Alanine Aminotransferase Normalization Rate Research Articles

A Comparison of Alanine Aminotransferase Normalization between Pemafibrate and Bezafibrate in Patients with Nonalcoholic Fatty Liver Disease.

Objective Pemafibrate is a recently developed selective peroxisome proliferator-activated receptor alpha modulator that can improve alanine aminotransferase (ALT) levels in patients with nonalcoholic fatty liver disease (NAFLD). However, the effectiveness of ALT normalization with pemafibrate and bezafibrate, a traditional fibrate, has not been compared. Methods In this retrospective study, we compared the effects of pemafibrate and bezafibrate on ALT normalization in patients with NAFLD. The primary endpoint was the ALT normalization rate at 12 months after administration. Patients Twenty and 14 patients with NAFLD receiving pemafibrate and bezafibrate, respectively, were included in this retrospective analysis. All patients had elevated ALT levels and dyslipidemia at entry. Results The ALT normalization rates at 3, 6, and 12 months were 40%, 55%, and 60% for pemafibrate and 14.3%, 28.6%, and 14.3% for bezafibrate, respectively. The ALT normalization rate at 12 months was significantly higher in patients treated with pemafibrate than in those treated with bezafibrate (p=0.01). Pemafibrate, when compared with bezafibrate, was shown to be a significant factor for ALT normalization in a multivariable analysis with an adjusted odds ratio (95% confidence interval) of 13.8 (1.6-115, p=0.01). Conclusion Pemafibrate is effective in ALT normalization in patients with NAFLD and may be used as a treatment for NAFLD.

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir.

Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate. To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV. A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters. At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% vs 66.7%, P = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 vs -2.4 Log10 IU/mL, P < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% vs -2.1%, P = 0.004; -0.6% vs -1.8%, P = 0.007, respectively). Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.

Evaluation of alanine aminotransferase responses in chronic hepatitis B patients using entecavir or tenofovir disoproxil fumarate

Background/Aim: An estimated 300 million individuals worldwide live with hepatitis B virus (HBV) infection. Alanine aminotransferase (ALT) levels, which indicate liver damage when elevated, are among the crucial laboratory parameters frequently monitored in the follow-up of chronic hepatitis B patients. The primary objectives of antiviral treatment are to reduce liver inflammation and prevent the development of hepatocellular carcinoma or cirrhosis by inhibiting HBV replication. This study evaluated ALT responses and identified factors influencing patient responses following initiating entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment. Methods: This retrospective cohort study collected data from treatment-naive and treatment-experienced patients with elevated ALT levels who received either ETV (0.5 or 1 mg per day) or TDF (245 mg per day) treatment between 2008 and 2018. Pregnant women and patients under 18 were excluded from the study. Elevated ALT levels were defined as greater than 35 IU/L for men and 25 IU/L for women. All patients underwent examinations for ALT, HBV DNA levels, HBeAg, and antiHBe at baseline and every 3–6 months. ALT levels of the patients were monitored for 60 months, and the presence of fatty liver was also documented. Results: Our study comprised 192 patients with a mean age of 53.7 (13.42) years. The majority of patients, 130 (67.7%), were male. Of these, 97 (50.5%) started ETV treatment, while 95 (49.5%) began TDF treatment. The median baseline ALT levels of the patients were 68 (44–133.5) IU/L, and the median ALT levels at the 60th month were 24 (18–32) IU/L. The median initial HBV DNA level was 114,282 (267.5–5,029,875) IU/mL, and the median HBV DNA levels from the 6th month onwards were 0 (0–0). ALT normalization was observed in 44.8% of men and 28.1% of women at 3 months, which was statistically significant (P=0.034). Normalization rates by gender remained consistent in all other months. No significant differences were noted in this regard. ALT normalization rates were 58.5% at the 6th month and 74.7% at the 24th month in the ETV group, significantly higher than in the TDF group (P=0.01, P=0.02, respectively). In patients with fatty liver, ALT normalization rates were significantly lower at 6, 12, 24, and 48 months than those without fatty liver (P=0.01, P=0.01, P=0.009, P=0.002, respectively). Conclusion: Although ALT responses to ETV treatment were more pronounced in specific months, both drugs demonstrated overall efficacy. ALT levels in patients with fatty liver remained elevated despite antiviral treatment. Therefore, patients with chronic hepatitis B and fatty liver may require additional support beyond antiviral therapy, including metabolic, nutritional, and lifestyle recommendations.

Comparison of Pegylated Interferon Alfa Therapy in Combination with Tenofovir Alafenamide Fumarate or Tenofovir Disoproxil Fumarate for Treatment of Chronic Hepatitis B Patients.

The study aims to evaluate the effectiveness of a tenofovir alafenamide fumarate (TAF) and pegylated interferon alfa (PegIFN-α) regimen compared to a tenofovir disoproxil fumarate (TDF) and PegIFN-α therapy in patients with chronic hepatitis B (CHB). Patients who were treated with PegIFN-α in combination with TAF or TDF were retrospectively enrolled. The primary outcome measured was the HBsAg loss rate. The rates of virological response, serological response for HBeAg, and normalization of alanine aminotransferase (ALT) were also calculated. The cumulative incidences of response rates were compared between the two groups using Kaplan-Meier analysis. A total of 114 patients were retrospectively enrolled in the study, with 33 receiving TAF plus PegIFN-α treatment and 81 receiving TDF plus PegIFN-α treatment. The HBsAg loss rate for the TAF plus PegIFN-α group was 15.2% at 24 weeks and 21.2% at 48 weeks, while the TDF plus PegIFN-α group had rates of 7.4% at 24 weeks and 12.3% at 48 weeks (P=0.204 at 24 weeks, P=0.228 at 48 weeks). In subgroup analysis of HBeAg positive patients, the TAF group had a higher HBsAg loss rate of 25% at week 48, compared to 3.8% in the TDF group (P=0.033). According to Kaplan-Meier analysis, the TAF plus PegIFN-α group achieved virological response more quickly than the TDF plus PegIFN-α group (p=0.013). There was no statistical difference in HBeAg serological rate or ALT normalization rate. There was no significant difference in the HBsAg loss between the two groups. However, subgroup analysis revealed that TAF plus PegIFN-α treatment had a higher HBsAg loss rate than TDF plus PegIFN-α treatment in HBeAg-positive patients. Additionally, TAF plus PegIFN-α treatment demonstrated better virological suppression for CHB patients. Therefore, TAF plus PegIFN-α treatment regimen is recommended for CHB patients who aim to achieve functional cure.

Entecavir/peginterferon alfa-2a combination in the treatment of two genotypes of chronic hepatitis B patients with lamivudine resistance

Purpose: To investigate the efficacy of entecavir plus peginterferon alfa-2a in the treatment of chronic hepatitis B (CHB) patients with different hepatitis B virus (HBV) genotypes resistant to lamivudine (LAM). &#x0D; Methods: 119 LAM-resistant CHB patients treated in Baoshan People's Hospital from May 2018 to May 2020 were selected. All patients received entecavir and peginterferon alfa-2a for 24 months and were scheduled for regular outpatient review and telephone follow-up. Polymerase chain reaction (PCR) was conducted to determine the HBV genotype and HBV-DNA clearance. Alanine aminotransferase (ALT) normalization rate, HBV-DNA clearance rates, and hepatitis B e-antigen (HBeAg) seroconversion rate were determined in CHB patients with different genotypes. Quality of life for all patients was assessed using SF-36 Scale. &#x0D; Results: Five out of 119 patients were lost during follow-up, with a follow-up rate of 95.80 %. Two HBV genotypes were identified, of which 42 (36.8 %) were type B and 72 (63.2 %) type C. At the 6th and 12th month of follow-up, the HBV-DNA clearance rate, ALT normalization rate, and HBeAg seroconversion rate were significantly higher in CHB patients with genotype B than in patients with genotype C (p &lt; 0.05). There were no significant differences between the three rates in the two groups at 18th and 24th month of follow-up (p &gt; 0.05). The quality of life (QOL) of the patients differed between the two groups (p &lt; 0.05). &#x0D; Conclusion: Entecavir plus peginterferon alfa-2a are effective in treating LAM-resistant CHB patients with different genotypes. Genotype B CHB patients are more suitable for this combination protocol.

One-year efficacy of tenofovir alafenamide in patients with chronic hepatitis B: An observational study.

Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited.We aimed to explore the efficacy after 1-year TAF treatment.A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF treatment ≥1 year were included. Virological suppression (<20 IU/mL or undetectable), HBsAg level, alanine aminotransferase (ALT) normalization (≤36 U/L), and estimated glomerular filtration rate (eGFR) were analyzed at 1 year. Multivariate logistic regression analysis was performed to determine the associated factors for virological suppression and ALT normalization.Virological suppression was achieved in 83% and the 1-year median decline of hepatitis B virus DNA was 5.18 log IU/mL. ALT normalization occurred in 75.7%. HBsAg level decreased at a median of 0.27 log IU/mL with significant difference from baseline (P < .001). Baseline ALT (odds ratio [OR] 1.005, 95% confidence interval [CI] 1.000–1.010, P = .036) and hepatitis B virus DNA (OR 0.222, 95% CI 0.079–0.621, P = .004) were significant factors for 1-year virological suppression. Age (OR 1.064, 95% CI 1.003–1.130, P = .041) was associated with ALT normalization. Significant changes were observed in creatinine (mean increase 0.03 mg/dL, P = .011) and eGFR (mean decrease 2.6 mL/min/1.73 m2, P = .004) after 1-year TAF treatment.One-year TAF treatment came to good virological response, modest ALT normalization rate and significant HBsAg decline. The observation of significant changes in eGFR warranted further studies.

Tenofovir alafenamide is associated with improved alanine aminotransferase and renal safety compared to tenofovir disoproxil fumarate.

Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir for the treatment of chronic hepatitis B (CHB) infection. We aimed to evaluate the impact of switching to TAF on alanine aminotransferase (ALT) normalization and renal safety. We also described the indications of switching to TAF. Consecutive adult CHB patients switched from tenofovir disoproxil fumarate (TDF) dominant therapy to TAF for more than 12 months were identified retrospectively. A subgroup of patients newly switched to TAF was prospectively invited to perform transient elastography examination and dual-energy X-ray absorptiometry. The time of switching to TAF was defined as baseline. Among 393 patients in the retrospective cohort, the median ALT at month 12 was significantly lower (21.0 [16.0-29.9] U/L vs. 25.0 [19.0-34.0] U/L; p < 0.001) and ALT normalization rate was higher (89.9% vs. 83.7%; p = 0.037) than those at baseline. Estimated glomerular filtration rate decreased from 12 months before baseline and then increased from baseline to month 12 significantly (69.7 ± 22.0 ml/min/1.73 m2 vs. 68.5 ± 21.5 ml/min/1.73 m2 vs. 69.2 ± 21.5 ml/min/1.73 m2 , p = 0.002 (-12 m vs. baseline), p = 0.004 (baseline vs. 12 m)). In the prospective cohort, 103 patients switched to TAF because of age > 60 years (63.1%), bone diseases (54.4%), and renal alteration (42.7%). TAF is associated with ALT improvement and better renal safety than TDF dominant therapy in CHB patients. Most CHB patients switched to TAF because of advanced age, followed by bone disease and renal alteration.

Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug‐induced liver injury: A multicenter, randomized, phase II trial

Evidence for using bicyclol in drug-induced liver injury (DILI) is limited. This study aimed to explore the efficacy and safety of bicyclol in acute DILI. This was a multicenter, randomized, double-blinded, double-dummy, active-controlled, superiority and phase II trial. Patients with idiosyncratic acute DILI were randomized 1: 1:1 to low-dose bicyclol (25 mg times a day [TID]), high-dose bicyclol (50 mg TID) and polyene phosphatidylcholine (control) groups. The primary endpoint was the decrease from baseline in serum alanine aminotransferase (ALT) levels at post-treatment for 4 weeks. Overall, 241 patients were included in the full analysis set, with 81, 82 and 78 patients in the low-dose bicyclol, high-dose bicyclol, and control groups respectively. ALT levels decreased across groups (-249.2 ± 151.1, -273.6 ± 203.1, and -180.8 ± 218.2U/L in the low-dose bicyclol, high-dose bicyclol and control groups, respectively; both p < .001, the bicyclol-dependent groups vs. control group). The ALT normalization rates at weeks 1, 2, 4, 6 and 8 were higher in the bicyclol-dependent groups than in the control group (p=.002 at week 1 and all p < .001 at weeks 2, 4, 6 and 8 respectively). The median times to ALT normalization in the low-dose bicyclol, high-dose bicyclol and control groups were 29, 16 and 43 days respectively. Adverse events, serious adverse events and adverse drug reactions were similar across groups. Bicyclol (25 and 50 mg TID) appeared efficacious and safe for treating idiosyncratic acute DILI, while bicyclol 50 mg TID showed higher efficacy. www. gov (registration no. NCT02944552).

An analysis of the efficacy and safety of compound glycyrrhizin injections in the treatment of drug-induced liver injury using a nationwide database

Background Drug-induced liver injury (DILI) refers to liver damage caused by drugs. DILI poses a significant challenge in the development of new drugs. The management of DILI mainly involves the withdrawal of the offending drug, and there is a lack of specific therapy. This study sought to evaluate the efficacy and safety of compound glycyrrhizin (CG) injections in DILI patients. Aim To evaluate the efficacy and safety of compound glycyrrhizin injections in DILI treatment. Methods The clinical data of DILI patients were collected from a nationwide DILI database. Patients were divided into two groups: the compound glycyrrhizin (CG) group who received CG injections, and the control group who received no treatment. The propensity score matching (PSM) method was applied to obtain an even distribution of characteristics between the two groups. The efficacy of the CG injections was assessed by the analysis of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels between the two groups. Results There were 152 patients in the compound glycyrrhizin group and 512 patients in the control group. The PSM method was used to acquire 152 matched pairs. The compound glycyrrhizin group had a significantly higher overall ALT and AST normalization rate than the control group (43.42% vs. 24.34%, p = 0.0004 and 63.82% vs. 38.82%, p ≤ .0001). There was no difference in the levels of renal and serum biochemical parameters between the two groups. Conclusions CG injections are effective in reducing ALT and AST levels in DILI patients, and their safety is comparable to the control group.

Body weight changes in treated hepatitis B patients switching to tenofovir alafenamide☆

Switching to a tenofovir alafenamide (TAF)-containing regimen has been reported to be associated with body weight gain in human immunodeficiency virus-infected subjects. We aimed to investigate the body weight change and virological, hepatic, and renal outcomes of TAF switching among chronic hepatitis B (CHB) patients. This retrospective study included 121 CHB patients who were switched to TAF after >12 months of treatment with another nucleot(s)ide analog (NUC). All patients were monitored for 12 months. The cohort was mostly Asian (96.7%) with a mean age of 55 years, 72% male, 14% cirrhosis, 21% HBeAg positive, and 75% with prior use of tenofovir disoproxil fumarate. At 12 months after TAF switching, their body weight significantly increased from 66.4±11.8 to 67.8±12.3kg (p<0.001), and 21.1% of the subjects had a ≥5% weight gain. Patients without diabetes or hypertension were more likely to have a body weight gain. Meanwhile, the complete viral suppression rate increased significantly from 89.3% to 96.2% (p=0.016). The rate of alanine aminotransferase normalization also increased significantly from 71.1% to 87.6% (p<0.001) by local criteria and from 58.7% to 70.2% (p=0.029) by AASLD criteria. The mean eGFR (mL/min/1.73m2) did not change (88.2±18.8 vs. 87.2±17.5, p=0.28). However, for the subgroup with GFR <90at TAF switching, there was a significant improvement in eGFR (72.9±12.0 vs. 75.7±14.2, p=0.027). In real-world NUC-experienced CHB patients, unexpected body weight gain was observed after TAF switching. The mechanism needs to be investigated in the future.

Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B

Tenofovir alafenamide fumarate (TAF) is a first-line drug for the antiviral treatment of patients with chronic hepatitis B (CHB) in China. In the present study, the efficacy and renal safety of TAF were evaluated in treatment-naive patients with CHB. Patients with CHB who had not been previously treated with nucleoside analogues (NAs) were recruited before TAF treatment was initiated. Changes in the levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were analyzed at 24 and 48 weeks using immunoassays. In addition, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were analyzed using transient elastography, while alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels, calcium (Ca) and inorganic phosphorus (IP) levels were measured using biochemistry assay. In addition, the estimated glomerular filtration rate (eGFR) was calculated. After 48 weeks, the ALT normalization rate was 95.24% (40/42), the complete virological response (HBV DNA <20 IU/ml) rate was 69.05% (29/42) and the HBeAg seroconversion rate was 8.57% (3/35). The levels of HBV DNA and HBsAg were significantly decreased from the baseline at 5.49±1.95 to 1.26±0.66 log10 IU/ml and from 3.59±0.81 to 3.32±0.55 log10 IU/ml after 48 weeks of treatment, respectively. Compared with that in the baseline measurements, LSM at 48 weeks was significantly decreased from 13.00±8.15 to 8.66±4.45 kPa. No significant differences were observed in the TG, TC, LDL-C, CAP, eGFR, Ca and IP measurements. According to the baseline ALT levels, patients were divided into group A [ALT ≤1 x upper limit of normal (ULN); ULN=50 U/l; n=21], group B (1 x ULN < ALT <2 x ULN; n=22) and group C (ALT ≥2 x ULN; n=18). A significant decrease in HBsAg levels was observed in group B (3.63±0.68 vs. 3.53±0.63 log10 IU/ml) and group C (4.15±0.57 vs. 3.66±0.48 log10 IU/ml) at 24 weeks compared with the baseline. In conclusion, TAF was found to be effective and safe in NA treatment-naive patients with CHB. Moreover, the higher the ALT levels, the more prominent the curative effect from TAF treatment. Therefore, NA treatment-naive CHB patients could benefit from TAF treatment in real world.

Bicyclol for the treatment of drug-induced liver injury: a propensity score matching analysis using a nationwide inpatient database.

ObjectiveTo evaluate the efficacy and safety of bicyclol in patients with drug-induced liver injury (DILI) using a nationwide database.MethodsWe retrospectively analyzed the clinical data of DILI patients in the DILI-R database. Propensity score matching was performed to balance the bicyclol and control groups, and alanine aminotransferase (ALT) recovery was compared between the two groups. Factors associated with ALT recovery and safety were identified.ResultsThe analysis included the data of 25,927 patients. Eighty-seven cases were included in the bicyclol group, with 932 cases in the control group. One-to-one propensity score matching created 86 matched pairs. The ALT normalization rate in the bicyclol group was significantly higher than that in the control group (50.00% vs. 24.42%), and statistical significance was found in the superiority test. After adjustment of baseline ALT levels, baseline total bilirubin levels, sex, age, acute or chronic liver diseases, and suspected drugs in the multivariate logic regression analysis, the major influencing factors for ALT recovery included the time interval between ALT tests (days) and the group factor (bicyclol treatment). There were no differences in the proportion of renal function impairment or blood abnormalities between the two groups.ConclusionsBicyclol is a potential candidate for DILI.

Comparison of the on-treatment risks for hepatocellular carcinoma between entecavir and tenofovir: A propensity score matching analysis.

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) may reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). However, it is not clear whether there is difference in the on-treatment HCC risks between ETV and TDF. In this retrospective cohort study, we compared the on-treatment HCC incidence of ETV and TDF in 1340 consecutive nucleos(t)ide analog-naïve CHB patients by propensity score (PS) matching analysis. PS was calculated by using age, sex, drinking history, diabetes, liver cirrhosis, hepatitis B e antigen positivity, hepatitis B virus DNA, hepatitis B s antigen titer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein, albumin, bilirubin, prothrombin time, platelet count, and calendar year of treatment initiation as covariates. The HCC risk was assessed by Cox regression with death and liver transplantation as competing risks in the 1:1 PS-matched cohorts (n=596). TDF had higher cumulative virologic response (P=0.027) whereas ETV showed higher AST and ALT normalization rates (P=0.005 and<0.001, respectively) in PS-matched cohorts. HCC risk was similar between ETV and TDF, either by PS-matching analysis (hazard ratio [HR] for TDF over ETV=2.06, 95% confidence interval [CI]=0.98-4.33, P=0.058) or inverse probability of treatment weighting analysis (HR=1.30, 95% CI=0.81-2.10; P=0.276). ETV and TDF treatment was associated with similar risk for HCC development in CHB patients.

Alanine aminotransferase normalization with antiviral therapies in hepatitis B

Currently, one-third of the world's chronic hepatitis B virus (HBV) carriers are in China. Therefore, it is important to develop treatment strategies that can accomplish virological suppression and improve clinical outcomes for China's huge HBV-infected population. Studies have shown that alanine aminotransferase (ALT) levels are significantly associated with the progression of liver disease, incidence of liver complications as well as an important indicator for deciding whether to initiate anti-HBV treatment. Clinically, antiviral therapy is usually only considered when the ALT level is greater than 2 times the upper limit of normal. However, a normal or low and elevated level of ALT does not mean that there is no change in liver tissues status. Several studies have suggested that normal or low and elevated levels of ALT are significantly associated with the progression of liver disease. In this context, if the level of ALT is considered as one of the mandatory requirements for the indication of anti-HBV therapy, many patients may be neglected and delayed in treatment, suggesting that the anti-HBV treatment threshold should be considered. Now, from the above discussion, this article mainly summarizes the guiding significance of ALT level in anti-HBV treatment and the value of ALT normalization in the state of illness and clinical prognosis, and also compares the difference of ALT normalization rates among different anti-HBV drugs for chronic hepatitis B patients. Besides this, it also states the limitations of current indications for anti-HBV therapy, so as to provide reference for improving the indications.

Efficacy and Safety of Tenofovir Disoproxil Fumarate in Treatment-Naïve Patients with Chronic Hepatitis B in Korea.

To evaluate the efficacy and safety of 144-week tenofovir disoproxil fumarate (TDF) therapy in treatment-naïve chronic hepatitis B (CHB) patients in Korean. In total, 579 treatment-naïve CHB patients at 11 medical centers were enrolled retrospective and prospective from September 2015 to January 2016 by design (NCT02533544). We evaluated the complete virologic response (CVR) rate and the renal safety of TDF. The overall CVR rate was 69.4%, 87.0%, and 89.7% at weeks 48, 96, and 144, respectively. In the HBeAg-positive CHB patients, the CVR rate at weeks 48, 96, and 144 was 61.4%, 83.1%, and 89.6%, respectively. The rates of HBeAg loss and seroconversion at weeks 48, 96, and 144 were 16.6%, 23.5%, 34.1%, and 7.6%, 8.9%, 13.3%, respectively. In HBeAg-negative CHB patients, the CVR rate at weeks 48, 96, and 144 was 82.5%, 93.2%, and 90.0%, respectively. The rate of alanine aminotransferase normalization was 36.9%, 45.4%, and 46.8% at weeks 48, 96, and 144, respectively. Of the CHB patients, 0.9% showed an elevated creatinine (> 0.5mg/dL from baseline). Age (≥ 60years) was significantly associated with a decline in renal function at week 144 (P < 0.0001). Comorbidities (diabetes or hypertension) showed the tendency to reduce renal function (P = 0.0624). Hepatocellular carcinoma developed in 10 (1.7%) patients and was related to cirrhosis. TDF therapy induced sustained viral suppression and had a favorable safety profile over a 3-year period. However, close monitoring of renal function should be mandatory in treating CHB patients receiving TDF, particularly older patients.

Long-term outcome of entecavir treatment of nucleos(t)ide analogue-naïve chronic hepatitis B patients in Japan.

We determined the antiviral potency and viral breakthrough rate after 10years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection. The cumulative rates of undetectable hepatitis B virus DNA (HBV-DNA, < 2.1logcopies/mL), alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroclearance, hepatitis B surface antigen (HBsAg) seroclearance, and viral breakthrough of 1094 nucleos(t)ide analogue-naïve CHB patients (HBeAg-positive: 47%) who were on continuous entecavir treatment for 10years were calculated. The median age was 50years and follow-up period was 5.5years, with 999, 804, 591, 390, 182 and 87 patients followed up for at least 1, 3, 5, 7, 9 and 10years, respectively. Incremental increases were noted in the rates of undetectable HBV-DNA, ALT normalization, HBeAg seroclearance, and HBsAg seroclearance, reaching 96, 79, 38 and 3.7%, respectively, by the tenth year. The mean decline in HBsAg level from baseline was - 0.08logIU/mL/year. Multivariate analysis identified HBsAg level and genotype (A) as independent predictors of HBsAg seroclearance. Sixteen patients experienced viral breakthrough. The cumulative percentages of patients with viral breakthrough analyzed by the Kaplan-Meier test were 1.5 and 2.5% at years 5 and 10, respectively. There were no serious adverse events during treatment. Long-term entecavir treatment of nucleos(t)ide analogue-naïve CHB patients was associated with an excellent viral response and a low rate of entecavir-resistant mutations at 10years. Baseline HBsAg levels and genotype were predictors of HBsAg seroclearance during entecavir treatment.

Compare the effect of combined therapy between telbivudine plus adefovir dipivoxil and lamivudine plus adefovir dipivoxil corresponding to renal function in patients with hepatitis B virus infection

Objective: To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients. Methods: A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ (2) test. Results: There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min(-1) ·(1.73 m(2))(-1)] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal. Conclusion: For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.

Clinical effect of entecavir versus tenofovir in treatment of HBeAg-positive chronic hepatitis B patients with a high viral load: a comparative analysis

Objective: To investigate the clinical effect and safety of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in the treatment of previously untreated HBeAg-positive chronic hepatitis B (CHB) patients with a high viral load. Methods: A retrospective analysis was performed for the clinical data of 152 HBeAg-positive CHB patients with a high viral load (HBV DNA≥10(6) IU/ml) who were firstly treated with ETV (ETV group) or TDF (TDF group), with 76 patients in each group. The serum levels of alanine aminotransferase (ALT), HBV DNA, HBeAg, anti-HBe, creatinine, and creatine kinase were measured at baseline, and the patients were followed up and evaluated at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 of treatment. The Kaplan-Meier survival curves were used to analyze cumulative complete virologic response, HBeAg seroconversion, and ALT normalization rate. The Cox proportional hazards regression model was used to identify the influencing factors for virologic response. P < 0.05 was considered statistically significant. Results: There were no significant differences in ALT normalization rate between the ETV group and the TDF group at weeks 4, 12, 24, 48, 72, and 96 of treatment (18.1%/55.6%/83.3%/90.3%/93.1%/97.2% vs 16.0%/53.6%/75.4%/94.2%/100%/100%, P > 0.05). There were also no significant differences in virologic response rate between the ETV group and the TDF group at weeks 48 and 96 of treatment (89.5%/97.3% vs 93.4%/98.7%, P > 0.05). The multivariate analysis showed that the baseline parameters were not predictive factors for virologic response. At week 48 of treatment, the TDF group had a significantly higher HBeAg seroconversion rate than the ETV group (14.5% vs 3.9%, P = 0.048); at week 96 of treatment, there was no significant difference in HBeAg seroconversion rate between the two groups (15.8% vs 7.9%, P = 0.132). The Kaplan-Meier survival analysis showed that there were no significant differences between the two groups in cumulative ALT normalization rate, cumulative HBV DNA undetectable rate, and cumulative seroconversion rate. Only one patient in the ETV group experienced virologic breakthrough from weeks 60 to 72 of treatment, and there were no serious adverse reactions. Conclusion: TDF and ETV had similar clinical effects, HBeAg seroconversion rate, and safety in previously untreated HBeAg-positive CHB patients with a high viral load.

Seven-Year Treatment Outcome of Entecavir in a Real-World Cohort: Effects on Clinical Parameters, HBsAg and HBcrAg Levels.

Objectives:We aimed to determine the levels of alanine aminotransferase (ALT), hepatitis B virus DNA (HBV DNA), HBsAg, and a novel viral marker (hepatitis B core-related antigen (HBcrAg)); hepatitis B e antigen (HBeAg) seroconversion and drug resistance rates after 7 years of entecavir treatment in chronic hepatitis B (CHB) patients.Methods:Two hundred and twenty-two Chinese CHB patients on continuous entecavir treatment were recruited. Serologic, virologic, biochemical outcomes, and the occurrence of entecavir signature mutations were determined.Results:The rates of ALT normalization, HBeAg seroconversion, and undetectable HBV DNA were 98.3%, 82.1%, and 98.7%, respectively, after 7 years of entecavir treatment. The genotypic resistance rate was 1.2%. Decline of HBsAg level was modest with a median decline rate of 0.107 log IU/ml/year. Among patients with baseline HBsAg <1,000 IU/ml and annual HBsAg decline rate of ≥0.166 log IU/ml, all have HBsAg of <200 IU/ml (a level highly predictive for HBsAg seroclearance) at year 7. In contrast, in patients with baseline HBsAg ≥1,000 IU/ml and annual HBsAg decline rate of <0.166 log IU/ml, 95.5% had HBsAg of ≥200 IU/ml at year 7. Decline of HBcrAg levels was moderate with a median decline rate of 0.244 log kU/ml/year. Forty-seven patients (32.0%) had undetectable HBcrAg level at year 7.Conclusions:Long-term entecavir therapy continued to have good responses with low drug resistance rate. However, the decline of HBsAg with treatment was suboptimal. HBcrAg level declined at a relatively better rate. Baseline HBsAg level of <1,000 IU/ml and annual decline of 0.166 log IU/ml could be used to predict HBsAg response.

Tenofovir Alafenamide: A Review in Chronic Hepatitis B.

Tenofovir alafenamide (AF) [Vemlidy®], an oral prodrug of tenofovir, was developed to optimize the antiviral potency and clinical safety of the active moiety tenofovir diphosphate (selective reverse transcriptase nucleotide inhibitor). In two identically designed, ongoing, multinational trials in treatment-naive and -experienced adult patients with hepatitis B e antigen (HBeAg)-positive or -negative chronic hepatitis B virus (HBV) infection, once-daily tenofovir AF 25mg provided effective and sustained viral suppression (120-week analysis), and was generally well tolerated. In the primary 48-week analysis, tenofovir AF was noninferior to once-daily tenofovir disoproxil fumarate (DF) 300mg in terms of the proportion of patients achieving viral suppression (HBV DNA <29 IU/mL) and was associated with significantly higher alanine aminotransferase (ALT) normalization rates than tenofovir DF based on AASLD criteria (but not central laboratory criteria). In pooled analyses and/or individual trials, ALT normalization rates by AASLD and central laboratory criteria were significantly higher in tenofovir AF than tenofovir DF recipients at most assessed timepoints up to 96 weeks. Given the bone and renal safety concerns associated with long-term tenofovir DF treatment, the more favourable pharmacological profile of tenofovir AF permits a marked reduction in the dosage of this tenofovir prodrug and thereby reduces systemic exposure to tenofovir, potentially improving the bone and renal safety of tenofovir AF versus tenofovir DF. Long-term clinical experience will more definitively establish the relative bone and renal safety of these tenofovir prodrugs. With its potential for an improved safety profile, tenofovir AF is an important emerging first-line option for the treatment of chronic HBV infection in adults and adolescents (aged ≥12 years and with a bodyweight of ≥35 kg).