Efficacy and Tolerability of Peginterferon alpha-2a and Peginterferon alpha-2b in Iranian Patients With Chronic Hepatitis C

Background:

Nearly 0.5% of Iranians are infected with HCV. Peginterferon-alpha-2a and Peginterferon-alpha-2b are the two available types of interferon for the treatment of hepatitis C. Comparing the results of these two treatments is still a challenge.

Objectives:

The aim of this study was to compare the results of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients with chronic hepatitis C.

Patients and Methods:

289 patients with chronic hepatitis C attending Tehran Hepatitis Center (THC) and Hepatitis Clinic of Tehran Blood Transfusion Organization (TBTO) from January 2008 to April 2013 and treated with combination of Peginterferon-alpha-2a or Peginterferon-alpha-2b plus Ribavirin were enrolled in this retrospective cross-sectional study. Treatment response and side effects were compared.

Results:

Among all naive patients, 82.0% achieved SVR, 5.4% were resistant to therapy and 11.0% withdrew the treatment. Relapse was seen in 12.2% of naive patients who finished the course of treatment. RVR and EVR were seen in 67.7% and 90.6% of naive patients, respectively. Patients divided into two groups. Group A consists of 247 patients treated with Peginterferon-alpha-2a and group B 42 patients treated with Peginterferon-alpha-2b. No significant difference in treatment response was observed between naive patients of the two groups. The rates of arthralgia/myalgia, alopecia, pruritus, insomnia, dyspnea and anorexia were higher in group A and the rates of dermal problems, coryza and bleeding were higher in group B. In a subgroup analysis, the two kinds of Peginterferon-alpha-2a available in Iran were compared. Rapid and early viral responses and relapse rates were lower in the one made in Iran and the long-term responses were not different. The rates of arthralgia/myalgia, fever, alopecia, pruritus, insomnia, dyspnea, anorexia, cough, headache and abdominal pain were higher and the rates of irritability and coryza were lower in the one made in Iran.

Conclusions:

There was no significant difference in the efficacy of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients. Physicians might choose the treatment regimen for every individual concerning the differences in side effects of Peginterferons.     

Direct Medical Care Costs Associated With Patients Diagnosed With Chronic HCV

Background

HCV virus (HCV) is a significant global problem with wide-ranging socio-economic impacts. Because of the high morbidity and mortality associated with end-stage liver disease, cirrhosis, and hepatocellular carcinoma (HCC), the economic burden of HCV infection is substantial.

Objectives

This study aimed to estimate the direct medical care costs of chronic HCV infection.

Patients and Methods

For this cross-sectional study, 365 courses of HCV treatment were extracted from medical records of 284 patients being referred to Tehran HCV clinic, a clinical clinic of Baqiyatallah Research Center for Gastroenterology and Liver diseases, from 2005 to 2010. All the patients had been diagnosed with HCV. Direct medical care costs for each course of HCV treatment have been calculated based on Purchasing Power Parity Dollar (PPP$).

Results

Average direct medical costs for the courses treated with conventional interferon plus ribavirin (INF-RBV) were 4,403 PPP$, and 20,010 PPP$ for peg-interferon plus ribavirin (PEG-RBV) courses. There was an increase of the direct costs in both courses of treatment to achieve Sustain Viral Response (SVR). The costs amounted to 10,072 PPP$ in (INF-RBV) treatment and 34,035 PPP$ in (PEG-RBV). The significant difference between the costs of these two courses of treatment is attributable to high cost of Peg-interferon. This indicates that the medication costs are the dominant costs.

Conclusions

According to the results, total direct medical costs for HCV patients in Iran exceeded 12 billion PPP$ in (INF-RBV) treatment and 55 billion PPP$ in (PEG-RBV).     

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.     

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.     

Cost-Effectiveness Analysis of Adding Low Dose Ribavirin to Peginterferon Alfa-2a for Treatment of Chronic Hepatitis C Infected Thalassemia Major Patients in Iran

Background

The prevalence of hepatitis C in Iran is 1% and 18% in general population and thalassemia patients respectively. The cost effectiveness analysis of adding Ribavirin to Peginterferon alfa-2a (PEG IFN alfa-2a) as a combination treatment strategy of chronic hepatitis C in thalassemia patients in comparison with monotherapy could help clinicians and policy makers to provide the best treatment for the patients.

Objectives

In this study we aimed to assess whether adding Ribavirin to PEG IFN alfa-2a is a cost effective strategy in different genotypes and different subgroups of 280 patients with chronic hepatitis C infection from the perspective of society in Iranian setting.

Patients and Methods

A cost effectiveness analysis including all costs and outcomes of treatments for chronic hepatitis C infected thalassemia major patients was conducted. We constructed a decision tree of treatment course in which a hypothetical cohort of 100 patients received “PEG IFN alfa-2a” or “Peg IFN alfa-2a plus Ribavirin.” The cost analysis was based on cost data for 2008 and we used 9300 Iranian Rials (IR Rial) as exchange rate declared by the Iranian Central Bank on that time to calculating costs by US Dollar (USD). To evaluate whether a strategy is cost effective, one time and three times of GDP per capita were used as threshold based on recommendation of the World Health Organization.

Results

The Incremental Cost Effectiveness Ratio (ICER) for combination therapy in genotype-1 and genotypes non-1 subgroups was 2,673 and 19,211 US dollars (USD) per one Sustain Virological Response (SVR), respectively. In low viral load and high viral load subgroups, the ICER was 5,233 and 14,976 USD per SVR, respectively. The calculated ICER for combination therapy in subgroup of patients with previously resistant to monotherapy was 13,006 USD per SVR. Combination therapy in previously resistant patients to combination therapy was a dominant strategy.

Conclusions

Adding low dose of Ribavirin to PEG IFN alfa-2a for treatment of chronic hepatitis C patients with genotype-1 was “highly cost effective” and in patients with low viral load and in previous monotherapy resistant patients was “cost effective.”     

The Impact of Interleukin 28b Gene Polymorphism on the Virological Response to Combined Pegylated Interferon and Ribavirin Therapy in Chronic HCV Genotype 4 Infected Egyptian Patients Using Data Mining Analysis

Background: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1.Objectives: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis.Patients and Methods: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene.Results: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response.Conclusions: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.     

Amino Acid Polymorphisms Within the Entire HCV NS5A Region in Estonian Chronic HCV 1b Patients With Different Treatment Response

Background

A substantial proportion of hepatitis C virus (HCV)-1b infected patients do not response to pegylated interferon-α plus ribavirin (PegIFNα/RBV) combination therapy that was partially associated with mutations in the non-structural 5A (NS5A) protein.

Objectives

Analysis of NS5A polymorphisms in HCV genotype 1b pre-treatment serum samples from Estonian patients and their effect on the treatment response.

Patients and Methods

Twenty-nine complete NS5A sequences obtained from patients with chronic HCV-1b infection who had received combined therapy with PegIFNα-2a/RBV were analyzed and compared with the prototype strain HCV-J. Twelve patients achieved a sustained virological response (SVR), 15 were non-SVR and 2 patients stopped treatment because of side effects.

Results

No significant difference in total number of amino acid mutations was observed between isolates from SVR and non-SVR patients in any known regions of the NS5A protein. However, specific amino acid substitutions at positions 1989 and 2283 correlated significantly with SVR, mutations at positions 1979, 2107, 2171 and 2382 were associated with non-response to treatment and amino acid substitution at position 2319 was observed in relapsers. At phylogenetic analysis, NS5A nucleotide sequences have been subdivided into four groups characterized by the different treatment response. Twenty-four novel nucleotide polymorphisms and 11 novel amino acid polymorphisms were identified based on the phylogenetic tree topology.

Conclusions

Specific amino acid substitutions correlating with the treatment response were found. Polymorphisms revealed by phylogenetic analysis may define the signature patterns for treatment susceptible and treatment resistant strains prevalent in Estonia.     

Serum IP-10 Levels Correlate with the Severity of Liver Histopathology in Patients Infected with Genotype-1 HCV

Background/Aims

Interferon-γ-inducible protein 10 (IP-10) plays important roles in the pathogenesis of hepatitis C virus (HCV) infection. We investigated the association between serum IP-10 levels and liver pathology in patients with chronic HCV infection.

Methods

The serum IP-10 concentration was assessed in 85 patients with chronic HCV infection using a solid phase sandwich enzyme-linked immunosorbent assay, and a liver biopsy specimen was obtained. The pathology was scored using the Knodell histologic activity index (HAI).

Results

Of the 85 patients, 58 had genotype 1 HCV infection, 21 had genotype non-1, and 6 were undetermined. The serum IP-10 levels did not differ between patients infected with genotype 1 and genotype non-1 (p=0.472). In patients with genotype 1 infection, the total HAI score and the stage of fibrosis were highly correlated with the serum IP-10 level (r=0.555, r=0.578, p<0.001). Furthermore, the serum IP-10 concentrations of patients with severe fibrosis (stages 3, 4) were higher than those of patients with mild fibrosis (stages 0 to 2; 214.4 vs. 72.3 pg/mL, p=0.002) among patients with genotype 1 infection. However, in patients without genotype 1 infection, the histopathology was not associated with the serum IP-10 level. A multivariate analysis showed that serum IP-10 was an independent predictor of fibrosis (stages 3, 4) in patients with genotype 1 infection (odds ratio, 1.034; 95% confidence interval, 1.006 to 1.064; p=0.018).

Conclusions

Serum IP-10 concentration was significantly correlated with the severity of liver histology in genotype 1 HCV infection.     

The comparative efficacy and safety of peginterferon alpha-2a vs. 2b for the treatment of chronic HCV infection: a meta-analysis

Background and Aims

Two types of peginterferon, alpha-2a (PEG-IFN-α2a) and 2b (PEG-IFN-α2b), are approved for the treatment of hepatitis C infection. Several high-quality studies have compared the efficacy of these two types of interferon, but it seems that any of these trials had inadequate statistical power on their own to find even a tiny difference between these two medicines. We pooled the available data in the literature to find any small difference between these two medicines.

Methods

In a systematic review of the literature, randomized controlled trials comparing the use of PEG-α2a vs. 2b were assessed. The DerSimonian and Laird method was employed to run meta-analysis. The end points were virological responses.

Results

In 7 randomized controlled trials, 3518 patients were randomized to receive PEG-IFN-α2a + ribavirin (n=1762) or PEG-IFN-α2b + ribavirin (n=1756). Early virological response (EVR), early treatment response (ETR), and sustained virological response (SVR) were greater for patients treated with PEG-IFN-α2a. Odds Ratios (ORs) were 1.38 (95% confidence interval [CI] 1.11-1.71), 1.67 (95% CI 1.24-2.24), and 1.38 (95% CI 1.02-1.88) respectively. In the subset of naïve patients with genotype 1/4 and 2, ORs of SVR were 1.38 (95% CI 1.02-1.88) and 4.06 (95% CI 1.67-9.86) respectively. PEG-IFN-α2a had significantly higher rate of neutropenia OR=1.50 (95% CI 1.25-1.79) but pooled OR for withdrawal rates was not significant [OR=0.78 (95% CI 0.47-1.29)].

Conclusions

PEG-IFN-α2a with similar safety is more effective than PEG-IFN-α2b. A longer duration of maximum serum concentration compared with PEG-IFN-α2b (168 vs. 48-72 h.) yields a greater SVR and higher neutropenia in PEG-IFN-α2a recipients.     

Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3

BACKGROUND/AIMS: Treatment duration in patients with chronic hepatitis C in the era of standard interferon-alpha plus ribavirin was tailored according to hepatitis C virus (HCV) genotype: patients infected with HCV-1 were treated for 48 weeks, patients infected with HCV-2/3 for 24 weeks. The aim of the present study was to investigate this schedule for HCV-2/3 infected patients in the era of pegylated interferon-alpha plus ribavirin. METHODS: Patients chronically infected with HCV-2 (n=42) or HCV-3 (n=182) were treated with peginterferon alfa-2b 1.5 microg/kg subcutaneously once weekly plus ribavirin 800-1400 mg/day based on body weight for 24 weeks. RESULTS: The end of treatment (EOT) and sustained virologic response (SVR) was higher in patients infected with HCV-2 (100 and 93%, respectively) than in patients infected with HCV-3 (93 and 79%, respectively). Baseline viremia (P=0.020), treatment duration >16 weeks (P<0.001) and steatosis (<5%, P=0.015) were significant independent predictors of SVR. Adverse events resulted in discontinuation in 5% and dose reduction in 22% of patients. CONCLUSIONS: Treatment for 24 weeks with peginterferon alfa-2b and ribavirin is sufficient in HCV 2 or 3 infected patients. The lower SVR in patients infected with HCV-3 compared with HCV-2 infected patients may be related to higher levels of steatosis in this population.     

Interferon Alfa-2b Alone or Combined with Recombinant Granulocyte-Macrophage Colony-Stimulating Factor as Treatment of Chronic Hepatitis C

Background: To compare the effect of combination therapy with interferon- α (INF- α ) and granulocytemacrophage colony-stimulating factor (GM-CSF) to monotherapy with INF- α in patients with chronic hepatitis C infection. Methods: Forty-five consecutive patients with chronic hepatitis C, all presenting with elevated serum alanine aminotransferases and viremia, were randomized to receive either 1) INF α + GM-CSF for 3 months followed by INF- α alone for 9 months ( n = 23) or 2) INF- α for 12 months ( n = 22). Both drugs were administered 3 times weekly in doses of 3 mU (INF- α ) and 50-100 μg depending on body weight (GM-CSF). Results: At baseline, there was no difference between the treatment groups in terms of age, sex, ALT level, viral load, genotype or histological activity and fibrosis in a pretreatment liver biopsy. After 12 months' treatment, more patients treated with GM-CSF + INF- α compared to patients receiving monotherapy had normalized ALT, 65% and 32%, respectively ( P = 0.03), but there was no difference in percentages of patients with viral clearance between the 2 groups, 48% and 32%, respectively ( P = 0.27). At 6 months' follow-up, the biochemical response had declined to 35% in the combination therapy group and to 23% in the monotherapy group ( P = 0.37); viral clearance had declined to 22% and 27%, respectively ( P = 0.67), and the overall sustained response rate was 22% and 23%, respectively ( P = 1.00). Conclusions: Even though patients receiving INF- α + GM-CSF had a significant better biochemical response during treatment compared to patients receiving monotherapy, the sustained biochemical and virological response was not increased. Thus, GM-CSF hardly plays any role in the future treatment of chronic hepatitis C.     

Impact of Pegylated Interferon-alfa-2a on Perforin Level in Patients With Chronic Hepatitis B; Preliminary Study

Background

Chronic hepatitis B is one of the most common causes of cirrhosis and hepatocellular toxicity in many countries, including Iran. Cytotoxic T lymphocyte (CTL) and Natural killer (NK) cells are the two of main cell populations considered as cytotoxic cells. One of the distinct pathways CTL and NK cells exert cytotoxicity is perforin/granzyme. After the cytotoxic cell/target cell junction, perforin is released from granules by exocytosis. Once it is anchored, perforin forms cylindrical pores through which granzymes and granulysin enter and induce apoptosis.

Objectives

Large controlled trials have demonstrated the efficacy of PEG-IFN-α-2a in treatment of chronic hepatitis B. This study was aimed to examine whether the enhancement of cytotoxicity by PEG-IFN-α-2a is mainly due to the perforin pathway.

Patients and Methods

This research work was performed on 50 patients and five healthy people. Patients with chronic hepatitis B were further subdivided into two groups: patients with inactive chronic hepatitis B (carriers, n = 30), and those with active chronic hepatitis B who were under treatment with PEG-IFN-alfa-2a (n = 20) for minimum six and maximum 12 months. Serum perforin level was measured using ELISA method (CUSABIO Company), HBV viral load was assessed using COBAS Taq-man, and we used Elecsys hepatitis B surface antigen (HBs Ag) II quantitative assay method for HBs Ag determination. HBeAg was evaluated by ELISA method, and AST and ALT were measured by routine laboratorymethods.

Results

Based on the results obtained serum perforin level in healthy group was 0.64 ng/mL, the mean of serum perforin level in inactive HBs Ag carriers was 2.63ng/mL, and 4.63 ng/mL in patients with active chronic hepatitis B under treatment with PEG-IFN-α-2a. The mean of serum perforin level in patients with and without virologic response to treatment were 5.45 ng/mL,and 3.4 ng/mL respectively. Finally in patients with virologic response and seroconverted serum perforin level was 7.23 ng/mL.

Conclusions

Based on our results higher perforin level in patients under treatment with PEG-IFN-α-2a, could be an indication of elevated cytotoxicity via perforin/granzyme pathway.     

A Study of CC-Chemokine Receptor 5 (CCR5) Polymorphism on the Outcome of HCV Therapy in Egyptian Patients

Background:

Chronic hepatitis C virus (HCV) infection is a globally serious public health issue.

Objectives:

In this study, we investigated CC chemokine receptor 5 (CCR5-59029) polymorphism which is considered an important component of the immune system in determining the outcome of HCV infection. Its critical role as a marker in response to interferon therapy of HCV infection is also investigated besides its effect on other clinical patient factors.

Patients and Methods:

This study was conducted on 82 Egyptian patients with chronic Hepatitis C Virus (HCV) infection who received PEG-INF + Ribavirin treatment for 48 weeks. The study was also conducted on 50 healthy controls (with negative results for HCV antibody and RNA PCR). Full history of patients in this study was recorded. Clinical and histological examinations, qualitative HCV nested RT-PCR, quantitative real –time PCR, and genotyping of HCV RNA genome were performed. CCR5-59029 polymorphism with nucleotide substitution from G to A was amplified. The amplicons were digested with restriction endonuclease Bsp 1286I, and produced RFLPs of the CCR5 genotypes were determined.

Results:

The present study showed a significant association between the functional SNP of CCR5 gene and the viral response to interferon in chronic HCV Egyptian patients. It was shown that the higher fibrosis stages (F2-F4) had significant association with nonresponse to treatment compared to the lower fibrosis stages (F0-F1) (95% confidence: 5.497 - 55.074, P = 0.0001). In addition, worse liver activity grade (A2-A3) had a very highly significant association with non-responder HCV patients compared to those with better liver activity grade (A1) (95% confidence: 2.242 - 20.974, P = 0.0007). Most importantly HCV patients with G allele had a high significant association with nonresponse to treatment, higher fibrosis stages and worse liver activity grades, while the A allele had a high significant association with sustained response, low fibrosis stages and relatively better liver activity grade (95% confidence: 3.347 - 15.036, P = 0.0001).

Conclusions:

SNPs within the CCR5 gene should be considered as an important factor used in combination with other host gene SNPs when developing a mathematical model for anticipating response to HCV therapy.     

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.     

Clinical Implications of Hepatic Steatosis in Patients with Chronic Hepatitis C: A Multicenter Study of U.S. Veterans

Studies have indicated a high prevalence of hepatic steatosis in patients with chronic hepatitis C (CHC). To address the impact of steatosis on the clinical course of CHC and treatment response requires large multicenter studies. The present study analyzed hepatitis C virus (HCV)-infected veterans enrolled in a U.S. Veteran Administration multicenter study of the epidemiology and response to interferon α-2b and ribavirin treatment. Of the 357 patients, 97.1% were males, with a mean age of 48.7±6.4 years, and 184 (51.5%) had hepatic steatosis. The mean body mass index (BMI) was 29.3±5.2 kg/m², including 37.1% who were obese (BMI, ≥30 kg/m²). Stage III–IV fibrosis was present in 111 of 334 (33.3%) of the patients. After adjusting for age, race, and history of alcohol use in the past 12 months, only stage III–IV fibrosis was independently and significantly associated with hepatic steatosis (P=0.03). There was a trend of association between obesity and steatosis independent of the other factors. Only HCV genotype was independently associated with a sustained virological response (SVR) to interferon α-2b and ribavirin treatment after adjusting for age, alcohol use, steatosis, BMI, stage III–IV fibrosis, serum AFP, and HCV load. In conclusion, analyses of our multicenter trial data demonstrated that the prevalence of hepatic steatosis is 51.5% in HCV-infected U.S. veterans. We found that steatosis is independently associated with stage III–IV fibrosis. However, only HCV genotype, and not steatosis, obesity, or stage III–IV fibrosis, was associated with SVR to interferon α-2b and ribavirin treatment. Other members of the VA HCV-001 Study Group are listed in the Appendix     

Real-Life Data on Sofosbuvir/Ledipasvir in Patients with Chronic Viral Hepatitis C Genotype 1b: A Single-Center Experience

BackgroundThe course of hepatitis C disease has changed with the use of direct-acting antiviral drugs in the treatment of the disease. The aim of this study was to evaluate the real-life efficacy and safety of the sofosbuvir/ledipasvir drug regimen in the treatment of patients with genotype 1b.MethodsTreatment-naive or -experienced 49 genotypes 1b patients treated with sofosbuvir/ledipasvir participated in the study. Laboratory and hepatitis C virus RNA values were evaluated at baseline, week 12, and week 24 of treatment (36th week for those who received 24 weeks of treatment).ResultsThe sustained virologic response rate was 100% in patients who completed treatment. At the end of the study, there was a significant decrease in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and alpha-fetoprotein levels (P = .000014, P = .000581, P = .000012, and P = .000821), respectively. Renal function tests (creatinine, estimated glomerular filtration rate) worsened (P = .003 and P = .007, respectively). Hepatocellular carcinoma (HCC) was developed in 2 patients during post-treatment follow-up. In Kaplan–Meier analysis, the probability of not developing HCC was 86.5% at 26 months.ConclusionThe sofosbuvir/ledipasvir combination is effective in treating genotype 1b chronic hepatitis C with high sustained virologic response rates. Because there are few drug interactions, it may be a suitable option for patients taking multiple medications or who are transplant recipients. Renal function should be monitored closely during and after treatment, as there is a risk of worsening renal function after treatment.     

解毒护肝冲剂联合干扰素α-1b治疗慢性丙型肝炎的临床观察

目的:探讨解毒护肝冲剂联合干扰素治疗慢性丙型肝炎的疗效。方法:将慢性丙型肝炎患者45例,按2:1随机分为两组,分别用解毒护肝冲剂联合干扰素α-1b与单用干扰素α-1b进行治疗,疗程3个月。结果:解毒护肝冲剂联合干扰素α-1b组治疗结束时有效率为86.66％,抗-HCV阴转率为66.67％,其降低ALT、TBil,提高白蛋白等均优于单用干扰素α-1b组(P<0.05或<0.01)。结论:解毒护肝冲剂联合干扰素α-1b治疗慢性丙型肝炎具有良好的疗效。     

Multicenter Study of Pegylated Interferon α‐2a Monotherapy for Hepatitis C Virus‐Infected Patients on Hemodialysis: REACH Study

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)‐infected dialysis patients. The rate of HCV‐infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α‐2a (PEG‐IFNα‐2a) monotherapy in HCV‐infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 μg PEG‐IFNα‐2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 μg PEG‐IFNα‐2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were <5.7 log IU/mL (SVR rate: 64% 9/14) and <6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG‐IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.     

A Comprehensive Long-Term Prognosis of Chronic Hepatitis C Patients With Antiviral Therapy: A Meta-Analysis of Studies From 2008 to 2014

Context:

Attaining a sustained virological response with antiviral therapy is a sign of clinical cure for chronic hepatitis C patients. The aim of this meta-analysis was to evaluate the long-term efficiency and outcome of antiviral therapy in patients with hepatitis C who attained a sustained virological response.

Evidence Acquisition:

A literature search was performed on published articles between January 2008 and February 2014. Patients with Hepatitis C who received interferon with or without ribavirin therapy were enrolled. Relative risks were estimated using either fixed or random effect models.

Results:

Patients who attained sustained virological response had a less risk (85%) for all-cause mortality and about 63% reduced risk of hepatocellular carcinoma incidence than those who did not achieve sustained virological response. Based on deeply analysis, the stage of liver fibrosis was a risk factor at baseline for the incidence of hepatocellular carcinoma.

Conclusions:

Sustained virological response can reduce all-cause mortality and the incidence of hepatocellular carcinoma of patients with hepatitis C. Advanced liver fibrosis is still a risk factor for the incidence of hepatocellular carcinoma, in spite of hepatitis C patients attained a sustained virological response.