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1.
Sung Soo Ahn Young Eun Chon Beom Kyung Kim Seung Up Kim Do Young Kim Sang Hoon Ahn Kwang-Hyub Han Jun Yong Park 《Clinical and molecular hepatology》2014,20(3):261-266
Background/Aims
This study assessed the antiviral efficacy and safety of tenofovir disoproxil fumarate (TDF) for up to 12 months in Korean treatment-naïve chronic hepatitis B (CHB) patients.Methods
A total of 411 treatment-naïve CHB patients who had been treated with TDF for at least 3 months (median 5.6) were consecutively enrolled. Clinical, biochemical, virological parameters and treatment adherence were routinely assessed every 3 months.Results
The median age was 51.3 years, 63.0% of the patients were male, 49.6% were HBeAg (+), and 210 patients had liver cirrhosis. The median baseline HBV DNA was 5.98 (SD 1.68) log10 IU/mL. Among the patients completing week 48, 83.3% had a complete virologic response (CVR, <12 IU/mL by HBV PCR assay), and 88.2% had normalized levels of alanine aminotransferase (ALT). The cumulative probabilities of CVR at 3, 6, 9 and 12 months were 22.8%, 53.1%, 69.3% and 85.0%. During the follow-up period, 9.8% patients achieved HBeAg loss and 7.8% patients achieved HBeAg seroconversion. There was no virological breakthrough after initiating TDF. The most common TDF-related adverse event was gastrointestinal upset, and three patients discontinued TDF therapy. However, no serious life-threatening side effect was noted.Conclusions
In a clinical practice setting, TDF was safe and highly effective when administered for 12 months to Korean treatment-naïve CHB patients. 相似文献2.
Comparison of the efficacies of entecavir 0.5 and 1.0 mg combined with adefovir in patients with chronic hepatitis B who had failed on prior nucleos(t)ide analogue treatments
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Yuri Cho Jeong-Hoon Lee Su Jong Yu Jung-Hwan Yoon Hyo-Suk Lee Yoon Jun Kim 《Journal of medical virology》2015,87(6):999-1007
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Han Na Choi Jeong Eun Song Hyeon Chul Lee Hyeong Ho Jo Chang Hyeong Lee Byung Seok Kim 《Clinical and molecular hepatology》2015,21(1):24-31
Background/Aims
The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined. The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naïve chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy.Methods
This study included 364 treatment-naïve CHB patients treated with ETV for ≥48 weeks and who received continuous ETV monotherapy for ≥96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log10 IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48.Results
Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for ≥96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up.Conclusions
Long-term ETV monotherapy is effective for achieving a VR in treatment-naïve CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response. 相似文献4.
Stefan Reuter Mark Oette Frank Clemens Wilhelm Bastian Beggel Rolf Kaiser Melanie Balduin Finja Schweitzer Jens Verheyen Ortwin Adams Thomas Lengauer Gerd F?tkenheuer Herbert Pfister Dieter H?ussinger 《Medical microbiology and immunology》2011,200(1):39-49
In HIV-infected treatment-na?ve patients, we analyzed risk factors for either chronic hepatitis B (HBV) infection, occult HBV infection (OHBV) or a positive hepatitis C (HCV) serostatus. A total of 918 patients of the RESINA-cohort in Germany were included in this study. Before initiating antiretroviral therapy, clinical parameters were collected and blood samples were analyzed for antibodies against HIV, HBV and HCV, HBs antigen and viral nucleic acids for HIV and HBV. Present or past HBV infection (i.e. HBsAg and/or anti-HBc) was found in 43.4% of patients. HBsAg was detected in 4.5% (41/918) and HBV DNA in 6.1% (34/554), resulting in OHBV infection in 2.9% (16/554) of patients. OHBV infection could not be ruled out by the presence of anti-HBs (50.1%) or the absence of all HBV seromarkers (25%). A HCV-positive serostatus was associated with the IVDU transmission route, non-African ethnicity, elevated liver parameters (ASL or GGT) and low HIV viral load. Replicative HBV infection and HCV-positive serostatus both correlated with HIV resistance mutations (P?=?0.001 and P?=?0.028). HBV and HCV infection are frequent co-infections in HIV treatment-naive patients. These co-infections influence viral evolution, clinical parameters and serological markers. Consequently, HIV patients should routinely be tested for HBV and HCV infection before initiating HIV treatment. OHBV infection constituted almost half of all HBV infections with detectable HBV DNA. Due to a lack of risk factors indicating OHBV infection, HBV diagnosis should not only include serological markers but also the detection of HBV DNA. 相似文献
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Recent studies have suggested that quantifying the serum HBsAg levels can predict the response to pegylated interferon. We aimed to determine the change in serum HBsAg levels during entecavir (ETV) treatment and the correlation with treatment response in chronic HBeAg‐positive and HBeAg‐negative hepatitis B patients. Serial HBsAg levels were measured using the Architect assay (Abbott Laboratories, Abbott Park, IL) in sera from 101 treatment‐naive chronic hepatitis B (CHB) patients receiving ETV. During treatment, in HBeAg‐positive patients, the mean HBsAg level was 3.51, 3.22, 3.34, 3.36, and 3.40 log10 IU/ml at baseline, 3, 6, 12, and 24 months, respectively, and there was no significant change compared with the baseline level, except the decline at 3 months (P = 0.009). In HBeAg‐negative patients, the mean level of serum HBsAg showed increase with 3.06, 3.09, 3.20, 3.26, and 3.27 log10 IU/ml at baseline, 3, 6, 12, and 24 months of treatment, respectively. In HBeAg‐positive patients, HBV‐DNA negativity (<2,000 copies/ml; P = 0.010) and HBsAg level <3,000 IU/ml (P = 0.026) at 3 months were independent predictors of HBeAg loss/seroconversion at 12 months. After 24 months of treatment, the HBsAg levels at baseline (P = 0.046) was an independent factor of HBeAg loss/seroconversion. In HBeAg‐negative patients, undetectable HBV DNA at 6 months was an independent factor predicting undetectable HBV DNA after 12 months of therapy. The level of serum HBsAg before and during therapy was a good predictor of HBeAg loss/seroconversion in naïve HBeAg‐positive CHB patients receiving entecavir. J. Med. Virol. 83:1178–1186, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
6.
The reasons for adefovir dipivoxil (ADV) treatment failures appear diverse. Few studies have reported full-length hepatitis
B virus (HBV) genome in patients with ADV treatment failures. The patients were from a phase III clinical trial that investigated
the antiviral response to ADV in China. Seven patients had increase in HBV-DNA (>1 log10 copies/ml above on-treatment nadir) at week 52. The serum HBV-DNA levels were above 104copies/ml at week 92 in four of them. Sixteen full-length HBV genomes from the four patients at four time points were sequenced
using cloning sequencing method. The frequency of substitutions at week 52 was higher than at weeks 28(16 wt) and 92(80).
HBV-DNA reduction was correlated negatively with the frequency of substitutions at the three time points. No published ADV-resistant
mutations were detected. The mutations, including substitutions in immunogenic epitopes and conserved sites of the polymerase
gene, were frequent during ADV treatment. Amino acid deletions in X gene and basal core promoter/pre-core mutations appeared
before or during ADV treatment. The substitutions in immunogenic epitopes (mainly of the surface gene) and conserved sites
of the polymerase gene other than ADV-resistant mutations may have influenced antiviral efficacy in the study. More potent
antiviral drugs may be important to rescue individual patients and for public health safety. It is needed to study how these
substitutions influence HBV replication, disease progression, and antiviral treatment efficacy. 相似文献
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Mohamad S. Hakim Michelle Spaan Harry L. A. Janssen Andre Boonstra 《Reviews in medical virology》2014,24(2):125-138
Chronic HBV and HCV infections are the leading cause of liver‐related morbidity and mortality. For effective antiviral immunity, virus‐specific T cells are required, but these cells have been shown to be weak or absent in chronic HBV and HCV patients. One of the mechanisms that underlies the impaired T‐cell response is the result of the continuously high viral load that causes HBV‐specific and HCV‐specific T cells to become exhausted, which is characterized by impaired proliferation, cytokine production and cytotoxic activity of T cells as well as high susceptibility to apoptosis. In vitro studies from chronic HBV and HCV patients as well as in vivo studies in animal models demonstrated a reversible state of T‐cell exhaustion, which can be manipulated to reinvigorate the specific antiviral immune responses. In chronic HCV infection, this concept has been explored in clinical trials by administration of specific antibody to block the inhibitory pathways. The manipulation of inhibitory receptors is a promising and potential strategy for immunotherapeutic interventions in chronic HBV and HCV patients to facilitate complete elimination of the viruses or sustained viral control. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
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Lee SH Kim HS Byun IS Jeong SW Kim SG Jang JY Kim YS Kim BS 《Journal of medical virology》2012,84(2):217-222
Although the rate at which mutations in the tyrosine‐methionine‐aspartate‐aspartate (YMDD) motif of hepatitis B virus polymerase form is high during prolonged lamivudine (LAM) therapy, these mutations sometimes occur naturally in treatment‐naïve patients with chronic hepatitis B. The prevalence of natural YMDD mutants differs geographically, and its clinical significance during LAM therapy is unknown. This study aimed to investigate whether pre‐existing YMDD mutants were selected during LAM therapy. It included 14 treatment‐naïve patients who were treated with LAM for at least 9 months. LAM resistance was evaluated before and at 3‐month intervals during treatment. Mutations were analyzed by direct sequencing, restriction fragment mass polymorphism (RFMP) assays, and a single‐step multiplex polymerase chain reaction (PCR) test using dual‐priming oligonucleotide (DPO) primers. DPO‐based multiplex PCR showed two YMDD mutations in two patients before LAM therapy; rtM204V and rtL180M + rtM204V/I. Further, two patients had an rtL180M mutation without an accompanying rtM204V/I mutation. No mutant was detected in any patient by direct sequencing or the RFMP assay before LAM therapy. A virological response was observed at 3 months in all patients with pre‐existing YMDD mutants. All mutations disappeared after 3 months of LAM therapy, and during the follow‐up period, no re‐emergence was detected by any of the three methods. Further, the viral load was suppressed optimally. In conclusion, pre‐existing YMDD mutants were cleared early during the course of LAM therapy, which produced a consistent virological response, and the mutants were not selected by LAM therapy. J. Med. Virol. 84:217–222, 2012. © 2011 Wiley Periodicals, Inc. 相似文献
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Wan Yue-Meng Yu-Hua Li Hua-Mei Wu Jing Yang Ying Xu Li-Hong Yang Jin-Hui Yang 《Clinical and experimental medicine》2017,17(2):233-241
The long-term effects of telbivudine (TBV) on decompensated hepatitis B virus (HBV)-related cirrhosis were still not established. This study aimed to investigate the efficacy and safety of TBV in such cohort of patients as compared to lamivudine (LAM) and entecavir (ETV). We retrospectively evaluated 130 treatment-naïve patients with HBV-related decompensated cirrhosis who started treatment with TBV (n = 31), LAM (n = 45) or ETV (n = 54). After 24 months of treatment, cumulative virological response (VR) rates (HBV DNA <500 copies/mL) were 83.7, 65.3 and 89.1 % in TBV, LAM and ETV groups, respectively (p = 0.009). Reduction in HBV DNA levels in TBV was ?3.66 ± 0.56, significantly higher than LAM (?3.34 ± 0.59; p < 0.05) and lower than ETV group (?3.98 ± 0.52; p < 0.05). The rates of HBeAg loss or seroconversion and normalization of alanine aminotransferase (ALT) were similar among the groups. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease score in TBV were significantly improved compared to at baseline without difference among the groups. TBV resulted in similar cumulative rates of survival and incidence of hepatocellular carcinoma (HCC) to LAM and ETV. Frequencies of complications from cirrhosis, including variceal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis, were comparable among the groups. Four patients (16.7 %) in TBV displayed virological breakthrough, lower than LAM and higher than ETV (p = 0.004). Cox regression analysis showed that baseline HBV DNA (hazard ratio 0.743; 95 % confidence interval 0.582–949, p = 0.017) was an independent predictor for VR at 24 months. Long-term therapy with TBV was effective and safe in HBV-related decompensated cirrhosis. 相似文献
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T.J.S. Cross A. Quaglia J. Nolan S. Hughes P.M. Harrison 《Journal of medical virology》2010,82(6):958-964
The impact of steatosis on treatment response in chronic hepatitis C infection is controversial. The aim of this study was to determine whether steatosis ± steatohepatitis on pre‐treatment liver biopsy influenced sustained virological response (HCV RNA negative 6 months after completing therapy) in patients with chronic hepatitis C infection treated with pegylated interferon‐α and ribavirin. One hundred and seventy‐nine patients, median age 46 years (interquartile range 40–52), treated between 2001 and 2005. Histological evidence of steatosis was present in 93 patients (52%) and steatohepatitis in 33 patients (18%), 31 patients (17.3%) were cirrhotic. There were 106 (59%) responders, who were similar to non‐responders in respect to gender, age, and pre‐treatment ALT. On univariate analysis, infection with genotype 2 or 3 was associated with sustained virological response (odds ratio 6.5 (95% CI, 3.3–12.5); P < 0.0001), whereas cirrhosis and patient weight were associated with a reduced response (odds ratios 0.23 (95% CI, 0.11–0.48); P < 0.0001, and 0.97 (95% CI, 0.95–0.99); P < 0.01, respectively); steatohepatitis but not steatosis impacted on the likelihood of achieving sustained virological response (odds ratio 0.37 (95% CI, 0.17–0.77); P = 0.009, and P = 0.18, respectively). Multivariate analysis revealed that infection with genotype 1 or 4 (odds ratio 0.09 (95% CI, 0.03–0.32); P < 0.001) and pre‐treatment weight (odds ratio 0.94 (95% CI, 0.90–0.98); P = 0.002) were the only variables associated independently with sustained virological response. In chronic hepatitis C infection, although steatosis was associated with steatohepatitis, neither was shown to affect sustained virological response, which was influenced by genotype, patient weight and the presence of cirrhosis. J. Med. Virol. 82:958–964, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
13.
Schneiders FL Scheper RJ von Blomberg BM Woltman AM Janssen HL van den Eertwegh AJ Verheul HM de Gruijl TD van der Vliet HJ 《Clinical immunology (Orlando, Fla.)》2011,140(2):130-141
For over a century, research has sought ways to boost the immune system in order to eradicate tumors and viruses that exist after escaping immunosurveillance. For the treatment of cancer and hepatitis immunotherapeutic strategies have overall had limited clinical success. An urgent need exists therefore to introduce more effective therapeutic approaches. Invariant (i)NKT cells constitute a conserved T lymphocyte lineage with dominant immunoregulatory, antitumor and antiviral effector cell properties. iNKT specifically recognize the glycolipid α-galactosylceramide in the context of CD1d resulting in their activation. Activated iNKT can promote the development of a long-lasting Th1 biased proinflammatory immune response as demonstrated in multiple tumor-metastasis and viral infection models. Here, we will provide a brief overview of the preclinical data of α-galactosylceramide that formed the basis for subsequent clinical trials in patients with advanced cancer and chronic hepatitis B/C, and elaborate on our own clinical experience with α-galactosylceramide in these patient groups. 相似文献
14.
Chung WG Kim HJ Choe YG Seok HS Chon CW Cho YK Kim BI Koh YY 《Clinical and molecular hepatology》2012,18(2):195-202
Background/Aims
The aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV) therapy in chronic hepatitis B (CHB) patients.Methods
The medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI) values and Alcohol Use Disorders Identification Test (AUDIT) scores were obtained at 6 months after the initiation of ETV (0.5 mg daily) treatment.Results
A BMI of 25 kg/m2 or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3%) were obese and 17 (19.3%) were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT) normalization, and hepatitis B virus (HBV)-DNA negativity (<300 copies/mL) at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033).Conclusions
Obesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users. 相似文献15.
Selabe SG Lukhwareni A Song E Leeuw YG Burnett RJ Mphahlele MJ 《Journal of medical virology》2007,79(11):1650-1654
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Burçin Tuncel Sedat Kaygusuz Derya Beyza Sayın Kocakap Emel Aksoy Ahmet Kürşat Azkur 《Journal of medical virology》2023,95(1):e28376
Hepatitis B virus (HBV) is still a significant health problem in human. HBV severity or sensitivity of patients may be based on the individual genetic factors significantly. The aim of this study is to investigate the association of CCR5 (CCR5Δ32), TLR3 (rs5743313) functional gene polymorphisms, interferon-gamma (IFN-ɣ) level in HBV infection, which are thought to play an important role in innate and acquired immunity in patients who have undergone HBV seroconversion and those who have chronic hepatitis B disease and receive treatment. One hundred patients who are became naturally immune against HBV infection (HBsAg negative, anti-HBc IgG, and anti-HBs IgG positive), and 100 patients with chronic hepatitis B infection (>6 months HBsAg positive) who are receiving oral antiviral therapy were compared for CCR5Δ32, TLR3 (rs5743313) genotypes and serum IFN-ɣ level. It was found that CCR5Δ32 polymorphism (Wt/Δ32 and Δ32/Δ32) was significantly higher in the chronic hepatitis B group (p = 0.048) but not for TLR3 gene polymorphism. However, serum IFN-ɣ level was significantly higher in the HBV seroconversion group (75 ± 89 ng/ml) than in the chronic hepatitis B group (4.35 ± 17.27 ng/ml) (p < 0.001). In conclusion, a higher CCR5Δ32 allele frequency in patients with chronic hepatitis B might be considered as a marker of progression to chronic hepatitis. 相似文献
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Persistent viruses, such as cytomegalovirus or human immunodeficiency virus, cause major perturbations of CD8+ T-lymphocyte subpopulations. To test whether chronic infection with hepatitis B virus (HBV) could also be responsible for such modifications, we analyzed the expression of CD27, CD28, CCR7, and perforin in blood CD8+ T lymphocytes. In comparison to healthy subjects and patients recovering from acute hepatitis B, chronic hepatitis B patients showed higher percentages of na?ve CD8+ T lymphocytes (CD45RA+CD27+CD28+), and lower percentages of intermediately-differentiated CD27+CD28?CD8+ T cells. The late differentiated CD45RA+CD27?CD28? subset was also present in a large percentage in some patients, but no statistically significant difference with healthy controls was observed. Removal from the circulation of intermediately-differentiated CD8+ T lymphocytes may occur during chronic HBV infection, favoring the recruitment of na?ve cells. This may result in impairment of the generation of functionally-competent memory cells, and an inability to achieve control of HBV replication. 相似文献
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