Canada-Escalating Costs Associated with Untreated Chronic Hepatitis C

New Analysis Reveals the Escalating Costs Associated with Untreated Chronic Hepatitis C

Experts say Canadian health care system not prepared for a 60 per cent increase in total health care costs in the next two decades

TORONTO--(BUSINESS WIRE)--

The Canadian Liver Foundation (CLF) today announced the publication of a new analysis on the long-term impact of hepatitis C virus infection in Canada prepared by leading specialists that projects that Canada will experience a significant increase in cases of advanced hepatitis C-related liver disease over the next 20 years. Associated health care costs will also increase dramatically, mainly attributable to cirrhosis and its complications including liver cancer and liver transplantation.

According to Burden of Disease and Cost of Chronic Hepatitis C Virus Infection in Canada, published in the Canadian Journal of Gastroenterology and Hepatology (May 2014), by 2035, the population with chronic hepatitis C who have cirrhosis and more advanced hepatitis C-related disease will rise to 23 per cent from 8.7 per cent in 2013. Compared to 2013, Canada will experience an increase of 89 per cent in cases of compensated cirrhosis (scarring of the liver with no loss of function) and an increase of 80 per cent in cases of decompensated cirrhosis (severe scarring of the liver with advanced symptoms and loss of function). The analysis projects an increase of 205 per cent in cases of liver cancer and an increase of 160 per cent in cases of liver-related deaths. The authors report that these increases are “substantially greater” than those previously projected by the Public Health Agency of Canada that underestimate the true burden of hepatitis C in Canada.

While the new report reveals that the prevalence of hepatitis C infection peaked in 2003, the longer-term associated health care costs will increase by 60 per cent to $258.4 million at the peak in 2032 from $161.4 million in 2013 as patients age and their liver disease progresses (Note: cost projections do not include antiviral therapy, virology testing and indirect medical costs). The analysis determines that by 2032, 81 per cent of the total health care costs of hepatitis C will be attributable to more advanced liver disease, up from 56 per cent in 2013. In addition, the authors estimate that the lifetime cost for a hypothetical male 35 to 39 years of age with hepatitis C is $64,694, but varies substantially according to disease state – ranging from $51,946 for a patient with no fibrosis in 2013 up to $327,608 for a patient requiring liver transplantation in 2013.

“The Canadian health care system is not prepared to confront the impending epidemic of advanced hepatitis C-related liver disease and associated health care costs,” said Dr. Robert Myers, Director of the Viral Hepatitis Clinic at the University of Calgary and lead author of the article. “There is an urgent need to initiate strategies to enhance the identification of new and existing cases of hepatitis C and to optimize the utilization of new antiviral therapies that treat multiple hepatitis C genotypes and have the highest cure rates with minimal side effects.”

The article states that at current levels of diagnosis and treatment in Canada, patients will face a significant risk of death due to complications of hepatitis C in the coming years. In fact, the authors estimate that more than 32,000 hepatitis C-infected individuals will die of liver-related causes between 2013 and 2035, and that premature death will be substantial with patients only living to an average age of 68 years compared with an average life expectancy in Canada of 81 years.

“We are already seeing increases in liver cancer rates that are linked to hepatitis C infection, and without a concerted effort to identify and treat patients we will be facing dire consequences to both individuals and health care systems,” said Dr. Morris Sherman, Chairman, Canadian Liver Foundation, and a co-author of the article. “Today, we are seeing significantly more patients with compensated cirrhosis than decompensated cirrhosis, but the annual costs of dealing with decompensated cirrhosis are four times greater. So with decompensated cirrhosis estimated to increase by 80 per cent by 2035, this emphasizes the need for early diagnosis and treatment.”

“With estimates that approximately 75 per cent of hepatitis C patients will have early-stage disease at any given point in time, this represents a window of opportunity to intervene before their health starts to rapidly deteriorate,” said Dr. Mel Krajden, Medical Head, Hepatitis and Associate Medical Director, BCCDC Public Health Microbiology and Reference Laboratory, BC Centre for Disease Control, and a co-author of the article. “Given that short-course, well-tolerated treatments are already available and will soon be able to cure greater than 95 per cent of infections, we must find solutions to make treatment accessible for those who need it.”

Another strategy outlined in the article, and recommended by the CLF, is to ensure Canadians born between 1945 and 1975 are screened for hepatitis C. The CLF has been urging the federal government to work with the provinces to develop strategies to eliminate hepatitis C.

“Hepatitis C is curable in most patients. We have an opportunity to act now to be proactive and treat more patients prior to them progressing to more advanced stages of disease when treatment becomes less effective and less well tolerated,” said Dr. Myers. “With these new projections around the future burden and costs of hepatitis C, it is time to shift our thinking from the short-term pain associated with the costs of screening and antiviral therapy, to the long-term gain attributable to preventing hepatitis C-related complications.”

About the Canadian Liver Foundation
Founded in 1969 by a group of doctors and business leaders concerned about the increasing incidence of liver disease, the Canadian Liver Foundation (CLF) was the first organization in the world devoted to providing support for research and education into the causes, diagnoses, prevention and treatment of all liver disease. Through its chapters across the country, the CLF strives to promote liver health, improve public awareness and understanding of liver disease, raise funds for research and provide support to individuals affected by liver disease.

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Brain Imaging Reveals Clues About Chronic Fatigue Syndrome

Brain Imaging Reveals Clues About Chronic Fatigue Syndrome

 Differences in basal ganglia, similarity to inflammation-induced fatigue

In previous published studies by Emory researchers, people taking interferon alpha as a treatment for hepatitis C, which can induce severe fatigue, also show reduced activity in the basal ganglia. Interferon alpha is a protein naturally produced by the body, as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other groups such as breast cancer survivors.

A brain imaging study shows that patients with chronic fatigue syndrome may have reduced responses, compared with healthy controls, in a region of the brain connected with fatigue. The findings suggest that chronic fatigue syndrome is associated with changes in the brain involving brain circuits that regulate motor activity and motivation.

Compared with healthy controls, patients with chronic fatigue syndrome had less activation of the basal ganglia, as measured by fMRI (functional magnetic resonance imaging). This reduction of basal ganglia activity was also linked with the severity of fatigue symptoms.

According to the Centers for Disease Control and Prevention, chronic fatigue syndrome is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be worsened by exercise or mental stress.

The results are scheduled for publication in the journal PLOS One.

“We chose the basal ganglia because they are primary targets of inflammation in the brain,” says lead author Andrew Miller, MD. “Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients.”

Miller is William P. Timmie professor of psychiatry and behavioral sciences at Emory University School of Medicine. The study was a collaboration among researchers at Emory University School of Medicine, the CDC’s Chronic Viral Diseases Branch, and the University of Modena and Reggio Emilia in Italy. The study was funded by the CDC.

The basal ganglia are structures deep within the brain, thought to be responsible for control of movements and responses to rewards as well as cognitive functions. Several neurological disorders involve dysfunction of the basal ganglia, including Parkinson’s disease and Huntington’s disease, for example.

In previous published studies by Emory researchers, people taking interferon alpha as a treatment for hepatitis C, which can induce severe fatigue, also show reduced activity in the basal ganglia. Interferon alpha is a protein naturally produced by the body, as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other groups such as breast cancer survivors.

“A number of previous studies have suggested that responses to viruses may underlie some cases of CFS,” Miller says. “Our data supports the idea that the body’s immune response to viruses could be associated with fatigue by affecting the brain through inflammation. We are continuing to study how inflammation affects the basal ganglia and what effects that has on other brain regions and brain function. These future studies could help inform new treatments.”

Treatment implications might include the potential utility of medications to alter the body’s immune response by blocking inflammation, or providing drugs that enhance basal ganglia function, he says.

The researchers compared 18 patients diagnosed with chronic fatigue syndrome with 41 healthy volunteers. The 18 patients were recruited [not referred] based on an initial telephone survey followed by extensive clinical evaluations. The clinical evaluations, which came in two phases, were completed by hundreds of Georgia residents. People with major depression or who were taking antidepressants were excluded from the imaging study, although those with anxiety disorders were not.

For the brain imaging portion of the study, participants were told they’d win a dollar if they correctly guessed whether a preselected card was red or black. After they made a guess, the color of the card was revealed, and at that point researchers measured blood flow to the basal ganglia.

The key measurement was: how big is the difference in activity between a win or a loss? Participants’ scores on a survey gauging their levels of fatigue were tied to the difference in basal ganglia activity between winning and losing. Those with the most fatigue had the smallest changes, especially in the right caudate and the right globus pallidus, both parts of the basal ganglia.

Ongoing studies at Emory are further investigating the impact of inflammation on the basal ganglia, including studies using anti-inflammatory treatments to reduce fatigue and loss of motivation in patients with depression and other disorders with inflammation including cancer.

Source: Emory Health Sciences

Risk Factors for Hepatocellular Carcinoma in Hepatitis C Patients

Journal of Viral Hepatitis 

Risk Factors for Hepatocellular Carcinoma in Hepatitis C Patients With Normal Alanine Aminotransferase Treated With Pegylated Interferon and Ribavirin 

N. Harada, N. Hiramatsu, T. Oze, N. Morishita, R. Yamada, H. Hikita, M. Miyazaki, T. Yakushijin, T. Miyagi, Y. Yoshida, T. Tatsumi, T. Kanto, A. Kasahara, M. Oshita, E. Mita, H. Hagiwara, Y. Inui, K. Katayama, S. Tamura, H. Yoshihara, Y. Imai, A. Inoue, N. Hayashi, T. Takehara

"All patients who developed HCC had HCV genotype 1 and a high viral load. The first reason is that the patient group with genotype 1 and high viral load is refractory to antiviral therapy. Non-SVR patients are liable to develop HCC. However, three of the 11 patients in this group had SVR. As some researchers have hypothesized, HCV genotype 1 may pose a higher carcinogenic hazard than other genotypes"

Abstract and Introduction
Abstract

Pegylated interferon (Peg-IFN) plus ribavirin combination therapy is effective in patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase levels (NALT). However, it remains unclear whether the risk of hepatocellular carcinoma (HCC) incidence is actually reduced in virological responders. In this study, HCC incidence was examined for 809 patients with NALT (ALT ≤ 40 IU/mL) treated with Peg-IFN alpha-2b and ribavirin for a mean observation period of 36.2 ± 16.5 months. The risk factors for HCC incidence were analysed by Kaplan–Meier method and Cox proportional hazards model. On multivariate analysis among NALT patients, the risk of HCC incidence was significantly reduced in patients with sustained virological response (SVR) or relapse compared with those showing nonresponse (NR) (SVR vs NR, hazard ratio (HR): 0.16, P = 0.009, relapse vs NR, HR: 0.11, P = 0.037). Other risk factors were older age (≥65 years vs <60 years, HR: 6.0, P = 0.032, 60–64 vs <60 years, HR: 3.2, P = 0.212) and male gender (HR: 3.9, P = 0.031). Among 176 patients with PNALT (ALT ≤ 30 IU/mL), only one patient developed HCC and no significant risk factors associated with HCC development were found. In conclusion, antiviral therapy for NALT patients with HCV infection can lower the HCC incidence in responders, particularly for aged and male patients. The indication of antiviral therapy for PNALT (ALT ≤ 30 IU/mL) patients should be carefully determined.
Introduction

The goal of treatment for patients with hepatitis C virus (HCV) infection is not only elimination of the virus, but also prevention of hepatocellular carcinoma (HCC) and thus of death due to liver disease. Therefore, the indication of antiviral therapy should be based on whether or not antiviral therapy can suppress the incidence of HCC.

In the era of interferon (IFN) monotherapy, patients with chronic HCV infection and normal alanine transaminase (NALT) were not considered as candidates for antiviral therapy because SVR rates were very low (6–15%) and ALT flare-up occurred in some cases (47–62%) on IFN therapy.[1–3] Recently, however, the antiviral efficacy of pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic HCV infection has led to equivalent antiviral effects for patients with NALT levels, compared with those with elevated ALT levels (EALT).[4,5] Moreover, ALT flare-up after Peg-IFN plus ribavirin combination therapy for patients with NALT has been reported to be rare.[4] Thus, patients with chronic HCV infection and NALT have come to be considered as candidates for Peg-IFN plus ribavirin combination therapy. What remains unknown is whether or not HCC incidence can be reduced in patients with HCV infection and NALT responding to antiviral therapy. In this study, this is what we tried to elucidate.

Another issue is the risk factors for HCC incidence in patients with HCV infection and NALT. For example, among chronic hepatitis patients with NALT, it is still controversial whether or not the viral load of HCV is related to HCC incidence, although high levels of HBV DNA have been revealed to be a risk factor for HCC incidence in patients with hepatitis B virus (HBV) infection.[6] We therefore also examined patients with chronic HCV infection and NALT, who are at high risk of HCC.

Patients and Methods

This retrospective, multicentre study was conducted by Osaka University Hospital and institutions participating in the Osaka Liver Forum. Of 4640 patients with chronic HCV infection who had been treated by Peg-IFN plus ribavirin combination therapy between December 2004 and December 2009, this study enrolled 809 patients with NALT (ALT ≤ 40 IU/mL) at the start of the therapy who had not suffered from HCC. Among them, 431 patients showed persistent normal alanine aminotransferase (PNALT), defined as an ALT value of ≤40 IU/mL (PNALT40) or ≤30 IU/mL (PNALT30), on two to three occasions separated by at least a month over a period of 6 months.[7,8] PNALT30–40 was defined as the observation of ALT values of 31–40 IU/mL on at least one occasion among PNALT40 patients. This study excluded patients who developed HCC within 12 months from the start of Peg-IFN plus ribavirin combination therapy, patients with co-infection with hepatitis B or human immunodeficiency virus, patients with drug-induced or alcoholic liver disorder and patients with autoimmune hepatitis. The protocol was performed after obtaining informed consent from each patient before treatment in accordance with the ethical guidelines of the 1975 Declaration of Helsinki amended in 2002.

Treatment Protocol

All patients received Peg-IFN alpha-2b (PEGINTRON; Merck & Co. Inc. Whitehouse Station, NJ, USA) plus ribavirin (REBETOL; Merck & Co). The serum HCV RNA levels were qualitatively analysed using the COBAS AMPLICOR HCV test, version 2.0 (lower limit of detection 50 IU/mL; Roche Diagnostics, Branchburg, NJ, USA), and the COBAS AMPLICOR HCV MONITOR test, version 2.0 (detection range 6–5000 K IU/mL; Roche Diagnostics). Among the patients with HCV genotype 1, as a rule, the treatment duration was 48 weeks. However, patients with detectable HCV RNA (≥50 IU/mL) at week 12 and undetectable HCV RNA (<50 IU/mL) at week 24 were treated for 72 weeks. Patients with HCV genotype 2 were treated for 24 weeks.
Definition of Virological Response

A sustained virological response (SVR) was defined as HCV RNA being undetectable at the end of treatment and at 24 weeks after completion of treatment. A relapse was defined as undetectable HCV RNA at the end of treatment, but detectable HCV RNA at 24 weeks after completion of treatment. A nonresponse (NR) was defined as detectable HCV RNA at the end of treatment.
Histological Evaluation

Liver biopsy was performed immediately before initiating the Peg-IFN plus ribavirin combination therapy. Liver biopsy specimens were scored using the METAVIR system, and the grade of activity and stage of fibrosis were evaluated.[9]
Surveillance of HCC

Ultrasonography or computed tomography (CT) was carried out before Peg-IFN plus ribavirin combination therapy and every 3–6 months during the follow-up period. New space-occupying lesions detected or suspected at the time of ultrasonography were further examined by CT or hepatic angiography. HCC was diagnosed by the presence of typical hypervascular characteristics on angiography, in addition to the CT findings. If no typical image of HCC was observed, fine-needle aspiration biopsy was carried out with the patient's consent, or the patient was carefully followed until a diagnosis was possible with a definite observation by CT or angiography.
End Point

The observation period started from the date of the start of Peg-IFN plus ribavirin combination therapy. Patients who developed HCC and patients who were retreated after completion of Peg-IFN plus ribavirin combination therapy were defined as censored cases at that point in time.
Statistical Analysis

Baseline data for various demographic, biochemical and virological characteristics of the patients were expressed as mean ± SD. The variables of age, sex, body mass index, HCV genotype, grading and staging of liver histology, platelet count, serum ALT level and virological response to the combination therapy were examined as correlates of HCC development. The Kaplan–Meier method was used to assess the cumulative incidence of HCC, and the groups were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent factors associated with developing HCC. A value of P < 0.05 (two-tailed) was considered to indicate significance. Statistical software IBM SPSS for Windows, version 19.0.0 (IBM, Armonk, NY, USA), was used for this analysis.

Results

Baseline Characteristics of Patients With Chronic HCV Infection and NALT

Baseline characteristics of the 809 HCV-infected patients with NALT are shown in  Table 1.  The mean age was 56.7 ± 11.0 years, and the ratio of men was 67%. A total of 550 patients (69%) were infected with HCV genotype 1. Liver biopsies were performed for 587 cases, and the ratio of patients with progression of liver fibrosis (METAVIR fibrosis score 3 or 4) was 7.8%. The rate of patients with SVR was 48.7% (263 of 550) in genotype 1 and 74.5% (184 of 247) in genotype 2. The mean observation period was 36.2 ± 16.5 months.

Baseline Characteristics of Patients Who Developed HCC

Eleven patients developed HCC during the observation period. The baseline clinical features before Peg-IFN plus ribavirin combination therapy and the features of the HCC that developed are shown in Table 2. HCC development was observed often in aged patients and male patients.

All who developed HCC were infected with HCV genotype 1 and had a high viral load.

Risk Factors Associated With Incidence of HCC Among Patients With Chronic HCV Infection and NALT

Patients with chronic HCV infection and NALT showed HCC incidences of 1.1% and 3.3% at 3 years and 5 years, respectively, in this study. Significant association with HCC development on univariate analysis was found for age, sex, platelet count and virological response to combination therapy, but not for the amount of HCV RNA (Table 3). Significant factors included older age, male gender and virological response, which were independent factors of HCC incidence in the Cox proportional hazards model (Table 3). The adjusted cumulative incidence of HCC at 3 years by the Cox proportional hazards model was 0.19% among patients <60 years of age, 0.59% among patients 60–64 years of age and 1.12% among patients ≥65 years of age. The cumulative incidence of HCC at 3 years was 0.96% in men and 0.25% in women. As shown in Fig. 1, patients with SVR or relapse had a significantly lower cumulative incidence of HCC than that of patients with NR (cumulative incidence of HCC at 3 years: SVR, 0.20%; relapse, 0.30%; NR, 1.89%).

Figure 1.Cumulative rate of HCC incidence by Cox proportional hazards model according to antiviral effect.

Baseline Characteristics and Risk Factors Associated With HCC Incidence Among Patients With Chronic HCV Infection and PNALT

In this study, patients who met the definition of PNALT40 were 431 of the 809 patients with NALT during the mean observation period of 35.5 ± 15.9 months. Baseline characteristics of the 431 HCV-infected patients with PNALT40 are shown in Table 1. Among the PNALT40 patients, three developed HCC during the observation period (Table 2, cases 4, 9 and 10). Significant association with HCC development by log-rank test was found for older age, male gender, lower platelet count and NR (Table 4). No significant risk factors were found in multivariate analyses of these four variables.

Baseline characteristics of the 176 HCV-infected patients with PNALT30 are shown in Table 1. There were more female PNALT30 patients, more HCV genotype 2 patients, lower BMI, lower activity and lower fibrosis compared with PNALT30–40 patients. Among them, one patient developed HCC during the mean observation period of 33.5 ± 15.9 months (Table 2, case 4). There were no significant risk factors associated with HCC development among these patients (Table 4).

Discussion

Continuous infection with HCV is a leading cause of liver fibrosis which may progress to cirrhosis and HCC.[10,11] HCV carriers with NALT levels are generally considered to have a low risk of carcinogenesis because of minimal liver inflammation and slow progression of liver fibrosis.[12,13] Thus, IFN therapy has not been used for NALT patients. Against this background, there has been no report of antiviral therapy for HCV carriers with NALT reducing HCC incidence. However, a simulation using the Markov model has suggested that Peg-IFN plus ribavirin combination therapy could decrease HCV-related morbidity and mortality in patients with NALT.[14] This needed to be evaluated with patients using Peg-IFN plus ribavirin combination therapy. In the present study, we examined the efficacy of antiviral therapy in patients with chronic HCV infection and NALT from the viewpoint of reducing the risk of HCC. This is the first report indicating that virological responders for antiviral therapy had a significantly lower cumulative incidence rate of HCC than those with NR in patients with chronic HCV infection and NALT.

In the present study, we examined whether successful virological response to Peg-IFN plus ribavirin combination therapy was associated with a low HCC incidence in NALT patients. Considering that reducing the risk of HCC incidence is the goal of antiviral therapy, this result indicates that patients with HCV infection and NALT can also be candidates for antiviral therapy. In particular, male patients ≥65 years of age should be treated earlier even if the ALT level is within the normal range because the factors of age ≥65 years and male gender were identified as independent risk factors for HCC incidence. Several studies have reported that patients ≥65 years of age or male patients generally had a higher risk of HCC incidence among CHC patients with EALT.[15–17] Our results suggest that older male patients with HCV infection should be treated even if they are NALT patients.

All patients who developed HCC had HCV genotype 1 and a high viral load. The first reason is that the patient group with genotype 1 and high viral load is refractory to antiviral therapy. Non-SVR patients are liable to develop HCC. However, three of the 11 patients in this group had SVR. As some researchers have hypothesized, HCV genotype 1 may pose a higher carcinogenic hazard than other genotypes.[18,19]

In Japanese treatment guidelines for patients with chronic HCV infection and NALT levels, HCV carriers with NALT (≤40 IU/mL) at the initial visit are classified into four groups according to their ALT levels (≤30 IU/mL or ≥31 IU/mL) and platelet counts (≥15 × 104 per mm3 or <15 × 104 per mm3). In the univariate analysis according to those categories, low platelet counts (<15 × 104 per mm3) were shown to be the only risk factor for HCC incidence, irrespective of the ALT levels.[20] In the present study, risk factors for HCC incidence were examined among NALT patients by multivariate analysis. As a result, no significant relationship was found between platelet counts or progression of liver fibrosis and HCC incidence. In fact, older patients who developed HCC in this study had relatively high platelet counts and minimal liver fibrosis. Previous studies have shown that older patients with HCV infection even without severe liver fibrosis are at risk of developing HCC.[21] Although the reason for this is not known, mechanisms such as those associated with telomeres may be in part responsible.[22,23] Older patients require extra attention with respect to HCC surveillance, regardless of the progression of liver fibrosis.

In the present study, 431 patients with PNALT40, identified by an ALT value of ≤40 IU/mL on two to three occasions separated by at least a month over a period of 6 months, were examined for HCC incidence. Univariate analysis showed that older age (≥65 years), male gender, lower platelet counts (<12 × 104 per μL) and SVR to combination therapy were significant risk factors for HCC incidence, which were very similar to those for NALT patients; the difference was only that being in relapse was not a significant risk factor for HCC incidence in patients with PNALT40. A longer observation period may reveal a reduction in HCC incidence among relapse patients with PNALT40.

If the definition of PNALT were an ALT value of ≤30 IU/mL on two to three occasions separated by at least a month over a period of 6 months, then 176 of our patients would fit this classification. There were no significant risk factors for HCC incidence among patients with PNALT30, and only one patient with relapse developed HCC during the observation period. No patients with SVR and NR developed HCC. Therefore, little or no liver inflammation among patients with HCV infection and PNALT30 might indicate a fairly low risk of HCC incidence; that is, it may suggest that patients with PNALT30 can be followed up without antiviral therapy from the viewpoint of reducing the risk of HCC incidence. On the other hand, significant risk factors, including male gender and viral response, were found among patients with PNALT30–40 from the univariate analysis. Considering the high risk of HCC incidence, this suggests that patients with HCV infection and PNALT30–40 should be candidates for antiviral therapy.

The limitation of this study was that the HCC incidence was not compared between the treatment and nontreatment groups. HCC incidence was significantly lower in patients with SVR or relapse compared with those with NR as a control group among patients with Peg-IFN plus ribavirin combination therapy. This does not show a clear suppressive effect of antiviral therapy for HCC incidence in NALT patients with HCV infection. However, patients with NR treated with antiviral therapy are reported to have about the same HCC incidence as patients without antiviral therapy.[24] Moreover, Peg-IFN plus ribavirin combination therapy in NALT patients is not effective if a successful virological response does not lead to the reduction in HCC incidence. Our findings that patients with SVR or relapse had significantly lower HCC incidence compared with those with NR suggest that patients with HCV infection and NALT should be candidates for Peg-IFN plus ribavirin combination therapy. A prospective randomized study should be performed to verify the suppressive effect of antiviral therapy for HCC.

In conclusion, among patients with chronic HCV infection and NALT, the cumulative incidence of HCC was significantly lower in patients with SVR and relapse than those with NR to Peg-IFN plus ribavirin combination therapy in the same manner as any EALT patient with HCV infection. Therefore, patients with chronic HCV infection and NALT should be considered as candidates for antiviral therapy from the viewpoint of reducing HCC incidence, especially aged patients (≥65 years) and/or male patients. However, the indication of antiviral therapy for PNALT (ALT ≤ 30 IU/mL) should be carefully examined.

References

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2. Pradat P, Alberti A, Poynard T et al. Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study. Hepatology 2002; 36(4 Pt 1): 973–977.
3. Tassopoulos NC. Treatment of patients with chronic hepatitis C and normal ALT levels. J Hepatol 1999; 31(Suppl 1): 193–196.
4. Zeuzem S, Diago M, Gane E et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology 2004; 127(6): 1724–1732.
5. Hiramatsu N, Inoue Y, Oze T et al. Efficacy of pegylated interferon plus ribavirin combination therapy for hepatitis C patients with normal ALT levels: a matched case-control study. J Gastroenterol 2011; 46(11): 1335–1343.
6. Chen CJ, Yang HI, Su J et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006; 295(1): 65–73.
7. EASL International Consensus Conference on hepatitis C. Paris, 26–27 February 1999. Consensus statement. J Hepatol 1999; 31(Suppl 1): 3–8.
8. Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004; 39(4): 1147–1171.
9. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996; 24(2): 289–293.
10. National Institutes of Health Consensus Development Conference Statement. Management of hepatitis C 2002 (June 10–12, 2002). Gastroenterology 2002; 123(6): 2082–2099.
11. Fattovich G, Giustina G, Degos F et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997; 112(2): 463–472.
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13. Martinot-Peignoux M, Boyer N, Cazals-Hatem D et al. Prospective study on anti-hepatitis C viruspositive patients with persistently normal serum alanine transaminase with or without detectable serum hepatitis C virus RNA. Hepatology 2001; 34(5): 1000–1005.
14. Deuffic-Burban S, Babany G, Lonjon-Domanec I et al. Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France. Hepatology 2009; 50(5): 1351–1359.
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16. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349(9055): 825–832.
17. Kurokawa M, Hiramatsu N, Oze T et al. Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis. Hepatol Res 2009; 39(5): 432–438.
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19. Hatzakis A, Katsoulidou A, Kaklamani E et al. Hepatitis C virus 1b is the dominant genotype in HCVrelated carcinogenesis: a case-control study. Int J Cancer 1996; 68(1): 51–53.
20. Harada N, Hiramatsu N, Oze T et al. Incidence of hepatocellular carcinoma in HCV-infected patients with normal alanine aminotransferase levels categorized by Japanese treatment guidelines. J Gastroenterol 2013; 48(4): 535–543.
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23. Hoare M, Das T, Alexander G. Ageing, telomeres, senescence, and liver injury. J Hepatol 2010; 53(5): 950–961.
24. Ikeda K, Saitoh S, Arase Y et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999; 29(4): 1124–1130.

Weekend Reading - HCV in Egypt and Gilead’s Sovaldi

 A longer version of this article was published in the South-North Development Monitor (SUNS), under the title "No sofosbuvir patent in Egypt, but Gilead deal still expensive", issue #7782, April 10, 2014.

This Article was published on Mada Masr on the 23rd of May 2014

Translated by: Amira Elmasry 

Egypt will not patent new hepatitis C drug

Sunday 25 May 2014

Local newspapers recently reported that the first batch of sofosbuvir, the new drug for treating the hepatitis C virus (HCV), is expected to arrive in August, and the National Committee for the Control of Viral Hepatitis will start identifying the cases that will receive priority treatment.

Sofosbuvir, marketed under the name Sovaldi, is produced by the US-based multinational pharmaceutical company, Gilead Sciences Inc. It is an oral antiviral drug with high cure rates compared to the other antivirals, and is considered a breakthrough in the treatment of HCV.

At the end of 2013, Gilead revealed its plan to launch the new product in the USA at US$30,000 per month. All interested groups around the world received the price unhappily. It is unrealistic and unaffordable for everyone, even state budgets. It is worth noting that the cost of production of one sofosbuvir tablet does not exceed US$2, approximately LE15.

For the past few months, Gilead has been aggressively negotiating with the Egyptian Ministry of Health — represented by the National Committee for the Control of Viral Hepatitis — to approve sofosbuvir for HCV patients. Egypt is certainly a lucrative market for sofosbuvir, not only because of its size but also for its strategic significance.

Negotiations resulted in an agreement on the price of US$300 per bottle, which covers one month of treatment for a single patient only. Some Egyptian and international newspapers started publishing headline stories about Egypt getting the medication at a 99 percent discount of the global price.

The agreed price, US$300 per month, is equivalent to approximately LE2,000, which is the average monthly income of an Egyptian family. However, the Egyptian Ministry of Health considered this price a success.

The treatment course using sofosbuvir is 3-6 months, which will be determined by clinical trials conducted on the most prevalent HCV genotype in Egypt, genotype-4. This means that the treatment cost of sofosbuvir will range from US$900 to US$1,200 per patient.

Do we have enough funds for all the patients who need the treatment?

Rejecting the patent application

While everyone was busy following the negotiations with the ministry, the Egyptian Patent Office (EGYPO) has been examining Gilead’s application to protect the compound sofosbuvir with a patent. But a senior official at EGYPO has said that Egypt will not grant sofosbuvir a patent.

The reason lies in the weakness of the application submitted by the company. Technical examination of the compound has revealed that it is not novel chemically, and therefore does not fulfill the criteria of novelty and inventiveness, both of which are necessary for a pharmaceutical compound to be patented.

The official decision to reject the patent application has not been issued yet. Gilead was notified with the results of the examination, but the EGYPO office has not received any response from the company.

A patent is a form of intellectual property protection. It is a right granted by the state, giving a company the exclusive right to manufacture and market a compound for 20 years, according to the Egyptian Intellectual Property Law and the Agreement on Trade-Related Aspects of Intellectual Property Rights (the TRIPS Agreement).

Without a patent for sofosbuvir, Gilead cannot prevent any other pharmaceutical company from producing and marketing it in Egypt. Hence, Egyptian pharmaceutical companies should be able to manufacture it in Egypt by producing the active pharmaceutical ingredient (API) or by importing and packaging it.

So why don’t Egyptian pharmaceutical companies produce sofosbuvir at a cheaper price?

HCV in Egypt and Gilead’s restrictive policies

Gilead seemed in a rush to close the deal with Egypt, which was on the top of its list to register sofosbuvir. Egypt has the highest prevalence rate of HCV in the world, reaching 14.7 percent of the general population, with infection rates considerably higher in some geographical areas, such as the Nile Delta and Upper Egypt, where prevalence reaches 28 percent and 26 percent, respectively.

There are 8-10 million Egyptians carrying the antibodies of the virus, 5 -7 million of whom suffer from chronic HCV infection. The incidence rate is estimated to be 2-6 per thousand per year, which means that there are at least 170,000 new cases every year — a very high rate. Egypt is a guaranteed market for Gilead to launch its new product.

But despite the fact that Egypt is on top of Gilead’s list to register sofosbuvir, the company has eliminated Egypt from the countries that are authorized to manufacture sofosbuvir under a voluntary license (VL).

This is according to the Treatment Expansion Program the company presented at an international conference held in Bangkok last February, attended by civil society representatives from 22 countries. This means that Egypt cannot locally produce a generic copy of sofosbuvir according to the company’s announced policy. Gilead’s measures for choosing those countries were based on the lack of funds, private funding with regard to HCV treatment and the health care infrastructure.

The company will also make deals for the voluntary licensing of sofosbuvir in some lower middle-income countries that have high infection rates and limited treatment funds. These countries include India, Pakistan, Sudan, South Sudan, Tanzania, Zambia, Zimbabwe and others.

Gilead is currently making licensing deals with several Indian companies to produce sofosbuvir, which makes India the first country to obtain VL to produce sofosbuvir generically at prices much lower than Gilead’s. But due to the company’s current policy, India might not be able to export the active pharmaceutical ingredient to countries that are not on the VL list, including Egypt.

It is quite strange to exclude Egypt from the VL list despite meeting all the criteria. It has the highest prevalence rate of HCV in the world, and has the manufacturing ability to generically produce sofosbuvir at a reasonable price that will cover the size of its market, instead of buying it at the expensive market price.

Cost of treatment and Egyptian government spending

Looking at the price offered to us, US$300 monthly, and considering what the Egyptian government spends on health care in general, and specifically on HCV treatment, it will cost the Egyptian government five times its total expenditure on health in 2011 should all HCV patients receive treatment.

It is also worth mentioning that until 2011, the National Control Strategy had managed to provide treatment for only 1.67 percent of the chronic HCV patients, and that the budget for the National Treatment Program covers only 40 percent of the total amount of the program’s actual spending.

Wahid Doss, head of the National Committee for the Control of Viral Hepatitis, told the Egyptian Initiative for Personal Rights (EIPR) that other entities will contribute to the treatment cost besides the HCV treatment program, such as the Health Insurance Organization and syndicates. There is also the possibility of patient co-payment.

The socio-economic nature of HCV in Egypt should not be ignored. It becomes clear when looking at the geographical distribution of the virus, and also its distribution in relation to wealth. In addition, there is the high private out-of-pocket expenditure on health care and treatment in Egypt, which amounts to 68 percent of the total treatment costs.

That being said, the high price remains the main obstacle to accessing treatment in Egypt.

It is not clear until now how the government — represented by the Ministry of Health and the National HCV Treatment Program — will be able to come up with the funds to buy sofosbuvir.

The details of the deal with Gilead were not disclosed, but members of the Ministry of Health who had attended a conference on hepatitis in Geneva last March revealed that the market price for the public — outside the HCV treatment program — will be set at five times the price of the Ministry of Health, which means US$4,500 for a 12-week treatment course.

According to Gilead, for the treatment of genotype-4, which is most prevalent in Egypt, sofosbuvir is administered in combination with interferon and ribavirin. But Doss told the EIPR that the company is trying to push for a six-month treatment regimen using sofosbuvir only. And this, beyond doubt, would guarantee an even more sizeable market for the company.

This six-month treatment will not be applied until the clinical trials on genotype-4 are finalized, and according to Gilead, the results of these trials are not final and have not been published yet.

It is also unclear whether the price offered for sofosbuvir includes the cost of the interferon and the ribavirin, in case a combination treatment is used. This is an extremely important point that might change all the calculations.

The Ministry of Health’s policy has always been based on negotiating medicine prices to reach a relatively low price for the ministry’s use in the public sector, in exchange for allowing higher prices in the market and the private sector.

Given the high private expenditure on treatment in Egypt — the amount patients pay out of their own pockets to purchase treatment without any insurance coverage — a large sector of HCV patients will remain untreated, because the market price exceeds their budget.

The importance of local manufacturing in Egypt

Several Egyptian pharmaceutical companies have recently expressed their wish to produce sofosbuvir locally, and some have even started communicating with the manufacturers of the APIs in other countries.

Local production does not only provide the patients and government with affordable medicines, but also creates competition, which forces the medicine's originator company to lower its prices in the Egyptian market.

There was a precedent in the case of HCV treatment when the Egyptian company Minapharm started producing a biosimilar version of pegylated interferon, forcing Roche to lower the price of its product.

The problem lies in the Ministry of Health’s lack of support for the pharmaceutical industry’s efforts, as some representatives of national companies have expressed. This was made clear when such an important issue did not come up on the agenda during negotiations with Gilead.

The decision makers in the Ministry of Health — represented by the Committee and the Central Administration for Pharmaceutical Affairs — were supposed to discuss the restrictive policy regarding local manufacturing applied by Gilead, and this unfair condition should have received more attention from the state.

According to the TRIPS Agreement signed by Egypt and the Intellectual Property Law, Egyptian companies can manufacture any compound that is not patented within the Egyptian territory, which should be the current case of sofosbuvir.

Also, according to the same texts, the Egyptian state can terminate the patent of any protected medicine it deems important to supply for Egyptian patients at lower prices — this practice is referred to as compulsory licensing. This is one of the options Egypt can resort to in case a medicine price is unaffordable, or in the case of an epidemic outbreak that threatens national security.

If we consider HCV to be a matter of national security, then the state needs to stand up against the abuse of international companies, whether in pricing its products or in hindering local manufacturing.

A longer version of this article was published in the South-North Development Monitor (SUNS), under the title "No sofosbuvir patent in Egypt, but Gilead deal still expensive", issue #7782, April 10, 2014.

This Article was published on Mada Masr on the 23rd of May 2014

How I Manage HCV Patients for Whom First-Generation Protease Inhibitors Failed

Post-EASL Update: How I Manage HCV Patients for Whom First-Generation Protease Inhibitors Failed

Stefan Zeuzem, MD - 5/19/2014  More from this author 

Successes and Failures With Protease Inhibitors

A few years ago, hepatitis physicians got excited about the approval of the first direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) therapy, the NS3/4A protease inhibitors boceprevir and telaprevir. In treatment-naive patients, an approximate 30% increase in sustained virologic response (SVR) rates was achieved with the addition of either boceprevir or telaprevir to the long-standing standard of care, peginterferon and ribavirin. In treatment-experienced patients, the response rates for virologic relapsers were excellent, but they were a good deal lower for previous peginterferon/ribavirin partial and null responders, particularly those with more advanced liver disease. The discussion was fierce as to whether or not previous null responders with advanced fibrosis or cirrhosis should be treated with these regimens, given that SVR rates in this population were only approximately 15%. Data from the real-world CUPIC cohort study in cirrhotic patients recently reminded us that interferon-based therapies have the potential to be dangerous and are associated with a high incidence of morbidity and mortality in patients with specific risk factors, including serum albumin < 3.5 g/dL and/or platelets < 100,000 cells/mm³.

Although only 10% to 20% of previously untreated patients and relapsers experienced virologic failure on first-generation protease inhibitors, the rate of virologic breakthrough and relapse was much higher in patients with cirrhosis and a previous partial or null response to peginterferon and ribavirin. The latter patients continue to have an urgent indication for therapy, but what can we offer?

The majority of patients who developed virologic failure on first-generation protease inhibitors selected for resistance associated variants (RAVs). Early studies showed that a proportion of RAVs reverted back to wild-type variants (faster for HCV genotype 1b than for genotype 1a isolates) most likely due to lower replication fitness of the RAVs compared with wild-type variants. In theory, patients with apparent disappearance of RAVs could be retreated with protease inhibitors in combination with peginterferon and ribavirin and perhaps a second DAA. This concept has never been investigated in larger clinical trials, although small case series supported its general plausibility. Treatment guidelines from the AASLD/IDSA recommend that patients in whom previous treatment with boceprevir or telaprevir has failed should not be retreated with peginterferon/ribavirin plus a protease inhibitor, however, given the shortage of data supporting this approach. 

My Approaches Now and In the Future
An approach I have used for patients who did not respond to triple therapy with a first-generation protease inhibitor is retreatment with peginterferon and ribavirin in combination with an agent from a different class of DAA. The combination of peginterferon and ribavirin with the nucleoside polymerase inhibitor sofosbuvir seems like an attractive option given its current clinical availability. However, this treatment strategy has not been formally investigated in large clinical studies of genotype 1 patients; indeed the NEUTRINO study that evaluated peginterferon/ribavirin plus sofosbuvir for genotype 1 infection did not enroll any treatment-experienced patients. This treatment strategy was recently evaluated by Pol and colleagues in a small trial in 80 patients who did not respond to treatment with peginterferon/ribavirin plus an investigational protease inhibitor with or without 1 or 2 additional DAAs. However, the data from this study are not yet fully published. Despite the presence of multiple resistance associated variants at baseline, the overall SVR12 rate among 50 evaluable patients was 74%. In my limited personal experience, the NEUTRINO-like approach (peginterferon, ribavirin, and sofosbuvir for 12 weeks) works well in patients who did not respond to boceprevir- or telaprevir-based triple therapy, and this approach is recommended in the AASLD/IDSA guidelines. Another strategy recommended in the AASLD/IDSA guidelines for this population is sofosbuvir for 12 weeks plus peginterferon and ribavirin for 24 weeks, whereas sofosbuvir plus ribavirin for 24 weeks or peginterferon, ribavirin, and sofosbuvir for 24 weeks are included as alternative approaches. None of these strategies, however, has been formally evaluated in large clinical trials. 

New Retreatment Strategies Presented at EASL
 Exciting data on the use of all-oral treatment for the management of patients who did not achieve SVR during protease inhibitor therapy have emerged during the past year. In a phase II study first presented at EASL 2013, patients who failed triple therapy with a protease inhibitor were retreated with only 2 DAAs (sofosbuvir and the NS5A inhibitor daclatasvir) with or without ribavirin, but without peginterferon, for 24 weeks. In this retreatment study, all patients receiving the ribavirin-free regimen and 95% of those who received 2 DAAs plus ribavirin achieved SVR12. The efficacy of this approach was confirmed in a recent phase III study presented at the 2014 EASL meeting, ION-2, where patients who failed previous peginterferon/ribavirin with or without a protease inhibitor were retreated with sofosbuvir and a different NS5A inhibitor, ledipasvir, with or without ribavirin for 12 or 24 weeks. SVR rates in this study exceeded 94%. Clearly, with these data, interferon-free retreatment strategies with a potent nucleoside polymerase inhibitor and an NS5A inhibitor will be the preferred option for patients failing protease inhibitor–containing triple therapy, whenever these drugs are accessible. 

Your Thoughts?
 I’m interested to hear about your own approach to managing patients who have failed boceprevir- or telaprevir-containing regimens, given the recent data presented at EASL 2014. What is your preferred strategy in this setting? Please use the comments section below to provide your insights.

Topics: HCV - Treatment 

New This Month: Clinical Thoughts

Post-EASL Update: What Is the Role of Treatment Guidelines in the Current HCV Era?

With the new era of HCV therapies comes a new era in clinical guidelines; although there is certainly overlap, the major guidelines serve different but important roles.

Post-EASL Update: Reconsidering Whether to Treat Genotype 1 HCV Patients or Wait for All-Oral Therapy

Following the presentation of phase III data on new all-oral regimens for genotype 1 HCV at EASL, which patients might wait for the approval of new therapies and which should be treated now?

Treating HBV Patients With Cirrhosis: The Need for Vigilant HCC Screening

Antiviral therapy can dramatically improve liver histology, even in cirrhotic patients, but it remains critical to screen patients with suppressed viral load for hepatocellular carcinoma.

Clinical Care Options

Tipping Point: The Unprecedented Hepatitis C Situation

Hepatitis C: A Brief Medical Primer
Rena Fox, Professor of Medicine, UCSF @UCSF 

Tipping Point: The Unprecedented Hepatitis C Situation
Moderated By:  James Hamblin, Senior Editor, The Atlantic
Richard Elion, Clinical Research Director, Whitman-Walker Health
Rena Fox, Professor of Medicine, UCSF
Donald Jensen, Director of the Center for Liver Diseases, University of Chicago
Steven Pearson, President, Institute for Clinical and Economic Review; Visiting Scientist, Department of Bioethics, National Institutes of Health

From AtlanticLIVE
Medicine, the Market, and You
We asked two industry experts a simple question: what are the market-based solutions to the high price of pharmaceuticals?

Source

Treatment of Hepatitis C: At Last the Holy Grail

Access Medicine from McGraw-Hill

Treatment of Hepatitis C: At Last the Holy Grail

Kurt J. Isselbacher
AccessMedicine from McGraw-Hill

Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma. In fact it is estimated that about 3% of the world’s population is chronically infected with the hepatitis C virus (HCV). Until recently the treatment of HCV has left a lot to be desired. One of the key limitations has been that the therapeutic regimen has included interferon, which in many patients is associated with disturbing and debilitating side effects. In addition, the current treatment leads to a sustained viral response in only 45–70% of patients as well as a high incidence of disease recurrence. Furthermore, the treatment requires parenteral rather than oral therapy.

Now a number of clinical trials have finally shown that an effective treatment can be achieved using an oral tablet containing two direct-acting antiviral agents (Afdhal and colleagues, 2014; Pawlotsky, 2014). These agents target key proteases and polymerases that are essential for HCV replication.

Most of these trials included the use of ledipasvir and sofosbuvir (or their variants), which have potent activity against HCV. These drugs were given daily as oral tablets for 8, 12, or 24 weeks with or without ribavirin. The results were consistent and striking—namely, the various regimens yielded rates of sustained virologic response of 93–99%. Even without ribavirin, the response rates after 12 weeks ranged from 94% to 99%. It is also noteworthy that the single-tablet regimen was easy to administer and had few side effects. Among the patients who received the two antiviral agents alone for 12 weeks, very few stopped therapy because of adverse events (Chung and Baumert, 2014).

We will hear much more about these and other direct-acting antiviral agents for the treatment of HCV, but one thing is certain—namely, we have reached a major milestone and now have available a spectrum of direct anti-HCV drugs that augur well for curing this terrible disease.

Unfortunately, there is one caveat that qualifies all of the good news. The cost of the treatment is enormous. At present, a 12-week treatment of sofosbuvir alone costs $84,000, or approximately $1000 per tablet (Hoofnagle and Sherker, 2014). The addition of ledipasvir obviously will add to this cost.

Source - Medscape

References

• Afdhal N et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370:1483. [PubMed: 24725238]
• Chung RT, Baumert TF. Curing chronic hepatitis C—the arc of a medical triumph. N Engl J Med. 2014;370:1576. [PubMed: 24720678]
• Hoofnagle JH, Sherker AH. Therapy for hepatitis C—the costs of success. N Engl J Med. 2014;370:1552. [PubMed: 24725236]
• Pawlotsky J. New hepatitis C therapies: The toolbox, strategies, and challenges. Gastroenterology. 2014:146:1176. [PubMed: 24631495]

HCV genotype 4 patients achieved SVR12 with triple therapy

HCV genotype 4 patients achieved SVR12 with triple therapy
May 23, 2014
Source - Healio

CHICAGO — Hepatitis C virus genotype 4-infected patients met sustained virologic response at 12 weeks with an all-oral triple therapy of daclatasvir, asunaprevir and the non-nucleoside NS5B inhibitor BMS-791325, according to research presented at Digestive Disease Week 2014.

Researcher Tarek Hassanein, MD, of the Southern California Liver Centers, and colleagues randomly assigned 21 treatment-naive hepatitis C virus genotype 4-infected patients to either 30 mg daclatasvir, 200 mg asunaprevir, and 75 mg BMS-791325 (Bristol-Myers Squibb; n=11) twice daily or 150 mg BMS-791325 (n=10) twice daily for 12 weeks. Patients were primarily men (62%), white (91%) and noncirrhotic.

According to data, 10 of the 75-mg BMS-791325 patients achieved sustained virologic response at 12 weeks (SVR12), with the other missing patient meeting SVR24. Nine patients in the 150-mg BMS-791325 group achieved SVR12, with one patient still being followed.

There were no reports of patients experiencing virologic failure or post-treatment relapses; no serious adverse events (AE) were reported. The most common AE were headache (29%), nausea (14%) and pain (14%).

“One hundred percent of the patients with genotype-4 achieved an SVR at or after post-treatment week 12,” Hassanein said during his presentation. “There were no differences between the doses of [BMS-791325], and they were both effective.”

For more information:
Hassanein T. #763. Presented at: Digestive Disease Week 2014; May 3-6; Chicago.
Disclosure: The researchers report numerous relevant financial disclosures.

View Slides and DDW Coverage @ NATAP
DDW: All-Oral Therapy With Daclatasvir in Combination With Asunaprevir and BMS-791325 for Treatment-Naive Patients With Chronic HCV Genotype 4 Infection - (05/06/14)