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Rare mixed HCV genotypes found in men who have sex with men
A low percentage of mixed genotypes of hepatitis C virus (HCV) was found in a small study of recently infected HIV+ and HIV– men who have sex with men (MSM) according to a report by Thuy Nguyen, PhD, of the University of North Carolina, Chapel Hill, and colleagues published in the International Journal of Antimicrobial Agents.
The researchers assessed 58 HCV-infected individuals with a median age of 38.5 years, 50 of whom were HIV positive and 18 of whom were HIV negative. Most of the patients were MSM (85.3%), with the rest of unknown sexual orientation. HCV genotyping by Sanger found types GT1a, GT4d, GT3a, and GT2k infection in 47.1%, 41.2%, 8.8%, and 2.9% of the individuals.
After eliminating suspected contaminations, three patients (4.4%) were found with mixed GT infections All three patients were infected with HCV for the first time; two-thirds were coinfected with HIV. The mixed GTs comprised only GT4d and GT1a at different ratios. Mixed infections are potentially problematic when using direct-acting antiviral therapy without broad-spectrum activity, according to the researchers. In this case, however, all HCV patients achieved treatment success.
“From a public health perspective, the MSM population engaging in high-risk behaviors still requires special attention in terms of mixed infections compared with the general HCV-infected population with a regular monitoring of anti-HCV treatment response, particularly when pangenotypic treatment is not used,” the researchers concluded.
The study was funded by the French government; the authors reported having no conflicts.
SOURCE: Nguyen T et al. Int J Antimicrobial Agents. 2019. 54[4]:523-7.
A low percentage of mixed genotypes of hepatitis C virus (HCV) was found in a small study of recently infected HIV+ and HIV– men who have sex with men (MSM) according to a report by Thuy Nguyen, PhD, of the University of North Carolina, Chapel Hill, and colleagues published in the International Journal of Antimicrobial Agents.
The researchers assessed 58 HCV-infected individuals with a median age of 38.5 years, 50 of whom were HIV positive and 18 of whom were HIV negative. Most of the patients were MSM (85.3%), with the rest of unknown sexual orientation. HCV genotyping by Sanger found types GT1a, GT4d, GT3a, and GT2k infection in 47.1%, 41.2%, 8.8%, and 2.9% of the individuals.
After eliminating suspected contaminations, three patients (4.4%) were found with mixed GT infections All three patients were infected with HCV for the first time; two-thirds were coinfected with HIV. The mixed GTs comprised only GT4d and GT1a at different ratios. Mixed infections are potentially problematic when using direct-acting antiviral therapy without broad-spectrum activity, according to the researchers. In this case, however, all HCV patients achieved treatment success.
“From a public health perspective, the MSM population engaging in high-risk behaviors still requires special attention in terms of mixed infections compared with the general HCV-infected population with a regular monitoring of anti-HCV treatment response, particularly when pangenotypic treatment is not used,” the researchers concluded.
The study was funded by the French government; the authors reported having no conflicts.
SOURCE: Nguyen T et al. Int J Antimicrobial Agents. 2019. 54[4]:523-7.
A low percentage of mixed genotypes of hepatitis C virus (HCV) was found in a small study of recently infected HIV+ and HIV– men who have sex with men (MSM) according to a report by Thuy Nguyen, PhD, of the University of North Carolina, Chapel Hill, and colleagues published in the International Journal of Antimicrobial Agents.
The researchers assessed 58 HCV-infected individuals with a median age of 38.5 years, 50 of whom were HIV positive and 18 of whom were HIV negative. Most of the patients were MSM (85.3%), with the rest of unknown sexual orientation. HCV genotyping by Sanger found types GT1a, GT4d, GT3a, and GT2k infection in 47.1%, 41.2%, 8.8%, and 2.9% of the individuals.
After eliminating suspected contaminations, three patients (4.4%) were found with mixed GT infections All three patients were infected with HCV for the first time; two-thirds were coinfected with HIV. The mixed GTs comprised only GT4d and GT1a at different ratios. Mixed infections are potentially problematic when using direct-acting antiviral therapy without broad-spectrum activity, according to the researchers. In this case, however, all HCV patients achieved treatment success.
“From a public health perspective, the MSM population engaging in high-risk behaviors still requires special attention in terms of mixed infections compared with the general HCV-infected population with a regular monitoring of anti-HCV treatment response, particularly when pangenotypic treatment is not used,” the researchers concluded.
The study was funded by the French government; the authors reported having no conflicts.
SOURCE: Nguyen T et al. Int J Antimicrobial Agents. 2019. 54[4]:523-7.
FROM THE INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Nivolumab boosts overall survival in HCC
BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.
Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.
The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.
The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.
At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.
Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.
Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.
“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”
He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.
Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).
She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.
“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.
She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.
Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.
“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.
CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.
SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.
Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.
The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.
The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.
At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.
Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.
Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.
“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”
He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.
Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).
She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.
“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.
She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.
Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.
“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.
CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.
SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.
Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.
The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.
The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.
At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.
Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.
Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.
“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”
He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.
Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).
She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.
“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.
She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.
Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.
“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.
CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.
SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
REPORTING FROM ESMO 2019
HCV+ kidney transplants: Similar outcomes to HCV- regardless of recipient serostatus
Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.
A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.
During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.
HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m2 (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.
Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.
“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.
“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.
This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.
SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.
Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.
A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.
During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.
HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m2 (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.
Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.
“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.
“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.
This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.
SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.
Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.
A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.
During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.
HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m2 (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.
Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.
“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.
“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.
This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.
SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.
FROM JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Direct-acting antiviral therapy boosts survival for infected HCC patients
Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.
Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.
In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”
A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.
A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).
The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.
The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.
The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.
SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.
Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.
Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.
In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”
A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.
A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).
The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.
The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.
The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.
SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.
Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.
Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.
In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”
A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.
A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).
The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.
The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.
The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.
SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.
FROM GASTROENTEROLOGY
Patients with viral hepatitis are living longer, increasing risk of extrahepatic mortality
Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.
Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.
This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.
While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.
“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.
“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”
The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).
Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.
“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”
In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.
Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.
For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).
Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”
The investigators reported no external funding or conflicts of interest.
SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.
Chronic liver disease is one of the leading causes of death in the United States. Whereas mortality from other causes (e.g., heart disease and cancer) has declined, age-adjusted mortality from chronic liver disease has continued to increase. There have been a few major advances in the treatment of several chronic liver diseases in recent years. These include nucleos(t)ide analogues for hepatitis B virus (HBV) and direct-acting antiviral agents for the treatment of hepatitis C virus infection (HCV). Many studies show that these treatments are highly effective in improving patient outcomes, including patient survival. However, whether these individual-level benefits have translated into population-level improvements remains unclear.
Overall, the results were mixed; they were encouraging for viral hepatitis but concerning for alcoholic and nonalcoholic liver disease. Specifically, all-cause mortality from HCV was on an upward trajectory in the first 7 years (from 2007 to 2014) but the trend shifted from 2014 onward. Importantly, this inflection point coincided with the timing of the new HCV treatments. Most of this positive shift post 2014 was related to a strong downward trend in liver-related mortality. In contrast, upward trends in mortality related to extrahepatic causes (such as cardiovascular mortality) continued unabated. The authors found similar results for HBV. The story, however, was different for alcohol and nonalcohol-related liver disease – both conditions lacking effective treatments; liver-related mortality for both continued to increase during the study period.
Although we cannot make causal inferences from this study, overall, the results are good news. They suggest that HBV and HCV treatments have reached enough infected people to result in tangible improvements in the burden of chronic liver disease. We may now need to shift the focus of secondary prevention efforts from liver to nonliver (extrahepatic) morbidity in the newer cohorts of patients with treated HCV and HBV.
Fasiha Kanwal, MD, MSHS, is an investigator in the clinical epidemiology and comparative effectiveness program for the Center for Innovations in Quality, Effectiveness, and Safety in collaboration with the Michael E. DeBakey VA Medical Center, as well as an associate professor of medicine in gastroenterology and hepatology at Baylor College of Medicine in Houston. She has no conflicts of interest.
Chronic liver disease is one of the leading causes of death in the United States. Whereas mortality from other causes (e.g., heart disease and cancer) has declined, age-adjusted mortality from chronic liver disease has continued to increase. There have been a few major advances in the treatment of several chronic liver diseases in recent years. These include nucleos(t)ide analogues for hepatitis B virus (HBV) and direct-acting antiviral agents for the treatment of hepatitis C virus infection (HCV). Many studies show that these treatments are highly effective in improving patient outcomes, including patient survival. However, whether these individual-level benefits have translated into population-level improvements remains unclear.
Overall, the results were mixed; they were encouraging for viral hepatitis but concerning for alcoholic and nonalcoholic liver disease. Specifically, all-cause mortality from HCV was on an upward trajectory in the first 7 years (from 2007 to 2014) but the trend shifted from 2014 onward. Importantly, this inflection point coincided with the timing of the new HCV treatments. Most of this positive shift post 2014 was related to a strong downward trend in liver-related mortality. In contrast, upward trends in mortality related to extrahepatic causes (such as cardiovascular mortality) continued unabated. The authors found similar results for HBV. The story, however, was different for alcohol and nonalcohol-related liver disease – both conditions lacking effective treatments; liver-related mortality for both continued to increase during the study period.
Although we cannot make causal inferences from this study, overall, the results are good news. They suggest that HBV and HCV treatments have reached enough infected people to result in tangible improvements in the burden of chronic liver disease. We may now need to shift the focus of secondary prevention efforts from liver to nonliver (extrahepatic) morbidity in the newer cohorts of patients with treated HCV and HBV.
Fasiha Kanwal, MD, MSHS, is an investigator in the clinical epidemiology and comparative effectiveness program for the Center for Innovations in Quality, Effectiveness, and Safety in collaboration with the Michael E. DeBakey VA Medical Center, as well as an associate professor of medicine in gastroenterology and hepatology at Baylor College of Medicine in Houston. She has no conflicts of interest.
Chronic liver disease is one of the leading causes of death in the United States. Whereas mortality from other causes (e.g., heart disease and cancer) has declined, age-adjusted mortality from chronic liver disease has continued to increase. There have been a few major advances in the treatment of several chronic liver diseases in recent years. These include nucleos(t)ide analogues for hepatitis B virus (HBV) and direct-acting antiviral agents for the treatment of hepatitis C virus infection (HCV). Many studies show that these treatments are highly effective in improving patient outcomes, including patient survival. However, whether these individual-level benefits have translated into population-level improvements remains unclear.
Overall, the results were mixed; they were encouraging for viral hepatitis but concerning for alcoholic and nonalcoholic liver disease. Specifically, all-cause mortality from HCV was on an upward trajectory in the first 7 years (from 2007 to 2014) but the trend shifted from 2014 onward. Importantly, this inflection point coincided with the timing of the new HCV treatments. Most of this positive shift post 2014 was related to a strong downward trend in liver-related mortality. In contrast, upward trends in mortality related to extrahepatic causes (such as cardiovascular mortality) continued unabated. The authors found similar results for HBV. The story, however, was different for alcohol and nonalcohol-related liver disease – both conditions lacking effective treatments; liver-related mortality for both continued to increase during the study period.
Although we cannot make causal inferences from this study, overall, the results are good news. They suggest that HBV and HCV treatments have reached enough infected people to result in tangible improvements in the burden of chronic liver disease. We may now need to shift the focus of secondary prevention efforts from liver to nonliver (extrahepatic) morbidity in the newer cohorts of patients with treated HCV and HBV.
Fasiha Kanwal, MD, MSHS, is an investigator in the clinical epidemiology and comparative effectiveness program for the Center for Innovations in Quality, Effectiveness, and Safety in collaboration with the Michael E. DeBakey VA Medical Center, as well as an associate professor of medicine in gastroenterology and hepatology at Baylor College of Medicine in Houston. She has no conflicts of interest.
Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.
Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.
This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.
While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.
“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.
“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”
The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).
Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.
“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”
In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.
Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.
For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).
Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”
The investigators reported no external funding or conflicts of interest.
SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.
Patients with viral hepatitis may live longer after treatment with direct-acting antiviral agents (DAAs), but their risk of extrahepatic causes of death may rise as a result, according to investigators.
Importantly, this increasing rate of extrahepatic mortality shouldn’t be seen as a causal link with DAA use, cautioned lead author Donghee Kim, MD, PhD, of Stanford (Calif.) University, and colleagues. Instead, the upward trend is more likely because of successful treatment with DAAs, which can increase lifespan, and with it, time for susceptibility to extrahepatic conditions.
This was just one finding from a retrospective study that used U.S. Census and National Center for Health Statistics mortality records to evaluate almost 28 million deaths that occurred between 2007 and 2017. The investigators looked for mortality trends among patients with common chronic liver diseases, including viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD), noting that each of these conditions is associated with extrahepatic complications. The study included deaths due to extrahepatic cancer, cardiovascular disease, and diabetes.
While the efficacy of therapy for viral hepatitis has improved markedly since 2014, treatments for ALD and NAFLD have remained static, the investigators noted.
“Unfortunately, there have been no significant breakthroughs in the treatment of [ALD] over the last 2 decades, resulting in an increase in estimated global mortality to 3.8%,” the investigators wrote in Gastroenterology.
“[NAFLD] is the most common chronic liver disease in the world,” they added. “The leading cause of death in individuals with NAFLD is cardiovascular disease, followed by extrahepatic malignancies, and then liver-related mortality. However, recent trends in ALD and NAFLD-related extrahepatic complications in comparison to viral hepatitis have not been studied.”
The results of the current study supported the positive impact of DAAs, which began to see widespread use in 2014. Age-standardized mortality among patients with hepatitis C virus rose until 2014 (2.2% per year) and dropped thereafter (–6.5% per year). Mortality among those with hepatitis B virus steadily decreased over the study period (–1.2% per year).
Of note, while deaths because of HCV-related liver disease dropped from 2014 to 2017, extrahepatic causes of death didn’t follow suit. Age-standardized mortality for cardiovascular disease and diabetes increased at average annual rates of 1.9% and 3.3%, respectively, while the rate of extrahepatic cancer-related deaths held steady.
“The widespread use, higher efficacy and durable response to DAA agents in individuals with HCV infection may have resulted in a paradigm shift in the clinical progression of coexisting disease entities following response to DAA agents in the virus-free environment,” the investigators wrote. “These findings suggest assessment and identification of risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals who have been successfully treated and cured of HCV infection.”
In sharp contrast with the viral hepatitis findings, mortality rates among patients with ALD and NAFLD increased at an accelerating rate over the 11-year study period.
Among patients with ALD, all-cause mortality increased by an average of 3.4% per year, at a higher rate in the second half of the study than the first (4.6% vs 2.1%). Liver disease–related mortality rose at a similar, accelerating rate. In the same group, deaths due to cardiovascular disease increased at an average annual rate of 2.1%, which was accelerating, while extrahepatic cancer-related deaths increased at a more constant rate of 3.6%.
For patients with NAFLD, all-cause mortality increased by 8.1% per year, accelerating from 6.1% in the first half of the study to 11.2% in the second. Deaths from liver disease increased at an average rate of 12.6% per year, while extrahepatic deaths increased significantly for all three included types: cardiovascular disease (2.0%), extrahepatic cancer (15.1%), and diabetes (9.7%).
Concerning the worsening rates of mortality among patients with ALD and NAFLD, the investigators cited a lack of progress in treatments, and suggested that “the quest for newer therapies must remain the cornerstone in our efforts.”
The investigators reported no external funding or conflicts of interest.
SOURCE: Kim D et al. Gastroenterology. 2019 Jun 25. doi: 10.1053/j.gastro.2019.06.026.
FROM GASTROENTEROLOGY
Some HCV medications associated with serious liver injury
Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.
In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.
Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.
The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.
Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.
In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.
Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.
The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.
Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.
In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.
Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.
The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.
USPSTF issues draft recommendation statement for HCV screening in adults
and now suggests that all adults aged 18-79 years receive screening.
This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).
“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.
To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.
Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.
Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.
Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.
The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.
and now suggests that all adults aged 18-79 years receive screening.
This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).
“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.
To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.
Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.
Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.
Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.
The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.
and now suggests that all adults aged 18-79 years receive screening.
This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).
“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.
To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.
Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.
Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.
Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.
The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.
HCV coinfection adds to cardiovascular risk in HIV-infected patients
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
Hepatitis C virus (HCV) coinfection, as well as an accumulation of viral and bacterial infections, was independently associated with the risk of developing a cardiovascular event in HIV-infected patients, according to the results of a large retrospective analysis.
The study comprised 823 patients at a single institution during 1982-2018. The researchers assessed those patients who had at least two visits to the HIV clinic, data concerning herpes varicella zoster virus (VZV) reactivation, and bacterial infections. Data on HCV coinfection status (as determined by HCV antibodies and qualitative HCV-PCR) were also available, according to Miguel Genebat, MD, of Virgen del Rocío University Hospital, Seville, Spain, and colleagues.
During the observational period, 58 patients (7%) experienced a cardiovascular event at a median age of 47 years. Most of these patients (50, 86%) had effective HIV treatment, with their viral load being persistently undetectable.
In terms of standard cardiovascular disease (CVD) risk factors, hypercholesterolemia was present in 31 patients (53%) and only 11 subjects (19%) had diabetes. This left 24 “low-risk” subjects, 5 of whom (21%) developed recurrent CVD and 8 of whom (33%) died after the development of cardiovascular disease.
The most frequent cardiovascular event was acute coronary syndrome (ACS), developed by 38 patients, with 14 (24%) of these individuals having recurrent CVD events. Among the 58 patients who experienced a cardiovascular event, 21 (36%) died, 17 from cardiovascular disease, 2 from cancer, and 2 each from acute bacterial infection and end-stage liver disease.
The researchers examined other variables potentially associated with the development of cardiovascular disease. They performed a multivariate analysis considering the added burden of infections and found that advanced age at HIV-1 diagnosis (OR, 1.07), a T-CD4 nadir of less than 200 cells/mcL (OR, 2.01), a diagnosis of HIV prior to combined antiretroviral therapy availability in 1996 (OR, 2.35), and cumulative infections greater than 2 (OR, 3.63), were all significantly and independently associated with the risk of developing a cardiovascular event.
They also found that HCV coinfection (OR, 2.84) on its own in simple multivariate analysis increased the risk of developing a CVD event in HIV-infected subjects. There was insufficient power to tease out the individual risk of other infections, such as herpes zoster virus and bacterial infections, hence the use of cumulative infections reported above.
The researchers concluded that potential strategies to minimize cardiovascular risk in these subjects could be treating HCV coinfection in all subjects independently of liver fibrosis stage, starting cART as soon as possible, and immunizing for those infections for which effective vaccine are available.
The authors reported that they had no conflicts of interest.
SOURCE: Genebat M. et al. Antiviral Res. 2019 Sep;169:104527.
FROM ANTIVIRAL RESEARCH
Statins hamper hepatocellular carcinoma in viral hepatitis patients
Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.
The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.
In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.
They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).
The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.
In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).
In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).
“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.
The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.
However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.
Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.
The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.
In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.
They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).
The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.
In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).
In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).
“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.
The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.
However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.
Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.
The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.
In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.
They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).
The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.
In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).
In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).
“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.
The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.
However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.
Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
FROM THE ANNALS OF INTERNAL MEDICINE
Key clinical point: Use of lipophilic statins significantly reduced incidence and mortality of hepatocellular cancer in adults with viral hepatitis.
Major finding: The 10-year risk of HCC was 8.1% among patients taking lipophilic statins, compared with 3.3% among those not on statins.
Study details: The data come from a population-based cohort study of 16,668 adult with viral hepatitis from a national registry in Sweden.
Disclosures: Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and MSD.
Source: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.
HCV-infected people who inject drugs also have substantial alcohol use
Curing hepatitis C virus (HCV) infection without addressing the high rate of alcohol use disorder in many patients may undermine the benefits of treatment to long-term liver health, according to the results of a large cohort study.
Because excess alcohol use is known to accelerate liver disease progression, researchers Risha Irvin, MD, and her colleagues from Johns Hopkins University, Baltimore, examined the prevalence of alcohol use in HCV-infected people who inject drugs (PWID). Their study examined the prevalence and associated correlates of alcohol use (Addictive Behaviors 2019;96:56-61).
They followed a large cohort of 1,623 HCV-antibody positive PWID from 2005 to 2013 from the AIDS Linked to the Intravenous Experience (ALIVE) study. They characterized alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Multivariable logistic regression with generalized estimated equations was used to examine sociodemographic, clinical, and substance use correlates of alcohol use.
At baseline, the median age was 47 years, 67% were men, 81% were black, and 34% were HIV positive. The majority (60%) reported injection drug use in the prior 6 months, while 46% reported noninjection cocaine or heroin, 31% reported street-acquired prescription drugs, and 22% reported marijuana use in the same time period. According to the AUDIT-C results, 41% of the patients reported no alcohol use, 21% reported moderate alcohol use, and 38% reported heavy alcohol use at their baseline visit.
The factors that were significantly associated with heavy alcohol use included male sex, black race, income of $5,000 or less, a Center for Epidemiologic Studies Depression Scale (range 0-60) score of 23 or greater, being homeless, being incarcerated, marijuana use, use of street-acquired prescription drugs, noninjection cocaine/heroin, injection drug use, and cigarette smoking. In a model that included the composite summary variable for substance use intensity, one drug type (adjusted odds ratio, 1.92), two drug types (AOR, 2.93), and three drug types (AOR, 3.65) were significantly associated with heavy alcohol use.
“While clinicians are undoubtedly concerned about any level of alcohol use in the setting of HCV infection due to the acceleration of liver fibrosis, there is particular concern for individuals with heavy alcohol use and their increased risk for cirrhosis and liver failure even after HCV cure. Without intervention, alcohol use will persist after HCV is cured with the potential to undermine the benefit of HCV cure. Therefore, our data point to the need to invest in and develop programs that effectively address alcohol use and co-occurring substance use in this population of PWID with HCV,” the researchers concluded.
The study was supported by the U.S. National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, and the National Institute on Alcohol Abuse and Alcoholism. The authors declared that they had no conflicts.
SOURCE: Irvin R et al. Addictive Behaviors. 2019;96:56-61.
Curing hepatitis C virus (HCV) infection without addressing the high rate of alcohol use disorder in many patients may undermine the benefits of treatment to long-term liver health, according to the results of a large cohort study.
Because excess alcohol use is known to accelerate liver disease progression, researchers Risha Irvin, MD, and her colleagues from Johns Hopkins University, Baltimore, examined the prevalence of alcohol use in HCV-infected people who inject drugs (PWID). Their study examined the prevalence and associated correlates of alcohol use (Addictive Behaviors 2019;96:56-61).
They followed a large cohort of 1,623 HCV-antibody positive PWID from 2005 to 2013 from the AIDS Linked to the Intravenous Experience (ALIVE) study. They characterized alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Multivariable logistic regression with generalized estimated equations was used to examine sociodemographic, clinical, and substance use correlates of alcohol use.
At baseline, the median age was 47 years, 67% were men, 81% were black, and 34% were HIV positive. The majority (60%) reported injection drug use in the prior 6 months, while 46% reported noninjection cocaine or heroin, 31% reported street-acquired prescription drugs, and 22% reported marijuana use in the same time period. According to the AUDIT-C results, 41% of the patients reported no alcohol use, 21% reported moderate alcohol use, and 38% reported heavy alcohol use at their baseline visit.
The factors that were significantly associated with heavy alcohol use included male sex, black race, income of $5,000 or less, a Center for Epidemiologic Studies Depression Scale (range 0-60) score of 23 or greater, being homeless, being incarcerated, marijuana use, use of street-acquired prescription drugs, noninjection cocaine/heroin, injection drug use, and cigarette smoking. In a model that included the composite summary variable for substance use intensity, one drug type (adjusted odds ratio, 1.92), two drug types (AOR, 2.93), and three drug types (AOR, 3.65) were significantly associated with heavy alcohol use.
“While clinicians are undoubtedly concerned about any level of alcohol use in the setting of HCV infection due to the acceleration of liver fibrosis, there is particular concern for individuals with heavy alcohol use and their increased risk for cirrhosis and liver failure even after HCV cure. Without intervention, alcohol use will persist after HCV is cured with the potential to undermine the benefit of HCV cure. Therefore, our data point to the need to invest in and develop programs that effectively address alcohol use and co-occurring substance use in this population of PWID with HCV,” the researchers concluded.
The study was supported by the U.S. National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, and the National Institute on Alcohol Abuse and Alcoholism. The authors declared that they had no conflicts.
SOURCE: Irvin R et al. Addictive Behaviors. 2019;96:56-61.
Curing hepatitis C virus (HCV) infection without addressing the high rate of alcohol use disorder in many patients may undermine the benefits of treatment to long-term liver health, according to the results of a large cohort study.
Because excess alcohol use is known to accelerate liver disease progression, researchers Risha Irvin, MD, and her colleagues from Johns Hopkins University, Baltimore, examined the prevalence of alcohol use in HCV-infected people who inject drugs (PWID). Their study examined the prevalence and associated correlates of alcohol use (Addictive Behaviors 2019;96:56-61).
They followed a large cohort of 1,623 HCV-antibody positive PWID from 2005 to 2013 from the AIDS Linked to the Intravenous Experience (ALIVE) study. They characterized alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Multivariable logistic regression with generalized estimated equations was used to examine sociodemographic, clinical, and substance use correlates of alcohol use.
At baseline, the median age was 47 years, 67% were men, 81% were black, and 34% were HIV positive. The majority (60%) reported injection drug use in the prior 6 months, while 46% reported noninjection cocaine or heroin, 31% reported street-acquired prescription drugs, and 22% reported marijuana use in the same time period. According to the AUDIT-C results, 41% of the patients reported no alcohol use, 21% reported moderate alcohol use, and 38% reported heavy alcohol use at their baseline visit.
The factors that were significantly associated with heavy alcohol use included male sex, black race, income of $5,000 or less, a Center for Epidemiologic Studies Depression Scale (range 0-60) score of 23 or greater, being homeless, being incarcerated, marijuana use, use of street-acquired prescription drugs, noninjection cocaine/heroin, injection drug use, and cigarette smoking. In a model that included the composite summary variable for substance use intensity, one drug type (adjusted odds ratio, 1.92), two drug types (AOR, 2.93), and three drug types (AOR, 3.65) were significantly associated with heavy alcohol use.
“While clinicians are undoubtedly concerned about any level of alcohol use in the setting of HCV infection due to the acceleration of liver fibrosis, there is particular concern for individuals with heavy alcohol use and their increased risk for cirrhosis and liver failure even after HCV cure. Without intervention, alcohol use will persist after HCV is cured with the potential to undermine the benefit of HCV cure. Therefore, our data point to the need to invest in and develop programs that effectively address alcohol use and co-occurring substance use in this population of PWID with HCV,” the researchers concluded.
The study was supported by the U.S. National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, and the National Institute on Alcohol Abuse and Alcoholism. The authors declared that they had no conflicts.
SOURCE: Irvin R et al. Addictive Behaviors. 2019;96:56-61.
FROM ADDICTIVE BEHAVIORS