Meta-analysis of patients with hepatitis C virus genotype 6: 48 weeks with pegylated interferon and ribavirin is superior to 24 weeks

Background

Hepatitis C virus genotype 6 (HCV-6) is common in patients from Southeast Asia and the surrounding regions. Optimal treatment duration for HCV-6 is unknown given the inconclusive evidence from studies with varying methodologies and small sample sizes.

Methods

A literature search for ‘genotype 6’ in MEDLINE and EMBASE in October 2013 produced 161 and 251 articles, respectively. Additional abstracts were identified from four major international GI/liver conferences in 2012/2013. Inclusion criteria were original studies with ≥10 HCV-6 treatment-naïve patients treated with pegylated interferon + ribavirin (PEG IFN+RBV). Exclusion criteria were coinfections with HBV, HIV, other HCV genotypes, and/or other liver diseases. Primary outcome was pooled sustained virologic response (SVR). Heterogeneity was defined by Cochrane Q test (p value of 0.10) and I ² statistic (≥50 %).

Results

A total of 13 studies with 641 patients were included. The pooled SVR estimate was 77 % (CI 70–83 %) (Q value = 38.4, p value <0.001, I ² = 68.7 %) overall, 79 % (CI 73–84 %) for the 48-week group and 59 % (CI 46–70 %) for 24-week group, respectively. In studies with direct comparison of the two groups, SVR was superior in patients treated for 48 versus 24 weeks, OR 1.9 (CI 1.08–3.2, p = 0.026). In studies with direct comparison of patients with rapid virologic response (RVR), there was no difference in SVR between 48 versus 24 weeks, OR 1.74 (CI 0.65–4.64, p = 0.27).

Conclusion

Hepatitis C virus genotype 6 patients should be treated for 48 weeks, and those who achieve RVR may receive the shorter 24-week treatment duration. The high SVR (~80 %) with 48 weeks of PEG IFN+RBV therapy may be a cost-effective option for HCV-6 patients from resource-poor regions.     

IL28B polymorphisms predict the virological response to standard therapy in patients with chronic hepatitis C virus genotype 4 infection

Background

Genome-wide association studies have recently revealed that several single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can predict the sustained virological response (SVR) to pegylated interferon-α2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However, data for patients infected with HCV genotype 4 (HCV-G4) are limited.

Aim

We analyzed the association of IL28B SNPs (hematological, biochemical, virological, and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients.

Patients and methods

One hundred twenty-nine treatment-naïve HCV-G4 patients undergoing treatment were recruited from three tertiary care centers in Saudi Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR was statistically correlated with various clinical, histopathological, virological, and genetic parameters.

Results

SVR was significantly associated with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004), respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039) showed significant differences in the SVR and No SVR groups. On multivariate analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6–6.2, p = 0.006) and albumin levels (OR, 1.2; 95 % CI 1.1–1.4, p = 0.001) independently predicted SVR.

Conclusions

IL28B polymorphism (CC allele of rs12979860) predicts the sustained response to antiviral therapy in HCV-G4.     

Extended treatment with pegylated interferon alfa/ribavirin in patients with genotype 2/3 chronic hepatitis C who do not achieve a rapid virological response: final analysis of the randomised N-CORE trial

Background and aims

The combination of pegylated interferon alfa/ribavirin will likely remain the treatment of choice for HCV genotype 2/3 patients in financially constrained countries for the foreseeable future. Patients with poor on-treatment response may benefit from treatment extension. This study examined the effect of 48 versus 24 weeks of peginterferon alfa-2a/ribavirin on the sustained virological response (SVR) in patients with HCV genotype 2/3 who did not achieve rapid virological response (RVR).

Methods

N-CORE was a multicentre, randomised, phase III study. HCV genotype 2/3 patients receiving peginterferon alfa-2a/ribavirin without a rapid but with an early virological response were randomised at week 24 to stop treatment (Arm A) or continue to 48 weeks (Arm B). The primary efficacy endpoint was SVR.

Results

Two hundred thirty-five patients were enrolled. End of treatment response was similar in both treatment arms. SVR24 rates were not significantly greater in the extended treatment arm compared with the standard 24-week treatment in either the intention-to-treat or the per-protocol populations (61 vs. 52 %, p = 0.1934 and 63 vs. 52 %, p = 0.1461, respectively). Serious adverse events occurred more frequently in patients receiving extended treatment duration (12 %) versus 24-week therapy (4 %).

Conclusions

It is unclear whether the extension of peginterferon alfa-2a/ribavirin treatment may benefit HCV genotype 2/3 patients who do not achieve RVR. The study was stopped early because recruitment was slower than anticipated, and this may have limited the statistical impact of these findings.     

Estimates of HCV-1 Patients Attaining RVR Following Dual Therapy with Peg-Interferon and Ribavirin

Background

Given the significant side-effects and healthcare costs associated with telaprevir- or boceprevir-combination therapy, identifying patients likely to respond to dual therapy peg-interferon (Peg-IFN)/ribavirin is highly desirable. Since the perception of how large the pool of patients who may achieve rapid virologic response (RVR) is vaguely ascertained, we searched the literature for this information.

Methods

Studies on patients treated with Peg-IFN/ribavirin were identified by searching MEDLINE and analyzed by meta-analysis. The primary end point was weighted estimates of RVR. The influence on race/ethnicity, baseline viremia, type of Peg-IFN, ribavirin dosage, and significant hepatic fibrosis on the results was evaluated.

Results

Across 38 studies on 13,219 patients, the fraction of RVR patients was 19.6 %. The only baseline factor influencing RVR was race/ethnicity, with higher rates in Asian (26.7 %) and Caucasian patients (22.5 %). Of the 1,735 RVR patients, 85.1 % attained sustained virologic response (SVR). In these, SVR was influenced by ribavirin dose (86.8 vs. 72.8 % for high or low), type of Peg-IFN (91.8 % for alpha-2b vs. 82.9 % for alpha-2a), and treatment duration (91.7 % for 48 weeks vs. 79.4 % for 24 weeks).

Conclusions

One fifth to one fourth of hepatitis C virus genotype 1 (HCV-1) patients can be safely treated with dual therapy of Peg-IFN/ribavirin, and may be spared from cost and inconvenience of regimens considering the addition of HCV protease inhibitors.     

U.S. Multicenter Pilot Study of Daily Consensus Interferon (CIFN) Plus Ribavirin for ��Difficult-to-Treat�� HCV Genotype 1 Patients

Background

Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection.

Methods

Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3?C4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1?C1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52?C72 weeks (from time of viral response +48 weeks) (group B, n = 31).

Results

Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8?C12 weeks, and late virologic response from 16?C24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients.

Conclusion

Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.     

Efficacy and safety of sofosbuvir-based therapy for chronic hepatitis C infection in “real-life” cohort

Background

The safety and efficacy of sofosbuvir-based treatment (sofosbuvir and ribavirin with or without pegylated interferon-α) for hepatitis C virus (HCV) infection has been established in clinical trials. However, there is limited data regarding safety and efficacy of sofosbuvir-based treatment for HCV infection in a “real-life” cohort. We describe our experience with sofosbuvir-based treatment for HCV infection in a real-life cohort.

Methods

This was a prospective, nonrandomized and observational study at a tertiary care centre in Surat, India. The primary end-point was proportion of the study patients who achieved a sustained virological response 12 weeks after cessation of treatment (SVR 12). Secondary end-points of the study include SVR 4, virological relapse and appearance of adverse events.

Results

A total of 107 patients with chronic HCV who received sofosbuvir-based treatment were included in the study. During study period, two patients died due to severity of liver complications. Hence, overall rate of SVR 4 and SVR 12 was 98.1 % (n = 103/105) and 94.3 % (n = 99/105), respectively. Among 67 patients with HCV genotype-3 infection, the SVR 12 rate was 92.5 % (n = 62/67), and among 38 patients with HCV genotype-1 infection, the rate of SVR 12 was 97.4 % (n=37/38). A total of 32 (29.9 %) patients reported adverse events during the course of sofosbuvir-based treatment. None of the patient discontinued treatment due to adverse event.

Conclusions

Sofosbuvir-based treatment is safe and efficacious in clinical practice in Indian patients with HCV genotype-1 and genotype-3 infection.

     

Immunological dysfunction during or after antiviral therapy for recurrent hepatitis C reduces graft survival

Introduction

Pegylated interferon and ribavirin (PEG-IFN/RBV) therapy for recurrent hepatitis C after liver transplantation (LT) is associated with a lower sustained virological response (SVR) rate as well as more frequent side effects compared to non-transplant patients. We aimed to determine the incidence and clinical characteristics of LT recipients with recurrent hepatitis C who developed immunological dysfunction (ID) during or after PEG-IFN/RBV therapy and to assess its impact on patient and graft survival.

Methods

Seventy-four deceased donor LT recipients with histological recurrence of hepatitis C were treated with PEG-IFN/RBV from 1/00 to 12/08. ID was defined as biopsy-proven rejection or moderate plasma cell hepatitis. Patients were followed up until death, re-LT or 30 September 2011.

Results

Twelve patients (16 %) had ID, 8 (10.7 %) had cholestasis without ID, while 54 had no ID/cholestasis during or after discontinuation of PEG-IFN/RBV therapy. Biopsy-proven acute cellular rejection prior to (hazard ratio = 4.87, p = 0.009) and type of immunosuppression at the time of initiation of PEG-IFN/RBV were the only independent predictors of ID. Patients who were on tacrolimus at the time of initiation of PEG-IFN/RBV had a significantly lower risk of ID compared to those who were on cyclosporine (HR 0.254, p = 0.023). Patients with ID had a trend toward a lower SVR rate (25 vs. 54 %, p = 0.18) and a significantly higher rate of graft failure (33 vs. 4 %, p = 0.004) compared to patients with no ID/cholestasis.

Conclusions

ID is common during or after PEG-IFN/RBV therapy for recurrent hepatitis C and frequently associated with decreased graft survival, trending toward low rates of SVR. Careful monitoring of liver biochemistries during or after PEG-IFN/RBV therapy with a low threshold to biopsy patients and particularly those receiving cyclosporine-based immunosuppression may improve outcomes in these patients.     

Using early viral kinetics to predict antiviral outcome in response-guided pegylated interferon plus ribavirin therapy among patients with hepatitis C virus genotype 1

Background

HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear.

Methods

Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis.

Results

The sustained virologic response (SVR) rate was 53 % for all patients, 60 % for those with genotype TT, and 19 % for those with genotype TG/GG according to IL28B (rs8099917) single nucleotide polymorphisms. The SVR rates increased with HCV decrease at week 4; 4 % (2/56) with <1 log₁₀ decrease, 13 % (7/56) with 1–2 log₁₀ decrease, 51 % (44/87) with 2–3 log₁₀ decrease, 64 % (56/87) with 3–4 log₁₀ decrease, 88 % (72/82) with more than 4 log₁₀ decrease but with detectable HCV RNA and 100 % (33/33) with undetectable HCV RNA (p < 0.001). Similarly, SVR rates increased step-by-step in proportion to HCV decrease in both IL28B TT and TG/GG groups, showing almost the same SVR rates for the same conditions. In multivariate analysis, age (p = 0.005) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with SVR. Advanced liver fibrosis (p = 0.004) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with non-response.

Conclusions

The magnitude of the HCV decrease at week 4 seems to be the most reliable marker for predicting antiviral outcome after starting Peg-IFN plus ribavirin therapy.     

Clinical Outcomes of Hepatitis C Treated with Pegylated Interferon and Ribavirin via Telemedicine Consultation in Northern California

Background

Patients in rural communities are less likely to receive treatment for their hepatitis C (HCV) infection. Telemedicine (TM) consultation can close the gap of access to specialists in remote and under-served areas.

Aim

To determine treatment response and side-effect profiles among HCV patients treated with pegylated interferon and ribavirin via TM consultation in different rural locations in Northern California compared with patients treated in traditional hepatology office visits.

Methods

We performed a retrospective analysis of 80 HCV patients treated at different TM sites (TM, n = 40) and at the University of California Davis Hepatology Clinic (HC, n = 40) between 2006 and 2010, comparing baseline characteristics and clinical outcomes.

Results

At baseline, response to therapy was similar for patients in both groups. Sustained virological response (SVR) was similar in both groups (TM: 55 vs. HC: 43 %; p = 0.36), and a higher proportion of patients treated via telemedicine completed treatment (TM: 78 vs. HC: 53 %; p = 0.03). TM patients had many more visits per week of therapy (TM: 0.61 vs. HC: 0.07; p < 0.001). Neutropenia, GI side effects, fatigue, depression, weight loss, insomnia, and skin rash were similar in both groups. For HC patients incidence of anemia was significantly higher (53 %) than for the TM group (25 %; p = 0.02).

Conclusions

The two groups had equivalent SVR. For the TM group therapy completion was superior and incidence of anemia was lower. This initial study suggests that, as a group, patients with HCV, can be safely and effectively treated via telemedicine.     

Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy

Purpose

A proportion of patients infected with genotype 2a hepatitis C virus (HCV) cannot achieve a sustained virological response (SVR) to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV) but the reason remains unclear. The present study aimed to clarify the possible correlation between viral sequence variations and final outcome.

Methods

The pretreatment complete open reading frame (ORF) sequences of genotype 2a HCV were determined by direct sequencing for two independent groups of patients (43 patients as test; group 1 and 35 as validation; group 2), and the correlation with the final outcome was explored.

Results

Patients with SVR (n = 58) and with non-SVR (n = 20) differed significantly in pretreatment HCV RNA level (p = 0.002), fibrosis score (p = 0.047), and cumulative RBV dosage (p = 0.003). By comparison of all amino acid positions in the complete HCV ORFs, threonine at amino acid (aa) 110 in the core region was remarkably frequent in SVR (p = 0.01 for group 1, p = 0.004 for group 2, and p = 5E?05 for combined). A sliding window analysis revealed that the total number of amino acid variations within the NS5A aa 2258–2306 region were significantly high in SVR compared to non-SVR patients (p = 0.01 for group 1, p = 0.006 for group 2, and p = 0.0006 for combined). Multivariate analyses revealed that core aa 110 (p = 0.02), NS5A aa 2258–2306 (p = 0.03), and cumulative RBV dosage (p = 0.02) were identified as independent variables associated with the final outcome.

Conclusions

The outcome of PEG-IFN/RBV therapy is significantly influenced by variation in the core and NS5A regions in genotype 2a HCV infection.     

Interferon-associated hepatic steatosis is related to discrepancies in biochemical and virological responses of chronic hepatitis C to IFN-based therapy

Background and aims

A discrepancy in virological and biochemical responses may occur throughout interferon-based therapy for hepatitis C virus (HCV). We aimed to explore the risk, associated factors, potential mechanisms, and impact on the treatment outcome of the discrepancy.

Subjects and methods

Consecutive 496, chronic HCV-infected patients receiving interferon/ribavirin or peginterferon/ribavirin for 24 weeks with a 24-week follow-up period were enrolled. Of 433 patients with pretreatment liver biopsy, 46 received serial liver biopsies at the end of treatment and end of follow-up to explore the corresponding change in liver histopathology. A virological/biochemical discrepancy was defined as persistently elevated alanine aminotransferase levels throughout the treatment period, despite the seronegativity for HCV RNA at least at the end of treatment. The sustained virological response (SVR) was defined as seronegativity for HCV RNA 6 months after the end of treatment.

Results

Virological/biochemical discrepancy was observed in 28.7 % (137/478) patients. The SVR rate was comparable between patients with (75.2 %, 103/137) and without discrepancy (81.2 %, 277/341, p = 0.14). For patients with discrepancy and SVR, 78 (75.7 %) had a subsequent normalization of alanine aminotransferase. Hepatic steatosis, advanced fibrosis, obesity, older age, peginterferon preparation, and low viral load were independently predictive of a virological/biochemical discrepancy. Serial liver histology showed that significant transient aggravation of hepatic steatosis during interferon-based therapy was observed among patients with a virological/biochemical discrepancy (difference 0.64 ± 0.93, p = 0.022), but not among those without it (difference 0.09 ± 0.69, p = 0.447).

Conclusions

A virological/biochemical discrepancy no longer exists after treatment cessation in most patients, and had little impact on the HCV treatment outcome. Treatment-related hepatic steatosis might play an important role in the pathogenesis of the discrepancy.     

Baseline risk factors for relapse in HIV/HCV co-infected patients treated with PEG-IFN/RBV

Purpose

Hepatitis C virus (HCV) viral relapse (VR) after end-of-treatment response (ETR) in human immunodeficiency virus (HIV) co-infected patients is observed in as many as one in three co-infected patients. The aim of the study was to identify baseline risk factors for VR in HIV/HCV co-infected patients treated with pegylated interferon plus ribavirin (PEG-INF/RBV).

Methods

A total of 212 Caucasian HIV-infected patients with chronic hepatitis C naïve for PEG-INF/RBV were followed prospectively. Patients were included in this prospective study if they had completed a full course of therapy with an ETR. We assessed the relationship between VR rate and potential predictors of relapse.

Results

Of the patients followed, 130 (61.3 %) attained ETR and 103 (79.2 %) achieved sustained virological response (SVR). Consequently, 27 (20.8 %) showed VR. Patients who relapsed were more often male (p = 0.036), carried the non-CC rs14158 genotype in the low-density lipoprotein receptor (LDLr) gene (p = 0.039), had higher baseline HCV RNA levels (p = 0.012), body mass index (BMI) ≥25 kg/m² (p = 0.034), significant liver fibrosis (p < 0.001), had been diagnosed with acquired immunodeficiency syndrome (AIDS)-defining criteria in the past (p = 0.001) and bore the HCV genotypes 1/4 (p = 0.046) when compared with SVR patients. The IL28B genotype was not associated with relapse. Multivariate binary logistic regression showed that high baseline HCV RNA, significant liver fibrosis, HCV genotypes 1/4, being overweight and being diagnosed with AIDS-defining criteria in the past were independently associated with relapse.

Conclusions

Our study shows that VR can be accurately predicted in HIV/HCV co-infected patients on the basis of risk factors which can be identified before treatment.     

Predictive value of FIB-4 and APRI versus METAVIR on sustained virologic response in genotype 1 hepatitis C patients

Purpose

Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications.

Methods

Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients.

Results

CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p < 0.1 × 10^?30) was stronger than that between METAVIR (p = 3.86 × 10^?13) or APRI (p = 5.48 × 10^?6) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio.

Conclusion

The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40  KD)/ribavirin.     

Once-daily simeprevir with peginterferon and ribavirin for treatment-experienced HCV genotype 1-infected patients in Japan: the CONCERTO-2 and CONCERTO-3 studies

Background

Efficacy of available therapies for patients with HCV who have previously failed treatment is limited. Two Phase III, open-label trials in Japan investigated efficacy and safety of simeprevir and peginterferon-α-2a/ribavirin (PR) combination therapy in treatment-experienced patients with genotype 1 HCV infection.

Methods

In CONCERTO-2, prior non-responders to IFN-based therapy (N = 106) received simeprevir (TMC435) 100 mg QD with PR for 12 (SMV12, n = 53) or 24 weeks (SMV24, n = 53) followed by response-guided therapy (RGT) with PR for 12/36 (SMV12) or 0/24 (SMV24) weeks. In CONCERTO-3, relapsers after IFN-based therapy (N = 49) received simeprevir 100 mg QD with PR for 12 weeks followed by RGT with PR for 12/36 weeks. Primary endpoints were the rates of sustained virologic response 12 weeks after treatment end (SVR12).

Results

SVR12 rates were 52.8 % (SMV12) and 35.8 % (SMV24) for prior non-responders, and 95.9 % for prior relapsers (SMV12; p ≤ 0.0001 vs null hypothesis, respectively). Most prior non-responders (SMV12: 81.1 %; SMV24: 73.6 %) and prior relapsers (95.9 %) met RGT criteria and completed PR to Week 24. Of these, 60.5 %, 48.7 %, and 95.7 %, respectively, achieved SVR12. Viral breakthrough occurred in 13.2 % (SMV12) and 11.3 % (SMV24) of prior non-responders; no viral breakthrough occurred in prior relapsers. Viral relapse occurred in 38.6 % (SMV12) and 51.1 % (SMV24) of prior non-responders and 8.2 % of prior relapsers. Simeprevir with PR was generally well tolerated in both studies.

Conclusion

Re-treatment with 12 weeks of simeprevir QD with PR provided high SVR in treatment-experienced patients with chronic HCV genotype 1 infection, and allowed most patients to complete treatment in 24 weeks.     

Pneumonia After Endoscopic Resection for Gastric Neoplasm

Background

Pneumonia following endoscopic procedures may affect the clinical course and prolong hospital stay.

Aim

To investigate the incidence and risk factors for pneumonia after endoscopic resection (ER) for gastric neoplasm.

Methods

Subjects who underwent ER for gastric neoplasm at the Asan Medical Center from January 1997 to March 2013 were included. To investigate risk factors, control patients were randomly selected from these subjects.

Results

Of the 7,149 subjects who underwent ER for gastric neoplasm, 44 (0.62 %) developed pneumonia. The median age of these 44 patients was 68 years (range 31–82 years), and the male to female ratio was 3:1. Twenty-five of the pneumonia patients (56.8 %) were smokers, and 8 (18.2 %) had underlying pulmonary diseases. The median procedure time was 23 min (range 2–126 min), and pathologic diagnoses included adenocarcinoma (n = 29), dysplasia (n = 10), and hyperplastic polyp (n = 5). Compared with the control group, smoking (current smoker vs. never smoker, odds ratio [OR] 2.366, p = 0.021), total procedure time (OR 1.011, p = 0.048), and hemostasis time (OR 1.026, p = 0.028) were risk factors for the development of pneumonia. In multivariate analysis, age >65 years (OR 2.073, p = 0.031), smoking (current smoker vs. never smoker, OR 2.324, p = 0.023), and hemostasis time (OR 1.025, p = 0.038) were independent risk factors. All patients recovered from pneumonia, and the duration of hospital stay did not differ between patients with pneumonia and the control group (p = 0.077).

Conclusions

Whereas old age, smoking, and longer hemostasis time are risk factors for pneumonia, its incidence after ER is not associated with clinically significant adverse outcomes.     

Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome

Purpose

With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome.

Methods

303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30).

Results

All patients were male, median age was 39 years. Main routes of transmission were MSM (95 %) and IVDU (3 %). 69 % of patients were infected with HCV GT 1, 4.3 % with GT 2, 10.6 % with GT 3, 16.1 % with GT 4. Overall SVR rate was 69.3 % (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94 % vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR.

Conclusions

Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.

     

Response to peginterferon-alpha 2b and ribavirin in Japanese patients with chronic hepatitis C genotype 1

Purpose

Patient age and gender may be associated with response to peginterferon alpha plus ribavirin, the current standard of care (SOC) for chronic hepatitis C genotype 1. We queried whether there was an association between age, gender, and treatment response to SOC in Japanese patients infected with hepatitis C virus (HCV) genotype 1.

Methods

Between 2006 and 2009, HCV-infected Japanese patients treated with peginterferon alpha-2b plus ribavirin for 48 weeks were enrolled. Patients were allocated into four groups according to age and gender, and epidemiological data and treatment outcomes were retrospectively analyzed. HCV RNA was measured with COBAS AMPLICOR HCV Monitor Test v. 2.0.

Results

The overall sustained virological response (SVR) rate was 49.8%: patients aged ≤65 and >65 years, 50.9 and 44.0%, respectively; male and female, 56.5 and 39.0%. SVR rates of SOC against HCV genotype-1 females aged >65 years (19.0%) were inferior to those in males aged >65 years (57.8%) in Japan. Multivariate logistic regression analysis showed that SVR was attained independently of adherence 80/80/80 in all groups.

Conclusions

Adherence to medication is also a key factor for the eradication of HCV in patients aged >65 years. As the SVR rate of patients aged ≤65 years was similar to that of patients aged >65 years, SOC could be useful for treating some of the elderly patients.     

Surgeon’s Volume Is Not Associated with Complication Outcome After Laparoscopic Cholecystectomy

Aim

Complication rates after laparoscopic cholecystectomy vary but are still reported to be up to 17 %. Identifying risk factors for an adverse complication outcome could help to reduce morbidity after laparoscopic cholecystectomy. Our aim was to analyze whether surgeon volume is a vital issue for complication outcome.

Methods

All complications—minor, major, local and general—were reviewed in a single institution between January 2004 and December 2008 and recorded in a database. Patient’s variables, disease related variables and surgeon’s variables were noted. The role of surgeon’s individual volume per year was analyzed. A stepwise logistic regression model was used.

Results

A total of 942 patients were analyzed, among which 70 (7 %) patients with acute cholecystitis and 52 (6 %) patients with delayed surgery for acute cholecystitis. Preoperative endoscopic retrograde cholangiography (ERC) had been performed in 142 (15 %) patients. Complication rates did not differ significantly for surgeon’s individual volume (≤10 vs. >10 LC/year, 5.2 vs. 8.2 %, p = 0.203) nor for specialization (laparoscopic vs. non-laparoscopic; 9.2 vs. 6.4 %, p = 0.085) and experience (specialty registration ≤5 vs. >5 years; 5.1 vs. 8.7 %, p = 0.069). The only significant predictors for complications were acute surgery (OR 3.9, 95 % CI 1.8–8.7, p = 0.001) and a history preceding laparoscopic cholecystectomy (LC) (ERC and delayed surgery for cholecystitis) (OR 8.1, 95 % CI 4.5–14.6: p <0.001).

Conclusion

Complications after LC were not significantly associated with a surgeon’s individual volume, but most prominently determined by the type of biliary disease.     

The Association of Genetic Variants with Hepatic Steatosis in Patients with Genotype 1 Chronic Hepatitis C Infection

Background

Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined.

Aim

We sought to validate these associations and to explore their impact on treatment response to peginterferon and ribavirin therapy.

Methods

A total of 972 G1 HCV-infected Caucasian patients were genotyped for the SNPs rs12979860 (IL28B) and rs2896019 (PNPLA3). Multivariable analysis tested IL28B and PNPLA3 for association with the presence of any steatosis (>0 %); clinically significant steatosis (>5 %); steatosis severity (grade 0–3/4); and the interacting associations of the SNPs and hepatic steatosis to sustained viral response (SVR).

Results

IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10^?7; rs2896019, p = 7.56 × 10^?4); clinically significant steatosis (rs12979860, p = 1.82 × 10^?3; rs2896019, p = 1.27 × 10^?4); and steatosis severity (rs12979860, p = 2.05 × 10^?8; rs2896019, p = 2.62 × 10^?6). Obesity, hypertriglyceridemia, hyperglycemia, liver fibrosis, and liver inflammation were all independently associated with worse steatosis. Hepatic steatosis was associated with lower SVR, and this effect was attenuated by IL28B. PNPLA3 had no independent association with SVR.

Conclusions

IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis. IL28B attenuates the association between steatosis and SVR. Remediable metabolic risk factors remain important, independently of these polymorphisms, and remain key therapeutic goals to achieve better outcomes for patients with HCV-associated hepatic steatosis.     

Favorable adverse event profile of sofosbuvir/ribavirin compared to boceprevir/interferon/ribavirin for treatment of hepatitis C

Background

Triple therapy for the treatment of hepatitis C virus (HCV) with first-generation directly acting antiviral agents, the non-structural serine protease inhibitors boceprevir (BOC) and telaprevir have resulted in improved sustained virologic response (SVR) rates. However, a high incidence of adverse events (AEs), high pill burdens and drug interactions remain significant barriers to successful completion of therapy. The aim of this study was to evaluate the AEs observed with BOC triple therapy in comparison to IFN-free sofosbuvir/ribavirin (SOF/RBV) therapy in HCV monoinfected, genotype-1 (GT-1) individuals.

Methods

We retrospectively evaluated HCV monoinfected, treatment-naïve or -experienced, GT-1 individuals treated with either BOC/IFN/RBV at the Veterans Affairs Medical Center, Baltimore (n = 97) or SOF/RBV in the NIAID SPARE clinical trial (n = 60). AEs, namely hematologic (hemoglobin, neutrophil and platelet counts), hepatic (alanine transaminase or bilirubin) and renal (eGFR), were measured according to the DAIDS toxicity table (version 1.0).

Results

BOC/IFN/RBV was associated with significantly more AEs, most commonly neutropenia, anemia and thrombocytopenia. In the SOF/RBV cohort, five (8 %) patients discontinued treatment early, but none (0 %) were because of AEs, while 60 (62 %) patients on triple therapy discontinued treatment early, 34 (57 %) because of AEs. SVR24 rates were 68 versus 34 % with SOF/RBV versus BOC/IFN/RBV.

Conclusions

SOF/RBV treatment was associated with fewer side effects than BOC-based triple therapy, appearing to be a safer and more tolerable alternative for HCV GT-1 subjects. These results show that emerging IFN-free therapies may enhance patient adherence, allowing treatment of larger number of patients with improved efficacy.