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Hamish Innes - One of the best experts on this subject based on the ideXlab platform.
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the risk of hepatocellular carcinoma in cirrhotic patients with hepatitis c and Sustained Viral Response role of the treatment regimen
Journal of Hepatology, 2017Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, Stephen T Barclay, Andrew Fraser, Adrian J Stanley, Andy BathgateAbstract:Background & Aims Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV clinical database. Methods We identified HCC-naive individuals with liver cirrhosis receiving a course of antiViral therapy in Scotland from 1997–2016 resulting in a Sustained virologic Response. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free vs. IFN-containing. Results A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48; p = 0.021). However, after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, p = 0.744). Conclusion These findings suggest that the higher incidence of HCC following Sustained virologic Response with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se. Lay summary We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiViral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer.
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mortality in hepatitis c patients who achieve a Sustained Viral Response compared to the general population
Journal of Hepatology, 2017Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, Sam Allen, David J Goldberg, P R MillsAbstract:Background & Aims The number of people living with previous hepatitis C infection that have attained a Sustained Viral Response (SVR) is expected to grow rapidly. So far, the prognosis of this group relative to the general population is unclear. Methods Individuals attaining SVR in Scotland in 1996–2011 were identified using a national database. Through record-linkage, we obtained cause-specific mortality data complete to Dec 2013. We calculated standardised mortality ratios (SMRs) to compare the frequency of mortality in SVR patients to the general population. In a parallel analysis, we used Cox regression to identify modifiable patient characteristics associated with post-SVR mortality. Results We identified 1824 patients, followed on average for 5.2years after SVR. In total, 78 deaths were observed. Overall, all-cause mortality was 1.9 times more frequent for SVR patients than the general population (SMR: 1.86; 95% confidence interval (CI): 1.49–2.32). Significant cause-specific elevations were seen for death due to primary liver cancer (SMR: 23.50; 95% CI: 12.23–45.16), and death due to drug-related causes (SMR: 6.58, 95% CI: 4.15–10.45). Together these two causes accounted for 66% of the total excess death observed. All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (SMR: 0.70; 95% CI: 0.41–1.18) Conclusions Mortality in Scottish SVR patients is higher overall than the general population. The excess was driven by death from drug-related causes and liver cancer. Health risk behaviours emerged as important modifiable determinants of mortality in this population. Lay summary Patients cured of hepatitis C through treatment had a higher mortality rate overall than the general population. Most of the surplus mortality was due to drug-related causes and death from liver cancer. A history of heavy alcohol and injecting drug use were associated with a higher mortality risk.
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toward a more complete understanding of the association between a hepatitis c Sustained Viral Response and cause specific outcomes
Hepatology, 2015Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, Sam Allen, David Goldberg, P R MillsAbstract:Sustained Viral Response (SVR) is the optimal outcome of hepatitis C virus (HCV) therapy, yet more detailed data are required to confirm its clinical value. Individuals receiving treatment in 1996-2011 were identified using the Scottish HCV clinical database. We sourced data on 10 clinical events: liver, nonliver, and all-cause mortality; first hospitalisation for severe liver morbidity (SLM); cardiovascular disease (CVD); respiratory disorders; neoplasms; alcohol-intoxication; drug intoxication; and violence-related injury (note: the latter three events were selected a priori to gauge ongoing chaotic lifestyle behaviours). We determined the association between SVR attainment and each outcome event, in terms of the relative hazard reduction and absolute risk reduction (ARR). We tested for an interaction between SVR and liver disease severity (mild vs. nonmild), defining mild disease as an aspartate aminotransferase-to-platelet ratio index (APRI) <0.7. Our cohort comprised 3,385 patients (mean age: 41.6 years), followed-up for a median 5.3 years (interquartile range: 3.3-8.2). SVR was associated with a reduced risk of liver mortality (adjusted hazard ratio [AHR]: 0.24; P < 0.001), nonliver mortality (AHR, 0.68; P = 0.026), all-cause mortality (AHR, 0.49; P < 0.001), SLM (AHR, 0.21; P < 0.001), CVD (AHR, 0.70; P = 0.001), alcohol intoxication (AHR, 0.52; P = 0.003), and violence-related injury (AHR, 0.51; P = 0.002). After 7.5 years, SVR was associated with significant ARRs for liver mortality, all-cause mortality, SLM, and CVD (each 3.0%-4.7%). However, we detected a strong interaction, in that ARRs were considerably higher for individuals with nonmild disease than for individuals with mild disease. Conclusions: The conclusions are 3-fold: (1) Overall, SVR is associated with reduced hazard for a range of hepatic and nonhepatic events; (2) an association between SVR and behavioral events is consistent with SVR patients leading healthier lives; and (3) the short-term value of SVR is greatest for those with nonmild disease. (Hepatology 2015;62:355–364
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what is the impact of a country wide scale up in antiViral therapy on the characteristics and Sustained Viral Response rates of patients treated for hepatitis c
Journal of Hepatology, 2015Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, David J Goldberg, P R Mills, Stephen T BarclayAbstract:Background & Aims The global burden associated with hepatitis C virus (HCV) infection has prompted a scale-up of antiViral therapy. Hitherto, no data exist on the impact of scaling-up, on the characteristics of treated populations, or on Sustained Viral Response (SVR) rates. We assessed the country-wide scale-up of antiViral therapy in Scotland, a country which nationally monitors uptake of and Response to HCV treatment. Methods Data for patients, initiated on combined pegylated interferon and ribavirin therapy at 13 specialist HCV clinics in 2001–2010, were extracted from the Scottish HCV Clinical Database (n=3895). Patient characteristics included age, genotype, PWID (people who inject drugs) status, prison referral, and diagnosed cirrhosis. Temporal trends in covariates and adjusted effects on a SVR were examined via mixed-effects regression. Results The number of patients starting treatment increased from 237 in 2001–2002 to 1560 in 2009–2010, with an increasing trend in SVR from 44% to 57% over this period. For a given clinic, between 2001/2 and 2010 there was a decrease in the odds of those treated being diagnosed with cirrhosis (odds ratio [OR]=0.84 per year), and increasing temporal trends for those treated being PWID (OR=1.08) and prison referrals (OR=1.06). Adjusting for covariates, the proportion of a given clinic's patients achieving SVR was positively associated with the percentage of PWID (OR=1.01 per percent increase; 95% confidence interval [CI]: 1.00–1.02) and genotype 2/3 (OR=1.03; 95% CI: 1.02–1.04). Conclusions Despite changes in patient characteristics, a country-wide scale-up of antiViral therapy did not compromise SVR rates. Results are highly relevant to countries planning on scaling-up treatment, given the forthcoming availability of new interferon-free therapies.
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ranking predictors of a Sustained Viral Response for patients with chronic hepatitis c treated with pegylated interferon and ribavirin in scotland
European Journal of Gastroenterology & Hepatology, 2012Co-Authors: Hamish Innes, John F Dillon, Sam Allen, David J Goldberg, Sharon J Hutchinson, Diptendu Bhattacharyya, Peter Bramley, Toby E S Delahooke, Bill Carman, Nicholas A KennedyAbstract:ObjectivesFrom the literature on the hepatitis C virus, the existence of a gap between a Sustained virologic Response (SVR) attainable in randomized clinical trials (RCTs) versus routine practice is not clear. Further, in terms of the pretreatment prediction of SVR, to date, studies have focused onl
Sammy Saab - One of the best experts on this subject based on the ideXlab platform.
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impact of Sustained Viral Response with direct acting agents on glycemic control and renal function in hepatitis c liver transplant recipients
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2018Co-Authors: Sammy Saab, Francisco Durazo, Mohammed M Elkabany, Abbey Barnard, Youssef Challita, Adetola Adeniyi, Antony Aziz, Gina Choi, Stevenhuy B Han, Ronald W BusuttilAbstract:Objectives The impact of achieving a Sustained Viral Response on extrahepatic manifestations after liver transplant is unclear. In this study, our aim was to evaluate whether Sustained Viral Responses in hepatitis C-positive liver transplant recipients can lead to improved nonhepatic outcomes. Materials and methods We studied 84 consecutive liver transplant recipients who achieved a Sustained Viral Response with direct-acting antiViral agents at the University of California Los Angeles. We collected laboratory data before and after the Sustained Viral Response was achieved. Paired t tests were performed. Results The mean age and standard deviation of our cohort was 62.4 ± 7.6 years. The mean time from achieving a Sustained Viral Response to last follow-up in our cohort was 19.5 ± 10.8 months. In the entire cohort, there were no changes in mean fasting blood glucose (123 ± 42 vs 120 ± 35 mg/dL; P = .49). We observed a significant improvement in renal function in recipients with stage 1 and 2 chronic kidney disease (82 ± 15 vs 71.16 ± 16 mL/min/1.73 m2; P ⟨ .001) and in those treated within 3 months of liver transplant (75 ± 28 vs 61 ± 16 mL/min/1.73 m2; P = .035). Fasting blood glucose decreased in recipients with a diagnosis of impaired fasting blood glucose (109 ± 16 vs 103 ± 13 mg/dL; P = .001). Conclusions The benefits on glucose metabolism and renal function after a Sustained Viral Response in liver transplant recipients appear to be limited to those with early chronic kidney disease and those treated soon after transplant. The potential benefits from direct-acting antiViral agents on these parameters may be overshadowed by the effects of immunosuppressant therapy.
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curing hepatitis c in liver transplant recipients is associated with changes in immunosuppressant use
Journal of clinical and translational hepatology, 2016Co-Authors: Sammy Saab, Sherona Bau, Francisco Durazo, Steven Han, Gina Choi, Melissa Jimenez, Mohammed El Kabany, Justin Rheem, Alexander Farid, Naadir JamalAbstract:Background and Aims: All-oral interferon-free antiVirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients. The aim of the study was to assess immunosuppression needs after achieving a Sustained Viral Response (SVR). Methods: We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with all-oral direct acting agents. Results: We identified 52 liver LT treated recipients who achieved a SVR. The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most recipients received tacrolimus (TAC) for their immunosuppressant regimen. After achieving SVR, there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05). However, there was a statistically significant decrease in daily dose of TAC adjusted per weight, serum levels of TAC, and the product of glomerular filtration rate and TAC. No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted. Conclusions: Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine. LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.
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sofosbuvir and simeprevir is effective for recurrent hepatitis c in liver transplant recipients
Liver International, 2015Co-Authors: Sammy Saab, Adam Eric Greenberg, Sherona Bau, Francisco Durazo, Mohammed M Elkabany, Steven Han, Ronald W BusuttilAbstract:Background & Aims Hepatitis C is the most common indication for liver transplantation (LT). Recurrent infection is universal and can lead to progressive liver disease. Widespread use of interferon-based therapy has been limited by intolerability and adverse effects. Methods We retrospectively evaluated the safety, tolerability, and efficacy of sofosbuvir and simeprevir in the treatment of recurrent hepatitis C in adult (age >18) LT recipients. Results Seventy-six percent of the recipients were male and the mean age [±standard deviation (SD)] was 61 (±6.0) years. The mean time (±SD) from LT to treatment initiation was 71.8 (±77.1) months. Of the 26 patients with Viral levels measured 4 weeks after starting antiViral therapy, 58% were undetectable. At the end of therapy, Viral load was undetectable in all transplant recipients. The 12 week Sustained Viral Response (SVR) was 93%. All recipients were able to complete therapy and no patients required growth factors of blood product transfusion during treatment. No patient required drug interruption of their immunosuppressant therapy. Conclusion The use of sofosbuvir and simeprevir is efficacious, safe, and tolerable and should be considered in LT recipients with recurrent HCV who are candidates for antiViral therapy.
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treating fibrosing cholestatic hepatitis c with sofosbuvir and ribavirin a matched analysis
Clinical Transplantation, 2015Co-Authors: Sammy Saab, Francisco Durazo, Melissa Jimenez, Difan Zhao, Mohammed El Kabany, Fady M Kaldas, Myron J Tong, Ronald W BusuttilAbstract:Author(s): Saab, Sammy; Jimenez, Melissa; Bau, Sherona; Goo, Tyralee; Zhao, Difan; Durazo, Francisco; Han, Steven; El Kabany, Mohammed; Kaldas, Fady; Tong, Myron J; Busuttil, Ronald W | Abstract: Fibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients.We matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin.Baseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The Sustained Viral Response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors.Our results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower Sustained Viral Response, patient survival, and graft survival in the FCH recipients.
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kidney transplantation threshold in patients with hepatitis c a decision analysis model
Transplantation, 2015Co-Authors: Gina Choi, Kristina Lee, Sammy SaabAbstract:Background There are no standard guidelines for the permissible degree of liver fibrosis in patients with chronic hepatitis C virus prohibiting cadaveric renal transplantation (CRT). Methods A decision analysis model was constructed to compare 5-year patient survival using three strategies for patients on hemodialysis. The probabilities of pretransplant and posttransplant survival, progression of liver fibrosis, CRT, and Sustained Viral Response were obtained from a systematic review of the literature. Sensitivity analyses were performed. Results Kidney transplantation was associated with improved 5-year survival for patients with fibrosis stages 1 to 3, but not stage 4 (cirrhosis). AntiViral therapy was associated with improvement in survival in patients with stage 3 fibrosis. The 5-year survival was similar for patients with stage 4 irrespective of the option of antiViral therapy. The model was sensitive to varying the probability of both pretransplant and posttransplant survival. Conclusion There appears to be no overall 5-year survival benefit in treating S1 and S2 fibrosis patients with hepatitis C virus antiViral therapy before CRT. There is no benefit in overall 5-year survival in patients with cirrhosis and thus should not be candidates for CRT.
Masataka Tsuge - One of the best experts on this subject based on the ideXlab platform.
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multicentric hepatocarcinogenesis at 6 and 13 years after Sustained Viral Response to hepatitis c virus
Clinical Journal of Gastroenterology, 2012Co-Authors: Yoshimasa Hashimoto, Daisuke Miyaki, Eisuke Murakami, Yuko Nagaoki, Yuki Kimura, Azakami Takahiro, Yoshio Katamura, Tomokazu Kawaoka, Shintaro Takaki, Masataka TsugeAbstract:A 68-year-old Japanese woman with chronic hepatitis C infection who achieved Sustained Viral Response (SVR) was followed up regularly. Six years after SVR, alpha fetoprotein (AFP) was increased. Hepatocellular carcinoma (HCC) was diagnosed by computed tomography and was excised by hepatic resection. Thirteen years after SVR, AFP increased again, and HCC recurrence was detected, which was excised by hepatic resection. Each HCC was <2 cm in diameter, with no vascular invasion. The primary HCC was moderately differentiated, while the secondary was well-to-moderately differentiated. Based on the clinicopathological features, the hepatocarcinogenesis was considered multicentric. Our case illustrates the importance of long-term follow-up of patients who achieve SVR.
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achievement of Sustained Viral Response after switching treatment from pegylated interferon α 2b to α 2a and ribavirin in patients with recurrence of hepatitis c virus genotype 1 infection after liver transplantation a case report
Intervirology, 2012Co-Authors: Tomokazu Kawaoka, Yoshimasa Hashimoto, Yuko Nagaoki, Yoshio Katamura, Shintaro Takaki, Masataka Tsuge, Nobuhiko Hiraga, Shoichi Takahashi, Daiki Miki, Akira HiramatsuAbstract:We report a case in which Sustained Viral Response was achieved after switching treatment from pegylated interferon (PEG-IFN) α-2b to α-2a and ribavirin (RBV) in patients with recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation. The patient was a 62-year-old man with liver cirrhosis due to HCV genotype 1b infection. The patient had 8 amino acid (aa) substitutions in the interferon sensitivity-determining region, and had substitutions for mutant and wild-type at aa70 and aa91, respectively, in the core region. The patient had minor genotype (GG) IL28B single nucleotide polymorphisms (rs8099917). He had initially received interferon α-2b and RBV for 2 years, and later developed hepatocellular carcinoma (HCC). After surgical resection of HCC, he subsequently received PEG-IFN α-2b and RBV for 1.5 years, without undetectable viremia during the treatment course. Due to recurrence of HCC, the patient received a living donor liver transplantation. Later on, hepatitis C relapsed. For the management of relapse, he received another course of PEG-IFN α-2b and RBV. However, breakthrough viremia occurred. PEG-IFN was thus switched from α-2b to α-2a and RBV for another 17 months. The patient eventually achieved a Sustained Viral Response.
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multicentric hepatocarcinogenesis at 6 and 13 years after Sustained Viral Response to hepatitis c virus yoshimasa hashimotodaisuke miyakieisuke murakamiyuko nagaokiyuki kimura azakami takahiroyoshio katamuratomokazu kawaokashintaro takakimasataka tsuge nobuhiko hiragaakira hiramatsukoji wakimichio imamurahiroshi aikatashoichi takahashi
2012Co-Authors: Yoshimasa Hashimoto, Daisuke Miyaki, Eisuke Murakami, Yuko Nagaoki, Yuki Kimura, Azakami Takahiro, Yoshio Katamura, Tomokazu Kawaoka, Shintaro Takaki, Masataka TsugeAbstract:A 68-year-old Japanese woman with chronic hepatitis C infection who achieved Sustained Viral Response (SVR) was followed up regularly. Six years after SVR, alpha fetoprotein (AFP) was increased. Hepatocellular carcinoma (HCC) was diagnosed by computed tomography and was excised by hepatic resection. Thirteen years after SVR, AFP increased again, and HCC recurrence was detected, which was excised by hepatic resection. Each HCC was \2 cm in diameter, with no vascular invasion. The primary HCC was moderately differentiated, while the secondary was well-to-moderately differentiated. Based on the clinicopathological features, the hepatocarcinogenesis was considered multicentric. Our case illustrates the importance of long-term follow-up of patients who achieve SVR.
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multicentric hepatocarcinogenesis at 6 and 13 years after Sustained Viral Response to hepatitis c virus yoshimasa hashimotodaisuke miyakieisuke murakamiyuko nagaokiyuki kimura azakami takahiroyoshio katamuratomokazu kawaokashintaro takakimasataka tsuge nobuhiko hiragaakira hiramatsukoji wakimichio imamurahiroshi aikatashoichi takahashi
2012Co-Authors: Yoshimasa Hashimoto, Daisuke Miyaki, Eisuke Murakami, Yuko Nagaoki, Yuki Kimura, Azakami Takahiro, Yoshio Katamura, Tomokazu Kawaoka, Shintaro Takaki, Masataka TsugeAbstract:A 68-year-old Japanese woman with chronic hepatitis C infection who achieved Sustained Viral Response (SVR) was followed up regularly. Six years after SVR, alpha fetoprotein (AFP) was increased. Hepatocellular carcinoma (HCC) was diagnosed by computed tomography and was excised by hepatic resection. Thirteen years after SVR, AFP increased again, and HCC recurrence was detected, which was excised by hepatic resection. Each HCC was \2 cm in diameter, with no vascular invasion. The primary HCC was moderately differentiated, while the secondary was well-to-moderately differentiated. Based on the clinicopathological features, the hepatocarcinogenesis was considered multicentric. Our case illustrates the importance of long-term follow-up of patients who achieve SVR.
John F Dillon - One of the best experts on this subject based on the ideXlab platform.
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the risk of hepatocellular carcinoma in cirrhotic patients with hepatitis c and Sustained Viral Response role of the treatment regimen
Journal of Hepatology, 2017Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, Stephen T Barclay, Andrew Fraser, Adrian J Stanley, Andy BathgateAbstract:Background & Aims Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV clinical database. Methods We identified HCC-naive individuals with liver cirrhosis receiving a course of antiViral therapy in Scotland from 1997–2016 resulting in a Sustained virologic Response. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free vs. IFN-containing. Results A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48; p = 0.021). However, after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, p = 0.744). Conclusion These findings suggest that the higher incidence of HCC following Sustained virologic Response with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se. Lay summary We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiViral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer.
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mortality in hepatitis c patients who achieve a Sustained Viral Response compared to the general population
Journal of Hepatology, 2017Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, Sam Allen, David J Goldberg, P R MillsAbstract:Background & Aims The number of people living with previous hepatitis C infection that have attained a Sustained Viral Response (SVR) is expected to grow rapidly. So far, the prognosis of this group relative to the general population is unclear. Methods Individuals attaining SVR in Scotland in 1996–2011 were identified using a national database. Through record-linkage, we obtained cause-specific mortality data complete to Dec 2013. We calculated standardised mortality ratios (SMRs) to compare the frequency of mortality in SVR patients to the general population. In a parallel analysis, we used Cox regression to identify modifiable patient characteristics associated with post-SVR mortality. Results We identified 1824 patients, followed on average for 5.2years after SVR. In total, 78 deaths were observed. Overall, all-cause mortality was 1.9 times more frequent for SVR patients than the general population (SMR: 1.86; 95% confidence interval (CI): 1.49–2.32). Significant cause-specific elevations were seen for death due to primary liver cancer (SMR: 23.50; 95% CI: 12.23–45.16), and death due to drug-related causes (SMR: 6.58, 95% CI: 4.15–10.45). Together these two causes accounted for 66% of the total excess death observed. All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (SMR: 0.70; 95% CI: 0.41–1.18) Conclusions Mortality in Scottish SVR patients is higher overall than the general population. The excess was driven by death from drug-related causes and liver cancer. Health risk behaviours emerged as important modifiable determinants of mortality in this population. Lay summary Patients cured of hepatitis C through treatment had a higher mortality rate overall than the general population. Most of the surplus mortality was due to drug-related causes and death from liver cancer. A history of heavy alcohol and injecting drug use were associated with a higher mortality risk.
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toward a more complete understanding of the association between a hepatitis c Sustained Viral Response and cause specific outcomes
Hepatology, 2015Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, Sam Allen, David Goldberg, P R MillsAbstract:Sustained Viral Response (SVR) is the optimal outcome of hepatitis C virus (HCV) therapy, yet more detailed data are required to confirm its clinical value. Individuals receiving treatment in 1996-2011 were identified using the Scottish HCV clinical database. We sourced data on 10 clinical events: liver, nonliver, and all-cause mortality; first hospitalisation for severe liver morbidity (SLM); cardiovascular disease (CVD); respiratory disorders; neoplasms; alcohol-intoxication; drug intoxication; and violence-related injury (note: the latter three events were selected a priori to gauge ongoing chaotic lifestyle behaviours). We determined the association between SVR attainment and each outcome event, in terms of the relative hazard reduction and absolute risk reduction (ARR). We tested for an interaction between SVR and liver disease severity (mild vs. nonmild), defining mild disease as an aspartate aminotransferase-to-platelet ratio index (APRI) <0.7. Our cohort comprised 3,385 patients (mean age: 41.6 years), followed-up for a median 5.3 years (interquartile range: 3.3-8.2). SVR was associated with a reduced risk of liver mortality (adjusted hazard ratio [AHR]: 0.24; P < 0.001), nonliver mortality (AHR, 0.68; P = 0.026), all-cause mortality (AHR, 0.49; P < 0.001), SLM (AHR, 0.21; P < 0.001), CVD (AHR, 0.70; P = 0.001), alcohol intoxication (AHR, 0.52; P = 0.003), and violence-related injury (AHR, 0.51; P = 0.002). After 7.5 years, SVR was associated with significant ARRs for liver mortality, all-cause mortality, SLM, and CVD (each 3.0%-4.7%). However, we detected a strong interaction, in that ARRs were considerably higher for individuals with nonmild disease than for individuals with mild disease. Conclusions: The conclusions are 3-fold: (1) Overall, SVR is associated with reduced hazard for a range of hepatic and nonhepatic events; (2) an association between SVR and behavioral events is consistent with SVR patients leading healthier lives; and (3) the short-term value of SVR is greatest for those with nonmild disease. (Hepatology 2015;62:355–364
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hcv treatment rates and Sustained Viral Response among people who inject drugs in seven uk sites real world results and modelling of treatment impact
Journal of Viral Hepatitis, 2015Co-Authors: John F Dillon, Natasha K Martin, Graham R Foster, J Vilar, Stephen D Ryder, Matthew E Cramp, F Gordon, Noel Craine, Heide BusseAbstract:Hepatitis C virus (HCV) antiViral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and Sustained Viral Response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antiVirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.
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what is the impact of a country wide scale up in antiViral therapy on the characteristics and Sustained Viral Response rates of patients treated for hepatitis c
Journal of Hepatology, 2015Co-Authors: Hamish Innes, Scott A Mcdonald, Peter C Hayes, John F Dillon, David J Goldberg, P R Mills, Stephen T BarclayAbstract:Background & Aims The global burden associated with hepatitis C virus (HCV) infection has prompted a scale-up of antiViral therapy. Hitherto, no data exist on the impact of scaling-up, on the characteristics of treated populations, or on Sustained Viral Response (SVR) rates. We assessed the country-wide scale-up of antiViral therapy in Scotland, a country which nationally monitors uptake of and Response to HCV treatment. Methods Data for patients, initiated on combined pegylated interferon and ribavirin therapy at 13 specialist HCV clinics in 2001–2010, were extracted from the Scottish HCV Clinical Database (n=3895). Patient characteristics included age, genotype, PWID (people who inject drugs) status, prison referral, and diagnosed cirrhosis. Temporal trends in covariates and adjusted effects on a SVR were examined via mixed-effects regression. Results The number of patients starting treatment increased from 237 in 2001–2002 to 1560 in 2009–2010, with an increasing trend in SVR from 44% to 57% over this period. For a given clinic, between 2001/2 and 2010 there was a decrease in the odds of those treated being diagnosed with cirrhosis (odds ratio [OR]=0.84 per year), and increasing temporal trends for those treated being PWID (OR=1.08) and prison referrals (OR=1.06). Adjusting for covariates, the proportion of a given clinic's patients achieving SVR was positively associated with the percentage of PWID (OR=1.01 per percent increase; 95% confidence interval [CI]: 1.00–1.02) and genotype 2/3 (OR=1.03; 95% CI: 1.02–1.04). Conclusions Despite changes in patient characteristics, a country-wide scale-up of antiViral therapy did not compromise SVR rates. Results are highly relevant to countries planning on scaling-up treatment, given the forthcoming availability of new interferon-free therapies.
Patrice Cacoub - One of the best experts on this subject based on the ideXlab platform.
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re treatment of chronic hcv infection in hiv co infected patients and predictors of Sustained Viral Response
Journal of Infection, 2014Co-Authors: F Banisadr, Evguenia Krastinova, Delphine Fromentin, Cecile Goujard, Mojgan Hessamfar, Patrice Cacoub, Yazdan Yazdanpanah, Christian Perronne, Fabrice CarratAbstract:Summary Background In HIV–HCV co-infected patients who failed to achieve Sustained Viral Response (SVR) with PEG-IFN + RBV, data on SVR rate after re-treatment with Peginterferon (PEG-IFN) + ribavirin (RBV) are scarce. Aim The aim of this study was to identify factors predictive of SVR after re-treatment in a large cohort of HIV/HCV co-infected patients – the ANRS-CO7 Ribavic cohort study, which is a long term follow-up study of patients who were included in the randomized controlled trial ANRS-HC02 RIBAVIC. Results Among the 176 patients who did not achieve a SVR during the RIBAVIC trial, sixty-six patients (38%) experienced a re-treatment with PEG-IFN + RBV. The SVR observed to the second course of HCV treatment was 44% overall, i.e. 93% in patients who were relapsers and 29% in nonresponders. In the nonresponders subgroup, the SVR rate was 42% in patients with genotype 2–3 and 26% in patients with genotype 1–4. In multivariate analysis, age ≤40 years (OR 12.4 95% CI 1.9–171, p = 0.003), genotype 2–3 versus 1–4 (OR 8.1 95% CI 8.1 1.2–97, p = 0.002) and relapser status at first treatment (OR 32.9 95% CI 3.2–278, p Conclusion Our findings strongly suggest that patients who relapse after first treatment, particularly those infected with HCV genotype 2–3, or living in countries with no access to the direct acting antiViral drugs for HCV, could be successfully re-treated with standard bi-therapy of PEG-IFN + RBV regimen.
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hepatitis c virus infection mixed cryoglobulinemia and kidney disease
American Journal of Kidney Diseases, 2013Co-Authors: Fabrizio Fabrizi, Emmanuelle Plaisier, D Saadoun, Paul Martin, Piergiorgio Messa, Patrice CacoubAbstract:Hepatitis C virus (HCV) may instigate mixed cryoglobulinemia; the most significant accompanying kidney lesion is type I membranoproliferative glomerulonephritis, usually occurring in the context of type II mixed cryoglobulinemia. Additionally, recent data support a link between HCV infection and proteinuria in population-based studies, raising the possibility that kidney diseases associated with HCV may be more common than previously thought. A number of strategies have been used to treat HCV-related glomerulonephritis, including antiViral agents, immunosuppressive therapies such as corticosteroids and cytotoxic agents, and plasma exchange. Limited but encouraging data about the utility of antiViral treatment in the setting of HCV-associated glomerulonephritis exist, with one pooled analysis noting a Sustained Viral Response of 42%, albeit with significant heterogeneity. Immunosuppressive therapy may be most useful for cryoglobulinemic kidney disease, with individualized approaches considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis based on the level of proteinuria and kidney failure. Of note, rituximab, a chimeric monoclonal antibody that blocks CD20 receptors on B cells, has been reported to be effective for the treatment of mixed cryoglobulinemia symptoms, including glomerulonephritis.
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progression of fibrosis in hiv and hepatitis c virus coinfected patients treated with interferon plus ribavirin based therapy analysis of risk factors
Clinical Infectious Diseases, 2008Co-Authors: F Banisadr, Fabrice Carrat, Nathanael Lapidus, Corinne Merle De Boever, Philippe Halfon, Christian Perronne, Pierre Bedossa, Patrice CacoubAbstract:BACKGROUND: We determined the prevalence and determinants of worsening fibrosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were receiving anti-HCV therapy. METHODS: Among 383 HIV-HCV-coinfected patients who received at least 1 dose of anti-HCV treatment (weekly subcutaneous injections of 1.5 mug/kg pegylated interferon-alpha-2b plus daily ribavirin or thrice-weekly subcutaneous injections of 3 MU of interferon-alpha-2b plus daily ribavirin for 48 weeks), paired pretreatment and posttreatment liver biopsy specimens were available and interpretable for 198 cases. Hepatic necroinflammation and fibrosis were graded with Ishak's classification. Histological worsening of fibrosis was defined as a score increase of > or =2 points in patients with fibrosis stage of <4 and as a score increase of 1 point in patients with stage-5 fibrosis. RESULTS: The mean interval +/- standard deviation between the 2 biopsies was 109 +/- 34 weeks. Fibrosis worsened in 34 patients (17.1%). In univariate analysis, ongoing antiretroViral therapy, failure to achieve a Sustained Viral Response, nucleoside reverse-transcriptase inhibitor therapy, didanosine therapy, and stavudine therapy were significantly associated with worsening of fibrosis. Didanosine (odds ratio, 3.34; 95% confidence interval, 1.39-7.96; P = .007) and failure to have a Sustained Viral Response (odds ratio, 9.05; 95% confidence interval, 2.06-39.66; P = .003) remained significantly associated with worsening of fibrosis. CONCLUSION: The mitochondrial toxicity of antiretroVirals, such as didanosine, seems to play a major role in worsening of fibrosis during HCV therapy. Therefore, anti-HCV therapy should ideally be administered before antiretroViral treatment initiation. If anti-HCV and anti-HIV treatments have to be administered concomitantly, then nucleoside reverse-transcriptase inhibitors with the lowest mitochondrial toxicity should be preferred.
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relapse of hepatitis c virus associated mixed cryoglobulinemia vasculitis in patients with Sustained Viral Response
Arthritis & Rheumatism, 2008Co-Authors: Danavi Landau, Philippe Halfon, D Saadoun, M Martinotpeignoux, Patrick Marcellin, Elena Fois, Patrice CacoubAbstract:Objective To investigate the clinical characteristics, outcomes, and results of hepatitis C virus (HCV) RNA analyses in a group of patients with HCV-associated mixed cryoglobulinemia (MC) vasculitis who experienced a relapse of vasculitis despite achieving a Sustained Viral Response to treatment with antiViral agents. Methods HCV RNA testing was performed by the transcription-mediated amplification (TMA) method in sera and cryoprecipitates (detection limit 2.5 IU/ml). HCV replication was assessed in peripheral blood mononuclear cells (PBMCs) by a modified real-time polymerase chain reaction assay (detection limit 15 IU/106 cells). Results We identified 8 patients with relapse of HCV-MC vasculitis despite their having achieved a Sustained Viral Response to treatment. Relapse appeared early after the end of treatment (mean ± SD 2.5 ± 3.5 months) and included mainly purpura (n = 7) and arthralgia (n = 5). Relapse was associated with an increase in serum cryoglobulin levels as compared with end-of-treatment levels (mean ± SD 0.3 ± 0.09 gm/liter and 0.08 ± 0.04 gm/liter, respectively; P < 0.01) and a decrease in C4 levels. In most patients, the relapse was brief, and the MC vasculitis manifestations subsided. A search for HCV RNA by TMA was negative in all patients tested (7 of 8 patients), both in sera and in cryoprecipitates. HCV replication was not found in PBMCs from any of the patients tested (6 of 8 patients). In 3 patients, the MC vasculitis symptoms persisted and were associated with elevated cryoglobulin levels. B cell lymphoma was diagnosed in 2 of these 3 patients. Conclusion Relapse of MC vasculitis does occur in a few patients with HCV infection, despite achieving a Sustained Viral Response, and this relapse is not related to persistence of virus. Relapse is short-lived and may be induced by the withdrawal of interferon alfa therapy. However, in patients with persistent MC vasculitis symptoms, a different underlying condition should be considered, especially B cell lymphoma.
