Differential response of HBV envelope-specific CD4 + T cells is related to HBsAg loss after stopping nucleos(t)ide analogue therapy.

BACKGROUND AND AIM: Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T-cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation. APPROACH AND RESULTS: Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96 weeks) or relapsers (relapsed patients who underwent NA retreatment for up to 48 weeks and reachieved stable viral control). HBV-specific T-cell responses were detected at baseline and longitudinally throughout the follow-up. We found responders had a greater magnitude of HBV polymerase (Pol)-specific T-cell responses than relapsers at baseline. After long-term NA discontinuation, simultaneously enhanced HBV Core-induced and Pol-induced responses were observed in responders. Particularly, responders with HBsAg loss possessed enhanced HBV Envelope (Env)-induced responses after short-term and long-term follow-up. Notably, CD4 + T cells accounted for the predominance of HBV-specific T-cell responses. Correspondingly, CD4-deficient mice showed attenuated HBV-specific CD8 + T-cell responses, reduced HBsAb-producing B cells, and delayed HBsAg loss; in contrast, in vitro addition of CD4 + T cells promoted HBsAb production by B cells. Besides, IL-9, rather than PD-1 blockade, enhanced HBV Pol-specific CD4 + T-cell responses. CONCLUSION: HBV-specific CD4 + T-cell responses induced by the targeted peptide possess specificities for long-term viral control and HBsAg loss in CHB patients undergoing NA discontinuation, indicating that CD4 + T cells specific to distinct HBV antigens may endow with divergent antiviral potential.

Effects of entecavir and tenofovir disoproxil fumarate on the incidence and severity of COVID-19 in patients with chronic hepatitis B.

BACKGROUND: Whether different anti-hepatitis B virus (HBV) drugs have different effects on COVID-19 is controversial. We aimed to evaluate the incidence of COVID-19 in chronic hepatitis B (CHB) patients receiving anti-HBV treatment, and to compare the impact of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the severity of COVID-19. METHODS: CHB outpatients were enrolled from December 2022 to February 2023. Questionnaires were used to collect whether subjects were currently or previously had COVID-19 within the past 2 months, and the information of symptoms, duration, and severity if infected. RESULTS: Six hundred thirty CHB patients were enrolled, 64.3% (405/630) patients were currently or previously had COVID-19. No COVID-19 patient required hospitalization, intensive care unit admission, oxygen support or died. Majority of patients reported mild (32.8% [133/405]) and moderate (48.1% [195/405]) symptoms. After propensity score matching, 400 matched patients were obtained (ETV: 238; TDF: 162), among which the incidences of COVID-19 were comparable between ETV and TDF-treated patients (60.1% [143/238] vs. 64.2% [104/162], p = 0.468). The proportion of patients complicated with any symptom caused by COVID-19 were also similar (ETV vs. TDF: 90.9% [130/143] vs. 91.3% [95/104], p = 1.000). In addition, the severity of overall symptom was comparable between ETV and TDF-treated patients, in terms of proportion of patients complicated with severe symptom (9.8% vs. 8.7%, p = 0.989), symptom duration (4.3 vs. 4.3 days, p = 0.927), and symptom severity score (4.1 vs. 4.0, p = 0.758). Subgroup analysis supported these results. CONCLUSIONS: During the current pandemic, the vast majority of CHB patients experienced non-severe COVID-19, and ETV and TDF did not affect COVID-19 severity differently.

Sexual Dysfunction in Patients with Chronic Hepatitis B: Prevalence and Risk Factors.

BACKGROUND: Sexual dysfunction (SD) is an increasingly serious global problem that has adverse effects on the physical and mental health of patients. AIM: This study aimed to investigate the prevalence of SD and its related factors in patients with chronic hepatitis B (CHB). METHODS: A total of 673 outpatients with CHB from October 2019 to December 2020 were included in the analysis. Demographic and clinical information was collected at enrolment. The Arizona Sexual Experiences Scale was used to evaluate SD. OUTCOMES: The primary outcome measure was the prevalence of SD in CHB patients and its associated factors. Secondary outcomes were the corresponding scores in five domains of ASEX: drive, arousal, lubrication and/or erection, orgasm and satisfaction from orgasm. RESULTS: The average age of patients was 47.0 years, with 85.6% male and 88.1% with cirrhosis. The SD prevalence was 25.4% and was increased with the decrease in liver function reserve (Child-Pugh A vs Child-Pugh B: 24.6% vs 44.8%, P = .016), the progression of liver fibrosis (FIB-4 < 1.45, 1.45-3.25, and > 3.25: 21.3%, 26.5%, and 34.4%, respectively; P < .001), and the aggravation of depression (without, mild, and moderate to severe: 18.1%, 33.6%, and 34.2%, respectively; P < .001). In multivariate analysis, SD was independently correlated with female sex (OR: 5.627, 95% CI: 3.501 - 9.044, P < .001), liver fibrosis (OR: 1.730, 95% CI: 1.054 - 2.842, P = .030), depression (OR: 2.290, 95% CI: 1.564 - 3.354, P < .001), and frequent diarrhea and/or upper respiratory tract infection/urinary system infection (OR: 2.162, 95% CI: 1.313-3.560, P = .002). CLINICAL IMPLICATIONS: This study revealed the current situation of SD in CHB patients in China, and appealed to clinicians to pay attention to the physical and mental health of the CHB patients. STRENGTHS AND LIMITATIONS: This study has a large sample size and detailed demographic and clinical data. It evaluated the relationship between SD and liver function reserve and liver fibrosis degree, and compared gender differences of SD. However, this study is a cross-sectional study design and does not include healthy controls. The effects of conflicts between the couple, SD in a partner, antidepressants and hormone changes on SD were not analyzed. CONCLUSION: SD in CHB patients was highly prevalent, and its prevalence increased significantly with the deterioration of liver function reserve, liver fibrosis and depression. Additional longitudinal studies are needed to further explore its causality. Xingmei L, Siru Z, Junhua Y, et al. Sexual Dysfunction in Patients with Chronic Hepatitis B: Prevalence and Risk Factors. J Sex Med 2022;19:207-215.

Off-Treatment Hepatitis B Virus (HBV) DNA Levels and the Prediction of Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy in Patients With Chronic Hepatitis B: A Prospective Stop Study.

Background: The optimal management remains unknown after nucleos(t)ide analogue (NA) discontinuation in patients with chronic hepatitis B (CHB). This prospective study investigated the role of off-treatment viral kinetics in predicting relapse after discontinuation of NA therapy. Methods: A total of 82 noncirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed. Patients with a hepatitis B virus (HBV) DNA level of >2000 IU/mL and an alanine aminotransferase (ALT) level of >2 times the upper limit of normal (clinical relapse) were retreated. Results: Sixty patients were HBV envelope antigen (HBeAg) positive at the start of treatment, and 22 were HBeAg negative. Clinical relapse developed in 28 patients (2-year rates, 31% among HBeAg-positive patients and 53% among HBeAg-negative patients). Age of ≤35 years (hazard ratio [HR], 0.37; P = .026) and end-of-treatment HBsAg level of ≤200 IU/mL (HR, 0.39; P = .078) were independently associated with lower relapse rates. A high risk of biochemical relapse (defined as an ALT level of >2 times the upper limit of normal) was observed if the HBV DNA level was >200000 IU/mL when the level was initially elevated, compared with HBV DNA levels of >2000 to ≤200000 IU/mL (HR, 8.42; P < .001). The risk of biochemical relapse was also high in patients with persistent elevation in the HBV DNA level (confirmed to be >2000 IU/mL within 3 months), compared with the group with transient elevation (HR, 6.87; P < .001). Conclusions: After NA discontinuation, a lower relapse rate was observed in younger patients and in those with low end-of-treatment HBsAg levels. The level and persistence of off-treatment elevated HBV DNA levels were useful in the prediction of a subsequent biochemical relapse and may thus be used to guide off-treatment management.

Optimization of hepatitis B cirrhosis detection by stepwise application of transient elastography and routine biomarkers.

BACKGROUND AND AIM: Significant inflammation may overestimate liver stiffness and result in false positive diagnosis by transient elastography for chronic hepatitis B (CHB) cirrhosis detection. This study tries to further improve the performance by stepwise combination with routine biomarkers. METHODS: A total of 236 compensated CHB patients with alanine transferase lower than five times upper limit of normal, liver biopsies, transient elastography, and routine blood tests were included. Performance of stepwise combination of transient elastography and routine biomarkers was analyzed. RESULTS: The area under the receiver operating characteristics curve for detecting cirrhosis was 0.876 for transient elastography, 0.794 for fibrosis index based on the four factors (FIB-4), 0.765 for age-platelet index (API), 0.715 for aspartate aminotransferase-platelet ratio index (APRI), and 0.661 for alanine-aspartate aminotransferase ratio, respectively. The numbers for significant fibrosis were 0.844, 0.662, 0.595, 0.695, and 0.510 in the same order. The proportion of patients determined as cirrhosis or non-cirrhosis was 66.5% by transient elastography, 41.1% by FIB-4, 14.4% by API, and 24.2% by APRI, respectively; the numbers for significant fibrosis were 55.5% by transient elastography, 11.9% by APRI, and none by the other serum markers. Stepwise combination of transient elastography and FIB-4/APRI increased positive predictive value of confirming cirrhosis diagnosis from 0.677 to 0.808 and 0.724, respectively; and the proportion of patients being determined in the state of cirrhosis and obviating liver biopsy was up to 76%. CONCLUSION: By transient elastography-based stepwise combination with readily available serum markers, performance of detecting compensated CHB cirrhosis could be significantly improved in terms of diagnosis accuracy and proportion of obviating liver biopsy.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis.

Background: The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. Patients and methods: A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire. Results: A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001). Conclusion: Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

Risk Factors Associated With Quality of Life in Patients With Hepatitis B Virus Related Cirrhosis.

Aim: To evaluate health-related quality of life (HRQoL) of chronic hepatitis B (CHB) and hepatitis B virus (HBV) related cirrhosis patients and analyzed specific differences in all dimensions of HRQoL. Methods: A total of 349 patients met selection criteria were enrolled. The 36-Item Short-Form Health Survey was adopted. Results: Results showed that the physiological HRQoL of the cirrhotic group was significantly lower than that of the non-cirrhotic group (P = 0.003), the psychological HRQoL was also lower (P = 0.006). HRQoL was significantly negatively correlated with liver stiffness (P = 0.001). We further evaluated the risk factors associated with poor HRQoL in HBV-related cirrhosis patients. Results showed that positive HBV DNA viral load (OR = 6.296, P = 0.041) and HCC family history (OR = 36.211, P = 0.001) were independent factors associated with HRQoL in HBV-related cirrhosis. For better risk stratification of patients, multivariable analyses were conducted to explore the independent factors that affected specific physiological and psychological HRQoL. In specific physiological HRQoL, results show that marital status (OR = 9.971, P = 0.034), positive HBV DNA viral load (OR = 6.202, P = 0.042) and antiviral drugs (OR = 0.45, P = 0.031) were independent factors associated with physiological HRQoL in cirrhosis patients. In psychological HRQoL, only HCC family history was independent risk factors associated with psychological HRQoL (OR = 42.684, P = 0.002). Conclusion: We found that the impaired HRQoL dimensions of HBV related cirrhosis patients differ between the various subpopulations. According to our results, risk stratification, medical decision making and personalizing interventions could be made.

The Landscape of Cell-Free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

Risk factors associated with fatigue in chronic hepatitis B patients.

AIM: To evaluate fatigue in chronic hepatitis B patients and its related independent factors, as well as the relationship between fatigue and health-related quality of life (HRQoL). MATERIALS AND METHODS: The study enrolled 400 patients who met the selection criteria, and their sociodemographic information was collected. The 36-item Short-Form Health Survey (SF-36) and Multidimensional fatigue inventory 20 (MFI-20) were adopted to evaluate HRQoL and fatigue level. RESULTS: Significant differences between the fatigue group and non-fatigue group were observed for the female proportion (p=0.021), height (p=0.003), and weight (p=0.010), with or without regular exercise (p=0.001). We further determined the dimensions of fatigue that were affected by these factors and found that male patients showed significantly lower results than female patients in terms of physical fatigue (p=0.048), mental fatigue (p=0.017), and reduced motivation (p=0.025). In patients who exercised regularly, the fatigue scores for the three dimensions of general fatigue (p<0.001), physical fatigue (p=0.046), and reduced activity (p=0.008) were significantly better than in those without exercise habits. Multivariate analysis was conducted, which suggested that only height and regular exercise habits were the independent factors affecting the patients' fatigue levels. We further analyzed the relationship between quality of life and fatigue. With respect to physiological HRQoL, the average fatigue score of patients with high HRQoL was 41.91, which was significantly lower than that of patients with low physiological HRQoL (56.18, p<0.001). Moreover, the average fatigue score in patients with low psychological HRQoL was 55.25, which was significantly higher than that of patients with high psychological HRQoL (41.23, p<0.001). Correlation analysis showed that the physiological HRQoL and psychological HRQoL scores were negatively correlated with fatigue score (r = -0.639, p<0.001 and r= -0.655, p<0.001, respectively). CONCLUSIONS: In this study, we found that the fatigue dimensions of chronic hepatitis B patients differed between various subpopulations. Height and regular exercise habits were the independent factors that affected the patients' fatigue levels. Moreover, HRQoL was correlated with fatigue level. For patients with risk factors of fatigue, target intervention is advised in order to decrease fatigue and increase HRQoL.

Factors associated with adherence to nucleos(t)ide analogs in chronic hepatitis B patients: results from a 1-year follow-up study.

Little is known about the factors associated with patient compliance with nucleos(t)ide analog (NUC) treatment for chronic hepatitis B (CHB). The purpose of this study was to examine the association between sociodemographic and clinical characteristics and adherence to NUCs among patients with CHB. A total of 211 CHB patients receiving NUC monotherapy were asked to report the number of prescribed doses of medication they had taken during the last 90 days. A total of four 3-month adherence scores were averaged to obtain a combined rate of NUC adherence during a 1-year follow up period. The mean age of the patients was 29.6 years, 79% were men, and 68% had no prior NUC treatment for CHB. Females, patients without a previous NUC treatment, and those who had NUC drug resistance showed better adherence to NUC treatment, and compliance was better with telbivudine than with lamivudine and entecavir.

Duck HBV DNA copy numbers in isolated hepatocyte nuclei vary dramatically and decline during entecavir therapy.

BACKGROUND: We aimed to develop a quantitative assay to measure duck HBV (DHBV) DNA in single hepatocyte nuclei from DHBV-infected animals and to observe intranuclear DHBV DNA kinetics undergoing entecavir (ETV) therapy. METHODS: DHBV DNA in isolated nuclei was amplified by quantitative real-time PCR. Liver tissues from chronically-infected ducks with or without ETV treatment were assessed. Cell cycle phases were defined with flow cytometry in single nuclei. RESULTS: We successfully established a quantitative assay to measure intranuclear DHBV DNA in single nuclei with high specificity, sensitivity and acceptable interassay variations. The intranuclear viral DNA copy numbers varied dramatically (2-204 copies/nuclei) in 11 ducks with active viral replication. Average intranuclear DHBV DNA copies from individual animals (7.57-57.67 copies/nuclei) significantly correlated with total intranuclear (rs=0.955, P<0.001) and serum (rs=0.745, P=0.008) viral DNA levels. The median intranuclear DHBV DNA copies in virus-positive nuclei were greater in gap 0/1 than those in gap 2/mitosis and synthesis phases (P<0.001). Median intranuclear viral DNA copies in virus-positive nuclei decreased from 21 to 6 (P<0.001) under 14-19 weeks of ETV therapy. However, subsequently, further reductions were not achieved in four animals after extended 16 week treatment (6 versus 11, P=0.034). CONCLUSIONS: Intranuclear DHBV DNA levels varied significantly, which could be partially attributed to effects of cell cycle phases, and could be decreased by ETV therapy.

[Influence of adefovir dipivoxil or telbivudine monotherapy on renal function of patients with chronic hepatitis B].

OBJECTIVE: To evaluate the changes in the renal function of patients with chronic hepatitis B (CHB) receiving adefovir dipivoxil (ADV) or telbivudine (L-DT) monotherapy. METHODS: This retrospective analysis involved 101 patients with CHB and liver cirrhosis receiving either ADV or L-DT monotherapy for 52 weeks. Serum creatinine, estimates of glomerular filtration rate (eGFR), and the percentage of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) at week 52 were compared with the baseline data between the two groups. RESULTS: The mean changes of CR at week 52 from baseline were +0.05 mg/dl in ADV group and -0.12 mg/dl in L-DT group, showing a significant difference between the two groups (P=0.000). No patient was found to have an elevation of creatinine over 0.50 mg/dl. The median change of eGFR at week 52 from baseline differed significantly between ADV and L-DT groups (-4.09 vs+18.32 ml·min(-1)·1.73 m(-2), P=0.000). Ninety-two percent (12/13) of the patients with baseline eGFR<90 ml·min(-1)·1.73 m(-2) shifted to eGFR ≥90 ml·min(-1)·1.73 m(-2) after 52 weeks of L-DT treatment, as compared to 38% (3/8) in ADV group. The proportion of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) in L-DT group increased from 76.36% (42/55) at baseline to 94.55% (52/55) at week 52, while that in ADV group decreased from 82.61% (38/46) at baseline to 78.26% (36/46). The constituent ratios of eGFR at different levels were similar at baseline (P=0.443) but significantly different at week 52 between the two groups (P=0.015). CONCLUSION: L-DT treatment is associated with a renoprotective effect in patients with CHB, but the mechanism remains unclear.