Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus (HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time, higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C. METHODS: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT). Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received low-dose ribavirin (10 mg(kg·d)) additionally. RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3 showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed (33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response (SVR) rate of only 11.8% (n = 4) could be achieved. CONCLUSION: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without ribavirin, if initial virological response develops early. This finding is worth to be confirmed in a prospective randomized study with pegylated IFN.     

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-α) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV.METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA.RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV(50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=-0.05).CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy.Response rate of SENV to the combination therapy depends on SENV DNA level.     

Hepatitis C virus： Virology, diagnosis and management of antiviral therapy

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.     

Coinfection with hepatitis C virus and schistosomiasis:Fibrosis and treatment response

AIM:To assess whether schistosomiasis coinfection with chronic hepatitis C virus (HCV) influences hepatic fibrosis and pegylated-interferon/ribavirin (PEG-IFN/ RIB) therapy response. METHODS:This study was designed as a retrospective analysis of 3596 chronic HCV patients enrolled in the Egyptian National Program for HCV treatment with PEG-IFN/RIB. All patients underwent liver biopsy and anti-schistosomal antibodies testing prior to HCV treatment. The serology results were used to categorize the patients into group A (positive schistosomal serology) or group B (negative schistosomal serology). Patients in group A were given oral antischistosomal treatment(praziquantel, single dose) at four weeks prior to PEG-IFN/RIB. All patients received a 48-wk course of PEG-IFN (PEG-IFNα2a or PEG-IFNα2b)/RIB therapy. Clinical and laboratory follow-up examinations were carried out for 24 wk after cessation of therapy (to week 72). Correlations of positive schistosomal serology with fibrosis and treatment response were assessed by multiple regression analysis. RESULTS:Schistosomal antibody was positive in 27.3% of patients (15.9% females and 84.1% males). The patients in group A were older (P = 0.008) and had a higher proportion of males (P = 0.002) than the patients in group B. There was no significant association between fibrosis stage and positive schistosomal serology (P = 0.703). Early virological response was achieved in significantly more patients in group B than in group A (89.4% vs 86.5%, P = 0.015). However, significantly more patients in group A experienced breakthrough at week 24 than patients in group B (36.3% vs 32.3%, P = 0.024). End of treatment response was achieved in more patients in group B than in group A (62.0% vs 59.1%) but the difference did not reach statistical significance (P = 0.108). Sustained virological response occurred in significantly more patients in group B than in group A (37.6% vs 27.7%, P = 0.000). Multivariate logistic regression analysis of patient data at treatment weeks 48 and 72 show     

Predictive factors for interferon and ribavirin combination therapy in patients with chronic hepatitis C

AIM： To confirm the predictive factors for interferon （IFN）-α and ribavirin combination therapy for chronic hepatitis patients with hepatitis C virus （HCV） genotype lb. METHODS： HCV RNA from 50 patients infected with HCV genotype lb was studied by cloning and sequencing of interferon sensitivity determining region （ISDR）, PKR- eIF2α phosphorylation homology domain （PePHD）. Patients were treated with IFN-α and ribavirin for 6 mo and grouped by effectiveness of the therapy. A variety of factors were analyzed. RESULTS： Our data showed that age, HCV RNA titer, and ISDR type could be used as the predictive factors for combined IFN-α and ribavirin efficacy. Characteristically, mutations in PePHD appeared only when the combination therapy was effective. Other factors, such as sex and alanine aminotransferase （ALT） level, were not related to its efficacy. Adjusting for age and HCV RNA titer indicated that the ISDR type was the most potent predictive factor. CONCLUSION： HCV RNA ISDR type is an important factor for predicting efficacy of IFN-α and ribavirin combination therapy in Korean patients.     

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM: TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations. PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection. This study investigated the responses ofTT virus(TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS: Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin(1 000 mg-1 200 mg/daily) for 48 weeks. Blood samples were drawn at the beginning and the end of the therapy. Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS: At the beginning of treatment, TIV infection was detected in 10/15 (66.6%) of HCV-infected patients. Loss of serum Trv DNA at the end of therapy occurred in 6/10(60%) patients. Out of these 6 patients, 4 (67%) became positive for TTV DNA after 6 months of therapy. Regarding HCV viremia, 11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy, 7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment. In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy, TTV DNA was detected as well. Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION: No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.     

Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection： A pilot study

AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients. METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs. RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy. CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- a may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.     

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM:TO clarify the effect of SEN virus (SENV) infection on acombination therapy including interferon alfa (IFN-α) orpegylated-IFN with ribavirin in patients with chronic hepatitisand the effect of a combination therapy on SENV.METHODS:SENV DNA was determined by polymerase chainreaction in serum samples from 95 patients with chronichepatitis C.Quantitative analysis was done for SENV H DNA.RESULTS:Twenty-one (22%) of 95 patients were positivefor SENV DNA.There was no difference in clinical andbiochemical parameters between patients with HCV infectionalone and coinfected patients.The sustained response ratefor HCV clearance after combination therapy did not differbetween patients with SENV (52%) and without SENV(50%,n.s.).SENV DNA was undetectable in 76% of theinitially SENV positive patients at the end of follow-up.SENVH response to combination therapy was significantlycorrelated with SENV DNA level (P=0.05).CONCLUSION:SENV infection had no influence on the HCVsustained response rate to the combination therapy.Response rate of SENV to the combination therapy dependson SENV DNA level.     

T29C genotype polymorphism of estrogen receptor alpha is associated with initial response to interferon-alpha therapy in chronic hepatitis B patients

BACKGROUND:Virological clearance,delayed progression to cirrhosis or liver cancer,and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients.Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment.This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha(ESR1) is associated with the initial response to interferon-alpha(IFN-α)therapy in chronic hepatitis B patients.METHODS:The initial responses of 100 patients to IFN-α therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1:T/T,T/C,and C/C genotype groups.Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C.RESULTS:The frequency of initially combined response was markedly higher in both the T/T and T/C groups than in the C/C group(Z=10.326,P=0.006 and Z=26.247,P=0.000, respectively).In addition,the initial virological response was higher in the T/T and T/C groups than the C/C group(χ2=5.674, P=0.017 andχ2=4.980,P=0.026,respectively).In 78 initially HBeAg-positive patients,however,the frequency of initial e-antigen disappearance or seroconversion among the T/T,T/C, and C/C genotype groups was 34.15%,27.78%and 15.79%, respectively,which were not significantly different.CONCLUSION:The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-αin patients with chronic hepatitis B,and might be a significant marker for predicting the initial response to IFN-α,at least in this study population.     

High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

AIM: To evaluate the daily high-dose induction therapy with interferon-α2b (IFN-α2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS: Seventy patients were enrolled in this study. Treatment was started with 10 MU IFN-α2b daily for 3 wk, followed by IFN-a2b 5 MU/TIW in combination with ribavirin (1 000-1 200 mg/d) for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 (IFN-α2b 3 MU/TIW+1 000-1 200 mg ribavirin/daily). RESULTS: The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response (EVR) was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response (EOT) and 40% obtained a sustained viral response (SVR). Patients with no response had a significantly lower response rate than those with a former relapse (SVR 30% vs 53%; P=0.049). Furthermore, lower response rates were observed in patients infected with genotype 1a/b than in patients with non-1-genotype (SVR 28% vs 74%; P=0.001). As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION: Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.     

Sustained virological response based on rapid virological response in genotype-3 chronic hepatitis C treated with standard interferon in the Pakistani population

AIM：To document the sustained virological response （SVR） in rapid virological responders （RVR） of genotype-3 chronic hepatitis C with standard interferon （SdIF）. METHODS：Hepatitis C genotype-3 patients during the period July 2006 and June 2007 were included. Complete blood counts, prothrombin time, ALT, albumin, qualitative HCV RNA were done. SdIF and ribavirin were given for 4 wk and qualitative HCV RNA was repeated. Those testing negative were allocated to group-A while the rest were allocated to group-B. Treatment was continued a total of 16 and 24 wk for group A and B respectively. HCV RNA was repeated after 24 wk of treatment. End virological and sustained virological responses were compared by χ^2 test. ROC of pretreatment age, ALT and albumin were plotted for failure to achieve SVR. RESULTS：Of 74 patients treated, RCV RNA after 16 wk of therapy became undetectable in 34 （45.9%） and was detectable in 40 （54.1%） and were allocated to groups A and B respectively. SVR was achieved in 58.8% and 27.8% in groups A and B respectively. SVR rates were significantly higher in patients who had RVR as compared to those who did not （P = 0.0;γ = 2）. Both groups combined ETR and SVR were 70% and 33% respectively. ROC plots of pretreatment age, ALT and albumin for SVR showed only ALT to have a significantly large area under the curve.CONCLUSION：SVR rates were higher in patients who had RVR with SdIF and high pre treatment ALT values correlated to probability of having RVR.     

Pegylated IFN-α2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B

AIM: To investigate the role of pegylated-interferon (IFN)α-2b in the management of patients with lamivudine-resistant chronic hepatitis B. METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFNα-2b (100μg sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS: Nine patients (45%) had a partial viro-logical end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P=0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P=0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n = 5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION: Pegylated IFNα-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases.     

A candidate DNA vaccine elicits HCV specific humoral and cellular immune responses

AIM: TO investigate the immunogenicity of candidate DNA vaccine against hepatitis C virus (HCV) delivered by two plasmids expressing HCV envelope protein 1 (El) and envelope protein 2 (E2) antigens respectively and to study the effect of CpG adjuvant on this candidate vaccine.METHODS: Recombinant plasmJds expressing HCV EI and E2 antigens respectively were used to simultaneously inoculate mice with or without CpG adjuvant. Antisera were then collected and tJters of antJ-HCV antibodies were analyzed by ELISA. One month after the last injection, animals were sacrificed to prepare single-cell suspension of splenocytes.These cells were subjected to HCV antigen specific proliferaion assays and cytokine secretion assays to evaluate the cellular immune responses of the vaccinated animals.RESULTS: Antibody responses to HCV EI and E2 antigens were detected in vaccinated animals. Animals receiving CpG adjuvant had slightly lower titers of anti-HCV antibodies in the sera, while the splenocytes from these animals showed higher HCV-antigen specific proliferation. Analysis of cytokine secretion from the splenocytes was consistent with the above results. While no antigen-specific IL-4 secretion was detected for all vaccinated animals, HCV antigen-specific INF-γ, secretion was detected for the splenocytes of vaccinated animals. CpG adjuvant enhanced the secretion of INF-γ, but did not change the profile of IL-4 secretion.CONCLUSION: Vaccination of mice with plasmids encoding HCV E1 and E2 antigens induces humoral and cellular immune responses. CpG adjuvant significantly enhances the cellular immune response.     

Treatment responses in Asians and Caucasians with chronic hepatitis C infection

AIM：To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C（CHC） treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians.
METHODS：Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases.Baseline demographic characteristics,biochemical,virological and histological data and details of treatment were collected.Sustained virological responses（SVR） in this cohort were then compared to that in Caucasian subjects,matched by genotype,age,gender and the stage of hepatic fibrosis.
RESULTS：A total of 108 Asians with genotype 1 CHC were identified.The end of treatment response（ETR） for the cohort was 79% while the SVR was 67%.Due to the relatively advanced age of the Asian cohort,only sixty-four subjects could be matched with Caucasians.The ETR among matched Asians and Caucasians was 81% and 56% respectively（P=0.003）,while the SVR rates were 73% and 36%（P 〈0.001） respectively.This difference remained significant after adjusting for other predictive variables.
CONCLUSION： Genotype 1 CHC in Asian subjects is associated with higher rates of virological response compared to that in Caucasians.     

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents

AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C(CHC) treated with new Direct-Acting Antiviral agents(DAAs) compared to pegylated interferon-2α plus ribavirin(P/R) therapy.METHODS This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus(HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index(PASI) scores and the Dermatology Quality of Life Index(DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different b DMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response(SVR) were considered as outcomes of HCV therapy.RESULTS Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower(P 0.001 and P 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group(0/27) compared to 8 patients of the P/R group(8/32) needed a shift in biological treatment.CONCLUSION DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.     

Impact of hepatitis C virus heterogeneity on interferon sensitivity:An overview

Hepatitis C virus(HCV)is a major cause of liver disease worldwide.HCV is able to evade host defense mechanisms,including both innate and acquired immune responses,to establish persistent infection,which results in a broad spectrum of pathogenicity,such as lipid and glucose metabolism disorders and hepatocellular carcinoma development.The HCV genome is characterized by a high degree of genetic diversity,which can be associated with viral sensitivity or resistance(reflected by different virological responses)to interferon(IFN)-based therapy.In this regard,it is of importance to note that polymorphisms in certain HCV genomic regions have shown a close correlation with treatment outcome.In particular,among the HCV proteins,the core and nonstructural proteins(NS)5A have been extensively studied for their correlation with responses to IFN-based treatment.This review aims to cover updated information on the impact of major HCV genetic factors,including HCV genotype,mutations in amino acids 70 and91 of the core protein and sequence heterogeneity in the IFN sensitivity-determining region and IFN/ribavirin resistance-determining region of NS5A,on virological responses to IFN-based therapy.     

Vitamin D status and viral response to therapy in hepatitis C infected children

AIM: To study the frequency of vitamin D deficiency in patients with hepatitis C virus(HCV) infection and to evaluate the role of vitamin D supplementation in improving antiviral therapy.METHODS: Sixty-six children aged from 7-14 years(mean ± SD, 11.17 ± 2.293) diagnosed with HCV infection were matched to 28 healthy controls. Serum levels of 25(OH) D3, calcium, phosphorus, alkaline phosphatase and plasma level of parathormone were measured. Quantitative PCR for HCV was performed Bone density was determined by dual energy X-ray absorptiometry. All cases received conventional therapy, and only 33 patients received vitamin D supplementation.RESULTS: Children with HCV showed significantly increased levels of HCV RNA(P 0.001), parathormone(P 0.01) and decreased vitamin D levels(P 0.05)(33.3% deficient and 43.3% insufficient) compared with controls. Abnormal bone status(Z score-1.98 ± 0.75) was found in ribs, L-spine, pelvis and total body. Cases treated with vitamin D showed significant higher early(P 0.04) and sustained(P 0.05) virological response. There was a high frequency of vitamin D deficiency among the Egyptian HCV children, with significant decrease in bone density. The vitamin D level should be assessed before the start of antiviral treatment with the correction of any detected deficiency. CONCLUSION: Adding vitamin D to conventional Peg/RBV therapy significantly improved the virological response and helped to prevent the risk of emerging bone fragility.     

Efficacy and safety of dual therapy with daclatasvir and asunaprevir in elderly patients

AIM To survey the efficacy and safety of dual therapy with daclatasvir and asunaprevir in the elderly hepatitis C virus(HCV) patients multicentricity.METHODS Interferon-ineligible/intolerant patients and non-responders to previous pegylated-interferon/ribavirin therapy with chronic HCV genotype 1b infection were enrolled. Child B, C cirrhotic patients were excluded.Patients received oral direct acting antiviral treatment consisting of 60 mg daclatasvir once daily plus 200 mg asunaprevir twice daily for 24 wk. We divided the patients into two groups of 56 elderly patients(≥ 75 years-old) and 141 non-elderly patients( 75 years old) and compared the efficacy and safety. RESULTS Ninety-one point one percent of elderly patients and 90.1% of non-elderly patients achieved sustained virological response at 24 wk(SVR24). In the former, 1.8% experienced viral breakthrough, as compared with 3.5% in the latter(not significant). Adverse events occurred in 55.4% of the former and 56.0% of the latter. In the former, 7 cases(12.5%) were discontinued due to adverse events, and in the latter 9 cases were discontinued(6.4%, not significant). CONCLUSION Dual therapy with daclatasvir and asunaprevir achieved the same high rates of SVR24 in HCV elderly patients without more adverse events than in the non-elderly patients.