment of NAFLD,” they concluded. “Physical activity is also associated with an improvement in blood levels of aminotransferases and is particularly beneficial in patients presenting with severe obesity at baseline.”

The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The investigators had no disclosures.

*Content was updated on 10/25/2016 

Regular physical exercise significantly improved measures of nonalcoholic fatty liver disease independently of dietary changes, according to a meta-analysis of randomized controlled* trials published in the October issue of Clinical Gastroenterology and Hepatology.

“On the basis of the current findings, physical activity should be recommended not only in combination with dietary changes but also independently as an effective approach to manage NAFLD,” wrote Lorenzo Orci, MD, and his associates at the University of Geneva. “We propose that the level of evidence surrounding the specific role of physical activity in the management of NAFLD is now sufficient to be awarded a grade of Ia.”

Nonalcoholic fatty liver disease, “the hepatic manifestation of metabolic syndrome,” affects at least one in four U.S. adults and 15%-35% of individuals in Europe, the Middle East, China, and Japan, the researchers noted. Dietary changes are the cornerstone of NAFLD management, and there is less evidence for how physical exercise affects liver fat content. Therefore, the researchers searched MEDLINE, Embase, and the Cochrane databases from inception through October 2015 to find randomized trials of the impact of physical activity on markers of liver steatosis and liver inflammation in patients diagnosed with NAFLD, obesity, type 2 diabetes, or metabolic syndrome. This approach yielded 28 trials with data from more than 1,600 patients. Only two trials were multicenter, 13 required participants to have an NAFLD diagnosis, four focused on type 2 diabetes, and most of the rest included sedentary obese patients without requiring a diagnosis of NAFLD, the researchers said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.036).

After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001). “Because effect sizes such as standard mean difference [SMD] are difficult to interpret, the translation of such a statistical measure into a clinically relevant notion has been the focus of research for more than a decade,” the investigators added. “A commonly used interpretation was proposed by Cohen, who suggested that SMDs of 0.2, 0.5, and 0.8 correspond to small, moderate, and large effect sizes, respectively. By using this rule of thumb, our results indicate that physical activity exerts a moderate-to-large impact on the reduction of intrahepatic lipid content.”

Exercise reduced liver fat content even more in pediatric patients (SMD, –0.75; 95% CI, –0.1 to –0.5; P less than .0001) and in patients who had been specifically diagnosed with NAFLD (SMD, –0.86; 95% CI, –1.26 to –0.46; P less than .0001). Patients with the highest baseline body mass index also seemed to benefit more than patients with lower baseline BMI (P = .04). Indeed, exercise reduced BMI itself by a weighted mean difference of 0.8 (95% CI, –1.22 to 0.38; P less than .001), the researchers noted. Exercise intensity did not seem to affect the likelihood of benefit. There was a trend toward a greater effect of aerobic over resistance training (P = .06), and few studies examined the effects of combining both types of exercise.

The multivariable analysis also linked physical activity to an average 3.30 IU/L drop in alanine aminotransferase levels (95% CI, –5.57 to –1.04) and to a 4.9 IU/L decrease in aspartate aminotransferase levels (95% CI, –8.68 to –1.02). The investigators were unable to assess the long-term effects of physical exercise, nor its effects on hepatic fibrosis or inflammation, they noted. Nonetheless, the moderate to large effect size “provides strong evidence for the recommendation of physical activity as an effective intervention in the treatment of NAFLD,” they concluded. “Physical activity is also associated with an improvement in blood levels of aminotransferases and is particularly beneficial in patients presenting with severe obesity at baseline.”

The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The investigators had no disclosures.

*Content was updated on 10/25/2016 

Regular physical exercise significantly improved measures of nonalcoholic fatty liver disease independently of dietary changes, according to a meta-analysis of randomized controlled* trials published in the October issue of Clinical Gastroenterology and Hepatology.

“On the basis of the current findings, physical activity should be recommended not only in combination with dietary changes but also independently as an effective approach to manage NAFLD,” wrote Lorenzo Orci, MD, and his associates at the University of Geneva. “We propose that the level of evidence surrounding the specific role of physical activity in the management of NAFLD is now sufficient to be awarded a grade of Ia.”

Nonalcoholic fatty liver disease, “the hepatic manifestation of metabolic syndrome,” affects at least one in four U.S. adults and 15%-35% of individuals in Europe, the Middle East, China, and Japan, the researchers noted. Dietary changes are the cornerstone of NAFLD management, and there is less evidence for how physical exercise affects liver fat content. Therefore, the researchers searched MEDLINE, Embase, and the Cochrane databases from inception through October 2015 to find randomized trials of the impact of physical activity on markers of liver steatosis and liver inflammation in patients diagnosed with NAFLD, obesity, type 2 diabetes, or metabolic syndrome. This approach yielded 28 trials with data from more than 1,600 patients. Only two trials were multicenter, 13 required participants to have an NAFLD diagnosis, four focused on type 2 diabetes, and most of the rest included sedentary obese patients without requiring a diagnosis of NAFLD, the researchers said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.036).

After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001). “Because effect sizes such as standard mean difference [SMD] are difficult to interpret, the translation of such a statistical measure into a clinically relevant notion has been the focus of research for more than a decade,” the investigators added. “A commonly used interpretation was proposed by Cohen, who suggested that SMDs of 0.2, 0.5, and 0.8 correspond to small, moderate, and large effect sizes, respectively. By using this rule of thumb, our results indicate that physical activity exerts a moderate-to-large impact on the reduction of intrahepatic lipid content.”

Exercise reduced liver fat content even more in pediatric patients (SMD, –0.75; 95% CI, –0.1 to –0.5; P less than .0001) and in patients who had been specifically diagnosed with NAFLD (SMD, –0.86; 95% CI, –1.26 to –0.46; P less than .0001). Patients with the highest baseline body mass index also seemed to benefit more than patients with lower baseline BMI (P = .04). Indeed, exercise reduced BMI itself by a weighted mean difference of 0.8 (95% CI, –1.22 to 0.38; P less than .001), the researchers noted. Exercise intensity did not seem to affect the likelihood of benefit. There was a trend toward a greater effect of aerobic over resistance training (P = .06), and few studies examined the effects of combining both types of exercise.

The multivariable analysis also linked physical activity to an average 3.30 IU/L drop in alanine aminotransferase levels (95% CI, –5.57 to –1.04) and to a 4.9 IU/L decrease in aspartate aminotransferase levels (95% CI, –8.68 to –1.02). The investigators were unable to assess the long-term effects of physical exercise, nor its effects on hepatic fibrosis or inflammation, they noted. Nonetheless, the moderate to large effect size “provides strong evidence for the recommendation of physical activity as an effective intervention in the treatment of NAFLD,” they concluded. “Physical activity is also associated with an improvement in blood levels of aminotransferases and is particularly beneficial in patients presenting with severe obesity at baseline.”

The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The investigators had no disclosures.

*Content was updated on 10/25/2016 

A once-daily regimen of two investigational, direct-acting anti-HCV agents, ABT-493 and ABT-530, was well tolerated and achieved sustained viral response at 12 weeks (SVR12) for nearly all patients with compensated cirrhosis and chronic genotype (GT) 1 or 3 hepatitis C virus infection, according to open-label phase II studies.

“The unique potency of these agents against all genotypes, even in the presence of common NS3 and/or NS5A baseline substitutions that confer resistance to most contemporary NS3/4A protease inhibitors and NS5A inhibitors, offers the potential for pangenotypic [HCV] therapy without ribavirin,” Edward J. Gane, MD, of the University of Auckland, New Zealand, and his associates wrote in the October issue of Gastroenterology. Phase III trials are now testing this hypothesis by focusing on cohorts of treatment-experienced, genotype 3–infected patients, on patients with renal impairment, and on patients who failed earlier-generation direct-acting antiviral regimens, they said.

The prevalence of HCV-related cirrhosis has yet to peak, and gold standard therapies for GT3 and GT1a infections can take weeks of treatment and the use of ribavirin, which causes undesirable side effects, the investigators noted. Attempts to surmount these residual barriers led to the development of ABT-493, an HCV nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530, an HCV NS5A inhibitor. During in vitro studies, both agents showed “potent” activity against all major HCV genotypes, including variants with mutations that confer resistance to earlier, direct-acting antivirals, the researchers said (Gastroenterology. 2016 Jul 22. doi: 10.1053/j.gastro.2016.07.020). Their two open-label phase II studies enrolled adults with compensated cirrhosis and chronic GT3 (55 patients) or GT1 (27 patients) infection. Among GT1 patients, 41% had baseline NS3 substitutions conferring resistance to earlier-generation drugs, 19% had NS5A substitutions, and 11% had both mutations. The GT1-infected patients received 200 mg ABT-493 and 120 mg of ABT-530. The GT3-infected patients received 300 mg ABT-493 and 120 mg ABT-530, and half (27 patients) also received ribavirin. Most patients were treatment-naive, male, and white, with Child-Pugh scores of 5 and HCV RNA levels averaging about 6.2-6.6 log10 IU/mL.

In all, 26 patients with GT1 infection (96%) achieved SVR12 (95% confidence interval, 82% to 99%). The remaining patient relapsed after completing treatment. All treatment-naive GT3 patients achieved SVR12 whether or not they received ribavirin. However, one treatment-experienced GT3 patient who did not receive ribavirin relapsed after 16 weeks of treatment. Thus, rates of SVR12 were 96% (95% confidence interval, 82%-99%) for GT3 patients who did not receive ribavirin and 100% (95% CI, 88%-100%) for those who did. Notably, 94% of patients with baseline substitutions in NS3 and NS5A achieved SVR12, and there was no apparent link between treatment failure and any demographic or clinical characteristics, the investigators wrote.

Adverse events affected about 74% of patients and were usually mild or moderate in severity. Patients who did not receive ribavirin were most likely to report headache (15%), diarrhea (13%), and fatigue (11%). Only 4% of GT1 patients and 7% of the GT3 cohorts developed serious adverse events, and the only serious adverse event considered possibly treatment related involved a delusional disorder in a 57-year-old male who was receiving ribavirin and admitted amphetamine and alcohol use on the day it occurred. Treatment-related laboratory abnormalities were uncommon, no patients stopped treatment because of adverse events, and there were no deaths. “The rates of some adverse events were numerically higher with the higher ABT-493 dose, though the sample sizes are small and this was a cross-study comparison,” the investigators added. “Though not included in this study, patients with severe or end-stage kidney disease are predicted to be able to be treated with ABT-493 and ABT-530 because both agents have negligible renal excretion. These drugs were well tolerated in HCV-uninfected patients with renal impairment and can be administered without dose adjustment.”AbbVie funded the study and makes ABT-493 and ABT-530. Dr. Gane disclosed ties to AbbVie, Achillion Pharmaceuticals, Alnylam, Janssen, Merck, Novartis, and Novira.

A once-daily regimen of two investigational, direct-acting anti-HCV agents, ABT-493 and ABT-530, was well tolerated and achieved sustained viral response at 12 weeks (SVR12) for nearly all patients with compensated cirrhosis and chronic genotype (GT) 1 or 3 hepatitis C virus infection, according to open-label phase II studies.

“The unique potency of these agents against all genotypes, even in the presence of common NS3 and/or NS5A baseline substitutions that confer resistance to most contemporary NS3/4A protease inhibitors and NS5A inhibitors, offers the potential for pangenotypic [HCV] therapy without ribavirin,” Edward J. Gane, MD, of the University of Auckland, New Zealand, and his associates wrote in the October issue of Gastroenterology. Phase III trials are now testing this hypothesis by focusing on cohorts of treatment-experienced, genotype 3–infected patients, on patients with renal impairment, and on patients who failed earlier-generation direct-acting antiviral regimens, they said.

The prevalence of HCV-related cirrhosis has yet to peak, and gold standard therapies for GT3 and GT1a infections can take weeks of treatment and the use of ribavirin, which causes undesirable side effects, the investigators noted. Attempts to surmount these residual barriers led to the development of ABT-493, an HCV nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530, an HCV NS5A inhibitor. During in vitro studies, both agents showed “potent” activity against all major HCV genotypes, including variants with mutations that confer resistance to earlier, direct-acting antivirals, the researchers said (Gastroenterology. 2016 Jul 22. doi: 10.1053/j.gastro.2016.07.020). Their two open-label phase II studies enrolled adults with compensated cirrhosis and chronic GT3 (55 patients) or GT1 (27 patients) infection. Among GT1 patients, 41% had baseline NS3 substitutions conferring resistance to earlier-generation drugs, 19% had NS5A substitutions, and 11% had both mutations. The GT1-infected patients received 200 mg ABT-493 and 120 mg of ABT-530. The GT3-infected patients received 300 mg ABT-493 and 120 mg ABT-530, and half (27 patients) also received ribavirin. Most patients were treatment-naive, male, and white, with Child-Pugh scores of 5 and HCV RNA levels averaging about 6.2-6.6 log10 IU/mL.

In all, 26 patients with GT1 infection (96%) achieved SVR12 (95% confidence interval, 82% to 99%). The remaining patient relapsed after completing treatment. All treatment-naive GT3 patients achieved SVR12 whether or not they received ribavirin. However, one treatment-experienced GT3 patient who did not receive ribavirin relapsed after 16 weeks of treatment. Thus, rates of SVR12 were 96% (95% confidence interval, 82%-99%) for GT3 patients who did not receive ribavirin and 100% (95% CI, 88%-100%) for those who did. Notably, 94% of patients with baseline substitutions in NS3 and NS5A achieved SVR12, and there was no apparent link between treatment failure and any demographic or clinical characteristics, the investigators wrote.

Adverse events affected about 74% of patients and were usually mild or moderate in severity. Patients who did not receive ribavirin were most likely to report headache (15%), diarrhea (13%), and fatigue (11%). Only 4% of GT1 patients and 7% of the GT3 cohorts developed serious adverse events, and the only serious adverse event considered possibly treatment related involved a delusional disorder in a 57-year-old male who was receiving ribavirin and admitted amphetamine and alcohol use on the day it occurred. Treatment-related laboratory abnormalities were uncommon, no patients stopped treatment because of adverse events, and there were no deaths. “The rates of some adverse events were numerically higher with the higher ABT-493 dose, though the sample sizes are small and this was a cross-study comparison,” the investigators added. “Though not included in this study, patients with severe or end-stage kidney disease are predicted to be able to be treated with ABT-493 and ABT-530 because both agents have negligible renal excretion. These drugs were well tolerated in HCV-uninfected patients with renal impairment and can be administered without dose adjustment.”AbbVie funded the study and makes ABT-493 and ABT-530. Dr. Gane disclosed ties to AbbVie, Achillion Pharmaceuticals, Alnylam, Janssen, Merck, Novartis, and Novira.

A once-daily regimen of two investigational, direct-acting anti-HCV agents, ABT-493 and ABT-530, was well tolerated and achieved sustained viral response at 12 weeks (SVR12) for nearly all patients with compensated cirrhosis and chronic genotype (GT) 1 or 3 hepatitis C virus infection, according to open-label phase II studies.

“The unique potency of these agents against all genotypes, even in the presence of common NS3 and/or NS5A baseline substitutions that confer resistance to most contemporary NS3/4A protease inhibitors and NS5A inhibitors, offers the potential for pangenotypic [HCV] therapy without ribavirin,” Edward J. Gane, MD, of the University of Auckland, New Zealand, and his associates wrote in the October issue of Gastroenterology. Phase III trials are now testing this hypothesis by focusing on cohorts of treatment-experienced, genotype 3–infected patients, on patients with renal impairment, and on patients who failed earlier-generation direct-acting antiviral regimens, they said.

The prevalence of HCV-related cirrhosis has yet to peak, and gold standard therapies for GT3 and GT1a infections can take weeks of treatment and the use of ribavirin, which causes undesirable side effects, the investigators noted. Attempts to surmount these residual barriers led to the development of ABT-493, an HCV nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530, an HCV NS5A inhibitor. During in vitro studies, both agents showed “potent” activity against all major HCV genotypes, including variants with mutations that confer resistance to earlier, direct-acting antivirals, the researchers said (Gastroenterology. 2016 Jul 22. doi: 10.1053/j.gastro.2016.07.020). Their two open-label phase II studies enrolled adults with compensated cirrhosis and chronic GT3 (55 patients) or GT1 (27 patients) infection. Among GT1 patients, 41% had baseline NS3 substitutions conferring resistance to earlier-generation drugs, 19% had NS5A substitutions, and 11% had both mutations. The GT1-infected patients received 200 mg ABT-493 and 120 mg of ABT-530. The GT3-infected patients received 300 mg ABT-493 and 120 mg ABT-530, and half (27 patients) also received ribavirin. Most patients were treatment-naive, male, and white, with Child-Pugh scores of 5 and HCV RNA levels averaging about 6.2-6.6 log10 IU/mL.

In all, 26 patients with GT1 infection (96%) achieved SVR12 (95% confidence interval, 82% to 99%). The remaining patient relapsed after completing treatment. All treatment-naive GT3 patients achieved SVR12 whether or not they received ribavirin. However, one treatment-experienced GT3 patient who did not receive ribavirin relapsed after 16 weeks of treatment. Thus, rates of SVR12 were 96% (95% confidence interval, 82%-99%) for GT3 patients who did not receive ribavirin and 100% (95% CI, 88%-100%) for those who did. Notably, 94% of patients with baseline substitutions in NS3 and NS5A achieved SVR12, and there was no apparent link between treatment failure and any demographic or clinical characteristics, the investigators wrote.

Adverse events affected about 74% of patients and were usually mild or moderate in severity. Patients who did not receive ribavirin were most likely to report headache (15%), diarrhea (13%), and fatigue (11%). Only 4% of GT1 patients and 7% of the GT3 cohorts developed serious adverse events, and the only serious adverse event considered possibly treatment related involved a delusional disorder in a 57-year-old male who was receiving ribavirin and admitted amphetamine and alcohol use on the day it occurred. Treatment-related laboratory abnormalities were uncommon, no patients stopped treatment because of adverse events, and there were no deaths. “The rates of some adverse events were numerically higher with the higher ABT-493 dose, though the sample sizes are small and this was a cross-study comparison,” the investigators added. “Though not included in this study, patients with severe or end-stage kidney disease are predicted to be able to be treated with ABT-493 and ABT-530 because both agents have negligible renal excretion. These drugs were well tolerated in HCV-uninfected patients with renal impairment and can be administered without dose adjustment.”AbbVie funded the study and makes ABT-493 and ABT-530. Dr. Gane disclosed ties to AbbVie, Achillion Pharmaceuticals, Alnylam, Janssen, Merck, Novartis, and Novira.

A combination of sofosbuvir/daclatasvir yielded sustained virological responses at 12 weeks after the last treatment in 95% of hepatitis C virus–infected patients with genotype 1.

“Real-life results of the sofosbuvir + ribavirin or sofosbuvir + simeprevir combination have been extensively reported, but there are few data regarding the sofosbuvir + daclatasvir combination in genotype 1–infected patients,” wrote Stanislas Pol, MD, of Hôpital Cochin, Institut Pasteur, Paris, and his colleagues.

To assess the effectiveness of the combination, researchers reviewed data from 768 patients with HCV genotype 1 who began treatments of 400 mg/day sofosbuvir and 60 mg/day daclatasvir prior to Oct. 1, 2014 (J Hepatol. 2016. doi: 10.1016/j.jhep.2016.08.021). Patients were treated for 12 or 24 weeks, and the primary endpoint was sustained virological response 12 weeks after the last treatment (SVR12).

A total of 92% of patients treated for 12 weeks and 99% of patients treated for 24 weeks with the combination met the primary endpoint of SVR12, for an average of 95% overall. Treatment duration and the presence or absence of ribavirin had no significant impact on the treatment responses in noncirrhotic patients. However, the SVR12 rate was significantly higher among cirrhotic patients in the 24-week treatment group than in the 12-week group (95% vs. 88%).

One patient died from cerebral hemorrhage 6 weeks after beginning treatment, and the death was considered possibly related to the combination treatment; two deaths from septic shock and two deaths from end-stage liver disease were not considered treatment related. Other serious adverse events were reported in 10% of patients independent of treatment duration or use of ribavirin. The six serious adverse events possibly related to treatment included three cardiac disorders. The most common adverse events included insomnia, headache, and asthenia, reported in at least 10% of patients.

Only decompensated cirrhosis and a prothrombin time greater than 70% were independently associated with serious adverse events.

The study was limited by several factors, including its observational nature and relatively low number of patients treated with ribavirin in the 12-week group, the researchers noted. However, the results suggest that “in real life, the sofosbuvir + daclatasvir combination in difficult-to-treat patients with HCV genotype 1 infection was associated with a high rate of SVR12,” they said.

Inserm-ANRS supported the study. The researchers disclosed funding from government organizations and pharmaceutical companies including MSD, Janssen, Gilead, AbbVie, BMS, and Roche.

A combination of sofosbuvir/daclatasvir yielded sustained virological responses at 12 weeks after the last treatment in 95% of hepatitis C virus–infected patients with genotype 1.

“Real-life results of the sofosbuvir + ribavirin or sofosbuvir + simeprevir combination have been extensively reported, but there are few data regarding the sofosbuvir + daclatasvir combination in genotype 1–infected patients,” wrote Stanislas Pol, MD, of Hôpital Cochin, Institut Pasteur, Paris, and his colleagues.

To assess the effectiveness of the combination, researchers reviewed data from 768 patients with HCV genotype 1 who began treatments of 400 mg/day sofosbuvir and 60 mg/day daclatasvir prior to Oct. 1, 2014 (J Hepatol. 2016. doi: 10.1016/j.jhep.2016.08.021). Patients were treated for 12 or 24 weeks, and the primary endpoint was sustained virological response 12 weeks after the last treatment (SVR12).

A total of 92% of patients treated for 12 weeks and 99% of patients treated for 24 weeks with the combination met the primary endpoint of SVR12, for an average of 95% overall. Treatment duration and the presence or absence of ribavirin had no significant impact on the treatment responses in noncirrhotic patients. However, the SVR12 rate was significantly higher among cirrhotic patients in the 24-week treatment group than in the 12-week group (95% vs. 88%).

One patient died from cerebral hemorrhage 6 weeks after beginning treatment, and the death was considered possibly related to the combination treatment; two deaths from septic shock and two deaths from end-stage liver disease were not considered treatment related. Other serious adverse events were reported in 10% of patients independent of treatment duration or use of ribavirin. The six serious adverse events possibly related to treatment included three cardiac disorders. The most common adverse events included insomnia, headache, and asthenia, reported in at least 10% of patients.

Only decompensated cirrhosis and a prothrombin time greater than 70% were independently associated with serious adverse events.

The study was limited by several factors, including its observational nature and relatively low number of patients treated with ribavirin in the 12-week group, the researchers noted. However, the results suggest that “in real life, the sofosbuvir + daclatasvir combination in difficult-to-treat patients with HCV genotype 1 infection was associated with a high rate of SVR12,” they said.

Inserm-ANRS supported the study. The researchers disclosed funding from government organizations and pharmaceutical companies including MSD, Janssen, Gilead, AbbVie, BMS, and Roche.

A combination of sofosbuvir/daclatasvir yielded sustained virological responses at 12 weeks after the last treatment in 95% of hepatitis C virus–infected patients with genotype 1.

“Real-life results of the sofosbuvir + ribavirin or sofosbuvir + simeprevir combination have been extensively reported, but there are few data regarding the sofosbuvir + daclatasvir combination in genotype 1–infected patients,” wrote Stanislas Pol, MD, of Hôpital Cochin, Institut Pasteur, Paris, and his colleagues.

To assess the effectiveness of the combination, researchers reviewed data from 768 patients with HCV genotype 1 who began treatments of 400 mg/day sofosbuvir and 60 mg/day daclatasvir prior to Oct. 1, 2014 (J Hepatol. 2016. doi: 10.1016/j.jhep.2016.08.021). Patients were treated for 12 or 24 weeks, and the primary endpoint was sustained virological response 12 weeks after the last treatment (SVR12).

A total of 92% of patients treated for 12 weeks and 99% of patients treated for 24 weeks with the combination met the primary endpoint of SVR12, for an average of 95% overall. Treatment duration and the presence or absence of ribavirin had no significant impact on the treatment responses in noncirrhotic patients. However, the SVR12 rate was significantly higher among cirrhotic patients in the 24-week treatment group than in the 12-week group (95% vs. 88%).

One patient died from cerebral hemorrhage 6 weeks after beginning treatment, and the death was considered possibly related to the combination treatment; two deaths from septic shock and two deaths from end-stage liver disease were not considered treatment related. Other serious adverse events were reported in 10% of patients independent of treatment duration or use of ribavirin. The six serious adverse events possibly related to treatment included three cardiac disorders. The most common adverse events included insomnia, headache, and asthenia, reported in at least 10% of patients.

Only decompensated cirrhosis and a prothrombin time greater than 70% were independently associated with serious adverse events.

The study was limited by several factors, including its observational nature and relatively low number of patients treated with ribavirin in the 12-week group, the researchers noted. However, the results suggest that “in real life, the sofosbuvir + daclatasvir combination in difficult-to-treat patients with HCV genotype 1 infection was associated with a high rate of SVR12,” they said.

Inserm-ANRS supported the study. The researchers disclosed funding from government organizations and pharmaceutical companies including MSD, Janssen, Gilead, AbbVie, BMS, and Roche.

The Food and Drug Administration has given an orphan drug designation to the compound BIV201 for the treatment of ascites, according to a press release from the drug’s manufacturer, BioVie.

The FDA designation for BIV201 is for the treatment of ascites due to all etiologies except cancer. Clinical trials could commence by 2017, if accepted by the FDA. If trials are successful, other applications for BIV201 could be tested. BIV201 is a vasoconstricter, and could also be used to treat diseases like type 1 hepatorenal syndrome, esophageal variceal bleeds, and sepsis.

Ascites, a common complication of liver cirrhosis, has no specific approved treatment, and 40% of patients diagnosed with ascites die within 2 years. Other treatments may work initially, but become ineffective as the patient worsens. Treatment costs in the United States for liver cirrhosis and related complications, including ascites, totals over $4 billion.

“Orphan drug designation represents a major milestone supporting the clinical development and eventual commercialization of BIV201 therapy. It recognizes the importance of pioneering a new therapeutic approach for this relatively small group of desperately ill patients,” Jonathan Adams, BioVie CEO, said in the press release.

Find the full press release on the BioVie website.

[email protected]

The Food and Drug Administration has given an orphan drug designation to the compound BIV201 for the treatment of ascites, according to a press release from the drug’s manufacturer, BioVie.

The FDA designation for BIV201 is for the treatment of ascites due to all etiologies except cancer. Clinical trials could commence by 2017, if accepted by the FDA. If trials are successful, other applications for BIV201 could be tested. BIV201 is a vasoconstricter, and could also be used to treat diseases like type 1 hepatorenal syndrome, esophageal variceal bleeds, and sepsis.

Ascites, a common complication of liver cirrhosis, has no specific approved treatment, and 40% of patients diagnosed with ascites die within 2 years. Other treatments may work initially, but become ineffective as the patient worsens. Treatment costs in the United States for liver cirrhosis and related complications, including ascites, totals over $4 billion.

“Orphan drug designation represents a major milestone supporting the clinical development and eventual commercialization of BIV201 therapy. It recognizes the importance of pioneering a new therapeutic approach for this relatively small group of desperately ill patients,” Jonathan Adams, BioVie CEO, said in the press release.

Find the full press release on the BioVie website.

[email protected]

The Food and Drug Administration has given an orphan drug designation to the compound BIV201 for the treatment of ascites, according to a press release from the drug’s manufacturer, BioVie.

The FDA designation for BIV201 is for the treatment of ascites due to all etiologies except cancer. Clinical trials could commence by 2017, if accepted by the FDA. If trials are successful, other applications for BIV201 could be tested. BIV201 is a vasoconstricter, and could also be used to treat diseases like type 1 hepatorenal syndrome, esophageal variceal bleeds, and sepsis.

Ascites, a common complication of liver cirrhosis, has no specific approved treatment, and 40% of patients diagnosed with ascites die within 2 years. Other treatments may work initially, but become ineffective as the patient worsens. Treatment costs in the United States for liver cirrhosis and related complications, including ascites, totals over $4 billion.

“Orphan drug designation represents a major milestone supporting the clinical development and eventual commercialization of BIV201 therapy. It recognizes the importance of pioneering a new therapeutic approach for this relatively small group of desperately ill patients,” Jonathan Adams, BioVie CEO, said in the press release.

Find the full press release on the BioVie website.

[email protected]

While real-time polymerase chain reaction (PCR) testing is the standard test for hepatitis E virus infection, an anti-HEV-specific enzyme-linked immunosorbent assay (ELISA) is more effective than is PCR at distinguishing between acute and chronic HEV infections.

“A clinical challenge in the management of immunocompromised patients with HEV infection is to differentiate between the acute and chronic course of infection [as] approximately 60% of infected immunocompromised individuals experience a chronic infection, which might require treatment with ribavirin,” said lead author Patrick Behrendt, Dr.med., of Hannover (Germany) Medical School.

CDC/Wikimedia Commons/Public Domain

The anti-HEV antigen (Ag) ELISA has recently become commercially available, making it an even bigger matter of interest. Dr. Behrendt and his coinvestigators analyzed sera from 18 patients with acute and 21 patients with chronic HEV, whose samples were collected between 2008 and 2015. The sera were retrospectively analyzed via both real-time PCR and ELISA to compare the efficacy of each in identifying HEV – more specifically, HEV genotype 3 – in each subject. For the ELISA analysis, 100 mcL of serum were added to each well of an ELISA plate, which was subsequently incubated at 37 degrees Celsius for 1 hour.

The researchers analyzed sera from four individuals with chronic HEV using serial dilutions to compare sensitivity of real-time PCR and ELISA. In three out of those four sera (75%), ELISA showed negative results due to HEV RNA levels of fewer than 10,000 copies/mL; on the other hand, real-time PCR showed a “linear reduction in levels,” indicating that it is the better option in detecting HEV genotype 3 (J Infect Dis. 2016 May 27;214[3]:361-8).

ELISA was also used on 20 chronic HEV patients and 17 acute HEV patients to determine its sensitivity at distinguishing between the two types of infection. In this cohort, only 64.7% of RNA-positive patients were deemed positive according to the ELISA testing, while ELISA results were positive in all of the cases of chronic HEV infections. None of the patients with chronic infection registered a false-negative, which indicates “a high reliability of the assay for this cohort,” according to the investigators.

“Comparison of chronically infected individuals with acutely infected patients revealed drastically increased ODs in chronically infected patients, while most of the positive samples from acutely infected patients displayed significantly lower values [which] led to a sensitivity of 100% (20 of 20) [ELISA] results for chronically HEV infected individuals,” the authors concluded. “Our study demonstrates that [ELISA] has a sensitivity of 65% and a specificity of 92% in detecting an ongoing HEV infection in a real-life cohort.”

The German Center for Infection Research, the Helmholtz Center for Infection Research, and the German Ministry for Education and Research funded the study. The researchers reported no relevant financial disclosures.

[email protected]

While real-time polymerase chain reaction (PCR) testing is the standard test for hepatitis E virus infection, an anti-HEV-specific enzyme-linked immunosorbent assay (ELISA) is more effective than is PCR at distinguishing between acute and chronic HEV infections.

“A clinical challenge in the management of immunocompromised patients with HEV infection is to differentiate between the acute and chronic course of infection [as] approximately 60% of infected immunocompromised individuals experience a chronic infection, which might require treatment with ribavirin,” said lead author Patrick Behrendt, Dr.med., of Hannover (Germany) Medical School.

CDC/Wikimedia Commons/Public Domain

The anti-HEV antigen (Ag) ELISA has recently become commercially available, making it an even bigger matter of interest. Dr. Behrendt and his coinvestigators analyzed sera from 18 patients with acute and 21 patients with chronic HEV, whose samples were collected between 2008 and 2015. The sera were retrospectively analyzed via both real-time PCR and ELISA to compare the efficacy of each in identifying HEV – more specifically, HEV genotype 3 – in each subject. For the ELISA analysis, 100 mcL of serum were added to each well of an ELISA plate, which was subsequently incubated at 37 degrees Celsius for 1 hour.

The researchers analyzed sera from four individuals with chronic HEV using serial dilutions to compare sensitivity of real-time PCR and ELISA. In three out of those four sera (75%), ELISA showed negative results due to HEV RNA levels of fewer than 10,000 copies/mL; on the other hand, real-time PCR showed a “linear reduction in levels,” indicating that it is the better option in detecting HEV genotype 3 (J Infect Dis. 2016 May 27;214[3]:361-8).

ELISA was also used on 20 chronic HEV patients and 17 acute HEV patients to determine its sensitivity at distinguishing between the two types of infection. In this cohort, only 64.7% of RNA-positive patients were deemed positive according to the ELISA testing, while ELISA results were positive in all of the cases of chronic HEV infections. None of the patients with chronic infection registered a false-negative, which indicates “a high reliability of the assay for this cohort,” according to the investigators.

“Comparison of chronically infected individuals with acutely infected patients revealed drastically increased ODs in chronically infected patients, while most of the positive samples from acutely infected patients displayed significantly lower values [which] led to a sensitivity of 100% (20 of 20) [ELISA] results for chronically HEV infected individuals,” the authors concluded. “Our study demonstrates that [ELISA] has a sensitivity of 65% and a specificity of 92% in detecting an ongoing HEV infection in a real-life cohort.”

The German Center for Infection Research, the Helmholtz Center for Infection Research, and the German Ministry for Education and Research funded the study. The researchers reported no relevant financial disclosures.

[email protected]

While real-time polymerase chain reaction (PCR) testing is the standard test for hepatitis E virus infection, an anti-HEV-specific enzyme-linked immunosorbent assay (ELISA) is more effective than is PCR at distinguishing between acute and chronic HEV infections.

“A clinical challenge in the management of immunocompromised patients with HEV infection is to differentiate between the acute and chronic course of infection [as] approximately 60% of infected immunocompromised individuals experience a chronic infection, which might require treatment with ribavirin,” said lead author Patrick Behrendt, Dr.med., of Hannover (Germany) Medical School.

CDC/Wikimedia Commons/Public Domain

The anti-HEV antigen (Ag) ELISA has recently become commercially available, making it an even bigger matter of interest. Dr. Behrendt and his coinvestigators analyzed sera from 18 patients with acute and 21 patients with chronic HEV, whose samples were collected between 2008 and 2015. The sera were retrospectively analyzed via both real-time PCR and ELISA to compare the efficacy of each in identifying HEV – more specifically, HEV genotype 3 – in each subject. For the ELISA analysis, 100 mcL of serum were added to each well of an ELISA plate, which was subsequently incubated at 37 degrees Celsius for 1 hour.

The researchers analyzed sera from four individuals with chronic HEV using serial dilutions to compare sensitivity of real-time PCR and ELISA. In three out of those four sera (75%), ELISA showed negative results due to HEV RNA levels of fewer than 10,000 copies/mL; on the other hand, real-time PCR showed a “linear reduction in levels,” indicating that it is the better option in detecting HEV genotype 3 (J Infect Dis. 2016 May 27;214[3]:361-8).

ELISA was also used on 20 chronic HEV patients and 17 acute HEV patients to determine its sensitivity at distinguishing between the two types of infection. In this cohort, only 64.7% of RNA-positive patients were deemed positive according to the ELISA testing, while ELISA results were positive in all of the cases of chronic HEV infections. None of the patients with chronic infection registered a false-negative, which indicates “a high reliability of the assay for this cohort,” according to the investigators.

“Comparison of chronically infected individuals with acutely infected patients revealed drastically increased ODs in chronically infected patients, while most of the positive samples from acutely infected patients displayed significantly lower values [which] led to a sensitivity of 100% (20 of 20) [ELISA] results for chronically HEV infected individuals,” the authors concluded. “Our study demonstrates that [ELISA] has a sensitivity of 65% and a specificity of 92% in detecting an ongoing HEV infection in a real-life cohort.”

The German Center for Infection Research, the Helmholtz Center for Infection Research, and the German Ministry for Education and Research funded the study. The researchers reported no relevant financial disclosures.

[email protected]

Standardization of liver diagnostic serology and clinical governance will improve understanding and diagnosis of primary biliary cholangitis (PBC), as will new biomarkers, according to a literature review from Nikolaos Gatselis, MD, PhD, and George Dalekos, MD, PhD, of the University of Thessaly, Greece.

Antimitochondrial antibodies are the most important diagnostic tool for the diagnosis of PBC, as AMA is seen in 90%-95% of patients with PBC. Indirect immunofluorescence assays using HEp-2 cells or cryostat sections of rat liver, kidney, and stomach remain the best way to detect AMA, but since the indirect immunofluorescence process cannot be fully automated, further analysis can be performed by immunoblotting. PBC-specific antinuclear antibodies are seen in 50%-70% of PBC cases, and are also important for the diagnosis of PBC.

©GunarsB/Thinkstock

Several new biomarkers have been proposed for improved diagnosis of PBC in recent years. The biomarkers include the autoantibodies KLHL12 and HK1, genetic markers in HLA regions, metabolomic profiling, miRNAs, and epigenetics.

“Development of clinical governance is of great importance in order to ensure that clinical standards are met, and that processes are in place to ensure continuing improvement and harmonization between laboratories. The guidance should include the whole testing process, beginning from the formulation of a reasonable clinical suspicion and the request of the most appropriate autoantibody test and continuing with handling of biological samples,” the investigators said.

Find the full review in Expert Review of Molecular Diagnostics (doi: 10.1080/14737159.2016.1217159).

[email protected]

Standardization of liver diagnostic serology and clinical governance will improve understanding and diagnosis of primary biliary cholangitis (PBC), as will new biomarkers, according to a literature review from Nikolaos Gatselis, MD, PhD, and George Dalekos, MD, PhD, of the University of Thessaly, Greece.

Antimitochondrial antibodies are the most important diagnostic tool for the diagnosis of PBC, as AMA is seen in 90%-95% of patients with PBC. Indirect immunofluorescence assays using HEp-2 cells or cryostat sections of rat liver, kidney, and stomach remain the best way to detect AMA, but since the indirect immunofluorescence process cannot be fully automated, further analysis can be performed by immunoblotting. PBC-specific antinuclear antibodies are seen in 50%-70% of PBC cases, and are also important for the diagnosis of PBC.

©GunarsB/Thinkstock

Several new biomarkers have been proposed for improved diagnosis of PBC in recent years. The biomarkers include the autoantibodies KLHL12 and HK1, genetic markers in HLA regions, metabolomic profiling, miRNAs, and epigenetics.

“Development of clinical governance is of great importance in order to ensure that clinical standards are met, and that processes are in place to ensure continuing improvement and harmonization between laboratories. The guidance should include the whole testing process, beginning from the formulation of a reasonable clinical suspicion and the request of the most appropriate autoantibody test and continuing with handling of biological samples,” the investigators said.

Find the full review in Expert Review of Molecular Diagnostics (doi: 10.1080/14737159.2016.1217159).

[email protected]

Standardization of liver diagnostic serology and clinical governance will improve understanding and diagnosis of primary biliary cholangitis (PBC), as will new biomarkers, according to a literature review from Nikolaos Gatselis, MD, PhD, and George Dalekos, MD, PhD, of the University of Thessaly, Greece.

Antimitochondrial antibodies are the most important diagnostic tool for the diagnosis of PBC, as AMA is seen in 90%-95% of patients with PBC. Indirect immunofluorescence assays using HEp-2 cells or cryostat sections of rat liver, kidney, and stomach remain the best way to detect AMA, but since the indirect immunofluorescence process cannot be fully automated, further analysis can be performed by immunoblotting. PBC-specific antinuclear antibodies are seen in 50%-70% of PBC cases, and are also important for the diagnosis of PBC.

©GunarsB/Thinkstock

Several new biomarkers have been proposed for improved diagnosis of PBC in recent years. The biomarkers include the autoantibodies KLHL12 and HK1, genetic markers in HLA regions, metabolomic profiling, miRNAs, and epigenetics.

“Development of clinical governance is of great importance in order to ensure that clinical standards are met, and that processes are in place to ensure continuing improvement and harmonization between laboratories. The guidance should include the whole testing process, beginning from the formulation of a reasonable clinical suspicion and the request of the most appropriate autoantibody test and continuing with handling of biological samples,” the investigators said.

Find the full review in Expert Review of Molecular Diagnostics (doi: 10.1080/14737159.2016.1217159).

[email protected]

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.