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.

Hepatitis C infected patients need vitamin D3 supplementation in the era of direct acting antivirals treatment

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.

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.

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

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

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.

Direct acting antiviral-induced dynamic reduction of serum a fetoprotein in hepatitis C patients without hepatocellular carcinoma

Direct acting antiviral(DAA)treatments may reduce the elevatedαfetoprotein(AFP),but data on how these treatments affect elevated AFP in patients with chronic hepatitis C(CHC)remain insufficient.In the present study,the frequency of baseline AFP elevations and their related factors,AFP dynamics during and after DAA treatment,and factors associated with AFP reduction was assessed.This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response.The details are as follows:mean post-treatment follow-up was 99 weeks(12–213);mean age,57.8 years old;52%,males;79%,genotype(GT)1;and 47%,cirrhosis.Pre-treatment AFP elevation(>5.5 ng/mL)was seen in 48.2%patients.On multivariate analysis,baseline AFP>5.5 was associated with the presence of cirrhosis(P=0.001),co-existing non-alcoholic steatohepatitis(NASH)(P=0.035),and GT 1(P=0.029).AFP normalization was seen in 28.2%patients at treatment week 2,in 52%at the end of treatment,and in 73.4%at the end of follow-up.Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis(P=0.003),Child--Pugh score<6(P=0.015),and baseline AFP<10(P=0.015).AFP elevation is common in patients with CHC and independently associated with NASH,cirrhosis,and GT 1.DAA treatment resulted in AFP normalization as early as treatment week 2.Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis,Child--Pugh score<6,and baseline AFP<10.

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.

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

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

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.

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.

Hepatitis C virus-associated B cell non-Hodgkin's lymphoma

The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin&#x02019;s lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin&#x02019;s lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they seem to be safe and highly effective. The use of chemotherapy in combination with rituximab for the treatment of BCNHL in patients infected with HCV can produce liver dysfunction. The addition of immunotherapy with rituximab can increase the viral replication, and severe complications can occure especially in patients co-infected with hepatitis B virus or immune immunodeficiency virus, in those with hepatocarcinoma, cirrhosis, or liver cytolysis. But the final result of standard immunochemotherapy applied to diffuse large BCNHL patients with HCV infection is not notably worse than in those without this viral infection. The treatment of patients chronically infected with HCV and having BCNHL is complex and requires a multidisciplinary approach and the risk / benefit ratio of rituximab treatment must be evaluated especially in those with liver cytolysis.

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.

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.

Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvirbased regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response(SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current managementof CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.

Retrospective study of the associations between hepatitis C virus infection and metabolic factors

AIMTo evaluate the bidirectional association between metabolic syndrome (MS) components and antiviral treatment response for chronic hepatitis C virus (HCV) infection. METHODSThis retrospective cohort study included 119 HCV + patients treated with pegylated-interferon-α and ribavirin. Metabolic characteristics and laboratory data were collected from medical records. Differences in baseline clinical and demographic risk factors between responders and non-responders were assessed using independent samples t-tests or χ2 tests. The effects of sustained viral response (SVR) to antiviral treatment on de novo impairments in MS components, including impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), were assessed using univariable and multivariable logistic regression analysis, while the effect of MS components on SVR was assessed using univariable logistic regression analysis. RESULTSOf the 119 patients, 80 (67%) developed SVR over the average 54 ± 13 mo follow-up. The cumulative risks for de novo T2DM and IFG were 5.07- (95%CI: 1.261-20.4, P = 0.022) and 3.87-fold higher (95%CI: 1.484-10.15, P = 0.006), respectively for non-responders than responders, when adjusted for the baseline risk factors age, sex, HCV genotype, high viral load, and steatosis. Post-treatment triglyceride levels were significantly lower in non-responders than in responders (OR = 0.27; 95%CI: 0.069-0.962, P = 0.044). Age and HCV genotype 3 were significantly different between responders and non-responders, and MS components were not significantly associated with SVR. Steatosis tended to attenuate SVR (OR = 0.596; 95%CI: 0.331-1.073, P = 0.08). CONCLUSIONSVR was associated with lower de novo T2DM and IFG incidence and higher triglyceride levels. Patients infected with HCV should undergo T2DM screening and antidiabetic treatment.

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.