gs-7340 and entecavir

Long-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogues is often necessary to achieve durable viral suppression. Therefore, current guidelines recommend the most potent drugs with optimal resistance profiles. Entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line monotherapies for CHB. All of these drugs are highly effective in suppressing viral replication but with slightly different safety profiles. This review provides an overview of the long-term efficacy and safety data that have become available over the 10 years since ETV and TDF were first approved for the treatment of chronic hepatitis, and recent data on TAF in patients with CHB.

Topics: Adenine; Administration, Oral; Alanine; Antiviral Agents; Drug-Related Side Effects and Adverse Reactions; Guanine; Hepatitis B, Chronic; Humans; Nucleosides; Randomized Controlled Trials as Topic; Tenofovir; Time Factors; Treatment Outcome

Entecavir (ETV) and tenofovir alafenamide fumarate (TAF) have been used widely to treat patients with chronic hepatitis B virus (HBV) infection, but it is still unclear how best to use these drugs. Although some studies compared the efficacies of treatment switch from ETV to TAF, there has been no randomized study.. We performed a prospective multicenter randomized controlled study in which subjects were enrolled from April 2018 to June 2019 and observed for 2 years until March 2021 to clarify the efficacy and safety of switching from ETV to TAF.. Thirty-three patients were enrolled and randomized into 2 groups, and a total of 30 patients were evaluated; a TAF-switching group (n = 16) and an ETV-continuing group (n = 14). The mean age of the 30 patients was 61 years old and 18 patients (60%) were male. The serum HBV DNA in all patients were below detection limit. The mean change in hepatitis B surface antigen (HBsAg) levels after 2 years was not significantly different between the TAF and ETV groups (-0.08 vs -0.20 log IU/mL, P = .07). Comparing the group with a HBsAg decline (≤ -0.1 log IU/mL) and a group without a HBsAg decline in an overall analysis, the prior ETV duration was significantly shorter in the HBsAg-declined group (49 vs 92 months, P = .03). Although the eGFR levels tended to decrease in the TAF group compared to ETV (-6.15 vs -2.26 mL/min/1.73 m2, P = .09), no significant differences were observed in patients with baseline eGFR < 60 (-2.49 vs 0.40 mL/min/1.73 m2, P = .25).. The efficacy and safety were comparable in the TAF-switching group and the ETV-continuing group. Because the present study was conducted in limited patients, a larger study will be required.

Topics: Adenine; Alanine; Antiviral Agents; DNA, Viral; Female; Fumarates; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Male; Middle Aged; Prospective Studies; Tenofovir; Treatment Outcome

There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF.. Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response.. Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported.. TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF.. This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019).

Topics: Acute-On-Chronic Liver Failure; Adenine; Adult; Alanine; Antiviral Agents; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Tenofovir; Treatment Outcome

Tenofovir alafenamide (TAF) is a newly developed prodrug of tenofovir (TFV). We divided 48 chronic hepatitis B patients who had taken entecavir (ETV) for ≥2 years into two groups: the ETV continuation (n = 24) and the TAF switching (n = 24) groups, and compared the antiviral effects and safety until 48 weeks after the start of the study. There were no significant differences in the alterations in the serum levels of HBs antigen (HBsAg) level between the ETV continuation and the TAF switching groups at 24 or 48 weeks. We also examined the effect of baseline HBsAg level on the decrease of HBsAg during the treatment; in the TAF switching group, the decrease of HBsAg level at 48 weeks was more significant in patients with low baseline HBsAg (<800 IU/mL) than those with high baseline HBsAg ( >800 IU/mL) (change of HBsAg; - 0.029 vs - 0.132 for high and low baseline HBsAg, respectively, P = .007). Also, the effect on renal function was found to be comparable between the TAF switch group and the ETV continuation group. In this study, switching from ETV to TAF may represent higher efficacy for a decrease of HBsAg than a continuation of ETV among the patients with low baseline HBsAg level.

Topics: Adenine; Adult; Aged; Alanine; Antiviral Agents; Female; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Male; Middle Aged; Tenofovir

Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting.. In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (n = 163), TDF (n = 154), or TAF (n = 46) from July 2007 to September 2019 were enrolled.. Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0-74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (p < 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (p = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (p = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (p = 0.894).. ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.

Topics: Alanine; Antiviral Agents; Carcinoma, Hepatocellular; Guanine; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Middle Aged; Retrospective Studies; Tenofovir; Treatment Outcome

To evaluate the long-term efficacy of switching of the nucleos(t)ide analog used for treatment from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in patients with chronic HBV infection.. A total of 103 patients with serum HBsAg levels of ≥100 IU/mL who had received ETV were enrolled. The nucleos(t)ide analog used for the treatment was switched from ETV to TAF, and the changes in serum HBsAg levels during the 144-week period before and after the drug switching were compared in 74 patients who had received ETV at least for 192 weeks.. Significant decreases of serum HBsAg levels were observed during both the ETV and the TAF administration period, although the degree of reduction was greater during the latter period than during the former period (P<0.001). Significant decreases of serum HBsAg levels were seen in both patients with genotype B HBV infection and genotype C HBV infection, irrespective of the serum HBsAg and HBcrAg levels at the time of the drug switching.. Switching of the nucleos(t)ide analog used for treatment from ETV to TAF merits consideration in patients with chronic HBV infection, since the extent of reduction of the serum HBsAg level was greater during the TAF treatment period than during the ETV treatment period.

Topics: Aged; Alanine; Antiviral Agents; Drug Substitution; Female; Follow-Up Studies; Fumarates; Genotype; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Nucleosides; Prospective Studies; Tenofovir; Treatment Outcome

Antiviral agents for chronic hepatitis B (CHB) reduced the risk of hepatocellular carcinoma (HCC) development. The outcomes of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) were compared in patients with CHB.. Between 2017 and 2019, treatment-naïve patients with CHB treated with ETV, TDF, and TAF were recruited from three Korean tertiary institutes. The cumulative incidences of HCC and orthotopic liver transplantation (OLT) or mortality were calculated and compared using Kaplan-Meier analysis before and after trimatch.. Among recruited 2082 patients, 43 patients developed HCC, whereas 66 developed OLT or mortality. Before trimatch, the cumulative incidence of HCC was statistically similar among patients treated with three antiviral agents (p = 0.340). However, the cumulative probability of OLT or mortality development in patients treated with ETV or TDF was significantly higher than that of patients with TAF before trimatch (all p < 0.05). On multivariate analysis, male sex [hazard ratio (HR) 2.990] and older age (HR 1.044) were independently associated with an increased risk of HCC development, whereas higher platelet count (HR 0.993) was independently associated with a decreased risk (all p < 0.05). The type of antiviral agents did not significantly influence the risk of HCC and OLT or mortality development (all p > 0.05). After trimatch, no significant difference in the cumulative probability for HCC and OLT or mortality according to antiviral agents was found (all p > 0.05).. The outcomes of ETV, TDF, and TAF on the risk of HCC and OLT or mortality were statistically similar in treatment-naïve patients with CHB.

Topics: Aged; Alanine; Antiviral Agents; Carcinoma, Hepatocellular; Guanine; Hepatitis B; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Tenofovir; Treatment Outcome

Tenofovir alafenamide (TAF), a new tenofovir prodrug, has been developed to circumvent the less favorable safety profile of tenofovir disoproxil fumarate (TDF). We investigated reductions in hepatitis B surface antigen (HBsAg) levels in patients with HBV infection who received continuous entecavir (ETV) monotherapy or sequential therapy with ETV and TAF.. This retrospective cohort study included 286 patients who were divided into two groups: continuous ETV monotherapy (ETV group, n = 168) and sequential therapy with ETV and TAF (ETV-TAF group, n = 108). Factors associated with a 90% reduction in HBsAg levels were analyzed by a Cox proportional hazards model using a time-dependent covariate in both groups.. In the multivariate Cox proportional hazards model, the ETV-TAF group [adjusted hazard ratio (aHR) 2.750; 95% confidence interval (CI), 1.265-3.405; P = 0.0038] and BMI ≤ 25.0 kg/m2 (aHR 0.520, 95% CI, 0.308-0.875; P = 0.0139) demonstrated a 90% reduction in HBsAg levels. HBsAg levels of patients in the TAF phase in the ETV-TAF group showed greater yearly percent reductions than those in the ETV group and those in the ETV phase in the ETV-TAF group (P = 0.0361 and P = 0.0022, respectively, Steel-Dwass test).. HBsAg levels decreased more rapidly after patients switched from ETV to TAF. Switching to TAF may be an effective treatment option to reduce HBsAg levels.

Topics: Adenine; Alanine; Antiviral Agents; Fumarates; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Retrospective Studies; Tenofovir; Treatment Outcome

Tenofovir alafenamide is a new prodrug of tenofovir that allows for the treatment of patients with hepatitis B virus (HBV) at a lower dose than with tenofovir disoproxil fumarate, due to the more efficient delivery of tenofovir to hepatocytes. In this study, we compared entecavir and tenofovir alafenamide in terms of their ability to reduce hepatitis B surface antigen (HBsAg) in the same group of patients with HBV infection.. During March and June 2018, 129 patients who received entecavir were switched to tenofovir alafenamide. Every 3- 6 months for 1 year before and after switching to tenofovir alafenamide, all patients underwent measurements of HBsAg, hepatitis core-related antigen (HBcrAg), calcium (Ca), inorganic phosphorus, and estimated glomerular filtration rate (eGFR).. The percent decline rate during the entecavir and tenofovir alafenamide phases at 6 months were 2.38% (-3.57 to 0.00) and -3.57% (-7.14 to 0.00), respectively, and those at 12 months were 3.03% (-6.57 to 0.00) and -5.56% (-7.41 to -2.50), respectively. HBsAg levels were reduced significantly more during the tenofovir alafenamide phase than during the entecavir phase (P < 0.0001). There were no significant differences in the percent declines of HBcrAg, Ca, inorganic phosphorus, or eGFR during the entecavir and tenofovir alafenamide phases after 1 year.. tenofovir alafenamide significantly decreased HBsAg levels compared to entecavir.

Topics: Alanine; Antiviral Agents; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Tenofovir; Treatment Outcome

About 20% of patients receiving nucleos(t)ide analogues treatment experienced low-level viraemia (LLV), which is associated with progression of liver fibrosis and high risk of hepatocellular carcinoma. We aimed to evaluate the effectiveness and safety of switching from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in ETV-treated patients with LLV.. In this prospective study, ETV-treated patients with LLV, presented to our hospital from December 2018 to October 2019, were enrolled. Switching to TAF or continuing ETV was given. The primary effectiveness endpoint was complete virological response (CVR) at 24 weeks, and the safety endpoint was the first occurrence of any clinical adverse event during the treatment.. Totally, 211 patients were recruited and propensity score matching (PSM) generated 75 patients in either TAF or ETV group. After PSM, baseline characteristics were balanced in two groups. After 24-week treatment, the CVR and ALT normalization in TAF group were 62.7% and 47.6%, which were higher than 9.3% and 10.5% in ETV group (OR 16.4, 95% CI 6.6-40.0, P < .001) respectively. Subgroup analysis showed that switching to TAF achieved favours CVR regardless of the status of sex, age, CHB family history, HBV DNA, HBeAg and cirrhosis, whereas alcohol consumption and diabetes mellitus might compromise the CVR of switching to TAF. Both therapies were well tolerated and had satisfying renal safety.. For ETV-treated patients with LLV, switching to TAF is safe enough and superior compared with continuing ETV monotherapy regarding both virological and biochemical benefits.

Topics: Adenine; Alanine; Antiviral Agents; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Prospective Studies; Tenofovir; Treatment Outcome; Viremia

To evaluate the impact of chronic hepatitis B virus infection (CHB) treatment on risk of cirrhosis, liver-related outcomes, and death among a diverse CHB cohort with a large proportion of African Americans.. Adults with noncirrhotic CHB without human immunodeficiency virus from 2010 to 2018 were retrospectively evaluated across 4 US safety-net health systems. CHB was identified with International Classification of Diseases, Ninth Revision/Tenth Revision diagnosis coding and confirmatory laboratory data. Propensity-score matching, Kaplan-Meier methods, and adjusted Cox proportional hazards models were used to evaluate impact of CHB treatment on risk of cirrhosis, hepatocellular carcinoma (HCC), death, and composite of cirrhosis, HCC, or death.. Among 4,064 CHB patients (51.9% female, 42.0% age <45 years, 31.6% African American, 26.6% Asian, 26.7% Hispanic), 23.2% received CHB antiviral therapy and 76.8% did not. Among the propensity score-matched cohort (428 treated and 428 untreated), CHB treatment was associated with lower risk of cirrhosis (hazards ratio 0.65, 95% confidence interval 0.46-0.92, P = 0.015) and composite of cirrhosis, HCC, or death (hazards ratio 0.67, 95% confidence interval 0.49-0.94, P = 0.023). Females vs males and African Americans vs non-Hispanic whites had significantly lower risk of cirrhosis. When treatment effects were stratified by age, sex, and ethnicity, the benefits of antiviral therapies in reducing risk of cirrhosis were seen primarily in CHB patients who were females, age <45 years, and of Asian ethnicity.. Our propensity score-matched cohort of noncirrhotic CHB patients demonstrated significant reductions in risk of cirrhosis due to CHB treatment.

Topics: Adult; Aged; Alanine; Antiviral Agents; Asian; Black or African American; Carcinoma, Hepatocellular; Female; Guanine; Hepatitis B, Chronic; Humans; Kaplan-Meier Estimate; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Mortality; Propensity Score; Proportional Hazards Models; Retrospective Studies; Safety-net Providers; Tenofovir; United States; Urban Population; White People

Aspirin may reduce the risk of chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in patients receiving antiviral treatment. We aimed to investigate the impact of aspirin on reducing HCC risk in patients treated with first-line oral nucleos(t)ide analogs (NAs; entecavir and/or tenofovir disoproxil fumarate).. We conducted a territorywide, retrospective cohort study in NA-treated CHB patients between 2000 and 2018 from the electronic healthcare data repository in Hong Kong. Subjects were classified into aspirin users for at least 90 days during NA treatment (aspirin group) or no aspirin or any other antiplatelet use during follow-up period (no aspirin group). Incidence rates of HCC and gastrointestinal bleeding (GIB) in 2 groups with propensity score matching with 1:3 ratio.. Of 35,111 NA-treated CHB patients of mean age of 53.0 years and 61.6% men, sixty-nine (4.0%) and 1,488 (4.5%) developed HCC at a median (interquartile range) of 2.7 (1.4-4.8) years and 3.2 (1.8-6.0) years in the aspirin group and no aspirin group, respectively. A duration-dependent association between aspirin and the risk of HCC was observed (subhazard ratio [sHR] 3 months-2 years: 0.65; 95% confidence interval [CI] 0.47-0.92; sHR 2-5 years: 0.63; 95% CI 0.43-0.94; sHR from ≥5 years: 0.41; 95% CI 0.18-0.91). Patients who took aspirin for ≤2 years had significantly higher risk of GIB (sHR: 1.73, 95% CI 1.07-2.79) than those not receiving aspirin. The risk of GIB started declining with the longer use of aspirin and becoming insignificant for ≥5 years' use (sHR: 0.79, 95% CI 0.19-3.21).. Long-term aspirin use is associated with a lower risk of HCC in a duration-dependent manner in NA-treated CHB patients without a significant increase in the risk of gastrointestinal adverse effects.

Topics: Adult; Aged; Alanine; Antiviral Agents; Aspirin; Carcinoma, Hepatocellular; Drug Therapy, Combination; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Guanine; Hepatitis B, Chronic; Hong Kong; Humans; Incidence; Liver Neoplasms; Male; Middle Aged; Retrospective Studies; Tenofovir

Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC.. From 2012 to 2019, treatment-naïve CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan-Meier method.. In total, 1810 patients (1525 and 285 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p = 0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR = 0.973; p = 0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR = 0.949; p = 0.743).. These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.

Topics: Alanine; Antiviral Agents; Carcinoma, Hepatocellular; Guanine; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Retrospective Studies; Tenofovir; Treatment Outcome

Standard literature procedures for the chemical synthesis of l-threose nucleosides generally employ l-ascorbic acid as starting material. Herein, we have explored two alternative routes that start from either l-arabitol or l-diethyl tartrate, both affording 2-

Topics: Adenine; Animals; Antiviral Agents; DNA, Circular; DNA, Viral; Drug Resistance, Viral; Guanine; Hepatitis B; Hepatitis B virus; Male; Mice; Mice, Inbred C57BL; Nucleosides; Prodrugs; Virus Replication

The significance of switching of the nucleos(t)ide analog used to treat patients with hepatitis B virus (HBV) from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) is uncertain. The subjects of this study were 159 patients with HBV who received treatment with ETV followed by TAF. Among these patients, serial changes in the HBV marker levels were monitored in 92 patients in whom the serum HBsAg levels were ≥100 IU/mL during the 48-week period immediately before and after the switching. A questionnaire survey for medication compliance was performed in 127 patients. The serum HBsAg levels (log IU/mL) decreased by 0.041 during the ETV treatment period and by 0.068 during the TAF administration period. The degree of reduction was higher during the TAF administration period than during the ETV administration period in patients without cirrhosis (P = .030), patients with genotype B HBV (P = .014), and patients with undetectable serum HBcrAg (P = .038). Multivariate analysis revealed the HBV genotype (B vs C; odds ratio, 3.400; P = .025) and serum aspartate aminotransferase level (every 1+; 1.111; P = .015) at the time of switching as factors influencing the treatment efficacy. Thirty-six patients (28%) responded that the number of days that they forgot to take the drug decreased after the drug switching, and 77 patients (61%) reported feeling satisfied with the drug switching. Switching of the nucleos(t)ide analog used from ETV to TAF may be useful in the treatment of patients with HBV infection, as it is associated with both a decrease in the serum HBsAg level and improvement of the medication compliance.

Topics: Adenine; Aged; Alanine; Antibodies, Viral; Antiviral Agents; Female; Fumarates; Genotype; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Japan; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Surveys and Questionnaires; Tenofovir; Transaminases; Treatment Outcome

The prediction of hepatocellular carcinoma (HCC) development during nucleotide/nucleoside analog (NA) therapy is clinically important in patients with chronic hepatitis B. Although several useful models for HCC prediction have been previously reported, their usefulness in the Japanese population is unclear. Therefore, this study examines the applicability of these models in Japanese patients.. Four hundred forty-three patients with no history of HCC who were treated with entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate were enrolled. PAGE-B, modified-PAGE-B, and REACH-B scores were calculated, and subsequent HCC development was investigated.. The mean follow-up duration was 5.1 years, and a total of 33 patients (7.4%) developed HCC during the follow-up period. Multivariate analysis revealed that old age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = 0.011), male gender (HR 2.62, 95% CI 1.06-6.49, P = 0.037), and low platelet count (HR 0.83, 95% CI 0.77-0.91, P < 0.001) were independent predictors of HCC development. These factors are the same as the factors identified in the PAGE-B model. Time-dependent area under the receiver operating characteristic (AUROC) curve revealed that the AUROCs for 3 and 7 years of PAGE-B (AUROC: 0.786 and 0.744 at 3 and 7 years, respectively) were continuously higher than those of REACH-B (0.658 and 0.543) and modified PAGE-B AUROC (0.772 and 0.731).. PAGE-B, which can easily identify high-risk cases, can be useful for predicting HCC development in Japanese patients treated with NA therapy.

Topics: Adenine; Adult; Alanine; Antiviral Agents; Asian People; Carcinoma, Hepatocellular; Cohort Studies; Female; Guanine; Hepatitis B, Chronic; Humans; Japan; Liver Neoplasms; Male; Middle Aged; Nucleotides; Platelet Count; Research Design; Risk; Tenofovir; Time Factors

Tenofovir alafenamide (TAF) has been newly approved for the treatment of chronic hepatitis B (CHB). We aimed to assess the effectiveness and renal safety of switching from entecavir (ETV) or nucleos(t)ide analogue (NA) combination therapy to TAF.. This multicentre, retrospective, cohort study included 313 consecutive CHB patients who switched to TAF monotherapy after treatment with ETV or a nucleos(t)ide analogue (NA) combination for over 2 years. Virological/laboratory responses were evaluated for 48 weeks after switchover. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m. Switching from ETV or an NA combination to TAF was effective for HBV suppression and continued HBsAg reduction. Moreover, the renal glomerular function of patients in the prior NA combination group with CKD was significantly improved compared to those with non-CKD.. Nucleos(t)ide analogues, such as entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide, inhibit hepatitis B virus (HBV) replication and are recommended as first-line oral agents for chronic HBV infection. We evaluated the virological/biochemical effects and renal safety when patients are switched from entecavir or nucleoside-nucleotide analogue combination therapy to tenofovir alafenamide. Our findings suggest that switching to tenofovir alafenamide was effective for HBV suppression and the improvement in renal function for patients with chronic kidney disease.

Topics: Adenine; Alanine; Antiviral Agents; Cohort Studies; Guanine; Hepatitis B, Chronic; Humans; Retrospective Studies; Tenofovir; Treatment Outcome

Topics: Adenine; Administration, Oral; Alanine; Carcinoma, Hepatocellular; DNA, Viral; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms; Nucleotides; Tenofovir

Acquired Fanconi syndrome has been associated with the long-term ingestion of several nucleoside analogs used to treat chronic hepatitis B virus infection. However, the nucleoside analog entecavir has not been found to cause nephrotoxicity. We report a case of entecavir-induced Fanconi syndrome. Our patient was a 73-year-old man admitted to our hospital because of renal dysfunction. He also presented with hyperaminoaciduria, renal diabetes, phosphaturia, hypophosphatemia, hypokalemia, hypouricemia, and hyperchloremic metabolic acidosis, supporting a diagnosis of Fanconi syndrome. In this case, the cause of Fanconi syndrome was most likely entecavir, which had been administered as needed depending on his renal function for 5 years. After drug discontinuation and replacement with tenofovir alafenamide fumarate therapy once a week, the patient's kidney function recovered and electrolyte anomalies partially improved. We highlight the fact that entecavir may induce severe renal dysfunction, which can cause the development of Fanconi syndrome; therefore, close monitoring of proximal tubular function is recommended during entecavir therapy.

Topics: Acidosis; Acute Kidney Injury; Adenine; Aged; Alanine; Antiviral Agents; Fanconi Syndrome; Guanine; Hepatitis B, Chronic; Humans; Hypokalemia; Hypophosphatemia; Male; Nucleosides; Tenofovir; Treatment Outcome; Withholding Treatment

Topics: Adenine; Alanine; Anti-HIV Agents; Guanine; HIV Infections; Humans; Tenofovir