doi: 10.1111/jvh.13150pmid: 31380584
Chronic hepatitis B virus (HBV) infection continues to pose a serious global health threat and a significant socio‐economic burden in many areas of the world. Almost all current clinical practice guidelines on the management of chronic hepatitis B (CHB) infection recommend that eligible patients pursue the optimal treatment endpoint, which is defined as HBsAg loss with or without anti‐HBs seroconversion. This review describes the effects of various regimens containing pegylated interferon (peg‐IFN)‐alpha on functional cure and the outcome of hepatocellular carcinoma (HCC) in patients with CHB. Peg‐IFN‐α monotherapy is a treatment option recommended by local and international clinical practice guidelines to help more CHB patients achieve a sustained off‐treatment virological response, which is particularly appropriate for relatively young patients who demand a finite treatment approach. Peg‐IFN‐α add‐on or sequential therapy in patients who have achieved a suppressed viral load after nucleos(t)ide analog (NA) therapy may offer further benefits on HBeAg seroconversion and HBsAg decline, although the effects of de novo combination therapy with peg‐IFN‐α and NAs on long‐term outcomes remain unclear. Evaluation of baseline and on‐treatment predictors is useful for selecting the patients who are likely to achieve additional benefits. Furthermore, some recent studies have shown that peg‐IFN‐α–based therapy results in better prevention of HBV‐related hepatocellular carcinoma (HCC), especially in high‐risk patients.
Li, Ming‐Hui; Yi, Wei; Zhang, Lu; Lu, Yao; Lu, Hui‐Hui; Shen, Ge; Wu, Shu‐Ling; Hao, Hong‐Xiao; Gao, Yuan‐Jiao; Chang, Min; Liu, Ru‐Yu; Hu, Lei‐Ping; Cao, Wei‐Hua; Chen, Qi‐Qi; Li, Jun‐Nan; Wan, Gang;
Xie, Yao; Yi, Wei; Zhang, Lu; Lu, Yao; Hao, Hong‐Xiao; Gao, Yuan‐Jiao; Ran, Chong‐Ping; Lu, Hui‐Hui; Chen, Qi‐Qi; Shen, Ge; Wu, Shu‐Ling; Chang, Ming; Ping‐Hu, Lei; Liu, Rui‐Yu; Sun, Lei; Wan, Gang;
Li, Guojun; Zhang, Qiran; Yu, Yiqi; Qiu, Chao; Zhang, Hanyue; Zhang, Miaoqu; Song, Zhangzhang; Yang, Yusheng; Hong, Jiemin; Lu, Jian; Li, Niuniu; Tang, Quanzhen; Xu, Long; Wang, Xuanyi; Zhang, Wenhong; Chen, Zhi
Zhang, Qiran; Li, Guojun; Yu, Yiqi; Qiu, Chao; Zheng, Jianming; Zhang, Hanyue; Zhang, Miaoqu; Song, Zhangzhang; Yang, Yusheng; Du, Xinfang; Hong, Jiemin; Lu, Jian; Li, Niuniu; Tang, Quanzhen; Xu, Long; Wang, Xuanyi;
Liu, Yunhua; Li, Hui; Yan, Xiaohui; Wei, Jia
doi: 10.1111/jvh.13154pmid: 31380585
Achieving ‘clinical cure’ in children with chronic hepatitis B (CHB) with safe and effective antiviral treatment is an unmet medical need. Peginterferon (PegIFN) has higher hepatitis B s antigen (HBsAg) clearance than nucleoside analogs (NUC). Currently, studies on interferon (IFN) in the treatment of Chinese children with CHB are relatively rare. This study aimed to further explore the efficacy of PegIFNα‐2a as an antiviral treatment in Chinese children and analyse the long‐term follow‐up after drug discontinuation. We enrolled 118 patients with CHB (2‐16 years old, 79 cases are males) treated with PegIFNα‐2a by the author in the Third People's Hospital of Kunming City from February 2009 to February 2015. The course of treatment was 52 weeks, with a follow‐up period of 104 weeks. All the patients completed at least 1 dose, of which 104 completed at least 36 weeks of treatment and 104 weeks of follow‐up. During treatment and follow‐up, indicators such as alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA and HBV serological markers were monitored, and the efficacy and safety of PegIFNα‐2a in the treatment of CHB patients were observed. Hepatitis B e antigen (HBeAg) clearance and seroconversion rates were 53.8% and 49%, respectively, when the drug was discontinued; 72.1% and 72.1%, respectively, at the end of the follow‐up; and 98.2% and 98%, respectively, for sustained response. HBsAg clearance and seroconversion rates were 48.1% and 47.1%, respectively, when the drug was discontinued; 53.8% and 52.9%, respectively, at the end of the follow‐up; and 94% and 95.9%, respectively, for sustained response. The HBV DNA suppression rate was 89.4% when the drug was discontinued, 90.4% at the end of the follow‐up and 97.8% for sustained response. Two patients had virological relapse (2.3%) during follow‐up; however, no clinical relapse occurred. Multivariate regression analysis showed that genotype B, weight < 25 kg or between 25 and 45 kg, and reduction of HBsAg by more than 1 log following 24 weeks of treatment were independent predictors of HBsAg clearance at the end of follow‐up. Adverse events that occurred during treatment were similar to those reported in previous clinical studies on PegIFN. The results of this study showed that PegIFN was safe and effective in the treatment of children with CHB, and sustained response could be achieved after treatment. PegIFN treatment of children with CHB helps more achieve ‘clinical cure’.
Fan, Huimin; Lin, Luping; Jia, Shijie; Xie, Min; Luo, Chun; Tan, Xinghua; Ying, Ruosu; Guan, Yujuan; Li, Feng
doi: 10.1111/jvh.13165pmid: 31380586
Chronic hepatitis B virus (HBV) infection (CHB) in children remains a public health challenge despite significant success in programme is established to prevent mother‐to‐child transmission. In particular, CHB in Chinese children are mostly acquired through vertical transmission, which differs from the common infection route reported in other countries and regions. This situation has resulted in a high endemic prevalence of CHB in Chinese adults. Thus, successful treatment of children with CHB will prevent the development of advanced liver diseases in late adulthood. However, there is still no consensus on the clinical guideline to treat paediatric CHB. In this study, we evaluated the potential of interferon alpha (IFNa) treatment for Chinese children with CHB. A total of 41 patients with CHB aged 3‐17 years were enrolled in this retrospective study: 21 patients were treated with pegylated (PEG)‐IFNa and 20 patients without treatment served as the control group. The rates of HBV DNA suppression, hepatitis B e antigen (HBeAg) clearance and hepatitis B surface antigen (HBsAg) clearance were significantly higher in the PEG‐IFNa treatment group than in the control group (P < 0.05 at 48 weeks). Unexpectedly, PEG‐IFNa treatment achieved a high rate of HBsAb production, far exceeding the clinical outcome in documented PEG‐IFNa‐treated CHB adults. Further analysis revealed that younger children (3‐6 years old) were more responsive to PEG‐IFNa treatment with respect to achieving a protective level of HBsAb in a short treatment cycle than adolescents (10‐17 years old). Overall, these results indicate that the immune system of children might have a preserved PEG‐IFNa‐mediated mechanism to completely control HBV, which can help to design new strategies to treat CHB patients.
Duan, Bin‐Wei; Tian, Lan‐Tian; Lin, Dong‐Dong; Zhang, Jing; Guo, Qing‐Liang; Wu, Ju‐Shan; Zeng, Dao‐Bing; Lu, Shi‐Chun
doi: 10.1111/jvh.13164pmid: 31380589
Showing 1 to 10 of 11 Articles
doi: 10.1111/jvh.13151pmid: 31380582
Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)‐negative CHB patients. In this prospective study, 176 HBeAg‐negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3‐6 months during the 48‐week follow‐up. The sustained functional cure was evaluated. After the 48‐week follow‐up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135‐127.151; P = 0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824‐37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure.
doi: 10.1111/jvh.13163pmid: 31380591
Liver necroinflammation is the indicator for treating patients with chronic hepatitis B (CHB) infection. However, there is no suitable non‐invasive index for diagnosing liver necroinflammation. This study aimed to create a non‐invasive index to predict liver necroinflammation in patients who lack clear‐cut clinical inflammation parameters. Patients who were hepatitis B e antigen (HBeAg)‐negative and underwent liver histological diagnosis, had a normal or minimally increased alanine aminotransferase (ALT) level were enrolled. Liver necroinflammation was defined as histological active index ≥4. A logistic regression model (LRM) was established based on the parameters independently associated with liver necroinflammation. Of all 550 patients, 36.73% had necroinflammation. In patients with an abnormal ALT level, the rate of necroinflammation was 52.49%. The area under the curve (AUC) of the ALT level for predicting necroinflammation was 0.655 (95% confidence interval [CI], 0.609‐0.702), and that of the HBV DNA level ≥2000 IU/mL combined with an abnormal ALT level was 0.618. By using the LRM, the AUC improved to 0.769 (95% CI, 0.723‐0.815) with a Youden index of 0.519 and diagnostic accuracy of 75.3%. The cutoff value ≥0.7 in the LRM had a specificity of 97.4% and positive predictive value of 85.0% for predicting necroinflammation. By using the cutoff value <0.15 in the LRM, the presence of necroinflammation could be excluded with a negative predictive value of 90.8%. This study indicated that the LRM can be used to effectively diagnose liver necroinflammation in HBeAg‐negative patients with CHB who have normal or minimally elevated ALT levels.
doi: 10.1111/jvh.13152pmid: 31380590
Although long‐term antiviral treatment with nucleos(t)ide analogs (NAs) can lead to histological improvement in patients with chronic hepatitis B (CHB), a substantial proportion of patients still fail to achieve regression of fibrosis. Here, we investigated whether peginterferon alpha (Peg‐IFNα) add‐on therapy had benefits on fibrosis regression in patients with sustained severe fibrosis even after long‐term NA treatment. We conducted a retrospective analysis of data from 50 patients with CHB receiving 48 weeks of Peg‐IFNα add‐on therapy. All enrolled patients had advanced fibrosis or cirrhosis (S score ≥ 3) at baseline and underwent NA treatment for at least 1 year before Peg‐IFNα addition. Paired liver biopsies before and after Peg‐IFNα add‐on treatment and laboratory tests at baseline, 24 weeks of treatment, 48 weeks of treatment and long‐term follow‐up were analysed. Of the 50 patients enrolled in this study, 34 patients (68.0%) had significant regression of fibrosis, and 42 (84.0%) showed significant remission of inflammation after Peg‐IFNα add‐on treatment. Compared with nonresponders, patients with significant histological improvement showed faster hepatitis B surface antigen (HBsAg) decline and tended to have higher cumulative hepatitis B e antigen (HBeAg) and HBsAg loss rates during long‐term follow‐up. Peg‐IFNα add‐on therapy led to significant regression of fibrosis and resolution of inflammation in patients with advanced fibrosis after long‐term NA treatment.
doi: 10.1111/jvh.13153pmid: 31380588
Although nucleos(t)ide analog (NA) monotherapy is effective in hepatitis B virus suppression and fibrosis regression, serological response rates are not satisfactory. Studies assessing the benefits of combination therapy with NAs and peginterferon alpha (PegIFNα) in patients with chronic hepatitis B (CHB) have produced conflicting results and mainly focused on serological outcomes. Histological changes in response to combination therapy have not been evaluated in real‐world practice. This study aimed to evaluate the histological changes in response to NA‐PegIFNα combination therapy in CHB patients and to comprehensively compare the efficacy of NA‐PegIFNα combination therapy and NA monotherapy. We conducted a retrospective analysis of data from 40 CHB patients who underwent either NA‐PegIFNα combination therapy or NA monotherapy. Changes in histology at 48 weeks after treatment initiation were evaluated. Serological characteristics were also analysed and compared between the NA‐PegIFNα combination therapy and NA monotherapy groups and between histological responders and nonresponders. Compared to baseline biopsies, both fibrosis staging and necroinflammatory grading scores were significantly lower in the second biopsies examined post‐treatment in both groups. Nearly all patients experienced a reduction in inflammation (87.5% in both groups), but there was a subgroup of patients who exhibited either no significant improvement or fibrosis progression (33.3% and 31.2% in the NA monotherapy and NA‐PegIFNα combination therapy groups, respectively). Nearly, all patients achieved ALT normalization and sustained virological response (SVR) after 48 weeks of antiviral treatment. Approximately one‐third of individuals (36.8% and 30% in the two groups, respectively) achieved HBeAg loss at 48 weeks after treatment initiation. Although there were no significant differences in overall rates of histological, biochemical, virological and serological responses between the two groups, an earlier virological response and a higher cumulative SVR rate over time were observed during long‐term follow‐up in patients treated with NA‐PegIFNα combination therapy (P = 0.0129). Trends of more rapid HBeAg loss and a higher cumulative HBeAg loss rate throughout long‐term follow‐up were also observed but were not statistically significant. The ALT normalization rates at 24 and 48 weeks after treatment initiation were associated with the histological response. Significant regression of fibrosis and resolution of necroinflammation were induced with either NA‐PegIFNα combination therapy or NA monotherapy. Significant biochemical, virological and serological responses were observed in both groups, and the response rates at 48 weeks were similar in the two groups. Over time during long‐term follow‐up, the virological and serological responses were faster and superior following the combination regimen.