Sustained Virological Response in Chronic Hepatitis C Patients after a 6- and a 36-Month Interferon-a2b Treatment Schedule. A Multicenter,Randomized, Controlled Study

With the introduction of medical treatment (chenodeoxycholic acid therapy) of cholesterol gallstones, the prediction of the gallstone type, cholesterol — non-cholesterol stones (i.e. cholesterol predominating or not), has become important. In 24 consecutive patients admitted for surgery because of gallstones, the value of various criteria for differentiation between the two types of stones was assessed. It is concluded that the combined requirements of radiolucency of the stones and a cholesterol saturation index in duodenal bile above 1.00 constitutes a fairly reliable method for selection of patients for dissolution therapy with chenodeoxycholic acid.     

Response of Combination Therapy on Viral Load and Disease Severity in Chronic Hepatitis C

Influence of genotypes on viral kinetics and disease severity in chronic hepatitis C (CH-C) patients has been implicated, but requires further investigation. The 41 HCV patients were genotyped by restriction fragment length polymorphism and included for 48 weeks of combination therapy on the basis of clinical (alanine amino transferase ≥60 IU/l) and histological features (histological activity index ≥3). A significant number (30/41) of patients (6/9 of genotype 1, 23/30 of genotype 3 and 1/2 of mixed genotype) attain sustained virological response despite high viral load at baseline. More aggressive treatment was required in genotype 1 than in genotype 3 due to slow response rate. Significant (P < 0.05) difference in the viral load of sustained virological responder and non-responder (NR) was observed after 12 weeks of therapy. Severe course of liver disease was observed in 81.81% (9/11) of NR patients at baseline. Data indicate that genotype 1 was a slow responder compared to genotype 3 on combination therapy. Response to combination therapy was almost independent of baseline viral load. However, a positive correlation of viral load with disease severity was observed. The viral kinetics at 12 weeks is an important tool for determination of virological response.     

α-干扰素联合阿昔洛韦治疗丙型肝炎的疗效分析

将21例丙型肝炎病毒(HCV)RNA阳性的丙型肝炎患者随机分成α-干扰素(IFN-α)联合阿昔洛韦(ACV)、单用IFN-α和支持治疗组。IFN-α3Mu隔日肌肉注射,共3个月。联合组并用ACV0.75静脉滴注,每日1次,共2个月。支持治疗组仅口服保肝药物。治疗结束时,3组谷丙酶(ALT)复常率分别为75％、50％和40％,HCV RNA转阴率分别为87.5％、25％和0％。随访10个月,3组的ALT正常率分别为100％、62.5％、20％,HCV RNA阴性率分别为87.5％、37.5％和20％。本研究表明,IFN-α联合ACV治疗丙型肝炎效果优于单用IFN-α和保肝支持治疗。5例HCV基因Ⅱ型者,治疗结束时仅1例HCV RNA转阴,提示Ⅱ型者耐IFN-α。     

慢性活动性肝炎,肝硬化患者HBV与HCV的合并感染及其意义

５８例慢性活动性肝炎，肝硬化患者中，发现乙肝表面抗原阳性４２例，抗ＨＣＶ阳性１６例，ＨＣＶ与ＨＢＶ合并感染１１例。１６例ＨＣＶ感染患者ＨＢｓＡｇ阳性率为５３．３％。ＨＣＶ与ＨＢＶ合并感染的慢性活动性肝炎患者，其谷丙转氨酶明显升高，而在肝硬化患者ＨＣＶ与ＨＶＢ合并感染对γ－ＧＴ，血清γ－球蛋白和血清白蛋白也有明显改变。     

HCV基因型对慢性丙型肝炎干扰素疗效的影响

目的 探讨HCV基因型对慢性丙型肝炎的干扰素（IFN）治疗效果的影响。方法 采用随机、开放和对照的多中心临床试验设计。208例受试者按1：1随机分到聚乙二醇干扰素α—2a(Peg-IFN）组和IFN-α-2a组。在治疗之前，用Simmonds基因分型法酶切分型，在治疗24周结束和完成24周的随访后检测患者的ALT和HCV RNA，以HCV RNA的阴转率作为主要评价指标，经ITT人群的统计学分析。结果 202例患者确定了HCV基因型，基因1型158例（78.2%），非基因1型44例（21.8%），治疗结束病毒应答率（ETVR）和持续病毒应答率（SVR）基因1型患者分别为53.8%和25.3%，非基因1型患者分别为61.4%和43.2%，SVR两组患者差异有显著性，x^2=5.313,P=0.021。Peg IFN组基因1型和非1型患者的ETVR分别为76.8%和81.0%，SVR分别为35.4%和66.7%，SVR两组患者差异有显著性，x^2=6.735,P=0.01。病毒复发率基因1型和非基因1型患者分别为55.6%和23.5%，差异有显著性，x^2=5.496,P=0.02.IFN-α-2a组，ETVR和SVR基因1型患者分别为29.0%和14.5%，非基因1型患者分别43.5%和21.7%，差异无显著性。病毒复发率基因1型患者为72.7%，非基因1型患者为50.0%，差异无显著性。结论 IFN对基因1型丙型肝炎患者的疗效低于非基因1型，HCV基因型主要影响IFN对慢性丙型肝炎的持续应答，也与药物和IFN的疗程相关。     

Cost-effectiveness of Interferon Alfa-2b With and Without Ribavirin as Therapy for Chronic Hepatitis C in Sweden

Background: Recent trials have shown that treatment with a combination of interferon alfa-2b and ribavirin results in sustained loss of detectable hepatitis C-virus (HCV) RNA in a higher proportion of patients than treatment with interferon alone. Combination therapy, however, is two to three times as expensive as monotherapy. Methods: Based on data from recent randomized clinical trials and a previously published decision model, we developed a Markov model to estimate the cost-effectiveness of initial combination therapy with interferon and ribavirin versus interferon alone for previously untreated patients with chronic HCV infection in Sweden. Clinical praxis and quality adjustments were based on expert estimates and costs were gathered from different health care providers in Sweden. Results: Combination therapy for 24 or 48 weeks, compared to interferon alone, prolonged quality adjusted life expectancy by 0.5 to 1.1 years at marginal cost-effectiveness ratios of US$ 1,400 to US$ 6,000 per DQALY (discounted quality-adjusted life-year) for patients with genotype 1. In genotype 1, 48 weeks compared to 24 weeks of combination therapy prolonged quality adjusted life expectancy by 0.6 years at a marginal cost-effectiveness ratio of $US 9,800 per DQALY. For patients with genotype non-1, combination therapy for 24 or 48 weeks, compared to interferon alone, prolonged quality adjusted life expectancy by 2.3 years, with combination therapy for 24 weeks being money-saving. The results were robust in sensitivity analyses. Conclusion: Combination therapy with interferon and ribavirin increased quality-adjusted life expectancy and was cost-effective for patients with chronic hepatitis C.     

Rapid Virological Response Represents the Highest Prediction Factor of Response to Antiviral Treatment in HCV-Related Chronic Hepatitis: a Multicenter Retrospective Study

Background:

Standard [i.e. pegylated interferon (Peg-IFN) + ribavirin] treatment of hepatitis C virus (HCV)-related chronic hepatitis is associated with a sustained virological response (SVR) in 50 - 90% of patients. A rapid virological response (RVR) (i.e. negative HCV-RNA after 4 weeks of treatment) predicts SVR in almost 90% of patients.

Objectives:

The main aim of this study was to assess the strength of RVR, as a predictive factor of antiviral treatment response.

Patients and Methods:

Using univariate and multivariate analysis, we retrospectively evaluated biochemical, metabolic, genetic and viral variables that might affect both RVR and SVR to Peg-IFN plus ribavirin, in 315 consecutive outpatients affected by HCV-related chronic hepatitis.

Results:

At univariate analysis, staging, body mass index, RVR, genotype and viral load were significantly related to SVR (P < 0.001). At multivariate analysis, RVR and genotype remained significant (P < 0.00001). The RVR had a predictive value of 83%. At univariate and multivariate analyses, diabetes (P = 0.003), genotype 2 (P = 0.000) and HCV-RNA values (P = 0.016) were independent predictors of RVR, even though at multivariate analyses, only genotype 2 was significantly related to RVR. When we stratified patients, according to genotype, no laboratory or clinical factors were predictive of RVR in genotype 1 patients at either univariate or multivariate analysis. In genotype 2 patients, staging (P = 0.029) and diabetes (P = 0.001) were the only significant predictors of RVR at univariate analyses, whereas no factor was independently related to RVR, at multivariate analysis.

Conclusions:

The RVR is the strongest factor of SVR and infection with HCV genotype 2 is significantly associated with RVR. Neither biochemical and/or metabolic factors seem to exert influence on RVR.     

Symptomatic and Virological Response to Antiviral Therapy in Hepatitis C Associated with Extrahepatic Complications of Cryoglobulimia

Mixed cryoglobulins are detected in 50% of patients with hepatitis C; fortunately, few have vasculitis affecting skin, peripheral nerves, kidneys, and synovia. This study was designed to identify the natural history of symptomatic cryoglobulinemia and evaluate the response to antiviral therapy. Patients with hepatitis C complicated by symptomatic cryoglobulinemia were assessed for their disease manifestations and response to antiviral therapy. Of 83 patients identified, 56 patients with a minimum of 12 months follow-up were reviewed. Manifestations included dermatologic (75%), rheumatologic (57%), neurologic (34%), and renal (proteinuria 25%). Antiviral therapy was given to 38, of whom 9 were retreated for symptomatic and/or virological nonresponse. Antiviral therapy included interferon monotherapy (n= 8), pegylated-interferon monotherapy (n= 5), consensus-interferon (n= 2), interferon + ribavirin (n= 18), and pegylated-interferon + ribavirin (n= 14). Treatment provided sustained symptomatic response in 31 (82%) and virological response in 16 (42%) patients. Symptomatic cryoglobulinemia responds well to antiviral therapy, even when virological response is not achieved.     

丙型肝炎病毒负荷和基因型与干扰素治疗应答关系的研究

目的　研究丙型肝炎 (简称丙肝 )病毒基因分型和病毒负荷与干扰素抗病毒治疗的应答关系。方法　用特异性引物PCR的改良法检测基因型 ,用荧光PCR方法检测病毒负荷 ,接受干扰素治疗的慢性丙肝患者根据不同的基因型及病毒负荷进行应答分组比较。结果　治疗前HCV -RNA负荷小于 10 9eq·L-1患者经干扰素治疗后表现为持续应答状态占总人数的 4 2 9% ,HCV -RNA负荷大于 10 9eq·L-1患者经干扰素治疗后呈部分应答(2 8 6 % )或无应答状态 (2 8 6 % )。统计学上差异非常显著 (P <0 0 0 1)。 2a型和 1b +2a型 (共 11例 )疗效明显优于 1b型 (2 2例 ) ,差异非常显著 (P <0 0 0 1)。结论　对HCV -RNA负荷小于 10 9eq·L-1及 2a +1b、2a型患者干扰素治疗效果较好。HCV病毒负荷及基因分型可能影响对干扰素治疗的应答。     

Hepatitis C Treatment in Patients With Porphyria Cutanea Tarda

Background

Hepatitis C virus (HCV) infection is a common susceptibility factor for porphyria cutanea tarda (PCT). Experience on HCV treatment in patients with PCT is limited. Recently, HCV treatment has improved with direct-acting antivirals (DAA). We review our experience on HCV treatment in patients with PCT with older and newer regimens.

Fas Antigen Expression on Hepatocytes Predicts the Short- and Long-term Response to Interferon Therapy in Patients with Chronic Hepatitis C

Background: Interaction between Fas antigen on hepatocytes and Fas ligand on cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV)-induced hepatocyte injury. We investigated the usefulness of Fas expression on hepatocytes as a predictor of short- and long-term response to interferon (IFN) therapy in 72 patients with chronic hepatitis C. Methods:     

The Effect of Combination Therapy with Interferon and Cryofiltration on Mesangial Proliferative Glomerulonephritis Originating from Mixed Cryoglobulinemia in Chronic Hepatitis C Virus Infection

Abstract: Cryofiltration, which has developed from double filtration plasmapheresis (DFPP) with a cooling unit, is an on-line technique to remove cryoglobulin. We report on a patient who suffered from progressive edema and renal insufficiency caused by cryoglobulinemic membranoproliferative glomerulonephritis (MPGN), probably due to chronic hepatitis C virus (HCV) infection. To remove cryoglobulins and terminate the HCV infection, we utilized combination therapy with cryofiltration and interferon-α injection with corticosteroids. Interferon-α was capable of decreasing proteinuria but not diminishing cryoglobulin. Additional cryofiltration could remove cryoglobulin to an undetectable level. This combination therapy was partially successful to reduce proteinuria and prevent the progressive deterioration of renal function. The major adverse effects of this therapy were bleeding and myelosuppression. We conclude that this combination therapy may be effective and should be considered as treatment for cryoglobulinemic MPGN.     

GB Virus C/Hepatitis G Virus Infections in Traumatologic Outpatients, Chronic Non-A-E Hepatitis and Extrahepatic Malignancies

Summary GB virus C/hepatitis G virus (GBV-C/HGV) is a recently discovered flavivirus of still unknown pathogenic relevance. We examined traumatologic outpatients to determine GBV-C/HGV viremia for further epidemiological studies, as blood donors hitherto used as controls represent healthy individuals without risk factors. Anti-GBV-C/HGV antibodies were detectable in 13.2% (95% confidence interval [CI] 9.3–18.2) and GBV-C/HGV RNA was detectable in 4.5% (95% CI 2.4–8.2) of the outpatients. In chronic non-A-E hepatitis patients GBV-C/HGV viremia was detectable at a significantly higher level of 16.1% (95% CI 6.1–:34.5), while the prevalence of anti-GBV-C/HGV antibodies was 12.9% (95% CI 4.2–30.8). The rate of GBV-C/HGV viremia in patients with malignant diseases (different types of tumors, blood recipients were excluded) was 12.5% (95% CI 8.4– 18.1), a significant elevation compared to traumatologic outpatients. The seroprevalence in the tumor group was 22.1% (95% CI 16.7–28.6), also significantly elevated. Thus, there are two messages. Firstly, testing for GBV-C/HGV may be a useful extension of the diagnostic procedure of viral hepatitis. Secondly, common risk factors or etiologic relations of GBV-C/HGV and extrahepatic malignancies should be discussed. Received: March 29, 1999 · Revision accepted: November 22, 1999     

Hepatitis C virus recurrence after liver transplantation:A 10-year evaluation

AIM: To evaluate the predictors of 10-year survival of patients with hepatitis C recurrence. METHODS: Data from 358 patients transplanted between 1989 and 2010 in two Italian transplant centers and with evidence of hepatitis C recurrence were analyzed. A χ2, Fisher's exact test and Kruskal Wallis' test were used for categorical and continuous variables, respectively. Survival analysis was performed at 10 years after transplant using the Kaplan-Meier method, and a log-rank test was used to compare groups. A P level less than 0.05 was considered significant for all tests. Multivariate analysis of the predictive role of different variables on 10-year survival was performed by a stepwise Cox logistic regression.RESULTS: The ten-year survival of the entire population was 61.2%. Five groups of patients were identified according to the virological response or lack of a response to antiviral treatment and, among those who were not treated, according to the clinical status(mild hepatitis C recurrence, "too sick to be treated" and patients with comorbidities contraindicating the treatment). While the 10-year survival of treated and untreated patients was not different(59.1% vs 64.7%, P = 0.192), patients with a sustained virological response had a higher 10-year survival rate than both the "non-responders"(84.7% vs 39.8%, P 0.0001) and too sick to be treated(84.7% vs 0%, P 0.0001). Sustained virological responders had a survival rate comparable to patients untreated with mild recurrence(84.7% vs 89.3%). A sustained virological response and young donor age were independent predictors of 10-year survival. CONCLUSION: Sustained virological response significantly increased long-term survival. Awaiting the interferon-free regimen global availability, antiviral treatment might be questionable in selected subjects with mild hepatitis C recurrence.     

Baseline High Viral Load and Unfavorable Patterns of Alanine Aminotransferase Change Predict Virological Relapse in Patients With Chronic Hepatitis C Genotype 1 or 2 Obtaining Rapid Virological Response During Antiviral Therapy

Background

Rapid virological response (RVR) strongly predicts sustained virological response (SVR) in patients with chronic hepatitis C (CHC), and abbreviates antiviral therapy in some patients.

Objectives

To identify factors predicting virological relapse (VR) in CHC patients who attained RVR.

Patients and Methods

Medical records of 133 CHC patients with an RVR after completing 24 weeks of antiviral therapy (a combination of pegylated interferon-α and ribavirin) were analyzed. Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR. Patients with normal alanine aminotransferase (ALT) levels at weeks 4 and 12 and at the end-of-treatment (EoT) and patients with elevated, but constantly decreasing, ALT levels were classified as having favorable patterns of ALT change. A trend of increasing ALT levels either between weeks 4 and 12 or between weeks 12 and EoT was classified as unfavorable. A high viral load (HVL) was defined as a baseline HCV RNA ≥ 600000 IU/mL.

Results

In total, 116 (87.2%) patients had a SVR and 14 (10.5%) had VR. The VR rates were comparable between patients with genotype-1 (13.1%) and genotype-2 infection (8.7%) (P = 0.572). Multivariate analysis revealed that HVL (P = 0.015; odds ratio [OR] = 14.754; 95% confidence interval (CI) = 1.671–130.240), and unfavorable ALT patterns (P = 0.039; OR = 4.397; 95% CI = 1.078–17.930) independently predicted VR. In subgroup analysis, low viral load (LVL) patients had a minimal VR rate (1.8%). Among the HVL patients, the VR rate of those using peg-IFN-α-2a was relatively low (9.1%). Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005).

Conclusions

In southern Taiwan, 24 weeks of antiviral therapy achieved a high SVR rate in patients with CHC attaining RVR, except in the subgroup of patients treated with peg-IFN-α-2b with HVL and on-treatment unfavorable ALT patterns.     

Real Response to Therapy in Chronic Hepatitis C Virus Patients: A Study From Iran

Background

Despite significant advances in the treatment of chronic hepatitis C in the past decades, factors which can affect response rates to combination therapy; peginterferon and ribavirin, are still under study and reaching sustained virological response (SVR) is affected by several different factors.

Objectives

To investigate predictor factors contributing to SVR in Iranian patients.

Patients and Methods

The present non-randomized, clinical trial was conducted on 100 patients referred to the Tehran Hepatitis Center in 2009-2011. The patients were administered combined peginterferon α-2a-ribavirin treatment, based on the standard protocol of the Iranian Ministry of Health. At the end of the treatment, the SVR rate and predictors were evaluated.

Results

The mean age of the patients was 42 and 78% were male. Genotype 1a was the most common (70%) and 55% of patients were treatment naïve. The outcomes showed that 12%, 16% and 22% patients were; non-responders, breakthroughs and relapsers, respectively, while 50% of the patients reached SVR. Patients reaching SVR were aged 40 years or lower, they were less likely to have been a non-responder in prior treatments, more likely to have a non-1a genotype and a higher number had an HCV RNA of less than 600 000 IU/ml. The multivariate analysis showed that an age of 40 or lower (OR = 3.74, CI95% = 1.52-9.22), a non-1a genotype (OR = 3.71, CI 95% = 1.40-9.81) and an HCV RNA less than 600 000 IU/ml (OR = 2.52, CI 95% = 1.03-6.15) may be useful SVR predictors.

Conclusions

The findings of the present study showed that half of the patients reached SVR through combined peginterferon α-2a and ribavirin treatment, the majority of whom had genotype 3a and a minority had genotype 1a. In addition, an age of 40 or lower, non-1a genotype and a viral load less than 600 000 IU/ml were strong SVR predictors.