Predictors of Direct-Acting Antivirals Failure in Patients with Chronic Hepatitis C Virus in Ivory Coast: About 5 Cases

Context and Aim: Direct-acting antivirals are the therapeutic revolution in the management of viral hepatitis C, but often with a few cases of failure. The aim of this study was to identify factors that may be implicated in the failure of direct-acting antiviral therapy in patients with hepatitis C virus in Ivory Coast. Methodology: This was a cross-sectional and descriptive study with a retrospective compendium of data from the year 2016 to the year 2018. This study included all patients with chronic viral hepatitis C, patients naive to antiviral treatment, or pre-treated patients in whom a failure to treatment with direct-acting antiviral has been diagnosed. Results: During the study period, 5 patients out of 14 cases of therapeutic failure were included, i.e. 35.71%. Most of the patients were over 50 years (4 out of 5) and predominantly female (3 out of 5). High blood pressure was the most common comorbidity (3 out of 5 patients). Genotype 1 was found in 4 patients versus 1 case of genotype 2. None of the patients had hepatitis B or HIV coinfection. A viral load > 6log was found in 4 patients at baseline. All our patients had hepatic cytolysis. Two of them were cirrhotic. All 4 cases of genotype 1 benefited from the combination sofosbuvir + ledipasvir for 12 weeks and the case of genotype 2 from the combination sofosbuvir + ribavirin for 24 weeks. The resistance mutations were observed mainly on the sequencing of NS5A at the Y93H, L31M, 28L, 30T, 31V, 58S and 93H genes and a case of mutation on the N3 gene sequencing. Conclusion: Age > 50 years, comorbidities (high blood pressure), polymedication, female gender, genotype 1b, viremia > 6log, and cytolysis were the profile of patients with treatment of HCV by direct-acting antiviral failure.

Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.

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.

Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era

To the Editor:Hepatocellular carcinoma (HCC) is the most common primary livertumorandthethirdcauseofcancer-relateddeathsworldwide. HCC is the consequence of malignant transformation of hepatocytes and mainly occurs in patients with cirrhosis. Hepatitis C virus (HCV) chronic infection is a leading cause of end-stage liver diseaseandHCCintheWesterncountries[1].Theapprovalof direct-acting antiviral agents (DAAs) for the treatment of HCV has revolutionized the management of the disease, as no absolute contraindication to treatment exists and sustained virological response

Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C:A systematic review and meta-analysis

AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.

Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis C virus genotypes 1, 2and 3 in northwest China

BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases of special adverse events.One case involved facial and bilateral lower extremity edema,and the other case showed an interesting change in lipid levels while on medication.No severe adverse events were noted.CONCLUSION The DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1,2 and 3,including those with cirrhosis.

Chronic hepatitis C,atherosclerosis and cardiovascular disease: What impact of direct-acting antiviral treatments?

Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. Several direct and indirect HCV pro-atherogenic mechanisms have been proposed. HCV lives and replicates within carotid plaques, promoting a local environment of pro-atherogenic factors. In addition, it causes conditions such as insulin resistance, diabetes, hepatic steatosis, cryoglobulinemia and endotoxinemia that are associated with the development of atherosclerosis and cardiovascular disease. Therapeutic regimens based on direct-acting antiviral agents (DAA) are currently available with high efficacy in HCV clearance and improvement of liver disease, but does HCV eradication also improve atherosclerosis and the risk of cardiovascular disease? Recently, a multi-center study has shown that elimination of HCV improves carotid atherosclerosis. Two studies have shown that DAA treatments significantly reduce the risk of cardiovascular events. Several studies have assessed the impact of HCV clearance on pro-atherosclerosis metabolic conditions showing improvement in cardiovascular risk biomarkers, disappearance or improvement of insulin resistance, reduction of risk of developing diabetes and improvement of glycemic control. There are also evidences that HCV clearance promotes the recovery of cytokines and inflammatory markers associated with atherosclerosis and the disappearance of cryoglobulinemia. Available data show that clearance of HCV by DAAs is associated with an improvement in atherosclerosis and metabolic and immunological conditions that promote the development of cardiovascular disease. However, the data are not sufficient to allow definitive conclusions and further studies will be needed to definitively clarify the impact of HCV clearance on atherosclerosis and cardiovascular disease.

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

With the introduction of direct-acting antiviral agents(DAA), the rate of sustained virological response(SVR) in the treatment of hepatitis C virus(HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma(HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4%(maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4%(maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection.

Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals

Chronic inflammation due to hepatitis C virus(HCV)infection leads to liver fibrosis and rearrangement of liver tissue,which is responsible for the development of portal hypertension(PH)and hepatocellular carcinoma(HCC).The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection,providing an overall eradication rate of over 90%.Despite a significant decrease after sustained virological response(SVR),the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease.Although the reasons are still unclear,cirrhosis itself has a residual risk for the development of HCC and other PH-related complications.Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis.Following the achievement of SVR,liver stiffness(LS)usually decreases,as a consequence of reduced inflammation and,possibly,fibrosis.Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease(functional decompensation,gastrointestinal bleeding,HCC)and to optimize long-term prognostic outcomes in clinical practice.

Histopathology and the predominantly progressive,indeterminate and predominately regressive score in hepatitis C virus patients after direct-acting antivirals therapy

BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-I-R)score,evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIM To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODS Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.Sustained virologic response(SVR)was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation.The Ishak system and P-I-R score were assessed.Inflammation improvement and fibrosis regression were defined as a≥2-points decrease in the histology activity index(HAI)score and a≥1-point decrease in the Ishak fibrosis score,respectively.Fibrosis progression was defined as a≥1-point increase in the Ishak fibrosis score.Histologic improvement was defined as a≥2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy.The P-I-R score was also assessed.“absolutely reversing or advancing”was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score;and“probably reversing or advancing”was defined as only one parameter showing directionality.RESULTS Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.The mean age of these patients was 40.9±14.6 years and there were 53%(20/38)males.Thirty-four percent(13/38)of patients were cirrhotic.Eighty-two percent(31/38)of patients achieved inflammation improvement.The median HAI score decreased significantly after SVR(pretreatment 7.0 vs posttreatment 2.0,Z=-5.146,P=0.000).Thirty-seven percent(14/38)of patients achieved fibrosis improvement.The median Ishak score decreased significantly after SVR(pretreatment 4.0 vs posttreatment 3.0,Z=-2.354,P=0.019).Eighty-two percent(31/38)of patients showed histological improvement.The P-I-R score was evaluated in 61%(23/38)of patients.The progressive group showed lower platelet(P=0.024)and higher HAI scores(P=0.070)before treatment.In patients with stable Ishak stage after treatment:Progressive injury was seen in 22%(4/18)of patients,33%(6/18)were classified as indeterminate and regressive changes were seen in 44%(8/18)of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSION Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy.The P-I-R score has potential in predicting fibrosis in HCV patients.

Retreatment of patients with treatment failure of directacting antivirals: Focus on hepatitis C virus genotype 1b

The recent development of direct-acting antiviral agents(DAAs) against hepatitis C virus(HCV) infection could lead to higher sustained virological response(SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions(RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1 b(GT1 b) is founded in 70% of HCVinfected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1 b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1 b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1 b-infected patients with treatment failure.

Sofosbuvir/Ribavirin therapy for patients experiencing failure of ombitasvir/paritaprevir/ritonavir + ribavirin therapy: Two cases report and review of literature

BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin(OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is unknown.CASE SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2 a who could not achieve a sustained virological response(SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with VogtKoyanagi-Harada(VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment(SVR12). Regarding adverse events(AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid arthralgia.CONCLUSION SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.

Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

Hepatitis C virus treatment failure:Clinical utility for testing resistance-associated substitutions

The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.

Review of Clinically Relevant Drug Interactions with Next Generation Hepatitis C Direct-acting Antiviral Agents

In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(Maviret®),and elbasvir/grazoprevir(Zepatier®).We searched MEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,Maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,2020.The search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference proceedings.All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted.Numerous clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed drugs.NS3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase inhibitor.The majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do occur.As expected,many drug interactions exist between newer generation DAAs and commonly prescribed medications.While the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting drugs.In select cases,severe and unpredictable drug interactions can occur.Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.

Efficacy and safety of direct-acting antiviral agent regimens in a real-world cohort of adult Chinese patients with chronic hepatitis C virus infection

Background and aims:To investigate the safety and efficacy of direct-acting antiviral(DAA)regimens in a cohort of Chinese patients with chronic hepatitis C virus(HCV)infection.Methods:A total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accor-dance with HCV management guidelines.Treatment responses were evaluated 4 weeks after treatment,at the end of treatment(EOT)and 12 weeks post-treatment.Virological responses,biochemical re-sponses,model for end-stage liver disease(MELD)and Child-Pugh(CP)scores were recorded.Results:A total of 218 patients(98.2%)achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed.The combined number of rapid virological responses for all six regimens was 170/222(76.6%),and 221/222(99.6%)had achieved virological responses by the end of treatment.In decompensated cirrhosis patients the baseline mean CP score was 6.8±1.3 and the mean MELD score was 10.1±3.3.Compared with the mean CP score at baseline,the mean score is significantly lower at the end of treatment(5.7±1.3)and 12 weeks post-treatment(5.6±1.0).Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment.The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172(24.4%),and in patients with decompensated cirrhosis it was 8/22(36.4%).The most frequently reported adverse events were elevated indirect bilirubin,fatigue and rash.There were no cases of serious adverse events,death or treatment discontinuation because of adverse events.Conclusion:DAA regimens were highly effective and well tolerated irrespective of HCV genotype,cirrhosis,liver or kidney transplantation,hepatocellular carcinoma,HCV/hepatitis B virus co-infection,or renal failure.

Direct-acting antivirals and hepatocellular carcinoma occurrence and recurrence in hepatitis C virus-related liver cirrhosis: fact or fiction

Since the widespread adoption of new direct-acting antiviral agents (DAAs), the approach to hepatitis C virus (HCV) infection has changed profoundly as almost all patients can be cured regardless of the stage of their liver disease. On the other hand, there are a few conflicting reports on the risk of hepatocellular carcinoma (HCC) occurring and recurring in patients given DAA-based therapy. The present review focuses on the latest and most relevant literature providing evidence on the occurrence and recurrence of HCC after HCV antiviral treatment with the new DAAs. Retaining the distinction between HCC occurrence and recurrence, we also discuss its patterns of presentation and speculate on the possible pathogenic mechanisms. We offer our personal viewpoints on this important issue, which has kept clinicians second-guessing in real-world clinical practice, when dealing with HCV eradication in the setting of advanced liver disease in this interferon-free era.

乙型肝炎肝衰竭的抗病毒治疗

我国2006年《肝衰竭诊疗指南》根据病理组织学特征和病情发展速度,将肝衰竭分为急性肝衰竭（acute liver failure,ALF）、亚急性肝衰竭（subacute liver failure,SALF）,慢加急性肝衰竭（acute-on-chronic liver failure,ACLF）以及慢性肝衰竭[1]。在我国,感染是导致肝衰竭的主要因素,其中HBV感染导致的慢性乙型肝炎急性炎症活动是主要原因。

索磷布韦在合并终末期肾病行血液透析的HCV感染者中的应用

对于慢性丙型肝炎合并终末期肾病行血液透析的患者,指南多建议以含蛋白酶抑制剂(PI)的直接抗病毒药物方案进行治疗,但临床中常有透析患者因合并严重肝损伤禁忌使用PI类药物。简述了行透析丙型肝炎患者中未满足的治疗需求,回顾了在此类患者中应用基于索磷布韦(SOF)的无PI抗病毒方案的临床试验及真实世界研究进展,探讨了基于SOF的方案在中国透析患者中的应用价值及有待进一步研究的问题。提示,基于全剂量SOF的方案在透析患者中的疗效、耐受性及安全性良好,为此类患者中合并中、重度肝损伤者提供了更多安全有效的抗病毒治疗选择。

核苷(酸)类似物治疗慢加急性肝衰竭研究进展

乙型肝炎是威胁全球的健康问题,每年约有60万人死于HBV感染所致的各种疾病,如肝炎、肝硬化和原发性肝癌等。乙型肝炎相关性慢加急性肝衰竭是我国肝衰竭主要类型,在治疗上除综合治疗外,是否进行抗病毒治疗是近年研究的热点。本文就该领域的研究现状作一综述。