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

Impact of sustained virologic response on chronic kidney disease progression in hepatitis C

AIM To determine how sustained virological response at 12 wk(SVR12) with direct acting antivirals(DAAs) for the treatment of hepatitis C virus(HCV) infection affects chronic kidney disease(CKD) progression. METHODS A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates.RESULTS Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate(e GFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 m L/min ± 0.75 m L/min per 1.73 m^2 compared to a decline in e GFR of 11.0 m L/min ± 2.81 m L/min per 1.73 m^2 in patients who did not achieve SVR12(P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in e GFR in those with untreated HCV over 2 years was 2.8 m L/min ± 1.0 m L/min per 1.73 m^2, which was not significantly different from the e GFR decline noted in HCV-treated patients who achieved SVR12(P = 0.43).CONCLUSION Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.

Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin

AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

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

AIM:To document the sustained virological response (SVR) in rapid virological responders (RVR) of genotype-3 chronic hepatitis C with standard interferon (SdIF). METHODS:Hepatitis C genotype-3 patients during the period July 2006 and June 2007 were included. Complete blood counts, prothrombin time, ALT, albumin, qualitative HCV RNA were done. SdIF and ribavirin were given for 4 wk and qualitative HCV RNA was repeated. Those testing negative were allocated to group-A while the rest were allocated to group-B. Treatment was continued a total of 16 and 24 wk for group A and B respectively. HCV RNA was repeated after 24 wk of treatment. End virological and sustained virological responses were compared by χ2 test. ROC of pretreatment age, ALT and albumin were plotted for failure to achieve SVR. RESULTS:Of 74 patients treated, RCV RNA after 16 wk of therapy became undetectable in 34 (45.9%) and was detectable in 40 (54.1%) and were allocated to groups A and B respectively. SVR was achieved in 58.8% and 27.8% in groups A and B respectively. SVR rates were significantly higher in patients who had RVR as compared to those who did not (P = 0.0;γ = 2). Both groups combined ETR and SVR were 70% and 33% respectively. ROC plots of pretreatment age, ALT and albumin for SVR showed only ALT to have a significantly large area under the curve.CONCLUSION:SVR rates were higher in patients who had RVR with SdIF and high pre treatment ALT values correlated to probability of having RVR.

Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment

AIM: To assess the clinical, biochemical, and virological outcome during long-term follow-up of chronic hepatitis C patients with sustained virological response following effective antiviral therapy.METHODS: This study was a retrospective cohort study including 171 sustained responders defi ned as HCV RNA PCR negative at 6 mo after the end of effective antiviral treatment (SVR-6). Clinical signs and symptoms, bio- chemical hepatic parameters, ultrasonography and HCV RNA PCR were followed.RESULTS: Mean follow-up period was 35.38 ± 22.2 mo after the end of treatment. Twenty-seven (15.8%) responders had evidence of cirrhosis before treatment. Forty-eight (28.1%), 107 (62.6%) and 6 (3.5%) patients were genotype 1, 3, and 6 respectively, while 10 patients (5.8%) were unclassifi ed. There were no virological and biochemical relapses during the period of follow-up. None of the patients showed evidence of hepatic decom- pensation. However, there were 3 patients (1.8%) de- veloping hepatocellular carcinoma at 14, 18, 29 mo after treatment discontinuation, two of whom had evidence of cirrhosis prior to therapy.CONCLUSION: The study shows that during a follow- up interval for about 3 years in 171 chronic hepatitis C patients with sustained viral response after effective antiviral treatment there were no evident signs of either biochemical or clinical relapse of liver disease in all but three patients who developed hepatocellular carcinoma.

Long-term follow-up of HCV patients with sustained virological response after treatment with pegylated interferon plus ribavirin

Background:The progress of liver diseases may not stop after viral eradication.This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV)infection who underwent pegylated interferon plus ribavirin(PR)regimen and achieved a sustained virological response 24 weeks post-treatment(SVR24).Methods:Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up.Baseline characteristics were profiled.The incidence of hepatocellular carcinoma(HCC),progression of liver disease(increase in liver stiffness or occurrence of decompensated complication),and HCV recurrence was all monitored.The accumulative and annualized incidence rates(AIRs)of these adverse events were analyzed,and the risk factors were also examined.Results:In total,151 patients reached a median follow-up time of 103 weeks.Among them,two had an incidence of HCC during the surveillance with AIR of 0.68%(95%CI:0.00-1.63%).Six patients showed progression of liver disease with AIR of 2.05%(95%CI:0.42%-3.68%).Three patients who had risky behaviors encountered HCV reinfection.The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients,including HCC and progression of liver disease(AIR:6.17%vs.1.42%,P=0.039).Conclusions:The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period,but the risk level was low.Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones.HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.

The Predictive Value of On-treatment Virological Response for Sustained Virological Response in Patients with Chronic Hepatitis C Receiving a Personalized Treatment Program

To investigate the effects of individualised treatment with peginterferon alpha-2a(40 kD)plus ribavirin in Chinese patients with CHC.Methods Total of 297 consecutive Chinese patients were enrolled,including 250 nave cases and 47 cases who were previously treated.Treatment duration was determined according to viral genotypes,prior treatment history and viral responses at week 4,12 and 24.Results Totally,235 patients(79.1%)completed treatment and 186(87.3%)achieved SVR.And 219 out of 289(75.8%)patients achieved HCV RNA negative at week 4(RVR)and 259 of 276(93.8%)at week 12.Among the 164 patients with RVR who completed follow-up,158(96.3%)achieved SVR.Patients with RVR had lower baseline viral loads than patients without RVR(P=0.034).The positive predictive value(PPV)of RVR for SVR was 90.7%(OR 2.10 vs.non-RVR,95%CI:0.50-8.7).Similar outcomes were observed among patients with HCV undetectable at week 12.Conclusions Viral suppression by week 4 is associated with a high rate of treatment success in treatment nave and experienced patients receiving individualized CHC therapy.

Sustained virological response in a predominantly hepatitis C virus genotype 4 infected population

AIM:To assess sustained virological response(SVR) rates in a predominantly hepatitis C virus(HCV) genotype 4 infected population. METHODS:Between 2003-2007,240 patients who were treated for chronic hepatitis C infection at our center were included.Epidemiological data,viral genotypes,and treatment outcomes were evaluated in all treated patients.Patients with chronic renal failure, previous non-responders,and those who relapsed after previous treatment were excluded from the study.Among all patients,57%were treated with PEG-interferon(IFN)α-2a and 43%patients were treated with PEG-IFNα-2b;both groups received a standard dose of ribavirin. RESULTS:89.6%of patients completed the treatment with an overall SVR rate of 58%.The SVR rate was 54%in genotype 1,44%in genotype 2,73%in genotype 3,and 59%in genotype 4 patients.There was no statistical difference in the SVR rate between patients treated with PEG-IFNα-2a and PEG-IFNα-2b (61.5%vs 53%).Patients younger than 40 years had higher SVR rates than older patients(75%vs 51%,P =0.001).SVR was also statistically significantly higher when the HCV RNA load(pretreatment)was below 800.000(64%vs 50%,P=0.023),in patients with a body mass index(BMI)less than 28(65%vs 49%,P =0.01),and in patients who completed the treatment duration(64%vs 8%,P≤0.00001).CONCLUSION:The SVR rate in our study is higher than in previous studies.Compliance with the standard duration of treatment,higher ribavirin dose,younger age,lower BMI,and low pretreatment RNA levels were associated with a higher virological response.

Hepatitis C: Problems to extinction and residual hepatic and extrahepatic lesions after sustained virological response

Loss of follow-up or reinfections hinder the expectations of hepatitis C eradicationdespite the existence of highly effective treatments. Moreover, the elimination ofthe infection does not imply the reversion of those chronic alterations derivedfrom the previous infection by hepatitis C virus (HCV). This review analyzes therisk factors associated with loss to follow-up in diagnosis or treatment, and thepossibility of reinfection. Likewise, it assesses the residual alterations induced bychronic HCV infection considering the liver alterations (inflammation, fibrosis,risk of decompensation, hepatocellular carcinoma, liver transplantation) and, onthe other hand, the comorbidities and extrahepatic manifestations (cryoglobulinemia,non-Hodgkin lymphoma, peripheral insulin resistance, and lipid, boneand cognitive alterations). Peculiarities present in subjects coinfected with humanimmunodeficiency virus are analyzed in each section.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis: Who to screen and for how long?

Hepatitis C virus(HCV)chronic infection is associated with fibrosis progression,end-stage liver complications and HCC.Not surprisingly,HCV infection is a leading cause of liver-related morbidity and mortality worldwide.After sustained virological response(SVR),the risk of developing hepatocellular carcinoma is not completely eliminated in patients with established cirrhosis or with advanced fibrosis.Therefore,lifelong surveillance is currently recommended.This strategy is likely not universally cost-effective and harmless,considering that not all patients with advanced fibrosis have the same risk of developing HCC.Factors related to the severity of liver disease and its potential to improve after SVR,the molecular and epigenetic changes that occur during infection and other associated comorbidities might account for different risk levels and are likely essential for identifying patients who would benefit from screening programs after SVR.Efforts to develop predictive models and risk calculators,biomarkers and genetic panels and even deep learning models to estimate the individual risk of HCC have been made in the direct-acting antiviral agents era,when thousands of patients with advanced fibrosis and cirrhosis have reached SVR.These tools could help to identify patients with very low HCC risk in whom surveillance might not be justified.In this review,factors affecting the probability of HCC development after SVR,the benefits and risks of surveillance,suggested strategies to estimate individualized HCC risk and the current evidence to recommend lifelong surveillance are discussed.

Metabolic and cardiovascular complications after virological cure in hepatitis C:What awaits beyond

The association between chronic hepatitis C(CHC)infection and extrahepatic manifestations(EHMs),particularly cardiometabolic diseases,has been extensively examined.However,there has still been insufficient evaluation for these EHMs after virological cure.Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus(HCV)developing EHMs,cardiometabolic ones,as well as the effect of antiviral therapy to resolve these EHMs.Data on these manifestations after achieving sustained virologic response(SVR)are still conflicting.However,current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile,which increases cardiovascular disease(CVD)risk.Additionally,most observations showed that metabolic alterations,such as insulin resistance and diabetes mellitus(DM),undergo some degree of reduction after viral clearance.These changes seem HCV-genotype dependent.Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM.Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results,with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones.In this review,we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR,which may have an impact on healthcare providers’clinical practice.

FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

Dramatic response of hepatitis C patients chronically infected with hepatitis C virus genotype 3 to sofosbuvirbased therapies in Punjab, Pakistan: A prospective study

AIM To prospectively evaluate the efficacy of sofobuvir(SOF) in hepatitis C patients infected with hepatitis C virus(HCV) genotype 3 in Pakistan.METHODS The present study was performed with the coordination of gastroenterology and pathology departments of Shalamar Hospital Lahore from August 2014 to May 2016. The total number of patients included in this study was 1375 and all of them were infected with HCV genotype 3. On the basis of drug combinations, all the patients were separated into two groups. The first group of patients was treated for 24 wk with SOF(Sovaldi? by Gilead Sciences) plus ribavirin(RBV) [Ribazol? by Getz Pharma Pakistan(PVT) Ltd], while the patients of the second group were treated with SOF + RBV + pegylatedinterferon(peg IFN) alfa-2 a(Ropegra by Roach) for 12 wk. HCV genotyping and viral load measurement were performed on fully automated Abbott Real-Time PCR system(Abbott m24 sp automated nucleic acid extraction system and Abbott m2000 rt amplification system; abbott Molecular, Des Plaines, IL, United States). For the assessment of sustained virological response(SVR), all HCV RNA negative patients were followed for 12weeks after the treatment completion. Any patient with less than 12 IU/m L viral load after 12 wk of treatment completion was considered as a sustained virological responder(SVR-12).RESULTS A total of 1375 patients chronically infected with HCV genotype 3 were treated with two drug combinations SOF + RBV and SOF + RBV + peg IFN alfa-2 a. On the basis of these drug combinations, patients were divided into two groups(first and second). Overall SVR-12 was excellent in both groups(99.17% and 97.91%). Older patients(> 40 years) of second group showed lower SVR-12(93.46%) compared to first group older patients(98.79%), while in the younger patients of both groups, the SVR-12 rate was almost the same(99.54% in first group and 99.05% in second group). No such difference regarding SVR-12 rate was seen in males and females of first group patients(99.68% and 98.88%, respectively), while in second group the males were found to be better responders compared to females(98.96% and 95%). The SVR-12 rate in previously treated patients of first group was better(99.34%) than second group(93.70%), while na?ve patients of second group were marginally better responders(99.25%) than first group(97.80%). Rapid viral response at week-4 was found to be a very effective predictor for assessing the SVR rate at this stage of therapy in both groups. Headache, anemia and fatigue were common side effects in both groups either treated with SOF + RBV or SOF + RBV + peg IFN alfa-2 a, while the overall percentage of the side effects was higher in second group.CONCLUSION The remarkable SVR response rate of HCV genotype 3 infected patients to SOF provided a new way to look forward to eliminate hepatitis C from our region.

Hepatitis C virus induced insulin resistance impairs response to anti viral therapy

Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

AIM: To evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA < 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.

Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment

To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODSSequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTSFor both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.

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.

Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance

BACKGROUND The treatment of hepatitis C with direct-acting antiviral agents(DAAs)produces a high rate of sustained virological response(SVR)with fewer adverse events than interferon(IFN)therapy with a similar effect in inhibiting carcinogenesis as IFN therapy.The age-male-albumin-bilirubin-platelets(aMAP)score is useful for stratifying the risk of hepatocellular carcinoma in chronic hepatitis patients,and the velocity of shear waves(Vs)measured by shear wave elastography has also been shown to be useful for diagnosing the level of fibrotic progression in hepatitis C and predicting carcinogenic risk.Combining these two may improve the prediction of carcinogenic risk.AIM To determine whether combining the aMAP score with Vs improves carcinogenic risk stratification in medium-to-high-risk hepatitis C patients.METHODS This retrospective,observational study involved hepatitis C patients treated with DAAs who achieved SVR.Vs was measured before treatment(baseline),at the end of treatment(EOT),and 12 wk(follow-up 12)and 24 wk(follow-up 24)after treatment.The patients were followed for at least six months after EOT to determine whether cancer developed.Multiple regression analysis was used to identify factors contributing to hepatic carcinogenesis.The diagnostic performances of clinical parameters for predicting the presence of hepatocellular carcinoma were evaluated using receiver-operating characteristic(ROC)curve analyses.RESULTS A total of 279 patients(mean age 65.9 years,118 males,161 females)were included in the analysis.Multiple regression analysis was performed with carcinogenesis as the target variable and alanine aminotransferase,platelets,α-fetoprotein,Vs,and the Fib-4 index as explanatory variables;only Vs was found to be significant(P=0.0296).The cut-off value for Vs for liver carcinogenesis calculated using the ROC curve was 1.53 m/s.Carcinoma developed in 2.0%(3/151)of those with Vs<1.53 m/s and in 10.5%(9/86)of those with Vs≥1.53 m/s.CONCLUSION In hepatitis C patients after SVR,combining the aMAP score and Vs to stratify the risk of carcinogenesis is more efficient than uniform surveillance of all patients.

Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine:Three case reports

BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment barriers.DAAs co-prescribed with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pibrentasvir due to potent cytochrome P450(CYP)3A4 induction.Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite time.Sofosbuvirvelpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment failure.This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible,impractical or unacceptable.However,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhibitory effect,may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction.CASE SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b,and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir,while co-prescribed carbamazepine for seizure disorders.Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants.DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration,and taken with meals to improve absorption.Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.CONCLUSION DAA therapies,including glecaprevir-pibrentasvir,warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine,particularly if AED substitution is not feasible.