Interferon Therapy For Chronic Hepatitis Research Articles

Comparative effectiveness of seven interventions for chronic hepatitis D: a systematic review and network meta-analysis of randomized controlled trials

ObjectiveTo compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs, and Placebo] to treat chronic hepatitis D.MethodsWe followed PRISMA-NMA guidelines, searched databases (Cochrane Library, PubMed, EMBASE, and Web Of Science) for eligible randomized controlled trials (RCTs), and applied STATA17.0 software to execute the meta-analysis.ResultsWe included 14 randomized controlled trials (814 patients) comparing seven different interventions. The results of the network meta-analysis showed that: ① Sustained virological response (after 24 weeks of follow-up): Four intervention groups (BLV + IFN, IFN alone, IFN + NAs, and NAs alone) were effective (relative risk (RR) = 13.30, 95% confidence interval (Cl) [1.68,105.32], RR = 12.13, 95% Cl [1.46,101.04], RR = 5.05, 95% Cl [1.68,15.19], RR = 5.03, 95% Cl [1.66,15.20]), with no statistically significant differences between the four groups. The top three in probability rankings were: BLV + NAs, BLV + IFN, and BLV alone (surface under the cumulative ranking curve (SUCRA) = 86.8%, 80.3%, and 48.4%; ② Sustained biochemical response (after 24 weeks of follow-up): BLV + IFN and IFN were superior to BLV (RR = 14.71, 95% Cl [1.14,189.07], RR = 16.67, 95% Cl [1.39,199.52]). The top three were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 86.9%,81.2%, and 64.3%). ③ Histological response: NAs were superior to BLV (RR = 2.08, 95% Cl [1.10,3.93]), whereas the difference between other treatment regimens was not statistically significant, and the top three in the probability ranking were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 75.6%, 75.6%, and 61.8%).ConclusionsIFN, IFN + BLV, and IFN + NAs were effective in clearing HDV RNA and normalizing alanine aminotransferase levels; however, IFN and IFN + NAs had a high rate of viral relapse at 24 weeks post-treatment follow-up. There was no additional benefit of adding NAs to IFN therapy for chronic hepatitis D; however, the combination of IFN + BLV significantly improved short-term HDV RNA clearance, which showed strong synergistic effects. The seven regimens included in the study did not contribute significantly to liver histological improvement. Therefore, the IFN + BLV combination has the most potential as a treatment option to improve the long-term prognosis or even cure chronic hepatitis D.Trial registrationThis systematic evaluation and meta-analysis was registered with PROSPERO under the registration number: CRD42022314544.)

Analysis of clinical characteristics of thyroid disorders in patients with chronic hepatitis B treated with pegylated-interferon alpha

BackgroundThyroid disorders (TD) is a common complication of pegylated-interferon alpha (Peg-IFNα) therapy. Few studies have investigated the relationship between TD and the efficacy of interferon therapy for chronic hepatitis B (CHB). Therefore, we analyzed the clinical characteristics of TD in patients with CHB treated with Peg-IFNα, and evaluated the correlation between TD and Peg-IFNα treatment efficacy.MethodsIn this retrospective study, the clinical data of 146 patients with CHB receiving Peg-IFNα therapy were collected and analyzed.ResultsDuring the course of Peg-IFNα therapy, positive conversion of thyroid autoantibodies and TD occurred in 7.3% (85/1158) and 8.8% (105/1187) patients, respectively, and was diagnosed more often in women. The most common thyroid disorder was hyperthyroidism (53.3%), followed by subclinical hypothyroidism (34.3%). We found that thyroid function returned to normal in 78.7% of patients with CHB, and thyroid antibody levels returned to the negative range in approximately 50% of patients after interferon treatment cessation. Only 25% of patients with clinical TD required treatment. Compared with patients with hypothyroidism/subclinical hypothyroidism, patients with hyperthyroidism/subclinical hyperthyroidism showed greater reduction and seroclearance of hepatitis B surface antigen (HBsAg) levels.ConclusionsTD are not an absolute contraindication for interferon therapy; however, patients should be monitored closely during interferon therapy. In pursuit of functional cure, a balance between efficacy and safety must be achieved.

Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies

In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33–0.43) for sustained virologic response (SVR) and 1.70 (1.61–1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19–0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19–0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence.

Interferon-related gene array in predicting the efficacy of interferon therapy in chronic hepatitis B

This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT 2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 ( t = 10.58, P < 0.001), 5.59 ( t = 3.37, P = 0.028) and 10.83 ( t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.

Serum miR-192-5p levels predict the efficacy of pegylated interferon therapy for chronic hepatitis B.

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and -6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24-weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor (Odds 4.5, P = 0.041). Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.

A Case of Intrahepatic Cholangiocarcinoma that Developed 12 Years after Sustained Virological Response was Achieved to Interferon Therapy for Chronic Hepatitis C

A Case of Intrahepatic Cholangiocarcinoma that Developed 12 Years after Sustained Virological Response was Achieved to Interferon Therapy for Chronic Hepatitis C

Treated with interferon and the gene polymorphism of CGRP and its receptor.

This case-control study aims to investigate the relationship of polymorphisms of four gene loci (CGRP rs155209 and rs3781719, RAMP1 rs3754701 and rs7590387) with the prognosis of interferon therapy for chronic hepatitis B (CHB). A total of 317 CHB patients receiving interferon alone for the first time were recruited in northern China, and peripheral blood samples were obtained. The single-nucleotide polymorphisms (SNPs) in rs155209, rs3781719, rs3754701, and rs7590387 were genotyped using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Univariate and multivariate logistic regression methods were employed to assess the correlation between CHB prognosis treated with interferon and polymorphisms of these gene loci. The study clearly demonstrated the relevance of polymorphisms of rs155209, rs3781719, rs3754701, and rs7590387 with DNA response and ALT response after interferon treatment. CHB patients with CGRP rs155209C had a lower risk of developing DNA response (CT vs. TT: OR = 0.159, 95% CI = 0.086-0.294, Padj < 0.001; CC vs. TT: OR = 0.131, 95% CI = 0.059-0.288, Padj < 0.001), as well as a lower risk of developing ALT response (CT vs. TT: OR = 0.530, 95% CI = 0.323-0.869, Padj < 0.05). Moreover, CHB patients with RAMP1 rs3754701T allele were more prone to develop DNA response (AT vs. AA: OR = 2.061, 95% CI = 1.237-3.435, Padj < 0.05; TT vs. AA: OR = 5.676, 95% CI =1.247-25.837, Padj < 0.05), and they also more likely to develop ALT response (AT vs. AA: OR = 1.766, 95% CI = 1.098-2.840, Padj < 0.05). We did not find a significant association between CGRP rs3781719 or RAMP1 rs7590387 and DNA response or ALT response. This study revealed that CGRP rs155209 and RAMP1 rs3754701 polymorphisms, but not CGRP rs3781719 and RAMP1 rs7590387, were correlated with interferon therapy prognosis for CHB in Han Chinese population, and RAMP1 rs3754701T was a protective factor for ALT response and DNA response, but CGRP rs155209C carriers were less prone to DNA and ALT responses.

A clinical study of clinical cure after the addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with nucleos(t)ide analogues

目的 探讨核苷(酸)类似物(NAs)经治的慢性乙型肝炎患者获得临床治愈的优势人群，为临床医生追求乙型肝炎临床治愈提供更多的方法。 方法 选取2017年10月—2019年10月在鹤壁市第三人民医院接受NAs治疗且HBsAg低水平的慢性乙型肝炎患者42例作为研究对象，分为联合治疗组(A组, n=22)和NAs单药治疗组(B组, n=20)。A组采用NAs联合聚乙二醇干扰素(PEG-IFN)抗病毒治疗48周，部分患者24周停用PEG-IFN继续NAs单药治疗。B组仅采用NAs抗病毒治疗，两组均观察至48周，通过乙型肝炎五项定量检测评估疗效。计量资料两组间比较采用t检验；计数资料两组间比较采用Fisher精确检验。影响因素相关分析采用logistic回归法。 结果 48周治疗终点A组的HBsAg清除率(45.5%)和HBsAg血清学转换率(31.8%)远高于B组(均为0)(P值均＜0.01)；HBsAg＜1000 IU/ml、＜500 IU/ml、＜100 IU/ml、＜10 IU/ml人群的HBsAg清除率分别为52.6%、61.5%、66.7%和100%；HBsAg在500~1000 IU/ml、100~500 IU/ml、10~100 IU/ml、＜10 IU/ml区间人群的HBsAg清除率分别为33.3%、50%、40%和100%。4例基线HBsAg＜10 IU/ml者(占联合治疗组18.2%)，联合治疗12周取得临床治愈，观察至48周时2例抗-HBs＞100 IU/ml，2例抗-HBs＞1000 IU/ml。HBsAg清除的多因素logsitic回归分析结果显示：开始联合治疗时的年龄对HBsAg清除存在影响(OR=0.877，95%CI：0.781~0.985，P=0.026)，HBsAg阴转患者的年龄集中在36~49(44.20±4.49)岁；基线HBsAg水平也对HBsAg清除存在影响(OR=0.996，95%CI：0.992~1.000，P=0.050)。 结论 加用IFN治疗核苷(酸)类似物经治的HBsAg低水平的慢性乙型肝炎患者能够显著提高临床治愈率，年龄越小、HBsAg水平越低，联合治疗时间越短，相较于NAs用药时间、种类，年龄和基线HBsAg水平更关键。

Direct acting antivirals are associated with more liver stiffness regression than pegylated interferon therapy in chronic hepatitis C patients

ABSTRACT Objectives Extent of post-treatment fibrosis change in patients with different stages of fibrosis not fully known. We aimed to study changes in liver fibrosis in chronic hepatitis C patients who were treated with pegylated interferon/ribavirin (PEG/RBV) or direct acting antivirals (DAAs). Methods Retrospective evaluation of results of transient elastography (TE) was done before and 1 year after end of treatment for patients treated with PEG/RBV (n = 268) and DAAs (n = 245). Results The average age was 45.54 ± 10.64 years; mainly males. All patients in the DAAs group achieved sustained virological response (SVR), unlike 56.3% of the patients in the PEG/RBV group. F3-F4 fibrosis was predominant in the PEG/RBV nonresponder patients (51.3%) and DAAs responders (57.1%). TE decreased 1 year after end of treatment (p = 0.001) in the viral responders of the PEG/RBV group (7.44 ± 4.02 vs. 10.24 ± 7.29 kPa) and DAAs group (12.12 ± 9.21 vs. 16.81 ± 12.84 kPa) respectively. The delta TE change in the DAAs responders was higher than the PEG/RBV responders (p = 0.001) and PEG/RBV nonresponders (p = 0.001). The percentage of patients with liver fibrosis regression was higher in DAAs responders (52.5%) than in PEG/RBV responders (23.3%). Conclusion Treatment with DAAs is associated with fibrosis improvement more than treatment with PEG/RBV in chronic hepatitis C patients.

IL-28B variant as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy.

Single-nucleotide polymorphisms (SNPs) of the interleukin-28B (IL-28B) gene are associated with the effectiveness of interferon therapy for chronic hepatitis C infection. Whether the IL-28B genotype affects the course of treatment and the outcomes of patients with advanced hepatocellular carcinoma (HCC) is unknown. We detected the IL-28B SNP (rs8099917) using TaqMan PreDesigned SNP Genotyping Assays to assess the effects of the IL-28B genotype on treatment efficacy and prognosis of patients with advanced HCC treated with hepatic arterial infusion chemotherapy (HAIC) between September 2003 and January 2015. The study included 154 patients who received HAIC to treat advanced HCC, among which 27 (17.5%) had the minor genotype, IL-28B rs8099917 TG or GG, and the others had the major genotype, IL-28B rs8099917 TT. The objective response rates of patients with the minor or major genotype were 51.9% and 29.1% (P=0.022), respectively. Multivariate analysis revealed that the minor genotype remained associated with the response to HAIC (odds ratio, 2.620; P=0.026). The median overall survival of patients with major or minor genotypes was 14.1 and 16.9months, respectively, and the overall survival of patients with the major genotype was significantly shorter than that of patients with the minor genotype (P=0.027). Multivariate analysis revealed that the major genotype was an independent, unfavorable prognostic factor (hazard ratio, 1.720; P=0.024). Consistent results were obtained in selected populations after propensity score matching analysis. The IL-28B SNP (rs8099917) will serve as a useful predictor of the outcomes of patients with advanced HCC treated with HAIC.

Retinal Vein Occlusion Associated with Interferon Therapy for Chronic Hepatitis C

Retinal Vein Occlusion Associated with Interferon Therapy for Chronic Hepatitis C

Maintenance interferon therapy in chronic hepatitis C patients who failed initial antiviral therapy: A meta-analysis.

Objectives:To evaluate the effect of pegylated interferon maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy.Methods:This is a meta-analysis of 6 randomized controlled trials that met the eligibility criteria. In all, 2438 chronic hepatitis C patients who failed to achieve sustained virologic response after initial treatment with pegylated interferon and ribavirin (antiviral therapy nonresponders or relapsers) were enrolled; 1237 patients received maintenance therapy (Maintenance group) and 1201 received no treatment (Observation group).Results:The pooled analyses found that patients in the Maintenance group had a significantly higher rate of normal alanine aminotransferase than did patients in the Observation group (pooled odds ratio [OR] 4.436, 95% confidence interval [CI] 1.225–16.064, P = .023), but there was no significant difference between the 2 groups in the incidence of hepatocellular carcinoma (pooled OR 0.872, 95% CI 0.501–1.519, P = .630), or the mortality rate (pooled OR 1.564, 95% CI 0.807–3.032, P = .185).Conclusions:Interferon-based maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy improved liver inflammation as indicated by blood chemistry (alanine aminotransferase).

Obesity and recurrence-free survival in patients with hepatocellular carcinoma after achieving sustained virological response to interferon therapy for chronic hepatitis C.

AimSome patients who achieve a sustained virological response (SVR) to interferon (IFN) treatment for chronic hepatitis C prior to hepatic resection for hepatocellular carcinoma (HCC) experience postoperative recurrence. This study investigated the relationship between obesity and postoperative HCC recurrence in SVR patients.MethodsFifty‐nine patients who had achieved SVR before hepatic resection were evaluated. Patients had a solitary tumor ≤5 cm in diameter or ≤3 lesions each ≤3 cm in size with no macroscopic vascular invasion (Milan criteria). Patient characteristics potentially associated with recurrence risk were investigated.ResultsThree‐, 5‐, and 7‐year recurrence‐free survival after surgery were 65%, 44%, and 41%, respectively. Univariate analysis showed that obesity (P < .01), hypertension (P = .038), and non‐anatomical resection (P = .022) were significantly associated with a lower recurrence‐free survival rate. In a multivariate analysis, obesity (hazard ratio, 2.8; 95% confidence interval [CI] 1.3‐6.1; P < .01) and non‐anatomical resection (hazard ratio, 2.7; 95% CI 1.1‐6.2; P = .025) were independently associated with postoperative recurrence. Three‐, 5‐, and 7‐year overall survival rates after surgery were 100%, 80%, and 64% in obese patients and 100%, 92%, and 82% in non‐obese patients, respectively (P = .014). However, other variables showed no significant difference in the overall survival rate.ConclusionsObesity and non‐anatomical resection were independent risk factors for HCC recurrence after hepatic resection and successful IFN therapy. Obesity is an important clinical problem to consider to improve postoperative outcomes in such patients.

FRI-259 - Basal values and on treatment decline of hepatitis B core-related antigen are predictive of response to interferon therapy in chronic hepatitis D

FRI-259 - Basal values and on treatment decline of hepatitis B core-related antigen are predictive of response to interferon therapy in chronic hepatitis D

A case of interstitial pneumonia induced by interferon therapy for chronic hepatitis C

A case of interstitial pneumonia induced by interferon therapy for chronic hepatitis C

Influence of OASL gene polymorphisms on host response to interferon therapy in chronic hepatitis C virus patients

Abstract Hepatitis C virus (HCV) infection becomes a major public health problem and leading cause of chronic liver disease and liver failure. Pegylated interferon-alfa and ribavirin are currently the standard treatment for chronic hepatitis C (CHC). It is indicated that genes that trace the interferon signaling could be associated with the host response to the therapy. In order to investigate the influence of these genes on host related response, we have analyzed seven single nucleotide polymorphisms (rs59248852, rs74390571, rs12811390, rs1169279, rs3213545, rs1083129 and rs2859398) in 2-5-Oligoadenylate- Synthetase-Like (OASL) gene in CHC cases from Republic of Macedonia. A simple and easy to use SNaPshot method was developed. A cohort of 100 HCV RNA positive patients - non responders and 109 patients with achieved virological response after the standard treatment were included in this study. We have found significant association in five of the seven studied SNP` s: rs59248852 [p = 6.5x10-31, OR=55.7 (20.0-155.3)]; rs12811390 [p = 2.2x10-11, OR=4.3 (2.3-6.7)]; rs2859398 [p=1.34x10-9, OR=3.4 (2.2-5.0)]; rs74390571 [p=4.3x10-7, OR=2.9 (1.9-4.4)], and rs1083129 [p=0.0139, OR=2.0 (1.1-3.5)]. The results from this study can be used as a predictive factor of future patient’s selection for the standard therapy, having an important cost benefit for the health insurance system.

Diabetic Ketoacidosis Due to Type 1 Diabetes Mellitus Induced by Interferon Therapy for Chronic Hepatitis C During the Course of Hashimoto’s Thyroiditis: Case Report

Interferon α (IFNα) has been reported to induce several autoimmune diseases, including autoimmune thyroiditis (AITD) and type 1 diabetes (T1D). In addition, co-occurrence of T1D and AITD is well known as one of the variants of the autoimmune polyglandular syndrome type 3. Meanwhile, there are no reports about the risk of development of IFN treatment-related T1D in patients with previously diagnosed AITD. We present a single case report about a 61-yearold Japanese woman with Diabetic Ketoacidosis (DKA) three months after the initiation of the combination therapy with peginterferon α-2b and ribavirin for chronic hepatitis C. She was diagnosed with T1D owing to severely impaired insulin secretion along with DKA and presence of positive GAD antibody. Her T1D was supposed to be induced by IFN therapy. She had received the replacement therapy for hypothyroidism resulting from Hashimoto’s thyroiditis for 30 years. The patient had human leukocyte antigens (HLA), DRB1*04:05 and DQB1*04:01, which are associated with a genetic predisposition for T1D and AITD. Patients with previously diagnosed AITD are assumed to be at high risk for IFN treatment-related T1D because most patients with T1D triggered by IFN were reported to have genetic susceptibilities similar to those with classical T1D and AITD. In conclusion, patients with known AITD should be carefully monitored for their glycemic condition to avoid life-threatening events such as DKA when they receive IFN therapy.

FRI-067 - Impact of sustained virological response to interferon therapy for chronic hepatitis C on recurrence and long-term survival in patients with hepatocellular carcinoma

FRI-067 - Impact of sustained virological response to interferon therapy for chronic hepatitis C on recurrence and long-term survival in patients with hepatocellular carcinoma

To Find out the Frequency of Depression During Interferon Therapy for Chronic Hepatitis C

To Find out the Frequency of Depression During Interferon Therapy for Chronic Hepatitis C

Liver Gene Expression Profiles Correlate with Virus Infection and Response to Interferon Therapy in Chronic Hepatitis B Patients

The natural course of chronic hepatitis B (CHB) infection and treatment response are determined mainly by the genomic characteristics of the individual. We investigated liver gene expression profiles to reveal the molecular basis associated with chronic hepatitis B and IFN-alpha (IFNα) treatment response in CHB patients. Expression profiles were compared between seven paired liver biopsy samples taken before and 6 months after successful IFNα treatment or between pretreatment biopsy samples of 11 IFNα responders and 11 non-responders. A total of 132 differentially up-regulated and 39 down-regulated genes were identified in the pretreated livers of CHB patients. The up-regulated genes were mainly related to cell proliferation and immune response, with IFNγ and B cell signatures significantly enriched. Lower intrahepatic HBV pregenomic RNA levels and 25 predictive genes were identified in IFNα responders. The predictive gene set in responders significantly overlapped with the up-regulated genes associated with the pretreated livers of CHB patients. The mechanisms responsible for IFNα treatment responses are different between HBV and HCV patients. HBV infection evokes significant immune responses even in chronic infection. The up-regulated genes are predictive of responsiveness to IFNα therapy, as are lower intrahepatic levels of HBV pregenomic RNA and pre-activated host immune responses.