By: DENISE NAPOLI, Internal Medicine News Digital Network
11/03/10
Having cirrhosis, diabetes, or substance use disorder increased the odds of treatment discontinuation in type 1 hepatitis C virus infection, whereas use of growth factor drugs correlated with treatment persistence, reported Dr. Lauren A. Beste and colleagues in the November issue of Clinical Gastroenterology and Hepatology.
The investigators looked at 11,019 patients in the VA health care system with hepatitis C genotype 1 who received at least two prescriptions for pegylated interferon and ribavirin between Jan. 1, 2002 and Dec. 31, 2007.
Patients who completed at least 80% (38.4 weeks) of the standard 48-week treatment regimen were considered to have completed treatment; overall, 5,795 patients (52.6%) reached this goal (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.07.012]).
Although "no indications currently exist for discontinuing treatment [before 12 weeks] due to lack of response," a total of 1,184 patients (roughly 10% of the total cohort) did just that, the authors said. Patients who stopped therapy before 12 weeks were significantly more likely to have cirrhosis, compared with patients who persisted with therapy (adjusted odds ratio [AOR] 1.42; P less than .01), and also were more likely to have diabetes (AOR, 1.25; P = .02) and pretreatment substance use disorder, or SUD (AOR, 1.24; P = .01).
They were also half as likely to use growth factor as were their counterparts who continued with therapy (AOR, 0.56; P less than .01). The growth factors included erythropoietin, darbepoetin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor.
The authors also assessed patients who discontinued treatment between 12 and 24 weeks of therapy (including 317 patients with known early virologic response who discontinued despite their response). These patients were more likely to have pretreatment depression (AOR, 1.59; P less than .01), were slightly less likely to have other mental illnesses (AOR, 0.65; P = .02), and – once again – were nearly half as likely to use growth factor as were patients who persisted with the therapy (AOR, 0.64; P less than .01).
Finally, the authors looked at patients who discontinued therapy before 38.4 weeks. "No variables significantly predicted discontinuation in this time period in bivariate or multivariate analyses," wrote Dr. Beste, of the VA Puget Sound Healthcare System in Seattle, and her coauthors.
Regarding SUD as a predictor of discontinuation, the authors wrote that "patients with history of substance abuse may benefit from early support and intervention during treatment in order to continue antiviral therapy."
Of the pretreatment depression that emerged as a predictor in the 12-24 week discontinuation group, they wrote: "Prior studies report that the depressive side effects of interferon peak by week 25, which may explain the observed association between depression and discontinuation midtreatment."
And regarding the links between cirrhosis and diabetes and discontinuation, they pointed to other studies showing that these patients "may be more susceptible to treatment side-effects." However, they also speculated that blood glucose derangements in diabetic patients receiving treatment may lead to discontinuation.
Finally, Dr. Beste and her colleagues commented on the use of growth factor, which correlated with reduced risk of discontinuation both before 12 weeks and from weeks 12 to 24. They speculated that growth factor use "leads to improvement in low blood counts, allowing providers to continue treatment when otherwise it would be stopped."
Therefore, "appropriate use of growth factors should be prospectively evaluated as a modifiable means to prevent treatment discontinuation," they recommended.
Dr. Beste and her colleagues had no relevant financial disclosures. The study was supported by the Department of Veterans Affairs and the Northwest Hepatitis C Resource Center.
Source
November 11, 2010
Polymorphism Associated With Good Antiviral Response But Also Depression in HCV
Nancy A. Melville
November 3, 2010 (San Antonio, Texas) — Researchers say they have identified a genetic polymorphism in the promoter region of interferon alpha/beta receptor 1 (IFNAR1), which increases the risk for major depression in patients with hepatitis C virus (HCV) being treated with pegylated interferon and ribavirin.
The study involved 170 treatment-naive patients with HCV infection who were genotyped for polymorphism –408 in the promoter regions of IFNAR1 (C/C C/T T/T) and treated with pegylated interferon and ribavirin. The results indicate that those carrying the C/C allele had a greater risk of developing major depression, but also had an increased likelihood of HCV viral clearance.
Previous research has shown that as much as 20% to 30% of hepatitis C patients receiving antiviral treatment experience major depression, which can result in dose reductions and a shorter duration of treatment. The need to identify patients at risk is therefore exceptionally pressing, according to the study's lead author, Muhamad Aly Rifai, MD, from the Lehigh Valley Health Network in Bethlehem, Pennsylvania.
"The identification of patients with this polymorphism may be useful in helping us determine who is at a greater risk of depression and tailor preventive treatment strategies to prevent discontinuation or adverse effects during their treatment," Dr. Rifai told attendees here at the American College of Gastroenterology 2010 Annual Scientific Meeting and Postgraduate Course.
In addition to genotyping, patients were assessed using the Center for Epidemiological Studies Depression Scale. Patients completed visual analog self-report questionnaires before HCV antiviral treatment, and at weeks 0, 2, 4, 6, 8, 12, 16, 20, and 24 of treatment. Kaplan–Meier analyses were used to compare the incidence of major depression between different genetic profiles.
As is consistent with previous research, the results indicated that 28% of patients receiving the antiviral treatment developed major depression (47 of 170).
According to the Mantel–Cox rank test, the C/C allele was associated with an increased rate of developing major depression (P < .05) and an increased rate of HCV viral clearance (P = .0081).
Dr. Rifai noted that previous research has also suggested an improved HCV clearance rate with the C/C allele. "There have been multiple reports from Japanese researchers that this allele is associated with an improved likelihood of HCV viral clearance; however, the numbers were low."
The C/T and T/T alleles, meanwhile, appeared protective regarding the risk of developing major depression (P = .012).
The differences in the genetic groups were significant in a Cox regression analysis that was adjusted for age, sex, response to interferon alpha treatment, viral genotype, and previous psychiatric history (χ2, 8.02; df, 1; P = .005).
"The findings suggest that incorporating genomic predictors in a treatment strategy may help guide the process of determining whether or not to initiate antiviral treatment in patients with hepatitis C," Dr. Rifai said.
The risk of depression among hepatitis C patients using antiviral medications represents a substantial concern for physicians, and the findings could represent valuable information to help address that concern, said session moderator Paul Pockros, MD, head of the Division of Gastroenterology/Hepatology and director of the Scripps Clinic Liver Research Consortium at The Scripps Clinic in La Jolla, California.
"The presentation was provocative because treatment-related depression is extremely common and is probably the single biggest reason patients fear [pegylated interferon and ribavirin] therapy and are poorly adherent to treatment," said Dr. Pockros.
"If this test were validated, it would offer another genomic pretreatment test that would be useful, just as [interleukin] 28B testing, and likely ITPA deficiency testing, will be."
The study received no funding. Dr. Rifai has disclosed no relevant financial relationships. Dr. Pockros reports being a consultant, speaker, and/or on the advisory board for Genentech, Vertex, Merck, Gilead, BMS, Abbott, Phenomix, Tibotec, Pharmasset, Pfizer, Conatus, 3RT, Novartis, J&J, Achillion, and Regulus; and receiving grants or contracts from Genentech, Vertex, Gilead, BMS, Abbott, Quest, Conatus, Tibotec, Pfizer, Globeimmune, Debio, Novartis, and Mochida.
American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Abstract 32. Presented October 19, 2010.
Source
November 3, 2010 (San Antonio, Texas) — Researchers say they have identified a genetic polymorphism in the promoter region of interferon alpha/beta receptor 1 (IFNAR1), which increases the risk for major depression in patients with hepatitis C virus (HCV) being treated with pegylated interferon and ribavirin.
The study involved 170 treatment-naive patients with HCV infection who were genotyped for polymorphism –408 in the promoter regions of IFNAR1 (C/C C/T T/T) and treated with pegylated interferon and ribavirin. The results indicate that those carrying the C/C allele had a greater risk of developing major depression, but also had an increased likelihood of HCV viral clearance.
Previous research has shown that as much as 20% to 30% of hepatitis C patients receiving antiviral treatment experience major depression, which can result in dose reductions and a shorter duration of treatment. The need to identify patients at risk is therefore exceptionally pressing, according to the study's lead author, Muhamad Aly Rifai, MD, from the Lehigh Valley Health Network in Bethlehem, Pennsylvania.
"The identification of patients with this polymorphism may be useful in helping us determine who is at a greater risk of depression and tailor preventive treatment strategies to prevent discontinuation or adverse effects during their treatment," Dr. Rifai told attendees here at the American College of Gastroenterology 2010 Annual Scientific Meeting and Postgraduate Course.
In addition to genotyping, patients were assessed using the Center for Epidemiological Studies Depression Scale. Patients completed visual analog self-report questionnaires before HCV antiviral treatment, and at weeks 0, 2, 4, 6, 8, 12, 16, 20, and 24 of treatment. Kaplan–Meier analyses were used to compare the incidence of major depression between different genetic profiles.
As is consistent with previous research, the results indicated that 28% of patients receiving the antiviral treatment developed major depression (47 of 170).
According to the Mantel–Cox rank test, the C/C allele was associated with an increased rate of developing major depression (P < .05) and an increased rate of HCV viral clearance (P = .0081).
Dr. Rifai noted that previous research has also suggested an improved HCV clearance rate with the C/C allele. "There have been multiple reports from Japanese researchers that this allele is associated with an improved likelihood of HCV viral clearance; however, the numbers were low."
The C/T and T/T alleles, meanwhile, appeared protective regarding the risk of developing major depression (P = .012).
The differences in the genetic groups were significant in a Cox regression analysis that was adjusted for age, sex, response to interferon alpha treatment, viral genotype, and previous psychiatric history (χ2, 8.02; df, 1; P = .005).
"The findings suggest that incorporating genomic predictors in a treatment strategy may help guide the process of determining whether or not to initiate antiviral treatment in patients with hepatitis C," Dr. Rifai said.
The risk of depression among hepatitis C patients using antiviral medications represents a substantial concern for physicians, and the findings could represent valuable information to help address that concern, said session moderator Paul Pockros, MD, head of the Division of Gastroenterology/Hepatology and director of the Scripps Clinic Liver Research Consortium at The Scripps Clinic in La Jolla, California.
"The presentation was provocative because treatment-related depression is extremely common and is probably the single biggest reason patients fear [pegylated interferon and ribavirin] therapy and are poorly adherent to treatment," said Dr. Pockros.
"If this test were validated, it would offer another genomic pretreatment test that would be useful, just as [interleukin] 28B testing, and likely ITPA deficiency testing, will be."
The study received no funding. Dr. Rifai has disclosed no relevant financial relationships. Dr. Pockros reports being a consultant, speaker, and/or on the advisory board for Genentech, Vertex, Merck, Gilead, BMS, Abbott, Phenomix, Tibotec, Pharmasset, Pfizer, Conatus, 3RT, Novartis, J&J, Achillion, and Regulus; and receiving grants or contracts from Genentech, Vertex, Gilead, BMS, Abbott, Quest, Conatus, Tibotec, Pfizer, Globeimmune, Debio, Novartis, and Mochida.
American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Abstract 32. Presented October 19, 2010.
Source
Infusion of autologous bone marrow mononuclear cells through hepatic artery results in a short-term improvement of liver function in patients with chronic liver disease: a pilot randomized controlled study
European Journal of Gastroenterology & Hepatology:
January 2010 - Volume 22 - Issue 1 - pp 33-42
doi: 10.1097/MEG.0b013e32832eb69a
Original Articles: Liver Function
Lyra, Andre Castro
Abstract
Aim: This randomized controlled study evaluated the effect of autologous infusion of bone marrow cells (BMC) in patients with hepatic cirrhosis.
Methods: Thirty patients on the liver transplant waiting list were randomly assigned to receive BMC therapy or no treatment. They were followed up for 1 year. The study was nonblinded. Autologous mononuclear-enriched BMC were infused into the hepatic artery; liver function scores/tests were chosen as endpoints to assess efficacy. Statistical analysis calculated mean relative changes (RC) from baseline and fitted a random-effects model.
Results: Mean age, baseline model for end-stage liver disease, and Child-Pugh score were similar in both groups. Child-Pugh score improved in the first 90 days in the cell therapy group compared with controls (P = 0.017, BMC group RC = -8%, controls RC = +5%). The model for end-stage liver disease score remained stable in the treated patients (RC -2 to +6%), whereas it increased during follow-up in the control group (RC +6 to +18%). Albumin levels improved in the treatment arm, whereas they remained stable among controls in the first 90 days (P = 0.034; BMC group RC = +16%, control group RC = +2%). Bilirubin levels increased among controls, whereas they decreased in the therapy arm during the first 60 days; INR RC differences between groups reached up to 10%. The changes observed did not persist beyond 90 days.
Conclusion: Transplantation of autologous BMC into the hepatic artery improved liver function in patients with advanced cirrhosis in the first 90 days. However, larger studies are necessary to define the role of BMC therapy in cirrhotic patients. Repeated autologous BMC infusions or combination therapy with granulocyte-colony-stimulating factor might improve or sustain the treatment response.
Source
January 2010 - Volume 22 - Issue 1 - pp 33-42
doi: 10.1097/MEG.0b013e32832eb69a
Original Articles: Liver Function
Lyra, Andre Castro
Abstract
Aim: This randomized controlled study evaluated the effect of autologous infusion of bone marrow cells (BMC) in patients with hepatic cirrhosis.
Methods: Thirty patients on the liver transplant waiting list were randomly assigned to receive BMC therapy or no treatment. They were followed up for 1 year. The study was nonblinded. Autologous mononuclear-enriched BMC were infused into the hepatic artery; liver function scores/tests were chosen as endpoints to assess efficacy. Statistical analysis calculated mean relative changes (RC) from baseline and fitted a random-effects model.
Results: Mean age, baseline model for end-stage liver disease, and Child-Pugh score were similar in both groups. Child-Pugh score improved in the first 90 days in the cell therapy group compared with controls (P = 0.017, BMC group RC = -8%, controls RC = +5%). The model for end-stage liver disease score remained stable in the treated patients (RC -2 to +6%), whereas it increased during follow-up in the control group (RC +6 to +18%). Albumin levels improved in the treatment arm, whereas they remained stable among controls in the first 90 days (P = 0.034; BMC group RC = +16%, control group RC = +2%). Bilirubin levels increased among controls, whereas they decreased in the therapy arm during the first 60 days; INR RC differences between groups reached up to 10%. The changes observed did not persist beyond 90 days.
Conclusion: Transplantation of autologous BMC into the hepatic artery improved liver function in patients with advanced cirrhosis in the first 90 days. However, larger studies are necessary to define the role of BMC therapy in cirrhotic patients. Repeated autologous BMC infusions or combination therapy with granulocyte-colony-stimulating factor might improve or sustain the treatment response.
Source
AASLD: Liver Damage Increases Tenofovir-Induced Kidney Impairment Risk
November 8, 2010
People coinfected with both HIV and hepatitis B virus (HBV) who have more significant liver damage (fibrosis) are much more likely to develop mild kidney problems after starting tenofovir (found in Viread, Truvada and Atripla) than people with little liver damage. These data were presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases, held October 29 to November 2 in Boston.
The antiretroviral (ARV) drug tenofovir—which is used to treat both HIV and HBV—has a rare but well-studied side effect: tubular kidney damage. In most people, reduced kidney function is mild to moderate. In just under 1 percent of people who take tenofovir, however, tubular kidney damage can be more severe and occasionally life-threatening. While rates of kidney damage in people with either HIV or HBV have been assessed—serious liver disease can affect the organ’s ability to handle toxins and blood flow, which can put a strain on the kidneys—little is known about the effect of liver fibrosis on the risk of developing tenofovir-induced kidney problems in people infected with both viruses.
To address this unanswered question, Anders Boyd, MPH, from the Hospital Saint Antoine in Paris, and his colleagues followed 137 HIV and HBV coinfected individuals after they started tenofovir therapy. All study participants had taken ARV drugs before. Their average age was 41, and about 90 percent were male. The average amount of time spent on tenofovir during the study was 34 months.
All participants underwent a liver biopsy before starting tenofovir, and 41 were found to have severe liver fibrosis and 96 to have mild liver fibrosis. Kidney function at 12, 24 and 36 months after starting tenofovir was measured by assessing the participants’ estimated glomerular filtration rate (eGFR).
Boyd and his colleagues found that liver fibrosis had a profound effect on the likelihood of having reduced kidney function after starting tenofovir. In fact, those who started tenofovir with the most liver fibrosis were 3.74 times more likely to have mild kidney impairment than those with little fibrosis. The greatest difference in kidney function between those with high and low fibrosis scores occurred within the first two years of treatment.
People with more severe liver disease are at increased risk for kidney dysfunction, regardless of whether they use tenofovir. To determine the actual contribution of tenofovir to this problem, future studies would need to compare individuals with high fibrosis scores who start tenofovir with similar people who do not take tenofovir.
“HIV and HBV coinfected patients treated with tenofovir are at higher risk of [kidney] impairment when exhibiting high liver fibrosis levels, and thereby warranting closer follow-up of [kidney function] in this patient population,” the authors concluded.
Source
People coinfected with both HIV and hepatitis B virus (HBV) who have more significant liver damage (fibrosis) are much more likely to develop mild kidney problems after starting tenofovir (found in Viread, Truvada and Atripla) than people with little liver damage. These data were presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases, held October 29 to November 2 in Boston.
The antiretroviral (ARV) drug tenofovir—which is used to treat both HIV and HBV—has a rare but well-studied side effect: tubular kidney damage. In most people, reduced kidney function is mild to moderate. In just under 1 percent of people who take tenofovir, however, tubular kidney damage can be more severe and occasionally life-threatening. While rates of kidney damage in people with either HIV or HBV have been assessed—serious liver disease can affect the organ’s ability to handle toxins and blood flow, which can put a strain on the kidneys—little is known about the effect of liver fibrosis on the risk of developing tenofovir-induced kidney problems in people infected with both viruses.
To address this unanswered question, Anders Boyd, MPH, from the Hospital Saint Antoine in Paris, and his colleagues followed 137 HIV and HBV coinfected individuals after they started tenofovir therapy. All study participants had taken ARV drugs before. Their average age was 41, and about 90 percent were male. The average amount of time spent on tenofovir during the study was 34 months.
All participants underwent a liver biopsy before starting tenofovir, and 41 were found to have severe liver fibrosis and 96 to have mild liver fibrosis. Kidney function at 12, 24 and 36 months after starting tenofovir was measured by assessing the participants’ estimated glomerular filtration rate (eGFR).
Boyd and his colleagues found that liver fibrosis had a profound effect on the likelihood of having reduced kidney function after starting tenofovir. In fact, those who started tenofovir with the most liver fibrosis were 3.74 times more likely to have mild kidney impairment than those with little fibrosis. The greatest difference in kidney function between those with high and low fibrosis scores occurred within the first two years of treatment.
People with more severe liver disease are at increased risk for kidney dysfunction, regardless of whether they use tenofovir. To determine the actual contribution of tenofovir to this problem, future studies would need to compare individuals with high fibrosis scores who start tenofovir with similar people who do not take tenofovir.
“HIV and HBV coinfected patients treated with tenofovir are at higher risk of [kidney] impairment when exhibiting high liver fibrosis levels, and thereby warranting closer follow-up of [kidney function] in this patient population,” the authors concluded.
Source
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