HBeAg Seroconversion Research Articles

Qingre Lishi Tuihuang therapy for acute icteric hepatitis B: A systematic review

ObjectiveTo assess the efficacy of Qingre Lishi Tuihuang therapy (QLTT) for acute icteric hepatitis B infection. MethodsEight electronic databases were searched from inception to December 2016 with no language restrictions for reports of randomized controlled trials evaluating the effect of QLTT treating acute icteric hepatitis B. Two researchers independently extracted detailed data and assessed methodological quality. Review Manager 5.3.0 software was used to analyze the data. ResultsA total of 13 randomized controlled trials involving 2238 participants were included in this review. The methodological quality was generally poor. The results indicated that supplemented Yinchenhao decoction combined with non-specific treatments was more effective in improving the cure rate (risk ratio = 1.80; 95% CI 1.21–2.68) and reducing the serum levels of total bilirubin (mean difference = −29.74; 95% CI −31.91 to −27.57) and aspartate aminotransferase. Other self-made prescriptions conforming to QLTT plus non-specific treatments had beneficial effect for acute icteric hepatitis B in curing this disease (risk ratio = 1.48; 95% CI 1.27–1.73), as well as for negative seroconversion of HBeAg (risk ratio = 1.39; 95% CI 1.11–1.74). Supplemented Yinchenhao decoction plus non-specific treatments was more effective than other self-made prescriptions conforming to QLTT in reducing serum total bilirubin level. ConclusionQingre Lishi Tuihuang therapy appears to improve effect based on non-specific treatments for the treatment of acute icteric hepatitis B. However, it is premature to draw confirmative conclusions, owing to the poor methodological quality and high clinical heterogeneity of the included trials. Further well-designed clinical randomized controlled trials with large sample sizes should be undertaken.

Predictors of HBeAg seroconversion after long-term nucleos(t)ide analogues treatment for chronic hepatitis B: a multicenter study in real clinical setting

AimsTo evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). Methods251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100mg daily), adefovir (ADV, 10mg daily), telbivudine (LDT, 600mg daily), entecavir (ETV, 0.5mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. ResultsIn real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p<0.001, Hazard Ratio (HR)=2.203), elevated alanine aminotransferase (ALT) levels (p<0.001, HR=2.049), and non-vertical transmission (p=0.006, HR=1.656) were predictors of HBeAg seroconversion. ConclusionAdherence, elevated ALT, and non-vertical transmission are predictors of HBeAg seroconversion in CHB patients treated with NAs.

On-treatment HBV DNA level could predict HBeAg seroclearance in patients with HBeAg-positive chronic hepatitis B with entecavir therapy

BackgroundHepatitis B e antigen (HBeAg) status is associated with clinical outcomes, and seroconversion of HBeAg is one of the treatment goals. In this study, we determined the association of on-treatment serum hepatitis B virus (HBV) DNA levels in HBeAg-positive chronic hepatitis B patients who were receiving entecavir (ETV) treatment. MethodsA retrospective cohort study was conducted involving 135 (78 male and 57 female; mean age, 42.3 ± 13 years) patients with HBeAg-positive chronic hepatitis B (CHB). Between August 2008 and March 2014, each patient was treated with ETV for at least 96 weeks, and their HBV DNA levels were evaluated every 3–6 months. HBeAg seroclearance at the 96th week was defined as an absence of serum HBeAg within 96 weeks after ETV treatment. Univariate and multivariate logistic regression analysis was used to identify the predictors of 96th week HBeAg seroclearance, and a multivariable model was constructed. ResultsAmong the 135 ETV-treated HBeAg-positive CHB patients, 37 patients achieved HBeAg seroclearance (Group 1), whereas 98 patients had persistent HBeAg-positive status (Group 2) at the 96th week check-up. The baseline laboratory data was not significantly different between both the two groups. At the 24th and 48th weeks, there were significant differences between Group 1 and Group 2 in the percentage of patients with HBV DNA levels < 20 IU/mL [17/77 (22.1%) and 11/23 (47.8%), p = 0.032; 45/89 (50.6%) and 26/35 (74.3%), p = 0.028, respectively). ConclusionOur study demonstrated that HBV DNA levels < 20 IU/mL at the 24th and 48th weeks could predict serum HBeAg loss in ETV-treated HBeAg-positive patients with CHB.

Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B

Early declines in serum hepatitis B surface (HBsAg) levels, their optimal cutoffs, and association with therapeutic endpoints in chronic hepatitis B (CHB) patients receiving entecavir treatment remain unclear. We prospectively enrolled 529 patients (195 hepatitis B e antigen [HBeAg]-positive and 334 HBeAg-negative) with a median treatment duration of 49.2 months. Median HBsAg levels declined significantly in both groups at Month 3, but only at Months 6–12 in the HBeAg-negative group. Both groups exhibited a significant HBsAg decline with each successive year of treatment. An HBsAg decline of ≥75% from baseline, assessed at Months 3 and 12 of treatment in the HBeAg-positive and -negative patients, respectively, independently predicted a virological response and HBeAg seroconversion in the HBeAg-positive patients, an HBsAg level of <100 IU/mL in the HBeAg-negative patients, and HBsAg loss in all the patients during treatment. HBsAg levels of <3,000 IU/mL at baseline combined with an HBsAg decline of ≥75% from baseline provided a predictive algorithm for HBsAg loss (positive and negative predictive values: 70% and 100%, respectively) during 5 years of treatment. The proposed cutoffs for defining an HBsAg decline may assist clinicians in early assessments of treatment responses in genotype B-infected or C-infected CHB patients receiving entecavir therapy.

Natural history of chronic hepatitis B virus infection in children in Japan: a comparison of mother-to-child transmission with horizontal transmission.

It is necessary to evaluate the natural history of children with hepatitis B virus (HBV) infection in each country to consider their long-term management. A multi-center observational study of children with chronic HBV infection who were diagnosed at age ≤15years was carried out in 18 hospitals in Japan. We reviewed children with HBV infection including 381 with mother-to-child transmission (MTCT) and 154 with horizontal transmission, genotype C being the most prevalent virus genotype (83%). Children with horizontal transmission were more frequently infected with HBV genotype A or B and more likely to receive interferon therapy than those infected by MTCT. The HBeAg seroconversion rate at 15years of age was 42% in the MTCT group and 38% in the horizontal group. It was lower in children with genotype C infection than in those infected with other genotypes (33 versus 45%). Hepatitis developed at any age but before 4years of age the incidence was high in the horizontal group. At 3years after the onset of the hepatitis, 26% of children with MTCT and 30% of those with horizontal transmission became inactive carriers. The incidences of hepatocellular carcinoma (HCC) at 30years of age were 6% in the MTCT group and 11% in the horizontal group. Patients with childhood-onset HBV infection with MTCT and horizontal transmission developed hepatitis and seroconverted to anti-HBe at any age and had a lifetime risk of developing HCC.

Pediatric hepatitis B treatment.

Although the introduction of hepatitis B vaccine has been contributing to the reduction in the prevalence of hepatitis B virus (HBV) carriers worldwide, the treatment of children with chronic HBV infection is a challenge to be addressed. HBeAg seroconversion, which induces low replication of HBV, is widely accepted as the first goal of antiviral treatment in children with chronic hepatitis B. However, spontaneous HBeAg seroconversion is highly expected in children with chronic HBV infection. Therefore, the identification of children who need antiviral treatment to induce HBeAg seroconversion is essential in the management of chronic HBV infection. Guidelines and experts' opinion show how to identify children who should be treated and how to treat them. If decompensated cirrhosis is absent, interferon-alpha is the first-line antiviral treatment. Nucleos(t)ide analogues (NAs), such as lamivudine, adefovir, entecavir and tenofovir, are also available for the treatment of children, although the approval age differs among them. If decompensated cirrhosis is present, NAs are the first-line antivirals. When the emergence of drug-resistant HBV variants is taken into consideration, entecavir (approved for age 2 years or older) and tenofovir (age 12 years or older), which have high genetic barriers, will play a central role in the treatment of HBV infection. However, the optimal duration of NA treatment and adverse events of long-term NA treatment remain unclear in children. In resource-constrained countries and regions, the financial burden of visiting hospitals, receiving routine blood examination and purchasing antiviral drugs is heavy. Moreover, there is no clear evidence that the induction of HBeAg seroconversion by antiviral treatment prevents the progression of liver disease to cirrhosis and hepatocellular carcinoma in children with chronic HBV infection. It is thus imperative to clarify the clinical impact of antiviral treatment in children with HBV infection.

HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis.

BackgroundHBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide analogs (NAs) on HBeAg seroconversion in treating CHB with lamivudine, adefovir, telbivudine, entecavir, and tenofovir.MethodsNetwork meta-analysis of NA treatment-induced HBeAg seroconversion after 1–2 years of treatment was performed. In addition, NA treatment-induced HBeAg seroconversion after 3–5 years of treatment was systematically evaluated.ResultsA total of 31 articles were included in this study. Nine and five studies respectively reporting on 1- and 2-year treatment were included in our network meta-analysis. In addition, 6, 5, and 5 studies, respectively reporting on 3-, 4-, and 5-year treatment were included in our systematic evaluation. Telbivudine showed a significantly higher HBeAg seroconversion rate after a 1 year treatment period compared to the other NAs (odds ratio (OR) = 3.99, 95% CI 0.68–23.6). This was followed by tenofovir (OR = 3.36, 95% CI 0.70–16.75). Telbivudine also showed a higher seroconversion rate compared to the other NAs after a 2 year treatment period, (OR = 1.38, 95% CI 0.92–2.22). This was followed by entecavir (OR = 1.14, 95% CI 0.72–1.72). No significant difference was observed between spontaneous induction and long-term telbivudine treatment-induced HBeAg seroconversion. However, entecavir and tenofovir treatment-induced HBeAg seroconversions were significantly lower than spontaneous seroconversion.ConclusionLong-term treatment with potent anti-HBV drugs, especially tenofovir and entecavir, may reduce HBeAg seroconversion compared with spontaneous HBeAg seroconversion rate. Telbivudine treatment, whether short term or long term, is associated with higher HBeAg seroconversion compared with the other NAs. However, the high rates of drug resistance likely limit the application of telbivudine.

NK cell phenotypic and functional shifts coincide with specific clinical phases in the natural history of chronic HBV infection

BackgroundChronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection. MethodsPeripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells. ResultsThe overall composition, phenotype, and cytolytic activity of the NK cells remained constant across all clinical phases, with the exception of a few specific markers (KIRs, NKp46). CD56bright NK cells of chronic HBV patients differed in their ability to produce IFN-γ between the clinical phases pre- and post-HBeAg seroconversion. ConclusionThis depicts a shift in NK cell characteristics between the immune active, under heavy viral or immune pressure, and inactive carrier phases, that coincides with HBeAg seroconversion. Although these changes in NK cells do not appear to be completely responsible for differences in liver damage characteristic of specific clinical phases, they could provide a step toward understanding immune dysregulation in chronic HBV infection.

Epidemiological characteristics of HBeAg reversion in chronic hepatitis B patients with HBeAg seroconversion in Jiangsu province, 2012-2014

Objective: To understand characteristics and influencing factors of reversion of HBeAg in chronic hepatitis B patients with HBeAg sero-conversion, and provide epidemiological evidence for the regular management of chronic hepatitis B patients. Methods: From 2012 to 2014, a cohort study was conducted among the chronic hepatitis B patients with sero-conversion of HBeAg in Jiangsu province. Association between participants' demographics, ALT, HBV DNA and incidence of HBeAg reversion was analyzed by Cox regression model. HBV DNA changing trend between patients with HBeAg reversion and patients with persistent HBeAg sero-conversion was compared by repeated measure data variance analysis. Results: In 2012, there were 5 068 HBeAg seroconverted chronic hepatitis B patients aged (51.9 ± 12.8) years enrolled. By 2014, HBeAg had reversed in 121 cases with the rate of 1.3/100 person-years. The probability of HBeAg reversion decreased with the age of the patients. By Cox regression analysis, HBV DNA level was an important influencing factor for the progress of HBeAg reversion. The patients with HBV DNA≥200 000 IU/ml had a higher HBeAg reversion rate DNA (3.8/100 person-years) than those with HBV DNA <2 000 IU/ml (1.1 person-years) (HR=3.44, 95% CI: 1.91-6.20, P=0.000). Compared with the persistent HBeAg sero-conversion group, HBV DNA and ALT showed a more dramatic increase in the HBeAg reversion group (P=0.000). Conclusions: There was a certain HBeAg reversion rate in chronic hepatitis B patients with HBeAg sero-conversion. Younger chronic CHB patients with HBeAg sero-conversion and those with higher HBV DNA lever had higher HBeAg reversion rate. Following up and management of chronic CHB patients with HBeAg sero-conversion is important and helpful for the control of hepatitis B.

When can we stop nucleoside analogues in patients with chronic hepatitis B?

Treatment with nucleoside analogue (NAs) is now the most common treatment for chronic hepatitis B (CHB) and is recommended by all guidelines. Stopping NAs is a controversial issue in these patients, unless the clinical endpoints of HBeAg seroconversion or HBsAg seroclearance are achieved. While HBeAg seroconversion can occur in a significant number of patients, HBsAg seroclearance rates are low. HBsAg seroclearance is increasingly accepted as the ideal end of treatment, representing a functional cure. Treatment withdrawal leads to relapse in 50% of patients who achieve HBeAg seroconversion and complete at least 12months of consolidation therapy. In HBeAg negative CHB, the Asian Pacific Association for the Study of the Liver (APASL) stopping rules show that although clinical relapse occurs in approximately 43% and virological relapse occurs in 70%, very few patients experience flare or decompensation. NAs treatment for >2years was associated with a lower rate of relapse. Recently, stopping NA therapy was shown to be associated with HBsAg in 20%-39% of HBeAg negative patients and more frequently in those with low quantitative HBsAg (qHBsAg). However, the most optimal level is unclear. Quantitative HBsAg is becoming a useful tool to predict a sustained response or relapse before stopping therapy. In conclusion, stopping NA therapy is generally safe and can be an option in specific situations such as HBeAg seroconversion. However, it is associated with disease relapse. Thus, patient selection based on qHBsAg may help identify patients who are more likely to achieve HBsAg seroclearance or a sustained response.

THU-162 - On-treatment decline in HBeAg level at week 24 predicts for HBeAg seroconversion during long-term tenofovir therapy for HBeAg-positive CHB

THU-162 - On-treatment decline in HBeAg level at week 24 predicts for HBeAg seroconversion during long-term tenofovir therapy for HBeAg-positive CHB

Hepatic flare after telbivudine withdrawal and efficacy of postpartum antiviral therapy for pregnancies with chronic hepatitis B virus.

The efficacy of telbivudine for breaking vertical transmission of hepatitis B virus has been well established. Data on the risk of postpartum flare after telbivudine withdrawal and efficacy of extended antiviral therapy after delivery are limited. Chronic hepatitis B virus-infected women who received telbivudine beginning at week 24 or 28 of gestation were enrolled and then followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed. Of the 241 women who finished 52 weeks of follow-up, 33.6% had elevated serum alanine aminotransferase (ALT) during pregnancy. Telbivudine administration resulted in ALT normalization in 85.2% before delivery. Compared with women having a normal ALT level throughout pregnancy, those with elevated ALT had a significantly higher rate of ALT flare after telbivudine withdrawal (25.0% vs 11.9%; χ2 = 4.273, P = 0.039). Multivariate analysis indicated that only ALT elevation during pregnancy correlated with postpartum flare after telbivudine withdrawal. Those women with elevated ALT during pregnancy continued antiviral treatment to 52 weeks postpartum and had a significantly higher HBeAg seroconversion rate (P = 0.001) and a notable decrease in HBsAg titers (P = 0.001). It is safe for the majority of women to withdraw telbivudine after delivery, whereas exciting serological response encourages extended antiviral therapy for mother with ALT elevation during pregnancy.

TDF Monotherapy Is Effective Regardless of Prior Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patients in China.

Background/Aims Many patients had to transfer to tenofovir disoproxil fumarate (TDF) if there is other nucleos(t)ide analogue (NA) resistance. We aimed to investigate antiviral effects of TDF monotherapy between NA-naive and NA-experienced chronic hepatitis B (CHB) patients in China. Methods A total of 102 NA-naive and NA-experienced CHB patients with TDF monotherapy (300 mg/day) were retrospectively analyzed for useful parameters up to 72 weeks. Results There were 36 and 66 patients with matched HBV DNA baseline level in NA-naïve and NA-experienced group, respectively. There were no significant differences between NA-naïve and NA-experienced groups in HBV DNA levels (all P > 0.05) and HBV DNA undetectable rates (all P > 0.05) at all time points. At the end of follow-up, HBV DNA undetectable rates in NA-naïve and NA-experienced group were 96.2% (25/26) and 91.8% (45/49), respectively (P = 0.476). Baseline HBV DNA level was the only independent predictor for HBV DNA negative time (P = 0.018). In addition, 27.8% (5/18) and 11.4% (4/35) achieved HBeAg seroconversion at the end of the follow-up, respectively (P = 0.133). Conclusions TDF monotherapy was effective regardless of prior NA experienced. Baseline HBV DNA was a key predictive factor for HBV DNA negative time in TDF monotherapy.

Antiviral response is not sustained after cessation of lamivudine treatment in chronic hepatitis B patients: A 10-year follow-up study

Although the ideal end point for antiviral treatment in patients with chronic hepatitis B (CHB) is loss of HBsAg, the typical clinical end points are HBeAg seroconversion in HBeAg-positive patients and long-term DNA suppression in HBeAg-negative patients. We evaluated the long-term antiviral response after cessation of lamivudine treatment in CHB patients. A total of 157 patients who had discontinued lamivudine between 1997 and 2014 were enrolled (97 HBeAg-positive and 60 HBeAg-negative CHB patients). The long-term durability of the antiviral response (viralogical relapse; HBV DNA ≥104 copies/ml) and the clinical course of these patients were analyzed retrospectively. In HBeAg-positive patients, the mean follow-up period after discontinuation was 72.3 months. The cumulative probabilities of virological relapse at 1, 12, 24, 48, 60, 96, and 120 months were 10.3%, 40.2%, 55.6%, 62.8%, 65.9%, 67.0%, and 67.0%, respectively. In HBeAg-negative patients, the cumulative probabilities of a virological relapse at 1, 12, 24, 48, 60, 96, and 120 months were 25.0%, 35.0%, 41.7%, 43.3%, 43.3%, 46.7%, and 48.3%, respectively. Younger age (HR 1.732, 95%CI: 1.058-2.835, P = 0.02) was predictive of non-virological relapse in HBeAg-positive patients. And achievement of undetectable HBV DNA level within 3 months of treatment discontinuation was associated with decreased rate of virological relapse (HR 0.159, 95%CI: 0.069-0.367 P < 0.01) in HBeAg-negative patients. Despite meeting the requirements for treatment discontinuation, approximately half of the CHB patients treated with lamivudine relapsed. Thus, the antiviral response is not reliably sustained after lamivudine treatment cessation. J. Med. Virol. 89:849-856, 2017. © 2016 Wiley Periodicals, Inc.

Comparison of efficacy of tenofovir and entecavir in initial treatment of chronic hepatitis B virus infection

Objective To compare the effects and safety of entecavir(ETV) and tenofovir disoproxil fumarate(TDF) in initial treatment of patients with chronic hepatitis B virus infection. Methods 52 chronic HBV infection cases were randomly divided into initially treated with tenofovir(TDF group) or entecavir(ETV group) in this retrospective study.The following parameters were assessed: HBeAg status, serum alanine aminotransferase(ALT), and HBV-DNA levels at weeks 4, 8, 12, 24, 36, 48, 72, and 96; total duration of follow-up and adverse reactions. Results The clinical characteristics of two groups had no statistically significant difference.At 8 weeks, the response rate was significantly higher in the TDF group than in ETV group(23.1% vs.50.0%, χ2=4.266, P=0.045). Less patients administered ETV showed undetectable HBV-DNA levels compared with the TDF group in late treatment(weeks 12-96), the differences were not statistically significant (all P>0.05), as well as HBeAg seroconversion rate(all P>0.05). No adverse reactions were found. Conclusion ETV and TDF are comparable in efficacy and safety to suppress HBV-DNA replication in CHB patients. Key words: Hepatitis, type B, chronic; Entecavir; Tenofovir disoproxil fumarate

A cohort study of hepatitis B virus carriers progressing to chronic hepatitis in Jiangsu province, 2012-2014

Objective: To understand epidemiological characteristics and influencing factors of hepatitis B virus (HBV) carriers progressing to chronic hepatitis B in Jiangsu, and provide evidence for regular management of HBV carriers. Methods: From 2012 to 2014, a cohort study was conducted among the HBV carriers in an area in Jiangsu province. Association between HBV carriers' demographics, HBeAg level and HBV DNA detection result and incidence of chronic hepatitis B was analyzed by Cox regression analyses. Results: In 2012, a total of 4 069 HBV carriers aged (52.0±12.8) years were surveyed. By 2014, chronic hepatitis B had developed in 1 444 cases, with the rate of 21.0/100 person-years. Cox regression analysis indicted that, in addition to gender, HBV DNA level was an important influencing factor for the incidence of chronic hepatitis B (P<0.05). In HBeAg positive carriers progressing to chronic hepatitis, 40.7% had HBeAg seroconversion, and reversion of HBeAg occurred in 1.7% of HBeAg negative carriers. Conclusion: Chronic hepatitis B developed in more than 1/5 (21.0/100 person-years) of HBV carriers in the surveyed area in Jiangsu. It is suggested to conduct regular ALT, HBV DNA detection and B ultrasonic examination in HBV carriers for the early detection of chronic hepatitis B.

Current Management of Hepatitis B in 2016

Chronic hepatitis B infection represents a global public health burden, infecting over 240 million persons worldwide. It is associated with significant morbidity and mortality and represents a leading cause for cirrhosis, liver failure, liver cancer, and liver-related death. Current treatment of hepatitis B is focused on identification of patients with active hepatitis within the immune clearance or reactivation phases of chronic infection, for whom antiviral therapy with peg-interferon or nucleos(t)ide analogs are recommended. Seven antiviral agents are currently approved by the US FDA for treatment of chronic hepatitis B, of which three are recommended as first-line agents by major liver societies. As none are associated with virologic cure, the primary objective of antiviral therapy in 2016 is long-term virologic suppression, which is associated with a decreased risk for cirrhosis and hepatocellular carcinoma, and may reverse liver fibrosis or cirrhosis in some patients. Although biochemical improvement in liver enzymes is common, HBeAg seroconversion occurs in only a minority of patients, and HBsAg seroconversion is rare. Due to ongoing deficits along multiple steps of the care cascade, including screening, diagnosis, linkage to care, and antiviral therapy, many patients with chronic hepatitis B remain undiagnosed, lack access to care by specialists with expertise in the management of CHB, or have not been treated with antiviral agents. Future therapies are currently in development with the aim of functional viral cure, which may transform the treatment of CHB and improve liver outcomes.

Association of vitamin-D-related genetic variations and treatment response to pegylated interferon in patients with chronic hepatitis B.

Vitamin D, a potent immune-modulator, has been linked to the pathogenesis of chronic hepatitis B (CHB). This study was aimed at investigating the association between single nucleotide polymorphisms (SNPs) in vitamin-D-related genes and treatment response to pegylated interferon (PEG-IFN) in patients with CHB. A total of 275 Thai patients (122 hepatitis B e antigen [HBeAg]-positive and 153 HBeAg-negative CHB) treated with 48-week PEG-IFN were recruited. Virological response (VR) at 48 weeks post-treatment was defined as HBeAg seroconversion plus HBV DNA <2,000 IU/ml for HBeAg-positive CHB and HBV DNA <2,000 IU/ml for HBeAg-negative CHB. The SNPs VDR (rs2228570), DBP (rs7041) and CYP27B1 (rs4646536) were analysed. The distribution of TT, CT and CC genotypes of rs4646536 in this cohort was 21.8%, 46.2% and 32.0%, respectively. There was no difference in its distribution according to HBeAg status. In HBeAg-positive CHB, patients with TT genotype, compared with non-TT genotype, achieved higher VR (53.3% versus 31.5%; P=0.032) and hepatitis B surface antigen (HBsAg) clearance (20.0% versus 5.4%; P=0.016). In HBeAg-negative CHB, the corresponding figures were 60.0% versus 30.9% (P=0.003) and 16.7% versus 5.7% (P=0.045), respectively. Patients with TT genotype had more rapid HBsAg decline than those with non-TT genotype. However, SNPs rs2228570 and rs7041were not associated with VR and HBsAg clearance. Logistic regression analysis demonstrated that SNP rs4646536 and baseline HBsAg level were independent predictors of VR in both HBeAg-positive and HBeAg-negative CHB. Our data suggest that SNP rs4646536 in the CYP27B1 gene is a predictive factor of response to PEG-IFN therapy in Thai patients with CHB.

Hepatocellular carcinoma in children and young patients with chronic HBV infection and the usefulness of alpha-fetoprotein assessment.

The aims of the study were to elucidate the clinical characteristics of patients who developed hepatocellular carcinoma (HCC) related to persistent HBV infection since childhood and to investigate usefulness of assessing alpha‐fetoprotein (AFP) in this population. A nationwide multicenter survey of children with chronic HBV infection was performed. Among 548 patients, 15 patients developed HCC at the median age of 15 years (range 9–36), including 13 males and 2 females. A case–control comparison showed that HBeAg seroconversion and liver cirrhosis were associated with the occurrence of HCC. Of the 15 HCC patients, 5 were treated with interferon and none of them responded to interferon therapy as compared with 12 of the 17 responders in the control group. Of the 15 patients, 10 died and 9 of the 10 who died never visited any medical facilities until diagnosis of HCC, while the remaining 5 surviving patients never stopped their clinic visits. The usefulness of AFP assessment was shown by the findings that AFP levels were elevated in all HCC cases, that elevations in AFP levels were detected prior to the diagnosis in the surviving patients, and that sensitivity of AFP as a diagnostic test for HCC was very high among 40 patients including our 14 and an additional 26 collected from the literature. HBeAg seroconversion and liver cirrhosis are associated with the occurrence of HCC. Regular measurement of AFP might be helpful to watch for the occurrence of HCC when following children and young patients with chronic HBV infection since childhood

Entecavir for Patients with Hepatitis B Decompensated Cirrhosis in China: a meta-analysis.

Evidence about the clinical effects of entecavir (ETV) for patients with hepatitis B decompensated cirrhosis remain controversial. Therefore, we perform this meta-analysis to assess the treatment outcomes of ETV in participants with hepatitis B decompensated cirrhosis. Relevant studies were identified by searching databases until the March 2016. A random-effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). GRADEprofiler3.6 was used to evaluate the quality of the evidence. A total of 26 studies (involving 2040 patients) were included. The quality of the evidence was classified from very low to high by the GRADED approach for all included RCTs. Meta-analysis showed that patients were more likely to experience HBV-DNA loss (RR:1.85, 95%CIs: 1.41 to 2.43, P < 0.0001 at 48 weeks), have normalized alanine aminotransferase levels (ALT) (P = 0.003 at 24 weeks, P = 0.02 at 48 weeks), and have a low mortality rate at 24 weeks (P = 0.003) when treated with ETV. There was no significant different between ETV and the control groups at the total mortality (P = 0.06) and HBeAg seroconversion (P = 0.14). In conclusion, ETV could be the first line therapy for patients with HBV related decompensated cirrhosis, because ETV could reduce the early mortality and move HBV DNA load down.