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Possible biomarkers found for progression to liver cancer in chronic HCV infection
according to the results of a biochemical analysis of human blood samples performed by PhD student Paywast J. Jalal of the University of Sulaimani (Iraq) and colleagues.
Archived HCV-positive serum samples, including those from 31 patients who had developed HCC, were retrieved from the Trent HCV clinical cohort. They were compared with each other over time and against samples from HCV-infected individuals in the cohort who did not develop HCC. In addition, HCV-negative serum samples were obtained commercially and assessed identically. Circulating liver-expressed lectins, ficolin-2, ficolin-3, and MBL were all examined as potential biomarkers for the development of HCC, the authors wrote in Virology.
Binding of ficolin-3 to reference ligands was greater in chronic HCV infection, while ficolin-2 and MBL were significantly elevated in individuals who develop HCC, compared with HCV-infected individuals without HCC. Ficolin-2 and MBL were found to be elevated at 1 and 3 years prior to HCC diagnosis, respectively, suggesting they could be used as prognostic serum markers for the development of HCC.
“The strong evidence for an association between elevated MBL binding activity and the development of HCC is supportive for a larger prospective study of these biomarkers in HCV-induced liver cancer,” the researchers concluded.
This study was funded by a split-site PhD scholarship between the University of Sulaimani and the University of Nottingham (England). The authors reported they had no conflicts.
SOURCE: Jalal PJ et al. Virology. 2019;530:99-106.
according to the results of a biochemical analysis of human blood samples performed by PhD student Paywast J. Jalal of the University of Sulaimani (Iraq) and colleagues.
Archived HCV-positive serum samples, including those from 31 patients who had developed HCC, were retrieved from the Trent HCV clinical cohort. They were compared with each other over time and against samples from HCV-infected individuals in the cohort who did not develop HCC. In addition, HCV-negative serum samples were obtained commercially and assessed identically. Circulating liver-expressed lectins, ficolin-2, ficolin-3, and MBL were all examined as potential biomarkers for the development of HCC, the authors wrote in Virology.
Binding of ficolin-3 to reference ligands was greater in chronic HCV infection, while ficolin-2 and MBL were significantly elevated in individuals who develop HCC, compared with HCV-infected individuals without HCC. Ficolin-2 and MBL were found to be elevated at 1 and 3 years prior to HCC diagnosis, respectively, suggesting they could be used as prognostic serum markers for the development of HCC.
“The strong evidence for an association between elevated MBL binding activity and the development of HCC is supportive for a larger prospective study of these biomarkers in HCV-induced liver cancer,” the researchers concluded.
This study was funded by a split-site PhD scholarship between the University of Sulaimani and the University of Nottingham (England). The authors reported they had no conflicts.
SOURCE: Jalal PJ et al. Virology. 2019;530:99-106.
according to the results of a biochemical analysis of human blood samples performed by PhD student Paywast J. Jalal of the University of Sulaimani (Iraq) and colleagues.
Archived HCV-positive serum samples, including those from 31 patients who had developed HCC, were retrieved from the Trent HCV clinical cohort. They were compared with each other over time and against samples from HCV-infected individuals in the cohort who did not develop HCC. In addition, HCV-negative serum samples were obtained commercially and assessed identically. Circulating liver-expressed lectins, ficolin-2, ficolin-3, and MBL were all examined as potential biomarkers for the development of HCC, the authors wrote in Virology.
Binding of ficolin-3 to reference ligands was greater in chronic HCV infection, while ficolin-2 and MBL were significantly elevated in individuals who develop HCC, compared with HCV-infected individuals without HCC. Ficolin-2 and MBL were found to be elevated at 1 and 3 years prior to HCC diagnosis, respectively, suggesting they could be used as prognostic serum markers for the development of HCC.
“The strong evidence for an association between elevated MBL binding activity and the development of HCC is supportive for a larger prospective study of these biomarkers in HCV-induced liver cancer,” the researchers concluded.
This study was funded by a split-site PhD scholarship between the University of Sulaimani and the University of Nottingham (England). The authors reported they had no conflicts.
SOURCE: Jalal PJ et al. Virology. 2019;530:99-106.
FROM VIROLOGY
Novel capsid assembly modulator shows promise in HBV
For adults with chronic hepatitis B virus infection, treatment with a novel investigational capsid assembly modulator was well tolerated and showed antiviral activity against HBV, according to the results of a phase 1 study of 73 patients.
“Substantial and correlated reductions in serum HBV DNA and HBV RNA levels were observed consistently with the higher-dose cohorts and were notably greatest for combination treatment with NVR 3-778 and pegIFN [pegylated interferon],” Man Fung Yuen, MD, of the University of Hong Kong, and his associates wrote in a report published in Gastroenterology. Hence, this first-in-class capsid assembly modulator might help prolong treatment responses, “most likely as a component of new combination treatment regimens for HBV-infected patients.” However, one patient developed severe rash immediately after completing treatment that took 6 months of intensive outpatient treatment to resolve, they noted.
Chronic viral hepatitis due to HBV is a major cause of early death worldwide, and new therapies are needed to help prevent severe liver disease and liver death from this infection. Current treatments for HBV infection consist of nucleoside or nucleotide analogs or pegylated interferon. These suppress HBV replication in many patients, but most patients do not achieve durable responses. Consequently, most patients require long-term treatment with HBV nucleosides and nucleotide analogs, which they may find difficult to tolerate or adhere to and to which their infections can become resistant, the researchers said.
The HBV virion contains a viral core protein (HBc) that is required to encapsidate viral polymerase and pregenomic HBV RNA into a nucleocapsid. To target this process, researchers developed NVR 3-778, a first-in-class, orally bioavailable small molecule that binds HBc so that HBc forms a defective capsid that lacks nuclear material. Hence, NVR 3-778 is intended to stop the production of HBV nucleocapsids and keep infected cells from releasing the enveloped infectious viral particles that perpetuate HBV infection.
To assess the safety, pharmacokinetics, and antiviral activity of NVR 3-778, the researchers conducted a phase 1 study of 73 patients with chronic HBV infection who tested positive for hepatitis B e-antigen (HBeAg) and had no detectable cirrhosis. Patients were randomly assigned to receive oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1,000 mg twice daily ) or placebo for 28 days. Some patients received combination therapy with pegylated interferon plus either NVR 3-778 (600 mg twice daily) or placebo. Treatment was generally well tolerated, and adverse events were usually mild and deemed unrelated to therapy. No patient stopped treatment for adverse effects.
The only serious adverse event in the study consisted of grade 3 rash that developed in a 42-year-old male after 22 days of treatment at the lowest dose of NVR 3-778 (100 mg per day). This patient completed treatment and ultimately developed a severe papulovesicular rash with a predominantly acral distribution over the hands, arm, side of neck, and one leg (palmar plantar erythrodysesthesia), the researchers said. “There were no perioral or mucosal lesions, no ecchymotic skin involvement, no bullae, and no systemic manifestations or hematological abnormalities,” they wrote. “The rash was subsequently managed with a psoriasis-like treatment regimen of psoralen, ultraviolet light, and topical steroid ointment during outpatient follow-up and resolved after approximately 6 months.”
Another three cases of “minor” skin rash were considered probably related to treatment in the cohort that received 600 mg NVR 3-778 b.i.d. plus pegylated interferon, the investigators said. Two additional cases of mild rash were deemed unrelated to treatment.
“The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778,” the researchers concluded. “This class of compounds can also inhibit replenishment of intranuclear covalently closed circular DNA over time and may have immunomodulatory properties.” Longer treatment periods would be needed to study these mechanisms and to quantify reductions in serum HBsAg and HBeAG, they noted.
Novira Therapeutics developed NVR 3-778 and is a Janssen Pharmaceutical Company. Janssen provided funding for editorial support. Dr. Yuen disclosed relationships with AbbVie, Biocartis, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Ionis, Roche, Vir Biotechnology, and several other pharmaceutical companies. Other coinvestigators disclosed ties to pharmaceutical companies; eight reported employment by Novira or a Janssen company.
SOURCE: Yuen MF et al. Gastroenterology. 2019 Jan 5. doi: 10.1053/j.gastro.2018.12.023.
For adults with chronic hepatitis B virus infection, treatment with a novel investigational capsid assembly modulator was well tolerated and showed antiviral activity against HBV, according to the results of a phase 1 study of 73 patients.
“Substantial and correlated reductions in serum HBV DNA and HBV RNA levels were observed consistently with the higher-dose cohorts and were notably greatest for combination treatment with NVR 3-778 and pegIFN [pegylated interferon],” Man Fung Yuen, MD, of the University of Hong Kong, and his associates wrote in a report published in Gastroenterology. Hence, this first-in-class capsid assembly modulator might help prolong treatment responses, “most likely as a component of new combination treatment regimens for HBV-infected patients.” However, one patient developed severe rash immediately after completing treatment that took 6 months of intensive outpatient treatment to resolve, they noted.
Chronic viral hepatitis due to HBV is a major cause of early death worldwide, and new therapies are needed to help prevent severe liver disease and liver death from this infection. Current treatments for HBV infection consist of nucleoside or nucleotide analogs or pegylated interferon. These suppress HBV replication in many patients, but most patients do not achieve durable responses. Consequently, most patients require long-term treatment with HBV nucleosides and nucleotide analogs, which they may find difficult to tolerate or adhere to and to which their infections can become resistant, the researchers said.
The HBV virion contains a viral core protein (HBc) that is required to encapsidate viral polymerase and pregenomic HBV RNA into a nucleocapsid. To target this process, researchers developed NVR 3-778, a first-in-class, orally bioavailable small molecule that binds HBc so that HBc forms a defective capsid that lacks nuclear material. Hence, NVR 3-778 is intended to stop the production of HBV nucleocapsids and keep infected cells from releasing the enveloped infectious viral particles that perpetuate HBV infection.
To assess the safety, pharmacokinetics, and antiviral activity of NVR 3-778, the researchers conducted a phase 1 study of 73 patients with chronic HBV infection who tested positive for hepatitis B e-antigen (HBeAg) and had no detectable cirrhosis. Patients were randomly assigned to receive oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1,000 mg twice daily ) or placebo for 28 days. Some patients received combination therapy with pegylated interferon plus either NVR 3-778 (600 mg twice daily) or placebo. Treatment was generally well tolerated, and adverse events were usually mild and deemed unrelated to therapy. No patient stopped treatment for adverse effects.
The only serious adverse event in the study consisted of grade 3 rash that developed in a 42-year-old male after 22 days of treatment at the lowest dose of NVR 3-778 (100 mg per day). This patient completed treatment and ultimately developed a severe papulovesicular rash with a predominantly acral distribution over the hands, arm, side of neck, and one leg (palmar plantar erythrodysesthesia), the researchers said. “There were no perioral or mucosal lesions, no ecchymotic skin involvement, no bullae, and no systemic manifestations or hematological abnormalities,” they wrote. “The rash was subsequently managed with a psoriasis-like treatment regimen of psoralen, ultraviolet light, and topical steroid ointment during outpatient follow-up and resolved after approximately 6 months.”
Another three cases of “minor” skin rash were considered probably related to treatment in the cohort that received 600 mg NVR 3-778 b.i.d. plus pegylated interferon, the investigators said. Two additional cases of mild rash were deemed unrelated to treatment.
“The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778,” the researchers concluded. “This class of compounds can also inhibit replenishment of intranuclear covalently closed circular DNA over time and may have immunomodulatory properties.” Longer treatment periods would be needed to study these mechanisms and to quantify reductions in serum HBsAg and HBeAG, they noted.
Novira Therapeutics developed NVR 3-778 and is a Janssen Pharmaceutical Company. Janssen provided funding for editorial support. Dr. Yuen disclosed relationships with AbbVie, Biocartis, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Ionis, Roche, Vir Biotechnology, and several other pharmaceutical companies. Other coinvestigators disclosed ties to pharmaceutical companies; eight reported employment by Novira or a Janssen company.
SOURCE: Yuen MF et al. Gastroenterology. 2019 Jan 5. doi: 10.1053/j.gastro.2018.12.023.
For adults with chronic hepatitis B virus infection, treatment with a novel investigational capsid assembly modulator was well tolerated and showed antiviral activity against HBV, according to the results of a phase 1 study of 73 patients.
“Substantial and correlated reductions in serum HBV DNA and HBV RNA levels were observed consistently with the higher-dose cohorts and were notably greatest for combination treatment with NVR 3-778 and pegIFN [pegylated interferon],” Man Fung Yuen, MD, of the University of Hong Kong, and his associates wrote in a report published in Gastroenterology. Hence, this first-in-class capsid assembly modulator might help prolong treatment responses, “most likely as a component of new combination treatment regimens for HBV-infected patients.” However, one patient developed severe rash immediately after completing treatment that took 6 months of intensive outpatient treatment to resolve, they noted.
Chronic viral hepatitis due to HBV is a major cause of early death worldwide, and new therapies are needed to help prevent severe liver disease and liver death from this infection. Current treatments for HBV infection consist of nucleoside or nucleotide analogs or pegylated interferon. These suppress HBV replication in many patients, but most patients do not achieve durable responses. Consequently, most patients require long-term treatment with HBV nucleosides and nucleotide analogs, which they may find difficult to tolerate or adhere to and to which their infections can become resistant, the researchers said.
The HBV virion contains a viral core protein (HBc) that is required to encapsidate viral polymerase and pregenomic HBV RNA into a nucleocapsid. To target this process, researchers developed NVR 3-778, a first-in-class, orally bioavailable small molecule that binds HBc so that HBc forms a defective capsid that lacks nuclear material. Hence, NVR 3-778 is intended to stop the production of HBV nucleocapsids and keep infected cells from releasing the enveloped infectious viral particles that perpetuate HBV infection.
To assess the safety, pharmacokinetics, and antiviral activity of NVR 3-778, the researchers conducted a phase 1 study of 73 patients with chronic HBV infection who tested positive for hepatitis B e-antigen (HBeAg) and had no detectable cirrhosis. Patients were randomly assigned to receive oral NVR 3-778 (100 mg, 200 mg, or 400 mg daily or 600 mg or 1,000 mg twice daily ) or placebo for 28 days. Some patients received combination therapy with pegylated interferon plus either NVR 3-778 (600 mg twice daily) or placebo. Treatment was generally well tolerated, and adverse events were usually mild and deemed unrelated to therapy. No patient stopped treatment for adverse effects.
The only serious adverse event in the study consisted of grade 3 rash that developed in a 42-year-old male after 22 days of treatment at the lowest dose of NVR 3-778 (100 mg per day). This patient completed treatment and ultimately developed a severe papulovesicular rash with a predominantly acral distribution over the hands, arm, side of neck, and one leg (palmar plantar erythrodysesthesia), the researchers said. “There were no perioral or mucosal lesions, no ecchymotic skin involvement, no bullae, and no systemic manifestations or hematological abnormalities,” they wrote. “The rash was subsequently managed with a psoriasis-like treatment regimen of psoralen, ultraviolet light, and topical steroid ointment during outpatient follow-up and resolved after approximately 6 months.”
Another three cases of “minor” skin rash were considered probably related to treatment in the cohort that received 600 mg NVR 3-778 b.i.d. plus pegylated interferon, the investigators said. Two additional cases of mild rash were deemed unrelated to treatment.
“The observed reductions in HBV RNA confirmed the novel mechanism of NVR 3-778,” the researchers concluded. “This class of compounds can also inhibit replenishment of intranuclear covalently closed circular DNA over time and may have immunomodulatory properties.” Longer treatment periods would be needed to study these mechanisms and to quantify reductions in serum HBsAg and HBeAG, they noted.
Novira Therapeutics developed NVR 3-778 and is a Janssen Pharmaceutical Company. Janssen provided funding for editorial support. Dr. Yuen disclosed relationships with AbbVie, Biocartis, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Ionis, Roche, Vir Biotechnology, and several other pharmaceutical companies. Other coinvestigators disclosed ties to pharmaceutical companies; eight reported employment by Novira or a Janssen company.
SOURCE: Yuen MF et al. Gastroenterology. 2019 Jan 5. doi: 10.1053/j.gastro.2018.12.023.
FROM GASTROENTEROLOGY
Baby boomers account for more than 74% of chronic HCV cases
The overall prevalence of chronic hepatitis C virus (HCV) in the United States was 1.19%, giving an estimate of 2,347,852 infected adults. Baby boomers had the highest prevalence at 2.23%, accounting for more than 74% of all chronic HCV cases, according to the results of a database analysis done by Kevin J. Moore, MD, of the University of Miami and his colleagues.
In the analysis, published in the Journal of Infection and Public Health, the researchers assessed data from National Health and Nutrition Examination Survey for the years 1999-2012. They separated three age categories: baby boomers (BB), younger than BB (YG), and older than BB (OG). BBs showed an HCV prevalence over four times higher than YG or OG. BBs also had more significant predictors of positive HCV status than YGs or OGs.
In addition to the overall difference in incidence of HCV infection in boomers and nonboomers, they found that significant predictors of chronic HCV positivity among BBs were being male or non-Hispanic black, having a positive blood transfusion history, being a current or former smoker, and living below the poverty line.
The most significant risk factor for HCV positivity differed across age groups – being a current smoker in YG and BB and being non-Hispanic black in OG, the researchers noted.
“These results show that HCV infection continues to be a significant public health issue and warrants further attention given the aging BB population. Future studies should seek to further identify age-specific risk factors for HCV infection to optimize HCV screening and prevention programs through public health interventions,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Moore KJ et al. J Infect Public Health. 2019 Jan-Feb;12(1):32-6.
The overall prevalence of chronic hepatitis C virus (HCV) in the United States was 1.19%, giving an estimate of 2,347,852 infected adults. Baby boomers had the highest prevalence at 2.23%, accounting for more than 74% of all chronic HCV cases, according to the results of a database analysis done by Kevin J. Moore, MD, of the University of Miami and his colleagues.
In the analysis, published in the Journal of Infection and Public Health, the researchers assessed data from National Health and Nutrition Examination Survey for the years 1999-2012. They separated three age categories: baby boomers (BB), younger than BB (YG), and older than BB (OG). BBs showed an HCV prevalence over four times higher than YG or OG. BBs also had more significant predictors of positive HCV status than YGs or OGs.
In addition to the overall difference in incidence of HCV infection in boomers and nonboomers, they found that significant predictors of chronic HCV positivity among BBs were being male or non-Hispanic black, having a positive blood transfusion history, being a current or former smoker, and living below the poverty line.
The most significant risk factor for HCV positivity differed across age groups – being a current smoker in YG and BB and being non-Hispanic black in OG, the researchers noted.
“These results show that HCV infection continues to be a significant public health issue and warrants further attention given the aging BB population. Future studies should seek to further identify age-specific risk factors for HCV infection to optimize HCV screening and prevention programs through public health interventions,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Moore KJ et al. J Infect Public Health. 2019 Jan-Feb;12(1):32-6.
The overall prevalence of chronic hepatitis C virus (HCV) in the United States was 1.19%, giving an estimate of 2,347,852 infected adults. Baby boomers had the highest prevalence at 2.23%, accounting for more than 74% of all chronic HCV cases, according to the results of a database analysis done by Kevin J. Moore, MD, of the University of Miami and his colleagues.
In the analysis, published in the Journal of Infection and Public Health, the researchers assessed data from National Health and Nutrition Examination Survey for the years 1999-2012. They separated three age categories: baby boomers (BB), younger than BB (YG), and older than BB (OG). BBs showed an HCV prevalence over four times higher than YG or OG. BBs also had more significant predictors of positive HCV status than YGs or OGs.
In addition to the overall difference in incidence of HCV infection in boomers and nonboomers, they found that significant predictors of chronic HCV positivity among BBs were being male or non-Hispanic black, having a positive blood transfusion history, being a current or former smoker, and living below the poverty line.
The most significant risk factor for HCV positivity differed across age groups – being a current smoker in YG and BB and being non-Hispanic black in OG, the researchers noted.
“These results show that HCV infection continues to be a significant public health issue and warrants further attention given the aging BB population. Future studies should seek to further identify age-specific risk factors for HCV infection to optimize HCV screening and prevention programs through public health interventions,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Moore KJ et al. J Infect Public Health. 2019 Jan-Feb;12(1):32-6.
FROM THE JOURNAL OF INFECTION AND PUBLIC HEALTH
HCV-infected patients in the ED should be tested for advanced liver fibrosis
More than one-third of hepatitis C virus-infected patients in the emergency department (ED) were found to have advanced liver fibrosis and higher mortality, according to the results of a retrospective study of 113 known patients with HCV at a single institution.
As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were retrospectively identified. Components of FIB-4 (a noninvasive serum fibrosis index, which includes age, alanine aminotransferase, aspartate aminotransferase, and platelet count), were abstracted. Patients with an FIB-4 greater than 3.25 were classified with advanced fibrosis and characterized with regard to downstream outcomes at 1 year after enrollment.
The 1-year outcomes after the ED encounter for the 113 patients showed 38 with and 75 patients without advanced fibrosis. Among these, 72 (96%) and 34 (89.5%), respectively, agreed to be linked to HCV care. Ten patients of the total number of patients died within the 1-year follow-up. For those HCV-infected patients with advanced liver fibrosis compared to those without, all-cause mortality was more than fourfold higher, (18.4% [7 patients] vs. 4.0% [3 patients], P = .030), according to Yu-Hsiang Hsieh, PhD, associate professor of emergency medicine at Johns Hopkins University, Baltimore, and his colleagues (Am J Emerg Med. 2019;37[2]:286-90).
“Given the substantial burden of HCV-related illness in urban ED patients nationally, and the recognized fact that EDs are often the only point of contact with the health care system for many of these patients, we propose incorporating FIB-4 based rapid assessment into ED-based HCV screening and LTC programs in order to prioritize LTC for patients with advanced liver fibrosis, as well as routine ED clinical practice,” the researchers concluded.
They reported having no conflicts.
SOURCE: Yu-Hsiang Hsieh Y-H, Am J Emerg Med. 2019;37[2]:286-90.
More than one-third of hepatitis C virus-infected patients in the emergency department (ED) were found to have advanced liver fibrosis and higher mortality, according to the results of a retrospective study of 113 known patients with HCV at a single institution.
As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were retrospectively identified. Components of FIB-4 (a noninvasive serum fibrosis index, which includes age, alanine aminotransferase, aspartate aminotransferase, and platelet count), were abstracted. Patients with an FIB-4 greater than 3.25 were classified with advanced fibrosis and characterized with regard to downstream outcomes at 1 year after enrollment.
The 1-year outcomes after the ED encounter for the 113 patients showed 38 with and 75 patients without advanced fibrosis. Among these, 72 (96%) and 34 (89.5%), respectively, agreed to be linked to HCV care. Ten patients of the total number of patients died within the 1-year follow-up. For those HCV-infected patients with advanced liver fibrosis compared to those without, all-cause mortality was more than fourfold higher, (18.4% [7 patients] vs. 4.0% [3 patients], P = .030), according to Yu-Hsiang Hsieh, PhD, associate professor of emergency medicine at Johns Hopkins University, Baltimore, and his colleagues (Am J Emerg Med. 2019;37[2]:286-90).
“Given the substantial burden of HCV-related illness in urban ED patients nationally, and the recognized fact that EDs are often the only point of contact with the health care system for many of these patients, we propose incorporating FIB-4 based rapid assessment into ED-based HCV screening and LTC programs in order to prioritize LTC for patients with advanced liver fibrosis, as well as routine ED clinical practice,” the researchers concluded.
They reported having no conflicts.
SOURCE: Yu-Hsiang Hsieh Y-H, Am J Emerg Med. 2019;37[2]:286-90.
More than one-third of hepatitis C virus-infected patients in the emergency department (ED) were found to have advanced liver fibrosis and higher mortality, according to the results of a retrospective study of 113 known patients with HCV at a single institution.
As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were retrospectively identified. Components of FIB-4 (a noninvasive serum fibrosis index, which includes age, alanine aminotransferase, aspartate aminotransferase, and platelet count), were abstracted. Patients with an FIB-4 greater than 3.25 were classified with advanced fibrosis and characterized with regard to downstream outcomes at 1 year after enrollment.
The 1-year outcomes after the ED encounter for the 113 patients showed 38 with and 75 patients without advanced fibrosis. Among these, 72 (96%) and 34 (89.5%), respectively, agreed to be linked to HCV care. Ten patients of the total number of patients died within the 1-year follow-up. For those HCV-infected patients with advanced liver fibrosis compared to those without, all-cause mortality was more than fourfold higher, (18.4% [7 patients] vs. 4.0% [3 patients], P = .030), according to Yu-Hsiang Hsieh, PhD, associate professor of emergency medicine at Johns Hopkins University, Baltimore, and his colleagues (Am J Emerg Med. 2019;37[2]:286-90).
“Given the substantial burden of HCV-related illness in urban ED patients nationally, and the recognized fact that EDs are often the only point of contact with the health care system for many of these patients, we propose incorporating FIB-4 based rapid assessment into ED-based HCV screening and LTC programs in order to prioritize LTC for patients with advanced liver fibrosis, as well as routine ED clinical practice,” the researchers concluded.
They reported having no conflicts.
SOURCE: Yu-Hsiang Hsieh Y-H, Am J Emerg Med. 2019;37[2]:286-90.
FROM THE AMERICAN JOURNAL OF EMERGENCY MEDICINE
DAAs reduce mortality, cancer risk in HCV study
Direct-acting antivirals significantly decrease risk of hepatocellular carcinoma and mortality in persons with hepatitis C, according to results of the first prospective, longitudinal study to evaluate the effect of the drugs on complications related to the infection.
Compared with no treatment, DAA therapy cut risk of hepatocellular carcinoma by about one-third and all-cause mortality by about half in the study, which included about 10,000 adult patients with chronic hepatitis C virus (HCV) infection treated at 1 of 32 hepatology centers in France (NCT01953458).
There were no signs of increased risk of hepatocellular carcinoma during treatment with DAAs, providing more evidence refuting earlier, single-center reports that had suggested an increased incidence early after treatment. These findings also counterbalance a recent Cochrane review that could not confirm or reject a potential benefit of drugs on long-term morbidity and mortality.
Results of the study, published in the Lancet, are based on analysis of 9,895 patients, including 7,344 who started DAA treatment and 2,551 who remained untreated at a median follow-up of more than 31 months. The median patient age was 56 years, and 53% were men.
Treatment with DAAs reduced risk of hepatocellular carcinoma when compared with no DAA treatment, with a hazard ratio of 0.66 (95% confidence interval, 0.46-0.93), and reduced risk of all-cause mortality, with an HR of 0.48 (95% CI, 0.33-0.70), investigators reported in a multivariable analysis that adjusted for variables including age, sex, fibrosis score, HCV genotype, alcohol use, and more.
“These inverse associations persisted in the subgroup of patients who achieved a sustained virological response, whereas those who did not achieve a sustained virological response were a higher risk for hepatocellular carcinoma,” said the investigators, led by Fabrice Carrat, PhD, of Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris.
Sustained virologic response was observed in 94% of patients who had known response status and sufficient follow-up, investigators said.
In patients with cirrhosis at baseline, DAA treatment had a similarly strong association with reduced hepatocellular carcinoma and mortality, with a sustained virologic response rate of 92% in those for whom sufficient data was available, they said.
There was no evidence for an increased risk of hepatocellular carcinoma on treatment, with an adjusted HR of 0.74 (95% CI, 0.49-1.13; P = 0.17), they added.
“Our results support urgent treatment of patients with advanced liver disease and extension of the follow-up of treated patients with less severe disease to assess the long-term clinical effect of direct-acting antiviral treatment,” Dr. Carrat and colleagues said in a commentary on their results.
However, the long-term effect of DAAs on liver decompensation has yet to be clarified, they added, noting that their study excluded patients with decompensated cirrhosis or a history of hepatocellular carcinoma.
Funding for the study came from INSERM, Agence Nationale de la Recherche, DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche. Dr. Carrat reported personal fees from Imaxio not related to the present study. Coauthors provided additional disclosures related to Gilead, AbbVie, Bristol-Myers Squibb, MSD, and Janssen, among others.
SOURCE: Carrat F et al. Lancet. 2019 Feb 11. doi: 10.1016/S0140-6736(18)32111-1
This study provides “substantive evidence” that curing hepatitis C virus with all-oral direct-acting antiviral regimens provides clinical benefits, according to Raymond T. Chung, MD, and his coauthors of a related editorial.
Investigators in this study provide the best evidence so far in support of guidelines that advise direct-acting antiviral (DAA) treatment for all patients with chronic hepatitis C virus (HCV) infection, the editorial’s authors stated.
Results of the French study provide a strong counterpoint to the findings of a recent Cochrane review of DAA trials that could not confirm or reject whether DAAs had effects on long-term morbidity and mortality related to HCV, added Dr. Chung and his coauthors. “Finally, they provide credence to the achievability of the goals set out by the World Health Organization (WHO), not only to eliminate HCV but also to substantially reduce its complications.”
The WHO targets were established in light of earlier evidence that sustained virologic responses are linked to reductions in hepatocellular carcinoma, liver transplantation, and mortality, they said.
“In view of the high sustained virological response and excellent tolerability achieved with DAAs, it seemed highly plausible to envision reductions in chronic HCV infection–related complications with these drugs,” they said in reference to the study by Carrat and colleagues.
This editorial appearing in the Lancet was authored by Jacinta A. Holmes, Stephanie M. Rutledge, and Raymond T. Chung of the Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston. Dr. Chung provided disclosures related to AbbVie, Gilead, Merck, Bristol-Myers Squibb, Roche, Janssen, and Boehringer Ingelheim.
This study provides “substantive evidence” that curing hepatitis C virus with all-oral direct-acting antiviral regimens provides clinical benefits, according to Raymond T. Chung, MD, and his coauthors of a related editorial.
Investigators in this study provide the best evidence so far in support of guidelines that advise direct-acting antiviral (DAA) treatment for all patients with chronic hepatitis C virus (HCV) infection, the editorial’s authors stated.
Results of the French study provide a strong counterpoint to the findings of a recent Cochrane review of DAA trials that could not confirm or reject whether DAAs had effects on long-term morbidity and mortality related to HCV, added Dr. Chung and his coauthors. “Finally, they provide credence to the achievability of the goals set out by the World Health Organization (WHO), not only to eliminate HCV but also to substantially reduce its complications.”
The WHO targets were established in light of earlier evidence that sustained virologic responses are linked to reductions in hepatocellular carcinoma, liver transplantation, and mortality, they said.
“In view of the high sustained virological response and excellent tolerability achieved with DAAs, it seemed highly plausible to envision reductions in chronic HCV infection–related complications with these drugs,” they said in reference to the study by Carrat and colleagues.
This editorial appearing in the Lancet was authored by Jacinta A. Holmes, Stephanie M. Rutledge, and Raymond T. Chung of the Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston. Dr. Chung provided disclosures related to AbbVie, Gilead, Merck, Bristol-Myers Squibb, Roche, Janssen, and Boehringer Ingelheim.
This study provides “substantive evidence” that curing hepatitis C virus with all-oral direct-acting antiviral regimens provides clinical benefits, according to Raymond T. Chung, MD, and his coauthors of a related editorial.
Investigators in this study provide the best evidence so far in support of guidelines that advise direct-acting antiviral (DAA) treatment for all patients with chronic hepatitis C virus (HCV) infection, the editorial’s authors stated.
Results of the French study provide a strong counterpoint to the findings of a recent Cochrane review of DAA trials that could not confirm or reject whether DAAs had effects on long-term morbidity and mortality related to HCV, added Dr. Chung and his coauthors. “Finally, they provide credence to the achievability of the goals set out by the World Health Organization (WHO), not only to eliminate HCV but also to substantially reduce its complications.”
The WHO targets were established in light of earlier evidence that sustained virologic responses are linked to reductions in hepatocellular carcinoma, liver transplantation, and mortality, they said.
“In view of the high sustained virological response and excellent tolerability achieved with DAAs, it seemed highly plausible to envision reductions in chronic HCV infection–related complications with these drugs,” they said in reference to the study by Carrat and colleagues.
This editorial appearing in the Lancet was authored by Jacinta A. Holmes, Stephanie M. Rutledge, and Raymond T. Chung of the Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston. Dr. Chung provided disclosures related to AbbVie, Gilead, Merck, Bristol-Myers Squibb, Roche, Janssen, and Boehringer Ingelheim.
Direct-acting antivirals significantly decrease risk of hepatocellular carcinoma and mortality in persons with hepatitis C, according to results of the first prospective, longitudinal study to evaluate the effect of the drugs on complications related to the infection.
Compared with no treatment, DAA therapy cut risk of hepatocellular carcinoma by about one-third and all-cause mortality by about half in the study, which included about 10,000 adult patients with chronic hepatitis C virus (HCV) infection treated at 1 of 32 hepatology centers in France (NCT01953458).
There were no signs of increased risk of hepatocellular carcinoma during treatment with DAAs, providing more evidence refuting earlier, single-center reports that had suggested an increased incidence early after treatment. These findings also counterbalance a recent Cochrane review that could not confirm or reject a potential benefit of drugs on long-term morbidity and mortality.
Results of the study, published in the Lancet, are based on analysis of 9,895 patients, including 7,344 who started DAA treatment and 2,551 who remained untreated at a median follow-up of more than 31 months. The median patient age was 56 years, and 53% were men.
Treatment with DAAs reduced risk of hepatocellular carcinoma when compared with no DAA treatment, with a hazard ratio of 0.66 (95% confidence interval, 0.46-0.93), and reduced risk of all-cause mortality, with an HR of 0.48 (95% CI, 0.33-0.70), investigators reported in a multivariable analysis that adjusted for variables including age, sex, fibrosis score, HCV genotype, alcohol use, and more.
“These inverse associations persisted in the subgroup of patients who achieved a sustained virological response, whereas those who did not achieve a sustained virological response were a higher risk for hepatocellular carcinoma,” said the investigators, led by Fabrice Carrat, PhD, of Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris.
Sustained virologic response was observed in 94% of patients who had known response status and sufficient follow-up, investigators said.
In patients with cirrhosis at baseline, DAA treatment had a similarly strong association with reduced hepatocellular carcinoma and mortality, with a sustained virologic response rate of 92% in those for whom sufficient data was available, they said.
There was no evidence for an increased risk of hepatocellular carcinoma on treatment, with an adjusted HR of 0.74 (95% CI, 0.49-1.13; P = 0.17), they added.
“Our results support urgent treatment of patients with advanced liver disease and extension of the follow-up of treated patients with less severe disease to assess the long-term clinical effect of direct-acting antiviral treatment,” Dr. Carrat and colleagues said in a commentary on their results.
However, the long-term effect of DAAs on liver decompensation has yet to be clarified, they added, noting that their study excluded patients with decompensated cirrhosis or a history of hepatocellular carcinoma.
Funding for the study came from INSERM, Agence Nationale de la Recherche, DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche. Dr. Carrat reported personal fees from Imaxio not related to the present study. Coauthors provided additional disclosures related to Gilead, AbbVie, Bristol-Myers Squibb, MSD, and Janssen, among others.
SOURCE: Carrat F et al. Lancet. 2019 Feb 11. doi: 10.1016/S0140-6736(18)32111-1
Direct-acting antivirals significantly decrease risk of hepatocellular carcinoma and mortality in persons with hepatitis C, according to results of the first prospective, longitudinal study to evaluate the effect of the drugs on complications related to the infection.
Compared with no treatment, DAA therapy cut risk of hepatocellular carcinoma by about one-third and all-cause mortality by about half in the study, which included about 10,000 adult patients with chronic hepatitis C virus (HCV) infection treated at 1 of 32 hepatology centers in France (NCT01953458).
There were no signs of increased risk of hepatocellular carcinoma during treatment with DAAs, providing more evidence refuting earlier, single-center reports that had suggested an increased incidence early after treatment. These findings also counterbalance a recent Cochrane review that could not confirm or reject a potential benefit of drugs on long-term morbidity and mortality.
Results of the study, published in the Lancet, are based on analysis of 9,895 patients, including 7,344 who started DAA treatment and 2,551 who remained untreated at a median follow-up of more than 31 months. The median patient age was 56 years, and 53% were men.
Treatment with DAAs reduced risk of hepatocellular carcinoma when compared with no DAA treatment, with a hazard ratio of 0.66 (95% confidence interval, 0.46-0.93), and reduced risk of all-cause mortality, with an HR of 0.48 (95% CI, 0.33-0.70), investigators reported in a multivariable analysis that adjusted for variables including age, sex, fibrosis score, HCV genotype, alcohol use, and more.
“These inverse associations persisted in the subgroup of patients who achieved a sustained virological response, whereas those who did not achieve a sustained virological response were a higher risk for hepatocellular carcinoma,” said the investigators, led by Fabrice Carrat, PhD, of Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris.
Sustained virologic response was observed in 94% of patients who had known response status and sufficient follow-up, investigators said.
In patients with cirrhosis at baseline, DAA treatment had a similarly strong association with reduced hepatocellular carcinoma and mortality, with a sustained virologic response rate of 92% in those for whom sufficient data was available, they said.
There was no evidence for an increased risk of hepatocellular carcinoma on treatment, with an adjusted HR of 0.74 (95% CI, 0.49-1.13; P = 0.17), they added.
“Our results support urgent treatment of patients with advanced liver disease and extension of the follow-up of treated patients with less severe disease to assess the long-term clinical effect of direct-acting antiviral treatment,” Dr. Carrat and colleagues said in a commentary on their results.
However, the long-term effect of DAAs on liver decompensation has yet to be clarified, they added, noting that their study excluded patients with decompensated cirrhosis or a history of hepatocellular carcinoma.
Funding for the study came from INSERM, Agence Nationale de la Recherche, DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche. Dr. Carrat reported personal fees from Imaxio not related to the present study. Coauthors provided additional disclosures related to Gilead, AbbVie, Bristol-Myers Squibb, MSD, and Janssen, among others.
SOURCE: Carrat F et al. Lancet. 2019 Feb 11. doi: 10.1016/S0140-6736(18)32111-1
FROM THE LANCET
Key clinical point:
Major finding: DAAs reduced risk of hepatocellular carcinoma (HR, 0.66; 95% confidence interval, 0.46-0.93) and all-cause mortality (HR, 0.48; 95% CI, 0.33-0.70).
Study details: A prospective study including about 10,000 adults with chronic HCV infection enrolled at 1 of 32 centers in France.
Disclosures: Funding for the study came from INSERM, Agence Nationale de la Recherche, DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche. Dr. Carrat reported personal fees from Imaxio not related to the present study. Coauthors provided additional disclosures related to the study pharma sponsors among others.
Source: Carrat F et al. Lancet. 2019 Feb 11. doi: 10.1016/20S0140-6736(18)32111-1.
Rise in HCV infection rates linked to OxyContin reformulation
Public health experts have attributed the alarming rise in hepatitis C virus (HCV) infection rates in recent years to the opioid epidemic, and a new Rand study suggests that an effort to deter opioid abuse – namely the 2010 abuse-deterrent reformulation of OxyContin – is partly to blame.
Between 2004 and 2015, HCV infection rates in the United States nearly tripled, but a closer look showed that states with above-median rates of OxyContin misuse prior to the reformulation had a 222% increase in HCV rates, compared with a 75% increase in states with below-median OxyContin misuse, said David Powell, PhD, a senior economist at Rand in Arlington, Va., and his colleagues, Abby Alpert, PhD, and Rosalie L. Pacula, PhD. The report was published in Health Affairs.
The coauthors found that hepatitis C infection rates were not significantly different between the two groups of states before the reformulation (0.350 vs. 0.260). But after 2010, there were large and statistically significant differences in the rates (1.128 vs. 0.455; P less than 0.01), they wrote, noting that the above-median states experienced an additional 0.58 HCV infections per 100,000 population through 2015 relative to the below-median states).
HCV infection rates declined during the 1990s followed by a plateau beginning around 2003, then rose sharply beginning in 2010, coinciding with the introduction of the release of the abuse-deterrent formulation of OxyContin, which is one of the most commonly misused opioid analgesics, the investigators said, explaining that the reformulated version was harder to crush or dissolve, making it more difficult to inhale or inject.
“Prior studies have shown that, after OxyContin became more difficult to abuse, some nonmedical users of OxyContin switched to heroin (a pharmacologically similar opiate),” they noted.
This led to a decline of more than 40% in OxyContin misuse but also to a sharp increase in heroin overdoses after 2010.
The investigators assessed whether the related increase in heroin use might explain the increase in HCV infections, which can be transmitted through shared needle use.
Using a quasi-experimental difference-in-differences approach, they examined whether states with higher exposure to the reformulated OxyContin had faster growth of HCV infection rates after the reformulations, and as a falsification exercise, they also looked at whether the nonmedical use of pain relievers other than OxyContin predicted post-reformulation HCV infection rate increases.
HCV infection rates for each calendar year from 2004 to 2015 were assessed using confirmed case reports collected by the Centers for Disease Control and Prevention, and nonmedical OxyContin use was measured using self-reported data from the National Survey on Drug Use and Health, which is the largest U.S. survey on substance use disorder.
The two groups of states had similar demographic and economic conditions, except that the above-median misuse states had smaller populations and a larger proportion of white residents.
Of note, the patterns of HCV infection mirrored those of heroin overdoses. There was small relative increase in HCV infection rates in 2010 in the above-median OxyContin misuse states, and the gap between above- and below-median misuse states widened more rapidly from 2011 to 2013. “This striking inflection point in the trend of hepatitis C infections for high-misuse states after 2010 mimics the inflection in heroin overdoses that occurred as a result of the reformulation,” they said, noting that heroin morality per 100,000 population was nearly identical in the two groups of states in the pre-reformulation period (0.859 and 0.847).
The falsification exercise looking at nonmedical use of pain relievers other than OxyContin in the two groups of states showed that after 2010 groups’ rates of hepatitis C infections grew at virtually identical rates.
“Thus, the differential risk in hepatitis C infections was uniquely associated with OxyContin misuse, rather than prescription pain reliever misuse more generally,” they said. “This suggests that it was the OxyContin reformulation, not other policies broadly affecting opioids, that drove much of the differential growth.”
The investigators controlled for numerous other factors, including opioid policies that might have an impact on OxyContin and heroin use, prescription drug monitoring programs and pain clinic regulations, as well as the role of major pill-mill crackdowns in 2010 and 2011.
The findings represent a “substantial public health concern,” they said, explaining that, while “considerable policy attention is being given to managing the opioid epidemic ... a ‘silent epidemic’ of hepatitis C has emerged as a result of a transition in the mode of administration toward injection drug use.”
In 2017, the CDC reported on this link between the opioid epidemic and rising HCV infection rates, as well.
Dr. Powell and his colleagues wrote.
Their findings regarding the unintended consequences of the OxyContin reformulation suggest that caution is warranted with respect to future interventions that limit the supply of abusable prescription opioids, they said, adding that “such interventions must be paired with polices that alleviate the harms associated with switching to illicit drugs, such as improved access to substance use disorder treatment and increased efforts aimed at identifying and treating diseases associated with injection drug use.”
However, policy makers and medical professionals also must recognize that reducing opioid-related mortality and increasing access to drug treatment might not be sufficient to fully address all of the public health consequences associated with the opioid crisis. As additional reformulations of opioids are promoted and more policies seek to limit access to prescription opioids, “both the medical and the law enforcement communities must recognize the critical transition from prescription opioids to other drugs, particularly those that are injected, and be prepared to consider complementary strategies that can effectively reduce the additional harms from the particular mode of drug use,” they concluded.
The coauthors cited several limitations, including the possibility that true hepatitis C infection rates might have been underestimated in the study.
He and Dr. Pacula received funding from the National Institute on Drug Abuse. Dr. Powell also cited funding from the Rand Alumni Impact Award.
SOURCE: Powell D et al. Health Aff. 2019;38(2):287-94.
Increases have been seen not only in infectious diseases but also in cardiovascular diseases as intravenous opioid use has risen, Mark S. Gold, MD, said in an interview. “These emerging co-occurring diseases tend to lag behind drug deaths and other data,” he said.
The study by Powell et al. shows that drugs of abuse are dangerous, and that, with addictive use, we find consequences. “Each change appears to bring with it intended consequences we study, but over time, unintended consequences emerge,” he said. “It is important to remain vigilant.”
Dr. Gold is 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis.
Increases have been seen not only in infectious diseases but also in cardiovascular diseases as intravenous opioid use has risen, Mark S. Gold, MD, said in an interview. “These emerging co-occurring diseases tend to lag behind drug deaths and other data,” he said.
The study by Powell et al. shows that drugs of abuse are dangerous, and that, with addictive use, we find consequences. “Each change appears to bring with it intended consequences we study, but over time, unintended consequences emerge,” he said. “It is important to remain vigilant.”
Dr. Gold is 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis.
Increases have been seen not only in infectious diseases but also in cardiovascular diseases as intravenous opioid use has risen, Mark S. Gold, MD, said in an interview. “These emerging co-occurring diseases tend to lag behind drug deaths and other data,” he said.
The study by Powell et al. shows that drugs of abuse are dangerous, and that, with addictive use, we find consequences. “Each change appears to bring with it intended consequences we study, but over time, unintended consequences emerge,” he said. “It is important to remain vigilant.”
Dr. Gold is 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis.
Public health experts have attributed the alarming rise in hepatitis C virus (HCV) infection rates in recent years to the opioid epidemic, and a new Rand study suggests that an effort to deter opioid abuse – namely the 2010 abuse-deterrent reformulation of OxyContin – is partly to blame.
Between 2004 and 2015, HCV infection rates in the United States nearly tripled, but a closer look showed that states with above-median rates of OxyContin misuse prior to the reformulation had a 222% increase in HCV rates, compared with a 75% increase in states with below-median OxyContin misuse, said David Powell, PhD, a senior economist at Rand in Arlington, Va., and his colleagues, Abby Alpert, PhD, and Rosalie L. Pacula, PhD. The report was published in Health Affairs.
The coauthors found that hepatitis C infection rates were not significantly different between the two groups of states before the reformulation (0.350 vs. 0.260). But after 2010, there were large and statistically significant differences in the rates (1.128 vs. 0.455; P less than 0.01), they wrote, noting that the above-median states experienced an additional 0.58 HCV infections per 100,000 population through 2015 relative to the below-median states).
HCV infection rates declined during the 1990s followed by a plateau beginning around 2003, then rose sharply beginning in 2010, coinciding with the introduction of the release of the abuse-deterrent formulation of OxyContin, which is one of the most commonly misused opioid analgesics, the investigators said, explaining that the reformulated version was harder to crush or dissolve, making it more difficult to inhale or inject.
“Prior studies have shown that, after OxyContin became more difficult to abuse, some nonmedical users of OxyContin switched to heroin (a pharmacologically similar opiate),” they noted.
This led to a decline of more than 40% in OxyContin misuse but also to a sharp increase in heroin overdoses after 2010.
The investigators assessed whether the related increase in heroin use might explain the increase in HCV infections, which can be transmitted through shared needle use.
Using a quasi-experimental difference-in-differences approach, they examined whether states with higher exposure to the reformulated OxyContin had faster growth of HCV infection rates after the reformulations, and as a falsification exercise, they also looked at whether the nonmedical use of pain relievers other than OxyContin predicted post-reformulation HCV infection rate increases.
HCV infection rates for each calendar year from 2004 to 2015 were assessed using confirmed case reports collected by the Centers for Disease Control and Prevention, and nonmedical OxyContin use was measured using self-reported data from the National Survey on Drug Use and Health, which is the largest U.S. survey on substance use disorder.
The two groups of states had similar demographic and economic conditions, except that the above-median misuse states had smaller populations and a larger proportion of white residents.
Of note, the patterns of HCV infection mirrored those of heroin overdoses. There was small relative increase in HCV infection rates in 2010 in the above-median OxyContin misuse states, and the gap between above- and below-median misuse states widened more rapidly from 2011 to 2013. “This striking inflection point in the trend of hepatitis C infections for high-misuse states after 2010 mimics the inflection in heroin overdoses that occurred as a result of the reformulation,” they said, noting that heroin morality per 100,000 population was nearly identical in the two groups of states in the pre-reformulation period (0.859 and 0.847).
The falsification exercise looking at nonmedical use of pain relievers other than OxyContin in the two groups of states showed that after 2010 groups’ rates of hepatitis C infections grew at virtually identical rates.
“Thus, the differential risk in hepatitis C infections was uniquely associated with OxyContin misuse, rather than prescription pain reliever misuse more generally,” they said. “This suggests that it was the OxyContin reformulation, not other policies broadly affecting opioids, that drove much of the differential growth.”
The investigators controlled for numerous other factors, including opioid policies that might have an impact on OxyContin and heroin use, prescription drug monitoring programs and pain clinic regulations, as well as the role of major pill-mill crackdowns in 2010 and 2011.
The findings represent a “substantial public health concern,” they said, explaining that, while “considerable policy attention is being given to managing the opioid epidemic ... a ‘silent epidemic’ of hepatitis C has emerged as a result of a transition in the mode of administration toward injection drug use.”
In 2017, the CDC reported on this link between the opioid epidemic and rising HCV infection rates, as well.
Dr. Powell and his colleagues wrote.
Their findings regarding the unintended consequences of the OxyContin reformulation suggest that caution is warranted with respect to future interventions that limit the supply of abusable prescription opioids, they said, adding that “such interventions must be paired with polices that alleviate the harms associated with switching to illicit drugs, such as improved access to substance use disorder treatment and increased efforts aimed at identifying and treating diseases associated with injection drug use.”
However, policy makers and medical professionals also must recognize that reducing opioid-related mortality and increasing access to drug treatment might not be sufficient to fully address all of the public health consequences associated with the opioid crisis. As additional reformulations of opioids are promoted and more policies seek to limit access to prescription opioids, “both the medical and the law enforcement communities must recognize the critical transition from prescription opioids to other drugs, particularly those that are injected, and be prepared to consider complementary strategies that can effectively reduce the additional harms from the particular mode of drug use,” they concluded.
The coauthors cited several limitations, including the possibility that true hepatitis C infection rates might have been underestimated in the study.
He and Dr. Pacula received funding from the National Institute on Drug Abuse. Dr. Powell also cited funding from the Rand Alumni Impact Award.
SOURCE: Powell D et al. Health Aff. 2019;38(2):287-94.
Public health experts have attributed the alarming rise in hepatitis C virus (HCV) infection rates in recent years to the opioid epidemic, and a new Rand study suggests that an effort to deter opioid abuse – namely the 2010 abuse-deterrent reformulation of OxyContin – is partly to blame.
Between 2004 and 2015, HCV infection rates in the United States nearly tripled, but a closer look showed that states with above-median rates of OxyContin misuse prior to the reformulation had a 222% increase in HCV rates, compared with a 75% increase in states with below-median OxyContin misuse, said David Powell, PhD, a senior economist at Rand in Arlington, Va., and his colleagues, Abby Alpert, PhD, and Rosalie L. Pacula, PhD. The report was published in Health Affairs.
The coauthors found that hepatitis C infection rates were not significantly different between the two groups of states before the reformulation (0.350 vs. 0.260). But after 2010, there were large and statistically significant differences in the rates (1.128 vs. 0.455; P less than 0.01), they wrote, noting that the above-median states experienced an additional 0.58 HCV infections per 100,000 population through 2015 relative to the below-median states).
HCV infection rates declined during the 1990s followed by a plateau beginning around 2003, then rose sharply beginning in 2010, coinciding with the introduction of the release of the abuse-deterrent formulation of OxyContin, which is one of the most commonly misused opioid analgesics, the investigators said, explaining that the reformulated version was harder to crush or dissolve, making it more difficult to inhale or inject.
“Prior studies have shown that, after OxyContin became more difficult to abuse, some nonmedical users of OxyContin switched to heroin (a pharmacologically similar opiate),” they noted.
This led to a decline of more than 40% in OxyContin misuse but also to a sharp increase in heroin overdoses after 2010.
The investigators assessed whether the related increase in heroin use might explain the increase in HCV infections, which can be transmitted through shared needle use.
Using a quasi-experimental difference-in-differences approach, they examined whether states with higher exposure to the reformulated OxyContin had faster growth of HCV infection rates after the reformulations, and as a falsification exercise, they also looked at whether the nonmedical use of pain relievers other than OxyContin predicted post-reformulation HCV infection rate increases.
HCV infection rates for each calendar year from 2004 to 2015 were assessed using confirmed case reports collected by the Centers for Disease Control and Prevention, and nonmedical OxyContin use was measured using self-reported data from the National Survey on Drug Use and Health, which is the largest U.S. survey on substance use disorder.
The two groups of states had similar demographic and economic conditions, except that the above-median misuse states had smaller populations and a larger proportion of white residents.
Of note, the patterns of HCV infection mirrored those of heroin overdoses. There was small relative increase in HCV infection rates in 2010 in the above-median OxyContin misuse states, and the gap between above- and below-median misuse states widened more rapidly from 2011 to 2013. “This striking inflection point in the trend of hepatitis C infections for high-misuse states after 2010 mimics the inflection in heroin overdoses that occurred as a result of the reformulation,” they said, noting that heroin morality per 100,000 population was nearly identical in the two groups of states in the pre-reformulation period (0.859 and 0.847).
The falsification exercise looking at nonmedical use of pain relievers other than OxyContin in the two groups of states showed that after 2010 groups’ rates of hepatitis C infections grew at virtually identical rates.
“Thus, the differential risk in hepatitis C infections was uniquely associated with OxyContin misuse, rather than prescription pain reliever misuse more generally,” they said. “This suggests that it was the OxyContin reformulation, not other policies broadly affecting opioids, that drove much of the differential growth.”
The investigators controlled for numerous other factors, including opioid policies that might have an impact on OxyContin and heroin use, prescription drug monitoring programs and pain clinic regulations, as well as the role of major pill-mill crackdowns in 2010 and 2011.
The findings represent a “substantial public health concern,” they said, explaining that, while “considerable policy attention is being given to managing the opioid epidemic ... a ‘silent epidemic’ of hepatitis C has emerged as a result of a transition in the mode of administration toward injection drug use.”
In 2017, the CDC reported on this link between the opioid epidemic and rising HCV infection rates, as well.
Dr. Powell and his colleagues wrote.
Their findings regarding the unintended consequences of the OxyContin reformulation suggest that caution is warranted with respect to future interventions that limit the supply of abusable prescription opioids, they said, adding that “such interventions must be paired with polices that alleviate the harms associated with switching to illicit drugs, such as improved access to substance use disorder treatment and increased efforts aimed at identifying and treating diseases associated with injection drug use.”
However, policy makers and medical professionals also must recognize that reducing opioid-related mortality and increasing access to drug treatment might not be sufficient to fully address all of the public health consequences associated with the opioid crisis. As additional reformulations of opioids are promoted and more policies seek to limit access to prescription opioids, “both the medical and the law enforcement communities must recognize the critical transition from prescription opioids to other drugs, particularly those that are injected, and be prepared to consider complementary strategies that can effectively reduce the additional harms from the particular mode of drug use,” they concluded.
The coauthors cited several limitations, including the possibility that true hepatitis C infection rates might have been underestimated in the study.
He and Dr. Pacula received funding from the National Institute on Drug Abuse. Dr. Powell also cited funding from the Rand Alumni Impact Award.
SOURCE: Powell D et al. Health Aff. 2019;38(2):287-94.
FROM HEALTH AFFAIRS
Key clinical point: Physicians and others must be “prepared to consider complementary strategies that can effectively reduce the additional harms from the particular mode of drug use.”
Major finding: HCV rates increased 222% in states that had above-median OxyContin misuse rates, compared with an increase of 75% in states with below-median misuse.
Study details: A review of data from 2004 to 2015.
Disclosures: Dr. Powell and Dr. Pacula received funding from the National Institute on Drug Abuse. Dr. Powell also cited funding from the Rand Alumni Impact Award.
Source: Powell D et al. Health Aff. 2019;38(2):287-94.
Elective hernia repair preferable in patients with chronic liver disease
Elective hernia repair in patients with chronic liver disease was far safer than emergent repair and carried an acceptable level of morbidity and mortality, according to an analysis of all cases performed at the Cleveland Clinic from 2001-2015.
In a chart review of 253 patients with chronic liver disease (CLD) who underwent hernia repair between January 2001 and December 2015, the rate of postoperative 30-day morbidity and mortality was 27% for nonemergent repairs, compared with 60% in emergent repairs.
The 90-day mortality rate also was higher for emergent repairs (10%) than for nonemergent repairs (3.7%), reported Clayton C. Petro, MD, of the Cleveland Clinic, and his coauthors.
Thirty-day morbidity and mortality was defined as incidence of surgical-site infection (SSI), wound dehiscence, bacterial peritonitis, decompensated liver failure, postoperative admission to the intensive care unit, unplanned hospital readmission, unplanned reoperation, and 30-day mortality. CLD severity was determined using the Charlson Comorbidity Index (CCI), age-adjusted CCI, Child-Turcott-Pugh Score, laboratory values, and Model for End-Stage Liver Disease (MELD) Score.
Of the 253 patients, 186 (74%) had nonemergent repairs and 67 (26%) had emergent repairs; 91 patients (36%) experienced a total of 159 morbidity and mortality events, Dr. Petro and coauthors said.
Emergent repairs had significantly higher rates of postoperative ICU admission than nonemergent repairs (27% vs. 5%; P less than .0001). Emergent repairs also had higher rates of bacterial peritonitis (10% vs 3%; P = .02), unplanned reoperation (9% vs 1%; P = .005), and unplanned readmission (27% vs 14%, P = .02).
“This large single-center cohort of 253 CLD patients suggests that non-emergent hernia repairs have relatively acceptable rates of [morbidity and mortality], even with advanced liver disease,” the authors wrote. “The dramatic increase in postoperative complications and 90-day mortality in the emergent setting supports the practice of elective repair when possible.”
No disclosures or conflicts of interest were reported.
SOURCE: Petro C et al. Am J Surg. 2019:217;59-65.
Elective hernia repair in patients with chronic liver disease was far safer than emergent repair and carried an acceptable level of morbidity and mortality, according to an analysis of all cases performed at the Cleveland Clinic from 2001-2015.
In a chart review of 253 patients with chronic liver disease (CLD) who underwent hernia repair between January 2001 and December 2015, the rate of postoperative 30-day morbidity and mortality was 27% for nonemergent repairs, compared with 60% in emergent repairs.
The 90-day mortality rate also was higher for emergent repairs (10%) than for nonemergent repairs (3.7%), reported Clayton C. Petro, MD, of the Cleveland Clinic, and his coauthors.
Thirty-day morbidity and mortality was defined as incidence of surgical-site infection (SSI), wound dehiscence, bacterial peritonitis, decompensated liver failure, postoperative admission to the intensive care unit, unplanned hospital readmission, unplanned reoperation, and 30-day mortality. CLD severity was determined using the Charlson Comorbidity Index (CCI), age-adjusted CCI, Child-Turcott-Pugh Score, laboratory values, and Model for End-Stage Liver Disease (MELD) Score.
Of the 253 patients, 186 (74%) had nonemergent repairs and 67 (26%) had emergent repairs; 91 patients (36%) experienced a total of 159 morbidity and mortality events, Dr. Petro and coauthors said.
Emergent repairs had significantly higher rates of postoperative ICU admission than nonemergent repairs (27% vs. 5%; P less than .0001). Emergent repairs also had higher rates of bacterial peritonitis (10% vs 3%; P = .02), unplanned reoperation (9% vs 1%; P = .005), and unplanned readmission (27% vs 14%, P = .02).
“This large single-center cohort of 253 CLD patients suggests that non-emergent hernia repairs have relatively acceptable rates of [morbidity and mortality], even with advanced liver disease,” the authors wrote. “The dramatic increase in postoperative complications and 90-day mortality in the emergent setting supports the practice of elective repair when possible.”
No disclosures or conflicts of interest were reported.
SOURCE: Petro C et al. Am J Surg. 2019:217;59-65.
Elective hernia repair in patients with chronic liver disease was far safer than emergent repair and carried an acceptable level of morbidity and mortality, according to an analysis of all cases performed at the Cleveland Clinic from 2001-2015.
In a chart review of 253 patients with chronic liver disease (CLD) who underwent hernia repair between January 2001 and December 2015, the rate of postoperative 30-day morbidity and mortality was 27% for nonemergent repairs, compared with 60% in emergent repairs.
The 90-day mortality rate also was higher for emergent repairs (10%) than for nonemergent repairs (3.7%), reported Clayton C. Petro, MD, of the Cleveland Clinic, and his coauthors.
Thirty-day morbidity and mortality was defined as incidence of surgical-site infection (SSI), wound dehiscence, bacterial peritonitis, decompensated liver failure, postoperative admission to the intensive care unit, unplanned hospital readmission, unplanned reoperation, and 30-day mortality. CLD severity was determined using the Charlson Comorbidity Index (CCI), age-adjusted CCI, Child-Turcott-Pugh Score, laboratory values, and Model for End-Stage Liver Disease (MELD) Score.
Of the 253 patients, 186 (74%) had nonemergent repairs and 67 (26%) had emergent repairs; 91 patients (36%) experienced a total of 159 morbidity and mortality events, Dr. Petro and coauthors said.
Emergent repairs had significantly higher rates of postoperative ICU admission than nonemergent repairs (27% vs. 5%; P less than .0001). Emergent repairs also had higher rates of bacterial peritonitis (10% vs 3%; P = .02), unplanned reoperation (9% vs 1%; P = .005), and unplanned readmission (27% vs 14%, P = .02).
“This large single-center cohort of 253 CLD patients suggests that non-emergent hernia repairs have relatively acceptable rates of [morbidity and mortality], even with advanced liver disease,” the authors wrote. “The dramatic increase in postoperative complications and 90-day mortality in the emergent setting supports the practice of elective repair when possible.”
No disclosures or conflicts of interest were reported.
SOURCE: Petro C et al. Am J Surg. 2019:217;59-65.
FROM THE AMERICAN JOURNAL OF SURGERY
Key clinical point: Emergent hernia repairs had higher morbidity and mortality than nonemergent repairs in patients with chronic liver disease.
Major finding: The rate of postoperative 30-day morbidity and mortality was 27% for nonemergent repairs, compared with 60% in emergent repairs.
Study details: Chart review of 253 CLD patients who underwent hernia repair between January 2001 and December 2015.
Disclosures: No disclosures or conflicts of interest were reported.
Source: Petro C et al. Am J Surg. 2019:217;59-65.
Residential HCV program improves veterans’ diagnosis and care
Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.
A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.
Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.
As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.
Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.
Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).
“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.
The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.
Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.
A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.
Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.
As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.
Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.
Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).
“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.
The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.
Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.
A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.
Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.
As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.
Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.
Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).
“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.
The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.
FROM THE JOURNAL OF SUBSTANCE ABUSE TREATMENT
HBV, HCV, HIV testing of new cancer patients advised
Oncologists should consider testing all patients with newly diagnosed cancers for infection with the hepatitis B and C viruses, a multicenter team has recommended.
A prospective study of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infections among 3,051 patients with newly diagnosed cancers showed that 6.5% of patients tested positive for previous HBV and 0.6% had chronic HBV infection. In addition, 2.4% of patients were positive for HCV, and 1.1% for HIV infections, reported Scott D. Ramsey, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.
“Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient. Thus, we believe our results warrant consideration of universal testing of patients with newly diagnosed cancer for HBV and HCV infection, particularly if such an approach is shown to be cost effective,” they wrote in JAMA Oncology.
The investigators noted that patients with undiagnosed hepatitis and/or HIV infections could transmit them to unsuspecting caregivers, adding that “with effective treatments available, not screening for these viruses misses an opportunity to reduce future morbidity associated with these infections and to avoid viral reactivation during treatment, with resulting morbidity and mortality.”
To estimate the prevalence of the infections in patients with newly diagnosed cancers, investigators looked at a cohort of 3,051 patients with a cancer diagnosis made within the previous 120 days at nine academic medical centers and nine community oncology centers representing a total of 41 cancer clinics affiliated with the SWOG Cancer Research Network (formerly the Southwest Oncology Group).
The median patient age was 60.6 years. Female patients constitute 60.4% of the sample; 18.1% were black, and 18.3% were of Hispanic heritage.
Of 3,050 patients for whom HBV testing results were available, 6.5% (197) were positive for previous HBV infection, compared with an estimated U.S. population prevalence of 4.7%. In addition, 0.6% (19 patients) were found to have chronic HBV, compared with an estimated 0.3% US population prevalence.
HCV infections were detected in 2.4% (71 of 2990 patients), compared with an estimated population prevalence of 1.3%, and HIV infections were detected in 1.1%, compared with a background estimated population prevalence of 0.3%.
In all, 32 patients were diagnosed with viral infections by testing performed for the study, including 8 patients with chronic HBV, 22 with HCV, and 2 with HIV.
Additionally, the authors found that 4 patients with chronic HBV, 23 with HCV, and 7 with HIV had no identifiable risk factors.
The highest prevalence of infections occurred among patients with liver cancer, nonliver and noncolorectal cancers of the gastrointestinal tract, head and neck cancers, lung cancers, and prostate cancer. A finding of viral positivity changed the treatment plan in only 8% of all infected patients, however.
“Given that most HIV-infected patients in our study knew their viral status, the yield of universal HIV testing among patients with newly diagnosed cancer may likely be low. Although age-directed screening is recommended for HIV and HCV, uptake rates in primary care are variable and low overall,” Dr. Ramsey and his colleagues wrote.
The study was supported by grants from the National Cancer Institute. Dr. Ramsey and several co-authors reported receiving NCI grants, and multiple co-authors reported grants and/or consulting fees from various companies.
SOURCE: Ramsey SD et al. JAMA Oncol. 2019 Jan 17. doi: 10.1001/jamaoncol.2018.6437.
Oncologists should consider testing all patients with newly diagnosed cancers for infection with the hepatitis B and C viruses, a multicenter team has recommended.
A prospective study of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infections among 3,051 patients with newly diagnosed cancers showed that 6.5% of patients tested positive for previous HBV and 0.6% had chronic HBV infection. In addition, 2.4% of patients were positive for HCV, and 1.1% for HIV infections, reported Scott D. Ramsey, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.
“Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient. Thus, we believe our results warrant consideration of universal testing of patients with newly diagnosed cancer for HBV and HCV infection, particularly if such an approach is shown to be cost effective,” they wrote in JAMA Oncology.
The investigators noted that patients with undiagnosed hepatitis and/or HIV infections could transmit them to unsuspecting caregivers, adding that “with effective treatments available, not screening for these viruses misses an opportunity to reduce future morbidity associated with these infections and to avoid viral reactivation during treatment, with resulting morbidity and mortality.”
To estimate the prevalence of the infections in patients with newly diagnosed cancers, investigators looked at a cohort of 3,051 patients with a cancer diagnosis made within the previous 120 days at nine academic medical centers and nine community oncology centers representing a total of 41 cancer clinics affiliated with the SWOG Cancer Research Network (formerly the Southwest Oncology Group).
The median patient age was 60.6 years. Female patients constitute 60.4% of the sample; 18.1% were black, and 18.3% were of Hispanic heritage.
Of 3,050 patients for whom HBV testing results were available, 6.5% (197) were positive for previous HBV infection, compared with an estimated U.S. population prevalence of 4.7%. In addition, 0.6% (19 patients) were found to have chronic HBV, compared with an estimated 0.3% US population prevalence.
HCV infections were detected in 2.4% (71 of 2990 patients), compared with an estimated population prevalence of 1.3%, and HIV infections were detected in 1.1%, compared with a background estimated population prevalence of 0.3%.
In all, 32 patients were diagnosed with viral infections by testing performed for the study, including 8 patients with chronic HBV, 22 with HCV, and 2 with HIV.
Additionally, the authors found that 4 patients with chronic HBV, 23 with HCV, and 7 with HIV had no identifiable risk factors.
The highest prevalence of infections occurred among patients with liver cancer, nonliver and noncolorectal cancers of the gastrointestinal tract, head and neck cancers, lung cancers, and prostate cancer. A finding of viral positivity changed the treatment plan in only 8% of all infected patients, however.
“Given that most HIV-infected patients in our study knew their viral status, the yield of universal HIV testing among patients with newly diagnosed cancer may likely be low. Although age-directed screening is recommended for HIV and HCV, uptake rates in primary care are variable and low overall,” Dr. Ramsey and his colleagues wrote.
The study was supported by grants from the National Cancer Institute. Dr. Ramsey and several co-authors reported receiving NCI grants, and multiple co-authors reported grants and/or consulting fees from various companies.
SOURCE: Ramsey SD et al. JAMA Oncol. 2019 Jan 17. doi: 10.1001/jamaoncol.2018.6437.
Oncologists should consider testing all patients with newly diagnosed cancers for infection with the hepatitis B and C viruses, a multicenter team has recommended.
A prospective study of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infections among 3,051 patients with newly diagnosed cancers showed that 6.5% of patients tested positive for previous HBV and 0.6% had chronic HBV infection. In addition, 2.4% of patients were positive for HCV, and 1.1% for HIV infections, reported Scott D. Ramsey, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.
“Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient. Thus, we believe our results warrant consideration of universal testing of patients with newly diagnosed cancer for HBV and HCV infection, particularly if such an approach is shown to be cost effective,” they wrote in JAMA Oncology.
The investigators noted that patients with undiagnosed hepatitis and/or HIV infections could transmit them to unsuspecting caregivers, adding that “with effective treatments available, not screening for these viruses misses an opportunity to reduce future morbidity associated with these infections and to avoid viral reactivation during treatment, with resulting morbidity and mortality.”
To estimate the prevalence of the infections in patients with newly diagnosed cancers, investigators looked at a cohort of 3,051 patients with a cancer diagnosis made within the previous 120 days at nine academic medical centers and nine community oncology centers representing a total of 41 cancer clinics affiliated with the SWOG Cancer Research Network (formerly the Southwest Oncology Group).
The median patient age was 60.6 years. Female patients constitute 60.4% of the sample; 18.1% were black, and 18.3% were of Hispanic heritage.
Of 3,050 patients for whom HBV testing results were available, 6.5% (197) were positive for previous HBV infection, compared with an estimated U.S. population prevalence of 4.7%. In addition, 0.6% (19 patients) were found to have chronic HBV, compared with an estimated 0.3% US population prevalence.
HCV infections were detected in 2.4% (71 of 2990 patients), compared with an estimated population prevalence of 1.3%, and HIV infections were detected in 1.1%, compared with a background estimated population prevalence of 0.3%.
In all, 32 patients were diagnosed with viral infections by testing performed for the study, including 8 patients with chronic HBV, 22 with HCV, and 2 with HIV.
Additionally, the authors found that 4 patients with chronic HBV, 23 with HCV, and 7 with HIV had no identifiable risk factors.
The highest prevalence of infections occurred among patients with liver cancer, nonliver and noncolorectal cancers of the gastrointestinal tract, head and neck cancers, lung cancers, and prostate cancer. A finding of viral positivity changed the treatment plan in only 8% of all infected patients, however.
“Given that most HIV-infected patients in our study knew their viral status, the yield of universal HIV testing among patients with newly diagnosed cancer may likely be low. Although age-directed screening is recommended for HIV and HCV, uptake rates in primary care are variable and low overall,” Dr. Ramsey and his colleagues wrote.
The study was supported by grants from the National Cancer Institute. Dr. Ramsey and several co-authors reported receiving NCI grants, and multiple co-authors reported grants and/or consulting fees from various companies.
SOURCE: Ramsey SD et al. JAMA Oncol. 2019 Jan 17. doi: 10.1001/jamaoncol.2018.6437.
FROM JAMA ONCOLOGY
Key clinical point: Patients with newly diagnosed cancers should be screened for viral infections that may pose a transmission risk or could be reactivated by cancer therapies.
Major finding: Infection rates of HBV, HCV, and HIV in patients with newly diagnosed cancers were 6.5%, 2.4%, and 1.1%, respectively.
Study details: Prospective study of viral infections in 3,051 patients with a diagnosis of cancer within the previous 120 days.
Disclosures: The study was supported by grants from the National Cancer Institute. Dr. Ramsey and several coauthors reported receiving NCI grants, and multiple coauthors reported grants and/or consulting fees from various companies.
Source: Ramsey SD et al. JAMA Oncology. 2019 Jan 17. doi: 10.1001/jamaoncol.2018.6437.
Host stress response may be a factor in early-stage HCV clearance
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
FROM VIRUS RESEARCH