Potential of Interferon Lambda as an Inhibitor of SARS-CoV-2.

This study provides an overview of scientific results on the feasibility of using type III interferons against SARS-CoV-2. We have analyzed data obtained from the PubMed electronic database for the period 2020‒2022. The results of our own studies of pharmacological substances based on recombinant IFN-λ1 and its pegylated form are also presented. Completed and ongoing investigations allow us to position IFN-λ as an effective therapeutic agent against SARS-CoV-2.

IL-22-producing CD3 + CD8- T cells increase in immune clearance stage of chronic HBV infection and correlate with the response of Peg-interferon treatment.

Interleukin (IL)-22 regulates host defense. This study investigated the predominant IL-22-producing cell subsets under HBV associated immune stages. We found circulating IL-22-producing CD3 + CD8- T cells were significantly increased in immune active (IA) stage than those in immunotolerant stage, inactive carrier and healthy controls (HCs). The plasma IL-22 level was higher in IA and HBeAg-negative CHB compared to HCs. Importantly, CD3 + CD8- T cells were identified as the predominant source of plasma IL-22 production. Up-regulated IL-22-producing CD3 + CD8- T cells obviously correlated with the grade of intrahepatic inflammation. The proportions of IL-22-producing CD3 + CD8- T cells were significantly down-regulated after 48 weeks of Peg-interferon treatment, and the differences were of great significance in patients with normalize ALT levels at 48 weeks, rather than those with elevated ALT levels. In conclusion, IL-22 might play a proinflammatory function in. chronic HBV infected patients with active inflammation and Peg-interferon treatment could attenuate the degree of liver inflammation through down-regulating IL-22-producing CD3 + CD8- T cells.

[Potential of Interferon Lambda as an Inhibitor of SARS-CoV-2].

This study provides an overview of scientific results on the feasibility of using type III interferons against SARS-CoV-2. We have analyzed data obtained from the PubMed electronic database for the period 2020-2022. The results of our own studies of pharmacological substances based on recombinant IFN-λ1 and its pegylated form are also presented. Completed and ongoing investigations allow us to position IFN-λ as an effective therapeutic agent against SARS-CoV-2.

Cytokine polymorphisms and genotypic susceptibility of HCV infection in ribavirin response to peg interferon

@#Immune responses are largely regulated by cytokines. Genetic polymorphisms of the regulatory coding regions are recognized to impact the expression of cytokines. The abnormal cytokine levels in hepatitis C virus (HCV) infection seems to be involved in disease progression, viral survival, and therapeutic response. The current study assesses the polymorphisms associated with IL-6, IL-10, IL28B, IFN-γ, TGF-β, and TNF-α on the genotypic susceptibility to HCV infection and Ribavirin response to Peg interferon. Droplet digital polymerase chain reaction (PCR) was used to assess the gene polymorphisms associated with IL-6 A/G (rs2069837), IL-10-1082 G/A (rs1800896)], IL28B C/T (rs12979860), IFN-γ +874 A/T (rs2430561), TGF-β 1-509 C/T (rs1800469) and TNF-α-308 G/A promoter (rs1800629) from stored samples of 200 healthy individuals and 300 HCV infected patients. There was a significant association of AG and AA genotypes of IL28B, IFN-γ, TGF-β1, and TNF-α over HCV susceptibility and treatment outcome. However, no association between IL-6 and IL-10 gene polymorphism to HCV susceptibility response to the treatment. The observations indicate IL28B CT, TGF-β1 CT, TT and TNF- AG with AA genotypes influence the cytokine expression, which is related to susceptibility and resistance to HCV infection and combined antiviral therapy.

Combination and Intermittent Therapy Based on Pegylated Interferon Alfa-2a for Chronic Hepatitis B with Nucleoside (Nucleotide) Analog-Experienced Resulting in Hepatitis B Surface Antigen Clearance: A Case Report.

Interferon (IFN) and nucleoside (nucleotide) analogs (NAs) are two effective antiviral drugs for chronic hepatitis B (CHB). More and more evidence shows that the combination of the two drugs can better inhibit viral replication and even achieve clinical cure. IFN intermittent therapy is also considered to be an important measure to resolve IFN fatigue when hepatitis B surface antigen (HBsAg) decline appears stagnated during IFN-based antiviral therapy. A 36-year-old male NA-experienced patient with hepatitis B e antigen (HBeAg)-positive CHB was admitted to our hospital. After a poor response to tenofovir disoproxil fumarate (TDF) monotherapy for 1 year, the patient was treated with pegylated interferon alfa-2a combination therapy and finally achieved HBsAg clearance. During the treatment and follow-up, HBsAg, HBeAg, hepatitis B virus (HBV) DNA, and serum alanine aminotransferase, etc. were monitored every 3 months. Between weeks 58 and 71 of combination therapy, IFN was discontinued because of a slow decline in HBsAg, and TDF alone was used for maintenance therapy. Complete virological response, HBeAg and HBsAg seroconversion were observed at weeks 44, 96, and 122, respectively. After 24 weeks of consolidation therapy, HBsAg, HBeAg, and HBV DNA were consistently negative, and hepatitis B surface antibody was 729.30 mIU/mL at week 146 of the combination therapy, then we stopped drugs. Following up after 28 weeks of cessation therapy, the patient still remained clinically cured.

A Systematic Review on Current Trends in the Treatment of Chronic Hepatitis B to Predict Disease Remission and Relapse.

Despite decreasing the prevalence of chronic hepatitis B (CHB), it is still a major health care challenge. Current antiviral regimens aim to suppress hepatitis B virus (HBV) deoxyribonucleic acid (DNA) activity to prevent the risk of hepatic decompensation, liver cirrhosis, and hepatocellular carcinoma (HCC). Currently, pegylated interferon (Peg-IFN) and nucleos(t)ide analogs (NA) are the first-line choices of drugs. Peg-IFN is now discontinued due to its mode of application and side effects. NA is used once daily to suppress HBV DNA activity but has little effect on covalently closed circular DNA (cccDNA), so continuous long-term therapy is required to suppress HBV DNA. Due to this effect, disease remission, relapse, and even clinical flare are common phenomena after the end of treatment (EOT). This review aimed to analyze the current regimens for treating chronic hepatitis B. Their mode of action, duration of treatment, and events after stopping therapy. The review was performed using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020 guidelines. A search was undertaken in PubMed, PubMed Central, Google Scholar, and ScienceDirect. Screening of articles was carried out to find relevant and appropriate articles. Articles were then quality-checked before inclusion. Our analysis showed that long-term finite therapy with nucleoside analogs could improve clinical outcomes and suppress viral DNA activity. However, a functional cure, loss of hepatitis B surface antigen (HBsAg), is rarely achieved. The decision to end treatment depends on quantitative HBsAg level (qHBsAg), alanine aminotransferase (ALT), HBV DNA (deoxyribonucleic acid), hepatitis B e antigen (HBeAg), and fibrosis assessment. It is concluded that patients with HBeAg negative without cirrhosis can be easily withdrawn from treatment if they have long-term viral remission and a high HBsAg loss rate. However, patients with positive HBeAg should continue treatment because there is a high chance of disease relapse and even acute flare. To predict whether patients will benefit from EOT, some immunomodulatory markers are studied, including interleukin (IL-20, IL-8), fas ligand (FASGL), and IFN gamma. Although these factors are reliable, none pose an independent effect on disease remission. Combination therapy (IFN alpha + oral nucleoside analogs) is promising but has clinical shortcomings.

Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model.

BACKGROUND: The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting. METHODS: An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447. FINDINGS: We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation. INTERPRETATION: Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes. FUNDING: The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.

Peg-interferon alpha add-on Tenofovir disoproxil fumarate achieved more HBsAg loss in HBeAg-positive chronic hepatitis B naïve patients.

Several studies have showed that combining peg-interferon alpha (Peg-IFNα) with nucleotide analogues has complementary effects in chronic hepatitis B (CHB), but the optimal regimen and potential mechanisms remain unclear. This was a prospective, longitudinal and multicentre clinical trial (NCT03013556). HBeAg-positive CHB naïve patients were randomly assigned to three groups: tenofovir disoproxil fumarate (TDF) monotherapy for 96 weeks, TDF alone for 48 weeks and sequentially Peg-IFNα added for 48 weeks, TDF de novo combination with Peg-IFNα for 48 weeks then TDF alone for 48 weeks. The primary endpoint was HBeAg seroconversion at week 96 and HBsAg loss as the secondary endpoint. Furthermore, the levels of 12 cytokines in serum were assessed at different time points. A total of 133 patients were included in the analysis. The rates of HBeAg seroconversion at 96 weeks were not significant different among the three groups (p = 0.157). Interestingly, patients in the Peg-IFNα add-on group showed markedly lower HBsAg level compared with the other two groups at week 96. In addition, only three patients in the Peg-IFNα add-on group achieved HBsAg loss. For the following 24 weeks from week 96, no HBsAg reappearance in the three patients and no new patients with HBsAg loss were observed in the three groups. Serum cytokine analysis showed that the baseline level of interferon-inducible protein-10 (IP-10) was strongly higher in HBeAg conversion patients and HBsAg loss patients. Compared with de novo combination and TDF alone, the addition of Peg-IFNα in TDF-treated group might be an effective strategy for HBsAg loss in HBeAg-positive CHB naïve patients.

Rates of Hepatocellular Carcinoma After Start of Treatment for Chronic Hepatitis C Remain High with Direct Acting Antivirals: Analysis from a Swiss Liver Transplant Center.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood. PATIENTS AND METHODS: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis. RESULTS: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5-4.7) for DAA and 9.3 years (IQR: 6.6-12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20-18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤0.001, depending on covariates). A HR of 6.62 (CI: 2.01-21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups. CONCLUSION: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.

Efficacy of peg-interferon-nucleoside analog sequential optimization therapy in HBeAg-positive patients with CHB.

OBJECTIVE: This study aimed to evaluate the efficacy of Peg-interferon (Peg-IFN)-nucleoside analog (NA) sequential optimization therapy (SOT) in HBeAg-positive patients with chronic hepatitis B (CHB). METHODS: In this prospective two-center study, 132 CHB patients were assigned to receive Peg-IFN standard therapy for 48 weeks (65 patients) or Peg-IFN monotherapy for 12-24 weeks and NA add-on for those without early virological response (EVR) (67 patients). Both patient groups were monitored and followed for 24 weeks after treatments stop. RESULTS: At week 24 after treatments stop, the Peg-IFN-NA SOT group achieved more HBsAg levels drop (- 1.35 vs - 0.67 log10 IU/mL, p = 0.016), higher HBsAg ≤ 100 IU/mL (32.8% vs 9.2%, p = 0.001), HBV DNA undetectable (79.1% vs 49.2%, p < 0.001), and ALT normalization (80.6% vs 38.5%, p < 0.001) rates compared with Peg-IFN monotherapy. At week 24 after treatments stop, no significant difference was found in HBeAg seroconversion (35.8% vs 27.7%, p = 0.316), HBsAg loss (8.9% vs 4.6%, p = 0.323) and HBsAg seroconversion rates (4.5% vs 1.5%, p = 0.325) between Peg-IFN monotherapy group and Peg-IFN-NA SOT group. CONCLUSION: Starting with Peg-IFN followed by addition of NA achieved more HBsAg levels drop, and higher HBsAg ≤ 100 IU/mL, HBV DNA undetectable, and ALT normalization rates compared with Peg-IFN monotherapy.

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.

A randomized controlled trial of pegylated interferon-alpha with tenofovir disoproxil fumarate for hepatitis B e antigen-negative chronic hepatitis B: A 48-week follow-up study.

BACKGROUND: Recent studies report incongruent finds regarding the addition of pegylated interferon -alpha (Peg- IFNα) to nucleos(t)ide analogues. This study was designed to compare the efficacy of Peg- IFNα and tenofovir disoproxil fumarate (TDF) combination therapy with each of the treatments separately. METHODS: In this open-label, randomized clinical trial, treatment-naive hepatitis B e antigen (HBeAg)-negative patients were randomly assigned to three treatment groups: Group A: Peg- IFNα (180 mcg/week) with TDF (300 mg/day); Group B: TDF (300 mg/day); and Group C: Peg- IFNα (180 mcg/week). The intervention spanned 48 weeks and patients were followed up every 12 weeks. The primary end-point was HBV DNA load <20 IU/mL. RESULTS: Groups A, B and C each comprised of 22, 23 and 22 patients, respectively. The number of patients with HBV DNA suppression in group A was significantly higher compared to groups B and C (P = 0.034). No significant difference was observed in the normalization trends of serum ALT levels between the three groups (P = 0.082). At week 48, combination therapy was significantly more effective in suppressing HBV DNA concentration to below the level of detection than TDF monotherapy (OR = 2.1, 95%CI: 1.18-4.15; P = 0.034). Furthermore, a comparison between monotherapy arms revealed that both interventions had similar effects on the overall outcome (OR = 1.24, 95%CI: 1.02-5.8; P = 0.062). CONCLUSION: A Peg- IFNα and TDF combination therapy resulted in improved virologic response and was safe in HBeAg negative patients. Monotherapy with Peg-IFNα or TDF procured limited benefits in comparison. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT20181113041635N1).

Sustained serological and complete responses in HBeAg-positive patients treated with Peginterferon alfa-2b: a 6-year long-term follow-up of a multicenter, randomized, controlled trial in China.

BACKGROUND: Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. METHODS: Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 µg/kg/wk. 24 weeks or 1.5 µg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL. RESULTS: The proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 µg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2-29.9%) and sustained CR (14.8-18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU. CONCLUSIONS: PEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.

Study on the association between the efficacy of peg-IFN and the complexity of TP and RT in chronic hepatitis B / 中华实验和临床病毒学杂志

Objective@#To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B.@*Methods@#Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation.@*Results@#Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response.@*Conclusions@#The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.

Effectiveness of sofosbuvir/pegylated-interferon plus ribavirin in treatment of hepatitis C virus genotype 4 patients.

INTRODUCTION: New regimens involving direct-acting antiviral agents (DAAs) have recently been approved for the treatment of hepatitis C virus (HCV) genotype 4 (GT4). The current study aims to assess the efficacy and safety of sofosbuvir (SOF) with pegylated interferon (PegINF)/ribavirin (RBV) for chronic HCV GT4 patients at the beginning of the interferon-free era. MATERIAL AND METHODS: Between March 2015 and November 2015, 99 patients (59 naïve and 40 experienced) infected with HCV GT4 were enrolled in the study. Eligible patients received daily oral 400 mg SOF, RBV (body weight: < 75 kg, 1000 mg; < 75 kg, 1200 mg), the dose modified according to patient tolerability, plus 180 µg PegINFα-2 once weekly for 12 weeks. RESULTS: Among the patient cohort, sustained virological response 12 weeks after the end of treatment (SVR12) was achieved by 88% (87/99) of all patients, by 93% (55/59) of naïve patients and by 80% (32/40) of experienced patients. Regarding treatment failure, the data recorded 12% (12/99) of patients (4 null responses and 8 relapsers). Otherwise, the most common adverse events observed during the study included headache, nausea, fatigue, dyspnea, influenza-like illness, anemia, and leukopenia. CONCLUSIONS: SOF combination-based therapies were considered promising choice regimens for chronic HCV infection. The present findings suggest that the combination of the SOF/PegINF/RBV regimen was effective for Egyptian patients with HCV GT4. The recorded adverse events and viral outcome revealed the high need for further efforts to minimize the side effects of the current regimen and/or replace PegINF with additional potent DAA(s) to increase SVR12 to achieve 100%.

Therapeutic effects of pegylated-interferon-α2a in a mouse model of multiple sclerosis.

INTRODUCTION: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. The aim of the present research was to examine the therapeutic efficacy of Peg interferon alpha 2a (Peg-IFN α-2a) as a serine protease inhibitor on EAE model. MATERIAL AND METHODS: EAE induction was performed in female C57BL/6 mice by myelin oligodendrocyte glycoprotein (35-55) (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion, and Peg-IFN α-2a was used for the treatment of EAE. During the course of the study, clinical evaluation was assessed, and on day 21 post-immunisation blood samples were taken from the heart of mice for evaluation of IL-6, and enzymatic and non-enzymatic antioxidants. The mice were sacrificed and the brains and cerebellums were removed for histological analysis. RESULTS: Our findings indicated that Peg-IFN α-2a had beneficial effects on EAE by attenuation of the severity and a delay in the onset of disease. Histological analysis showed that treatment with Peg-IFN α-2a can reduce inflammation criteria. Moreover, in Peg-IFN α-2a-treated mice the serum level of IL-6 was significantly less than in controls, and total antioxidant capacity was significantly more than in the control animals. CONCLUSIONS: These data indicate that Peg-IFN α-2a as an anti-serine protease with immunomodulatory properties may be useful for the treatment of MS.

HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog: New Switch Study.

Background and Aims: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusions: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Factors Affecting the Virological Response Among Chronic Hepatitis C Virus Patients in Yemen.

Hepatitis C virus (HCV) infection is increasingly seen as a major public health problem, threat, and concern worldwide. In Yemen about 1.7% of the population is infected with chronic hepatitis C. This study aimed to detect the predictors for response to pegylated interferon and ribavirin (Peg-IFN/RBV) in chronic HCV Yemeni patients. The study was conducted on 100 patients with chronic HCV who received Peg-IFN/RBV in the 48th Military Hospital in Sana'a Yemen, from 2011 to 2013. All patients were subjected to complete history taking, thorough clinical examinations, routine laboratory investigation, and abdominal ultrasonography. The HCV RNA was assessed at week 72 of treatment to detect whether the patient achieved sustained virological response (SVR). The SVR was achieved in 64% of the samples. Age above 40, Khat chewing, and obesity were the sociodemographic factors that predict good response for Peg-IFN/RBV combined therapy. Platelet count, alpha feto-protein (AFP), aspartate transaminase (AST), and alanine transaminase (ALT) levels were the basic laboratory investigations that gave favorable response. Significant predictors of sustained response included: older than 40 years (OR = 0.136, P = 0.042), Khat chewer (OR = 0.016, P = 0.008), body mass index (BMI) (OR = 0.055, P = 0.029) and increase in fasting blood glucose (OR = 0.925, P = 0.004), alkaline phosphatase (OR = 0.969, P = 0.001), total and bilirubin (OR = 0.058, P = 0.017), AST (OR = 1.033, P = 0.002), and albumin (OR = 6.490, P = 0.021). Studying the independent variables of response, we revealed that male gender, BMI, ALT >40, AFP >10, viremia >600, and hemoglobin and thyroid stimulating hormone (TSH) levels are variables associated with failure of end of treatment response (ETR) and SVR.

Change of serum lipid profiles during antiviral therapy in chronic hepatitis C / Монголын Анагаах Ухаан

Background @#Low triglycerides and cholesterol was associated with hepatitis C virus (HCV) infection. Chronic HCV infection is the main cause of liver injury and it may influence to serum lipid levels. We aimed to evaluate the effect of antiviral treatment on the change of lipid profiles during interferon-based anti-HCV treatment. @*Material and Methods @#Totally 863 patients who completed the interferon-based antiviral therapy in Kaohsiung Medical University Hospital were included in this present study. The lipid profile measured and assessed in the baseline of the treatment and after 6 months of completion of the treatment. @*Results @#The most of the patients (81.2%) were achieved sustained virological response (SVR) by antiviral therapy. There was no significant difference between baseline triglycerides (TG) levels in the SVR group and non SVR groups. The TG levels at 6 months after completion of the treatment was significantly elevated in SVR group (102.9±57.0 mg/dL, p=0.0001) but did not elevated in non SVR group (94.5±45.6 mg/dL, p=0.690) compared with baseline TG levels. </br> After adjusting patients by four indexes for fibrosis (FIB4) in cut-off point 3.25, serum TG levels significantly increased in low FIB4 group (103.2±57.9 mg/dL, p=0.0001) but not in high FIB4 group (98.1±49.6 mg/dL, p=0.095) after 6 months end of the treatment. Serum TG level was increased greater in patients who had low FIB4 score and patients who achieved SVR (baseline 89.1±34.8 mg/dL; 6 months after treatment 104.3±59.3 mg/dL, paired T test p=0.0001). @*Conclusion@#The eradication of HCV is the main cause of the increase of lipids after Pegylated Interferon and Ribavirin treatment. </br> However advanced fibrosis also has an effect in increase of TG after the treatment.

The experience of management of chronic hepatitis B in China.

During the past 30 years, with the possible biggest population with chronic HBV infection in the world, the physicians and scientists in China have unique experience in the fight against HBV. Even though some drugs are not recommended anymore, but this kind of experience are very helpful for the development of new medicine and strategy against HBV.