Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

Objective: To investigate the efficacy of sequential therapy with telbivudine in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients with partial response after a standard course of interferon therapy. Methods: A retrospective cohort study was performed for 58 HBeAg-positive CHB patients with partial response at the end of interferon therapy (48-60 weeks) from January 2009 to December 2013. According to whether telbivudine was used sequentially or withdrawn at the end of the course of treatment, the patients were divided into telbivudine sequential therapy group and withdrawal group, and the two groups were compared with in terms of biochemical, virological, and serological response rates. The chi-square test, the t-test, and the non-parametric test were used based on data type. Results: A total of 58 patients were enrolled in this study, with 31 in the telbivudine sequential therapy group and 27 in the withdrawal group. At 12 and 24 weeks after interferon therapy ended, the telbivudine sequential therapy group had a significantly higher HBeAg clearance rate than the withdrawal group (22.6%/29.0% vs 0%/3.7%, P < 0.05). At week 48 of follow-up, the telbivudine sequential therapy group had a significantly higher combined response rate than the withdrawal group (22.6% vs 0%, P = 0.015). Among the 31 patients in the telbivudine sequential therapy group, 11 had an increase in creatine kinase during the administration of telbivudine. No patient in either group experienced serious adverse reactions during follow-up, such as muscular soreness, myositis, peripheral neuropathy, renal dysfunction, and liver function decompensation. Conclusion In HBeAg-positive CHB patients with partial response to interferon therapy, sequential therapy with telbivudine can increase serological HBeAg clearance rate and combined response rate at week 48, and it is safe in HBeAg-positive CHB patients achieving partial response at the end of interferon therapy.

Objective: 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 < 1 500 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. Conclusion 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.

The incidence rate of hepatocellular carcinoma (HCC) is increasing around the world and tends to decrease in East Asia and several regions in China;however, China still has higher incidence rate and mortality rate of HCC than most countries.Studies have shown that long-term antiviral therapy can inhibit HBV replication to a very low level or help patients with HCV infection achieve sustained virologic response, which can further reduce the incidence rate of virus-related HCC.New evidence suggests that compared with nucleos(t)ide analogues, PEG-IFNα has a better effect of secondary prevention.Studies also indicate that interferons play an important role in tertiary prevention of virus-related HCC.This article reviews the epidemiological studies on virus-related HCC in recent years and the role of antiviral therapy in second and tertiary prevention and points out that adequate and effective antiviral therapy is the basis for preventing the development and recurrence of HCC.

Objective To investigate the distribution of serum hepatitis B surface antigen (HBsAg) levels in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Methods A total of 226 cases of HBV-related HCC were collected from June 2009 to December 2013.Demographic characteristics of patients with different barcelona clinica liver cancer (BCLC) stages,the status of cirrhosis and HBsAg levels with different virological indicators were compared.HBsAg quantification was tested by chemiluminescence.The statistical analysis was conducted by t test,x2 test,Kruskal-Wallis H rank sum test and Mann-Whitney U rank sum test.Results A total of 226 cases were included with 201male patients and 25 female patients.HBsAg levels in HBV-related HCC patients with different ages were significantly different (x2=12.30,P =0.015),but with no statistical difference in those with different gender (Z=-0.35,P＞0.05).The HBsAg levels were not significantly different between patients with or without liver cirrhosis (Z =-0.80,P =0.419).HBsAg levels in liver cirrhosis cases with different liver function stages were not significant different (x2=2.15,P=0.341).HBsAg levels in HBeAg-positive group or HBV DNA positive group were significantly higher than those in HBeAg-negative group or HBV DNA negative group,respectively (Z =-3.67 and-4.80,respectively,both P＜0.01).The HBsAg levels in patients with different BCLC stages were not significantly different (x2 8.05,P =0.09).No significant differences were found in HBsAg levels between patients with or without portal vein violation,lymph node transfer or distant transfer (Z=-0.65,-0.03 and-1.24,respectively,all P＞ 0.05).The constituent ratios of patients with different HBsAg levels in different BCLC stages were statistically different (x2 =28.17,P-0.005).Conclusions There are no significant differences of HBsAg levels in patients with different BCLC stages,indicating that HBsAg may not be a contributor for disease progression after emergence of HCC.

Objective To investigate the correlation between non-alcoholic fatty liver disease and serum and histological viral parameters in patients with chronic hepatitis B (CHB).Methods Clinical and laboratory data from patients with CHB who received liver biopsy from 2009 to 2015 were collected. Patients were divided into steatosis and non-steatosis groups based on the presence of steatosis in liver biopsies.Propensity score matching (PSM)was conducted to adjust the confounding bias including age, sex,body mass index (BMI),total cholesterol (TC)and triglyceride (TG).Correlation of liver fatty and viral parameters was compared between steatosis and non-steatosis groups.Student t test,χ2 test,rank sum test and Pearson correlation test were employed to analyze the data.Results A total of 874 patients with a mean age of (37.0±10.1)years were enrolled in the study,with 690 males and 184 females,and 270 (30.9%)patients were diagnosed with steatosis by liver biopsy.Age,gender,BMI,TC and TG were significantly different between the two groups before PSM (all P <0.05),but those were comparable after PSM (all P >0.05 ).Serum hepatitis B virus (HBV)DNA,hepatitis B surface antigen (HBsAg) level,proportion of hepatitis B e antigen (HBeAg )positivity,HBsAg and hepatitis B core antigen (HBcAg)immunohistological staining in liver tissue were not significantly different between steatosis and non-steatosis groups after PSM (all P >0.05).Patients in steatosis group were stratified into two groups according to the degree of steatosis confirmed by liver biopsies:mild steatosis group (F1 )and medium to severe steatosis group (F2-F4).The serum alanine aminotransferase (ALT),HBV DNA,HBsAg level, proportion of HBeAg positivity,immunohistological HBsAg and HBcAg staining in liver tissue between those two groups showed no differences (all P >0.05).The mean rank of liver inflammation and fibrosis in F1 group were 129.9 and 128.2,respectively,which were both significantly higher than those in F2-F4 group (105 .9 and 108.5 ,respectively;both P <0.05).Steatosis was negatively correlated with either inflammatory grade (r=-0.183,P =0.005)or fibrosis stage (r=-0.150,P =0.020).Conclusions There is no correlation between serum viral factors and hepatic steatosis. Hepatic steatosis is not associated with the expressions of HBsAg and HBcAg in liver tissue.The severity of steatosis is negatively correlated with both liver inflammation and fibrosis.

Objective To investigate the early diagnostic value and cost‐effectiveness analysis of common inflammatory markers , including interleukin‐6 (IL‐6 ) , procalcitonin (PCT ) and C‐reactive protein (CRP) in cirrhotic patients with infectious fever .Methods From January 2012 to January 2015 , cirrhotic patients hospitalized in liver center of First Affiliated Hospital ,Fujian Medical University who were excluded with community‐acquired infections and developed fever 48 hours after admission were selected .According to having infection or not ,they were divided into infection group and non‐infection group .White blood cell count (WBC) ,neutrophil percentage (N % ) ,IL‐6 ,PCT ,and CRP at admission (baseline) and at the time point of fever were recorded .The diagnostic threshold of WBC ,N% ,IL‐6 , PCT ,and CRP for infectious fever in cirrhotic patients were analyzed by receiver operating characteristic analysis curve (ROC) .The cost‐effectiveness (C/E) of those biomarkers were compared .Results A total of 299 cases were enrolled ,with 162 in infection group and 137 in non‐infection group .Two hundred and forty‐four were male and 55 were female .The mean age was 55 .1 ± 13 .0 years .Upon the onset of fever , WBC ,N% ,IL‐6 ,PCT ,and CRP of infection group were all significantly higher than those of non‐infection group (all P< 0 .05) .The area under the curve of IL‐6 for infectious fever was 0 .939 (95% CI 0 .910 - 0 .968) ,which was significantly higher than those of PCT and CRP (Z = 5 .718 and 9 .048 , respectively ,both P< 0 .01) .The optimal cut‐off point of IL‐6 was 184 .5 ng/L ,with the sensitivity of 85 .2% and specificity of 94 .9% .C/E value was 38 .3 for N% ,and 51 .2 for CRP . However ,both specificity and specificity of CRP and N % were low .C/E value was 389 .0 for PCT and 63 .4 for IL‐6 .IL‐6 had the highest sensitivity (85 .2% ) and specificity (94 .9% ) among all the biomarkers .Conclusions Compared to PCT and CRP ,IL‐6 has the highest sensitivity and specificity with lower cost‐effectiveness for diagnosis of infectious fever in cirrhotic patients .

Esophagogastric variceal bleeding and hepatorenal syndrome are common complications in patients with decompensated liver cirrhosis and portal hypertension. Terlipressin can lead to the constriction of visceral vessels, reduce portal venous pressure, and increase renal perfusion and is the first-line drug. In recent years, it has been reported that some patients experienced hyponatremia during the treatment with terlipressin. Since patients with liver cirrhosis tend to develop hyponatremia, the application of terlipressin may have an adverse effect on the management of serum sodium level in such patients. This article summarizes the incidence rate of hyponatremia during terlipressin treatment and related risk factors and introduces the pathogenesis of hyponatremia during terlipressin treatment in patients with decompensated liver cirrhosis and the treatment principles for hyponatremia. If the occurrence of hyponatremia can be controlled, terlipressin may be an effective drug for the treatment of portal hypertension.