Predictive Value of Serum pgRNA on HBeAg Clearance in Patients with Chronic Hepatitis B with Low HBeAg Levels Treated with Pegylated Interferon

Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis B patients with HBeAg positive and quantitative<50S/CO were selected for this study.The subjects underwent pegylated interferon therapy for 48-96 weeks and were followed up in the outpatient clinic after treatment.The patients were then divided into groups based on whether their HbeAg turned negative.The predictive ability of each indicator for HBeAg negative conversion was evaluated in the HBeAg negative group and the HBeAg positive group.Results:The results of logistic regression analysis suggested that pgRNA and HBcrAg were better indicators for predicting the clearance of HBeAg after treatment.Conclusion:For patients with chronic hepatitis B with low HBeAg levels,pgRNA is a good indicator in predicting HBeAg clearance during pegylated interferon therapy.

Combination Therapy with Pegylated Interferon alpha-2b and Adefovir Dipivoxil in HBeAg-positive Chronic Hepatitis B versus Interferon Alone: A Prospective, Randomized Study

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

Combination of pegylated interferon and lamivudine for patients with chronic hepatitis B who have failed treatment

BACKGROUND: Treatment of chronic hepatitis B (CHB) alone with interferon or lamivudine alone or in combination is effective in only a small proportion of patients. Treatment of patients in whom antiviral therapy fails is challenging. This study was made to determine the efficacy of combined pegylated interferon alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to antiviral treatment. METHODS: Twenty patients with CHB proven by liver biopsy, with ALT levels >1.5×ULN,HBV DNA levels>141 500 copies/ml, and previous treatment failure with an adequate regimen were treated with a combination of peg-IFN 1.5μg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a further 24 weeks. Biochemical response was defined as normalization of ALT and DNA response as HBV DNA<141 500 copies/ml. Secondary efficacy measures included HBsAg loss, HBeAg loss and appearance of anti-HBe (in cases of HBeAg-positive patients). RESULTS: Twenty patients were treated, of whom 16 were HBeAg positive. At 52 weeks, normal ALT was seen in 10 (50%) (8 of 16 HBeAg+ and 2 of 4 HBeAg), HBV DNA response in 5 (25%) (5 of 16 in HBeAg+ and none in HBeAg-), and HBeAg loss with appearance of anti-HBe in 5 (31.3%) of the 16 HBeAg positive patients. At 76 weeks, 8 (80%) of the 10 patients with normal ALT at 52 weeks relapsed, with normal ALT only in 2 (10%) (1 of 16 HBeAg+ and 1 of 4 HBeAg-), and all 5 patients who had a DNA response at 52 weeks relapsed at 76 weeks and had no DNA response. HBeAg loss with appearance of anti-HBe was seen in 1 (6.3%) of 16 HBeAg-positive patients. None of the patients lost HBsAg. CONCLUSIONS: The combination of peg-IFN and lamivudine for 52 weeks is not effective for treatment of CHB patients with a failed treatment. New treatment strategies need to be developed.

The Predictive Value of Baseline HBs Ag Level and Early Response for HBs Ag Loss in Patients with HBe Ag-positive Chronic Hepatitis B during Pegylated Interferon Alpha-2a Treatment

Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Pegylated interferon α-2b plus ribavirin for older patients with chronic hepatitis C

AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk.RESULTS:At 24 wk after the end of combination therapy,the overall sustained virological response(SVR) for genotypes 1 and 2 were 40.7% and 79.6%,respectively.The SVR rate decreased signif icantly with age in each genotype,and was markedly reduced in genotype 1(P<0.001).Moreover,the SVR was significantly higher in patients with genotype 1 who were less than 65 years(47.3% of 685) than in those 65 years or older(22.9% of 253)(P<0.001) and was higher in patients with genotype 2 who were less than 65 years(82.9% of 252) than in those 65 years or older(65.6% of 61)(P=0.004).When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV,the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older(P<0.001).Adverse effects resulted in treatment discontinuation more often in patients with genotype 1(14.4%) than in patients with genotype 2(7.3%),especially by patients 65 years or older(24.1%).CONCLUSION:PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.

Treatment of Hepatitis C with Pegylated Interferon Alpha-2a and Ribavirin:Experience from Benin

Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.

Treatment of Chronic Viral Hepatitis with Pegylated Interferon in Ivory Coast

Background: In the Ivory Coast, chronic infection by hepatitis B and C virus is the leading cause of cirrhosis and hepatocellular carcinoma. The absence of universal health coverage makes the treatment inaccessible to all. Objectives: To assess the efficacy of Pegylated Interferon in clinical practice in patients with chronic viral hepatitis B and C and determine the hematologic side effects. Patients and Methods: A descriptive retrospective study from January 2012 to November 2013 on a cohort of patients chronic carriers of hepatitis B virus (n = 11) treated with Pegylated Interferon to 180 mcg per week and hepatitis C virus (n = 30) treated with a combination therapy associating pegylated Interferon to 180 mcg per week and Ribavirin assayed according to the genotype. Results: Out of 1860 patients seen in hepatogastroenterology consultation 422 had viral hepatitis B or C that is a prevalence of 22.7% and 41 patients were treated (9.7%) by Pegylated Interferon. Among these 41 patients mentioned earlier, 30 had HCV (73.17%) with a case of HIV + HVC co-infection, 11 patients had HBV (26.83%) including 3 cases of HBV + HDV co-infection. Patients’ age ranged from 24 - 69 years with an average of 49.2 ± 12.2 years including 46.5 years for HBV and 51.9 years for HCV. The sex ratio was 1.56. The original transaminases were on average 93.37 IU/l for AST and 110.47 for ALT. The average RNA HCV was 1,685,331 IU/ml and the DNA HBV 33,312,767 IU/ml. Patients with HCV were of genotype 1 in 56.66%, genotype 2 in 40% and one case of genotype 4 (3.34%) from Central Africa. Fibrosis score at institution of treatment was significant (≥A2 and/or ≥F2) in 86.9% of cases of Fibrotest®, 100% of cases of Fibrometer®. We observed 48.8% of neutropenia < 750/mm3, 33.3% of anemia and 29.3% of thrombocytopenia < 100,000/mm3. There was no dose reduction of Pegylated Interferon and Ribavirin. For HBV there were 3 partial responses, 3 responders including 1 HBV + HDV co-infected non responder to HDV, 2 non responders including 1 HBV + HDV co-infected to Week 48. For HCV, there was 52.94% of cases of sustained viral response (SVR) including 44.44% of genotype 1, 83.33% of genotype 2 and 100% of genotype 4. Conclusion: The free antiviral treatment program helped treat 10% of chronic viral hepatitis B and C. Our results are not different from those of the literature. Difficulties remain in the performance of non supported diagnostic tests.

Liver Histopathological Features Influencing HBeAg Seroconversion in Patients with HBeAg-positive Chronic Hepatitis B Treated with Pegylated Interferon α

Objective To investigate the efficiency of pegylated interferon α therapy for patients with HBe Ag-positive chronic hepatitis B(CHB) and explore whether liver histopathological features and other factors might influence HBe Ag seroconversion.Methods Total of 80 HBe Ag-positive CHB patients who received liver puncture were treated with pegylated interferon α once a week for 48 weeks. The rate of HBe Ag seroconversion was determined after therapy, and the factors influencing HBe Ag seroconversion were analyzed.Results The rate of HBe Ag seroconversion was 30.00% at the end of treatment. The rate of HBe Ag seroconversion gradually increased with the elevation of liver inflammatory activity(χ2 = 9.170, P = 0.027). But liver fibrosis has little correlation with the rate of HBeA g seroconversion(χ2 = 5.917, P = 0.116). Except HBeA g, other baseline indexes including gender, age, serum ALT and serum HBV DNA 1evels had no statistical difference between the patients with HBe Ag seroconversion and the patients without HBe Ag seroconversion. By binary logistic regression analysis, liver inflammation and HBeA g were influencing factors for HBeA g seroconversion. Conclusions Pegylated interferon α therapy induces a higher rate of HBeA g seroconversion in HBeA g-positive chronic hepatitis B patients with severe liver inflammation, so the liver biopsies should be performed in time.

Predictive value of Th17 and Treg cells at baseline for HBsAg loss in chronic hepatitis B patients with low HBsAg quantification treated with pegylated interferon and nucleos(t)ide analogue

Background and aims:The primary goal of chronic hepatitis B(CHB)treatment is to reduce hepatitis B surface antigen(HBsAg).T helper 17(Th17)and regulatory T(Treg)cells are essential for the development of CHB.However,how Th17 and Treg cells contribute to HBsAg loss is still unknown.Therefore,this study aimed to search for the predictive value of Th17 and Treg cells for HBsAg loss in CHB patients with low HBsAg quantification.Methods:The study included 99 hepatitis B e antigen(HBeAg)-negative CHB patients who had completed a year of nucleos(t)ide analogue(NA)monotherapy and had received both NA and pegylated interferon(PEG-IFN)treatment for less than 96 weeks(96 wk).In the cured group,48 patients lost HBsAg within 48 wk,while 51 patients did not(uncured group).Blood samples and clinical data were collected for research.Results:During PEG-IFN and NA combination therapy,the proportion of Th17 cells in the cured group increased significantly,while the proportion of Treg cells in the uncured group increased.From 0 to 24 wk,the proportion of Th17 cells in the cured group was significantly higher than in the uncured group,while the opposite was true for Treg cells.Patients with alanine aminotransferase(ALT)2.5 upper limit of normal(ULN)at 12 wk had a higher proportion of Th17 cells and a lower proportion of Treg cells than those with ALT<2.5 ULN at 12 wk.Additionally,the proportion of Th17 cells is inversely associated with the level of HBsAg,whereas the level of Treg cells is positively related to HBsAg quantification.The clinical cure index,including age,HBsAg quantification,and the proportions of Th17 and Treg cells,had a higher area under the curve(0.957)for predicting HBsAg loss when compared to the proportions of Th17 and Treg cells and HBsAg quantification alone.Conclusions:Combined with quantification of HBsAg,the proportions of Th17 cells and Treg cells at baseline can be used as good predictors of HBsAg loss in patients with low HBsAg quantification treated with NA and PEG-IFN.

Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

Background： Hepatitis B surfhce antigen （HBsAg） Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B （CHB）. This study aimed to assess the patterns of ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon （PEG-IFN） α-2a. Methods： A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen （H BeAg）-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators （HBsAg, anti-HBs, HBeAg, and anti-HBe） were determined before and every 3 months during PEG-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results： Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3%, and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients （2.9 ± 1.1 log 1U/ml） compared with HBeAg-negative patients （2.0 ± 1.3 log I U/ml; t = 4.733, P 〈 0.001）, but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions： Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.

Early Serum HBsAg Kinetics as Predictor of HBsAg Loss in Patients with HBeAg-Negative Chronic Hepatitis B after Treatment with Pegylated Interferonα-2a

Hepatitis B surface antigen(HBsAg)loss is an ideal treatment endpoint for patients with chronic hepatitis B(CHB).We investigated the predictive value of on-treatment HBsAg levels for HBsAg loss in hepatitis B e antigen(HBe Ag)-negative CHB patients who received 120-week PEG-IFNα-2a treatment.Serum HBV DNA,HBsAg,and anti-HBs levels were assayed at baseline and every 3 months during the treatment.Of 81 patients,12 achieved HBsAg loss,20 achieved HBsAg\100 IU/mL,and 49 maintained HBs Ag C 100 IU/mL.HBsAg loss rate was only 3.7%at 48 weeks,while it reached to 11.1%and 14.8%after treatment of 96 weeks and 120 weeks.The cutoff HBs Ag levels at 12 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 400 IU/mL and 750 IU/mL,with AUC 0.725 and 0.722,positive predictive value(PPV)29.41%and 30.56%,and negative predictive value(NPV)93.75%and 97.78%,respectively.The cutoff HBsAg levels at 24 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 174 IU/m L and 236 IU/mL respectively,with AUC 0.925 and 0.922,PPV 40.0%and 46.15%,and both NPV 100%.The predictive ability of the cutoff HBsAg levels at 24 weeks was better than that at 12 weeks for HBs Ag loss at either 96 or 120 weeks(χ~2=3.880,P=0.049 andχ~2=4.412,P=0.036).These results indicate that extended therapy is critical to HBsAg loss in HBe Ag-negative CHB patients during PEG-IFN treatment,and the HBsAg level at 24 weeks can be used to predict HBsAg loss during tailoring PEG-IFN therapy.

Frequency ofT-cell FoxP3＋ Treg and CD4＋/CD8＋ PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon

Background Host immune responses against hepatitis B virus （HBV） induced by antiviral therapy play a crucial role in viral clearance. To further investigate the immune mechanisms underlying the differences between respondents and non-respondents, we analyzed myeloid dendritic cells （mDCs）, plasmacytoid dendritic cells （pDCs）, FoxP3＋ regulatory T cells （FoxP3＋ Treg） and programmed death 1 （PD-1） expression in CD4＋/CD8＋ T cells in chronic hepatitis B patients undergoing pegylated interferon （PeglFN）α-2b treatment. Methods Patients received PeglFNα-2b for 24 or 48 weeks, with follow-up at 24 weeks. The frequencies of mDCs, pDCs, FoxP3＋ Treg, and PD-1 expression by CD4＋/CD8＋ T cells were evaluated by flow cytometry at baseline, weeks 4 and 12, end of treatment, and follow-up （12/24 weeks）. Results In HBeAg seroconverters （respondents）, the mDC relative frequency decreased at week 4 and then rebounded at week 12. The pDC relative frequency decreased consistently. In non-HBeAg seroconverters （non-respondents）, both mDC and pDC frequencies decreased slightly. The FoxP3＋ Treg relative frequency decreased during treatment and remained low during follow-up in respondents, while in non-respondents it decreased slightly during therapy but rebounded after discontinuation. In patients with HBeAg 〈17.55 PEI-U/ml at week 12 and 〈8.52 PEI-U/ml at week 24, the FoxP3＋ Treg frequency decreased during treatment and at follow-up. In respondents, CD4~PD-1 and CD8＋PD-1 levels decreased at week 4 and remained low at week 12. In non-respondents, PD-1 expression decreased at week 4 but rebounded at week 12. Conclusions The results indicate that the dynamic changes in DCs, FoxP3＋ Treg frequency, and PD-1 expression by CD4＋ and CD8＋ T cells exhibit different trends in HBeAg and non-HBeAg seroconversion patients. During PeglFNa-2b treatment of chronic hepatitis B patients, these changes may be of predictive value for HBeAg seroconversion. HBsAg and HBeAg levels are related to FoxP3＋ Treg frequency.

HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b

Background： We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens （HBcrAg） for predicting hepatitis B e antigen （HBeAg） seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon （IFN） alfh-2b or pegylated IFN. Methods： Fifty-eight patients were enrolled： 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up （LTFU）, during which time the dynamics of the HBcrAg was monitored. Results： The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group （from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were II0,245 kU/ml, 3760 kU/ ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively）. HBcrAg 〈19,565 kU/ml at week 24, HBcrAg 〈34,225 kU/ml at 12-week follow-up, and HBcrAg decrease 〉0.565 log10 kU/ml from the baseline to the end of treatment （EOT） had negative predictive values （NPVs） of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values （PPVs） were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions： Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory （all 〈31%）. The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.

Pegylated interferons in the treatment of chronic hepatitis C

Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C Data sources An English language literature search (MEDLINE 1988-2001) was performed and a total of 19 original articles related to the issue were selected Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria The papers reviewed pertained mainly to the efficacy and safety profiles of peginterferons in the treatment of chronic hepatitis C Results Peginterferon can effectively prolong the half-life of interferon and can be effectively administered conveniently as a once-a-week dose The antiviral effect using peginterferon was enhanced compared with that of standard interferon, but the frequency and severity of adverse events were typical of those associated with interferon-α Conclusions Based on its efficacy, safety and convenient dosing, peginterferon is more favorable than standard interferon in the treatment of chronic hepatitis C

Interferon-alfa in the treatment of chronic hepatitis B

BACKGROUND: Interferon-alfa has been used in the treat-ment of chronic hepatitis B for more than 20 years and hasits own advantages including a definite course of therapy,no production of drug-resistant variants, and sustained effi-cacy. This review was to understand the role of interferon-alfa therapy in chronic hepatitis B.DATA RESOURCES: An English-language literature searchusing Medscape and MEDLINE was performed and a totalof 48 articles on the treatment of chronic hepatitis with in-terferon-alfa or pegylated interferon-alfa were selected.RESULTS: Interferon-alfa therapy was associated with ahigher HBV DNA inhibition rate and HBeAg loss rate com-pared with controls, and it may have long-term beneficialeffects in terms of HBV clearance, reduction of hepatocel-lular carcinoma, and prolongation of survival. Pegylatedinterferon-alfa was more effective than conventional inter-feron-alfa in the treatment of chronic hepatitis B as well aschronic hepatitis C, and was also associated with greater ef-ficacy than conventional interferon in difficult-to-treat dis-ease.CONCLUSIONS: Interferon-alfa is still regarded as one ofthe first-line drugs for the treatment of chronic hepatitis B.Pegylated interferon is a more promising therapy than con-ventional interferon-alfa, especially in patients with refrac-tory chronic hepatitis B.

聚乙二醇干扰素治疗慢性丙型肝炎诱发糖尿病酮症1例及文献回顾

目前,聚乙二醇干扰素联合利巴韦林已成为治疗慢性丙型肝炎的标准方案。本文报道1例男性慢性丙型肝炎患者,在使用标准治疗24周时,出现了1型糖尿病及酮症。

Clinical cure and liver fibrosis reversal after postoperative antiviral combination therapy in hepatitis B-associated non-cirrhotic hepatocellular carcinoma: A case report

BACKGROUND The incidence of hepatocellular carcinoma(HCC)is high in China,and approximately 15%-20%of HCC cases occur in the absence of cirrhosis.Compared with patients with cirrhotic HCC,those with non-cirrhotic HCC have longer postoperative tumor-free survival.However,the overall survival time is not significantly increased,and the risk of postoperative recurrence remains.Strategies to improve the postoperative survival rate in these patients are currently required.CASE SUMMARY A 47-year-old man with a family history of HCC was found to have hepatitis B virus(HBV)infection 25 years ago.In 2000,he was administered lamivudine for 2 years,and entecavir(ETV 0.5 mg)was administered in 2006.In October 2016,magnetic resonance imaging revealed a tumor in the liver(5.3 cm×5 cm×5 cm);no intraoperative hepatic and portal vein and bile duct tumor thrombi were found;and postoperative pathological examination confirmed a grade II HCC with no nodular cirrhosis(G1S3).ETV was continued,and no significant changes were observed on imaging.After receiving pegylated interferon alfa-2b(PEG IFNα-2b)(180μg)+ETV in February 2019,the HBsAg titer decreased significantly within 12 wk.After receiving hepatitis B vaccine(60μg)in 12 wk,HBsAg serological conversion was realized at 48 wk.During the treatment,no obvious adverse reactions were observed,except for early alanine aminotransferase flares.The reexamination results of liver pathology were G2S1,and reversal of liver fibrosis was achieved.CONCLUSION The therapeutic regimen of ETV+PEG IFNα-2b+hepatitis B vaccine for patients with HBV-associated non-cirrhotic HCC following hepatectomy can achieve an HBV clinical cure and prolong the recurrence-free survival.

Alkaline phosphatase predicts relapse in chronic hepatitis C patients with end-of-treatment response

AIM: To investigate relapse predictors in chronic hepatitis C (CHC) patients with end-of-treatment response (ETR), after pegylated interferon-α (PegIFN-α) and ribavirin treatment. METHODS: In a retrospective study we evaluated a spectrum of predictors of relapse after PegIFN-α and ribavirin treatment in 86 CHC patients with ETR. Viral loads were determined with real-time reverse transcrip-tion polymerase chain reaction. Hepatitis C virus geno-typing was performed by sequencing analysis. Patients with genotype 1 were treated for 48 wk with 180 μg PegIFN-α2a or 1.5 μg/kg PegIFN-α2b once weekly plus ribavirin at a dosage of 1000 mg/d for those under 75 kg or 1200 mg/d for those over 75 kg. Patients with geno- types 2 and 3 were treated for 24 wk with 180 μgPegIFN-α2a or 1.5 μg/kg PegIFN-α2b once weekly plus ribavirin at a dosage of 800 mg/d. RESULTS: In all ETR patients, binary logistic regression analysis identif ied absence of complete early virological response (cEVR) (OR 27.07, 95% CI: 3.09-237.26, P < 0.005), serum alkaline phosphatase (ALP) levels prior to therapy < 75 U/L (OR: 6.16, 95% CI: 2.1-18.03, P < 0.001) and body mass index > 26 kg/m2 (OR: 8.27, 95% CI: 2.22-30.84, P < 0.005) as independent predictors of relapse. When cEVR patients were analyzed exclusively, ALP prior to therapy < 75 U/L remained the only predictor of relapse. CONCLUSION: Lower levels of ALP prior to, during and after therapy seem to be associated with a higher risk of relapse in CHC patients with ETR.

The Predictive Value of On-treatment Virological Response for Sustained Virological Response in Patients with Chronic Hepatitis C Receiving a Personalized Treatment Program

To investigate the effects of individualised treatment with peginterferon alpha-2a(40 kD)plus ribavirin in Chinese patients with CHC.Methods Total of 297 consecutive Chinese patients were enrolled,including 250 nave cases and 47 cases who were previously treated.Treatment duration was determined according to viral genotypes,prior treatment history and viral responses at week 4,12 and 24.Results Totally,235 patients(79.1%)completed treatment and 186(87.3%)achieved SVR.And 219 out of 289(75.8%)patients achieved HCV RNA negative at week 4(RVR)and 259 of 276(93.8%)at week 12.Among the 164 patients with RVR who completed follow-up,158(96.3%)achieved SVR.Patients with RVR had lower baseline viral loads than patients without RVR(P=0.034).The positive predictive value(PPV)of RVR for SVR was 90.7%(OR 2.10 vs.non-RVR,95%CI:0.50-8.7).Similar outcomes were observed among patients with HCV undetectable at week 12.Conclusions Viral suppression by week 4 is associated with a high rate of treatment success in treatment nave and experienced patients receiving individualized CHC therapy.

Taurocholic acid inhibits the response to interferon-αtherapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8^(+)T and NK cell function

Pegylated interferon-alpha (PegIFNα) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNα therapy in CHB patients. Here, we used mass spectrometry to determine serum BA profiles in 110 patients with chronic HBV infection and 20 healthy controls (HCs). We found that serum BAs, especially TCA, were significantly elevated in HBeAg-positive CHB patients compared with those in HCs and patients in other phases of chronic HBV infection. Moreover, serum BAs, particularly TCA, inhibited the response to PegIFNα therapy in HBeAg-positive CHB patients. Mechanistically, the expression levels of IFN-γ, TNF-α, granzyme B, and perforin were measured using flow cytometry to assess the effector functions of immune cells in patients with low or high BA levels. We found that BAs reduced the number and proportion and impaired the effector functions of CD3^(+)CD8^(+) T cells and natural killer (NK) cells in HBeAg-positive CHB patients. TCA in particular reduced the frequency and impaired the effector functions of CD3^(+)CD8^(+) T and NK cells in vitro and in vivo and inhibited the immunoregulatory activity of IFN-α in vitro. Thus, our results show that BAs, especially TCA, inhibit the response to PegIFNα therapy by impairing the effector functions of CD3^(+)CD8^(+) T and NK cells in HBeAg-positive CHB patients. Our findings suggest that targeting TCA could be a promising approach for restoring IFN-α responsiveness during CHB treatment.