Lower Serum HBV DNA Levels Research Articles

Comparison of HBV DNA Quantitative Log in Patients Hepatitis B with Telbivudine Therapy Compared with Tenofovir Therapy in Saiful Anwar General Hospital Malang: January 2016 - December 2017

Background: Hepatitis B is a health problem with high endemic in Indonesia. Hepatitis B virus infection is transmitted parenterally, has a risk of liver cirrhosis and hepatocellular carcinoma. Detection and quantification of HBV DNA are markers of active HBV replication and determine treatment options for hepatitis B. Methods: compare log reduction of HBV DNA in patients treated with Telbivudine and Tenofovir. Results: There was no significant difference in HBV DNA levels between before and after Tenofovir treatment, namely 6 months follow-up (OR 95% CI = 5.41 [0.83 - 35.16], p = 0.0770) and 12 months (OR 95% CI = 5.39 [0.83 - 34.99], p = 0.0780). Telbivudine administration showed a significant difference in HBV DNA levels between before and after treatment at 6 months follow-up (OR 95% CI = 13.69 [4.53 - 41.40], p = 0.0001) and 12 months (OR 95% CI = 13.69 [ 4.53 - 41.41], p = 0.0001). Comparison of Tenofovir and Telbivudine therapy showed no significant difference at 6 months follow-up (OR 95% CI = 0.44 [0.10 - 1.88], p = 0.2690) but significant at 12 months follow-up (OR 95% CI = 6.23). [1.39 - 27.97], p = 0.0170). Conclusion: Â There was a significant difference between the administration of Telbivudine as a treatment for hepatitis B with lower serum HBV DNA levels compared with the administration of Tenofovir at 12-month follow-up therapy.

O‐044: Low serum HBsAg and HBV DNA levels identify strongest responders of pegylated interferon addition to entecavir in HBeAg positive chronic hepatitis B

Journal of Viral HepatitisVolume 25, Issue S2 p. 27-28 Abstracts O-044: Low serum HBsAg and HBV DNA levels identify strongest responders of pegylated interferon addition to entecavir in HBeAg positive chronic hepatitis B First published: 12 June 2018 https://doi.org/10.1111/jvh.38_12922Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume25, IssueS2Special Issue: 16th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) held from June 14th to 17th, 2018, in Toronto, CanadaJune 2018Pages 27-28 RelatedInformation

Inverse relationship between hepatic steatosis and hepatitis B viremia: Results of a large case-control study.

The potential interaction between chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD), two of the most prevalent liver diseases worldwide, has not been well defined. We performed liver stiffness (LS) and controlled attenuation parameter (CAP) measurements using transient elastography in 1202 CHB patients. Of these, 601 steatotic patients were matched with nonsteatotic controls in a 1:1 ratio by age, gender, nucleoside analogue treatment status, and treatment duration. Severe fibrosis was defined according to EASL-ALEH criteria, and steatosis was defined as CAP ≥222dBm-1 . Anthropometric measurements and metabolic-related parameters were recorded. The mean age of the 1202 patients (51.4% male) was 51.8years. 696 patients (57.9%) were on nucleoside analogues for a median duration of 76.2months. Among treatment-naïve patients, median serum HBV DNA was lower in steatotic individuals than in controls (3.0 vs 3.4 log IUmL-1 , P<.05), with this inverse relationship remaining significant in multivariate analysis (odds ratio 0.859, 95% CI 0.743-0.994, P<.05). With increased steatosis severity, there was a stepwise decrease in median HBV DNA levels (3.1 and 2.6 log IUmL-1 in no steatosis and severe steatosis, respectively, P=.032). Steatosis was associated with a higher median LS (5.4kPa vs 5.0kPa, P<.001). Severe steatosis, when compared to mild/moderate steatosis, was associated with an increased percentage of severe fibrosis (23.2% and 12.6%, respectively, P=.005). We conclude that severe steatosis was associated with increased fibrosis in CHB patients. Increasing steatosis was independently associated with lower serum HBV DNA levels, suggesting its potential negative effects on viral replication.

Perioperative antiviral therapy for patients with hepatitis B virus related hepatocellular carcinoma with low HBV DNA levels

Objective To investigate the role of perioperative antiviral therapy with Entecavir for patients with hepatitis B virus related hepatocellular carcinoma (HBV-HCC) with low serum HBV DNA levels. Methods The HVB-HCC patients were randomly divided into 2 groups. Patients in the antiviral group received Entecavir 4 days before hepatic resection while patients in the control group received no antiviral treatment. The serum HBV DNA, liver function, morbidity and length of hospital stay were compared between the two groups. Results Sixteen patients in the control group (n=44) developed HBV reactivation. On the other hand, only 1 patient in the antiviral group (n=44) developed HBV reactivation. Recovery in liver function in the antiviral group was much faster than the control group, especially for glutamic-pyruvic transaminase level. The antiviral group had significantly lower morbidity and shorter total or postoperative hospitalization (all P<0.05). Conclusions Patients with HBV-HCC with low levels of HBV DNA have a high risk of developing HBV reactivation in the perioperative period. Perioperative antiviral therapy was safe and efficacious in preventing HBV reactivation, improved liver function, reduced postoperative complications and shortened hospitalization. Key words: Hepatitis B; Hepatocellular carcinoma; Antiviral therapy; Perioperative period

Factors associated with spontaneous HBsAg clearance in chronic hepatitis B patients followed at a university hospital

Introduction. Few studies have evaluated the factors involved in the spontaneous HBsAg seroclearance in patients with chronic hepatitis B (HBV) followed up on a long-term basis from areas with a low prevalence of HBV infection. We aimed to determine the rate of spontaneous HBsAg seroclearance and the factors related to it in patients with chronic HBV infection followed up at the Hepatitis Outpatient Clinic of HCFMRP from 1992-2008.Materials and methods. A total of 548 patients with chronic HBV infection (366 with chronic hepatitis B and 182 inactive carriers) were followed for 15 years and 9 months with an annual measurement of HBV-DNA, ALT, AST and GGT (average of 4 annual determinations) and serology (HBsAg, HBeAg, Anti-HBeAg and Anti-HBsAg).Results. Spontaneous HBsAg seroclearance occurred in 40 patients (7.3%) with a mean age of 46.0 ± 14.4 years, corresponding to an annual rate of 0.7%.The factors related to spontaneous HBsAg seroclearance were inactive carrier status (67.5 vs. 32.5%, p = 0.000191) and age of more than 40 years (p = 0.0007). There was no difference in the rate of spontaneous HBsAg seroclearance when comparing males and females (p = 0.383). Patients with spontaneous HBsAg seroclearance did not progress to more severe forms of the disease during follow-up.Conclusion. Spontaneous HBsAg seroclearance has a favorable long-term prognosis in patients with chronic HBV infection. HBsAg seroclearance occurred at rates compatible with low prevalence areas and was associated with low serum HBV-DNA levels and an age older than 40 years.

Preventing hepatitis B reactivation in HBsAg-positive patients with untreated diffuse large B-cell lymphoma with R-CHOP chemotherapy: A prospective study to compare entecavir and lamivudine.

8503 Background: Hepatitis B reactivation is a serious complication in lymphoma patients treated with rituximab-contained chemotherapy despite lamivudine prophylaxis. The optimal prophylactic antiviral protocol is undetermined. This prospective study was designed to compare the efficacy of prophylactic entecavir and lamivudine in preventing hepatitis B reactivation in HbsAg-positive patients with untreated diffuse large B cell lymphoma (DLBCL) under R-CHOP treatment. Methods: HBsAg carriers with untreated DLBCL, normal liver function and low serum HBV DNA levels (less than 103copys/ml)were randomized to receive entecavir or lamivudine during R-CHOP treatment and for 6 months after completion of chemotherapy. HBsAg, HBsAb, HBeAg, HBeAb and HBcAb were performed prior to initiation of treatment. Serum alanine aminotransferase (ALT), and HBV-DNA levels were prospectively monitored before every cycle of chemo and every month after completion of chemotherapy. Results: Between February 2008 and December 2012, a total of 229 patients older than 18y with newly diagnosed DLBCL were included. The present analysis is based on 121 HBsAg-positive patients, including 61 patients randomly assigned to entecavir and 60 patients to lamivudine .The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end point was chemotherapy disruption due to hepatitis. Compared with the lamivadine group, the entecavir group had significantly lower rates of hepatitis(8.2% vs 23.3%,P=0.022), hepatitis B reactivation (0 vs 13.3%,P=0.003),HBV reactiviation(6.6% vs 30.0%,P=0.001), delayed HBV-related hepatitis (0 vs 8.3%,P=0.027) and disruption of chemotherapy (1.6% vs 18.3%,P=0.002). 7 of 8 patients with hepatitis B reactivation had advanced stage(III–IV) disease. Conclusions: In HBsAg-positive DLBCL patients undergoing R-CHOP chemotherapy, entecavir is more effective than lamivudine in preventing hepatitis B reactivation. For patients with advanced stage disease, entecavir should be considered the primary preventive therapy. Clinical trial information: CTR-TRC-11001687.

Hepatitis B virus genotypes, precore mutations, and basal core promoter mutations in HBV-infected Chinese patients with persistently normal alanine aminotransferase and low serum HBV-DNA levels

Hepatitis B virus (HBV) genotype and precore and basal core promoter (BCP) mutants in the patients with persistently normal alanine aminotransferase (ALT) and low serum HBV-DNA levels are unclear. The aim of this study was to determine HBV genotypes, precore and BCP mutations, and their association with chronic hepatitis and liver fibrosis in HBV-infected patients with persistently normal ALT, and low serum HBV-DNA levels in northeast China. Patients (n = 89) with normal ALT and serum HBV-DNA levels below 20000 IU/mL but detectable with real-time PCR were included in this study. HBV genotypes were determined by real-time PCR. The precore and BCP mutations were detected by sequencing. All the patients had biopsy results. Of the 89 patients, 11 (12.4%) were genotype B and 78 (87.6%) were genotype C. The most common mutations were G1896A (23.6%), G1764A (9.0%), and A1762T (6.7%). The prevalence of precore mutation was significantly higher in genotype B patients than in genotype C patients (54.5% vs. 19.2%, p < 0.01). There was no significant difference in the prevalence of BCP mutations between genotype B and genotype C (18.2% vs. 10.2%). Multivariate analysis showed that old age (> 40 years) and BCP mutations were independent predictors of liver necroinflammation and fibrosis. Thus, BCP mutations may be associated with liver necroinflammation and fibrosis in patients with persistently normal ALT and low serum HBV-DNA levels in northeast China.

Hepatitis B virus genotypes, precore mutations, and basal core promoter mutations in HBV-infected Chinese patients with persistently normal alanine aminotransferase and low serum HBV-DNA levels

Hepatitis B virus (HBV) genotype and precore and basal core promoter (BCP) mutants in the patients with persistently normal alanine aminotransferase (ALT) and low serum HBV-DNA levels are unclear. The aim of this study was to determine HBV genotypes, precore and BCP mutations, and their association with chronic hepatitis and liver fibrosis in HBV-infected patients with persistently normal ALT, and low serum HBV-DNA levels in northeast China. Patients (n = 89) with normal ALT and serum HBV-DNA levels below 20000 IU/mL but detectable with real-time PCR were included in this study. HBV genotypes were determined by real-time PCR. The precore and BCP mutations were detected by sequencing. All the patients had biopsy results. Of the 89 patients, 11 (12.4%) were genotype B and 78 (87.6%) were genotype C. The most common mutations were G1896A (23.6%), G1764A (9.0%), and A1762T (6.7%). The prevalence of precore mutation was significantly higher in genotype B patients than in genotype C patients (54.5% vs. 19.2%, p < 0.01). There was no significant difference in the prevalence of BCP mutations between genotype B and genotype C (18.2% vs. 10.2%). Multivariate analysis showed that old age (> 40 years) and BCP mutations were independent predictors of liver necroinflammation and fibrosis. Thus, BCP mutations may be associated with liver necroinflammation and fibrosis in patients with persistently normal ALT and low serum HBV-DNA levels in northeast China.

Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B

We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo (monotherapy) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily (combination therapy) for 104 weeks in a randomized double-blind study. Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups (p=0.936). At week 104, median serum HBV DNA change from baseline (log(10)copies/mL) for monotherapy and combination therapy was -3.41 versus -5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group (p=0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated. Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.

Viral genotype and baseline load predict the response to adefovir treatment in lamivudine-resistant chronic hepatitis B patients

To determine the factors associated with virological response (VR), HBeAg loss or the emergence of adefovir (ADV)-related mutations in ADV-treated chronic hepatitis B (CHB) patients with lamivudine (LAM) resistance. Fifty-four LAM-resistant CHB patients (46% HBeAg-positive) were treated with ADV monotherapy (n=28) or ADV plus LAM (n=26) for a mean of 30.4 months. Thirty-eight patients (70.4%) achieved VR defined as HBV-DNA levels <10(4)copies/ml within the first 12 months of treatment. Six (24%) of 25 HBeAg-positive patients exhibited HBeAg loss and 20% seroconverted to anti-HBe. Eight patients (14.8%) developed ADV-related mutations. In the multivariate analysis, female gender (HR=0.20, 95% CI: 0.05-0.76, p=0.018), HBeAg-negative (HR=0.37, 95% CI: 0.14-0.96, p=0.040) and low baseline HBV-DNA levels (HR=0.65, 95% CI: 0.45-0.95, p=0.027) were independent predictors of VR, whereas low HBV-DNA levels (HR=0.36, 95% CI: 0.11-1.20, p=0.095) and HBV-genotype D (HR=0.06, 95% CI: 0.004-0.84, p=0.037) independently predicted HBeAg loss. ADV therapy suppresses viral replication in more than 70% of LAM-R patients. Factors associated with virologic response are female gender, HBeAg-negative status and low baseline serum HBV-DNA levels. Genotype D HBV infection and low baseline HBV-DNA levels independently predict HBeAg loss.

Limited lamivudine and long-term hepatitis B immunoglobulin immunoprophylaxis for prevention of hepatitis B recurrence after liver transplantation.

No consensus exists concerning dosage and duration of prophylactic hepatitis B immunoglobulin and lamivudine for prevention of hepatitis B recurrence after liver transplantation (LT). Lamivudine was discontinued 12 months after LT, maintaining hepatitis B immunoglobulin prophylaxis in eight patients who received lamivudine treatment before LT. At LT, six patients were serum hepatitis B virus (HBV)-DNA negative, whereas two patients had low serum HBV-DNA levels. Hepatitis B surface (HBs) antigen and hepatitis B core antigen stained positively by immunohistochemistry in all hepatectomy specimens. All patients remained recurrence free during the 12 months on combination therapy with normal liver histological examination and negative HBs and HB core staining on biopsy specimens. No relapse occurred after lamivudine withdrawal during a median follow-up of 17.5 months (normal transaminases, negative serum HBs antigen, and HBV-DNA). Discontinuation of lamivudine 12 months after LT is feasible and safe even in patients with ongoing low viral replication at LT, providing adequate prophylaxis with hepatitis B immunoglobulins.

Lamivudine resistance in hepatitis B: mechanisms and clinical implications.

Lamivudine (beta-L-(-)-2',3'-dideoxy-3'-thiacytidine) has been a major breakthrough in the care of patients with hepatitis B. With prolonged monotherapy the development of resistance is an increasingly recognized problem that limits the long term efficacy of this nucleoside analogue. The most common mutations associated with lamivudine resistance occur within the highly conserved YMDD motif in the C domain of the viral polymerase and are often associated with a compensatory mutation in the proximal B domain. The structural and functional relationship of resistance mutations is reflected in different in vitro sensitivities to lamivudine and changes in replication capacities. During prolonged lamivudine treatment there can be successive changes of different resistant mutants (genotypic succession) or a single mutant can remain the dominant viral species. In patients treated for chronic hepatitis B infection the cumulative incidence of viral resistance reaches over 50% after 3 years. Most patients will have lower serum HBV DNA levels after the emergence of resistance which is ascribed to the decreased replication capacity of these mutants. Although severe flares and ongoing HBe antigen seroconversion can occur in these patients with lamivudine-resistant HBV, the impact of continued therapy on the long-term outcome is still insufficiently studied. In the setting of liver transplantation for HBV-associated disease the clinical course after the emergence of viral resistance is variable but still may lead to disease progression and graft failure. Analogous to the success of combination therapies to delay the emergence of antiviral-resistant HIV, it will be important to combine anti-HBV agents with additive or synergistic antiviral properties and different resistance profiles for future de novo combination therapies for hepatitis B infection.

Interferon monotherapy in chronic hepatitis B.

Interferon-alpha (IFN-alpha) has been the only approved agent for the treatment of chronic hepatitis B in most countries, but this is rapidly changing. It is expensive, associated with frequent and unpleasant side effects, has limited efficacy and is ineffective in subjects with no/mild liver necro-inflammation. Loss of HBsAg and viral replication markers occur 6% and 20%, more often in IFN-treated subjects than controls. The most important factors that will predict favourable response to IFN-alpha therapy are elevated ALT and low serum HBV DNA levels. Chinese patients and children with active liver have similar response rates as Caucasian adults with equivalent ALT levels. Patients with HBeAg negative disease fare less well. Long-term follow up has shown that most IFN responders maintained their response although very few people have complete eradication of HBV.