Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

Chronic infection with the hepatitis C virus(HCV)remains a major health problem affecting approximately 58 million people worldwide.In the era of interferon(IFN)-based regimens,patients particularly infected with genotypes 1 and 4 achieved a low response rate.The implementation of direct-acting antivirals changed the landscape of HCV treatment.The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030.In the following years,there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution.The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time.Patients treated with antiviral therapies were younger in successive periods,less burdened with comorbidities and comedications,more frequently treatment-naïve and had less advanced liver disease.Before the IFN-free era,specific subpopulations such as patients with HCV/HIV coinfection,those with a history of previous treatment,patients with renal impairment or with cirrhosis had lower chances for a virologic response.Currently,these populations should no longer be considered difficult to treat.Despite the high effectiveness of HCV therapy,there is a small percentage of patients with treatment failure.However,they can be effectively retreated with pangenotypic rescue regimens.

Editorial:Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

In the management of the growing population of hepatitis C virus-infected patients,a significant clinical challenge exists in determining the most effective methods for assessing liver impairment.The prognosis and treatment of chronic hepatitis C depend,in part,on the evaluation of histological activity,specifically cell necrosis and inflammation,and the extent of liver fibrosis.These parameters are traditionally obtained through a liver biopsy.However,liver biopsy presents both invasiveness and potential sampling errors,primarily due to inadequate biopsy size.To circumvent these issues,several non-invasive markers have been proposed as alternatives for diagnosing liver damage.Different imaging techniques and blood parameters as single markers or combined with clinical information are included.This Editorial discusses the identification of a set of six distinctive lipid metabolites in every fibrosis grade that appear to show a pronounced propensity to create clusters among patients who share the same fibrosis grade,thereby demonstrating enhanced efficacy in distinguishing between the different grades.

Acute-on-chronic liver failure induced by antiviral therapy for chronic hepatitis C: A case report

BACKGROUND There have been no reports of acute-on-chronic liver failure(ACLF)during treatment of chronic hepatitis C(CHC)with direct-acting antivirals(DAAs).CASE SUMMARY We report a 50-year-old male patient with CHC.The patient sought medical attention from the Department of Infectious Diseases at our hospital due to severe yellowing of the skin and sclera,which developed 3 mo previously and attended two consecutive hospitals without finding the cause of liver damage.It was not until 1 mo ago that he was diagnosed with CHC at our hospital.After discharge,he was treated with DAAs.During treatment,ACLF occurred,and timely measures such as liver protection,enzyme lowering,anti-infective treatment,and suppression of inflammatory storms were implemented to control the condition.CONCLUSION DAA drugs significantly improve the cure rate of CHC.However,when patients have factors such as autoimmune attack,coinfection,or unclear hepatitis C virus genotype,close monitoring is required during DAA treatment.

Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

BACKGROUND Chronic Hepatitis C(CHC)affects 71 million people globally and leads to liver issues such as fibrosis,cirrhosis,cancer,and death.A better understanding and prognosis of liver involvement are vital to reduce morbidity and mortality.The accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting outcomes.Tests used to grade fibrosis include histological analysis and imaging but have limitations.Blood markers such as molecular biomarkers can offer valuable insights into fibrosis.AIM To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the disease.METHODS Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1(n=13),F2(n=12),F3(n=6),and F4(n=15).To ensure that the identified biomarkers were exclusive to liver lesions(CHC fibrosis),healthy volunteer participants(n=50)were also included.An untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database verification.Statistical analyses were performed to identify differential biomarkers among groups.RESULTS Six differential metabolites were identified in each grade of fibrosis.This six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis;thus,they showed greater efficiency in discriminating grades.CONCLUSION This study suggests that some of the observed biomarkers,once validated,have the potential to be applied as prognostic biomarkers.Furthermore,it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

Detection of colorectal adenomas using artificial intelligence models in patients with chronic hepatitis C

BACKGROUND Hepatitis C virus is known for its oncogenic potential,especially in hepatocellular carcinoma and non-Hodgkin lymphoma.Several studies have shown that chronic hepatitis C(CHC)has an increased risk of the development of colorectal cancer(CRC).AIM To analyze this positive relationship and develop an artificial intelligence(AI)-based tool using machine learning(ML)algorithms to stratify these patient populations into risk groups for CRC/adenoma detection.METHODS To develop the AI automated calculator,we applied ML to train models to predict the probability and the number of adenomas detected on colonoscopy.Data sets were split into 70:30 ratios for training and internal validation.The Scikit-learn standard scaler was used to scale values of continuous variables.Colonoscopy findings were used as the gold standard and deep learning architecture was used to train six ML models for prediction.A Flask(customizable Python framework)application programming interface(API)was used to deploy the trained ML model with the highest accuracy as a web application.Finally,Heroku was used for the deployment of the web-based API to https://adenomadetection.herokuapp.com.RESULTS Of 415 patients,206 had colonoscopy results.On internal validation,the Bernoulli naive Bayes model predicted the probability of adenoma detection with the highest accuracy of 56%,precision of 55%,recall of 55%,and F1 measure of 54%.Support vector regressor predicted the number of adenomas with the least mean absolute error of 0.905.CONCLUSION Our AI-based tool can help providers stratify patients with CHC for early referral for screening colonoscopy.Along with providing a numerical percentage,the calculator can also comment on the number of adenomatous polyps a gastroenterologist can expect,prompting a higher adenoma detection rate.

Serum omentin-1 is correlated with the severity of liver disease in patients with chronic hepatitis C

BACKGROUND Patients with chronic hepatitis C virus(HCV)infection have increased serum omentin-1.Omentin-1 is an anti-inflammatory adipokine,and higher levels may be a direct effect of HCV infection.Successful elimination of HCV by direct acting antivirals almost normalized circulating levels of various molecules with a role in inflammation.AIM To evaluate the effect of HCV infection on serum omentin-1,serum omentin-1 levels of HCV patients were measured before therapy and at 12 wk after therapy end.Associations of serum omentin-1 with parameters of inflammation and liver function were explored at both time points.Serum omentin-1 levels of patients with and without liver cirrhosis,which was defined by ultrasound or the fibrosis-4(FIB-4)score,were compared.METHODS Serum omentin-1 levels were measured by enzyme-linked immunosorbent assay in 84 chronic HCV patients before therapy and at 12 wk after therapy end where sustained virological response 12(SVR12)was achieved in all patients.Serum omentin-1 of 14 non-infected controls was measured in parallel.RESULTS In patients with chronic HCV,serum omentin-1 levels were not related to viral load or viral genotype.HCV patients with liver steatosis and HCV patients with diabetes had serum omentin-1 levels comparable to patients not suffering from these conditions.Serum omentin-1 levels at SVR12 were similar in comparison to pretreatment levels.In addition,serum levels did not differ between HCV-infected patients and non-infected controls.Serum omentin-1 levels did not correlate with leukocyte count or C-reactive protein.Positive correlations of serum omentin-1 with bilirubin and the model for end-stage liver disease score(MELD)were detected before therapy and at SVR12 in the whole cohort.Bilirubin and the MELD score also positively correlated with serum omentin-1 levels in the subgroup of patients with ultrasound diagnosed liver cirrhosis before therapy.At SVR12,serum omentin-1 levels of patients with liver cirrhosis negatively correlated with albumin.Before therapy start,patients with high FIB-4 scores had increased serum omentin-1 in comparison to patients with a low score.Serum omentin-1 levels of patients with liver cirrhosis defined by ultrasound were increased at baseline and at SVR12.CONCLUSION Present study showed that liver cirrhosis,but not HCV infection per se,is related to elevated serum omentin-1 levels.

Stages of care for patients with chronic hepatitis C at a hospital in southern Brazil

BACKGROUND Hepatitis C virus(HCV)is defined as a public health problem by the World Health Organization(WHO)and since then has defined targets through the HCV elimination.The HCV cascade of care highlights the progress towards these goals and essential interventions that need to be delivered along this continuum care.AIM To document the treatment cascade for patients with HCV infection at the Hospital Nossa Senhora da Conceição(HNSC),defining the percentage of antibody-positive patients who collected molecular biology tests(polymerase chain reaction),attended outpatient clinic assistance,underwent treatment,and achieved a virologic cure termed sustained virologic response(SVR).METHODS With the retrospective cohort design,patients diagnosed with HCV infection in the period between January 1,2015 and December 31,2020 were included.Data from HCV notification forms,electronic medical records,Computerized Laboratory Environment Manager System,and Medicine Administration System(evaluation of special medications)were collected in 2022 and all information up to that period was considered.The data were analyzed with IBM SPSS version 25,and Poisson regression with robust simple variance was performed for analysis of variables in relation to each step of the cascade.Variables with P<0.20 were included in the multivariate analysis with P<0.05 considered significant.Pearson’s chi-square test was applied to compare the groups of patients who persisted in follow-up at the HNSC and who underwent follow-up at other locations.RESULTS Results were lower than expected by the WHO with only 49%of candidates receiving HCV treatment and only 29%achieving SVR,despite the 98%response rate to direct acting antivirals documented by follow-up examination.The city of origin and the place of follow-up were the variables associated with SVR and all other endpoints.When comparing the cascade of patients who remained assisted by the HNSC vs external patients,we observed superior data for HNSC patients in the SVR.Patients from the countryside and metropolitan region were mostly assisted at the HNSC and the specialized and continuous care provided at the HNSC was associated with superior results,although the outcomes remain far from the goals set by the WHO.CONCLUSION With the elaboration of the HCV cascade of care using local data,it was possible to stratify and evaluate risk factors associated with losses between each step of the cascade,to inform new strategies to guide elimination efforts in the future.

Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.

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.

Impact of virus genotype on interferon treatment of patients with chronic hepatitis C: a multicenter controlled study

BACKGROUND: Some factors have been reported to besassociated with a greater likelihood of sustained viral re-sponse ( SVR) in the interferon (IFN) treatment of chronichepatitis C. The factors include HCV genotype, HCVRNA level in serum, state of liver disease, baseline bodyweight, age, sex, and race. The aim of this trial was to in-vestigate the influence of HCV genotype on the IFN treat-ment of patients with chronic hepatitis C.METHODS: The genotypes of HCV virus were determinedin the patients with chronic hepatitis C from several hospi-tals of China enrolled into the randomized, opened andcontrolled trial of Peg-IFN alpha-2a (pegasys) treatment,controlled with IFN-α-2a (roferon-A). The serum ALTlevels and HCV RNA concentrations of the patients weredetected before and at the end of treatment and during thefollow-up. The influence of HCV genotype on the IFNtreatment of patients with chronic hepatitis C was analyzedin intention-to-treat (ITT) population.RESULTS: The HCV genotypes of 202 patients were deter-mined. Of these patients, 158(78.22%) were infected withgenotype 1 HCV and 44(21.78%) with genotype non-1.The viral response at the end of treatment (ETVR) andsustained viral response (SVR) rates were 53.80% and25.32% respectively in patients with genotype 1 HCV, butthey were 61.36% and 43.18% in patients with genotypenon-1. The difference of SVR between patients with geno-type 1 HCV and those with genotype non-1 was significant(P =0.021). After being grouped by the used drugs, theETVR rates of patients infected with genotype 1 and non-1HCV were 76.83% and 80.95% in the patients treated withpegasys (P =0.686); but their SVR rates were 35.37% and66.67% (P =0. 01). The viral relapse rate of genotype 1HCV (55.56%) was significantly higher than that of geno-type non-1 HCV (23.53%) (P=0.02). In roferon-A group,the ETVR and SVR rates of patients with genotype 1 HCVwere 28.95% and 14.47% respectively, which were lowerbut not more significant than those of patients with geno-type non-1 HCV (43.48% and 21.74%). Moreover, the vi-ral relapse rate of genotype 1 HCV (72.73%) was higherbut not more significant than that of genotype non-1 HCV(50.00%) (P=0.21).CONCLUSION: HCV genotype could affect the efficacies,mainly sustained responses, of IFN treatment in patientswith chronic hepatitis C, and the effects of IFN are relatedto drugs and therapeutic course.

Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil

BACKGROUND Hepatitis C virus(HCV)treatment has undergone major changes in recent years.Previous interferon-based therapies have been replaced by oral direct-acting antivirals(DAA)regimens,with high sustained virologic response(SVR)rates,and a lower incidence of adverse events(AEs).AIM To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil.METHODS This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C(CHC),undergoing treatment with interferon-free regimens from November 2015 to November 2019.The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment.Demographic,anthropometric,clinical,and laboratory variables were evaluated.SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat(ITT),and modified ITT(m-ITT)analysis.AEs and serious adverse events(SAEs)were registered.In the statistical analysis,a P value of<0.05 was considered significant.RESULTS The mean age was 56.88 years,with 415(78.5%)being HCV genotype 1,followed by genotype 3(20.1%).Moreover,306(57.5%)subjects had cirrhosis,and a third of them had decompensated cirrhosis.Sofosbuvir(SOF)plus daclatasvir±ribavirin was the most frequently used treatment(66.9%),followed by SOF plus simeprevir(21.2%).The overall ITT SVR was 92.6%(493/532),while the m-ITT SVR was 96.8%(493/509).Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy(OR:4.320;95%CI:1.920-9.721,P=0.0004),presence of esophageal varices(OR:2.381;95%CI:1.137-4.988,P=0.0215),previous portal hypertensive bleeding(OR:2.756;95%CI:1.173-6.471,P=0.02),higher model for end-stage liver disease scores(OR:1.143,95%CI:1.060–1.233,P=0.0005),lower serum albumin levels(OR:0.528,95%CI:0.322-0.867,P=0.0115),higher serum creatinine(OR:1.117,95%CI:1.056-1.312,P=0.0033),and international normalized ratio(INR)levels(OR:5.542,95%CI:2.023-15.182,P=0.0009).AEs were reported in 41.1%(211/514)of patients,and SAEs in 3.7%.The female gender,higher body mass index,esophageal varices,higher INR values,and longer treatment duration were independently associated with AE occurrence.CONCLUSION Treatment with oral DAAs attains a high SVR rate,with fewer SAEs in a real-life cohort of subjects with CHC,from two tertiary university centers in Brazil.

A randomized trial of a 4- vs 12-week daily interferon dose regimen combined with ribavirin in treatment of patients with chronic hepatitis C

BACKGROUND: Standard combination-therapy of ribavi- rin with alternate day interferon (IFN) in patients with chronic hepatitis C ( CHC) has been reported to achieve 30%-55% sustained viral response. Early reduction of viral load by daily dosage of IFN could enhance viral clearance. However, the duration of daily dosage protocol and the likely side-effects have not been well studied. We compared the efficacy and safety of a 4- vs 12-week daily IFN dosage in patients with CHC. METHODS: Fifty-nine, histologically proven CHC patients having ALT levels >1.5 ×ULN were divided randomly into 2 groups, group I was given IFN 3 MIU daily for 4 weeks, followed by tiw up to 12 months and group was given IFN 3 MIU daily for 12 weeks, followed by tiw up to 12 months. Ribavirin was given in a dose of 800-1200 mg/d for 12 months. RESULTS: Fifty-two of the 59 patients (group group completed the study. The pretreatment vari- ables and the prevalence of HCV genotype 1 were compara- ble between the groups. Nine patients (29%) in group and 6 (25%) in group had stage 3, 4 fibrosis. At the end of 4, 12, 24 and 52 weeks, HCV RNA negativity was ob- served in 27%, 54%, 65% and 71% in group I and 38%, 54%, 71% and 75% in group respectively (P =ns). Four of the eight (50%) patients with genotype 1 and 30 (69.8%) of 43 patients with genotype non-1 responded to therapy (P =ns). Sustained viral response was achieved in 61% and 71% in groups respectively. None of the variables predicted non-response precisely. No serious adverse effects were observed and they were comparable between the two groups. CONCLUSION: Daily IFN dosage with ribavirin is safe and can achieve response in up to 65% patients. Since the effica- cy of a 4-week daily dosage of IFN is comparable to a 12- week schedule, we recommend the former regimen.

Cascade of care for children and adolescents with chronic hepatitis C

Chronic hepatitis C virus(HCV)infection presents a significant global public health burden.In 2015,over 400000 deaths worldwide were attributed to HCV infection.This led the World Health Organization(WHO)in 2016 to set the ambitious goal of eliminating HCV by 2030.Adult-centered guidelines have been established in order to provide direction for healthcare professionals,allowing integration of the newest screening policies and therapeutic strategies into their practices.However,for children and adolescents,HCV is a significant,unrecognized public health problem.HCV infection rates in the United States in women of childbearing age and those who are pregnant have increased in parallel with the rising opioid epidemic.An estimated 29000 women with HCV infection gave birth each year from 2011 to 2014 in the United States,with approximately 1700 of their infants being infected with HCV.Newer HCV-specific therapeutics,namely direct acting antivirals(DAA),has brought a new and highly successful approach to treatment of hepatitis C.Recent studies have confirmed similar levels of effectiveness and safety of DAA therapies in the pediatric population.Thus,an enhanced cascade of care,which should include the population under 18 years of age,can help achieve the WHO goal by focusing on elimination in the youngest populations.This review will present an overview of the natural history,clinical features,and management of HCV in children and adolescents.

Logistic Regression Analysis of Influencing Factors on Serum ALT and HCV RNA Changes in Patients with Chronic Hepatitis C

Objective This study was undertaken to investigate the influencing factors on serum ALT level and hepatitis C virus(HCV)RNA titer in chronic hepatitis C(CHC)patients.Methods All patients enrolled into this study were anti-HCV positive.Retrospective tracing method was applied to detect serum ALT level and HCV RNA titer and to collect general information of the patients such as genders,age groups,interferon medication history,infection pathways,height and weight.Then the multi-factor analysis was adopted with the application of binominal logistic regression mode.Results The abnormal rate of ALT level was positively correlated to HCV RNA and gender while negatively correlated to interferon medication history and age group,with Wald value of the 4 factors as 39.604,11.823,18.991 and 7.389,respectively.The positive rate of HCV RNA was negatively correlated to interferon medication history and gender while positively correlated to ALT level,with corresponding Wald value of the 3 factors as81.394,7.618 and 27.562,respectively.Conclusions The normal ALT level in HCV infected patients was associated with viral load,age,gender and interferon medication history,while the normal rate of HCV RNA titer was closely associated with gender,interferon medication history and ALT level.

Serum and ascites levels of macrophage migration inhibitory factor, TNF-α and IL-6 in patients with chronic virus hepatitis B and hepatitis cirrhosis

Objective: To study the potential role of macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the development of chronic virus hepatitis B (CH) and hepatitis cirrhosis (HC). Methods: The serum concentrations of MIF, TNF-α and IL-6 in 18 patients with chronic virus hepatitis B and in 14 patients with hepatitis cirrhosis without as- citic fluid, and the serum and ascites cytokine con- centrations in 22 HC patients with ascitic fluid were detected by enzyme linked immunity sorbed assay. Results: The cytokine concentrations of the patients were significantly higher than those of the controls. The serum levels of MIF, TNF-α and IL-6 of the 22 patients with ascitic fluid were higer than those of 14 HC patients without ascites. In the 18 patients with CH, the serum cytokine concentrations were the low- est. The serum cytokine concentrations of the 22 HC patients with ascites were significantly higher than those of the 14 HC patients without ascites (P< 0. 01). Their serum cytokine concentrations were sig- nificantly higher than those in the 18 patients with CH (P<0. 01). The concentration of IL-6 in ascites was the highest among all the groups. The serum le- vels of MIF, TNF-α and IL-6 are correlated with al- anine aminotransferase (ALT) in the patients with CH, but not in those with HC with or without asci- tes. Conclusions: These results indicated that MIF, TNF- α and IL-6 may participate in the pathological process of CH and cirrhosis, that IL-6 seems to play an important role in ascites formation, and that se- rum levels of MIF, TNF-α and IL-6 appear to reflect the severity of tissue injury in HBV disease.

Hepatoprotective effects of antioxidants in chronic hepatitis C

We have read with interest the paper published in issue 2, volume 16 of World Journal of Gastroenterology 2010 by Nakamura et al, demonstrating that the antioxidant resveratrol (RVT) enhances hepatitis C virus (HCV) replication, consequently, they conclude that RVT is not a suitable antioxidant therapy for HCV chronic infection. The data raise some concern regarding the use of complementary and alternative medicine since the most frequent supplements taken by these patients are antioxidants or agents that may be beneficial for different chronic liver diseases. A recent study by Vidali et al on oxidative stress and steatosis in the progression of chronic hepatitis C concludes that oxidative stress and insulin resistance contribute to steatosis, thus accelerating the progression of fibrosis. We are particularly interested in investigating how the oxidative and nitrosative stress mechanisms are involved in the pathogenesis of different chronic liver diseases.

Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C

Interstitial pneumonitis(IP) is an uncommon pulmonary complication associated with interferon(IFN) therapy for chronic hepatitis C virus(HCV) infection.Pneumonitis can occur at any stage of HCV treatment,ranging from 2 to 48 wk,usually in the first 12 wk.Its most common symptoms are dyspnoea,dry cough,fever,fatigue,arthralgia or myalgia,and anorexia,which are reversible in most cases after cessation of IFN therapy with a mean subsequent recovery time of 7.5 wk.Bronchoalveolar lavage in combination with chest high resolution computed tomography has a high diagnostic value.Prompt discontinuation of medication is the cornerstone,and corticosteroid therapy may not be essential for patients with mild-moderate pulmonary functional impairment.The severity of pulmonary injury is associated with the rapid development of IP.We suggest that methylprednisolone pulse therapy followed by low dose prednisolone for a short term is necessary to minimize the risk of fatal pulmonary damage if signs of significant pulmonary toxicity occur in earlier stage.Clinicians should be aware of the potential pulmonary complication related to the drug,so that an early and opportune diagnosis can be made.

Clearance of HCV RNA in peripheral blood mononuclear cell as a predictor of response to antiviral therapy in patients with chronic hepatitis C

BACKGROUND: The resolution of hepatitis C, evidenced by normalization of liver function and disappearance of hepatitis C virus RNA from serum as determined by conventional laboratory assays, reflects virus eradication. But in interferon treated patients the HCV RNA in serum sometimes could not show the virus in cells. Such factors as virus genotype, HCV RNA contents in serum, HCV specific cellular immunities after treatment were reported to predict the response to interferon therapy. In most patients, HCV RNA could detect the virus in peripheral blood mononucle-ar cell. The aim of this study was to investigate the predictive value of HCV RNA in PBMC of patients with chronic hepatitis C after interferon treatment. METHODS: Sixteen patients with chronic hepatitis C were treated with interferon for 24 weeks, and they all get complete responses at 12 weeks of treatment. At the end of treatment, the HCV RNA in PBMC and serum were detected by RT-PCR, and after stopping treatment, HCV RNA in serum was monitored continually. RESULTS: In 9 patients who were HCV RNA positive in their PBMC at the end of treatment, 8 showed serum HCV RNA positive after 24 weeks and another 1 after 1 year. In 7 patients with negative HCV RNA in their PBMC, only 2 patients relapsed in serum HCV RNA after 1-year follow-up, and others remained viral response after 3.5 years. CONCLUSION: HCV RNA in PBMC at the end of IFN treatment is a predictor of durable response to antiviral therapy in patients with chronic hepatitis C.

Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C

AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis C.METHODS:Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 wk.The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ) and interleukin-10(IL-10).RESULTS:Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values,but the patients who received Viusid showed a more marked reduction as compared with the control group(P=0.001).TNF-α levels significantly increased from 6.9 to 16.2 pg/mL(P< 0.01) in the patients who received placebo in comparison with almost unchanged levels,from 6.6 to 7.1 pg/mL(P=0.26),in the patients treated with Viusid(P=0.001).In addition,IL-10 levels were markedly increased in the patients treated with Viusid(from 2.6 to 8.3 pg/mL,P=0.04) in contrast to the patients assigned to placebo(from 2.8 to 4.1 pg/mL,P=0.09)(P=0.01).Likewise,the administration of Viusid markedly increased mean IFN-γ levels from 1.92 to 2.89 pg/mL(P< 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL(P=0.70) in the placebo group(P< 0.0001).Viusid administration was well tolerated.CONCLUSION:Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.

Hepatitis C virus genotypes, HLA-DRB alleles and their response to interferon-α and ribavirin in patients with chronic hepatitis C

BACKGROUND: Hepatitis C virus (HCV) is a worldwide common disease. Some predictive factors influencing the response to interferon alpha (IFN-α) therapy have been identified, but the conclusions differ in various counties and areas. The aim of this study was to study the associa- tions between HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin in Chinese patients with chronic hepatitis C in Northeast China. METHODS: HCV genotypes of 113 patients with HCV were investigated. Gene chips were used to analyze the fre- quency of HLA-DRB in 25 of these patients and their re- sponse to IFN-α and ribavirin. The associations of HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin were also studied. RESULTS: The response rates differed in several types of HCV, with HCV 2b being the highest (57.78% ), HCV 1a and 2a lower (46.15% and 47.62% ) and HCV 1b the low- est (11.76% ). The response rates to IFN-α and ribavirin in patients with DRB1 07 were higher than those with DRB1 04. Sex, HCV type and HLA-DRB were all related to the response. Most female patients with HCV 2b and HLA- DRB1 07 presented complete response, whereas male pa- tients with HCV 1b and HLA-DRB1 04 usually demon- strated no response. DRB1 07 allele and HCV 2b were the factors closely related to the response. CONCLUSIONS: The response rate of HCV 1b may be the lowest even IFN-α and ribavirin are combined in treat- ment. Not only virus but also the host plays an important role in anti-virus therapy. Thus, it is necessary to adjust the host's immune status to accelerate the clearance of HCV.