Unraveling the Impact of Direct-Acting Antivirals on Hepatitis-Linked Cirrhosis: A Comprehensive Analysis of Fibrosis, Child Score, and Disease Progression

The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).

Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study

BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce the occurrence of hepatocellular carcinoma(HCC)in patients with HCV-associated cirrhosis who are at high risk have not been concluded.AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCVassociated cirrhosis after achieving SVR.METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020.118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group,and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group.Demographic information and laboratory data were collected from baseline and the following up.Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups.Cox proportional risk regression was used to re-evaluate the risk factors for HCC.RESULTS HCC incidence was 4.68/100PY(95%CI,3.09-6.81)in the DAAs treatment group,while it was 3.00/100PY(95%CI,1.50-5.37)in the non-antiviral treatment group,and the relative risk was 1.82(95%CI,0.93-3.53,P>0.05).The incidence of HCC at 12,24,36 and 48 months was 3.39%,6.36%,8.47%and 10.17%in the DAAs treatment group,and it was 0%,0%,3.39%and 9.32%in the non-antiviral treatment group,respectively.Age>58[hazard ratio(HR)=1.089;95%CI,1.033-1.147;P=0.002]and liver stiffness measurement>27.85 kPa(HR=1.043;95%CI,1.022-1.065;P=0.000)were risk factors for HCC in all patients(n=427),and DAAs treatment didn’t show protective efficacy.CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months,and even increased the incidence of HCC in 36 months.

Alkaloids as potential antivirals.A comprehensive review

Alkaloids are a diverse group of natural phytochemicals.These phytochemicals in plants provide them protection against pests,and herbivorous organisms and also control their development.Numerous of these alkaloids have a variety of biological effects,and some have even been developed into medications with different medicinal properties.This review aims to provide a broad overview of the numerous naturally occurring alkaloids(isolated from both terrestrial and aquatic species)along with synthetically produced alkaloid compounds having prominent antiviral properties.Previous reviews on this subject have focused on the biological actions of both natural and synthetic alkaloids,but they have not gone into comprehensive detail about their antiviral properties.We reviewed here several antiviral alkaloids that have been described in the literature in different investigational environments i.e.(in-vivo,in-ovo,in-vitro,and in-silico),and found that these alkaloid compounds have significant antiviral properties against several infectious viruses.These alkaloids repressed and targeted various important stages of viral infection at non-toxic doses while some of the alkaloids reported here also exhibited comparable inhibitory activities to commercially used drugs.Overall,these anti-viral effects of alkaloids point to a high degree of specificity,implying that they could serve as effective and safe antiviral medicines if further pursued in medicinal and pharmacological investigations.

Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.

Antiviral treatment standards for hepatitis B:An urgent need for expansion

The present letter to the editor is related to the review with the title“Past,present,and future of long-term treatment for hepatitis B virus.”Chronic hepatitis B(CHB)represents an important and pressing public health concern.Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus(HBV)substantially.However,the current global treatment rates for CHB remain conspicuously low,with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates.Nevertheless,recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries.An impending need arises for a novel paradigm for the classification of patients with CHB,the expansion of antiviral treatment eligibility for HBV-infected individuals,and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.

Natural Products and Antiviral Resistance

Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.

Black Garlic as an Antiviral for Herpes Simplex Virus-2 in Lung Cells

Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants than fresh garlic. Antioxidants play a vital role in alleviating cellular stress during viral infections. Viral infections result in oxidative stress through the production of reactive oxidative species (ROS). A prolonged state of oxidative stress can result in cell death, DNA damage, and disease progression. In this study, black garlic extract (BGE) is evaluated for its ability to mitigate cytopathic effects and oxidative stress caused by herpes simplex virus-2 (HSV-2) infections in vitro. Antiviral assays were performed to determine the percent of viral inhibition resulting from treatment with the BGE. ROS-GloTM H2O2 assays were then completed to measure the post-infection ROS levels of BGE-treated virus and cells. The results thus far suggest that BGE may inhibit viral infection and decrease levels of oxidative stress.

Improving clinical outcomes of patients with hepatocellular carcinoma:Role of antiviral therapy,conversion therapy,and palliative therapy

In this editorial,I comment on three articles published in the recent issue of the World Journal of Gastrointestinal Oncology.Hepatocellular carcinoma(HCC)is an important public health concern,and there are three articles on the theme of HCC in this issue.I focus on the articles by Mu et al,Chu et al,and Ma et al for this editorial.While these articles may be considered as low-quality evidence,and the results cannot be generalized to non-hepatitis-B or C virus patients,the discussion of the results is important.In addition,though all the articles are from China,the relevance of the results is not minuscule.As resection is the main form of curative treatment modality owing to a donor liver shortage,surgeons need to be aware that preoperative long-course antiviral therapy can improve clinical outcomes by reducing postoperative liver dysfunction and recurrence of HCC following resection.Similarly,patients with super-giant HCC(defined as≥15 cm diameter)should also be carefully considered for liver resection,and if it is unresectable upfront,then a combination of liver-directed therapy and systemic therapy may downstage HCC.If,following downstaging,the patient qualifies for liver resection based on locally prevalent resectability criteria,then such therapy is labelled as conversion(from unresectable to resectable)therapy.In unresectable patients treated by a combination of treatment options,serological markers like neutrophil-to-lymphocyte ratio and alpha-fetoprotein are reported to predict treatment responses,thus enabling personalized medicine.

Anti-infective immune functions of type Ⅳ interferon in grass carp(Ctenopharyngodon idella):A novel antibacterial and antiviral interferon in lower vertebrates

Type Ⅳ interferon(IFN-υ)is a recently discovered cytokine crucial for host defense against viral infections.However,the role and mechanisms of IFN-υin bacterial infections remain unexplored.This study investigated the antibacterial and antiviral functions and mechanisms of grass carp(Ctenopharyngodon idella)IFN-υ(CiIFN-υ)both in vivo and in vitro.The CiIFN-υgene was first identified and characterized in grass carp.Subsequently,the immune expression of CiIFN-υsignificantly increased following bacterial challenge,indicating its response to bacterial infections.The eukaryotic recombinant expression plasmid of CiIFN-υwas then constructed and transfected into fathead minnow(FHM)cells.Supernatants were collected and incubated with four bacterial strains,followed by plate spreading and colony counting.Results indicated that CiIFN-υexhibited more potent antibacterial activity against gram-negative bacteria compared to gram-positive bacteria and aggregated gram-negative bacteria but not gram-positive bacteria.In vivo experiments further confirmed the antibacterial function,showing high survival rates,low tissue edema and damage,reduced tissue bacterial load,and elevated proinflammatory response at the early stages of bacterial infection.In addition,the antiviral function of CiIFN-υwas confirmed through in vitro and in vivo experiments,including crystal violet staining,survival rates,tissue viral burden,and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR).This study highlights the antibacterial function and preliminary mechanism of IFN-υ,demonstrating that IFN-υpossesses dual functions against bacterial and viral infections.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

Timing of antiviral therapy in patients with hepatitis B virus related hepatocellular carcinoma undergoing hepatectomy

Globally,hepatocellular carcinoma(HCC)is among the most prevalent and deadly cancers.Hepatitis B virus(HBV)infection is an important etiology and disease progression factor for HCC.Hepatectomy is a widely accepted curative treatment for HCC,but the long-term survival rate is still unsatisfactory due to the high recurrence rate after resection.Preoperative or postoperative antiviral therapy plays an important role in improving the prognosis for HBV-related HCC patients who underwent hepatectomy.However,many patients miss out on the chance to receive long-term preoperative antiviral medication because their HBV and HCC infections are discovered concurrently,necessitating the start of remedial antiviral therapy in the perioperative phase.Therefore,it is of great value to know when antiviral therapy is more appropriate and whether perioperative rescue antiviral therapy can achieve the effect of preoperative long-term antiviral therapy.

UV,five wavelengths fusion and electrochemical fingerprints combined with antioxidant activity for quality control of antiviral mixture

Aiming to ensure the consistency of quality control of Traditional Chinese Medicines(TCMs),a combination method of high-performance liquid chromatography(HPLC),ultraviolet(UV),electrochemical(EC)was developed in this study to comprehensively evaluate the quality of Antiviral Mixture(AM),and Comprehensive Linear Quantification Fingerprint Method(CLQFM)was used to process the data.Quantitative analysis of three active substances in TCM was conducted.A fivewavelength fusion fingerprint(FWFF)was developed,using second-order derivatives of UV spectral data to differentiate sample levels effectively.The combination of HPLC and UV spectrophotometry,along with electrochemical fingerprinting(ECFP),successfully evaluated total active substances.Ultimately,a multidimensional profiling analytical system for TCM was developed.

Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals

AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.

Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals

BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.

Emerging antivirals for the treatment of hepatitis B

Chronic infection with hepatitis B virus(HBV)constitutes a major global public health threat,causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma,thus representing high unmet medical needs.Currently available therapies are safe,well tolerated,and highly effective in decreasing viremia and improving measured clinical outcomes with low rates of antiviral resistance.However,long-term management remains a clinical challenge,mainly due to the slow kinetics of HBV surface antigen clearance.In this article,we review emerging antivirals directed at novel targets derived from mechanisms of viral cellular entry,viral replication,viral assembly,and the host immune response,leading to preclinical and clinical trials for possible future therapeutic intervention.The recent therapeutic advances in the development of all categories of HBV inhibitors may pave the way for regimens of finite duration that result in long-lasting control of chronic hepatitis B infection.

Impact of direct acting antivirals on occurrence and recurrence of hepatocellular carcinoma: Biologically plausible or an epiphenomenon?

Hepatocellular carcinoma(HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection(HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals(DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC.

Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance

The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting

AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3%(45/54) achieved rapid virological response at 2 wk after treatment initiation(RVR 2) and 94.4%(51/54)achieved sustained virological response at 24 wk after the end of treatment(SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels(83.6 ± 17.9 vs 88.8 ± 19.4, P 01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P 01 < 0.001), and no significant improvements were observed at 24 w after the end of treatment(83.6 ± 17.9 vs 86.8 ± 19.1, P 02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P 02 = 0.001). The total frequency of adverse events(AEs) during treatment was 33.3%(18/54), with major AEs being fatigue(16.7%), headache(7.4%), anorexia(7.4%), and insomnia(5.6%). CONCLUSION Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.