Sustained Virological Response In Patients Research Articles

Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment

BackgroundChronic hepatitis C virus (HCV) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease. Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end-stage renal disease than those who have chronic kidney disease without HCV infection. Patients with both HCV infection and advanced chronic kidney disease have limited treatment options.MethodsWe conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease (with or without cirrhosis) with severe renal impairment, dependence on dialysis, or both. Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon, ribavirin, sofosbuvir, or a combination of these medications. The primary end point was a sustained virologic response 12 weeks after the end of treatment.ResultsAmong the 104 patients enrolled in the trial, 52% had genotype 1 infection, 16% had genotype 2 infection, 11% had genotype 3 infection, 19% had genotype 4 infection, and 2% had genotype 5 or 6 infection. The sustained virologic response rate was 98% (102 of 104 patients; 95% confidence interval, 95 to 100). No patients had virologic failure during treatment, and no patients had a virologic relapse after the end of treatment. Adverse events that were reported in at least 10% of the patients were pruritus, fatigue, and nausea. Serious adverse events were reported in 24% of the patients. Four patients discontinued the trial treatment prematurely because of adverse events; three of these patients had a sustained virologic response.ConclusionsTreatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection. (Funded by AbbVie; ClinicalTrials.gov number, NCT02651194.)

De novo Occurrence and Recurrence of HCC in HCV Infected Patients Treated With DAAʼs: A Single Center 2-Year Experience

Introduction: Multiple studies have shown the efficacy of new direct-acting antivirals (DAA) with cure rate of over 90% in HCV infected patients. Recently published studies have suggested increased incidence of de novo and recurrent HCC(Hepatocellular carcinoma) in cirrhotic patients in SVR(sustained virological response) after completing therapy. A possible mechanism is breakdown of immune surveillance after starting DAA. We report a small case series in a population of chronic HCV infected patients, with and without prior history of HCC, who developed HCC after receiving direct acting antivirals (DAAs) with the aim of adding to existing literature.Table: Table. Clinical Variables Related To HCV and HCCTable. DAA: therapy associated variablesMethods: We retrospectively reviewed 16 patients reported to have HCC out of 290 patients who were treated with DAA at the Oklahoma City VA Medical Center over 2 years (2014-2015). Descriptive analysis including mean and standard deviation for different variables was performed. Results: All 16 patients were male, with the majority (75%) being white. Mean age was 66 years. All patients had cirrhosis as indicated by Fib-4 score > 3.25 and confirmed by imaging. Average Fib-4 score was 7.88. Most were Child Pugh Class A, with average MELD of 11. 6 (37.5%) were treatment naïve. Majority, 9 (56.25%) were genotype 1a. The frequencies of other HCV genotypes 1b, 2 and 3 were 3 (18.75%), 2 (12.5%) and 2 (12.5%) respectively. The median pretreatment HCV viral load was 1,286,176. EVR(Early viral response) was achieved in all patients. ETR(end treatment response) and Sustained Viral Response (SVR) was achieved in 12 (75%) and 10 (62.5%) patients respectively. In patients who achieved SVR, average number of weeks from SVR to HCC detection was 33.3 weeks. All HCC were diagnosed on surveillance ultrasound (USG) imaging (6 monthly) later confirmed via CT-Scan/MRI. 11/16 had denovo occurance of HCC Average time period from DAA therapy to HCC diagnosis was 48.2 weeks. 9/16 patients had more than 1 nodule at diagnosis, and only 7 fulfilled Milan Criteria. Conclusion: Our case series reiterates previously confirmed concern of increased HCC recurrence in patients with history of eradicated HCC. It may be associated with more aggressive occurance (given multiple nodules in >50% patients). It also adds to growing literature which suggest SVR may not be protective against HCC occurrence. It is unclear if treatment with DAA leads to increased HCC occurrence. There is a need of statistically stronger studies on larger cohorts before further conclusions are drawn.

Dendritic cells activation is associated with sustained virological response to telaprevir treatment of HCV-infected patients

First anti-HCV treatments, that include protease inhibitors in conjunction with IFN-α and Ribavirin, increase the sustained virological response (SVR) up to 80% in patients infected with HCV genotype 1. The effects of triple therapies on dendritic cell (DC) compartment have not been investigated. In this study we evaluated the effect of telaprevir-based triple therapy on DC phenotype and function, and their possible association with treatment outcome.HCV+ patients eligible for telaprevir-based therapy were enrolled, and circulating DC frequency, phenotype, and function were evaluated by flow-cytometry. The antiviral activity of plasmacytoid DC was also tested.In SVR patients, myeloid DC frequency transiently decreased, and returned to baseline level when telaprevir was stopped. Moreover, an up-regulation of CD80 and CD86 on mDC was observed in SVR patients as well as an improvement of IFN-α production by plasmacytoid DC, able to inhibit in vitro HCV replication.

Long-term follow-up of patients with chronic hepatitis C treated with α-interferon and ribavirin antiviral therapy: clinical and fibrosis impact of treatment response.

The slow progression of chronic hepatitis C (CHC) infection requires long observation periods to detect clinical changes. We compare the incidence of clinical events, hepatocellular carcinoma (HCC), overall mortality, liver-related mortality, and fibrosis progression between patients with a sustained virological response (SVR) and nonresponders (NR) after a 13-year follow-up period. One hundred and eighty-two CHC patients, who received interferon and ribavirin treatment between 1996 and 2000, were included. Clinical events were evaluated during follow-up. At the end of follow-up, transient elastography was used to assess fibrosis progression. Of the 182 patients, 46.7% (n=85) achieved an SVR. Twenty-seven patients developed hepatic decompensation (one SVR) and 15 developed HCC (three SVR). Twenty-nine patients died (eight SVR). Twelve of the 29 deaths were liver related (two SVR). Independent factors associated with hepatic decompensation were NR to treatment [hazard ratio (HR)=23.35; 95% confidence interval (CI): 2.90-189.25; P=0.003], advanced fibrosis at baseline (HR=9.11; 95% CI: 4.13-20.09), and treatment delay after diagnosis (HR=1.02; 95% CI: 1.00-1.03; P=0.012). Only the latter two were associated with HCC development and liver-related mortality. An assessment of liver fibrosis was performed on 125 patients (66 SVR). Fibrosis values were significantly lower in SVR patients, showing less progression to advanced stages of fibrosis [SVR: 6.6 (2.8); 95% CI: 5.8-7.3] than NR [NR: 14.0 (11.1); 95% CI: 11.1-16.9; P<0.001]. In patients with CHC, SVR is durable and reduces clinical events. The risk of HCC development is lower, but not eliminated. Sustained responders showed fibrosis stabilization or improved fibrosis values.

Impact of antiviral therapy on hepatocellular carcinoma and mortality in patients with chronic hepatitis C: systematic review and meta-analysis

BackgroundThe long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and mortality according to the response to antiviral therapy. This study aimed to assess the impact of antiviral treatment on the development of HCC and mortality in patients with chronic HCV infection.MethodsA systematic review was conducted for studies that evaluated the antiviral efficacy for patients with chronic hepatitis C or assessed the development of HCC or mortality between SVR (sustained virologic response) and non-SVR patients. The methodological quality of the enrolled publications was evaluated using Risk of Bias table or Newcastle-Ottawa scale. Random-effect model meta-analyses and meta-regression were performed. Publication bias was assessed.ResultsIn total, 59 studies (4 RCTs, 15 prospective and 40 retrospective cohort studies) were included. Antiviral treatment was associated with reduced development of HCC (vs. no treatment; OR 0.392, 95% CI 0.275–0.557), and this effect was intensified when SVR was achieved (vs. no SVR, OR: 0.203, 95% CI 0.164–0.251). Antiviral treatment was associated with lower all-cause mortality (vs. no treatment; OR 0.380, 95% CI 0.295–0.489) and liver-specific mortality (OR 0.363, 95% CI 0.260–0.508). This rate was also intensified when SVR was achieved [all-cause mortality (vs. no SVR, OR 0.255, 95% CI 0.199–0.326), liver-specific mortality (OR 0.126, 95% CI 0.094–0.169)]. Sensitivity analyses revealed robust results, and a small study effect was minimal.ConclusionsIn patients with chronic hepatitis C, antiviral therapy can reduce the development of HCC and mortality, especially when SVR is achieved.

Time-Degenerative Factors and the Risk of Hepatocellular Carcinoma after Antiviral Therapy among Hepatitis C Virus Patients: A Model for Prioritization of Treatment.

Purpose: Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma over time. We aimed to explore their impact at the initiation of antiviral therapy on hepatocellular carcinoma among chronic hepatitis C (CHC) patients.Experimental Design: A total of 1,281 biopsy-proven CHC patients receiving IFN-based therapy were followed for a mean period of 5.5 years.Results: The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-sustained virological response (SVR) and SVR patients who were <40 years old (7.7% vs. 0.5%, P = 0.1) but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P < 0.001) and >55 years old (15.1% vs. 7.9%, P = 0.03). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients 40 to 55 years old [HR/95% confidence intervals (CI), 10.92/3.78-31.56; P < 0.001] and >55 years old (HR/CI, 1.96/1.06-3.63; P = 0.03) but not in patients <40 years old (HR/CI, 2.76/0.41-18.84; P = 0.3). The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-SVR and SVR patients whose fibrosis stage was F0-1 (4.6% vs. 1.9%, P = 0.25) but was higher in non-SVR patients with F2-3 (21.4% vs. 4.3%, P < 0.001) or F4 (33.5% vs. 8.4%, P = 0.002). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients with F2-3 (HR/CI, 4.36/2.10-9.03; P < 0.001) and F4 (HR/CI, 3.84/1.59-9.30; P = 0.03) but not in those with F0-1 (HR/CI, 1.53/0.49-4.74; P = 0.47).Conclusions: Delayed hepatitis C virus clearance for patients with CHC >40 years old or with a fibrosis stage >2 increases the risk of hepatocellular carcinoma over time. Clin Cancer Res; 23(7); 1690-7. ©2016 AACR.

Sa1525 - Lower Sustained Virologic Response in Patients with Hepatocellular Carcinoma Treated for Hepatitis C with Direct Acting Antivirals

Sa1525 - Lower Sustained Virologic Response in Patients with Hepatocellular Carcinoma Treated for Hepatitis C with Direct Acting Antivirals

Characterization of fibrosis changes in chronic hepatitis C patients after virological cure: A systematic review with meta-analysis.

Virological cure becomes available for most patients with chronic hepatitis C (CHC), but residual fibrosis can be an independent risk factor for liver-related complications. We aimed to characterize fibrosis change in CHC patients achieved virological cure. We did a systematic literature search for studies that had pre and post-treatment evaluations of histologic fibrosis in CHC patients with sustained virological response (SVR). We identified the association of SVR with the incidence, extent, and velocity of fibrosis change. Overall, 3243 patients were included. Interferon-based regimens were used for all the patients, achieving a median SVR prevalence of 36.2%. Biopsy interval ranged from 1 to 10 years. Mean baseline fibrosis score (METAVIR) was 2.3 points. Compared with non-SVR patients, SVR patients could have higher incidence of fibrosis regression (35.1% vs 17.0%; OR: 3.3; P < 0.001), regardless of baseline fibrosis severity, way of biopsy evaluation, treatment regimen, or study design, and could have more extent of reduction (-0.31 points vs -0.00 points; P = 0.004). Baseline advanced fibrosis (F > 2) was associated with more rapid regression in both SVR and non-SVR patients (P < 0.05 for both). SVR patients could have lower incidence of fibrosis progression and maintenance than non-SVR patients by 4.8% versus 23.1% (OR: 0.20; P = 0.008) and 42.9% versus 55.2% (OR: 0.53; P < 0.001), respectively. There could be a favorable characteristic of fibrosis regression in SVR patients. However, residential fibrosis may remain an issue because of a non-ignorable prevalence of fibrosis maintenance among these patients.

Assessment of baseline pretreatment factors and on‐treatment virological response to predict sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin

SummaryBackgroundsPegalated interferon (PEG‐IFN) combination with ribavirin (RBV) (PR) in accordance to response‐guide therapy (RGT) is a treatment option for chronic hepatitis C (CHC) in the past decade. Baseline host and viral factors and early viral kinetics are important determinants for patient using combination therapy.AimsWe aimed to investigate the effects of host and viral factors on sustained virus response (SVR). We researched the possible predictors of an SVR.MethodsWe retrospectively analyzed a total of 158 CHC patients who had been treated with a PR dual therapy. Clinical parameters and virological responses were analyzed for their relationship with SVR.ResultsThe overall SVR rate was 71.5% (113/158). Factors associated with an SVR were ALT levels &gt; 3xULN, non‐AST/ALT &gt; 1, non‐genotype 1 and non‐cirrhosis. Non‐genotype 1 (OR: 3.154; 95% CI: 1.309‐7.601; P = 0.010), and non‐cirrhosis (OR: 2.696; 95% CI: 1.045‐6.956; P = 0.004) were the predictors of an SVR. An SVR significantly increased in patients with an RVR and significantly reduced in patients with cEVR, pEVR, null response and relapse. In addition, an RVR was a powerful independent predictor of an SVR (OR: 38.263; 95% CI: 10.184‐143.757; P = 0.000). The positive predictive value (PPV) of an RVR on SVR was 92.2% (94/102).ConclusionsNon‐cirrhosis, non‐genotype 1 and achievement of an RVR are independent predictors of SVR. A 4 week RVR is the best predictor of an SVR in CHC patients with a PR dual treatment. An RVR predicts treatment success early.Copyright © 2016, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.

P.09.14: Magnitude of Liver Stiffness Regression after Achieving Sustained Virologic Response in Patients with Chronic Hepatitis C: A Meta-Analysis

P.09.14: Magnitude of Liver Stiffness Regression after Achieving Sustained Virologic Response in Patients with Chronic Hepatitis C: A Meta-Analysis

Differences in IP‑10, TLR4 and IRF5/3 between SVR and non‑SVR HCV‑1 patients treated with PEG‑IFN and ribavirin.

The present study aimed to investigate alterations in Toll‑like receptor4 (TLR4), interferon regulatory factor5 (IRF5) and interferon‑γ‑inducible protein‑10 (IP‑10), and evaluate whether these factors may be associated with a sustained virological response (SVR) among patients with hepatitisC virus genotype‑1 (HCV‑1) who were treated with peginterferon plus ribavirin (PEG‑IFN‑RBV). A total of 31 Chinese patients infected with HCV‑1 were enrolled in the present study and 25patients obtained SVR. The expression levels of IP‑10 declined significantly during PEG‑IFN‑RBV therapy at the 24 and 48week time‑points, compared with the baseline (P<0.005, 0.001 and 0.001, respectively). In addition, it was observed that IRF5 mRNA expression and the number of TLR4+ peripheral blood mononuclear cells exhibited similar correlations with IP‑10 concentration (R2=0.0726, P=0.001, R2=0.1634, P<0.0001, respectively) in the SVR group patients; however, these correlations were not observed to be present in the non‑SVR group patients. In conclusion, the results of the present study suggest that marked alterations in IP‑10, TLR4 and IRF5 expression may serve as indicators for the development of SVR in patients with HCV‑1 treated with PEG‑IFN‑RBV.

Risk Factors for Hepatitis C Virus Reinfection After Sustained Virologic Response in Patients Coinfected With HIV.

Highly effective hepatitis C virus (HCV) therapies have spurred a scale-up of treatment to populations at greater risk of reinfection after sustained virologic response (SVR). Reinfection may be higher in HIV-HCV coinfection, but prior studies have considered small selected populations. We assessed risk factors for reinfection after SVR in a representative cohort of Canadian coinfected patients in clinical care. All patients achieving SVR after HCV treatment were followed with HCV RNA measurements every 6 months in a prospective cohort study. We used Bayesian Cox regression to estimate reinfection rates according to patient reported injection drug use (IDU) and sexual activity among men who have sex with men (MSM). Of 497 patients treated for HCV, 257 achieved SVR and had at least 1 subsequent RNA measurement. During 589 person-years of follow-up (PYFU) after SVR, 18 (7%) became HCV RNA positive. The adjusted reinfection rate (per 1000 PYFU) in the first year after SVR was highest in those who reported high-frequency IDU (58; 95% credible interval [CrI], 18-134) followed by MSM reporting high-risk sexual activity (26; 95% CrI, 6-66) and low-frequency IDU (22; 95% CrI, 4-68). The rate in low-risk MSM (16; 95% CrI, 4-38) was similar to that in reference patients (10; 95% CrI, 4-20). Reinfection rates did not diminish with time. HCV reinfection rates varied according to risk. Measures are needed to reduce risk behaviors and increase monitoring in high-risk IDU and MSM if HCV elimination targets are to be realized.

Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.

Background/AimsBoth spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groupsMethodsA total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis.ResultsNineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15).ConclusionsCompared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.

The effectiveness of daclatasvir based therapy in European patients with chronic hepatitis C and advanced liver disease

BackgroundThere is limited evidence for the effectiveness of daclatasvir in patients whose hepatitis C threatens their life expectancy. The Named Patient Program in Europe included patients with advanced chronic hepatitis C, a life expectancy of less than 12 months and no other treatment options.MethodsA retrospective multi-country cohort of patients with chronic hepatitis C who received daclatasvir as part of the Named Patient Program in Austria, Denmark, Spain, Sweden, Switzerland and the United Kingdom. Treatment response was defined as a sustained virologic response (unquantifiable hepatitis C RNA) at 12 weeks post treatment. We summarised the characteristics of the patients in this cohort and estimated the rate of sustained virologic response for patients receiving daclatasvir and sofosbuvir with or without ribavirin using hierarchical Bayesian modelling.ResultsThe 249 patients included had a median age of 56 years; most were male (78%), hepatitis C genotype 1 (75%), treatment experienced (65%) and with decompensated cirrhosis (59%). Many had had a liver transplant before receiving daclatasvir (40%). Of the 249 patients, 242 patients received daclatasvir and sofosbuvir and either reached 12 weeks post treatment or died during (n = 9) or after treatment (n = 4) or were lost to follow up during treatment (n = 1). The estimated rate of sustained virologic response at 12 weeks post treatment was 87% (95% credible interval 75 to 94%) for previously treated genotype 1 patients with decompensated cirrhosis.ConclusionsDaclatasvir with sofosbuvir is an effective treatment in clinical practice for hepatitis C genotype 1 patients with decompensated cirrhosis.

FRI-264 - Lower sustained virologic response in patients with hepatocellular carcinoma treated for hepatitis C with direct acting antivirals

FRI-264 - Lower sustained virologic response in patients with hepatocellular carcinoma treated for hepatitis C with direct acting antivirals

FRI-190 - Long-term fibrosis improvement after sustained virologic response in patients with chronic hepatitis C and advanced fibrosis or cirrhosis – pre-treatment cirrhosis, older age and high body mass index increases the risk for persisting fibrosis

FRI-190 - Long-term fibrosis improvement after sustained virologic response in patients with chronic hepatitis C and advanced fibrosis or cirrhosis – pre-treatment cirrhosis, older age and high body mass index increases the risk for persisting fibrosis

Ongoing Alcohol Consumptions Counteracts the Benefits of Sustained Virological Response in Patients with Well Compensated Hepatitis C Cirrhosis: an Observational Study

Ongoing Alcohol Consumptions Counteracts the Benefits of Sustained Virological Response in Patients with Well Compensated Hepatitis C Cirrhosis: an Observational Study

The Current Status of Renal Transplant Recipients with Hepatitis C: A Single Center Experience

Renal transplantation (RTx) may result in the development of liver disorder/hepatic cancer or hepatitis C virus (HCV)- related membranoproliferative glomerulonephritis, which may lead to graft loss, in renal failure patients with previously untreated HCV infection. Long-term survival is longer in HCV antibody-positive renal transplant recipients than in HCV antibody-negative/-positive dialysis patients, whereas renal graft survival and patient survival are lower in HCV antibody-positive renal transplant recipients than in HCV antibody-negative patients; thus, HCV treatment should be administered to HCV antibodypositive renal transplant recipients. Interferon/ribavirin (IFN/Rib) therapy is one of the current HCV treatments in Japan. In renal failure patients including those undergoing hemodialysis, Rib is contraindicated because of possible kidney function problems; IFN monotherapy is indicated for these patients. However, in clinical practice, IFN monotherapy is not performed adequately because of efficacy problems or adverse reactions to IFN, leading to the presence of many HCV carriers and patients with previous HCV infection among hemodialysis patients in the RTx waiting list. The sustained virological response in patients receiving IFN therapy after RTx is low. Many patients discontinue the therapy and some develop graft loss because of IFN-related acute rejection. Therefore, dialysis patients with HCV infection who are scheduled for RTx should first receive IFN therapy. In Japan, daclatasvir/ asunaprevir combination therapy was introduced as an IFN-free antiviral therapy in September 2015. However, its safety in dialysis patients has not been established, and these patients still require IFN therapy. We report the current state of renal transplant recipients with HCV at our hospital.

Shear wave elastography in hepatitis C patients before and after antiviral therapy.

AIMTo investigate shear wave (SW) propagation velocity in patients with untreated hepatitis C and patients with sustained virological response (SVR).METHODSA total of 136 hepatitis C patients [85 patients who had not received antiviral therapy (naïve group) and 51 patients who had received antiviral therapy and subsequently achieved SVR of at least 24 wk (SVR group)] and 58 healthy volunteers and outpatients without liver disease (control group) underwent evaluation of liver stiffness by SW elastography (SWE). Various parameters were evaluated in the chronic hepatitis C patients at the time of SWE.RESULTSSW propagation velocity (Vs) was 1.23 ± 0.14 m/s in the control group, 1.56 ± 0.32 m/s in the SVR group, and 1.69 ± 0.31 m/s in the naïve group. Significant differences were seen between the control group and the SVR group (P = 0.0000) and between the SVR group and the naïve group (P = 0.01417). All four fibrosis markers were higher in the naïve group than in the SVR group. In the naïve group, Vs was positively correlated with alanine aminotransferase (ALT) (r = 0.5372), α feto protein (AFP) (r = 0.4389), type IV collagen (r = 0.5883), procollagen III peptide (P-III-P) (r = 0.4140), hyaluronic acid (r = 0.4551), and Mac-2 binding protein glycosylation isomer (M2BPGi) (r = 0.6092) and negatively correlated with albumin (r = -0.4289), platelets (r = -0.5372), and prothrombin activity (r = -0.5235). On multiple regression analysis, Vs was the most strongly correlated with ALT (standard partial regression std β = 0.4039, P = 0.00000). In the SVR group, Vs was positively correlated with AFP (r = 0.6977), type IV collagen (r = 0.5228), P-III-P (r = 0.5812), hyaluronic acid (r = 0.5189), and M2BPGi (r = 0.6251) and negatively correlated with albumin (r = -0.4283), platelets (r = -0.4842), and prothrombin activity (r = -0.4771). On multiple regression analysis, Vs was strongly correlated with AFP (standard partial regression std β = 0.5953, P = 0.00000) and M2BPGi (standard partial regression std β= 0.2969, P = 0.03363).CONCLUSIONIn hepatitis C patients, liver stiffness is higher in treatment-naïve patients than in those showing SVR. SWE may be a predictor of hepatocarcinogenesis in SVR patients.

Increase of Soluble Programmed Cell Death Ligand 1 in Patients with Chronic Hepatitis C.

Objectives: To determine whether the soluble programmed cell death ligand 1 (sPD-L1) levels in patients with chronic hepatitis C (CHC) are associated with the clinical features of the disease and the efficacy of treatment, including interferon (IFN)-α.Methods: We investigated the sPD-L1 levels in the sera of 80 genotype 1b Japanese patients with CHC who underwent 12 weeks of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy followed by 12 weeks of dual therapy with pegylated IFN-α plus ribavirin. Serum was also obtained from 22 patients with chronic hepatitis B (CHB) and from 10 healthy donors (HC). The sPD-L1 levels were measured using an ELISA kit. In addition, we examined the PD-L1 expression on the cell surface of immortalized hepatocytes (HPT1) after incubation with cytokines, including IFN-γ.Results: The pretreatment serum sPD-L1 levels were significantly increased in patients with CHC (median 109.3 pg/ml, range 23.1-402.3) compared with patients with CHB (69.2 pg/ml, 15.5-144.8; P <0.001) and HC (100.3 pg/ml, 40.1-166.6; P = 0.039). No significant differences in the sustained virological response (SVR) rates were found between the TVR- (85.0%, n=40) and SMV-treated (80.0%, n=40) groups, and the pretreatment levels of serum sPD-L1 were not significantly different between patients who achieved SVR (105.0 pg/ml, 23.1-402.3) and non-SVR patients (133.5 pg/ml, 39.9-187.2; P = 0.391). The pretreatment level of sPD-L1 was positively correlated with the alanine aminotransferase and alpha-fetoprotein levels (R2 = 0.082, P = 0.016, and R2 = 0.149, P = 0.002, respectively). Although immortalized hepatocytes do not express PD-L1, we confirmed that PD-L1 expression was induced after stimulation with IFN-γ.Conclusions: In this study, we first found that sPD-L1 was increased in patients with CHC. Our results indicate that the level of serum sPD-L1 might be associated with the progression of CHC and the generation of hepatocellular carcinoma.