Sustained Virological Response Status Research Articles

DAA treatment for HCV reduce risk of hepatocellular carcinoma: a 10-years follow-up study based on Chinese patients with hepatitis C

The long-term benefits of direct-acting antiviral (DAA) therapy after achieving sustained virological response (SVR) remain uncertain in the Chinese population. This study evaluates the incidence of hepatocellular carcinoma (HCC), hepatic decompensation, and all-cause mortality among Chinese hepatitis C patients treated with DAAs. We included patients diagnosed since 2011 and followed them until November 1, 2022. The primary outcomes were HCC, hepatic decompensation, and mortality. Multivariable proportional hazards model was used to assess the impact of SVR and cirrhosis status. The cohort consisted of 1272 patients with SVR (92.1%) and 109 without SVR (7.9%), with a median follow-up of 61 months. The incidence of HCC was significantly lower in the SVR group (5.1 per 1000 person-years) compared to the no-SVR group (15.0 per 1000 person-years). Achieving SVR was associated with a significantly reduced risk of HCC (adjusted hazard ratio: 0.32; 95% CI 0.16–0.67). Cirrhosis was linked to an increased risk of developing HCC and hepatic decompensation. These findings highlight the importance of early DAA treatment, particularly for patients with cirrhosis.

Sustained virological response after treatment with direct antiviral agents in individuals with HIV and hepatitis C co-infection.

Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing. We included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment. A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered. Our estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.

Real-world Effectiveness of sofosbuvir/velpatasvir for the Treatment of Hepatitis C Virus in Prison Settings

Background: People in prison are at high risk of hepatitis C virus (HCV) infection and often have a history of injection drug use and mental health disorders. Simple test-and-treat regimens which require minimal monitoring are critical. Methods: This integrated real-world analysis evaluated the effectiveness of once daily sofosbuvir/velpatasvir (SOF/VEL) in 20 prison cohorts across Europe and Canada. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with a valid SVR status. Secondary outcomes were reasons for not achieving SVR, adherence and time between HCV RNA diagnosis and SOF/VEL treatment. Results: Overall, 526 people in prison were included with 98.9% SVR achieved in the EP (n = 442). Cure rates were not compromised by drug use or existence of mental health disorders. Conclusion: SOF/VEL for 12 weeks is highly successful in prison settings and enables the implementation of a simple treatment algorithm in line with guideline recommendations and test-and-treat strategies.

Real-World Evidence of Sofosbuvir/Velpatasvir as an Effective and Simple Hepatitis C Virus Treatment and Elimination Tool in Homeless Populations

Background: People experiencing homelessness are disproportionately affected by hepatitis C virus (HCV) and can face specific barriers to care. Simple treatment algorithms could increase linkage to care in this population. Methods: This retrospective real-world analysis pooling data from 15 clinical cohorts evaluated effectiveness of a once-daily sofosbuvir/velpatasvir (SOF/VEL) regimen in HCV-infected people experiencing homelessness. The primary outcome was sustained virological response (SVR) in the effectiveness population (patients with confirmed SVR status). Secondary outcomes included reasons for not achieving SVR, adherence and time between diagnosis and SOF/VEL treatment start. Results: Of 153 patients treated with SOF/VEL for 12 weeks without ribavirin, SVR was 100% in the effectiveness population (n = 122), irrespective of various baseline factors including active injecting drug use and presence of mental health disorders. Conclusion: HCV-infected people experiencing homelessness can successfully be treated with SOF/VEL. SOF/VEL enables implementation of simple treatment algorithms and can support test-and-treat strategies through rapid treatment starts and minimal monitoring.

The spectrum of histopathological findings after SVR to DAA for recurrent HCV infection in liver transplant recipients.

Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p < 0.001) and in the IFN group (n = 21; p = 0.001) but not in the DAA group (p = 0.093). Of all subjects, 21% had worsening stage, 31% had improvement, and 48% had no change in stage. Of the treatment groups, 27% in the IFN and 17% in the DAA groups had worsening stage; however, the results were not statistically significant in all subjects or by treatment modality. Persistent inflammatory infiltrates and fibrosis was noted in allograft tissue of patients cured with DAA. Significant improvement in grade was noted in the IFN group, without a significant change in stage.

Impact of Interferon on the Prognosis of Hepatitis C Virus-Related Hepatocellular Carcinoma Patients with a Sustained Virological Response -An Additional Comparison Between Preoperative and Postoperative Sustained Virological Response.

Several studies have reported that interferon (IFN) therapy improves the prognosis of patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), especially for patients who have achieved a sustained virological response (SVR). We retrospectively evaluated the clinicopathological outcomes of patients who acquired an SVR through IFN therapy pre- or post-hepatectomy for treatment naïve HCC. Among the 305 HCV-related HCC patients entered in this study, 59 patients (SVR group) achieved an SVR after IFN therapy and received hepatectomy either after or before achieving an SVR (n=36 and n=23, respectively), while the remaining 179 patients (control group) did not receive IFN therapy, or did not achieve an SVR through IFN therapy (n=67). In the SVR group, the overall survival (OS) and disease-free survival (DFS) rates were significantly higher than in the control group. We evaluated the prognosis of patients with an SVR achieved pre- or post-hepatectomy separately. There were no significant differences in OS and DFS. This result suggests that the prognosis of naïve HCC may be improved by additional INF therapy to achieve SVR status after hepatectomy.

Impact of direct-acting antiviral agents on liver function in patients with chronic hepatitis C virus infection.

Whilst the benefit of direct-acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well-accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon-based therapy. Liver function was assessed by the albumin-bilirubin (ALBI) score or grade. Overall survival according to SVR status and baseline ALBI grade was examined. We also studied time to first decompensation according to ALBI grade, as well as longitudinal changes in ALBI score over time according to SVR. Among the patients receiving DAAs, 89% achieved SVR (Japan=99%, UK=78%). Amongst the decompensated patients in the UK cohort, three distinct risk groups according to ALBI grade at baseline were observed. The UK patients receiving DAAs, who had predominantly decompensated disease, showed clear evidence of improvement of liver function detectable within 2years of the start of treatment, especially in those achieving SVR. These early changes in liver function were very similar to those observed in the first 2-3years after interferon-based therapy. DAAs improve liver function especially in those with decompensated disease who achieve SVR. Experience with interferon-based therapy suggests that failure to achieve SVR is associated with long-term decline in liver function and, in contrast, patients who do achieve SVR can expect long-term disease improvement and subsequent stabilization of liver function. Our initial analysis suggests that those receiving DAAs are likely, in the long term, to follow a similar course.

Fibroscan liver stiffness after anti-viral treatment for hepatitis C is independently associated with adverse outcomes.

Fibroscan-derived liver stiffness decreases after anti-viral treatment for hepatitis C virus (HCV) infection, which may affect the associations and interpretation of liver stiffness. To assess whether liver stiffness pre- or post-anti-viral therapy is associated with the development of decompensated cirrhosis, hepatocellular carcinoma (HCC) or death. In this retrospective cohort study, we identified US veterans who initiated HCV treatment and had at least one liver stiffness before (n=492) or after (n=877) HCV therapy. We used Cox proportional hazards regression (adjusting for age, race/ethnicity, history of cirrhosis, body mass index, diabetes, FIB-4 score, Charlson comorbidity index, alcohol use disorder, Model for end-stage liver disease score and sustained virological response status) to determine the associations between pre- or post-treatment liver stiffness values and the development of decompensated cirrhosis, HCC, death or liver transplant. In the post-treatment liver stiffness cohort, during a mean follow-up of 27.3months, 21 (2.4%) developed decompensated cirrhosis, 26 (3.0%) developed HCC and 57 (6.5%) died or underwent liver transplant. Compared to patients with post-treatment liver stiffness ≤12.5kPa, those with post-treatment liver stiffness >20kPa, had higher rates of developing decompensated cirrhosis (adjusted HR 3.85, 95% CI 1.29-11.50) and the composite outcome of death, liver transplant, decompensated cirrhosis or HCC (adjusted HR 1.95, 95% CI: 1.07-3.56). There were no significant associations between pre-treatment liver stiffness and any outcomes on multivariable analysis. Post-treatment liver stiffness >20kPa, but not pre-treatment liver stiffness, was independently associated with the development of decompensated cirrhosis and the composite outcome in multivariable analyses. Measuring liver stiffness should be considered after anti-viral treatment because it predicts adverse outcomes even beyond routinely available clinical predictors.

Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs.

It is crucial to identify risk factors for life prognosis after hepatitis C virus (HCV) eradication among patients with or without a high risk of liver cancer or complications. This is a prospective, multicenter and observational study using the database of 1031 patients after HCV eradication by direct-acting antiviral agents (DAAs) to evaluate the development of hepatocellular carcinoma (HCC) and patients' survival after a sustained virological response (SVR). The Cox proportional hazards regression model was used to estimate hazard ratios associated with HCC development and survival. AFP at SVR was significantly associated with HCC recurrence in the adjusted model. Liver fibrosis, Mac-2 binding protein glycosylation isomer (M2BPGi) at SVR and smoking status before treatment were positively associated with the development of HCC and M2BPGi was positively associated with HCC recurrence, although not reaching statistical significance. Among patients without a history of HCC, M2BPGi and estimated glomerular filtration rate (eGFR) at SVR were significantly associated with death after viral eradication [M2BPGi (HR 4.07, 95% CI 1.22, 13.57), eGFR (HR 0.97, 95% CI 0.94, 0.99)]. Strikingly, of 16 patients who died, among participants without a history of HCC, only two died of liver cancer associated with HCV, whereas 11 died of non-HCV- related cancer or cardiovascular diseases. M2BPGi at SVR is a potential predictor for patients' survival and a candidate biomarker for detecting individuals who are at greater risk of death due to cancer-related and unrelated to HCV, as well as cardiovascular diseases, after viral eradication.

Outcomes of Treatment and Predictors of Response to Sofosbuvir Plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection.

Treatment plan of chronic HCV infection has dramatically improved after the introduction of different groups of Direct-Acting Antiviral (DAA) drugs. These drugs have been found to be safe and effective. Sofosbuvir (SOF) plus simeprevir (SMV) regimen has been shown to be tolerable and effective in treatment of patients with HCV genotype 1. The aim of the study was to evaluate the safety and the efficacy of combined sofosbuvir plus simeprevir treatment in genotype 4 chronic HCV patients. This open-label multicenter prospective study was carried out on 381 Egyptian patients with chronic hepatitis C virus- infection. Treatment experienced and treatment-naive patients were included. Subjects administrated a regimen of sofosbuvir (400 mg/ day) plus semiprevir (150 mg /day) for twelve weeks. Sustained Virological Response (SVR) was confirmed by undetectable HCV RNA by quantitative PCR 3 months after the end of the treatment. 97.6% (372 /381) of patients had SVR. None of the studied clinical and demographic characteristics were associated with the SVR status. However, patients who failed to achieve SVR showed low albumin level and high total leucocyte. The most common side effects of the studied regimen were headache, fatigue, itching, photosensitivity, and cough. Twelve weeks' regimen of sofosbuvir plus simeprevir was considered to be safe and tolerable in the treatment of HCV genotype 4; also it was associated with high SVR (97.6%).

Personalized surveillance for hepatocellular carcinoma in cirrhosis – using machine learning adapted to HCV status

Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status. Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n= 668 enrolled between 08/2012-01/2014). Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF]. Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs. Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction.

Non-invasive fibrosis tests to predict complications in compensated post-hepatitis C cirrhosis

Markers predicting complications of post-hepatitis C cirrhosis are needed. We asked whether changes in noninvasive markers of fibrosis can predict liver-related complications. This was a case-controlled study using a prospective national cohort (ANRS-CO12-CIRVIR) of 1323 HCV-infected patients with compensated cirrhosis: 97patients who developed liver-related complications such as hepatocellular carcinoma or hepatic decompensation (cases) matched in age, sex and follow-up duration were compared with 257 patients without complications (controls). Actitest/Fibrotest™, Inflameter/Fibrometer™, ELF™ and Fibroscan™ were performed at baseline and yearly. Samples based on Propensity score matching were built and mixed linear models performed. Outcomes in a sustained virological response (SVR) negative population and a SVR-positive population were also described. At baseline, all characteristics of patients were similar between the groups. All fibrosis tests were statistically higher for cases compared to controls, Fibroscan™ excepted: Fibrotest™: 0.83±0.13 vs. 0.77±0.16; Fibrometer™: 0.93±0.07 vs. 0.90±0.11; ELF™: 11.4±1.0 vs. 11.0±1.2 (P<0.02). The mean follow-up was 5.7±1.9 years. Over a 3-year period, the significant difference in fibrosis marker values between cases and controls remained constant; with a trend toward a decrease in inflammation markers in controls, independent of SVR status. Baseline noninvasive serum fibrosis and inflammation markers were significantly higher in patients developing a complication than in controls. During the follow-up only inflammatory markers decreased in controls, but not in cases, and thus could potentially be used to predict the occurrence of complications in cirrhotic patients.

Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients

BackgroundDiabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted. AimsWe investigated whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients. MethodsA cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC was studied. After excluding patients with biopsy-proven or ultrasound-identified cirrhosis, there were 684 patients without cirrhosis. All 684 patients underwent hepatocellular carcinoma surveillance using ultrasound every 6 months, with a median duration of follow-up evaluation of 102.4 months. During the follow-up period, 60 patients developed cirrhosis according to ultrasound findings. ResultsFor the subgroup of 684 patients without cirrhosis, Kaplan–Meier survival analyses showed no significantly different cumulative incidences of cirrhosis (log-rank test; P = 0.71) among the patients with diabetes as compared to those without. However, after making adjustments for age, gender, fibrosis, steatosis, sustained virological response status, and obesity using Cox’s proportional hazard model, diabetes was found to be an independent predictor for cirrhosis (HR = 1.9; 95% CI = 1.05–3.43, P = 0.03). ConclusionsDiabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

Histological assessment of the liver explant in transplanted hepatitis C virus patients achieving sustained virological response with direct-acting antiviral agents.

The use of direct-acting anti-viral agents (DAAs) has resulted in extremely high sustained virological response (SVR) rates in patients being treated while on liver transplantation (LT) waiting lists. The aim of this study was to evaluate the histological findings of hepatitis C virus (HCV) patients who achieved SVR after receiving DAA treatment [SVR(+)] prior to LT, and compare them with HCV patients who had not achieved SVR [SVR(-)]. Fifty-eight adult HCV patients who underwent LT at our institution from 2014 to 2016 were included in the study. Two pathologists, blinded to SVR status, simultaneously evaluated the histological sections. Assessment included the Histology Activity Index (HAI/modified Knodell score), fibrosis stage (Ishak score), and Laennec cirrhosis stage. The study group comprised 25 SVR(+) patients (56% male; mean age, 63.8 years), and the control group comprised 33 SVR(-) patients (69% male; mean age, 61.7 years). There was no significant difference in HAI between the groups (P = 0.414). Patients who achieved SVR also did not show less portal inflammation (P = 0.787), interface hepatitis (P = 0.999), confluent necrosis (P = 0.627) or spotty necrosis (P = 0.093) than the control group. There was a trend towards a higher degree of inflammation in patients who achieved SVR in <24 weeks (P = 0.07). The degree of focal lytic necrosis/apoptosis and portal inflammation was more prominent in SVR(+) patients with shorter SVR-LT intervals. Our study is the first to report persistent inflammation in HCV patients who received DAAs prior to LT. This supports the notion that inflammation is immunologically driven and that inflammation persists despite the absence of virus.

Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: impact of a sustained virological response.

Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma (HCC). A sustained virological response (SVR) is associated with improved outcomes, however, its impact on different ethnic groups is unknown. To evaluate ethnic differences in the natural history of CHC and the impact of SVR. We conducted a cohort study of 8039 consecutive adult CHC patients seen at two medical centres in California between January 1997 and June 2016. Individual chart review confirmed CHC diagnosis. Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was independently associated with increased cirrhosis (adjusted HR 1.37, CI, confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13-1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic ethnicity was no longer independently associated with cirrhosis (adjusted HR 1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01, CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall survival among the ethnicities by SVR status. Hispanic and Asian ethnicity was independently associated with increased cirrhosis and HCC risk. Achieving an SVR eliminates the ethnic disparity in liver disease progression and overall survival between Hispanic and Asian vs Caucasian CHC patients.

The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia.

BackgroundSeveral genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes.MethodsThe study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR) based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR) was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA) and PLINK v1.07 software.ResultsPatients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034). All but one of the patients with CC genotype achieved SVR (93%), whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients’ age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16–4.68, P = 0.019). Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population.DiscussionThe rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population.

Regression of liver stiffness after sustained hepatitis C virus (HCV) virological responses among HIV/HCV-coinfected patients.

We assessed the impact of a sustained virological response (SVR) on liver stiffness among HIV/hepatitis C virus (HCV)-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort. We studied HIV/HCV-coinfected patients who received at least one dose of any anti-HCV treatment and who had documented SVR status, a pretreatment FibroScan value of at least 7.1 kPa, and at least one posttreatment FibroScan value. The time required to achieve at least a 30% decrease in liver stiffness was analyzed by constructing Kaplan-Meier curves and using Cox proportional hazards models. Among 98 patients treated for HCV infection with either pegylated interferon along with ribavirin (n = 89) or protease inhibitor-based triple therapy (n = 9), 53 patients (54%) had an SVR. Median follow-up was 44.6 (interquartile range: 28.8-58.9) months. The probability of achieving a 30% decrease in FibroScan values was 51% [95% confidence interval (CI): 39-66] in patients with an SVR and 21% in nonresponders (95% CI: 11-36) at 1 year, and 74% (61-86) and 28% (17-44) at 2 years, respectively. In the subgroup of 35 cirrhotic patients (pretreatment liver stiffness ≥12.5 kPa), 14 of 18 patients with an SVR and three of 17 nonresponders had a fibrosis score below 12.5 kPa at the last follow-up examination. Multivariable analysis showed that SVR was independently associated with a ≥30% reduction in liver stiffness, both in the overall study group (hazard ratio: 5.77; 95% CI: 2.00-16.62; P = 0.0012) and in cirrhotic patients (hazard ratio: 8.21; 95% CI: 2.15-31.34; P = 0.0021). Robustness analyses using FIB4 values showed similar results. SVR is significantly associated with improvement in liver stiffness in HIV/HCV-coinfected patients, including those with cirrhosis.

High MIG (CXCL9) plasma levels favours response to peginterferon and ribavirin in HCV‐infected patients regardless of DPP4 activity

Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV)-infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response. African-American and Caucasian HCV genotype 1-infected patients (n = 401) were treated with pegIFN/RBV for 48 weeks (ViraHep-C cohort). Pretreatment plasma levels of MIG (CXCL9), I-TAC (CXCL11) and the type III interferon IL29 were investigated by Luminex and DPP4 activity by using a luciferase assay. Patients achieving SVR had higher baseline MIG plasma levels and lower DPP4 activity than non-SVR patients. MIG was higher in Caucasians, IL28B CC (rs1297860) genotype carriers and patients with higher ALT levels. MIG correlated with IP-10 in SVR patients, but not in non-SVRs. A high DPP4 activity correlated with higher IP-10 levels, while DPP4 activity was not associated with MIG or I-TAC levels. The associations of MIG with SVR status and IL28B genotype imply that higher MIG plasma levels could reflect a beneficial immunological state for response to pegIFN/RBV treatment. The correlation between MIG and IP-10 observed only in SVR patients may contribute to a better treatment response, whereas this MIG/IP-10 balance might be disrupted in non-SVR patients because of the increased DPP4 cleavage of IP-10 into a dysfunctional form.

Long‐term cohort study of chronic hepatitis C according to interferon efficacy

We investigated the prognosis of patients with C-viral chronic liver disease (C-CLD) according to the efficacy of interferon (IFN) therapy in a long-term retrospective cohort study. Of 721 patients with C-CLD who underwent liver biopsy between January 1986 and December 2005, 577 were treated with IFN, and 221 of these patients achieved sustained virological response (SVR) with a follow-up period of 9.9 ± 5.3 years. The annual rate of HCC development was 2.71%/year, 2.31%/year, and 0.24%/year in untreated, non-SVR, and SVR patients, respectively. Multivariate Cox proportional regression analysis showed that the risk of HCC development was significantly lower in SVR patients than in untreated or non-SVR patients; moreover, this risk was similar in non-SVR patients and untreated patients. The annual mortality rate in overall death was 3.19%/year, 1.98%/year, and 0.44%/year in untreated, non-SVR, and SVR patients, respectively. Multivariate Cox proportional hazards regression analysis showed that the SVR status reduced the risk ratio for overall death to 0.173, whereas the non-SVR status did not significantly reduce the risk ratio. The risk ratio of overall death and HCC development was significantly reduced in SVR patients, whereas no significant reduction was found in non-SVR patients in a long-term cohort study.

Optimizing Hepatitis C Therapy in HIV/hepatitis C Virus (HCV) Coinfected Patients: Analysis of HCV Viral Kinetics on Treatment

Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy. Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy.