Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C

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.

Effectiveness and safety of generic and brand direct acting antivirals for treatment of chronic hepatitis 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.

Chronic Viral Hepatitis C: Before and after Direct Acting Antivirals (DAA) in Morocco

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.

Direct acting antivirals therapy and hepatocellular carcinoma risk in patients with hepatitis C virus

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.

Hepatitis C virus eradication with directly acting antivirals improves health-related quality of life and psychological symptoms

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.

Effect of treating chronic hepatitis C with direct-acting antivirals on extrahepatic cutaneous manifestations

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.

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

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.

Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acidenhanced magnetic resonance imaging for evaluating fibrosis regression in chronic hepatitis C patients after direct-acting antiviral

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.

Hepatitis C virus eradication in people living with human immunodeficiency virus:Where are we now?

Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation(LT)provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma.Despite the increasing number of liver transplants performed each year,the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality.Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates.Nevertheless,further strategies can be implemented to increase the pool of potential donors in deceased donor LT,such as reducing the rate of organ discards.Utilizing hepatitis C virus(HCV)seropositive liver grafts is one of the expanded donor organ criteria.A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients.Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation.The American Society of Transplantation advises against performing transplants from HCV-infected liver donors(D+)into HCV-negative recipient(R-)unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants.Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is im-portant.National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Expanding Treatment Access for Chronic Hepatitis C with Task-shifting in the Era of Direct-acting Antivirals

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.

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

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

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

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

Treatment efficacy for patients with chronic hepatitis C and preexisting hepatocellular carcinoma by directly acting antivirals

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.

Pediatric perspectives on treating uncommon genotypes of hepatitis C in the United States

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.

Breakthroughs and challenges in the management of pediatric viral hepatitis

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.

Improved Hepascore in hepatitis C predicts reversal in risk of adverse outcome

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.

Efficacy and safety of sofosbuvir and ledipasvir in Japanese patients aged 75 years or over with hepatitis C genotype 1

AIM To evaluate the efficacy and safety of a regimen containing sofosbuvir(SOF) and ledipasvir(LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1.METHODS This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects(AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger(aged < 75 years) and elderly(aged ≥ 75 years). Virological data and AEs were analyzed by age group.RESULTS The sustained virological response(SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.

Hepatitis C Virus Clearance by Direct-acting Antiviral Results in Rapid Resolution of Hepatocytic Injury as Indicated by Both Alanine Aminotransferase and Aspartate Aminotransferase Normalization

Background and Aims:Hepatitis C virus(HCV)infection results in hepatocytic injury with elevation of both alanine aminotransferase(ALT)and aspartate aminotransferase(AST).It remains to be determined if direct-acting antiviral treatment can terminate hepatocytic injury following viro-logic response.To this end,we evaluated the pattern and predicting factors of ALT and AST normalization during and after direct-acting antiviral treatment with sustained virologic response at 12 weeks(SVR12).Methods:Single-center ret-rospective study on 115 HCV-infected patients who achieved SVR12 was performed.Results:At treatment week 2,100%and 45.9%showed decline in HCV RNA to<700 IU/mL and undetectable levels,respectively,and this was associated with 85.5%,83.9%and 77.4%ALT normalization,AST nor-malization and ALT and AST normalization.At end of treat-ment,85.6%of patients with baseline elevation of both ALT and AST had normalization of both ALT and AST.At posttreat-ment weeks 12 and 24,90.8%and 94.8%had normalization of both ALT and AST.HCV clearance also resulted in further decline of both ALT and AST in those with baseline<40 IU.Univariate analysis showed baseline Child-Pugh score of<6,model for end-stage liver disease score of<10,HCV geno-type 1,and HCV RNA of<500 IU/mL at treatment week 2 were associated with sustained normalization of both ALTand AST at posttreatment week 12.On multivariate analysis,baseline model for end-stage liver disease score of<10 was significantly associated with normalization of both ALT and AST at posttreatment week 12,independent of baseline Child-Pugh score<6,HCV genotype 1,and HCV RNA of<500 IU/mL at treatment week 2.Conclusions:During direct-acting antiviral therapy,85.5%and 83.9%had nor-malization of both ALTand ASTas early as in week 2,providing;biochemical evidence of hepatocytic injury resolution.Sustained normalization of both ALT and AST was seen in 90.8%at posttreatment weeks 12,and was independently associated with baseline model for end-stage liver disease score of<10.

Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease

The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.