Complete Virological Response Research Articles

Interleukin 28B Genetic Polymorphisms Play a Minor Role in Identifying Optimal Treatment Duration in HCV Genotype 1 Slow Responders to Pegylated Interferon plus Ribavirin

Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear. Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 (n=168) or 72 (n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration. Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75-88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91-100% versus 13-44%; P=0.001). Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.

Long-term antiviral treatment for recurrent hepatitis C after liver transplantation

Background and aimsThe management of patients treated for hepatitis C recurrence after liver transplantation and not achieving virological response following treatment with interferon plus ribavirin is controversial. MethodsA retrospective analysis of the outcomes of 70 patients non-responders to antiviral treatment after liver transplantation was performed. Twenty-one patients (30.0%; Group A) were treated for ≤12 months and 49 (70.0%; Group B) for more than 12 months. ResultsThe 2 groups were comparable for main demographic, clinical and pathological variables. Median duration of antiviral treatment was 8.2 months in Group A and 33.4 months in Group B. No patient achieved a complete virological response. The 5-year patient hepatitis C-related survival rate was 49.2% in Group A and 88.3% in Group B (P=0.002), while the 5-year graft survival rate was 49.2% in Group A and 85.9% in Group B (P=0.007). The median yearly fibrosis progression rate was 1.21 per year in Group A and 0.40 per year in Group B (P=0.001). ConclusionsProlonged antiviral treatment showed an overall beneficial effect in transplanted patients with a recurrent hepatitis C infection and not responding to conventional therapy. The treatment should be continued as long as it is permitted, in order to improve clinical and histological outcomes.

The Response of HIV-Associated Lymphadenopathic Kaposi Sarcoma to Highly Active Antiretroviral Therapy Evaluated by 18F-FDG PET/CT

The use of PET/CT for determining systemic Kaposi sarcoma (KS) involvement and treatment response remains to be formally assessed. Pretreatment human herpes virus-8 (HHV-8) viral load may predict clinical response of KS to therapy; however, its role in treatment monitoring and correlation with PET/CT findings is unknown. We report PET/CT findings and HHV-8 viral loads of a 46-year-old man with HIV-associated lymphadenopathic KS. After treatment with highly active antiretroviral therapy, an interval PET/CT showed partial response, despite an undetectable HHV-8 viral load. Chemotherapy was initiated, and the patient achieved a complete clinical, PET/CT, and virological response. PET/CT enabled monitoring of treatment response and led to changes in management.

Results of antiviral treatment of patients with chronic hepatitis C: experience of Poznan centre

Hepatitis C virus (HCV) infection in Poland affects approximately 750 thousand persons. The prevention of cirrhosis and hepatocellular carcinoma, of which approximately 20% of patients with chronic hepatitis C virus are at risk, aims at eradication of the virus by applying antiviral treatment with pegylated interferon alpha with ribavirin. In this paper the results of the standard treatment of chronic hepatitis C in a population of 169 adult patients in whom it was started in the period of 01.01.2007-30.06.2008 are analyzed. Moreover, the influence of various clinical, biochemical and viral factors on achieving therapeutic success in the form of the sustained virological response (SVR) was studied. In the group of 128 patients who received the full course of antiviral treatment, the SVR was achieved by 67.2% of patients (86 persons), whereas regarding all 169 patients who started the therapy, the sustained disappearance of viremia was found in 53.2% of patients (90 persons). Regarding 155 persons in whom the treatment was not interrupted for reasons others than virology, this value was 55.5%. For the sustained disappearance of viremia the following was favorable: genotype 3 virus, age under 40 years, body mass up to 75 kg, correct value of body mass index (BMI), low gamma-glutamyl transpeptidase (GGTP) activity before the treatment, minimum advancement of liver fibrosis in a liver biopsy (S1), complete early biochemical response (cEBR), and moreover, the achievement of negation of viremia after 12 weeks of the treatment in a group of patients infected with genotype 1 (complete early virological response, cEVR). These factors were strongly correlated with each other and that is why an analysis by the method of logistic multiple regression was impossible. Adverse reactions to the treatment and other health problems were the reasons for earlier discontinuation of the standard therapeutic scheme in 14 patients, whereby the lack of an SVR occurred in 10 of them (71.5% which is 5.9% of the studied population).

Efficacy of lamivudine on acute-on-chronic liver failure in patients with chronic hepatitis B

To observe the therapeutic effects of lamivudine treatment in patients with early- to mid-stage hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of 73 hospitalized patients with HBV-ACLF were retrospectively analyzed. Prothrombin time (PT, active coagulation), HBV DNA, and model for end-stage liver disease (MELD) score data from treatment weeks 4, 8, 24, and 48 were collected and analyzed using the statistical t-test. During the treatment duration, the complete virologic response rates were 57.5% (42/73) at 4 weeks, 71.0% (44/62) at 8 weeks, 83.1% (49/59) at 24 weeks, and 86.5% (45/52) at 48 weeks. The partial virologic response rates were 30.1% (22/73) at 4 weeks, 25.8% (16/62) at 8 weeks, 17.0% (10/59) at 24 weeks, and 13.5% (7/52) at 48 weeks. At week 48, the survival rate was 71.2% (52/73) and the probability of survival was higher in the complete virological response rate (VRR) group than in the partial VRR group [45/73 (61.6%) vs. 7/73 (30.1%), respectively; P = 0.000]. In addition, there were significant improvements in the serum normalization rate of HBV DNA, alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, PT and MELD score in surviving patients compared to baseline (P less than 0.05) and in the complete VRR group compared to the partial VRR group (P less than 0.05). Antiviral therapy using lamivudine may be an effective therapeutic option for patients with HBV-ACLF.

PMO-154 Plasma HBSAG levels decline was similar during subsequent pegylated interferon and nucleos(T)IDE analogues treatment in chronic hepatitis B patients

IntroductionPegylated interferon (Peg-IFN) therapy responses in chronic hepatitis B (CH-B) are associated with decline of HBsAg plasma levels (qHBsAg) (>10% in HBeAg− and >0.5 log10IU/ml in HBeAg+) and HBV DNA...

Treatment extension may benefit female genotype 1 chronic hepatitis C patients with complete early virological response to peginterferon‐alpha‐2b and ribavirin combination therapy

Little is known about the appropriate use of peginterferon-α-2b (PEG IFN-α-2b) or ribavirin (RBV) in genotype 1 chronic hepatitis C (CH-C) patients with complete early virological response (cEVR). Female patients, especially the older, are known to experience inferior treatment outcomes. A total of 150 CH-C patients with cEVR treated for 48 weeks (n = 104) or 52-64 weeks (n = 46) with PEG IFN-α-2b and RBV combination therapy were retrospectively analyzed to evaluate the benefits of extended treatment. In the 48-week group, patients without a sustained virological response (SVR) were more often female (P = 0.004) and had received a significantly lower total RBV dose (P = 0.003) than those with SVR. The SVR rate in these female patients was similar to males with hepatitis C virus (HCV) RNA negativity at treatment week 8 (P = 0.413); however, it was lower than that in males with HCV RNA negativity at treatment week 12 (P = 0.005). In the 52-64-week group, although the total RBV dose (mg/kg) after treatment week 48 was less in females than in males (P = 0.027), the SVR rate in females was equivalent to that in males (P = 0.604). Genotype 1 CH-C patients treated with PEG IFN-α-2b and RBV combination therapy without SVR were more often female and had received a lower total RBV dose than males. The smaller SVR rate in female patients with cEVR compared to males may be overcome by extending treatment even if the RBV dose is lowered due to anemia.

Genetic Factors and Hepatitis C Virus Infection

It is now possible to comprehensively screen the human genome for genetic variation that influences the outomes of human disease and pharmacotherapy. The most opular approach remains the genome-wide association tudy (GWAS), in which many hundreds of thousands of enetic markers, representing common variation across he genome, are tested for association with disease. Two uccess stories of the GWAS era are reviewed here: the iscoveries of the association between interleukin-28B IL28B) polymorphism and peginterferon(pegIFN) and ribavirin (RBV) treatment response for genotype 1 HCV, as well as spontaneous clearance of acute HCV infection, and the association between inosine triphosphatase (ITPA) variation and RBV-induced hemolytic anemia. The discovery that IL28B variation is associated with the response to treatment with peginterferon alfa (pegIFN) and ribavirin (RBV) for genotype 1 hepatitis C virus (HCV) was made by 4 independent groups in late 2009 and early 2010.1–4 All identified single nucleotide polymorphisms SNPs) that tag a haplotype block on chromosome 19 spaning IL28B, coding for IFN3, and which strongly predict the outcomes for treatment of chronic genotype 1 HCV infection. Individuals who carry the good response variant have an approximately 2-fold higher rate of sustained virological response (SVR) (Table 1). The top discovery SNPs identified in the GWAS included rs129798601 and rs80999171–4 (note that rs12979860 was only included on the enotyping chip used for the Ge study; rs8099917 was included n the genotyping chips used in all 4 studies). A more compreensive discussion of GWAS methodology is detailed in Manoio et al,5 Pearson et al,6 and Hardy et al.7 In most populations, these 2 SNPs are in strong linkage disequilibrium and are similarly informative, the exception being individuals of African American ancestry, where rs12979860 is more closely associated with treatment outcome. The frequency of the good response allele differs according to ethnic background; it is more common in individuals of Asian Caucasian Hispanic African ancestry.1,8 IL28B allele frequency explains much of the difference in treatment response rates that have been observed between different populations. The good response variant was also noted to be less common among individuals chronically infected with HCV than healthy controls,1 consistent with geetic selection. IL28B variation was subsequently found to be ssociated with spontaneous clearance of HCV infection as ell.4,8–10 The effect size is similar, with patients carrying the ood response variant being 2-fold more likely to naturally clear cute infection. IL28B polymorphism is strongly associated with the iral kinetics of IFN response, where the major influence f the good response variant is to enhance phase 1 deline,11 increasing the rates of critical on-treatment milestones and decreasing relapse (Table 1).12 IL28B genotype is the strongest pretreatment predictor of IFN responsiveness.12 Once treatment has been started, on-treatment iral decline remains the strongest predictor of viral clearnce. Patients carrying the good response IL28B variant re more likely to achieve week-4 rapid virological reponse and week-12 complete early virological response, ut once these milestones have been achieved, SVR rates re high regardless of IL28B genotypes (Table 1). IL28B enotyping and on-treatment viral kinetics can therefore e considered complementary, one being informative prereatment, the other requiring a trial of treatment. The association between IL28B genotype and pegIFN nd RBV treatment response has been considered in a umber of different clinical scenarios. IL28B genotype is relevant to the outcomes of pegIFN and RBV treatment for genotype 1 HCV patients co-infected with human immunodeficiency virus, with similar effect size to that seen in HCV monoinfection.13 It is also relevant to the treatment of genotype 1 HCV in patients after orthotopic liver transplantation.14,15 Both donor and recipient IL28B genotypes have an additive influence on IFN treatment

A comparison of clevudine and entecavir for treatment-naïve patients with chronic hepatitis B: results after 2years of treatment.

This study was undertaken to compare the efficacy, safety, and resistance profile of clevudine (CLV) and entecavir (ETV) following a 2-year treatment period. One hundred and eight Korean patients from the prior 48-week study were followed with continuous therapy for up to 2years and monitored for hepatitis B virus (HBV) DNA levels, HBeAg seroconversion, serum ALT, emergence of drug-resistant mutant HBV, and drug-related adverse events. A complete virological response during the 2-year treatment period occurred in 68.0% in the CLV group and in 84.5% in the ETV group (p=0.043). The cumulative percentage of patients with sustained virological responses at 2years was 54.0 and 77.6% in the CLV and ETV group, respectively (p=0.010). Virological breakthrough occurred in 12 patients in the CLV group; however, there were none in the ETV group (p<0.001). HBeAg seroconversion rates were not different between the two groups. In patients who maintained sustained virological responses at 2years, the mean reduction in HBsAg titer was -0.24 and -0.06logIU/ml in the CLV and ETV group, respectively (p>0.05). Clinical myopathy occurred in seven patients in the CLV group; however, this was not observed in the ETV group (p=0.004). ETV was associated with a significantly higher virological response rate than CLV at 2years. ETV was superior to CLV in terms of the drug resistance profile and the development of clinical myopathy. Further studies to see whether the unique characteristic of CLV to reduce HBsAg titer is associated with the removal of ccc-DNA from hepatocytes and the remission of the disease are needed.

A randomized trial of 48 versus 24 weeks of combination pegylated interferon and ribavirin therapy in genotype 6 chronic hepatitis C

Genotype 6 chronic hepatitis C (HCV) is encountered predominantly in Southeast Asia and data on optimal treatment strategy is limited. This study was aimed at assessing the rate and predictors of sustained virological response (SVR) in genotype 6 chronic HCV following 48 and 24 weeks of pegylated interferon and ribavirin therapy. This investigator-initiated, open-label randomized trial was conducted in Vietnam between 2008 and 2010. One hundred and five treatment-naïve HCV genotype 6 patients were randomized to either 48-week (N=70) or 24-week (N=35) duration of pegylated interferon (PEG-IFN) alfa-2a 180 mcg/week and ribavirin (RBV) 15mg/kg/day; 92 patients completed the study (63 in the 48-week and 29 in the 24-week group, respectively). Primary outcome was sustained virological response (SVR) as intention-to-treat analysis. There was no statistical difference in SVR between 48-week and 24-week treated groups (71% vs. 60%, respectively; p=0.24). In the 48-week and 24-week treatment groups, 81% and 80% of cases achieved rapid virological response (RVR) (p=0.86), and 86% and 80% achieved complete early virological response (p=0.45). Among those patients with RVR, SVR was in 86% (48-weeks), and 75% (24-weeks) of cases, whereas following non-RVR, only 8% of cases had an SVR with 48-week treatment duration. Overall, RVR was achieved in the majority of genotype 6 patients and, in those patients, similar and high rates of SVR were noted following 24-week and 48-week therapy. This observation, however, needs validation in a larger study to demonstrate non-inferiority of the shorter duration therapy. In non-RVR patients, even 48-week therapy achieved low SVR rates.

The Correlation of Il28B Genotype With Sustained Virologic Response In Romanian patients With Chronic Hepatitis C

: Background: Multiple variables influencing the sustained virologic response (SVR) in chronic hepatitis C have been evaluated. One of them is genetic polymorphism near the IL28B gene.Objectives: The aim of this study was to evaluate the influence of IL28B genotypes on SVR rates in a group of patients with chronic hepatitis C from the western part of Romania.Patients and Methods: A retrospective study was performed in 107 consecutive patients, previously treated with standard-of-care medication for chronic hepatitis C, identified from the databases of 2 centers. Patient demographics, viral load before treatment and at 12, 24, and 72 weeks from the treatment start, and IL28B genotype were evaluated.Results: Among the 107 patents in the study group, 54 patients had SVR (50.5%), and 62 (57.9%) showed a complete early virologic response (cEVR). The SVR rates according to IL28B genotype were as follows: 73.1% in patients with genotype C/C, 40.9% in those with genotype C/T, and 57.1% in those with genotype T/T (i.e., 73.1% among patients with the C/C genotype vs. 43.7% among those with non-C/C genotypes; P = 0.0126). The cEVR rates were 80.8% in patients with the C/C genotype vs. 51.2% in those with non-C/C genotypes (P = 0.011).Conclusions: In our cohort of 107 Caucasian HCV patients, the SVR rate was 50.5% with standard-of-care treatment. The SVR rate was directly related to the IL28B genotype: 73.1% in the C/C genotype vs. 43.7% in non-C/C genotypes (P = 0.0126). Implication for health policy/practice/research/medical education:Chronic C hepatitis is a global healthcare problem, affecting approximately 3% of world population, with sustained virologic response rates after treatment ranging from 34 to 61%. The genetic polymorphism near the IL28B gene, encoding interferon-lambda-3, is associated with different response rates to treatment. Reading this article is recommended to all interested in this subject. Please cite this paper as:Sporea I, popescu A, Curescu M, Sirli R, Dan I, Goldis A, et al. The Correlation of Il28B Genotype With Sustained Virologic Response In Romanian patients With Chronic Hepatitis C. Hepat Mon. 2011;11(12):975-9. DoI:10.5812/kowsar.1735143X.793

Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures

To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures. A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo). All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects. TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.

Vitamin D improves viral response in hepatitis C genotype 2-3 naïve patients

To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of inflammation were measured. The treatment group with vitamin D had higher BMI (30 ± 6 vs. 26 ± 3, P < 0.02), and high viral load (> 400,000 IU/mL, 65% vs. 40%, P < 0.01) than controls. Ninety-five percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/mL). Logistic regression analysis identified vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 significantly improves viral response.

The Interaction among Insulin Resistance, Liver Fibrosis and Early Virological Response in Egyptian Patients with Chronic Hepatitis C

Hepatitis C virus (HCV) infection may induce insulin resistance (IR) irrespective of the severity of liver disease, and there is evidence of a central role for IR in failure to achieve sustained virological response (SVR) in HCV patients. To assess IR as a predictor of the severity of hepatic fibrosis in Egyptian HCV patients, and its effect on early viral kinetics and virological response to HCV therapy. A total of 140 chronic HCV patients were divided into two groups according to the homeostasis model assessment-IR (HOMA-IR). Group 1 consisted of 48 chronic HCV patients with HOMA-IR >=2, and group 2 consisted of 92 chronic HVC patients without IR (HOMA IR <2). All patients were treated with combination therapy (pegylated interferon-alpha 2a plus ribavirin) for 48 weeks and studied for viral kinetics throughout the period of therapy. The study revealed that older age, higher body mass index and HOMA-IR >=2 were significantly associated with advanced fibrosis. Rapid virological response, complete early virological response and SVR were significantly lower in the IR-HCV group compared with the non-IR-HCV group. Univariate and multivariate analyses revealed that older age, fibrosis (F>=3), high viral load (>600,000 IU⁄mL) and HOMA-IR >=2 were significantly associated with a lack of viral kinetics as well as SVR. However, HOMA-IR >=2 was the main independent variable associated with lack of SVR. On the other hand, body mass index, plasma insulin level and HOMA-IR decreased significantly compared with starting levels in patients who achieved SVR. This suggests a cause and effect relationship between HCV infection and IR. IR in chronic HCV patients is associated with progressive fibrosis and slow viral kinetics, and could be a predictor for lack of rapid and early virological response. Therefore, HOMA-IR levels should be measured and improved before starting antiviral treatment.

Impact of ribavirin dose on retreatment of chronic hepatitis C patients

To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients. Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV), 165 (13%) had a relapse. Among these, 62 patients were retreated with PEG-IFN-α2a or -α2b and RBV. Clinical, biological, virological and histological data were collected. Initial doses and treatment modifications were recorded. The efficacy of retreatment and predictive factors for SVR were analyzed. An SVR was achieved in 42% of patients. SVR was higher in young (< 50 years) (61%) than old patients (27%) (P = 0.007), and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P = 0.023). Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%, P = 0.04). Also, a better SVR rate was observed with RBV dose/body weight > 15.2 mg/kg per day (70% vs 35%, P = 0.04). In logistic regression, predictors of a response were age (P = 0.018), genotype (P = 0.048) and initial RBV dose/body weight (P = 0.022). None of the patients without a complete early virological response achieved an SVR (negative predictive value = 100%). Retreatment with PEG-IFN/RBV is eff-ective in genotype 2 or 3 relapsers, especially in young patients. A high dose of RBV seems to be important for the retreatment response.

Entecavir plus Adefovir Combination Treatment for Chronic Hepatitis B Patients after Failure of Nucleoside/Nucleotide Analogues

The combination of entecavir, a nucleoside analogue, and adefovir, a nucleotide analogue, would be a promising salvage treatment for chronic hepatitis B (CHB) patients who fail nucleoside/nucleotide analogue (NA) regimens. A total of 89 CHB patients who had failed NA regimens and were treated with entecavir plus adefovir combination for at least 12 months were included. Mean baseline HBV DNA of patients was 6.16 ±1.44 log(10) IU/ml. Patients were classed by the number of previously failed NAs; 1 NA (lamivudine; n=15; Group 1), 2 NAs (lamivudine and either adefovir or entecavir; n=39; Group 2) and 3 NAs (lamivudine, adefovir and entecavir; n=35; Group 3). After 12 months of treatment, the mean reduction in HBV DNA was greater in Group 1 than in Group 2 or 3 (-5.81 ±1.71, -3.20 ±1.36 and -2.93 ±1.56 log(10) IU/ml, respectively; P<0.01). The rates of virological response (HBV DNA<2,000 IU/ml) were 100%, 79.5% and 34.3% (P<0.01), and the rates of complete virological response (HBV DNA<60 IU/ml) were 53.3%, 25.6% and 14.3% in Group 1, 2 and 3, respectively (P<0.01) at 12 months. Higher baseline HBV DNA (odds ratio =0.59; P=0.02) and increasing number of previously failed NAs (P<0.01) were independently associated with a lower rate of complete virological response at 12 months. Entecavir plus adefovir combination treatment was effective in achieving virological response in CHB patients after failure of NAs. However, its effect progressively decreased as the number of previously failed NAs increased.

High‐dose silibinin rescue treatment for HCV‐infected patients showing suboptimal virologic response to standard combination therapy

Incomplete suppression of hepatitis C virus (HCV) replication with persistence of minimal viremia (partial virologic response) leading to treatment failure can be observed in a significant proportion of HCV type 1-infected patients during antiviral therapy. Recently, high-dose intravenous silibinin has demonstrated strong antiviral activity against HCV. We were therefore interested in whether patients with partial virologic response can be rescued by the on-treatment addition of a short-term course of high-dose intravenous silibinin infusions. Twenty patients who failed to achieve a complete virologic response to different interferon-based regimens qualified for the rescue strategy and received 1400 mg/day silibinin infusions on two consecutive days. Complete viral suppression (below the limit of detection <6 IU/mL, TMA assay) could be induced in 13 of 20 patients within the first week after the short-term silibinin infusion, and all but one of them also remained HCV RNA negative during the subsequent follow-up period on continued peginterferon plus ribavirin treatment. In the remaining seven patients, no complete suppression could be achieved although four showed a significant HCV RNA reduction in response to silibinin. Silibinin infusions were generally well tolerated, and activation of abdominal peristalsis with nausea, diarrhoea and vomiting were the most prominent side effects. Of the twelve patients who exhibited a durable response to peginterferon and ribavirin treatment, three achieved an SVR, two achieved a week 12 SVR and four suffered a viral relapse. Three patients could not complete the assigned antiviral treatment with peginterferon alpha and ribavirin for nonvirological reasons. Short-term administration of high-dose intravenous silibinin might be an interesting approach to rescue patients with ongoing minimal residual viremia while on interferon-based therapy. These preliminary findings may stimulate further studies to evaluate more refined therapeutic strategies.

Exploratory Study on the Effects of Treatment with Two Mistletoe Preparations on Chronic Hepatitis C

Twenty-one patients with chronic hepatitis C were treated with a mistletoe preparation as monotherapy (either Iscador or Abnoba viscum) during one year. The treatment was well tolerated. Patients entering the study with elevated transaminases had a significant improvement, both for AST (aspartate aminotransferase) (p = 0.01) and for ALT (alanine aminotransferase) (p = 0.04). Quality of life significantly improved (p = 0.006) in patients with a low initial quality of life. Although one patient obtained a complete virological response, few effects on viral load were seen in the whole group. These results suggest an effect comparable to glycyrrhicin treatment: improvement of liver inflammation and thus possibly reduction of the long term complications, viz cirrhosis and liver cancer. Mistletoe preparations have the advantage of easy administration and low cost.

Efficacy of Entecavir and Adefovir Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B

The optimal treatment of patients with chronic hepatitis B (CHB) who develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential monotherapy of LMV and ETV remains little known. We evaluated the efficacy of entecavir (ETV) plus adefovir dipivoxil (ADV) combination therapy for patients with resistance to LMV and ETV. We reviewed the medical records of 12 patients, and treated all 12 patients with ETV plus ADV combination therapy for at least 18months. Quantitative hepatitis B virus (HBV) DNA levels, serologic markers, and hepatic panel values were monitored at baseline and 3-month intervals thereafter for 18months. The baseline mean serum HBV DNA level was 7.26±1.11log(10)copies/ml. The mean reductions in serum HBV DNA levels from baseline to 3, 6, 9, 12, 15, and 18months were -1.98±1.03, -2.87±1.02, -3.32±1.10, -3.92±1.30, -4.36±1.22, and -4.57±1.18log(10)copies/ml, respectively. Complete virological response (HBV DNA of <2log(10)copies/ml) at 6, 12, and 18months was observed in 1 (8.3%), 4 (33.3%), and 6 (50.0%) patients, respectively. The 2 patients with baseline HBV DNA of <6log(10)copies/ml achieved complete virological response at 18months, while 4 of 10 patients with baseline HBV DNA of ≥6log(10)copies/ml achieved complete virological response at 18months. None of the 12 patients experienced virological breakthrough during follow-up. ETV plus ADV combination therapy effectively reduced serum HBV DNA levels in patients with CHB who developed resistance to both LMV and ETV. Additional long-term studies are needed to assess the effect of long-term treatment with these drugs.

Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept

fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.