Search

Background & Aim: Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation., Methods: All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation., Recommendations: We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation., (© 2021. Asian Pacific Association for the Study of the Liver.)

Fibroblast growth factor 21 (FGF21), a stress-induced hormone in the liver, has been shown the protective functions in pathological conditions. The study investigated the association of circulating FGF21 with hepatitis B virus (HBV) infection and its related diseases. Serum FGF21 levels were measured in 33 acute hepatitis B (AHB), 75 chronic hepatitis B (CHB) and 66 CHB patients with advanced liver diseases including liver cirrhosis, acute-on-chronic liver failure (ALCF) and hepatocellular carcinoma (HCC) together with 200 age- and BMI-matched healthy controls. FGF21 levels were significantly increased in AHB patients and rapidly returned to normal levels after treatment. FGF21 levels reflected the degree of liver injury caused by AHB. However, serum FGF21 levels were decreased in CHB patients especially in those who developed cirrhosis and were associated with hepatic protein synthesis capacity. Serum FGF21 in CHB patients were increased with the occurrence of ACLF. Notably, in CHB patients who developed HCC, serum FGF21 exhibited a dramatic increase, which may provide important information on monitoring tumorigenesis in CHB patients. In conclusion, we revealed the diverse changes of circulating FGF21 in HBV-related diseases. FGF21 may be a useful biomarker in monitoring the tumorigenesis in patients with CHB.

Goals: To evaluate provider knowledge, attitudes and barriers to hepatitis B virus (HBV) care and management practices across diverse primary care settings., Background: Factors influencing adherence to recommended HBV screening and management guidelines are poorly defined., Materials and Methods: Providers across various health care settings in San Francisco were surveyed. Multivariate analyses were used to identify factors associated with recommended HBV screening, vaccination, and disease monitoring., Results: Of 277 (41.3%) responding providers, 42% reported performing HBV screening in >50% of at-risk patients, and 49%, HBV vaccination in >50% of eligible patients. Most reported appropriate monitoring of a majority of HBV-infected patients with alanine aminotransferase (79%) and HBV viral load (67%) every 6 to 12 months, but performed any hepatocellular carcinoma screening in 49%. Provider factors significantly associated with HBV screening were speaking an Asian language [odds ratio (OR), 3.27], offering HBV treatment (OR, 3.00), having >25% of Asian patients in practice (OR, 2.10), practicing in safety net settings (OR, 7.51) and having higher barrier score (OR, 0.74). Appropriate HBV monitoring was associated with provider speaking an Asian language (OR, 3.43) and provider age (OR, 0.68/decade). Hepatocellular carcinoma screening was associated with having >25% of patients speaking English as a second language (OR, 4.26) and practicing in safety net settings (OR, 0.14)., Conclusions: Rates of adherence to HBV guidelines were suboptimal irrespective of practice setting and were influenced by certain provider, patient and practice factors. This study reinforces the importance of engaging primary care providers in development, dissemination, and implementation of evidence-based HBV practice guidelines.

Hepatitis due to reactivation of hepatitis B virus (HBV) has been reported in patients treated with direct-acting antiviral (DAA) agents for chronic hepatitis C virus infection. We performed an observational study to determine the incidence of and factors associated with hepatitis in 327 patients receiving pan-oral DAA agents for HCV infections in areas endemic for HBV in China. Ten patients were positive for hepatitis B surface antigen (HBsAg), and 124 patients had occult HBV infection. HBV reactivation was determined by measuring HBV DNA and HBsAg status in serial serum samples collected every 2 weeks during DAA treatment and then every 4 weeks after treatment until week 12. In the total study population, 10 patients (3.1%) had hepatitis; 3 cases were associated with HBV reactivation (1 case not in the icteric phase, 1 case in the icteric phase, and 1 case with liver failure) and 7 from other causes. Testing positive for HBsAg before DAA treatment was a strong risk factor for developing hepatitis during treatment (hazard ratio, 15.0; P < .001)., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

While student-run clinics are often important healthcare safety nets for underserved populations, their efficacy for improving patient health knowledge has not been thoroughly explored. From September 2011 to April 2012, we assessed patients' retention of hepatitis B virus (HBV) knowledge after receiving student-led education at two student-run HBV screening and vaccination clinics. Patient education was provided by trained first and second-year medical, nursing, and pharmacy students, aided by a script and interpreters. Patient knowledge of HBV was evaluated at three points: before education, after the initial visit, and at one-month follow-up. Student-led education produced improved knowledge of HBV transmission, prevention, and management, which was retained 1 month after education for 52 patients tracked through time. Mean scores on an HBV knowledge survey improved from 56.4 % (SD = 15.2 %) at baseline to 66.6 % (SD = 15.1 %) after education, and 68.3 % (SD = 15.2 %) after one month. There was a statistically significant difference between the first and second (paired T test, p < 0.001) and the first and third tests (paired T test, p < 0.001), but no difference between the second and third tests (paired T test, p = 0.45). Multivariate analysis demonstrated that retention was correlated with patient educational background but independent of patient age, gender, income, primary language and number of years lived in the United States. Our study suggests that trained health professional students can effectively impart health knowledge that is retained by patients for at least 1 month. These results warrant consideration of student-led educational sessions at SRCs as a promising community health education model.

Treatment of chronic hepatitis B virus (HBV) infection is aimed at suppressing viral replication to the lowest possible level, and thereby to halt the progression of liver disease and prevent the onset of complications. Two categories of drugs are used in HBV therapy: the interferons, including standard interferon alfa or pegylated interferon alfa, and specific nucleoside or nucleotide HBV inhibitors that target the reverse-transcriptase function of HBV-DNA polymerase. The reported results of clinical trials have used varying definitions of efficacy, failure, and resistance based on different measures of virologic responses. This article discusses HBV virologic markers and tests, and their optimal use both for planning and reporting clinical trials and in clinical practice.

Background/aim: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown., Method: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72., Results: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37)., Conclusion: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.

Background: The hepatic outcome of hepatitis B surface antigen (HBsAg) positive patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is unknown., Aims: To examine the occurrence of hepatitis B virus (HBV) reactivation after withdrawal of pre-emptive lamivudine., Methods: Pre-emptive lamivudine was started one week before initiation of chemotherapy in 46 consecutive HBsAg positive patients and continued for the entire duration of chemotherapy. Pre-emptive lamivudine was stopped at a median 3.1 (range 3.0-3.4) months after completion of chemotherapy. Patients were longitudinally followed up after withdrawal of pre-emptive lamivudine., Results: Median time of follow up after withdrawal of lamivudine was 25.7 (range 5.7-75.7) months. Eleven of the 46 patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) compared with three of the 30 patients with low pre-chemotherapy HBV DNA (<10(4) copies/ml) developed HBV reactivation (50.0% v 10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%), respectively; p = 0.041). A high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) was the most important risk factor for HBV reactivation after withdrawal of pre-emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13, (95% confidence interval 2.99-87.01; p = 0.001)., Conclusions: HBV reactivation is more likely to occur in patients with high pre-chemotherapy HBV DNA after withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral therapy may be necessary in these patients after completion of chemotherapy in order to reduce post-chemotherapy HBV reactivation.

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.

We used a new real-time polymerase chain reaction (PCR)-based assay that is sensitive, has a wide dynamic linear range, and is highly reproducible to quantify hepatitis B virus (HBV) DNA in the serum of infected individuals undergoing potent antiviral therapy. In addition, we made frequent measurements of viral load after initiation of treatment and maintained follow-up to about 12 weeks. To analyze the data we used a new model of HBV decay, which takes into account that existing drug treatments do not completely block de novo infection and the possibility of noncytolytic loss of infected cells. On initiation of therapy, there was a mean delay of 1.6 days followed by a biphasic or muliphasic decay of plasma HBV DNA. The slope of the first phase varied considerably, with one individual having rapid decay, corresponding to a virion half-life of 1 hour, but others showing half-lives of up to 92 hours. Individuals either had a slow second-phase decline (t((1/2)) = 7.2 +/- 1.2 days) or a flat second phase. Some individuals exhibited a complex "staircase pattern" of decay, with further phases of viral DNA decline and phases with little change in viral load.

A 26-year-old female bone marrow transplant (BMT) recipient was hepatitis B surface antigen (HBsAg) and hepatitis B e antibody (HBeAb) positive. The donor, her human leucocyte antigen (HLA)-compatible sister, was HBsAg negative but hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) positive. Twelve weeks post-BMT the patient became HBsAg negative, as determined using a monoclonal antibody-based assay. At 16 weeks post-BMT, HBsAg became undetectable by monoclonal and polyclonal immunoassay with seroconversion to HBsAb; however, at 24 weeks post-BMT the patient again became HBsAg positive. Both the recipient and the donor were retrospectively tested by hepatitis B virus (HBV) polymerase chain reaction (PCR) and found to be positive. The recipient displayed variants at amino acids 4 and 47 of the surface (S) gene prior to BMT. These mutations were not detected 32 weeks post-BMT when the S gene sequence was identical to that of an adr prototype. The donor was found to have four unique amino acid substitutions at positions 30, 98, 101 and 210 of the S gene. However, in vitro-expressed HBsAg from the donor was detected by commercial kits and an immunofluorescence assay, indicating that antigenic alteration did not explain HBsAg negativity. This donor highlights the value of PCR as the gold standard test for current HBV infection. It also demonstrates that discordance between two commercial HBsAg assays may not always be caused by antigenic variants. The second episode of hepatitis may theoretically have been caused by reactivation, selection of an escape mutant by HBsAb, reinfection or recombination. We suggest it was reactivation because none of the donor variants was seen in the recipient post-BMT.

Thirteen hepatitis B surface antigen-positive Chinese patients who received hepatitis B surface antibody-positive marrow (hepatitis B core antibody-positive or -negative: 6 and 7, respectively) via allogeneic bone marrow transplantation (BMT) were studied. After BMT, 4 recipients had serologic clearance of hepatitis B surface antigen from hepatitis B core antibody-positive marrow, but none of the recipients of hepatitis B core antibody-negative marrow had serologic clearance (P=.02). There was no significant difference in the donors' hepatitis B surface antibody titer before BMT for patients with or without serologic clearance of hepatitis B surface antigen (2255.2+/-4244.0 vs. 854.2+/-2306.7 mIU/mL; P=not significant). Adoptive immunity clearance of hepatitis B surface antigen was favored by hepatitis B core antibody positive-donor marrow and was not related to donor pre-BMT hepatitis B surface antibody titer.

Delayed clearance of hepatitis B surface antigen was previously reported in a 38 year old woman after high dose chemotherapy with autologous peripheral blood stem cell rescue. Sixteen months later, this patient remained hepatitis B surface antigen negative, hepatitis B surface antibody positive, and serum hepatitis B DNA negative by polymerase chain reaction. Serial liver biopsies (one at hepatitis B e antigen positive stage, one at hepatitis B e antibody positive stage, and one at hepatitis B surface antigen negative and hepatitis B surface antibody positive stage) showed a gradual resolution of the inflammatory activity with loss of hepatitis B e antigen and then hepatitis B surface antigen in the serum. However, the degree of fibrosis, though mild, remained the same. With the serological clearance of hepatitis B surface antigen, a small amount of hepatitis B virus DNA was still detectable in the nuclei of liver cells.

Hepatitis B reactivation following chemotherapy withdrawal may result in hepatitis, hepatic failure and death. We studied the clinical outcome and the causes of hepatic events of hepatitis B surface antigen positive recipients undergoing bone marrow transplantation. Twenty-four hepatitis B surface antigen patients were matched with 24 hepatitis B surface antigen negative patients for age, sex, CMV positive serology, underlying hematological disease and type of bone marrow transplantation. Post-BMT, there were 18 patients in the hepatitis B surface antigen positive group and four patients in the hepatitis B surface antigen negative group who suffered from hepatitis (P < 0.05). Thirteen of the 18 hepatitis were related to HBV reactivation in the hepatitis B surface antigen positive group and none of the four hepatitis in the hepatitis B surface antigen negative group (P = 0.01). The hepatitis B surface antigen positive group also had an increased incidence of acute graft-versus-host disease of liver (6 vs 1, P = 0.03). However, there was no significant increase in the incidence of veno-occlusive disease (10 vs 7, P = 0.40) and persistent hepatitis (3 vs 0, P = 0.07) in the hepatitis B surface antigen positive group. Using the log-rank test, there was no significant difference in survival between the hepatitis B surface antigen positive and negative recipients.

Background: Hepatitis B virus (HBV) DNA has been detected in the peripheral blood leukocytes (PBL) during acute and chronic HBV infection. Possible pathobiologic significance includes infectivity and altered immunity. There are few data relating PBL HBV-DNA with severity of the liver disease, in particular with hepatocellular carcinoma (HCC)., Methods: HBV-DNA was detected by dot-spot hybridization technique in PBL separated from venous blood samples of 209 hepatitis B surface antigen-positive patients (28 healthy carriers and 95 chronic hepatitis, 29 cirrhotic, and 57 HCC patients). Serum HBV-DNA and hepatitis B e-antigen (HBeAg) were also measured., Results: Thirty percent of HCC patients were hepatitis e-antigen-positive compared to 50%, 84% (P < 0.0001), and 69% (P < 0.00001) of healthy carriers and chronic hepatitis and cirrhotic patients, respectively. Furthermore, only 11% of HCC patients had detectable serum HBV-DNA compared to 39% (P < 0.001), 58% (P < 0.001), and 31% (P < 0.05) of these respective patient groups. despite low viral replication among HCC patients, 58% had PBL HBV-DNA. Corresponding figures for healthy carriers and for chronic hepatitis and cirrhotic patients were 39%, 58%, and 56%. Fifty-two percent of HCC patients had positive PBL HBV-DNA in the absence of serum HBV-DNA, compared with 25% in healthy carriers (P < 0.05) and 22% in chronic hepatitis (P < 0.001) and 35% in cirrhotic patients (P = NS)., Conclusion: The high detection rate of PBL HBV-DNA among HCC patients may reflect certain pathogenetic processes of HBV infection and indicate a higher risk of development of HCC.

Background Clevudine is a polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients which may be related to its pharmacokinetics. Aim To characterize pharmacokinetic and pharmacodynamic profile of clevudine, a potent hepatitis B polymerase inhibitor. Methods A multicenter, randomized study comparing 10, 30 and 50 mg clevudine once daily for 12 weeks with 24 weeks off-treatment follow-up. Patients had chronic HBV infection, were nucleoside-naïve without co-infection. HBV viral load (VL) was assayed using Digene Hybrid Capture II with a lower limit of detection of 4700 copies/mL (940 IU/mL). Clevudine levels were measured using a liquid chromatography/mass spectrometery method. Results A total of 31 patients were enrolled into the 10 mg ( n = 10), 30 mg ( n = 11) and 50 mg ( n = 10) groups, respectively. At week 12, the median VL change was −3.2, −3.7 and −4.2 log10 copies/mL (−0.64, −0.74 and −0.84 log10 IU/mL) in the 10, 30 and 50 mg groups, respectively ( P = 0.012). At week 12, one of 10, five of 11 and two of 10 patients had VL below the assay lower limit of detection. Clevudine was well tolerated with no severe/serious adverse events. The mean plasma half-life of clevudine was 70 h and consequently is not the cause of the delayed viral rebound seen in some patients. Through modelling, 97% of the maximal treatment effect was reached with a 30 mg daily dose. Six patients had genomic changes without viral rebound. Conclusion Clevudine appears to be a potent and tolerable (over 12 weeks) anti-viral and the optimal dosage appears to be 30 mg once daily. [ABSTRACT FROM AUTHOR]

Objective: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon α-2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated. Methods: Multivariate analyses were performed using available data from 518 patients treated with peginterferon α-2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20 000 copies/ml. Results: In logistic regression analyses across all treatment arms, peginterferon α-2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon α-2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon α-2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon α-2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon α-2a with or without lamivudine therapy. Conclusions: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon α-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon α-2a with or without lamivudine. [ABSTRACT FROM AUTHOR]

Background: The hepatic outcome of hepatitis B surface antigen (HBsAg) positive patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is unknown. Aims: To examine the occurrence of hepatitis B virus (HBV) reactivation after withdrawal of pre-emptive lamivudine. Methods: Pre-emptive lamivudine was started one week before initiation of chemotherapy in 46 consecutive HBsAg positive patients and continued for the entire duration of chemotherapy. Pre-emptive lamivudine was stopped at a median 3.1 (range 3.0-3.4) months after completion of chemotherapy. Patients were longitudinally followed up after withdrawal of pre-emptive lamivudine. Results: Median time of follow up after withdrawal of lamivudine was 25.7 (range 5.7-75.7) months. 1 Eleven of the 46 patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (⩾104 copies/ml) compared with three of the 30 patients with low pre-chemotherapy HBV DNA (<104 copies/ml) developed HBV reactivation (50.0% v 10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%), respectively; p = 0.041). A high pre-chemotherapy HBV DNA (⩾104 copies/ml) was the most important risk factor for HBV reactivation after withdrawal of pre-emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13, (95% confidence interval 2.99-87.01; p=0.001). Conclusions: HBV reactivation is more likely to occur in patients with high pre-chemotherapy HBV DNA after withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral therapy may be necessary in these patients after completion of chemotherapy in order to reduce post-chemotherapy HBV reactivation. [ABSTRACT FROM AUTHOR]