Liver Disease

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.

Chronic hepatitis B virus patients are insufficiently monitored for disease activity and hepatocellular carcinoma (HCC), according to Philip R. Spradling, MD, and his associates of the Centers for Disease Control and Prevention.

Betty Partin/CDC

In a cohort study of 2,992 patients with CHB, 2,338 were used for assessment. Researchers used alanine aminotransferase (ALT) monitoring, HBV DNA monitoring, assessment for cirrhosis, and HBV antiviral therapy for examination. For ALT monitoring, 1,814 (78%) of patients had at least one ALT level obtained per year of follow-up. Only 876 patients (37%) had at least one HBV DNA level assessment per year of follow-up and 1,037 (44%) had less than annual testing, and 18% of patients never had an HBV DNA level assessed. Among patients with cirrhosis, 297 (54%) had HBV DNA testing done at least annually, 189 (35%) had testing done but less frequently than annually, and 61 (11%) never had an HBV DNA test done. And of the 547 patients with cirrhosis, 305 (56%) were prescribed HBV antiviral therapy.

It was noted that patients were monitored during 2006-2013. Only 68% of patients had not been prescribed treatment, and 72% had received liver-related specialty care.

“Our findings reiterate the need for clinicians who treat patients with [chronic HBV] to provide ongoing, continual assessment of disease activity based on HBV DNA and ALT levels, as well as liver imaging surveillance among patients at high risk for HCC,” researchers concluded. “As antiviral therapy for [chronic HBV] now includes potent and highly efficacious oral agents that have few contraindications and minimal side effects, as well as a high barrier to resistance, clinicians should be vigilant for opportunities to decrease the likelihood of poor clinical outcomes.”

Read the full study in Clinical Infectious Diseases here.

[email protected]

Chronic hepatitis B virus patients are insufficiently monitored for disease activity and hepatocellular carcinoma (HCC), according to Philip R. Spradling, MD, and his associates of the Centers for Disease Control and Prevention.

Betty Partin/CDC

In a cohort study of 2,992 patients with CHB, 2,338 were used for assessment. Researchers used alanine aminotransferase (ALT) monitoring, HBV DNA monitoring, assessment for cirrhosis, and HBV antiviral therapy for examination. For ALT monitoring, 1,814 (78%) of patients had at least one ALT level obtained per year of follow-up. Only 876 patients (37%) had at least one HBV DNA level assessment per year of follow-up and 1,037 (44%) had less than annual testing, and 18% of patients never had an HBV DNA level assessed. Among patients with cirrhosis, 297 (54%) had HBV DNA testing done at least annually, 189 (35%) had testing done but less frequently than annually, and 61 (11%) never had an HBV DNA test done. And of the 547 patients with cirrhosis, 305 (56%) were prescribed HBV antiviral therapy.

It was noted that patients were monitored during 2006-2013. Only 68% of patients had not been prescribed treatment, and 72% had received liver-related specialty care.

“Our findings reiterate the need for clinicians who treat patients with [chronic HBV] to provide ongoing, continual assessment of disease activity based on HBV DNA and ALT levels, as well as liver imaging surveillance among patients at high risk for HCC,” researchers concluded. “As antiviral therapy for [chronic HBV] now includes potent and highly efficacious oral agents that have few contraindications and minimal side effects, as well as a high barrier to resistance, clinicians should be vigilant for opportunities to decrease the likelihood of poor clinical outcomes.”

Read the full study in Clinical Infectious Diseases here.

[email protected]

Chronic hepatitis B virus patients are insufficiently monitored for disease activity and hepatocellular carcinoma (HCC), according to Philip R. Spradling, MD, and his associates of the Centers for Disease Control and Prevention.

Betty Partin/CDC

In a cohort study of 2,992 patients with CHB, 2,338 were used for assessment. Researchers used alanine aminotransferase (ALT) monitoring, HBV DNA monitoring, assessment for cirrhosis, and HBV antiviral therapy for examination. For ALT monitoring, 1,814 (78%) of patients had at least one ALT level obtained per year of follow-up. Only 876 patients (37%) had at least one HBV DNA level assessment per year of follow-up and 1,037 (44%) had less than annual testing, and 18% of patients never had an HBV DNA level assessed. Among patients with cirrhosis, 297 (54%) had HBV DNA testing done at least annually, 189 (35%) had testing done but less frequently than annually, and 61 (11%) never had an HBV DNA test done. And of the 547 patients with cirrhosis, 305 (56%) were prescribed HBV antiviral therapy.

It was noted that patients were monitored during 2006-2013. Only 68% of patients had not been prescribed treatment, and 72% had received liver-related specialty care.

“Our findings reiterate the need for clinicians who treat patients with [chronic HBV] to provide ongoing, continual assessment of disease activity based on HBV DNA and ALT levels, as well as liver imaging surveillance among patients at high risk for HCC,” researchers concluded. “As antiviral therapy for [chronic HBV] now includes potent and highly efficacious oral agents that have few contraindications and minimal side effects, as well as a high barrier to resistance, clinicians should be vigilant for opportunities to decrease the likelihood of poor clinical outcomes.”

Read the full study in Clinical Infectious Diseases here.

[email protected]

Patients with chronic hepatitis B who are aged under 35 years or do not see the same clinician consistently are more likely to not take their antiviral medication, finds the largest study of its kind to date.

According to the authors of the research led by Nicole Allard, PhD, from the WHO collaborative Centre for Viral Hepatitis and the Peter Doherty Institute for Infection and Immunity in Melbourne, their findings illustrate the need for clinicians to reinforce the importance of medication adherence at each patient consultation.

CDC/Dr. Erskine Palmer

Furthermore, “providing more flexible and convenient care arrangements, reminder systems, and working with the individual to maximize medication adherence should be a routine part of clinical practice,” they wrote in their paper published in the Journal of Viral Hepatitis. Previous research had shown that adherence to antiviral therapy in the treatment of hepatitis B was associated with improved patient outcomes. Suboptimal adherence could lead to antiviral resistance or antiviral breakthrough, potentially leading to liver cirrhosis and liver cancer.

Understanding poor adherence in clinical settings, together with the factors associated with lower adherence, was important in informing efforts for promoting adherence, the research team said (J Viral Hepat. 2016. doi: 10.1111/jvh.12582).

In their retrospective study they assessed the pharmacy records of 1,026 patients who were dispensed antiviral therapy for hepatitis B across four Australian public hospital outpatient clinics between 2010 and 2013.

They discovered that one in five patients were “nonadherent” to therapy based on a medication possession ratio of less than 0.90 – a cutoff shown in previous studies to be correlated with virologic breakthrough.

One significant factor that affected adherence to medication was being aged under 35 years (P = .002), the research team reported.

This finding was similar to other studies of chronic diseases that had shown younger patients were at a higher risk of nonadherence, the authors noted.

“Recognition of the challenges faced by a younger person regularly taking medication at a time in their lives when they feel well is important,” they wrote.

Poor adherence was also associated with seeing multiple clinicians over shorter periods of time.

“While hospitals accommodate trainees and staffing changes occur regularly, seeking to maximize the consistency of clinical care delivery may be an important strategy to support better adherence and optimizing care for individuals,” they said.

Factors such as variations in the amount of medication, duration of treatment, sex, and cultural background did not affect adherence to medication.

“Adherence is a dynamic process and needs to be addressed regularly in a nonjudgmental way working with individuals towards improved health,” they concluded.

Patients with chronic hepatitis B who are aged under 35 years or do not see the same clinician consistently are more likely to not take their antiviral medication, finds the largest study of its kind to date.

According to the authors of the research led by Nicole Allard, PhD, from the WHO collaborative Centre for Viral Hepatitis and the Peter Doherty Institute for Infection and Immunity in Melbourne, their findings illustrate the need for clinicians to reinforce the importance of medication adherence at each patient consultation.

CDC/Dr. Erskine Palmer

Furthermore, “providing more flexible and convenient care arrangements, reminder systems, and working with the individual to maximize medication adherence should be a routine part of clinical practice,” they wrote in their paper published in the Journal of Viral Hepatitis. Previous research had shown that adherence to antiviral therapy in the treatment of hepatitis B was associated with improved patient outcomes. Suboptimal adherence could lead to antiviral resistance or antiviral breakthrough, potentially leading to liver cirrhosis and liver cancer.

Understanding poor adherence in clinical settings, together with the factors associated with lower adherence, was important in informing efforts for promoting adherence, the research team said (J Viral Hepat. 2016. doi: 10.1111/jvh.12582).

In their retrospective study they assessed the pharmacy records of 1,026 patients who were dispensed antiviral therapy for hepatitis B across four Australian public hospital outpatient clinics between 2010 and 2013.

They discovered that one in five patients were “nonadherent” to therapy based on a medication possession ratio of less than 0.90 – a cutoff shown in previous studies to be correlated with virologic breakthrough.

One significant factor that affected adherence to medication was being aged under 35 years (P = .002), the research team reported.

This finding was similar to other studies of chronic diseases that had shown younger patients were at a higher risk of nonadherence, the authors noted.

“Recognition of the challenges faced by a younger person regularly taking medication at a time in their lives when they feel well is important,” they wrote.

Poor adherence was also associated with seeing multiple clinicians over shorter periods of time.

“While hospitals accommodate trainees and staffing changes occur regularly, seeking to maximize the consistency of clinical care delivery may be an important strategy to support better adherence and optimizing care for individuals,” they said.

Factors such as variations in the amount of medication, duration of treatment, sex, and cultural background did not affect adherence to medication.

“Adherence is a dynamic process and needs to be addressed regularly in a nonjudgmental way working with individuals towards improved health,” they concluded.

Patients with chronic hepatitis B who are aged under 35 years or do not see the same clinician consistently are more likely to not take their antiviral medication, finds the largest study of its kind to date.

According to the authors of the research led by Nicole Allard, PhD, from the WHO collaborative Centre for Viral Hepatitis and the Peter Doherty Institute for Infection and Immunity in Melbourne, their findings illustrate the need for clinicians to reinforce the importance of medication adherence at each patient consultation.

CDC/Dr. Erskine Palmer

Furthermore, “providing more flexible and convenient care arrangements, reminder systems, and working with the individual to maximize medication adherence should be a routine part of clinical practice,” they wrote in their paper published in the Journal of Viral Hepatitis. Previous research had shown that adherence to antiviral therapy in the treatment of hepatitis B was associated with improved patient outcomes. Suboptimal adherence could lead to antiviral resistance or antiviral breakthrough, potentially leading to liver cirrhosis and liver cancer.

Understanding poor adherence in clinical settings, together with the factors associated with lower adherence, was important in informing efforts for promoting adherence, the research team said (J Viral Hepat. 2016. doi: 10.1111/jvh.12582).

In their retrospective study they assessed the pharmacy records of 1,026 patients who were dispensed antiviral therapy for hepatitis B across four Australian public hospital outpatient clinics between 2010 and 2013.

They discovered that one in five patients were “nonadherent” to therapy based on a medication possession ratio of less than 0.90 – a cutoff shown in previous studies to be correlated with virologic breakthrough.

One significant factor that affected adherence to medication was being aged under 35 years (P = .002), the research team reported.

This finding was similar to other studies of chronic diseases that had shown younger patients were at a higher risk of nonadherence, the authors noted.

“Recognition of the challenges faced by a younger person regularly taking medication at a time in their lives when they feel well is important,” they wrote.

Poor adherence was also associated with seeing multiple clinicians over shorter periods of time.

“While hospitals accommodate trainees and staffing changes occur regularly, seeking to maximize the consistency of clinical care delivery may be an important strategy to support better adherence and optimizing care for individuals,” they said.

Factors such as variations in the amount of medication, duration of treatment, sex, and cultural background did not affect adherence to medication.

“Adherence is a dynamic process and needs to be addressed regularly in a nonjudgmental way working with individuals towards improved health,” they concluded.

A genetic predisposition to autoimmune liver disease can cause overlapping cases of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) within the same family, according to a case report from Japanese researchers.

A 68-year-old woman and her 49-year-old daughter were admitted to the hospital for liver dysfunction, 4 years apart. The mother had been diagnosed with PBC at a previous hospital, but was moved after treatment with 600 mg ursodeoxycholic acid (UDCA) was ineffective. The daughter had no previous diagnosis and had a variety of symptoms at admission, including jaundice, general fatigue, and darkness of the urine.

Both the mother and the daughter were negative for hepatitis A, B, and C. A simplified International Autoimmune Hepatitis Group score revealed probable AIH for both patients, and both patients were diagnosed with autoimmune liver disease with overlapping features of PBC and AIH. Treatment with UDCA and prednisolone was effective for both patients.

In a familial study, the mother and her two daughters were tested for liver function, autoantibodies, and human leukocyte antigen (HLA) haplotype. The second daughter, who was healthy with no history of liver dysfunction, had normal liver function, negative ANA, and positive AMA-M2 antibody, but had an HLA haplotype different from that of the mother and the first daughter. No difference in medication use, smoking status, alcohol consumption, or obstetric history was seen.

“The exact mechanism underlying the onset of PBC and AIH overlap within the same family remains unclear. Therefore, it is very important to monitor the healthy second daughter closely as she was positive for the AMA-M2 antibody, as this might yield further knowledge with regard to what factors influence the onset of PBC and AIH overlap within the same family,” the investigators noted.

Find the full study in the Journal of Clinical Gastroenterology (doi: 10.1007/s12328-016-0676-1)

[email protected]

A genetic predisposition to autoimmune liver disease can cause overlapping cases of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) within the same family, according to a case report from Japanese researchers.

A 68-year-old woman and her 49-year-old daughter were admitted to the hospital for liver dysfunction, 4 years apart. The mother had been diagnosed with PBC at a previous hospital, but was moved after treatment with 600 mg ursodeoxycholic acid (UDCA) was ineffective. The daughter had no previous diagnosis and had a variety of symptoms at admission, including jaundice, general fatigue, and darkness of the urine.

Both the mother and the daughter were negative for hepatitis A, B, and C. A simplified International Autoimmune Hepatitis Group score revealed probable AIH for both patients, and both patients were diagnosed with autoimmune liver disease with overlapping features of PBC and AIH. Treatment with UDCA and prednisolone was effective for both patients.

In a familial study, the mother and her two daughters were tested for liver function, autoantibodies, and human leukocyte antigen (HLA) haplotype. The second daughter, who was healthy with no history of liver dysfunction, had normal liver function, negative ANA, and positive AMA-M2 antibody, but had an HLA haplotype different from that of the mother and the first daughter. No difference in medication use, smoking status, alcohol consumption, or obstetric history was seen.

“The exact mechanism underlying the onset of PBC and AIH overlap within the same family remains unclear. Therefore, it is very important to monitor the healthy second daughter closely as she was positive for the AMA-M2 antibody, as this might yield further knowledge with regard to what factors influence the onset of PBC and AIH overlap within the same family,” the investigators noted.

Find the full study in the Journal of Clinical Gastroenterology (doi: 10.1007/s12328-016-0676-1)

[email protected]

A genetic predisposition to autoimmune liver disease can cause overlapping cases of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) within the same family, according to a case report from Japanese researchers.

A 68-year-old woman and her 49-year-old daughter were admitted to the hospital for liver dysfunction, 4 years apart. The mother had been diagnosed with PBC at a previous hospital, but was moved after treatment with 600 mg ursodeoxycholic acid (UDCA) was ineffective. The daughter had no previous diagnosis and had a variety of symptoms at admission, including jaundice, general fatigue, and darkness of the urine.

Both the mother and the daughter were negative for hepatitis A, B, and C. A simplified International Autoimmune Hepatitis Group score revealed probable AIH for both patients, and both patients were diagnosed with autoimmune liver disease with overlapping features of PBC and AIH. Treatment with UDCA and prednisolone was effective for both patients.

In a familial study, the mother and her two daughters were tested for liver function, autoantibodies, and human leukocyte antigen (HLA) haplotype. The second daughter, who was healthy with no history of liver dysfunction, had normal liver function, negative ANA, and positive AMA-M2 antibody, but had an HLA haplotype different from that of the mother and the first daughter. No difference in medication use, smoking status, alcohol consumption, or obstetric history was seen.

“The exact mechanism underlying the onset of PBC and AIH overlap within the same family remains unclear. Therefore, it is very important to monitor the healthy second daughter closely as she was positive for the AMA-M2 antibody, as this might yield further knowledge with regard to what factors influence the onset of PBC and AIH overlap within the same family,” the investigators noted.

Find the full study in the Journal of Clinical Gastroenterology (doi: 10.1007/s12328-016-0676-1)

[email protected]

Obeticholic acid reduced alkaline phosphatase level, total bilirubin level, and other biomarkers of cholestasis, hepatocellular injury, inflammation, and apoptosis in patients with primary biliary cholangitis participating in a phase III clinical trial, which was reported online August 17 in the New England Journal of Medicine.

A study to assess the drug’s effects on clinical outcomes is currently enrolling patients (NCT02308111), said Frederik Nevens, MD, PhD, of University Hospitals Leuven (Belgium) and his associates.

©Ricardo Gaudêncio/News Farma

They assessed treatment with obeticholic acid, a selective farnesoid X receptor agonist, in a manufacturer-sponsored double-blind randomized trial involving 217 patients treated at 59 sites in 13 countries. Participants were assigned to receive a once-daily oral placebo (73 patients), obeticholic acid at an initial dose of 5 mg with escalation to 10 mg if possible (71 patients), or a daily 10-mg dose of obeticholic acid (73 patients). All were also given standard ursodiol (13-15 mg per kg) at the same time, with the expectation that many would have to discontinue that drug due to adverse events. The study participants were treated for 1 year, when the double-blind phase of the study was completed and all were offered entry into a 5-year open-label phase.

The primary composite endpoint was 1) an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% below baseline level, and 2) a total bilirubin level at or below the upper limit of the normal range. After 1 year of treatment, 46% of the 5-mg group and 47% of the 10-mg group achieved this endpoint, compared with only 10% of the placebo group. The response to treatment was rapid, with patients in the active-treatment groups showing significantly lower alkaline phosphatase and bilirubin levels than the placebo group within 2 weeks of starting therapy.

In addition, the percentage of patients who showed at least a 15% reduction in alkaline phosphatase level was significantly higher with 5-10 mg active treatment (77%) and with 10 mg active treatment (77%) than with placebo (29%). And total bilirubin level progressively decreased in both active treatment groups but progressively increased in the placebo group, Dr. Nevens and his associates said (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMoa1509840). Obeticholic acid also reduced levels of IgM and interleukin-12, as well as levels of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and conjugated bilirubin. It did not induce significant symptom relief as measured by a disease-specific quality of life questionnaire, and it didn’t reduce liver fibrosis as measured by noninvasive techniques.

In the open-label extension phase of the study, treatment efficacy was similar.

The most common adverse event was pruritus, which is also characteristic of the disease itself. The incidence was higher in both active-treatment groups (56% with 5-10-mg therapy and 68% with 10-mg therapy) than in the placebo group (38%). One patient (1%) in the 5-10-mg group and seven patients (10%) in the 10-mg group discontinued treatment because of pruritus, compared with no patients in the placebo group.

The treatment’s beneficial effects persisted for 2 years, but that is a relatively short follow-up for a chronic disease that will require lifelong therapy. Future research must address longer-term benefits as well as adverse events, the investigators said.

Obeticholic acid reduced alkaline phosphatase level, total bilirubin level, and other biomarkers of cholestasis, hepatocellular injury, inflammation, and apoptosis in patients with primary biliary cholangitis participating in a phase III clinical trial, which was reported online August 17 in the New England Journal of Medicine.

A study to assess the drug’s effects on clinical outcomes is currently enrolling patients (NCT02308111), said Frederik Nevens, MD, PhD, of University Hospitals Leuven (Belgium) and his associates.

©Ricardo Gaudêncio/News Farma

They assessed treatment with obeticholic acid, a selective farnesoid X receptor agonist, in a manufacturer-sponsored double-blind randomized trial involving 217 patients treated at 59 sites in 13 countries. Participants were assigned to receive a once-daily oral placebo (73 patients), obeticholic acid at an initial dose of 5 mg with escalation to 10 mg if possible (71 patients), or a daily 10-mg dose of obeticholic acid (73 patients). All were also given standard ursodiol (13-15 mg per kg) at the same time, with the expectation that many would have to discontinue that drug due to adverse events. The study participants were treated for 1 year, when the double-blind phase of the study was completed and all were offered entry into a 5-year open-label phase.

The primary composite endpoint was 1) an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% below baseline level, and 2) a total bilirubin level at or below the upper limit of the normal range. After 1 year of treatment, 46% of the 5-mg group and 47% of the 10-mg group achieved this endpoint, compared with only 10% of the placebo group. The response to treatment was rapid, with patients in the active-treatment groups showing significantly lower alkaline phosphatase and bilirubin levels than the placebo group within 2 weeks of starting therapy.

In addition, the percentage of patients who showed at least a 15% reduction in alkaline phosphatase level was significantly higher with 5-10 mg active treatment (77%) and with 10 mg active treatment (77%) than with placebo (29%). And total bilirubin level progressively decreased in both active treatment groups but progressively increased in the placebo group, Dr. Nevens and his associates said (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMoa1509840). Obeticholic acid also reduced levels of IgM and interleukin-12, as well as levels of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and conjugated bilirubin. It did not induce significant symptom relief as measured by a disease-specific quality of life questionnaire, and it didn’t reduce liver fibrosis as measured by noninvasive techniques.

In the open-label extension phase of the study, treatment efficacy was similar.

The most common adverse event was pruritus, which is also characteristic of the disease itself. The incidence was higher in both active-treatment groups (56% with 5-10-mg therapy and 68% with 10-mg therapy) than in the placebo group (38%). One patient (1%) in the 5-10-mg group and seven patients (10%) in the 10-mg group discontinued treatment because of pruritus, compared with no patients in the placebo group.

The treatment’s beneficial effects persisted for 2 years, but that is a relatively short follow-up for a chronic disease that will require lifelong therapy. Future research must address longer-term benefits as well as adverse events, the investigators said.

Obeticholic acid reduced alkaline phosphatase level, total bilirubin level, and other biomarkers of cholestasis, hepatocellular injury, inflammation, and apoptosis in patients with primary biliary cholangitis participating in a phase III clinical trial, which was reported online August 17 in the New England Journal of Medicine.

A study to assess the drug’s effects on clinical outcomes is currently enrolling patients (NCT02308111), said Frederik Nevens, MD, PhD, of University Hospitals Leuven (Belgium) and his associates.

©Ricardo Gaudêncio/News Farma

They assessed treatment with obeticholic acid, a selective farnesoid X receptor agonist, in a manufacturer-sponsored double-blind randomized trial involving 217 patients treated at 59 sites in 13 countries. Participants were assigned to receive a once-daily oral placebo (73 patients), obeticholic acid at an initial dose of 5 mg with escalation to 10 mg if possible (71 patients), or a daily 10-mg dose of obeticholic acid (73 patients). All were also given standard ursodiol (13-15 mg per kg) at the same time, with the expectation that many would have to discontinue that drug due to adverse events. The study participants were treated for 1 year, when the double-blind phase of the study was completed and all were offered entry into a 5-year open-label phase.

The primary composite endpoint was 1) an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% below baseline level, and 2) a total bilirubin level at or below the upper limit of the normal range. After 1 year of treatment, 46% of the 5-mg group and 47% of the 10-mg group achieved this endpoint, compared with only 10% of the placebo group. The response to treatment was rapid, with patients in the active-treatment groups showing significantly lower alkaline phosphatase and bilirubin levels than the placebo group within 2 weeks of starting therapy.

In addition, the percentage of patients who showed at least a 15% reduction in alkaline phosphatase level was significantly higher with 5-10 mg active treatment (77%) and with 10 mg active treatment (77%) than with placebo (29%). And total bilirubin level progressively decreased in both active treatment groups but progressively increased in the placebo group, Dr. Nevens and his associates said (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMoa1509840). Obeticholic acid also reduced levels of IgM and interleukin-12, as well as levels of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and conjugated bilirubin. It did not induce significant symptom relief as measured by a disease-specific quality of life questionnaire, and it didn’t reduce liver fibrosis as measured by noninvasive techniques.

In the open-label extension phase of the study, treatment efficacy was similar.

The most common adverse event was pruritus, which is also characteristic of the disease itself. The incidence was higher in both active-treatment groups (56% with 5-10-mg therapy and 68% with 10-mg therapy) than in the placebo group (38%). One patient (1%) in the 5-10-mg group and seven patients (10%) in the 10-mg group discontinued treatment because of pruritus, compared with no patients in the placebo group.

The treatment’s beneficial effects persisted for 2 years, but that is a relatively short follow-up for a chronic disease that will require lifelong therapy. Future research must address longer-term benefits as well as adverse events, the investigators said.