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Thyroid disease does not affect primary biliary cholangitis complications
While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.
“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).
Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.
“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”
No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.
While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.
“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).
Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.
“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”
No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.
While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.
“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).
Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.
“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”
No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.
Key clinical point:
Major finding: 150 of 921 PBC patients had TD (16.3%), but there was no correlation between PBC patients who had TD and their histologic stage either at diagnosis, hepatic decompensation events, occurrence of hepatocelluler carcinoma, or liver transplantation rates.
Data source: Prospective study of 921 PBC patients in Padua and Barcelona from 1975 to 2015.
Disclosures: No funding source was disclosed; authors reported no relevant financial disclosures.
Fragmented readmission after liver transplant linked to adverse outcomes
CORONADO, CALIF. – Postdischarge surgical care fragmentation significantly increases the risk of both 30-day mortality and subsequent readmission in the first year following orthotopic liver transplantation, results from a study of national data showed.
“In an era of regionalization and centers of excellence, the likelihood for postdischarge fragmentation, defined as readmission to any hospital other than the hospital at which the surgery was performed, is an increasing reality,” Anai N. Kothari, MD, said at the annual meeting of the Western Surgical Association. “In many different surgical subspecialties – major vascular operations, bariatric surgery, oncologic resections – it’s known to be a risk factor for adverse events and poor quality. Postdischarge fragmentation is common, [and related to] as often as one in four readmissions. It increases the risk for short- and long-term morbidity and mortality, decreases survival, and increases cost.”
Dr. Kothari reported results from 2,996 patients with 7,485 readmission encounters at 299 hospitals. Of the 7,485 readmissions, 6,249 (83.5%) were nonfragmented, and 1,236 (16.5%) were fragmented. The mean age of patients was 55 years. There were no significant differences in baseline characteristics between patients with nonfragmented and fragmented admissions in terms of patient age, sex, preoperative and postoperative length of stay, Charlson comorbidity index, and comorbidities, with the exception of renal failure, which was more common among patients in the fragmented admission group.
Compared with the patients in the nonfragmented admission group, those in the fragmented admission group had a greater number of average readmissions per patient (3.3 vs. 2.5, respectively; P less than .0001) and a greater number of average days to readmission (168 vs. 105; P less than .0001). Reasons for readmission differed among the two groups. Patients readmitted to the index transplant center were more likely to have a biliary, hematologic, or neurologic complication, while those in the fragmented admissions group were more likely to be readmitted for things like electrolyte disturbances, respiratory issues, gastrointestinal issues, or hematologic-related issues. There was no difference in overall cost of care between the two groups (an average of $11,621.68 vs. $11.585.39, respectively).
After the investigators adjusted for age, sex, reason for readmission, cost of the index liver transplant, readmission length of stay, number of previous readmissions, and time from transplant, postdischarge fragmentation increased the odds of both 30-day mortality (OR, 1.75) and 30-day readmission (OR, 2.14). “It looks like just having a fragmented readmission is an independent predictor for an adverse event,” Dr. Kothari said.
Significant predictors of adverse events following a fragmented readmission included an increased number of previous readmissions (OR, 1.07) and readmission within 90 days of orthotopic liver transplant (OR, 2.19). “These two factors may be important for guiding providers to say, ‘If you have these things, this patient should likely come back to their index transplant center,’” Dr. Kothari said.
He reported having no relevant financial disclosures.
CORONADO, CALIF. – Postdischarge surgical care fragmentation significantly increases the risk of both 30-day mortality and subsequent readmission in the first year following orthotopic liver transplantation, results from a study of national data showed.
“In an era of regionalization and centers of excellence, the likelihood for postdischarge fragmentation, defined as readmission to any hospital other than the hospital at which the surgery was performed, is an increasing reality,” Anai N. Kothari, MD, said at the annual meeting of the Western Surgical Association. “In many different surgical subspecialties – major vascular operations, bariatric surgery, oncologic resections – it’s known to be a risk factor for adverse events and poor quality. Postdischarge fragmentation is common, [and related to] as often as one in four readmissions. It increases the risk for short- and long-term morbidity and mortality, decreases survival, and increases cost.”
Dr. Kothari reported results from 2,996 patients with 7,485 readmission encounters at 299 hospitals. Of the 7,485 readmissions, 6,249 (83.5%) were nonfragmented, and 1,236 (16.5%) were fragmented. The mean age of patients was 55 years. There were no significant differences in baseline characteristics between patients with nonfragmented and fragmented admissions in terms of patient age, sex, preoperative and postoperative length of stay, Charlson comorbidity index, and comorbidities, with the exception of renal failure, which was more common among patients in the fragmented admission group.
Compared with the patients in the nonfragmented admission group, those in the fragmented admission group had a greater number of average readmissions per patient (3.3 vs. 2.5, respectively; P less than .0001) and a greater number of average days to readmission (168 vs. 105; P less than .0001). Reasons for readmission differed among the two groups. Patients readmitted to the index transplant center were more likely to have a biliary, hematologic, or neurologic complication, while those in the fragmented admissions group were more likely to be readmitted for things like electrolyte disturbances, respiratory issues, gastrointestinal issues, or hematologic-related issues. There was no difference in overall cost of care between the two groups (an average of $11,621.68 vs. $11.585.39, respectively).
After the investigators adjusted for age, sex, reason for readmission, cost of the index liver transplant, readmission length of stay, number of previous readmissions, and time from transplant, postdischarge fragmentation increased the odds of both 30-day mortality (OR, 1.75) and 30-day readmission (OR, 2.14). “It looks like just having a fragmented readmission is an independent predictor for an adverse event,” Dr. Kothari said.
Significant predictors of adverse events following a fragmented readmission included an increased number of previous readmissions (OR, 1.07) and readmission within 90 days of orthotopic liver transplant (OR, 2.19). “These two factors may be important for guiding providers to say, ‘If you have these things, this patient should likely come back to their index transplant center,’” Dr. Kothari said.
He reported having no relevant financial disclosures.
CORONADO, CALIF. – Postdischarge surgical care fragmentation significantly increases the risk of both 30-day mortality and subsequent readmission in the first year following orthotopic liver transplantation, results from a study of national data showed.
“In an era of regionalization and centers of excellence, the likelihood for postdischarge fragmentation, defined as readmission to any hospital other than the hospital at which the surgery was performed, is an increasing reality,” Anai N. Kothari, MD, said at the annual meeting of the Western Surgical Association. “In many different surgical subspecialties – major vascular operations, bariatric surgery, oncologic resections – it’s known to be a risk factor for adverse events and poor quality. Postdischarge fragmentation is common, [and related to] as often as one in four readmissions. It increases the risk for short- and long-term morbidity and mortality, decreases survival, and increases cost.”
Dr. Kothari reported results from 2,996 patients with 7,485 readmission encounters at 299 hospitals. Of the 7,485 readmissions, 6,249 (83.5%) were nonfragmented, and 1,236 (16.5%) were fragmented. The mean age of patients was 55 years. There were no significant differences in baseline characteristics between patients with nonfragmented and fragmented admissions in terms of patient age, sex, preoperative and postoperative length of stay, Charlson comorbidity index, and comorbidities, with the exception of renal failure, which was more common among patients in the fragmented admission group.
Compared with the patients in the nonfragmented admission group, those in the fragmented admission group had a greater number of average readmissions per patient (3.3 vs. 2.5, respectively; P less than .0001) and a greater number of average days to readmission (168 vs. 105; P less than .0001). Reasons for readmission differed among the two groups. Patients readmitted to the index transplant center were more likely to have a biliary, hematologic, or neurologic complication, while those in the fragmented admissions group were more likely to be readmitted for things like electrolyte disturbances, respiratory issues, gastrointestinal issues, or hematologic-related issues. There was no difference in overall cost of care between the two groups (an average of $11,621.68 vs. $11.585.39, respectively).
After the investigators adjusted for age, sex, reason for readmission, cost of the index liver transplant, readmission length of stay, number of previous readmissions, and time from transplant, postdischarge fragmentation increased the odds of both 30-day mortality (OR, 1.75) and 30-day readmission (OR, 2.14). “It looks like just having a fragmented readmission is an independent predictor for an adverse event,” Dr. Kothari said.
Significant predictors of adverse events following a fragmented readmission included an increased number of previous readmissions (OR, 1.07) and readmission within 90 days of orthotopic liver transplant (OR, 2.19). “These two factors may be important for guiding providers to say, ‘If you have these things, this patient should likely come back to their index transplant center,’” Dr. Kothari said.
He reported having no relevant financial disclosures.
AT WSA 2016
Key clinical point:
Major finding: After investigators adjusted for numerous variables, postdischarge fragmentation following orthotopic liver transplantation increased the odds of both 30-day mortality (OR, 1.75) and 30-day readmission (OR, 2.14).
Data source: An analysis of data from the Healthcare Cost and Utilization Project State Inpatient Databases for Florida and California between 2006 and 2011 to identify 2,996 patients who underwent orthotopic liver transplantation.
Disclosures: Dr. Kothari reported having no relevant financial disclosures.
FDA approves tenofovir alafenamide for patients with chronic hepatitis B and liver disease
The Food and Drug Administration has approved tenofovir alafenamide (marketed as Vemlidy by Gilead Sciences) for the treatment of adults with chronic hepatitis B virus infection with compensated liver disease.
Tenofovir alafenamide is a novel, targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to tenofovir disoproxil fumarate (Viread) at significantly lower doses.
Compared with tenofovir disoproxil fumarate, tenofovir alafenamide has “greater plasma stability and more efficiently delivers tenofovir to hepatocytes” which allows tenofovir alafenamide to be administered in daily doses of 25mg while tenofovir disoproxil fumarate requires a dose of 300 mg to be as effective.
In addition, patients treated with tenofovir alafenamide demonstrated “improvements in certain bone and renal laboratory parameters.”
Overall, tenofovir alafenamide was well tolerated. Only 1% of patients discontinued treatment because of adverse events, and the most common adverse events were headache, abdominal pain, fatigue, cough, nausea, and back pain. Vemlidy has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis and severe acute exacerbation of hepatitis B with discontinuation.
“Vemlidy is the first medication approved to treat this disease in nearly a decade,” said President and Chief Executive Officer of Gilead Sciences John Milligan. “We are excited to offer a new, effective option to help advance long-term care for patients.”
[email protected]
On Twitter @jessnicolecraig
The Food and Drug Administration has approved tenofovir alafenamide (marketed as Vemlidy by Gilead Sciences) for the treatment of adults with chronic hepatitis B virus infection with compensated liver disease.
Tenofovir alafenamide is a novel, targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to tenofovir disoproxil fumarate (Viread) at significantly lower doses.
Compared with tenofovir disoproxil fumarate, tenofovir alafenamide has “greater plasma stability and more efficiently delivers tenofovir to hepatocytes” which allows tenofovir alafenamide to be administered in daily doses of 25mg while tenofovir disoproxil fumarate requires a dose of 300 mg to be as effective.
In addition, patients treated with tenofovir alafenamide demonstrated “improvements in certain bone and renal laboratory parameters.”
Overall, tenofovir alafenamide was well tolerated. Only 1% of patients discontinued treatment because of adverse events, and the most common adverse events were headache, abdominal pain, fatigue, cough, nausea, and back pain. Vemlidy has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis and severe acute exacerbation of hepatitis B with discontinuation.
“Vemlidy is the first medication approved to treat this disease in nearly a decade,” said President and Chief Executive Officer of Gilead Sciences John Milligan. “We are excited to offer a new, effective option to help advance long-term care for patients.”
[email protected]
On Twitter @jessnicolecraig
The Food and Drug Administration has approved tenofovir alafenamide (marketed as Vemlidy by Gilead Sciences) for the treatment of adults with chronic hepatitis B virus infection with compensated liver disease.
Tenofovir alafenamide is a novel, targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to tenofovir disoproxil fumarate (Viread) at significantly lower doses.
Compared with tenofovir disoproxil fumarate, tenofovir alafenamide has “greater plasma stability and more efficiently delivers tenofovir to hepatocytes” which allows tenofovir alafenamide to be administered in daily doses of 25mg while tenofovir disoproxil fumarate requires a dose of 300 mg to be as effective.
In addition, patients treated with tenofovir alafenamide demonstrated “improvements in certain bone and renal laboratory parameters.”
Overall, tenofovir alafenamide was well tolerated. Only 1% of patients discontinued treatment because of adverse events, and the most common adverse events were headache, abdominal pain, fatigue, cough, nausea, and back pain. Vemlidy has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis and severe acute exacerbation of hepatitis B with discontinuation.
“Vemlidy is the first medication approved to treat this disease in nearly a decade,” said President and Chief Executive Officer of Gilead Sciences John Milligan. “We are excited to offer a new, effective option to help advance long-term care for patients.”
[email protected]
On Twitter @jessnicolecraig
PBC patients show brain abnormalities before cirrhosis occurs
Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.
In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.
An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.
“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.
Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).
Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.
In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.
An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.
“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.
Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).
Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.
In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.
An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.
“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.
Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).
FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Interferon-free HCV treatment can lead to herpesvirus reactivation, experts say
Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.
Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.
In all, 2% of patients had herpesvirus reactivations a median of 8 weeks after starting an interferon-free DAA regimen. Seven patients had cirrhosis, three were liver transplant recipients, and all achieved a sustained viral response. Seven patients were receiving sofosbuvir with ledipasvir, either with or without ribavirin; two patients were receiving ombitasvir with paritaprevir and ritonavir plus dasabuvir, with or without ribavirin; and one patient was receiving sofosbuvir with simeprevir plus ribavirin. Median age was 67 years. Seven cases involved cutaneous herpes, two involved ocular herpes, and one was herpes labialis. Two patients developed postherpetic neuralgia requiring gabapentin or pregabalin therapy, and one developed keratouveitis that was treated with valacyclovir (1 g every 8 hours for 7 days). Two other patients also received valacyclovir, three received famciclovir, and the remaining four received acyclovir. When the study was published, one patient, a 68-year-old male with postherpetic neuralgia, had residual symptoms even after undergoing antiviral therapy and nerve ablation. This patient was a liver transplantee and therefore was immunosuppressed, but like the others, he only developed herpesvirus reactivation after starting DAA HCV treatment, the researcher said.
In contrast, there were no reactivations among historical controls during a median of 37 months of follow-up. “Even when a causal relationship is not definitive, based on the temporal association and recent experience we conclude that the incidence of herpesvirus reactivation may be increased among patients on interferon-free regimens,” the researchers concluded. “More research is necessary in this new field because unexpected events might be arising in patients treated with direct-acting antivirals.”
The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.
Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.
In all, 2% of patients had herpesvirus reactivations a median of 8 weeks after starting an interferon-free DAA regimen. Seven patients had cirrhosis, three were liver transplant recipients, and all achieved a sustained viral response. Seven patients were receiving sofosbuvir with ledipasvir, either with or without ribavirin; two patients were receiving ombitasvir with paritaprevir and ritonavir plus dasabuvir, with or without ribavirin; and one patient was receiving sofosbuvir with simeprevir plus ribavirin. Median age was 67 years. Seven cases involved cutaneous herpes, two involved ocular herpes, and one was herpes labialis. Two patients developed postherpetic neuralgia requiring gabapentin or pregabalin therapy, and one developed keratouveitis that was treated with valacyclovir (1 g every 8 hours for 7 days). Two other patients also received valacyclovir, three received famciclovir, and the remaining four received acyclovir. When the study was published, one patient, a 68-year-old male with postherpetic neuralgia, had residual symptoms even after undergoing antiviral therapy and nerve ablation. This patient was a liver transplantee and therefore was immunosuppressed, but like the others, he only developed herpesvirus reactivation after starting DAA HCV treatment, the researcher said.
In contrast, there were no reactivations among historical controls during a median of 37 months of follow-up. “Even when a causal relationship is not definitive, based on the temporal association and recent experience we conclude that the incidence of herpesvirus reactivation may be increased among patients on interferon-free regimens,” the researchers concluded. “More research is necessary in this new field because unexpected events might be arising in patients treated with direct-acting antivirals.”
The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.
Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.
In all, 2% of patients had herpesvirus reactivations a median of 8 weeks after starting an interferon-free DAA regimen. Seven patients had cirrhosis, three were liver transplant recipients, and all achieved a sustained viral response. Seven patients were receiving sofosbuvir with ledipasvir, either with or without ribavirin; two patients were receiving ombitasvir with paritaprevir and ritonavir plus dasabuvir, with or without ribavirin; and one patient was receiving sofosbuvir with simeprevir plus ribavirin. Median age was 67 years. Seven cases involved cutaneous herpes, two involved ocular herpes, and one was herpes labialis. Two patients developed postherpetic neuralgia requiring gabapentin or pregabalin therapy, and one developed keratouveitis that was treated with valacyclovir (1 g every 8 hours for 7 days). Two other patients also received valacyclovir, three received famciclovir, and the remaining four received acyclovir. When the study was published, one patient, a 68-year-old male with postherpetic neuralgia, had residual symptoms even after undergoing antiviral therapy and nerve ablation. This patient was a liver transplantee and therefore was immunosuppressed, but like the others, he only developed herpesvirus reactivation after starting DAA HCV treatment, the researcher said.
In contrast, there were no reactivations among historical controls during a median of 37 months of follow-up. “Even when a causal relationship is not definitive, based on the temporal association and recent experience we conclude that the incidence of herpesvirus reactivation may be increased among patients on interferon-free regimens,” the researchers concluded. “More research is necessary in this new field because unexpected events might be arising in patients treated with direct-acting antivirals.”
The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Key clinical point: Latent herpesvirus infection may reactivate with interferon-free direct-acting antiviral treatment for chronic hepatitis C virus infection.
Major finding: In all, 2% of recipients of these regimens had herpesvirus reactivation a median of 8 weeks after starting treatment. Historical controls had no documented reactivations.
Data source: A multicenter retrospective study of 576 HCV-infected patients treated with interferon-free DAA regimens and 230 historical matched controls.
Disclosures: The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Selected liver-transplant patients thrive off immunosuppression
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point: Selected pediatric liver-transplant patients who successfully weaned off immunosuppression responded with significantly improved quality of life scores.
Major finding: Patient and parent treatment satisfaction improved by 6-7 points when patients stopped immunosuppression and fell by 2-3 points when they did not.
Data source: iWISH, a multicenter study with 88 enrolled patients.
Disclosures: Dr. Mohammad had no disclosures.
Frailty stratifies pediatric liver disease severity
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: The pediatric frailty score identified patients with end-stage liver disease with sensitivity of 47% and specificity of 98%.
Data source: A series of 71 pediatric patients with liver disease compiled from 17 U.S. and Canadian centers.
Disclosures: Dr. Lurz had no relevant financial disclosures.
Hepatitis Outlook: August 2016
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
On Twitter @richpizzi
Ombitasvir, paritaprevir, ritonavir, and dasabuvir in CKD patients with HCV
Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak) achieved sustained viral response in 90% of patients with noncirrhotic chronic hepatitis C virus (HCV) genotype 1 infection and comorbid stage 4 or 5 chronic kidney disease, according to a small, single-arm, industry-sponsored trial reported in the November issue of Gastroenterology.
Adverse effects were usually mild or moderate, and serious adverse effects were considered unrelated to treatment, Paul Pockros, MD, at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates reported in Gastroenterology. No patients stopped direct-acting antivirals because of adverse effects, although nearly half had to interrupt or discontinue ribavirin because of worsening anemia. “The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with direct-acting antiviral therapy but who may not yet have seen sufficient data to initiate [it] in patients with end-stage renal disease,” the researchers said. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent end-stage sequelae of HCV.”
All patients completed treatment, and 18 (90%) achieved sustained viral response (95% confidence interval, 70%-97%). The most common adverse events were anemia (45% of patients), fatigue (35%), diarrhea (25%), and nausea (25%). Among the two patients who did not achieve sustained viral response, one relapsed and the other died. The relapse occurred in a 49-year-old black man on hemodialysis who took about 91% of his medication doses, compared with about 97% for the rest of the cohort, the investigators said. This patient also had to interrupt ribavirin after his hemoglobin level dropped below 10 g/dL. The death occurred in a 60-year-old male hemodialysis patient who had hypertensive nephropathy and developed hypertensive urgency and cardiomyopathy soon after finishing treatment. His death, although considered unrelated to HCV treatment, underscores the need for close monitoring and collaboration between physicians treating HCV and nephrologists, the researchers said.
Most patients in this study were in stage 5 chronic kidney disease. However, the median baseline hemoglobin level was relatively high at 12 g/dL, implying that these patients would tolerate ribavirin better than would those with more pronounced anemia, the researchers noted. Nonetheless, 9 of 13 patients had to interrupt discontinue ribavirin because of worsening anemia. “Therefore, this study does not provide guidance for chronic kidney disease patients with much lower baseline hemoglobin levels, who might not tolerate even a small decrease,” the investigators cautioned.
AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak) achieved sustained viral response in 90% of patients with noncirrhotic chronic hepatitis C virus (HCV) genotype 1 infection and comorbid stage 4 or 5 chronic kidney disease, according to a small, single-arm, industry-sponsored trial reported in the November issue of Gastroenterology.
Adverse effects were usually mild or moderate, and serious adverse effects were considered unrelated to treatment, Paul Pockros, MD, at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates reported in Gastroenterology. No patients stopped direct-acting antivirals because of adverse effects, although nearly half had to interrupt or discontinue ribavirin because of worsening anemia. “The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with direct-acting antiviral therapy but who may not yet have seen sufficient data to initiate [it] in patients with end-stage renal disease,” the researchers said. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent end-stage sequelae of HCV.”
All patients completed treatment, and 18 (90%) achieved sustained viral response (95% confidence interval, 70%-97%). The most common adverse events were anemia (45% of patients), fatigue (35%), diarrhea (25%), and nausea (25%). Among the two patients who did not achieve sustained viral response, one relapsed and the other died. The relapse occurred in a 49-year-old black man on hemodialysis who took about 91% of his medication doses, compared with about 97% for the rest of the cohort, the investigators said. This patient also had to interrupt ribavirin after his hemoglobin level dropped below 10 g/dL. The death occurred in a 60-year-old male hemodialysis patient who had hypertensive nephropathy and developed hypertensive urgency and cardiomyopathy soon after finishing treatment. His death, although considered unrelated to HCV treatment, underscores the need for close monitoring and collaboration between physicians treating HCV and nephrologists, the researchers said.
Most patients in this study were in stage 5 chronic kidney disease. However, the median baseline hemoglobin level was relatively high at 12 g/dL, implying that these patients would tolerate ribavirin better than would those with more pronounced anemia, the researchers noted. Nonetheless, 9 of 13 patients had to interrupt discontinue ribavirin because of worsening anemia. “Therefore, this study does not provide guidance for chronic kidney disease patients with much lower baseline hemoglobin levels, who might not tolerate even a small decrease,” the investigators cautioned.
AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak) achieved sustained viral response in 90% of patients with noncirrhotic chronic hepatitis C virus (HCV) genotype 1 infection and comorbid stage 4 or 5 chronic kidney disease, according to a small, single-arm, industry-sponsored trial reported in the November issue of Gastroenterology.
Adverse effects were usually mild or moderate, and serious adverse effects were considered unrelated to treatment, Paul Pockros, MD, at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates reported in Gastroenterology. No patients stopped direct-acting antivirals because of adverse effects, although nearly half had to interrupt or discontinue ribavirin because of worsening anemia. “The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with direct-acting antiviral therapy but who may not yet have seen sufficient data to initiate [it] in patients with end-stage renal disease,” the researchers said. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent end-stage sequelae of HCV.”
All patients completed treatment, and 18 (90%) achieved sustained viral response (95% confidence interval, 70%-97%). The most common adverse events were anemia (45% of patients), fatigue (35%), diarrhea (25%), and nausea (25%). Among the two patients who did not achieve sustained viral response, one relapsed and the other died. The relapse occurred in a 49-year-old black man on hemodialysis who took about 91% of his medication doses, compared with about 97% for the rest of the cohort, the investigators said. This patient also had to interrupt ribavirin after his hemoglobin level dropped below 10 g/dL. The death occurred in a 60-year-old male hemodialysis patient who had hypertensive nephropathy and developed hypertensive urgency and cardiomyopathy soon after finishing treatment. His death, although considered unrelated to HCV treatment, underscores the need for close monitoring and collaboration between physicians treating HCV and nephrologists, the researchers said.
Most patients in this study were in stage 5 chronic kidney disease. However, the median baseline hemoglobin level was relatively high at 12 g/dL, implying that these patients would tolerate ribavirin better than would those with more pronounced anemia, the researchers noted. Nonetheless, 9 of 13 patients had to interrupt discontinue ribavirin because of worsening anemia. “Therefore, this study does not provide guidance for chronic kidney disease patients with much lower baseline hemoglobin levels, who might not tolerate even a small decrease,” the investigators cautioned.
AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
FROM GASTROENTEROLOGY
Key clinical point: Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin was relatively well tolerated and cured most genotype 1 chronic hepatitis C virus infections in patients with severe or end-stage renal disease.
Major finding: All patients completed treatment and 18 (90%) achieved sustained viral response. The most common adverse effect was anemia (45% of patients).
Data source: A single-arm, multicenter study of 20 treatment-naive, noncirrhotic adults with HCV genotype 1 infection and stage 4 or 5 chronic kidney disease.
Disclosures: AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
Fulminant HBV reactivation associated with HCV treatment
Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.
HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.
“The mechanism through which HBV reactivation occurs with DAAs is currently unknown. These medicines are not known to cause immunosuppression, but HBV reactivation may result from a complex interplay of host immunologic responses in the setting of infection with two hepatitis viruses.”
In response to the findings, the FDA will require a black box warning on all DAA medications. Before prescribing the drugs, clinicians should screen patients for evidence of current or prior HBV infection. Patients with evidence of current or prior HBV infection should be monitored for HBV surface antigen and HBV DNA, as well as serum aminotransferase bilirubin levels, and watched for signs of hepatitis flare or HBV reactivation during and after DAA treatment. Suspected cases should be reported to FDA MedWatch.
The reactivations occurred within 4-8 weeks of beginning a DAA, the FDA said. “A common sequence of events was initiation of DAA-based HCV treatment, rapid drop of HCV RNA to undetectable levels within 1-2 weeks after normalization of transaminase levels (if they were elevated), followed by a rise in HBV DNA with or without increase in transaminases between weeks 4 and 8.”
Half of the patients did eventually receive HBV antiviral treatment (tenofovir or entecavir). Treatment data were absent on six patients. The remaining six patients did not receive HBV treatment, for unclear reasons.
In eight cases, the initial transaminase increase was interpreted as a DAA drug reaction and the medicine was discontinued. These patients either failed to improve or deteriorated, prompting concerns about HBV reactivation. FDA couldn’t find any commonalities in the cases.
“The patients who developed HBV reactivation were heterogeneous in terms of HCV genotype. These patients were also heterogeneous in terms of baseline HBV disease, fitting into three general categories of patients: those with detectable HBV viral load (seven), those with positive HB surface antigen and undetectable HBV viral load (four), and those with negative HB surface antigen and undetectable HBV viral load (three).”
For the remaining 10 patients, HB surface antigen status was either not known or baseline HBV could not be interpreted.
Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.
HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.
“The mechanism through which HBV reactivation occurs with DAAs is currently unknown. These medicines are not known to cause immunosuppression, but HBV reactivation may result from a complex interplay of host immunologic responses in the setting of infection with two hepatitis viruses.”
In response to the findings, the FDA will require a black box warning on all DAA medications. Before prescribing the drugs, clinicians should screen patients for evidence of current or prior HBV infection. Patients with evidence of current or prior HBV infection should be monitored for HBV surface antigen and HBV DNA, as well as serum aminotransferase bilirubin levels, and watched for signs of hepatitis flare or HBV reactivation during and after DAA treatment. Suspected cases should be reported to FDA MedWatch.
The reactivations occurred within 4-8 weeks of beginning a DAA, the FDA said. “A common sequence of events was initiation of DAA-based HCV treatment, rapid drop of HCV RNA to undetectable levels within 1-2 weeks after normalization of transaminase levels (if they were elevated), followed by a rise in HBV DNA with or without increase in transaminases between weeks 4 and 8.”
Half of the patients did eventually receive HBV antiviral treatment (tenofovir or entecavir). Treatment data were absent on six patients. The remaining six patients did not receive HBV treatment, for unclear reasons.
In eight cases, the initial transaminase increase was interpreted as a DAA drug reaction and the medicine was discontinued. These patients either failed to improve or deteriorated, prompting concerns about HBV reactivation. FDA couldn’t find any commonalities in the cases.
“The patients who developed HBV reactivation were heterogeneous in terms of HCV genotype. These patients were also heterogeneous in terms of baseline HBV disease, fitting into three general categories of patients: those with detectable HBV viral load (seven), those with positive HB surface antigen and undetectable HBV viral load (four), and those with negative HB surface antigen and undetectable HBV viral load (three).”
For the remaining 10 patients, HB surface antigen status was either not known or baseline HBV could not be interpreted.
Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.
HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.
“The mechanism through which HBV reactivation occurs with DAAs is currently unknown. These medicines are not known to cause immunosuppression, but HBV reactivation may result from a complex interplay of host immunologic responses in the setting of infection with two hepatitis viruses.”
In response to the findings, the FDA will require a black box warning on all DAA medications. Before prescribing the drugs, clinicians should screen patients for evidence of current or prior HBV infection. Patients with evidence of current or prior HBV infection should be monitored for HBV surface antigen and HBV DNA, as well as serum aminotransferase bilirubin levels, and watched for signs of hepatitis flare or HBV reactivation during and after DAA treatment. Suspected cases should be reported to FDA MedWatch.
The reactivations occurred within 4-8 weeks of beginning a DAA, the FDA said. “A common sequence of events was initiation of DAA-based HCV treatment, rapid drop of HCV RNA to undetectable levels within 1-2 weeks after normalization of transaminase levels (if they were elevated), followed by a rise in HBV DNA with or without increase in transaminases between weeks 4 and 8.”
Half of the patients did eventually receive HBV antiviral treatment (tenofovir or entecavir). Treatment data were absent on six patients. The remaining six patients did not receive HBV treatment, for unclear reasons.
In eight cases, the initial transaminase increase was interpreted as a DAA drug reaction and the medicine was discontinued. These patients either failed to improve or deteriorated, prompting concerns about HBV reactivation. FDA couldn’t find any commonalities in the cases.
“The patients who developed HBV reactivation were heterogeneous in terms of HCV genotype. These patients were also heterogeneous in terms of baseline HBV disease, fitting into three general categories of patients: those with detectable HBV viral load (seven), those with positive HB surface antigen and undetectable HBV viral load (four), and those with negative HB surface antigen and undetectable HBV viral load (three).”
For the remaining 10 patients, HB surface antigen status was either not known or baseline HBV could not be interpreted.
Key clinical point:
Major finding: HBV reactivation has been reported in 24 patients since 2013.
Data source: Reports were made to the FDA MedWatch system.
Disclosures: No conflicts of interest were reported.