Virological Response In Hepatitis Research Articles

Frequency of Sustained Virologic Response in Hepatitis C Positive, Treatment Naïve Patients on Sofosbuvir and Daclatasvir

Frequency of Sustained Virologic Response in Hepatitis C Positive, Treatment Naïve Patients on Sofosbuvir and Daclatasvir

Performance of the tetra-primer PCR technique compared to PCR-RFLP in the search for rs12979860 (C/T) and rs8099917 (T/G) single nucleotide polymorphisms (SNPs) in the IFNL4 gene

Single nucleotide polymorphisms (SNPs, rs12979860 e rs8099917) in the Interferon Lambda 4 gene (IFNL4, formerly IFNL3 and/or IL28B) has been associated with failure in the innate immune response, sustained virological response in hepatitis C, and HTLV-1-associated myelopathy (HAM) development. To search for these polymorphisms several methodologies can be employed, such as sequencing, real-time or quantitative polymerase chain reaction (qPCR), restriction fragment length polymorphism analysis in PCR products (PCR-RFLP), and tetra-primer PCR. The present study compared the performance of the tetra-primer PCR in relation to the PCR-RFLP, both optimized in the Research HTLV Laboratory of the Center of Immunology of Instituto Adolfo Lutz in São Paulo. One hundred DNA samples obtained from patients of STD/Aids Reference Centre in São Paulo, previously analyzed for IL28B SNPs by PCR-RFLP were selected for analysis, after confirming that they represent all IL28B SNPs patterns described in the literature. The results obtained showed concordance between the PCR-RFLP and the tetra-primer PCR SNPs results, and because of the low cost, easy to perform, and minor employment of biological specimen and reagents, the tetra- primer PCR is of choice to be used in routine.

Performance of the tetra-primer PCR technique compared to PCR-RFLP in the search for rs12979860 (C/T) and rs8099917 (T/G) single nucleotide polymorphisms (SNPs) in the IFNL4 gene

Single nucleotide polymorphisms (SNPs, rs12979860 e rs8099917) in the Interferon Lambda 4 gene (IFNL4, formerly IFNL3 and/or IL28B) has been associated with failure in the innate immune response, sustained virological response in hepatitis C, and HTLV-1-associated myelopathy (HAM) development. To search for these polymorphisms several methodologies can be employed, such as sequencing, real-time or quantitative polymerase chain reaction (qPCR), restriction fragment length polymorphism analysis in PCR products (PCR-RFLP), and tetra-primer PCR. The present study compared the performance of the tetra-primer PCR in relation to the PCR-RFLP, both optimized in the Research HTLV Laboratory of the Center of Immunology of Instituto Adolfo Lutz in São Paulo. One hundred DNA samples obtained from patients of STD/Aids Reference Centre in São Paulo, previously analyzed for IL28B SNPs by PCR-RFLP were selected for analysis, after confirming that they represent all IL28B SNPs patterns described in the literature. The results obtained showed concordance between the PCR-RFLP and the tetra-primer PCR SNPs results, and because of the low cost, easy to perform, and minor employment of biological specimen and reagents, the tetra- primer PCR is of choice to be used in routine.

Risk of hepatocellular carcinoma after sustained virologic response in hepatitis C virus patients without advanced liver fibrosis.

Hepatocellular carcinoma (HCC) after sustained virologic response (SVR) has been observed even in hepatitis C virus (HCV) patients without advanced liver fibrosis. Identifying predictors for HCC incidence in patients without advanced liver fibrosis will enable efficient post-SVR HCC surveillance. This study aimed to develop a scoring system to predict the incidence of HCC after SVR in HCV patients without advanced liver fibrosis. A total of 1682 HCV patients without advanced liver fibrosis (defined as Fibrosis-4 index <3.25) with no history of HCC who initiated direct-acting antiviral treatment between September 2014 and October 2020 at 26 institutions, and achieved SVR24, were included. We divided 1682 patients into training (1122) and validation (560) cohorts. In the multivariate analysis, baseline age ≥65years (p=0.030), alanine aminotransferase (ALT) levels at SVR24≥30 U/l (p=0.001), and α-fetoprotein (AFP) levels at SVR24≥5.0ng/ml (p=0.001) were independent predictors for HCC incidence in the training cohort. We developed a scoring system to predict HCC incidence after SVR24 using these three factors (1 point was added for each factor). The cumulative HCC incidence rates at 5years were 7.1% in patients who scored 2 or 3, and no patients developed HCC in those who scored 0 in the validation cohort. Our scoring system using the three factors of baseline age, ALT levels at SVR, and AFP levels at SVR is useful for post-SVR HCC surveillance of patients without advanced liver fibrosis.

Comparison of Frequency of Rapid Virological Response in Patients of Hepatitis C being Treated with 25-OH Vitamin D along with Sofosbuvir/Ribavirin with Those Treated with Sofosbuvir/Ribavirin only

Background: Hepatitis C is the leading cause of liver damage that lead to death if left untreated. Sofosbuvir has recently attained enormous success due to high rate of virological response. Recent studies have shown that addition of vitamin D to antiviral therapy improves the efficacy of treatment in patients with Hepatitis C. Objective: To compare the frequency of virological response in hepatitis C patients treated with vitamin D along with sofosbuvir plus ribavirin to those treated with sofosbuvir plus ribavirin only Study Design: Randomized-controlled-trial Place and Duration of Study: Department of Medicine, Pak Emirates Military Hospital, Rawalpindi from 1st November 2017 to 30th April 2018. Methodology: One hundred patients of chronic hepatitis C were included. Patients were randomly divided into two groups; group A receiving vitamin D along with sofosbuvir plus ribavirin and group B receiving sofosbuvir plus ribavirin therapy only. Patients were treated for 6 months and their RVR was monitored. Results: The mean age of patients in combination group was 39.0±12.92 years and in control group were 36.66±13.80years. After 4 weeks, RVR (no HCV RNA detected on PCR) was achieved in 31 (62%) cases in combination group while in 19 (38%) cases there was still HCV RNA present. In control group, RVR could be achieved in 18 (36%) cases while in 32 (64%) cases, RVR could not be achieved. The difference was significant between both groups (p&lt;0.05). Conclusion: The addition of vitamin D can help in achieving RVR in &gt;50% cases within 4 weeks. So addition of vitamin D in standard therapy may help to improve the quality of treatment. Keywords: Rapid virological response, Hepatitis C, 25-OH vitamin D, Sofosbuvir, Ribavirin

Hepatitis C virologic response in hepatitis B and C coinfected persons treated with directly acting antiviral agents: Results from ERCHIVES

BackgroundThere are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. MethodsAll HCV infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. Logistic regression model was used to determine factors associated with SVR. ResultsAmong 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pre-treatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). ConclusionHBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. Though not statistically significant, the virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores.

294. Hepatitis C Virologic Response in Hepatitis B and C Coinfected Persons Treated with Directly Acting Antiviral Agents: Results from ERCHIVES

BackgroundThere are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown.MethodsAll HCV-infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. A logistic regression model was used to determine factors associated with SVR.ResultsAmong 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pretreatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87).ConclusionHBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. The virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores. Disclosures All authors: No reported disclosures.

Management of betablocked patients after sustained virological response in hepatitis C cirrhosis.

BACKGROUNDCurrent guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option.AIMTo assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population.METHODSInclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after direct-acting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician.RESULTSSample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/µL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk.CONCLUSIONPortal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.

PS-189-Toronto HCC risk index and albumin predict low risk of hepatocellular carcinoma after sustained virological response in hepatitis C infection

PS-189-Toronto HCC risk index and albumin predict low risk of hepatocellular carcinoma after sustained virological response in hepatitis C infection

Determination of Sustained Virological Response in Hepatitis C Virus Genotypes by the Number of Mutations in the E2 and NS5A-ISDR Regions: A Meta-Analysis

Since last few decades hepatitis C virus (HCV) has been a major cause of death due to the involvement of acute and chronic type of liver diseases throughout the world. Genotype variability and mutations occurring at different regions of HCV genome provides a critical parameter for the study of sustained virological response (SVR) against mono and combinational therapies. Most of these mutations occurring in E2 and NS5A-ISDR regions in HCV genotypes play a significant role in SVR against Interferon-monotherapy and combination therapy. Therefore, the aim of the present study is to evaluate the SVR in various genotypes and the role of mutations in specific regions. In line with this, the NS5A and E2 proteins of HCV genotype 1 were found to suppress the double-stranded (ds) RNA-dependent protein kinase (PKR), which in turn is entailed in the cellular antiviral response stimulated by interferon (IFN). The response to IFN therapy varies between genotypes, with response rates among patients infected with types 2 and 3 nearly two-three-fold greater than in patients infected with type 1. Surprisingly, a considerable percentage of HCV genotype 3a infected patients do not react to treatment at all. In Japan, a link was observed between the numbers of mutations in an “interferon sensitivity determining region” (ISDR) and the result of interferon treatment in genotype 1b infected patients. Therefore, we published data on E2 (PePHD) and NS5A-ISDR regions including our data on SVR of different HCV genotypes, the relationship between the number and patterns of mutations in the E2 (PePHD) and NS5A-ISDR regions and responsiveness to IFN therapy.

Impact of IFNL4-∆G genotype on sustained virologic response in hepatitis C genotype 1 patients treated with direct-acting antivirals

In direct acting antiviral (DAA)-treated HCV genotype 1, the sustained virologic response rate with the ∆G/∆G genotype of IFNL4 rs368234815 (86.8%) was significantly lower than with ∆G/TT (95.9%, P = 0.03) or TT/TT (98.6%, P = 0.01). The SVR odds ratio for ∆G/∆G compared to TT/TT was 0.10 (P = 0.03). IFNL4 genotype might predict DAA-response.

Cirrhosis, high age and high body mass index are risk factors for persisting advanced fibrosis after sustained virological response in chronic hepatitis C.

We aimed to assess fibrosis with liver stiffness measurement long-term after sustained virological response of chronic hepatitis C and to identify risk factors associated with persisting fibrosis. In this cross-sectional study, patients with chronic hepatitis C and pretreatment advanced fibrosis or cirrhosis treated successfully at Karolinska University Hospital with an interferon-containing regimen underwent liver stiffness measurement with FibroScan. The impact of potential risk factors for persisting fibrosis was estimated. We included 269 patients with a median follow-up time of 7.7years (range 0-20), 84 with a follow-up time of ≥10years. Patients with pretreatment cirrhosis had a significantly higher median liver stiffness level (8.5 kPa 95% CI 7-9.1) at follow-up, than patients with advanced fibrosis (6 kPa 95% CI 5.5-6.4). A majority improved their fibrosis stage after sustained virological response, but 24% had persisting advanced fibrosis with a liver stiffness level of ≥ 9.5 kPa. Among patients with pretreatment cirrhosis, the proportion with persisting advanced fibrosis diminished with longer follow-up time, from 48% after <5years to 21% after >10years. The main risk factors for persisting advanced fibrosis were pretreatment cirrhosis, high age and body mass index. In conclusion, fibrosis improves substantially during long-term follow-up after sustained virological response in hepatitis C patients with pretreatment advanced liver fibrosis. Lifestyle intervention to decrease weight in obese persons and treatment before establishment of cirrhosis should therefore be recommended to avoid persistence of advanced fibrosis after virological cure.

Treatment of hepatitis C genotype 1 infection in Germany: effectiveness and safety of antiviral treatment in a real-world setting.

In pivotal studies with direct-acting antivirals (DAAs), rates of sustained virological response in hepatitis C genotype 1 infection are >90%. The objective of this article is to assess real-world safety and effectiveness of DAA treatment in a prospective multicenter registry study. The German Hepatitis C-Registry includes 6606 patients with genotype 1 from 246 centers, treated between February 2014 and June 2016 at the discretion of the physician. A total of 4846 patients completed treatment and follow-up; 51% of these patients were treatment experienced and 28% had liver cirrhosis. Comorbidities were reported in 76% of patients, including HIV co-infection in 8%. SVR12 was 92% with 91% in GT1a and 93% in GT1b. HIV co-infected patients (n = 247) had an SVR12 of 92%. Treatment was discontinued prematurely in 2.5%. In multivariate analysis, SVR12 was dependent on the choice of antiviral regimen (OR 1.33 (1.24-1.43); p < 0.001), negatively associated with presence of liver cirrhosis (OR 0.71 (0.56-0.89); p < 0.003) and positively associated with female gender (OR 1.52 (1.21-1.91); p < 0.001). Data from this real-world registry show SVR12 rates close to those obtained in clinical studies. Discontinuation rates are low, confirming good tolerance of the regimens and good adherence of patients (Trial registration number DRKS00009717, German Clinical Trials Register, DRKS).

Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals.

In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7)mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60)mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28mg/L was the optimal lower cut-off for achieving SVR and 3.61mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin<10g/dL). In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR.

Hepatitis B s antigen kinetics during treatment with nucleos(t)ides analogues in patients with hepatitis B e antigen-negative chronic hepatitis B.

Serum hepatitis B s antigen (HBsAg) levels might be used as a predictor of virological breakthrough or of sustained off-treatment virological response in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. We evaluated the changes of HBsAg in those patients under nucleos(t)ide analogue(s) [NA(s)] therapy for ≥12months. We included 99 HBeAg-negative CHB patients treated with low-genetic barrier NA(s) for a mean of 66months (lamivudine: 66, adefovir: 6, lamivudine plus adefovir: 11 and telbivudine: 16) and 86 HBeAg-negative CHB patients treated under entecavir or tenofovir for a mean of 30months as the comparison group. Compared to baseline, HBsAg levels decreased by a median of 162, 1525, 943, 1545, 2163 and 3859IU/mL at 6, 12, 24, 36, 48 and 60months of therapy with low-genetic barrier NA(s) respectively. The 6-, 12-, 24-, 36-, 48- and 60-month cumulative rates of HBsAg<100IU/mL were 2%, 3%, 3%, 5%, 5% and 5%, and <1000IU/mL 6%, 9%, 15%, 19%, 24% and 61% respectively. Baseline HBsAg levels were the only significant variable associated with the time to HBsAg drop <1000IU/mL. HBsAg loss occurred in 3.0% of patients. The high-genetic barrier NAs were not found to offer a greater or faster HBsAg decline. In HBeAg-negative CHB patients, long-term therapy with low-genetic barrier NA(s) decreases serum HBsAg levels, but the rate of decline is slow. Lower baseline HBsAg levels are significantly associated with on-therapy HBsAg drop <1000IU/mL. Serum HBsAg decline is similar during therapy with low- or high-genetic barrier NAs.

Achieving Sustained Virological Response in Hepatitis C Reduces the Long-Term Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis Employing Relative and Absolute Outcome Measures.

We studied the effect of achieving sustained virological response (SVR) on the risk of developing hepatocellular carcinoma (HCC) in patients with hepatitis C receiving anti-hepatitis C virus treatment. Avoiding HCC is considered the main long-term benefit of successful antiviral treatment. Our literature search extended up to June 2015. We identified all studies that assessed the risk of HCC in patients achieving or not achieving SVR. Meta-analysis was based on a standard random-effect model. The end-point was occurrence of HCC compared between patients with and without SVR; this end-point was expressed as an odds ratio and percent reduction in risk and was also presented separately for patients with and without cirrhosis. All results estimates presented with 95% confidence intervals (CIs). The presence of any temporal trend in these indexes was investigated by standard meta-regression. Our search identified 25 observational studies (19,822 patients). The odds ratio of HCC for SVR versus no-SVR was 0.19 (95% CI 0.15-0.24) in the overall series of 25 studies. The difference in this index between patients with any stage of fibrosis/cirrhosis and those with cirrhosis was small. With regard to risk difference, the 25 studies indicated an overall reduction of 10% (95% CI 8.00-12.0); this effect was much less pronounced in the group with any stage of fibrosis/cirrhosis (risk difference 6.7%) than in the selected group with cirrhosis (risk difference 22%). Meta-regression showed no temporal trend. Our analysis was successful in providing an updated overview on this controversial topic. Some pharmacoeconomic assessments are also presented to interpret the clinical results of our analysis.

Effectiveness, safety and cost per sustained virological response in Hepatitis C patients treated with Sofosbuvir based therapies in clinical practice in Germany

Introduction: Real-world (RW) clinical outcomes of sofosbuvir (SOF)-based treatment from Germany have recently been presented but no study to date has evaluated these economic outcomes. The aim of this study was to estimate the total costs, RW effectiveness, safety and cost per sustained viral response (SVR) of chronic hepatitis C (CHC) patients treated with SOF-based therapies in Germany.

Cognitive impairment in relation to depression, anxiety and virological response in hepatitis C patients in Egypt

Objective. Cognitive impairment commonly occurs in hepatitis C virus (HCV) patients. The objective of this study was to estimate the prevalence and sociodemographic and clinical correlates of cognitive impairment in HCV patients before and after 12 weeks of interferon treatment in comparison with a control group. Methods. Hundred and sixteen consecutive HCV patients were included in the study and divided into treated and untreated groups. All patients were assessed using sociodemographic and clinical questionnaire, Montreal Cognitive Assessment Scale (MOCA) and Hospital Anxiety and Depression Scale (HADS) before and after 12 weeks of treatment or observation. Results. Thirty-eight percent of treated patients showed cognitive impairment at baseline, which increased to 69% after 12 weeks of interferon treatment. This cognitive impairment was reflected in the total MOCA score and in visuo-constructional skills, attention, concentration, working memory, language, and short-term memory, which was not shown by untreated group after 12 weeks of observation. Cognitive impairment was associated with low education, but not with depression, anxiety, or virological response. Conclusions. Cognitive impairment is common in HCV patients and increases significantly after interferon treatment. It is not related to depression or anxiety in HCV patients. Future research should focus on prevention, treatment and outcome of cognitive impairment in HCV patients, particularly those receiving interferon therapy.

P0381 : Clinical impact of achieving sustained virological response in hepatitis C virus-infected patients with early stage hepatocellular carcinoma

P0381 : Clinical impact of achieving sustained virological response in hepatitis C virus-infected patients with early stage hepatocellular carcinoma

Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.

BackgroundVirological response to peginterferon + ribavirin (P+R) at week 4 can predict sustained virological response (SVR). While patients with rapid virological response (RVR) do not require triple therapy, patients with a decline <1log10 IU/ml HCVRNA (D1L) should have treatment discontinued due to low SVR rate.AimTo develop a tool to predict first 4 weeks’ viral response in patients with hepatitis C genotype 1&4 treated with P+R.MethodsIn this prospective and multicenter study, HCV mono-infected (n=538) and HCV/HIV co-infected (n=186) patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model) and a validation cohort (to validate the model).ResultsD1L was reached in 509 (80.2%) and RVR in 148 (22.5%) patients. Multivariate analyses demonstrated that HIV co-infection, Forns’ index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC) for D1L was: 0.81 (95%CI: 0.76 — 0.86) in the estimation cohort and 0.71 (95%CI: 0.62 — 0.79) in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 — 0.88) in the estimation cohort and 0.82 (95%CI: 0.76 — 0.88) in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented.ConclusionsThe combination of genetic (IL28B polymorphism) and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.