Pegylated Interferon Group Research Articles

A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study.

Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.

Pegylated Interferon Treatment for the Effective Clearance of Hepatitis B Surface Antigen in Inactive HBsAg Carriers: A Meta-Analysis.

BackgroundExpanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs.MethodsWe searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis.ResultsA total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate.ConclusionThis study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured.Systematic Review Registration http://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.

Changes in the Cytokine Profiles of Patients with Chronic Hepatitis B during Antiviral Therapy

ObjectiveTo investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment. MethodsHepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months. ResultsIn all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3–6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) (P < 0.001) and a significant increase in interferon-alpha 2(IFN-α2) (P < 0.001). In the ETV group, IL-10 and TGF-β1 decreased significantly (P < 0.001). After 3 months, the levels of IFN-α2, IL-17A, and tumor necrosis factor-alpha(TNF-α) in the PEG-IFN group were significantly higher than those in the ETV group (P < 0.01). The levels of IL-6 and TGF-β3 were significantly lower than those in the ETV group (P < 0.01). After 6 months, the levels of IFN-α2, IFN-γ, and TNF-α in the PEG-IFN group were significantly higher than those in the ETV group (P < 0.01), while the levels of IL-6 and TGF-β3 were significantly lower than those in the ETV group (P < 0.01). Compared with ETV, PEG-IFN had higher HBeAg and HBsAg disappearance rates. ConclusionDuring antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.

Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

PurposeThe loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent. MethodsA total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ2 test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan–Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1. FindingsAt week 72, the Kaplan–Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log10 IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort. ImplicationsA 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log10 IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.

Patterns of Hepatocellular Carcinoma After Direct Antiviral Agents and Pegylated-Interferon Therapy.

Introduction: The impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial and a part of the scientific community believes it as a biased interpretation of data. Many studies have reported an aggressive pattern of HCC after DAA use. In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs or PI (PEG, pegylated-interferon).Methods: A total of 37 HCC patients after DAA treatment and 21 HCC patients after PI treatment were included. The diagnosis of HCC was made and information about demographics, HCC infiltrative pattern, portal vein thrombosis (PVT), time at initial presentation, Child-Turcotte-Pugh (CTP) score, and Barcelona Clinic Liver Cancer (BCLC) stage were compared in the two groups.Results: The total number of male patients in the DAA group was 62% while either gender was almost equal in PI. The age group of 40-60 was more prevalent in the DAA group while the PI group comprised more patients who were above 60 years. Patients in the DAA group presented after 3.35 years on average while patients in the PI group presented after about seven years. Most of the patients presented with the CTP stage of A. That is true for both groups. For BCLC staging, most of the patients had stage C, which means multiple lesions. At the initial presentation, most of the patients presented with multifocal lesions.Conclusion: Our study found no significant difference in the initial presentation between both groups. However, HCC patients with prior DAA therapy presented early than those with PI therapy.

Hepatocellular Carcinoma Risk According to Regimens for Eradication of Hepatitis C Virus; Interferon or Direct Acting Antivirals.

Simple SummaryOwing to pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against chronic hepatitis C virus infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it still remains controversial whether there is any difference in prognosis depending on treatment regimens—PegIFN or DAAs. After adjusting for imbalance between patients treated with PegIFN-based vs. DAA-based regimens, the post-SVR risk of hepatocellular carcinoma development was comparable according to treatment regimens. Furthermore, the risk was also similar between patients treated with sofosbuvir-based vs. sofosbuvir-free DAA regimens. Further studies with a longer follow-up period are required.By pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it remains controversial whether there is any difference in prognosis depending on regimens—PegIFN or DAAs. We compared the probabilities of hepatocellular carcinoma (HCC) development between patients achieving an SVR by PegIFN/ribavirin (PegIFN group, n = 603) and DAAs (DAAs group, n = 479). The DAAs group was significantly older and had a higher proportion of cirrhosis than the PegIFN group. Before adjustment, the DAAs group had a higher HCC incidence than the PegIFN group (p < 0.001). However, by multivariate analyses, the DAAs (vs. PegIFN) group was not associated with HCC risk (adjusted hazard ratio 0.968, 95% confidence interval 0.380–2.468; p = 0.946). Old age, male, higher body mass index, cirrhosis, and lower platelet count were associated with increased HCC risk (all p < 0.05). After propensity score matching (PSM), a similar HCC risk between the two groups was observed (p = 0.372). We also compared HCC incidences according to sofosbuvir (SOF)-based and SOF-free DAAs, showing a similar risk in both groups before adjustment (p = 0.478) and after PSM (p = 0.855). In conclusion, post-SVR HCC risks were comparable according to treatment regimens; PegIFN- vs. DAA-based regimens and SOF-based vs. SOF-free DAA regimens. Further studies with a longer follow-up period are required.

Anti-viral effect in chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase

Background & aimsNormal/mildly elevated ALT (<2 × ULN) CHB patients are potentially at risk of progression to cirrhosis and/or hepatocellular carcinoma (HCC). We aimed to assess the outcomes of anti-viral therapy for normal/mild elevation of ALT CHB patients. MethodsCHB patients (n = 432) who have had liver biopsied were determined. It was determined that the outcomes of anti-viral therapy in CHB patients with normal/mild elevation of ALT, in response to nucleoside/nucleotide analogues (NAs) (n = 190) and pegylated interferon (PEG-IFN) (n = 30) treatment for up to 72 weeks. Non-anti-viral treated patients were used as control (n = 40). ResultsThere was about 50% of the CHB patients showed hepatic inflammatory necrosis ≥ G2 and/or fibrosis ≥ S2 among >30-years-old. The rate of undetectable HBV DNA in NAs and PEG-IFN groups was ~50%, ~80% or ~90% at week 24, 48 or 72, respectively. HBeAg clearance rate was lower in NAs treated than that in PEG-IFN group at week 48 (6% vs 20%, P < 0.05). ALT normalization rate was increased by 1.18-fold at week 72. HBsAg decline in HBeAg+ patients treated with NAs or PEG-IFN was 0.418 or 1.217 log IU/mL (P < 0.0001) at week 48; whereas HBsAg decline was 0.176 or 0.816 log IU/mL (P < 0.001) in HBeAg− patients. HBsAg at baseline and week 24 were strong predictors of “low HBsAg at week 48”. ConclusionLong term anti-viral therapy inhibits HBV replication effectively in ALT<2 × ULN CHB patients. PEG-IFN therapy is recommended for HBeAg+ patients with baseline HBsAg<4.37 log IU/ml and HBeAg− patients with baseline HBsAg<2.66 log IU/ml to achieve “low HBsAg at week 48”.

Evolution of patients' socio-behavioral characteristics in the context of DAA: Results from the French ANRS CO13 HEPAVIH cohort of HIV-HCV co-infected patients.

BackgroundDirect-acting antivirals (DAA) have dramatically increased HCV cure rates with minimal toxicity in HIV-HCV co-infected patients. This study aimed to compare the socio-behavioral characteristics of patients initiating pegylated-interferon (PEG-IFN)-based HCV treatment with those of patients initiating DAA-based treatment.MethodsANRS CO13 HEPAVIH is a national multicenter prospective cohort started in 2005, which enrolled 1,859 HIV-HCV co-infected patients followed up in French hospital outpatient units. Both clinical/biological and socio-behavioral data were collected during follow-up. We selected patients with socio-behavioral data available before HCV treatment initiation.ResultsA total of 580 patients were included in this analysis. Of these, 347 initiated PEG-IFN-based treatment, and 233 DAA-based treatment. There were significant differences regarding patient mean age (45 years±6 for the PEG-IFN group vs. 52 years±8 for the DAA group, p<0.001), unstable housing (21.4% vs. 11.2%, p = 0.0016), drug use (44.7% vs. 29.6%, p = 0.0003), regular or daily use of cannabis (24.3% vs. 15.6%, p = 0.0002), a history of drug injection (68.9% vs 39.0%, p<0.0001) and significant liver fibrosis (62.4% vs 72.3%, p = 0.0293). In multivariable analysis, patients initiating DAA-based treatment were older than their PEG-IFN-based treatment counterparts (aOR = 1.17; 95%CI [1.13; 1.22]). Patients receiving DAA treatment were less likely to report unstable housing (0.46 [0.24; 0.88]), cannabis use (regular or daily use:0.50 [0.28; 0.91]; non-regular use: 0.41 [0.22; 0.77]), and a history of drug injection (0.19 [0.12; 0.31]).ConclusionIt is possible that a majority of patients who had socio-economic problems and/or a history of drug injection and/or a non-advanced disease stage were already treated for HCV in the PEG-IFN era. Today, patients with unstable housing conditions are prescribed DAA less frequently than other populations. As HCV treatment is prevention, improving access to DAA remains a major clinical and public health strategy, in particular for individuals with high-risk behaviors.

Pre-emptive Treatment of HCV after Living Donor Liver Transplantation with Direct-Acting Antiviral Agents

BackgroundHepatitis C virus (HCV) universally recurs after liver transplantation (LT). Although the introduction of direct-acting antiviral agents (DAAs) has revolutionized the treatment of HCV infection, no optimal treatment for HCV recurrence after LT has been developed. MethodsThis study retrospectively evaluated the efficacy of DAAs as a pre-emptive treatment for recurrent HCV infection after living donor liver transplantation (LDLT). From January 2010 to December 2016, 70 patients received pegylated interferon (PegIFN) and 35 patients were treated with DAA-based regimens to treat recurrent HCV after LDLT. All antiviral treatments were pre-emptive. ResultsGenotype 1b was the most common HCV type (61.9%). Twenty-two recipients in the DAA group were treated with ledipasvir/sofosbuvir, nine received daclatasvir plus asunaprevir, three received sofosbuvir, and one received sofosbuvir plus daclatasvir. All 35 patients (100%) in the DAA group achieved a sustained virologic response (SVR), a percentage significantly higher than that (71.4%) in the PegIFN group (p<0.001). In the PegIFN group, the 1-, 3-, and 5-year graft survival rates were 85.7, 73.9, and 70.7%, respectively, whereas those in the DAA group were 100, 100, and 100%, respectively (p=0.008). ConclusionDAA-based regimens are an effective treatment for HCV recurrence after LDLT, resulting in an improved SVR and better graft survival than PegIFN.

Altered expression of interferon-stimulated genes is strongly associated with therapeutic outcomes in hepatitis B virus infection

Our previous OSST study shows that switching to pegylated interferon (Peg-IFN)-α2a results in higher rates of response hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss at the end of treatment, compared with nucleot(s)ide analogues (NAs) monotherapy in long term NA-treated chronic hepatitis B (CHB) patients. In order to characterize the correlation between Peg-IFN-α antiviral effect and IFN-inducing signaling in CHB patients who switched to Peg-IFN from long time entecavir (ETV) treatment, we investigated the dynamic expression of interferon-stimulated genes (ISGs), including STAT1, MX, and a negative regulatory factor, suppressor of cytokine signaling 3(SOCS3), which negatively regulate IFN JAK-STAT signaling pathway by interacting with STAT1 and STAT2, in peripheral blood and paired liver samples, obtained from 54 CHB patients enrolled in a clinical trial, OSST study. In Peg-IFN group, responders showed a more significant decline in HBsAg, compared with non-responders. Following the treatment, peripheral blood and hepatic STAT1 and MX expression levels were higher in Peg-IFN responders, while SOCS3 expression was higher in non-responders. Fold induction of STAT1 at week 4 and MX at week 12 in PBMCs directly correlated with HBsAg decline at week 48 relative to the baseline. Responders showed a significantly increased activation and nuclear localization of phospho-STAT1 following Peg-IFN treatment, compared with non-responders in liver. Whereas, non-responders exhibited significantly higher hepatic expression of SOCS3 before the treatment compared with the responders and even higher expression levels after the treatment compared with the baseline, which may be involved in the mechanism of IFN resistance.

FRI-158 - Altered expression of interferon-stimulated genes is strongly associated with therapeutic outcomes in hepatitis B virus infection

Our previous OSST study shows that switching to pegylated interferon (Peg-IFN)-α2a results in higher rates of response hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss at the end of treatment, compared with nucleot(s)ide analogues (NAs) monotherapy in long term NA-treated chronic hepatitis B (CHB) patients. In order to characterize the correlation between Peg-IFN-α antiviral effect and IFN-inducing signaling in CHB patients who switched to Peg-IFN from long time entecavir (ETV) treatment, we investigated the dynamic expression of interferon-stimulated genes (ISGs), including STAT1, MX, and a negative regulatory factor, suppressor of cytokine signaling 3(SOCS3), which negatively regulate IFN JAK-STAT signaling pathway by interacting with STAT1 and STAT2, in peripheral blood and paired liver samples, obtained from 54 CHB patients enrolled in a clinical trial, OSST study. In Peg-IFN group, responders showed a more significant decline in HBsAg, compared with non-responders. Following the treatment, peripheral blood and hepatic STAT1 and MX expression levels were higher in Peg-IFN responders, while SOCS3 expression was higher in non-responders. Fold induction of STAT1 at week 4 and MX at week 12 in PBMCs directly correlated with HBsAg decline at week 48 relative to the baseline. Responders showed a significantly increased activation and nuclear localization of phospho-STAT1 following Peg-IFN treatment, compared with non-responders in liver. Whereas, non-responders exhibited significantly higher hepatic expression of SOCS3 before the treatment compared with the responders and even higher expression levels after the treatment compared with the baseline, which may be involved in the mechanism of IFN resistance.

The impact of pegylated-interferon α-2b on partial and massive hepatectomy model in rats.

The impact of pegylated-interferon (PEG-IFN) α-2b on liver regeneration has not yet been elucidated. Rats were divided into the following four groups: 70% hepatectomy (Hx); 70% Hx+PEG-IFN; 90% Hx and 90% Hx+PEG-IFN group (n=6 each). Rats were pretreated with subcutaneous of PEGIFN α-2b (1.5 μg/kg) administration 24 hours before Hx. Samples were taken 24, 48 and 72 hours after Hx and the following parameters were investigated: blood analysis (AST, WBC, PLT); liver weight to body weight ratio (Lw/Bw ratio); survival and PCNA labeling index (LI). In the 90% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group in blood analysis; AST after postoperative 24 hours (2511 vs. 2466 IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x 10⁴/mm³), in Lw/Bw ratio at postoperative 0, 24, 48, 72 hours, respectively (0.38, 0.60, 1.14, 1.69 vs. 0.37, 0.64, 1.12, 1.63), in postoperative survival (40% vs. 45%), and in PCNA LI at postoperative 0, 24, 48, 72 hours, respectively (10.4%, 16.8%, 14.6%, 12.8% vs. 10.0%, 17.1%, 15.6%, 13.7%). In the 70% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group for all parameters. Our data demonstrated that PEG-IFN α-2b did not affect liver regeneration and the early use of PEG-IFN α-2b would cause no problems after liver transplantation using partial grafts including living donor liver transplantation.

Results of interferon-based treatments in Alaska Native and American Indian population with chronic hepatitis C

BackgroundThere have been few reports of hepatitis C virus (HCV) treatment results with interferon-based regimens in indigenous populations.ObjectiveTo determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI) population.DesignIn an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined.ResultsSustained virologic response (SVR) with standard interferon was 16.7% (3/18) and with standard interferon and ribavirin was 29.7% (11/37). Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%), including 10 of 46 with genotype 1 (21.7%), 38 of 51 with genotype 2 (74.5%) and 13 of 22 with genotype 3 (59.1%). By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p=0.002), estimated duration of infection (p=0.034) and HCV genotype (p<0.0001). There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%). Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%).ConclusionsWe had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1.

Retrospective analysis of total direct medical costs associated with hepatitis B patients with oral antiviral versus pegylated interferon therapy in Turkey

To explore healthcare costs associated with antiviral treatment of hepatitis B virus (HBV) in Turkey. Research-identified data from a claims processing system for all Turkish health insurance funds were analysed. Adult patients prescribed oral antiviral and pegylated interferon treatment were identified between 1 January 2010 and 31 December 2010. The first prescription date was defined as the index date. Patients were required to have HBV diagnosis within the 6-month pre-index period. Pharmacy, outpatient and inpatient claims were compiled over the study period for the selected patients, and risk-adjusted 1-year healthcare costs of patients with oral antiviral and pegylated interferon treatment were compared. Risk adjustment was carried out using propensity score matching, controlling for baseline demographic and clinical characteristics. A total of 9618 patients were identified, of which 9074 were treated with oral antiviral medication and 544 with pegylated interferon medication. The oral antiviral treatment group was older (45.28 vs 42.19, P < 0.001), less likely to be female (32.17% vs 39.71%, P < 0.001) and to reside in Southeastern Anatolia (8.29% vs 13.97%, P < 0.001) or Mediterranean region (8.90% vs 11.76%, P < 0.03) and had higher Elixhauser comorbidity index scores (60.22% vs 74.08%, P < 0.001) than the pegylated interferon group. After adjusting for confounding factors, total medical costs for pegylated interferon patients were €2771 higher than for oral antiviral patients (P < 0.001), due to higher outpatient and prescription costs. For annual healthcare costs for antiviral treatment options for HBV patients in Turkey, after adjusting for age, gender, region and comorbid condition differences, oral antiviral treatment is more costly than pegylated interferon treatment.

Safety and efficacy of adjuvant pegylated interferon therapy for metastatic tumor antigen 1‐positive hepatocellular carcinoma

Metastatic tumor antigen 1 (MTA1) overexpression is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). It has been suggested that pegylated interferon (Peg-IFN) can prevent the occurrence of HCC in patients who have chronic viral hepatitis. In this study, the authors examined whether postoperative adjuvant Peg-IFN therapy can reduce the recurrence of MTA1-positive HCC after curative surgical resection. In this case-control study, 93 patients with MTA1-positive HCC who underwent curative surgical resection were prospectively enrolled. The median patient age was 53 years (range, 27-78); there were 65 men and 28 women; the etiology was hepatitis B virus (HBV) in 77 patients, hepatitis C virus (HCV) in 6 patients, and non-HBV/non-HCV in 10 patients; 31 patients received Peg-IFN (Peg-INTRON) subcutaneously at a dose of 50 μg per week for 12 months (the Peg-IFN group); and the remaining 62 patients were followed only and did not receive any adjuvant therapies (control group). Patients were followed every 1 to 3 months for a median of 24 months. HCC recurred postoperatively in 26 of 93 patients (28%), and 9 patients (10%) died during follow-up. The overall cumulative recurrence rates were significantly lower in the Peg-IFN group than in the control group (7% and 14% vs. 24% and 34% at 1 year and 2 years, respectively; P < .05). In addition, the 1-year and 2-year cumulative survival rates were higher in the Peg-IFN group compared with the control group (100% vs. 93% and 100% vs. 87%, respectively; P < .05). In multivariate analysis, the receipt of adjuvant Peg-IFN therapy, in addition to having a lower Cancer of the Liver Italian Program score and being a woman, was an independent, favorable factor for a lower risk of postoperative recurrence. The current data indicate that adjuvant Peg-IFN therapy may reduce the recurrence of HCC in patients who have MTA1-positive HCC after curative surgical resection.

Combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon alpha-2b for advanced hepatocellular carcinoma.

216 Background: Two recent phase III clinical trials have shown that sorafenib improves the survival in patients with advanced hepatocellular carcinoma (HCC). However, patients with HCC and portal vein tumor thrombosis (PVTT) usually have very short survival even when treated with sorafenib. On the other hand, recent advances in implantable drug delivery systems have made it possible to administer repeated hepatic arterial infusion chemotherapy (HAIC) agent. Since 2006, we have treated the patients displaying advanced HCC with PVTT by combined HAIC of 5-fluorouracil (5-FU) and systemic pegylated interferon (PEG-IFN)α-2b, and reported favorable results. In this article, we evaluated the efficacy of combined 5-FU and PEG-IFN α-2b, and compared outcomes between advanced HCC patients with PVTT treated using sorafenib. Methods: Forty patients with HCC and PVTT were enrolled. Of these, 21 patients were treated using subcutaneous administration of PEG-IFNα-2b and intra-arterial infusion of 5-FU [5-FU / PEG-IFN group], 19 patients were treated using continuous oral treatment with 400-800 mg of sorafenib [Sorafenib group]. We compared the early response to the therapy and the cumulative survival rate between these two groups. Results: The objective early response rate in the 5-FU / PEG-IFN group was significantly higher than that in the Sorafenib group (71.4 vs. 10.5%, P&lt;0.01). The cumulative survival rates at 6, 12, 18, and 24 months, respectively, were 83.8, 77.8, 55.6, and 55.6% in the 5FU / PEG-IFN group, and 68.4, 37.7, 16.2, and 16.2% in the Sorafenib group. The cumulative survival rates was significantly higher in the 5FU / PEG-IFN group than in the Sorafenib group (P=0.03). Serious complications and treatment-related deaths were not observed in the 5FU / PEG-IFN group. On the other hand, the rate of discontinuation of treatment due to adverse events was 36.8% of the patients who were treated sorafenib. Conclusions: Based on our findings, this newly developed combination therapy may be useful for patients with advanced HCC, although a large-scale randomized controlled study by comparison with sorafenib is needed.

Similar Virological Responses in a Cohort of Chronic Hepatitis C Patients Treated with Standard or Pegylated Interferon, Rawalpindi, Pakistan

Purpose: In a Low-Income Country (LIC), the decision to use Standard Interferon (SI) or Pegylated Interferon (PI) with Ribavirin in a naïve chronic hepatitis C virus (HCV) is based on patients' income status. This study compared the virological response rates in naïve chronic hepatitis C virus (HCV) patients treated with SI with Ribavirin to those treated with PI with Ribavirin in a LIC. Study design: Retrospective cohort study. Setting: Holy Family Hospital, Rawalpindi, Pakistan. Methods: Records of consecutive patients of chronic hepatitis C treated from 2006 to 2009 were retrospectively evaluated for treatment responses based on qualitative Polymerase Chain Reaction (PCR) tests at standardized intervals: Rapid Virological Response (RVR) at 4 weeks, Early Virological Response (EVR) at 12 weeks, Early Treatment Response (ETR) at 24 weeks, and Sustained Viral Response (SVR) at 48 weeks. Results: A total of 431 records were evaluated, of which 206 patients received SI and Ribavirin for 24 weeks (group I) whereas 225 patients received PI with Ribavirin for six months (group II). In SI group data were available for RVR in 21.8%, EVR 78.1%, ETR 53.4%, and SVR 19.9% of cases. In PI group data were available on RVR in 55.5%, EVR 62.2%, ETR 76.8%, and SVR 46.2% of cases. No significant differences (P≥0.45) were observed for any treatment response between SI and PI therapy: RVR 68.9% vs. 68.0%; EVR: 77.6% vs. 75.8%; ETR: 70.9% vs. 76.6%; and SVR 63.2% vs. 60.5%. Conclusion: Treatment responses from both regimens were comparable in this Pakistani HCV cohort and findings were consistent with high prevalence of genotype 2 and 3 regionally. This suggests that SI with Ribavirin may still be used as an initial choice of treating naïve HCV patients with low socioeconomic status in Pakistan.

Hepatic arterial infusion chemotherapy in combination with pegylated interferon-α-2b for advanced hepatocellular carcinoma.

We previously reported that combination therapy comprising hepatic arterial infusion chemotherapy (HAIC) with 3 drugs, namely, cisplatin (CDDP), 5-fluorouracil (5-FU) (low-dose FP) and isovorin and interferon (IFN)-α-2b was not beneficial for patients with advanced hepatocellular carcinoma (HCC). In this study, we investigated the efficacy of combination therapy comprising HAIC and pegylated interferon (PEG-IFN)-α-2b in advanced HCC patients by comparing our results with previous data. From a total of 29 patients, 12 received HAIC and PEGIFN- α-2b (PEG-IFN group) and 17 received HAIC and IFN-α-2b (IFN group). There were no significant differences in clinical characteristics between the 2 groups. The response rate was 33.3% (complete response (CR)=1; partial response (PR)=3) in the PEGIFN group and 47.1% (PR=8) in the IFN group. The 1-, 2- and 3-year cumulative survival rates were 50%, 25% and 8%, respectively, in the PEG-IFN group, whereas they were 53%, 18% and 12%, respectively, in the IFN group. There were no significant differences in the response rate (p=0.251) and survival (p=0.938) between the two groups. We found that combination therapy comprising HAIC using low-dose FP with isovorin and PEG-IFN-α-2b was not beneficial for advanced HCC.

Effect of pegylated interferon therapy on intrahepatic recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma

We wished to determine whether pegylated interferon (PEG-IFN) therapy after curative treatment of hepatocellular carcinoma (HCC) prevents a recurrence of HCC. Thirty-seven HCC patients with hepatitis C virus (HCV) infection who were treated with PEG-IFN after curative treatment (PEG-IFN group) and 145 controls without IFN therapy (non-IFN group) were enrolled. The overall survival and recurrence-free survival rates were compared between the groups, and the predisposing factors for recurrence and survival were analyzed. The rates were also examined by propensity score (PS) matched analysis that could minimize selection biases. The median follow-up period was 3.7 years. The 5-year survival rate in the PEG-IFN group (91%) was significantly higher than that in the non-IFN group (56%; P < 0.01). The rate of the second recurrence but not that of the first recurrence of HCC in the sustained virological responder (SVR) group was lower than that in the non-IFN group (P = 0.03). Improvement of survival by PEG-IFN and low rate of second recurrence in the SVR group were also observed in PS matched analysis. Multivariate analysis revealed that PEG-IFN therapy and high serum albumin were good prognostic factors for survival. Although low serum albumin and large and multiple tumors were risk factors for the first recurrence, non-SVR and low serum albumin were risk factors for the second recurrence. PEG-IFN-therapy after curative treatment of HCC improved the rate of survival, and SVR was found to be closely correlated with the prevention of recurrence.

C型慢性肝炎に対するinterferon治療の副作用の比較-従来型interferonとpeginterferon

We compared the adverse events among the same patients with chronic hepatitis C who were treated with standard interferon (IFN) with no response and again treated with pegylated interferon (PEG-IFN) combined with or without ribavirin (RIB), based on a questionnaire and blood count analysis. Patients were divided into four groups; standard IFN group, standard IFN+RIB group, PEG-IFN group, and PEG-IFN+RIB group. As a result, allergic reactions, such as itching, stomatitis, sneezing were much less seen in the standard IFN group, compared to PEG-IFN group. On the other hand, flu-like symptoms were more seen in the former than the latter. Hemoglobin and neutrophilic leukocyte counts significantly decreased until 16 weeks after starting the therapy in the groups with RIB than the groups without it. Platelet level significantly decreased at 2 weeks in the standard IFN+RIB group compared with PEG-IFN+RIB. As a whole, patients were satisfied with PEG-IFN therapy in view of visiting a doctor only once a week and its physical and mental easiness.