Critical issues in the treatment of hepatitis C virus infection in methadone maintenance patients

AIMS: Hepatitis C virus (HCV) infection is a common chronic complication of injection drug use. Methadone maintenance programs contain large numbers of patients infected with HCV. This paper reviews HCV infection with emphasis on the medical care of HCV-infected, or HCV and human immunodeficiency virus co-infected, patients on methadone or buprenorphine maintenance. METHODS: Literature searches using PubMed, PsycINFO and SocINDEX were used to identify papers from 1990-present on antiviral therapy for HCV in methadone maintenance patients and on liver transplantation in methadone maintenance patients. RESULTS: Injection drug use is the most significant risk factor for HCV infection in most western countries. The prevalence of HCV antibody is high in injection drug users (53-96%) and in patients enrolled in methadone maintenance programs (67-96%). Studies of antiviral therapy for HCV in methadone maintenance patients show rates of sustained virological response (SVR), defined as negative HCV-RNA 24 weeks after the end of treatment, of 28-94%. In studies with contrast groups, no significant differences in SVR between methadone and contrast groups were found. Excellent completion rates of antiviral therapy (72-100%) were found in five of six studies. There are many barriers to methadone maintenance patients' receiving antiviral therapy, and research on overcoming barriers is discussed. Liver transplantation has been successful in methadone maintenance patients but has not been utilized widely. CONCLUSION: High quality medical care for all aspects of HCV infection can be provided to methadone maintenance patients. The literature supports the effectiveness of such services, but the reality is that most patients do not receive them.     

Hepatitis C treatment in "difficult-to-treat" psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects

We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric-risk patients and controls with pegylated interferon alpha (pegIFN-alpha) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders. Seventeen patients without psychiatric diseases or drug addiction (controls), 22 patients with psychiatric disorders, 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN-alpha plus ribavirin. Sustained virological response (SVR), adherence, and psychiatric side effects (using the Montgomery-Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale) in the groups were compared. An SVR was found in 58.6% of all patients: 58.8% of the controls, 50% of psychiatric patients, 72.2% of methadone patients, and 53.8% of former drug users. Methadone-substituted patients and former drug users had significantly higher dropout rates. Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment. However, the controls had lower pretreatment scores, followed by a significant higher increase to maximum scores. A stepwise logistic regression model showed that only genotype, not group (control, psychiatric, methadone, or former drug abuse), type of psychiatric diagnosis (affective disorder, personality disorder, or schizophrenic disorder), depression scores before and during treatment, change in depression score, antidepressive treatment, sex, or liver enzymes before treatment, was associated with SVR. CONCLUSION: In an interdisciplinary treatment setting psychiatric diseases and/or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN-alpha and ribavirin.     

Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin

BACKGROUND AND AIM: The therapeutic effect of pegylated interferon (peg-IFN)-alpha-2a combination with ribavirin on patients with chronic hepatitis C virus (HCV) infection is dependent on the rapidity of the virological response. The aim of this study was to investigate the predictive value of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in HCV patients treated with peg-IFN-alpha-2a and ribavirin. METHODS: The HCV genotypes of 105 patients with chronic hepatitis C were detected by enzyme-immunoassay. Patients received subcutaneous 180 microg peg-IFN-alpha-2a once weekly plus daily ribavirin. Patients with genotype 1 were treated for 48 weeks and patients with genotype 2 or 3 were treated for 24 weeks. HCV RNA was assessed by qualitative PCR at pretreatment, at weeks 4 and 12 during treatment, and at week 24 of follow-up. Virological response rates at different weeks were investigated, with RVR defined as serum HCV RNA undetectable after 4 weeks and EVR defined as HCV RNA either undetectable or decrease by >or=2 log(10) after 12 weeks. The effects of virological response rates at different weeks on SVR were analyzed. RESULTS: Of the 105 patients, 44 (41.9%) were genotype 1, 46 (43.8%) were genotype 2, and 15 (14.3%) were genotype 3. RVR rates (19.5%) of patients with genotype 1 were significantly lower than those (60.7%) of genotype 2 or 3 (chi(2) = 16.836, P = 0.000); and EVR rates (73.2%) of patients with genotype 1 were significantly lower than those (96.7%) of genotype 2 or 3 (chi(2) = 12.220, P = 0.000). The SVR rates (86.7%) of patients who had achieved RVR were significantly higher than those (43.9%) of patients who had not achieved RVR (chi(2) = 19.713, P = 0.000). The positive predictive value of RVR in all patients was higher than that of EVR, but there was no significant difference between RVR and EVR. The negative predictive value of RVR in all patients or with genotype 1 was significantly lower than that of EVR. In univariate analysis, HCV RNA level (P = 0.014), genotype (P = 0.001), RVR (P = 0.000) and EVR (P = 0.000) were associated with effect of treatment. However, in stepwise regression analysis, the independent factors associated with effect of antiviral therapy were RVR (OR = 6.501, P = 0.001), EVR (OR = 2.776, P = 0.003) and genotype (OR = 3.061, P = 0.024). CONCLUSIONS: The RVR and EVR rates of patients with genotype 1 were significantly lower than those of patients with genotype 2 or 3. RVR had a similar predictive value as EVR on SVR. Genotype, HCV RNA level, RVR and EVR were associated with SVR. Genotype, RVR and EVR were independent factors for predicting the effect of antiviral therapy.     

广西和贵州部分美沙酮维持治疗门诊服药人员HIVHCV梅毒及HSV-2感染状况

目的了解广西、贵州美沙酮维持治疗（MMT）门诊服药人员中,艾滋病病毒（HIV）、丙型肝炎病毒（HCV）、梅毒螺旋体（TP）及单纯疱疹病毒Ⅱ型（HSV-2）的感染情况。方法对两省（自治区）艾滋病疫情较重地区的16个美沙酮门诊的1 678名服药人员进行问卷调查,同时检测抗-HIV抗体、抗-HCV抗体、梅毒抗体,并对HIV抗体阳性者检测HSV-2抗体。结果 1 652人中,抗-HIV、抗-HCV及梅毒抗体的阳性率分别为26.63%（440/1 652）、83.36%（1 377/1 652）和5.08%（84/1 652）。440例HIV阳性者中,433人检测了HSV-2,HSV-2抗体阳性率为57.27%（248/433）。结论被调查人群中,HIV、HCV、梅毒感染率均高,而且抗-HIV阳性者中,HSV-2感染率很高,应加强对该人群的管理和服务,以防止这些疾病进一步蔓延。     

The GNB3 C825T polymorphism affects response to HCV therapy with pegylated interferon in HCV/HIV co-infected but not in HCV mono-infected patients

BACKGROUND/AIMS: Response to HCV treatment with pegylated interferon-alpha is variable but might at least in part depend on genetic host factors. The G protein beta3 unit (GNB3) C825T polymorphism has been shown to affect treatment response in HCV mono-infection. Here, we analyzed the impact of the GNB3 genotype in the context of HCV/HIV co-infection. METHODS: HIV/HCV co-infected (n=112) and HCV mono-infected patients (n=150), receiving therapy with pegylated IFN-alpha/ribavirin, were enrolled into this study. Furthermore, we analyzed 220 healthy and 92 HIV mono-infected patients. GNB3 genotype was defined and correlated with respect to treatment response. RESULTS: GNB3 genotype distribution differed significantly between HIV/HCV co-infected patients and HIV-positive/HCV-negative (p=0.0002) or healthy controls (p=0.03). Patients with a GNB3 CC genotype had significantly lower SVR rates as compared to carriers of a non-CC genotype (52% versus 77%; p=0.018). In a logistic regression analysis the GNB3 genotype and the HCV genotype were significantly associated with response to treatment (p=0.018). In contrast to HIV/HCV co-infected patients, GNB3 genotype did not affect response to treatment in HCV mono-infected patients. CONCLUSIONS: The GNB3 825 CC genotype is associated with poor SVR rates in HIV/HCV co-infected patients. This underlines the impact of genetic host factors for treatment response.     

The Hepatitis C virus treatment cascade at an urban postincarceration transitions clinic

Transitions clinics, which provide medical care to individuals who have been released from incarceration, reach a population at high risk for hepatitis C Virus (HCV) infection. We used the HCV treatment cascade to describe HCV care at an urban postincarceration transitions clinic, identifying gaps in care and determining reasons for lapses in care. In this retrospective cohort study, we reviewed electronic health records for all formerly incarcerated individuals receiving care at the Bronx Transitions Clinic. HCV treatment cascade measures included the following: detection of HCV antibodies, confirmation of chronic infection, specialist referral, specialist evaluation, initiation of treatment, completion of treatment and achievement of SVR. We recorded reasons for lapses in care. Of 451 patients accessing care, 317 (70%) were screened for HCV antibodies, and 106 (33%) tested positive. Of the 106 antibody‐positive patients, 93 (88%) were evaluated for HCV viremia and 84 (79%) were confirmed to have chronic HCV infection; 19% of the total sample had chronic HCV infection. Of these 84 with chronic HCV, 48 (57%) received specialist referral, 30 (36%) were evaluated, 8 (10%) initiated treatment, and 5 (6%) completed treatment and achieved SVR. Some treatment lapses occurred because patients were deemed unstable for treatment (12%) or were re‐incarcerated (5%). Chronic HCV infection was common among transitions clinic patients. Few were treated and cured. Patients lost contact with providers before consideration for antiviral therapy. Referral to specialty providers was a gap in care. Increasing HCV treatment in this population will likely require intensive delivery models.     

Role of individualization of hepatitis C virus (HCV) therapy duration in HIV/HCV-coinfected individuals

OBJECTIVE: The aim of this study was to assess the efficacy, safety and tolerability of pegylated interferon and ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients, prescribed for the same duration and at the same dosage as that used in HCV monoinfection studies. DESIGN: It was an open-label, single-centre, prospective study. METHODS: Forty-five patients coinfected with HIV and HCV with CD4 counts >200 cells/microL were treated with pegylated interferon-alpha2b 1.5 microg/kg/week and ribavirin 1000-1200 mg/day for 24-48 weeks depending on HCV genotype. Safety and tolerability were assessed weekly for the first month and monthly thereafter. Virological response was assessed at weeks 4, 12 and 24 and at the end of treatment and 12 and 24 weeks post completion of treatment. The primary endpoint was defined as undetectable HCV RNA at 24 weeks post completion of treatment [sustained virological response (SVR)]. RESULTS: The majority of patients were male and had been injecting drug users. Sixty per cent were on antiretroviral therapy. In an intention-to-treat analysis, 53% had an SVR (genotype 1, 19% and genotype 2/3, 75%). All patients who had undetectable HCV RNA at week 4 of HCV treatment [very early virological response (VEVR)] had a SVR. On multivariate analysis only HCV genotype predicted SVR. Adverse events occurred frequently. CONCLUSIONS: These results indicate that 24 weeks of HCV treatment may be adequate for HIV-infected individuals coinfected with HCV genotype 2 or 3. VEVR can predict SVR in this group and may be used to guide the subgroup of genotype 2/3 individuals who will respond to 24 weeks of treatment.     

Hepatitis C in injection drug users:It is time to treat

Injection drug users(IDUs)are at risk of hepatitis C virus(HCV)infection,due to needle and syringe sharing.Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antiviral treatment leading to sustained viral response(SVR).It is well demonstrated that,when close cooperation between specialists in drug addiction and psychiatrists is assured,patients on maintenance treatment with methadone/buprenorphine can be treated for HCV with response rate,tolerability and side effects similar to those reported in non-IDUs.Current guidelines recommend that active injection drug use should not exclude patients from HCV treatment,but many services remain reluctant to treat IDUs.No significant pharmacodynamic interactions were reported between approved direct anti-viral agents(DAAs)and buprenorphine or methadone.Dose adjustments are not recommended;therefore DAAs appear to be the"perfect"therapy for patients taking opiate substitutive therapy.These suggestions have been recently recognized by the European Association for the Study of the Liver(EASL)and included in EASL Recommendations on Treatment of Hepatitis C 2016.Guidelines confirm that HCV treatment for IDUs should be considered on an individualized basis and delivered within a multidisciplinary team setting;a history of intravenous drug use and recent drug use at treatment initiation are not associated with reduced SVR and decisions to treat must be made on a case-by-case basis.     

Current and future treatment options for HCV

Aim of antiviral therapy of patients with chronic hepatitis C is the sustained elimination of the hepatitis C virus (HCV). The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. Overall, approximately half of the patients can be cured by SOC. Based on baseline viral load and the speed of virologic response during treatment, individualization of treatment duration is possible. However, this approach is not sufficient to substantially improve the sustained virologic response (SVR) rates. This goal can be achieved with new HCV specific inhibitors against the NS3/4A polymerase and the NS5B polymerase. Recent trials reported SVR rates in the order of 67-69% and 67-75% for the combination of SOC with the protease inhibitors telaprevir and boceprevir, respectively, in patients with HCV genotype 1 infection. Several new HCV specific inhibitors such as protease inhibitors, nucleoside and non-nucleoside polymerase inhibitors as well as non HCV specific compounds with anti-HCV activity such as cyclophilin inhibitors, silibinin, and nitazoxanide are currently in clinical evaluation. The review describes recent developments and discusses limitations posed by resistance development and drug toxicity.     

Intravenous drug use: not a barrier to achieving a sustained virological response in HCV infection

Hepatitis C virus (HCV) is commonly transmitted by intravenous drug use (IDU) but drug users are under represented in many treatment cohorts, this is because of the assumption of lowered treatment success. We assessed HCV treatment outcomes in active intravenous drug users and patients on opiate substitution therapy. The Tayside HCV treatment database was retrospectively analysed for consecutively treated patients based on risk factor for acquisition of HCV. Primary end point was sustained virological response (SVR). Two hundred and ninety-one consecutively treated patients were assessed. The overall SVR rate was 55.3%. The SVR rates by risk factor were; Non-IDU 61.4%, Ex-IDU 54.8% and Active IDU 47.1% (P = n/s). In the groups G1 patients SVR was; Non-IDU 52.7%, Ex-IDU 30.7% and active IDU 35.4% (P = n/s). In the non-G1 patients: non-IDU 65.1%, Ex-IDU 76.7% and active IDU 53.5%. Ex-IDU had a significantly better SVR than active IDU, other differences were not significant. Our results demonstrate that SVR rates in the active drug users and those on opiate substitution therapy can be achieved which are comparable with non-IDU infected individuals. Intravenous drug use in those engaged with treatment services should not be seen as a barrier to treatment of HCV.     

Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open‐label,phase 3 trial

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open‐label study to assess the efficacy and safety of an all‐oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment‐naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight‐based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment‐naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment‐naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.     

Determinants of antiviral treatment initiation in a hepatitis C-infected population benefiting from universal health care coverage.

BACKGROUND AND AIMS: In view of increasing therapeutic efficacy, the delivery of hepatitis C virus (HCV) antiviral treatment is expected to increase. Yet practical experience reveals a low rate of treatment, particularly among intravenous drug users. The aim of the present study was to examine the prevalence of HCV treatment and identify factors associated with HCV treatment in a population of patients evaluated in an academic hepatology outpatient clinic between 2001 and 2002. PATIENTS AND METHODS: The charts of HCV-infected patients who attended the outpatient clinic of the liver division between January 2001 and December 2002 were retrospectively reviewed. Regression analyses were conducted to compare patients according to HCV treatment initiation. RESULTS: Of 378 eligible patients (past intravenous drug users 61%), 143 (38%) initiated antiviral treatment. Enrolment in a methadone maintenance program and a strong willingness to get treatment were independently associated with treatment initiation, while current intravenous drug use, alcoholic liver damage on biopsy, precarious housing arrangements and personality disorders were negatively associated with treatment initiation. Among patients who were offered treatment, 40% refused (they did not differ from the treated group for past or current substance abuse). CONCLUSIONS: Only 38% of eligible patients initiated treatment; treatment refusal was very common. The results of the present study showed that a significant barrier to therapy involved patient perceptions.     

Methadone maintenance therapy promotes initiation of antiretroviral therapy among injection drug users

Aims Despite proven benefits of antiretroviral therapy (ART), many human immunodeficiency virus (HIV)‐infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. Design We examined prospectively a cohort of opioid‐using antiretroviral‐naive HIV‐infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors associated independently with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. Findings Between May 1996 and April 2008, 231 antiretroviral‐naive HIV‐infected opioid‐using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 [95% confidence interval (CI): 25.9–35.6] per 100 person‐years. After adjustment for time‐updated clinical characteristics and other potential confounders, use of MMT was associated independently with more rapid uptake of antiretroviral therapy [relative hazard = 1.62 (95% CI: 1.15–2.28); P = 0.006]. Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation [odds ratio = 1.49 (95% CI: 1.07–2.08); P = 0.019]. Conclusion These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid‐using HIV‐infected IDU. Addressing international barriers to the use and availability of methadone may increase dramatically uptake of HIV treatment among this population.     

Liver transplantation in the setting of chronic HCV

Recurrent HCV disease is the most common cause of graft loss and patient mortality in HCV-infected liver transplant (LT) recipients. Risk factors for more severe recurrence that are potentially modifiable are older donor age, prolonged cold ischaemia time, prior treated acute rejection, CMV hepatitis, IL28B donor genotype, and post-LT insulin resistance. The most effective means of preventing HCV recurrence is eradicating HCV prior to LT. Select wait-list candidates with compensated or mildly decompensated disease can be considered for antiviral treatment with peginterferon, ribavirin (and protease inhibitor if genotype 1). For the majority of LT patients, HCV treatment must be delayed until post-transplant. Treatment is generally undertaken if histologic severity reaches grade 3 or 4 necroinflammation or stage ≥2 fibrosis, or if cholestatic hepatitis. Achievement of sustained viral response (SVR) post-LT is associated with stabilization of fibrosis and improved graft survival. SVR is attained in ～30% of patients treated with peginterferon and ribavirin. Poor tolerability of therapy is a limitation. Combination therapy with telaprevir or boceprevir added to peginterferon and ribavirin is anticipated to increase efficacy but with higher rates of adverse effects and challenges in managing drug–drug interactions between the protease inhibitors and calcineurin inhibitors/sirolimus.     

Early decline of the HCV core antigen can predict SVR in patients with HCV treated by Pegylated interferon plus ribavirin combination therapy

OBJECTIVE: Pegylated interferon (PEG‐IFN) plus ribavirin (RBV) combination therapy is now a popular treatment for patients with chronic hepatitis C; however, the reported sustained virologic response (SVR) rate remains at nearly 50% in genotype 1b infected patients. Therefore, it is of clinical benefit to be able to predict the effect of combination therapy on individual patients earlier in the treatment. We estimated the predictive serum HCV core antigen levels for SVR in the early therapeutic stage of combination therapy. METHODS: The HCV core antigen in patients with high‐level HCV viremia, in whom standard PEG‐IFNα2b plus RBV combination therapy had been completed, was measured at baseline and at 3, 7, 14, 28 and 84 days of treatment, and their SVR was determined at 24 weeks after treatment. Sixty genotype 1b‐ and 30 genotype 2‐infected patients were included. RESULTS: Thirty (50%) genotype 1b and 27 (90%) genotype 2 patients achieved a SVR. In genotype 1b patients the decline of HCV core antigen levels was statistically different between the SVR and non‐SVR groups. When we defined a separation level at 500 fmol/L, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for SVR at day 7 was 79.4%, 88.5%, 90%, 76.7%, and 83.3%, respectively. In genotype 2 patients, there was no significant difference in the HCV core antigen values between the SVR and non‐SVR groups. CONCLUSION: In genotype 1b patients, 500 fmol/L of HCV core antigen level at day 7 was the best predictor for therapeutic response in the early stage of treatment.     

Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection: NORDynamIC trial and real-life experience

Objective: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment. Material and methods: The impact of established response predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12–16 weeks in accordance with national guidelines. Results: In the NORDynamIC trial, age <40 years or achieving HCV RNA?<1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12–16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR. Conclusions: Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation.     

Exploring differences in response to treatment with peginterferon alpha 2a (40kD) and ribavirin in chronic hepatitis C between genotypes 2 and 3

Chronic hepatitis C virus (HCV) infections with genotype 2 or 3 are associated with favourable sustained virologic response (SVR) rates. However, genotype 3 may respond less well. We reassessed all treatment-naive patients with genotype 2 and 3 participating in a large expanded-access, non-randomized, open-label trial, evaluating 180microg pegylated interferon (peg-IFN) alpha-2a (40kD) once weekly and 800 mg/day ribavirin for 24-48 weeks. Factors measured prior to initiation of antiviral therapy were considered in the multiple logistic regression model for predicting SVR. In total, 180 patients were analysed of which 72 (40%) were infected by genotype 2 and 108 (60%) genotype 3. The baseline characteristics between patients infected by genotype 2 or 3 were no different including the distribution of hepatic fibrosis stages by METAVIR score. Overall SVR was lower in those patients infected with genotype 3. The significant multivariate predictors of lack of SVR were hepatic fibrosis (P = 0.014) and genotype 3 (P = 0.030). The negative impact of cirrhosis (METAVIR score F4) on treatment response was more evident among subjects with genotype 3 than those with genotype 2 (P = 0.027). There is significant interaction between cirrhosis and genotype 3 leading to a poor antiviral response in such patients requiring an alternate management strategy. This finding should be confirmed in a larger population.     

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact

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.     

HCV基因型对慢性丙型肝炎干扰素疗效的影响

目的 探讨HCV基因型对慢性丙型肝炎的干扰素（IFN）治疗效果的影响。方法 采用随机、开放和对照的多中心临床试验设计。208例受试者按1：1随机分到聚乙二醇干扰素α—2a(Peg-IFN）组和IFN-α-2a组。在治疗之前，用Simmonds基因分型法酶切分型，在治疗24周结束和完成24周的随访后检测患者的ALT和HCV RNA，以HCV RNA的阴转率作为主要评价指标，经ITT人群的统计学分析。结果 202例患者确定了HCV基因型，基因1型158例（78.2%），非基因1型44例（21.8%），治疗结束病毒应答率（ETVR）和持续病毒应答率（SVR）基因1型患者分别为53.8%和25.3%，非基因1型患者分别为61.4%和43.2%，SVR两组患者差异有显著性，x^2=5.313,P=0.021。Peg IFN组基因1型和非1型患者的ETVR分别为76.8%和81.0%，SVR分别为35.4%和66.7%，SVR两组患者差异有显著性，x^2=6.735,P=0.01。病毒复发率基因1型和非基因1型患者分别为55.6%和23.5%，差异有显著性，x^2=5.496,P=0.02.IFN-α-2a组，ETVR和SVR基因1型患者分别为29.0%和14.5%，非基因1型患者分别43.5%和21.7%，差异无显著性。病毒复发率基因1型患者为72.7%，非基因1型患者为50.0%，差异无显著性。结论 IFN对基因1型丙型肝炎患者的疗效低于非基因1型，HCV基因型主要影响IFN对慢性丙型肝炎的持续应答，也与药物和IFN的疗程相关。     

Effectiveness of direct-acting antiviral therapy among Aboriginal and Torres Strait Islander peoples with HCV infection in Australia: A national real-world cohort (REACH-C)

Aboriginal and Torres Strait Islander peoples experience a disproportionate burden of hepatitis C virus (HCV) infection. This study assessed the effectiveness of direct-acting antiviral (DAA) therapy among Aboriginal peoples in the three years following universal access in Australia. REACH-C, a national multicentre prospective cohort study, evaluated HCV treatment outcomes from sequential DAA initiations across 33 health services between March 2016 and June 2019. DAA effectiveness was assessed by sustained virological response (SVR) in the total (full analysis set) and effectiveness (modified analysis set excluding those lost to follow-up) populations. Overall, 915 (10%) Aboriginal and 8095 (90%) non-Indigenous people commenced DAA therapy, of whom 30% and 16% reported current injecting drug use and 73% and 42% were treated in primary care, respectively. SVR in the total and effectiveness populations was 74% and 94% among Aboriginal people and 82% and 94% among non-Indigenous people, with loss to follow-up contributing to lower SVR in the total population analysis (22% Aboriginal, 13% non-Indigenous). Among Aboriginal people, returning for follow-up was positively associated with older age (aOR 1.20; 95% CI 1.04, 1.39) and SVR was negatively associated with cirrhosis (aOR 0.39; 95% CI 0.19, 0.80) and prior DAA treatment (aOR 0.14; 95% CI 0.04, 0.49). Factors reflecting higher vulnerability or inequity were not associated with returning for testing or SVR. DAA therapy was highly effective among Aboriginal peoples with HCV treated through primary and tertiary services. Tailored community-led interventions are necessary to optimize follow-up and engagement. Sustained DAA uptake and equitable access to care, treatment and prevention are required for HCV elimination.