BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the saf...BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the safety and efficacy of the generic sofosbuvir(SOF)/ledipasvir(LED)in Egyptian HCV-infected children and to compare the results with the brand form.METHODS This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing>35 kg.Collected data included:Age,sex,risk factors of HCV acquisition,comorbidities,liver functions,HCV viral load,degree of hepatic fibrosis,sustained virologic response(SVR)and frequency of treatment adverse effects.Patients who received the generic form of SOF/LED(Ledisbuvir)were compared to patients who received the brand form(Harvoni®)regarding SVR and frequency of adverse events.RESULTS The study included 43 patients who received Ledisbuvir and 73 who received Harvoni®.All patients achieved SVR.Treatment side effects were mild,transient and comparable in both groups.CONCLUSION The use of generic SOF/LED in HCV infected children is safe and effective.It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.展开更多
Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of n...Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.展开更多
It has been reported that the serum level of vitamin D3(Vit D3) could affect the natural course of chronic hepatitis C(CH-C) and the response to treatment with pegylated interferon(Peg-IFN) and ribavirin. Although sev...It has been reported that the serum level of vitamin D3(Vit D3) could affect the natural course of chronic hepatitis C(CH-C) and the response to treatment with pegylated interferon(Peg-IFN) and ribavirin. Although several mechanisms for the favorable effects of Vit D3 supplementation were reported, the total effect of Vit D3 supplementation remains unclear. Previously, we reported that supplementation with 1(OH)Vit D3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control. Recently, the main treatment of CH-C should be direct acting antivirals(DAAs) without PegIFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of Vit D3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding Vit D3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD 3.展开更多
BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of c...BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations.AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain.METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018.There were 149 patients who were treated with brand DAAs,while 140 patients were treated with generic DAAs.Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir±Dasabuvir±Ribavirin,and Sofosbuvir/Daclatasvir±Ribavirin.SVR at 12 wk post treatment was the main outcome variable.RESULTS Overall,87 patients(30.1%)had cirrhosis and 68.2%had genotype 1 HCV infection.At 12 wk post treatment,SVR was achieved by 271(93.8%)of the patients.In patients who were treated with generic medications,134(95.7%)achieved SVR at 12 wk post treatment,compared to 137(91.9%)among those treated with brand medications(P=0.19).Having cirrhosis[odds ratio(OR):9.41,95%confidence interval(CI):2.47–35.84]and having HCV genotype 3(OR:3.56,95%CI:1.03–12.38)were significant independent predictors of not achieving SVR.Alanine transaminase,gamma-glutamyl transpeptidase,and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs.CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients.Both are safe and equally effective in improving biochemical markers of hepatic inflammation.展开更多
For a long time, a combination of interferon and ribavirin has been used to treat viral hepatitis C, but the sustained virological response was only achieved in 45% of cases and side effects were serious [1]. Dir...For a long time, a combination of interferon and ribavirin has been used to treat viral hepatitis C, but the sustained virological response was only achieved in 45% of cases and side effects were serious [1]. Direct acting antivirals (DAA) have provided a cure for almost everyone with hepatitis C, with few side effects. The Purpose of Our Work is to compare the results of treatment for viral hepatitis C before and after DAA. Patients and Methods: This is a retrospective study, bringing together all patients with chronic viral hepatitis C treated between January 2009 and March 2020 at the University Hospital Hassan II in Fez, Morocco. The epidemiological, clinical, biological, virological characteristics of the included patients were collected from the two groups: A, treated with interferon and ribavirin or by triple therapy and B, treated with DAA. Results: 162 patients were included, the average age was 55 y/o, with 90 women and 72 men. 88 patients (54.3%) were already cirrhotic, of which 61 were compensated and 27 were decompensated. Genotype 1 was dominant with a frequency of 71.6%, 107 patients (66%) initially treated with old HCV treatments and 55 (34%) treated with DAA. Sustained viral response was obtained in 59 cases (55.14%) in group A versus 54 cases (98.18%) in group B with a very significant difference (p < 0.0001). Treatment failure was observed in 14 patients (13.1%) in group A and only one patient, i.e. 2% in group B (p = 0.019). 14 patients relapsed in group A (13.1%) versus 0 patient in group B (p = 0.003). The tolerance of the treatment was excellent in group B as a whole with only five patients (9%) reported side effects which were minor, not leading to the discontinuation of treatment while the side effects were major in 49 patients (45.7%) in group A with led to the permanent discontinuation of treatment in 6 patients. The difference in side effects between the two groups was very significant with (p Conclusion: Our study has shown the superiority of DAA in terms of efficacy and tolerance compared to the old treatments for chronic hepatitis C. In addition, these treatments allow almost systematic viral elimination and therefore consequently a reduction in the risk of complications hepatic with a short time of treatment.展开更多
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 ...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).展开更多
The estimated number of people with active hepatitis C virus infection worldwide is about 70 million.The estimated number of people with active hepatitis C virus infection worldwide is about 70 million.Approximately 3...The estimated number of people with active hepatitis C virus infection worldwide is about 70 million.The estimated number of people with active hepatitis C virus infection worldwide is about 70 million.Approximately 30%of infected individuals develop cirrhosis,whilst some develop liver cancer,the fifth most common cancer worldwide.Currently available treatments,high-efficacy antiviral agents mostly short-term(8-12 weeks)and pangenotypic,have efficacy rates of over 96%.Some patients,especially those with cirrhosis,develop primary liver cancer even after effective hepatitis C virus treatment.In order to diagnose hepatocellular carcinoma early,patients at risk should be enrolled in a surveillance program.展开更多
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 trea...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.展开更多
BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL aft...BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL after HCV eradication,no data exists on the modifications of neuropsychological symptoms.AIM To investigate the effect of directly acting antivirals(DAAs)treatment on HRQoL and neuropsychological symptoms.METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment,including Zung-Self Depression-Rating-Scale,Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment.HRQoL was detected by Short-Form-36(SF-36).RESULTS All HRQoL domains,but role limitation physical and bodily pain,significantly improved after treatment.Interestingly,after DAAs treatment,all domains of HRQoL returned similar to those of controls.Each neuropsychological test significantly improved after HCV eradication.A significant correlation was observed among each psychological test and the summary components of SF-36.At multiple linear regression analysis including each psychological test as possible covariates,Zung-Self Depression Rating Scale(Zung-SDS)score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment.CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.展开更多
BACKGROUND Hepatitis C virus(HCV)is a disease with a significant global impact,affecting approximately 2%-2.5%of the world’s population.New direct-acting antivirals(DAAs)have been introduced over the past few years w...BACKGROUND Hepatitis C virus(HCV)is a disease with a significant global impact,affecting approximately 2%-2.5%of the world’s population.New direct-acting antivirals(DAAs)have been introduced over the past few years with great success in viral eradication.The association of chronic HCV infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature.AIM To assess the effect of treating HCV with DAAs on the extrahepatic cutaneous manifestations of HCV.METHODS This prospective observational study included 1039 HCV positive Egyptian patients who were eligible to receive DAAs.A total of 30 patients were diagnosed with extrahepatic cutaneous manifestations and fulfilled the inclusion criteria of the study.Of these patients,6 had classic lichen planus,8 were diagnosed with psoriasis vulgaris and 16 had pruritus.All patients received DAAs from October 2018 to July 2019 in the form of a three-month course of sofosbuvir/daclatasvir combination.Patients with lichen planus or psoriasis were dermoscopically evaluated before treatment and 6 mo after treatment,while patients with hepatic pruritus were assessed using the 12-Item Pruritus Severity Scale over the same period.RESULTS All patients with psoriasis showed significant improvement in all psoriatic plaques,and all patients with hepatic pruritus scored 0 on the 12-Item Pruritus Severity Scale indicating total improvement of pruritus.In addition,four of six patients with lichen planus showed complete improvement.CONCLUSION Treatment of HCV with DAAs was significantly effective in improving virusrelated extrahepatic cutaneous manifestations.展开更多
Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Cons...Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.展开更多
BACKGROUND Direct acting antiviral(DAA)therapy has enabled hepatitis C virus infection to become curable,while histological changes remain uncontained.Few valid noninvasive methods can be confirmed for use in surveill...BACKGROUND Direct acting antiviral(DAA)therapy has enabled hepatitis C virus infection to become curable,while histological changes remain uncontained.Few valid noninvasive methods can be confirmed for use in surveillance.Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid(Gd-EOB-DTPA)is a liver-specific magnetic resonance imaging(MRI)contrast,related to liver function in the hepatobiliary phase(HBP).Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C(CHC)has not been investigated.AIM To investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC.METHODS Patients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment,and those with paired qualified MRI and liver biopsy specimens were included.Transient elastography(TE)and blood tests were also arranged.Patients treated with DAAs who achieved 24-wk sustained virological response(SVR)underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again.The signal intensity(SI)of the liver and muscle were measured in the unenhanced phase(UEP)(SI_(UEP-liver),SI_(UEP-muscle))and HBP(SI_(HBP-liver),SI_(HBP-muscle))via MRI.The contrast enhancement index(CEI)was calculated as[(SI_(HBP-liver)/SI_(HBP-muscle))]/[(SI_(UEP-liver)/SI_(UEP-muscle))].Liver stiffness measurement(LSM)was confirmed with TE.Serologic markers,aspartate aminotransferase-to-platelet ratio index(APRI)and Fibrosis-4(FIB-4),were also calculated according to blood tests.The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index(mHAI)and Ishak fibrosis score,respectively.Fibrosis regression was defined as a≥1-point decrease in the Ishak fibrosis score.The correlation between the CEI and liver pathology was evaluated.The diagnostic and follow-up values of the CEI,LSM,and serologic markers were compared.RESULTS Thirty-nine patients with CHC were enrolled[average age,42.3±14.4 years;20/39(51.3%)male].Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR.The mHAI median significantly decreased after SVR[baseline 6.0(4.5-13.5)vs SVR 2.0(1.5-5.5),Z=3.322,P=0.017],but the median stage of fibrosis did not notably change(P>0.05).Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology.The CEI was negatively correlated with the mHAI(r=-0.56,P<0.001)and Ishak score(r=-0.69,P<0.001).Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation.For patients with Ishak score≥5,the areas under receiver operating characteristics curve of the CEI,LSM,APRI,and FIB-4 were approximately at baseline,0.87–0.93,and after achieving SVR,0.83–0.91.The CEI cut-off value was stable(baseline 1.58 and SVR 1.59),but those of the APRI(from 1.05 to 0.24),FIB-4(from 1.78 to 1.28),and LSM(from 10.8 kpa to 7.1 kpa)decreased dramatically.The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score≥3(P>0.05).Seven patients achieved fibrosis regression after achieving SVR.In these patients,the CEI median increased(from 1.71 to 1.83,Z=-1.981,P=0.048)and those of the APRI(from 1.71 to 1.83,Z=-2.878,P=0.004)and LSM(from 6.6 to 4.8,Z=-2.366,P=0.018)decreased.However,in patients without fibrosis regression,the medians of the APRI,FIB-4,and LSM also changed significantly(P<0.05).CONCLUSION Gd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC.It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.展开更多
In the United States,the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years,but the results have been less than ideal.Historically,patients with chronic hepatitis C (CHC) were treated...In the United States,the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years,but the results have been less than ideal.Historically,patients with chronic hepatitis C (CHC) were treated with interferon-based regimens,which were associated with frequent adverse effects,suboptimal response rates,and long durations of treatment-of up to 48 weeks.Expertise from specialistphysicians,such as hepatologists and gastroenterologists,was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse effects.However,the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety,tolerability,lack of adverse effects,efficacy,and truncated duration of therapy-12 weeks or less-thereby making the need for close monitoring by specialist-physicians obsolete.With the recent approval of DAA agents by the Food and Drug Administration,the treatment model for CHC no longer relies on the limited number of specialist-physicians,which represented a major barrier to treatment access in the past,especially in underserved areas of the United States.We propose and share our experiences in adapting a task-shifting treatment model,one that utilizes a relatively larger pool of non-specialist healthcare providers,such as nursing staff (medical assistants,vocational licensed nurses,registered nurses,etc.) and advanced practice providers (nurse practitioners and physician assistants),to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV infection.Most recently,task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging results.Based on our experiences in implementing this model at our outreach clinics,the majority of HCV-infected patients treated with DAA agents can be easily monitored by non-specialist healthcare providers and physician extenders.Task-shifting can effectively address one of the major rate-limiting factors in expanding treatment access for HCV infection.展开更多
Aim:Despite the high cure rate of interferon-free directly acting antivirals(DAAs)for chronic hepatitis C(CHC)patients,the treatment efficacy for patients with preexisting hepatocellular carcinoma(HCC)remains undefine...Aim:Despite the high cure rate of interferon-free directly acting antivirals(DAAs)for chronic hepatitis C(CHC)patients,the treatment efficacy for patients with preexisting hepatocellular carcinoma(HCC)remains undefined.We aimed in the present study to address the issue by using novel DAAs in treating CHC patients who were adherent to treatment in Taiwan.Methods:CHC patients with or without HCC were consecutively enrolled.The primary objective was sustained virological response(SVR)defined as undetectable HCV RNA throughout 12 weeks of a post-treatment follow-up period(SVR12).Only patients with available SVR12 were enrolled for final analysis.Results:A total of 1237 patients(1113 non-HCC,101 inactive HCC and 23 active HCC)were enrolled.The overall SVR12 rate was 98.9%,and was similar between HCV patients with and without pre-existing HCC(98.4%vs.98.9%,P=0.64).While HCC patients were classified as those who had active or inactive HCC,the SVR12 was also similar between patients with and without active HCC(95.7%vs.99.0%,P=0.34).Among the 101 patients without viable HCC at the time of DAA initiation,eighty-four patients exhibited curative therapy and the other 17 ;patients experienced HCC recurrence before DAAs.Among the 23 patients with viable HCC at the time of DAA treatment,10 patients had received curative therapy for HCC whereas the remaining 13 patients had HCC that was never cured.The SVR12 rates were also similar among the four subpopulations,being 98.8%(83/84),100%(17/17),90%(9/10)and 100%(13/13)respectively.Conclusion:CHC patients with HCC who were adherent to potent DAAs achieved similar SVR12 rate compared to those without HCC and could be effectively treated.展开更多
Worldwide,more than one million people die each year from hepatitis C virus(HCV)related diseases,and over 300 million people are chronically infected with hepatitis B or C.Egypt used to be on the top of the countries ...Worldwide,more than one million people die each year from hepatitis C virus(HCV)related diseases,and over 300 million people are chronically infected with hepatitis B or C.Egypt used to be on the top of the countries with heavy HCV burden.Some countries are making advances in elimination of HCV,yet multiple factors preventing progress;remain for the majority.These factors include lack of global funding sources for treatment,late diagnosis,poor data,and inadequate screening.Treatment of HCV in Egypt has become one of the top national priorities since 2007.Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients.Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014.Yet,with the development of highly-effective direct acting antivirals(DAAs)for HCV,elimination of viral hepatitis has become a real possibility.The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs.Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV.This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols.Also,it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.展开更多
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 eliminat...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.展开更多
AIMTo study impact of baseline mental health disease on hepatitis C virus(HCV)treatment;and Beck’s Depression Inventory(BDI)changes with sofosbuvir-and interferon-based therapy.METHODSThis is a retrospective...AIMTo study impact of baseline mental health disease on hepatitis C virus(HCV)treatment;and Beck’s Depression Inventory(BDI)changes with sofosbuvir-and interferon-based therapy.METHODSThis is a retrospective cohort study of participants from 5 studies enrolled from single center trials conducted at the Clinical Research Center of the National Institutes of Health,Bethesda,MD,United States.All participants were adults with chronic HCV genotype 1 infection and naïve to HCV therapy.Two of the studies included HCV mono-infected participants only(SPARE,SYNERGY-A),and 3 included human immunodeficiency virus(HIV)/HCV co-infected participants only(ERADICATE,PFINPK,and ALBIN).Patients were treated for HCV with 3 different regimens:Sofosbuvir and ribavirin in the SPARE trial,ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials,and pegylated interferon(IFN)and ribavirin for 48 wk in the PIFNPK and ALBIN trials.Participants with baseline mental health disease(MHD)were identified(defined as either a DSM IV diagnosis of major depression,bipolar disorder,schizophrenia,generalized anxiety,and post-traumatic stress disorder or requiring anti-depressants,antipsychotics,mood stabilizers or psychotropics prescribed by a psychiatrist).For our first aim,we compared sustained virologic response(SVR)and adherence(pill counts,study visits,and in 25 patients,blood levels of the sofosbuvir metabolite,GS-331007)within each study.For our second aim,only patients with HIV coinfection were evaluated.BDI scores were obtained pre-treatment,during treatment,and post-treatment among participants treated with sofosbuvir-based therapy,and compared to scores from participants treated with interferon-based therapy.Statistical differences for both aims were analyzed by Fisher’s Exact,and t-test with significance defined as a P value less than 0.05.RESULTSBaseline characteristics did not differ significantly between all participants with and without MHD groups treated with sofosbuvir-based therapy.Among patients treated with sofosbuvir-based therapy,the percentage of patients with MHD who achieved SVR was the same as those without(SPARE:60.9%of those MHD compared to 67.6%in those without,P=0.78;SYNERGY-A:100%of both groups;ERADICATE:100%compared to 97.1%).There was no statistically significant difference in pill counts,adherence to study visits between groups,nor mean serum concentrations of GS-331007 for each group at week 2 of treatment(P=0.72).Among patients with HIV co-infection,pre-treatment BDI scores were similar among patients treated with sofosbuvir,and those treated with interferon(sofosbuvir-based 5.24,IFN-based 6.96;P=0.14);however,a dichotomous effect on was observed during treatment.Among participants treated with directly acting antiviral(DAA)-based therapy,mean BDI scores decreased from 5.24(pre-treatment)to 3.28 during treatment(1.96 decrease,P=0.0034)and 2.82 post-treatment.The decrease in mean score from pre-to post-treatment was statistically significant(-2.42,P=0.0012).Among participants treated with IFN-based therapy,mean BDI score increased from 6.96 at pre-treatment to 9.19 during treatment(an increase of 2.46 points,P=0.1),and then decreased back to baseline post-treatment(mean BDI score 6.3,P=0.54).Overall change in mean BDI scores from pre-treatment to during treatment among participants treated with DAA-based and IFN-therapy was statistically significant(-1.96 and+2.23,respectively;P=0.0032).This change remained statistically significant when analysis was restricted to participants who achieved SVR(-2.0 and+4.36,respectively;P=0.0004).CONCLUSIONSofosbuvir-based therapy is safe and well tolerated in patients with MHD.A decline in BDI associated with sofosbuvir-based HCV treatment suggests additional MHD benefits,although the duration of these effects is unknown.展开更多
Rationale:Hepatitis C in the pediatric population is a large health burden globally.With its diverse genotypes as well as genotypic subtypes,there is a discrepancy in the genotypes used in research compared to their p...Rationale:Hepatitis C in the pediatric population is a large health burden globally.With its diverse genotypes as well as genotypic subtypes,there is a discrepancy in the genotypes used in research compared to their prevalence.HCV genotype 6 which is endemic to South China and Southeast Asia comprises approximately one-third of all HCV infections worldwide,but make up a minority of cases studied in HCV research.Patient concerns:We report a case of HCV-6 seen in an 11-yearold Burmese immigrant to the U.S.and describe the new direct acting antiviral treatment guidelines for pediatrics with HCV genotype 6.Interventions:The patient completed a 12-week course of ledipasvir/sofosbuvir(90 mg/400 mg),per FDA weight-based recommendations for treatment-naive HCV genotypes 4-6,without any complications.Outcomes:The patient was treated successfully with an undetectable HCV viral load one month after treatment completion.Lessons:HCV-6,although previously uncommon in the U.S.,is becoming more prevalent.Updated guidelines include the use of direct acting antivirals,which have been proven effective for HCV-6.Lessons on barriers to care in the immigrant population as well as the value of HCV genotyping are also discussed.展开更多
Chronic infections by hepatitis B virus(HBV)and hepatitis C virus(HCV)major causes of advanced liver disease and mortality worldwide.Although regarded as benign infections in children,their persistence through adultho...Chronic infections by hepatitis B virus(HBV)and hepatitis C virus(HCV)major causes of advanced liver disease and mortality worldwide.Although regarded as benign infections in children,their persistence through adulthood is undoubtedly of concern.Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment,which is currently far from being curative.Herein we describe direct-acting antivirals available for pediatric HCV(sofosbuvir/ledipasvir,sofosbuvir/velpatasvir,glecaprevir/pibrentasvir)and their real-world use.A critical review of the HBV pediatric classification is provided.Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population,including capsid assembly modulators,antigen secretion inhibitors,silencing RNAs,and immune modifiers.Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.展开更多
AIM To establish if serial Hepascore tests(referred to as delta Hepascore)in those with chronic hepatitis C(CHC)correlate with the increase and/or decrease in risk of liver related complications.METHODS Three hundred ...AIM To establish if serial Hepascore tests(referred to as delta Hepascore)in those with chronic hepatitis C(CHC)correlate with the increase and/or decrease in risk of liver related complications.METHODS Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied.During 1944 patient years follow-up 28(8.1%)reached an endpoint.The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis andsubsequent clinical outcomes in chronic liver disease.RESULTS Patients with a baseline Hepascore>0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma,liver death,and/or decompensation(P<0.001).In those with an initial Hepascore>0.75,a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint(P=0.004).There were no negative outcomes in those with a stable or improved delta Hepascore.The minimum time between tests that was found to give a statically significant result was in those greater than one year(P=0.03).CONCLUSION In conclusion,Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients.Of note,we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore.Repeat Hepascore tests,when performed at a minimum one-year interval,may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.展开更多
文摘BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the safety and efficacy of the generic sofosbuvir(SOF)/ledipasvir(LED)in Egyptian HCV-infected children and to compare the results with the brand form.METHODS This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing>35 kg.Collected data included:Age,sex,risk factors of HCV acquisition,comorbidities,liver functions,HCV viral load,degree of hepatic fibrosis,sustained virologic response(SVR)and frequency of treatment adverse effects.Patients who received the generic form of SOF/LED(Ledisbuvir)were compared to patients who received the brand form(Harvoni®)regarding SVR and frequency of adverse events.RESULTS The study included 43 patients who received Ledisbuvir and 73 who received Harvoni®.All patients achieved SVR.Treatment side effects were mild,transient and comparable in both groups.CONCLUSION The use of generic SOF/LED in HCV infected children is safe and effective.It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.
文摘Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.
文摘It has been reported that the serum level of vitamin D3(Vit D3) could affect the natural course of chronic hepatitis C(CH-C) and the response to treatment with pegylated interferon(Peg-IFN) and ribavirin. Although several mechanisms for the favorable effects of Vit D3 supplementation were reported, the total effect of Vit D3 supplementation remains unclear. Previously, we reported that supplementation with 1(OH)Vit D3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control. Recently, the main treatment of CH-C should be direct acting antivirals(DAAs) without PegIFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of Vit D3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding Vit D3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD 3.
文摘BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations.AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain.METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018.There were 149 patients who were treated with brand DAAs,while 140 patients were treated with generic DAAs.Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir±Dasabuvir±Ribavirin,and Sofosbuvir/Daclatasvir±Ribavirin.SVR at 12 wk post treatment was the main outcome variable.RESULTS Overall,87 patients(30.1%)had cirrhosis and 68.2%had genotype 1 HCV infection.At 12 wk post treatment,SVR was achieved by 271(93.8%)of the patients.In patients who were treated with generic medications,134(95.7%)achieved SVR at 12 wk post treatment,compared to 137(91.9%)among those treated with brand medications(P=0.19).Having cirrhosis[odds ratio(OR):9.41,95%confidence interval(CI):2.47–35.84]and having HCV genotype 3(OR:3.56,95%CI:1.03–12.38)were significant independent predictors of not achieving SVR.Alanine transaminase,gamma-glutamyl transpeptidase,and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs.CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients.Both are safe and equally effective in improving biochemical markers of hepatic inflammation.
文摘For a long time, a combination of interferon and ribavirin has been used to treat viral hepatitis C, but the sustained virological response was only achieved in 45% of cases and side effects were serious [1]. Direct acting antivirals (DAA) have provided a cure for almost everyone with hepatitis C, with few side effects. The Purpose of Our Work is to compare the results of treatment for viral hepatitis C before and after DAA. Patients and Methods: This is a retrospective study, bringing together all patients with chronic viral hepatitis C treated between January 2009 and March 2020 at the University Hospital Hassan II in Fez, Morocco. The epidemiological, clinical, biological, virological characteristics of the included patients were collected from the two groups: A, treated with interferon and ribavirin or by triple therapy and B, treated with DAA. Results: 162 patients were included, the average age was 55 y/o, with 90 women and 72 men. 88 patients (54.3%) were already cirrhotic, of which 61 were compensated and 27 were decompensated. Genotype 1 was dominant with a frequency of 71.6%, 107 patients (66%) initially treated with old HCV treatments and 55 (34%) treated with DAA. Sustained viral response was obtained in 59 cases (55.14%) in group A versus 54 cases (98.18%) in group B with a very significant difference (p < 0.0001). Treatment failure was observed in 14 patients (13.1%) in group A and only one patient, i.e. 2% in group B (p = 0.019). 14 patients relapsed in group A (13.1%) versus 0 patient in group B (p = 0.003). The tolerance of the treatment was excellent in group B as a whole with only five patients (9%) reported side effects which were minor, not leading to the discontinuation of treatment while the side effects were major in 49 patients (45.7%) in group A with led to the permanent discontinuation of treatment in 6 patients. The difference in side effects between the two groups was very significant with (p Conclusion: Our study has shown the superiority of DAA in terms of efficacy and tolerance compared to the old treatments for chronic hepatitis C. In addition, these treatments allow almost systematic viral elimination and therefore consequently a reduction in the risk of complications hepatic with a short time of treatment.
文摘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).
文摘The estimated number of people with active hepatitis C virus infection worldwide is about 70 million.The estimated number of people with active hepatitis C virus infection worldwide is about 70 million.Approximately 30%of infected individuals develop cirrhosis,whilst some develop liver cancer,the fifth most common cancer worldwide.Currently available treatments,high-efficacy antiviral agents mostly short-term(8-12 weeks)and pangenotypic,have efficacy rates of over 96%.Some patients,especially those with cirrhosis,develop primary liver cancer even after effective hepatitis C virus treatment.In order to diagnose hepatocellular carcinoma early,patients at risk should be enrolled in a surveillance program.
基金Supported by National Natural Science Foundation of China,No.81373056Beijing Municipal Committee of Science and Technology,No.D161100002716003National Major Project for Infectious Diseases Control,No.2012ZX10002003-004-003
文摘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.
文摘BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL after HCV eradication,no data exists on the modifications of neuropsychological symptoms.AIM To investigate the effect of directly acting antivirals(DAAs)treatment on HRQoL and neuropsychological symptoms.METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment,including Zung-Self Depression-Rating-Scale,Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment.HRQoL was detected by Short-Form-36(SF-36).RESULTS All HRQoL domains,but role limitation physical and bodily pain,significantly improved after treatment.Interestingly,after DAAs treatment,all domains of HRQoL returned similar to those of controls.Each neuropsychological test significantly improved after HCV eradication.A significant correlation was observed among each psychological test and the summary components of SF-36.At multiple linear regression analysis including each psychological test as possible covariates,Zung-Self Depression Rating Scale(Zung-SDS)score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment.CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.
文摘BACKGROUND Hepatitis C virus(HCV)is a disease with a significant global impact,affecting approximately 2%-2.5%of the world’s population.New direct-acting antivirals(DAAs)have been introduced over the past few years with great success in viral eradication.The association of chronic HCV infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature.AIM To assess the effect of treating HCV with DAAs on the extrahepatic cutaneous manifestations of HCV.METHODS This prospective observational study included 1039 HCV positive Egyptian patients who were eligible to receive DAAs.A total of 30 patients were diagnosed with extrahepatic cutaneous manifestations and fulfilled the inclusion criteria of the study.Of these patients,6 had classic lichen planus,8 were diagnosed with psoriasis vulgaris and 16 had pruritus.All patients received DAAs from October 2018 to July 2019 in the form of a three-month course of sofosbuvir/daclatasvir combination.Patients with lichen planus or psoriasis were dermoscopically evaluated before treatment and 6 mo after treatment,while patients with hepatic pruritus were assessed using the 12-Item Pruritus Severity Scale over the same period.RESULTS All patients with psoriasis showed significant improvement in all psoriatic plaques,and all patients with hepatic pruritus scored 0 on the 12-Item Pruritus Severity Scale indicating total improvement of pruritus.In addition,four of six patients with lichen planus showed complete improvement.CONCLUSION Treatment of HCV with DAAs was significantly effective in improving virusrelated extrahepatic cutaneous manifestations.
文摘Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.
基金Supported by National Natural Science Foundation of China,No. 81870406Nature Science Foundation of Beijing Municipality,No. 7182174
文摘BACKGROUND Direct acting antiviral(DAA)therapy has enabled hepatitis C virus infection to become curable,while histological changes remain uncontained.Few valid noninvasive methods can be confirmed for use in surveillance.Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid(Gd-EOB-DTPA)is a liver-specific magnetic resonance imaging(MRI)contrast,related to liver function in the hepatobiliary phase(HBP).Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C(CHC)has not been investigated.AIM To investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC.METHODS Patients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment,and those with paired qualified MRI and liver biopsy specimens were included.Transient elastography(TE)and blood tests were also arranged.Patients treated with DAAs who achieved 24-wk sustained virological response(SVR)underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again.The signal intensity(SI)of the liver and muscle were measured in the unenhanced phase(UEP)(SI_(UEP-liver),SI_(UEP-muscle))and HBP(SI_(HBP-liver),SI_(HBP-muscle))via MRI.The contrast enhancement index(CEI)was calculated as[(SI_(HBP-liver)/SI_(HBP-muscle))]/[(SI_(UEP-liver)/SI_(UEP-muscle))].Liver stiffness measurement(LSM)was confirmed with TE.Serologic markers,aspartate aminotransferase-to-platelet ratio index(APRI)and Fibrosis-4(FIB-4),were also calculated according to blood tests.The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index(mHAI)and Ishak fibrosis score,respectively.Fibrosis regression was defined as a≥1-point decrease in the Ishak fibrosis score.The correlation between the CEI and liver pathology was evaluated.The diagnostic and follow-up values of the CEI,LSM,and serologic markers were compared.RESULTS Thirty-nine patients with CHC were enrolled[average age,42.3±14.4 years;20/39(51.3%)male].Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR.The mHAI median significantly decreased after SVR[baseline 6.0(4.5-13.5)vs SVR 2.0(1.5-5.5),Z=3.322,P=0.017],but the median stage of fibrosis did not notably change(P>0.05).Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology.The CEI was negatively correlated with the mHAI(r=-0.56,P<0.001)and Ishak score(r=-0.69,P<0.001).Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation.For patients with Ishak score≥5,the areas under receiver operating characteristics curve of the CEI,LSM,APRI,and FIB-4 were approximately at baseline,0.87–0.93,and after achieving SVR,0.83–0.91.The CEI cut-off value was stable(baseline 1.58 and SVR 1.59),but those of the APRI(from 1.05 to 0.24),FIB-4(from 1.78 to 1.28),and LSM(from 10.8 kpa to 7.1 kpa)decreased dramatically.The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score≥3(P>0.05).Seven patients achieved fibrosis regression after achieving SVR.In these patients,the CEI median increased(from 1.71 to 1.83,Z=-1.981,P=0.048)and those of the APRI(from 1.71 to 1.83,Z=-2.878,P=0.004)and LSM(from 6.6 to 4.8,Z=-2.366,P=0.018)decreased.However,in patients without fibrosis regression,the medians of the APRI,FIB-4,and LSM also changed significantly(P<0.05).CONCLUSION Gd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC.It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.
文摘In the United States,the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years,but the results have been less than ideal.Historically,patients with chronic hepatitis C (CHC) were treated with interferon-based regimens,which were associated with frequent adverse effects,suboptimal response rates,and long durations of treatment-of up to 48 weeks.Expertise from specialistphysicians,such as hepatologists and gastroenterologists,was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse effects.However,the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety,tolerability,lack of adverse effects,efficacy,and truncated duration of therapy-12 weeks or less-thereby making the need for close monitoring by specialist-physicians obsolete.With the recent approval of DAA agents by the Food and Drug Administration,the treatment model for CHC no longer relies on the limited number of specialist-physicians,which represented a major barrier to treatment access in the past,especially in underserved areas of the United States.We propose and share our experiences in adapting a task-shifting treatment model,one that utilizes a relatively larger pool of non-specialist healthcare providers,such as nursing staff (medical assistants,vocational licensed nurses,registered nurses,etc.) and advanced practice providers (nurse practitioners and physician assistants),to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV infection.Most recently,task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging results.Based on our experiences in implementing this model at our outreach clinics,the majority of HCV-infected patients treated with DAA agents can be easily monitored by non-specialist healthcare providers and physician extenders.Task-shifting can effectively address one of the major rate-limiting factors in expanding treatment access for HCV infection.
文摘Aim:Despite the high cure rate of interferon-free directly acting antivirals(DAAs)for chronic hepatitis C(CHC)patients,the treatment efficacy for patients with preexisting hepatocellular carcinoma(HCC)remains undefined.We aimed in the present study to address the issue by using novel DAAs in treating CHC patients who were adherent to treatment in Taiwan.Methods:CHC patients with or without HCC were consecutively enrolled.The primary objective was sustained virological response(SVR)defined as undetectable HCV RNA throughout 12 weeks of a post-treatment follow-up period(SVR12).Only patients with available SVR12 were enrolled for final analysis.Results:A total of 1237 patients(1113 non-HCC,101 inactive HCC and 23 active HCC)were enrolled.The overall SVR12 rate was 98.9%,and was similar between HCV patients with and without pre-existing HCC(98.4%vs.98.9%,P=0.64).While HCC patients were classified as those who had active or inactive HCC,the SVR12 was also similar between patients with and without active HCC(95.7%vs.99.0%,P=0.34).Among the 101 patients without viable HCC at the time of DAA initiation,eighty-four patients exhibited curative therapy and the other 17 ;patients experienced HCC recurrence before DAAs.Among the 23 patients with viable HCC at the time of DAA treatment,10 patients had received curative therapy for HCC whereas the remaining 13 patients had HCC that was never cured.The SVR12 rates were also similar among the four subpopulations,being 98.8%(83/84),100%(17/17),90%(9/10)and 100%(13/13)respectively.Conclusion:CHC patients with HCC who were adherent to potent DAAs achieved similar SVR12 rate compared to those without HCC and could be effectively treated.
文摘Worldwide,more than one million people die each year from hepatitis C virus(HCV)related diseases,and over 300 million people are chronically infected with hepatitis B or C.Egypt used to be on the top of the countries with heavy HCV burden.Some countries are making advances in elimination of HCV,yet multiple factors preventing progress;remain for the majority.These factors include lack of global funding sources for treatment,late diagnosis,poor data,and inadequate screening.Treatment of HCV in Egypt has become one of the top national priorities since 2007.Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients.Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014.Yet,with the development of highly-effective direct acting antivirals(DAAs)for HCV,elimination of viral hepatitis has become a real possibility.The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs.Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV.This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols.Also,it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.
文摘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.
文摘AIMTo study impact of baseline mental health disease on hepatitis C virus(HCV)treatment;and Beck’s Depression Inventory(BDI)changes with sofosbuvir-and interferon-based therapy.METHODSThis is a retrospective cohort study of participants from 5 studies enrolled from single center trials conducted at the Clinical Research Center of the National Institutes of Health,Bethesda,MD,United States.All participants were adults with chronic HCV genotype 1 infection and naïve to HCV therapy.Two of the studies included HCV mono-infected participants only(SPARE,SYNERGY-A),and 3 included human immunodeficiency virus(HIV)/HCV co-infected participants only(ERADICATE,PFINPK,and ALBIN).Patients were treated for HCV with 3 different regimens:Sofosbuvir and ribavirin in the SPARE trial,ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials,and pegylated interferon(IFN)and ribavirin for 48 wk in the PIFNPK and ALBIN trials.Participants with baseline mental health disease(MHD)were identified(defined as either a DSM IV diagnosis of major depression,bipolar disorder,schizophrenia,generalized anxiety,and post-traumatic stress disorder or requiring anti-depressants,antipsychotics,mood stabilizers or psychotropics prescribed by a psychiatrist).For our first aim,we compared sustained virologic response(SVR)and adherence(pill counts,study visits,and in 25 patients,blood levels of the sofosbuvir metabolite,GS-331007)within each study.For our second aim,only patients with HIV coinfection were evaluated.BDI scores were obtained pre-treatment,during treatment,and post-treatment among participants treated with sofosbuvir-based therapy,and compared to scores from participants treated with interferon-based therapy.Statistical differences for both aims were analyzed by Fisher’s Exact,and t-test with significance defined as a P value less than 0.05.RESULTSBaseline characteristics did not differ significantly between all participants with and without MHD groups treated with sofosbuvir-based therapy.Among patients treated with sofosbuvir-based therapy,the percentage of patients with MHD who achieved SVR was the same as those without(SPARE:60.9%of those MHD compared to 67.6%in those without,P=0.78;SYNERGY-A:100%of both groups;ERADICATE:100%compared to 97.1%).There was no statistically significant difference in pill counts,adherence to study visits between groups,nor mean serum concentrations of GS-331007 for each group at week 2 of treatment(P=0.72).Among patients with HIV co-infection,pre-treatment BDI scores were similar among patients treated with sofosbuvir,and those treated with interferon(sofosbuvir-based 5.24,IFN-based 6.96;P=0.14);however,a dichotomous effect on was observed during treatment.Among participants treated with directly acting antiviral(DAA)-based therapy,mean BDI scores decreased from 5.24(pre-treatment)to 3.28 during treatment(1.96 decrease,P=0.0034)and 2.82 post-treatment.The decrease in mean score from pre-to post-treatment was statistically significant(-2.42,P=0.0012).Among participants treated with IFN-based therapy,mean BDI score increased from 6.96 at pre-treatment to 9.19 during treatment(an increase of 2.46 points,P=0.1),and then decreased back to baseline post-treatment(mean BDI score 6.3,P=0.54).Overall change in mean BDI scores from pre-treatment to during treatment among participants treated with DAA-based and IFN-therapy was statistically significant(-1.96 and+2.23,respectively;P=0.0032).This change remained statistically significant when analysis was restricted to participants who achieved SVR(-2.0 and+4.36,respectively;P=0.0004).CONCLUSIONSofosbuvir-based therapy is safe and well tolerated in patients with MHD.A decline in BDI associated with sofosbuvir-based HCV treatment suggests additional MHD benefits,although the duration of these effects is unknown.
文摘Rationale:Hepatitis C in the pediatric population is a large health burden globally.With its diverse genotypes as well as genotypic subtypes,there is a discrepancy in the genotypes used in research compared to their prevalence.HCV genotype 6 which is endemic to South China and Southeast Asia comprises approximately one-third of all HCV infections worldwide,but make up a minority of cases studied in HCV research.Patient concerns:We report a case of HCV-6 seen in an 11-yearold Burmese immigrant to the U.S.and describe the new direct acting antiviral treatment guidelines for pediatrics with HCV genotype 6.Interventions:The patient completed a 12-week course of ledipasvir/sofosbuvir(90 mg/400 mg),per FDA weight-based recommendations for treatment-naive HCV genotypes 4-6,without any complications.Outcomes:The patient was treated successfully with an undetectable HCV viral load one month after treatment completion.Lessons:HCV-6,although previously uncommon in the U.S.,is becoming more prevalent.Updated guidelines include the use of direct acting antivirals,which have been proven effective for HCV-6.Lessons on barriers to care in the immigrant population as well as the value of HCV genotyping are also discussed.
文摘Chronic infections by hepatitis B virus(HBV)and hepatitis C virus(HCV)major causes of advanced liver disease and mortality worldwide.Although regarded as benign infections in children,their persistence through adulthood is undoubtedly of concern.Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment,which is currently far from being curative.Herein we describe direct-acting antivirals available for pediatric HCV(sofosbuvir/ledipasvir,sofosbuvir/velpatasvir,glecaprevir/pibrentasvir)and their real-world use.A critical review of the HBV pediatric classification is provided.Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population,including capsid assembly modulators,antigen secretion inhibitors,silencing RNAs,and immune modifiers.Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.
文摘AIM To establish if serial Hepascore tests(referred to as delta Hepascore)in those with chronic hepatitis C(CHC)correlate with the increase and/or decrease in risk of liver related complications.METHODS Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied.During 1944 patient years follow-up 28(8.1%)reached an endpoint.The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis andsubsequent clinical outcomes in chronic liver disease.RESULTS Patients with a baseline Hepascore>0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma,liver death,and/or decompensation(P<0.001).In those with an initial Hepascore>0.75,a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint(P=0.004).There were no negative outcomes in those with a stable or improved delta Hepascore.The minimum time between tests that was found to give a statically significant result was in those greater than one year(P=0.03).CONCLUSION In conclusion,Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients.Of note,we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore.Repeat Hepascore tests,when performed at a minimum one-year interval,may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.
