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Type 2 diabetes (T2D) is common among patients with chronic hepatitis B infection (CHB) and has been associated with increased risk of carcinogenesis, including HCC. We investigated factors associated with HCC and fibrosis progression among patients with CHB with T2D (CHB+T2D).Chinese patients with CHB were prospectively recruited for the incidence of HCC and fibrosis progression defined by transient elastography. Among patients with CHB+T2D, glycemic control was assessed by mean glycated hemoglobin (HbA1c) and HbA1c variability determined using HbA1c measurements in the 5 years preceding recruitment. A total of 2330 patients with CHB were recruited (mean age 54.6 ±11.8 years old, 55.5% male, 57.9% antiviral-treated), with 671 (28.8%) having CHB+T2D (mean T2D duration 7.2 ± 4.6 years, mean HbA1c 7.2 ± 0.9%). T2D was independently associated with HCC (HR 2.080, 95% CI 1.343-3.222) and fibrosis progression (OR 4.305, 95% CI 3.416-5.424) in the overall cohort. In patients with CHB+T2D, factors reflecting glycemic burden (T2D duration [HR 1.107, 95% CI 1.023-1.198]), mean HbA1c (HR 1.851, 95% CI 1.026-3.339), time reaching target HbA1c (HbA1c-TRT; HR 0.978, 95% CI 0.957-0.999), liver stiffness (HR 1.041-1.043), and smoking (HR 2.726-3.344) were independently associated with HCC (all p 0.05), but not HbA1c variability or controlled attenuation parameter. The same glycemic burden-related factors (T2D duration, mean HbA1c, and HbA1c-TRT), in addition to baseline fasting glucose, baseline HbA1c, AST and antiviral therapy, were independently associated with fibrosis progression at 3 years.High glycemic burden was associated with HCC development and fibrosis progression among patients with CHB+T2D, highlighting the importance of glycemic control in reducing liver-related complications.

Large-scale comprehensive studies on HBV RNA in chronic hepatitis B are lacking. We aimed to study the HBV RNA profile and its correlation with other viral markers in patients with chronic hepatitis B who are treatment-naïve and patients receiving nucleos(t)ide analogues (NA).Biomarkers, including HBV RNA and hepatitis B core-related antigen (HBcrAg), were measured in 388 patients. Of these, 246 were treatment-naïve and were categorized into HBeAg-positive chronic infection (n = 41), HBeAg-positive chronic hepatitis (n = 81), HBeAg-negative chronic infection (n = 39), HBeAg-negative chronic hepatitis (n = 66), and HBsAg seroclearance (n = 19). These biomarkers were also measured in 142 patients who were NA-treated receiving tenofovir or entecavir at baseline, week 48, and week 96. The pattern of serum HBV RNA levels mirrored HBV DNA (1-2 logs higher than HBV RNA) and HBcrAg in patients who were treatment-naïve. HBV RNA correlated best with HBcrAg (r = 0.84) and to a lesser extent with HBV DNA (r = 0.737) (both P 0.001). In patients with HBsAg seroclearance, 15.8% and 15.8% had detectable serum HBV RNA and HBcrAg, respectively. NA treatment reduced serum HBV RNA by 1.46 logs and 1.77 logs at weeks 48 and 96, respectively. At week 96 of NA therapy, only 19.1% patients who were tenofovir-treated and 25.7% patients who were entecavir-treated had unquantifiable HBV RNA (P 0.05). In patients who were treated and had undetectable HBV DNA, 77.5% and 30% had quantifiable HBV RNA and HBcrAg, respectively.HBV RNA showed distinct and corresponding profiles in patients with HBV in different disease phases. HBV RNA and HBcrAg could be used to monitor residual transcriptional activities in patients with HBsAg seroclearance. NA led to reduction of serum HBV RNA. Monitoring of viral activities can still be achieved in patients with undetectable HBV DNA by serum HBV RNA.

Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined.HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU mlOne hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4-104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43-6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35-9.86 and P=0.032, 95% CI: 1.10-7.37, respectively).Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can cause systemic, respiratory, and gastrointestinal manifestations, with many patients requiring mechanical ventilation and ICU-level care Proton-pump inhibitor (PPI) use has previously been linked to increased hospital-acquired and ventilator-associated pneumonias, although a causative relationship remains debated The effect of PPI use in COVID-19 outcomes in unknown We aimed to evaluate the relationship between PPI exposure and clinical outcomes of hospitalized COVID- 19 patients METHODS: This was a retrospective cohort study of consecutive adults hospitalized across nine US centers with COVID-19 The primary outcome measure was the need for mechanical ventilation in patients with and without PPI exposure during their non-ICU ward stay The secondary outcome measure was in-hospital, all-cause mortality among patients with and without any PPI exposure PPI use was further stratified by dosage and timing of initiation Univariate analyses were performed using student's t-test and Fisher's exact test, and multivariable analyses were performed using logistic regression RESULTS: A total of 389 patients were included (mean age 62 9 years, 43 7% women), with 138 (35 5%) receiving PPI, 161 (41 3%) ICU admissions, and 57 (15 0%) deaths PPI exposure during non-ICU ward stay correlated with increased need for mechanical ventilation [aOR 2 31 (95% CI: 1 28-4 18);P = 0 0057] after controlling for potential confounders (Table 1) For our secondary analysis, PPI use was associated with higher in-hospital, all-cause mortality [aOR 2 13 (95% CI: 1 10-4 14);P = 0 027] (Table 2) When stratified by dosage, highdose PPI use, but not low-dose use, remained an independent predictor of both outcomes (Tables 1 and 2) CONCLUSION: PPI use among hospitalized COVID-19 patients was independently associated with greater need for mechanical ventilation and increased mortality Further studies are needed to determine whether this indicates a causal relationship, or whether PPI use represents underlying GERD or other comorbidities with prognostic implications (Table Presented)

INTRODUCTION: Liver injury has been described with COVID-19, and early reports suggested 2-11% of patients had chronic liver disease (CLD) However, there are limited reports on the nature of liver disease among COVID-19 patients and how underlying CLD influences clinical outcomes Given the high prevalence of NAFLD in the US, as well as metabolic syndrome and obesity being potential poor prognostic factors for COVID-19, we hypothesized that CLD, particularly NAFLD, may be associated with more severe clinical course and worse outcomes among patients with COVID-19 We aimed to study the effect of existing liver-related comorbidities on the manifestations and outcomes of hospitalized adults with COVID-19 METHODS: This was a multicenter retrospective study of hospitalized adults with laboratory-confirmed COVID-19 The primary outcome was the impact of CLD on disease severity, including hospital length of stay, ICU admission, need for mechanical ventilation, and death Secondary outcomes included the comparisons of patient characteristics, other clinical manifestations of disease, and laboratory results on admission between patients with and without CLD Further analyses were performed by stratifying patients with CLD into those with and without cirrhosis, and into NAFLD and non-NAFLD Student's t-test/Fisher Exact test were performed for univariate analyses;logistic regression were performed for multivariable analyses RESULTS: Of 363 patients included, 69 (19%) had CLD, including 55 (15 2%) with NAFLD Patients with CLD had longer length of stay (Table 1) After controlling for age, gender, obesity, cardiac diseases, hypertension, hyperlipidemia, diabetes, and pulmonary disorders, CLD and NAFLD were independently associated with ICU admission [(aOR 1 77, 95% CI 1 03-3 04) and (aOR 2 30, 95% CI 1 27-4 17)] and mechanical ventilation [(aOR 2 08, 95% CI 1 20-3 60) and (aOR 2 15, 95% CI 1 18-3 91)] (Table 2) Presence of cirrhosis was an independent predictor of mortality (aOR 12 5, 95% CI 2 16-72 5) CONCLUSION: Overall, nearly one-fifth of hospitalized COVID-19 patients had CLD, which was associated with more critical illness This association was observed in patients with NAFLD but not in those with non-NAFLD CLD This difference might, in part, be secondary to the association between NAFLD and obesity, inflammation and oxidative stress While patients with NAFLD were more likely to be admitted to the ICU and require mechanical ventilation, only those with cirrhosis had an increased risk of mortality (Table Presented)

INTRODUCTION: Patients with COVID-19 most commonly present with fever, dry cough, myalgia, or fatigue;however, the disease may progress rapidly to cause acute respiratory distress syndrome (ARDS) and death Gastrointestinal (GI) symptoms have also been reported with SARS-CoV-2 infection, but data on the prevalence and severity of GI symptoms in patients with cancer are limited We sought to characterize the GI manifestations of COVID-19 in oncology patients Methods: We performed a multicenter cohort study of adult patients hospitalized with COVID-19 in 9 Massachusetts medical centers and identified those with an active malignancy We evaluated the prevalence and severity of GI symptoms among hospitalized COVID-19 patients with cancer, as well as their disease severity and clinical outcomes Results: Of 395 hospitalized patients with COVID-19, 36 (9%) had an active malignancy Of the 36 cancer patients, 23 (63%) reported ≥1 new GI symptom The most prevalent symptoms were anorexia (12, 52%), diarrhea (9, 39%), and vomiting (8;35%) GI symptoms were the initial symptom in 4 (11%) patients, the predominant symptom in 5 (14%) patients, and were severe in 4 (17%) patients Four of 5 patients with GI symptoms at presentation reported concurrent fever, notably 1 patient had no fever or respiratory symptoms Twelve (33%) patients had elevations in liver trans-aminases at presentation Patients with elevated transaminases were more likely to have associated GI symptoms (83 vs 54%, P = 0 04) (Table 1) COVID-related GI symptoms were seen in 73% of patients on active treatment as compared with 52% of patients who were not on active treatment However, these results were not statistically significant There were no differences in the incidence of GI symptoms on COVID-19 based on the specific treatment modality (Table 2) Conclusion: Acute GI symptoms associated with COVID-19 are highly prevalent in hospitalized cancer patients and can occur as a presenting symptom without respiratory symptoms Symptoms are severe in a small subset of patients Fever was not a universal symptom in our cohort of cancer patients Increased awareness of GI symptoms as a manifestation of COVID-19 in patients with cancer may provide opportunities for early identification and management

INTRODUCTION: Gastrointestinal manifestations including diarrhea are prevalent among COVID-19 patients Given the frequent use of broad-spectrum antibiotics, COVID-19 patients are also at substantial risk for hospital-acquired diarrheal illnesses We aimed to evaluate the prevalence and outcomes of Clostridioides difficile infection (CDI) among hospitalized patients with COVID-19 METHODS: This was a retrospective cohort study of patients hospitalized with laboratory confirmed COVID-19 across 9 hospitals in Massachusetts in 3/11/2020-4/2/2020 All patients underwent stool testing for CDI with glutamate dehydrogenase (GDH) and ELISA immunoassay (EIA) for toxin Inconclusive GDH/EIA with high clinical suspicion were confirmed with polymerase chain reaction (PCR) Positive CDI rate in COVID-19 patients was compared with local historical inpatient CDI testing data from 2019 Outcomes and mortality were also compared amongst COVID-19 patients with and without CDI RESULTS: Of the 390 hospitalized patients with COVID-19, 97 (24 9%) were tested for CDI and included in the study All patients received ≥2 antibiotics (median = 4, IQR 2-5 5) Compared to historical controls, COVID-19 patients did not have higher overall CDI positive rate (5 2% [n = 5] vs 9 8% [n = 280];P = 0 16) Specifically, GDH/EIA positive rates were similar between both groups (5 2% vs 5 3%) There were no statistically significant differences in median antibiotic use, PPI use, laboratory data or need for ICU care between CDI vs non-CDI patients However, all-cause mortality was significantly higher among CDI patients (80% vs 12 2%;P < 0 0001) Table 1 CONCLUSION: The prevalence of CDI was not higher among COVID-19 patients despite widespread use of broad-spectrum antibiotics With strict isolation of COVID-19 patients in most hospitals, together with aggressive hand washing and donning/doffing protocols, it is possible that such rigorous measures resulted in the unintended benefit of reducing nosocomial CDI However, albeit a limited sample size, development of CDI was associated with significantly worse outcomes and higher mortality As such, early CDI testing should be implemented among patients with COVID-19 to ensure prompt diagnosis and management

The objective of this study was to determine factors associated with hepatitis B surface antigen (HBsAg) seroclearance after hepatitis B e-antigen (HBeAg) seroclearance.This is a cohort study of HBeAg-positive patients with HBeAg seroclearance. Factors associated with subsequent HBsAg seroclearance were examined.A total of 775 patients were included. At 1, 5, 10, 15, 20, and 25 years after HBeAg seroclearance, the HBsAg seroclearance rate was 0.3, 1.3, 3.0, 8.9, 15.7, and 23.6%, respectively. The rate of HBsAg seroclearance was highest in those who underwent spontaneous HBeAg seroclearance and required no treatment afterward (group 1), compared with those who underwent treatment-induced HBeAg seroclearance (group 2), and those who required antiviral therapy after spontaneous HBeAg seroclearance (group 3). At 25 years after HBeAg seroclearance, the HBsAg seroclearance rate was 38.0, 14.9, and 0% in groups 1, 2, and 3, respectively (P0.001). There was no difference in the rate of HBsAg seroclearance between those who received interferon-based therapy compared with nucleos(t)ide analogs. The median HBV DNA level was similar between those with and without HBsAg seroclearance. The median HBsAg level was significantly lower in those who had HBsAg seroclearance compared with those who did not achieve loss of HBsAg (2.81 vs. 3.52 log IU/ml, respectively, P=0.009). The area under receiver operating characteristic curve for HBsAg at 1 year after HBeAg seroclearance for predicting HBsAg seroclearance was 0.742, with an optimal cutoff of 751 IU/ml.Spontaneous HBeAg seroclearance without need for subsequent antiviral therapy was associated with the highest rate of subsequent HBsAg seroclearance. Lower HBsAg levels were also associated with higher chance of HBsAg seroclearance.

The kinetics of hepatitis B surface antigen (HBsAg) levels preceding spontaneous HBsAg seroclearance has not been fully investigated. The kinetics of HBsAg and hepatitis B virus (HBV) DNA of 203 treatment-naive, hepatitis B e antigen (HBeAg)-negative patients with spontaneous HBsAg seroclearance were compared with 203 age- and sex-matched HBeAg-negative controls. Serum samples at 3 years, 2 years, 1 year, and 6 months before HBsAg seroclearance and at the time of HBsAg loss were tested. Median HBsAg levels at these respective time points before HBsAg seroclearance were 23.5, 3.51, 0.524, and 0.146 IU/mL. For all time points, patients with HBsAg seroclearance had significantly lower median HBsAg and HBV DNA levels, compared to those of the controls (all P < 0.001). Median HBsAg and HBV DNA levels declined significantly until HBsAg seroclearance (P < 0.001). Although median HBsAg levels also decreased significantly with time (P = 0.006) in controls, median HBV DNA levels remained similar (P = 0.414). Serum HBsAg levels, followed by HBsAg log reduction, were the best predictors of HBsAg seroclearance, with an area under the receiving operator characteristic (AUROC) of 0.833 (95% confidence interval [CI]: 0.792-0.873) and 0.803 (95% CI: 0.755–0.849), respectively. The optimal cut-off HBsAg level and HBsAg reduction to predict HBsAg seroclearance were

The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving oral antiviral therapy is controversial. We aimed to determine the HBsAg response in chronic hepatitis B patients treated with entecavir 0.5 mg daily for 2 years.A total of 166 patients were included. Liver biochemistry, hepatitis B virus (HBV) serological markers, HBV DNA, and quantitative HBsAg levels were performed at baseline, year 1, and year 2 after commencing entecavir. Additional HBsAg levels were measured at 12 and 24 weeks in patients with available sera.In all, 68 patients were hepatitis B e-antigen (HBeAg) positive. Age, HBV DNA, and alanine aminotransferase (ALT) were significantly correlated with HBsAg levels at baseline (r=-0.429, 0.607, and 0.254, respectively, all P0.05). The correlation with HBV DNA and ALT levels was reduced by entecavir treatment, and was lost after 2 years of treatment. There was an overall decline in HBsAg levels from baseline to year 1 to year 2 (3,377.4 vs. 2,316.5 vs. 1,903.0 IU/ml, respectively, P0.001). However, at year 2, 102 patients (61%) had no significant changes (0.5 log difference), 50 (30%) had significant decline (≥0.5 log decrease), whereas 14 (9%) had significant increase (≥0.5 log increase). Of the patients, 151 (91%) had undetectable HBV DNA; 25 (37%) underwent HBeAg seroconversion. Neither HBsAg at baseline nor early decline at weeks 12 or 24 was predictive of HBeAg seroconversion at 2 years.Despite HBV DNA suppression, the majority did not show significant decline in HBsAg levels. Early decline of HBsAg levels at 12/24 weeks was not associated with HBV DNA suppression or HBeAg seroconversion.

We aimed to investigate the incidence of occult hepatitis B infection (OBI) in patients with ‘‘cryptogenic’’ hepatocellular carcinoma (HCC) and to study the HBV replicative activity in these patients. Tumorous and adjacent nontumorous liver tissues were obtained from 33 cryptogenic HCC patients and 28 HCC patients with identifiable causes (13 with chronic hepatitis B [CHB], six with chronic hepatitis C, and nine alcohol-related). OBI was identified by nested polymerase chain reaction (PCR). Intrahepatic HBV DNA, covalently closed circular DNA (cccDNA), and pregenomic RNA (pgRNA) were quantified by real-time PCR and reverse-transcription PCR (RT-PCR), respectively. OBI was identified in 24 (73%) cryptogenic HCC patients, one (17%) HCC patient with HCV, and five (56%) patients with alcohol-related HCC. In HCC patients with OBI, HBV DNA were detected in � 2 HBV genomic regions more often in nontumorous tissues than in tumorous tissues (90% versus 57%, respectively; P 5 0.007). Cryptogenic HCC patients with OBI had lower intrahepatic total HBV DNA levels than HCC patients with CHB (median: 0.010 versus 3.19 copies/cell, respectively; P < 0.0001). Only six (26%) cryptogenic HCC patients with OBI had detectable cccDNA (median

Liver stiffness measurement has been shown to be increased in severe acute flares of hepatitis. Whether lesser degree of hepatitis can also increase liver stiffness is not known. The present study aimed to investigate the effect of mild-to-moderate elevations of alanine aminotransferase (ALT) on liver stiffness in chronic hepatitis B.Fifty-eight patients with chronic hepatitis B with ALT levels from 1 to 10 × upper limit of normal were recruited. Liver stiffness measurements were performed at the time of ALT elevation, and liver stiffness measurement was repeated once normalization of ALT occurred after antiviral therapy. Liver biopsies were performed in 38 patients.All 58 patients achieved normalization of ALT after antiviral therapy, with a median time of 3 months between the first and second liver stiffness measurement. There was a significantly lower median liver stiffness measurement after commencement of antiviral therapy, with the normalization of ALT levels compared with pre-treatment levels (6.4 vs. 7.9 kPa, respectively; P0.001). The area under the receiver operator characteristic curve for diagnosing F2 fibrosis in elevated ALT was 0.68, compared with 0.73 after ALT normalization. Twelve (32%) patients would have been misclassified as having cirrhosis using liver stiffness measurements taken at the time of ALT elevation, compared with 16% after normalization of ALT.Even mild-to-moderate elevation in ALT levels may increase liver stiffness independent of underlying liver fibrosis. Higher levels of ALT were associated with higher discrepancies in liver stiffness. Therefore, the timing of liver stiffness measurement is important.

Mac-2-binding protein glycosylation isomer (M2BPGi), a novel serum marker for liver fibrosis, was seldom studied in chronic hepatitis B (CHB). We aimed to evaluate its role on diagnosing significant fibrosis and cirrhosis in treated CHB patients.CHB patients treated with nucleos(t)ide analogues (NAs) with baseline liver biopsies and retrievable serum samples were recruited. Paired liver biopsies were performed in patient subgroups at 1 and 3 years.In total, 327 NA-treated CHB patients (M:F = 229:98; median age 38.1 years) were recruited. The median M2BPGi values were 0.26, 0.34, 0.57 and 1.21 cutoff index (COI), in liver histology with Ishak F0-1, F2, F3 and F4, respectively (p 0.01). M2BPGi levels correlated with the Ishak scores (ρ = 0.312, p 0.001). Using the cutoff values of 0.25, 0.45 and 0.96 COI for ≥F2, ≥F3 and F4, the AUROCs were 0.653, 0.795 and 0.914, respectively. Multivariate analysis with several other serum indices showed that M2BPGi was the most significant independent factor for ≥F3 (OR: 8.197, 95% CI: 2.699-24.897, p 0.001). In patient subgroups with serial liver biopsies, both the proportion of F3/F4 and M2BPGi decreased at 1 year (8.3% vs. 2.8% and 0.32 vs. 0.21 COI, respectively; both p 0.001). Histological fibrosis progression after ≥3 years of NA therapy accompanied with an increase in M2BPGi level, compared to patients without progression (+0.14 vs -0.03 COI, p = 0.045).Serum M2BPGi is a reliable non-invasive marker for diagnosing ≥F2, ≥F3 and F4. It is the only significant marker for ≥F3 among several other indices. NA produced concordant dynamic changes in M2BPGi levels and histological fibrosis.

The aim of this study was to compare the virological and biochemical relapse rates in Asian chronic hepatitis B patients with lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion, between those who stopped therapy after HBeAg seroconversion and those who continued to receive lamivudine.All patients with lamivudine-induced HBeAg seroconversion were included. Patients who stopped lamivudine after HBeAg seroconversion (n=22) were compared with 79 patients who continued to receive lamivudine (n=79). Demographic, virological, and biochemical parameters were recorded at baseline, and throughout the duration of follow-up.In patients who stopped lamivudine, the median follow-up after stopping lamivudine was 20 months. Of these patients, 14 (64%) had virological rebound, with a cumulative incidence of 82% at 4 years. There was no significant difference in number of flares between patients with normal alanine aminotransferase (ALT) and undetectable hepatitis B virus (HBV) DNA at the time of stopping lamivudine compared with that in patients with either abnormal ALT, detectable HBV DNA, or both (P=0.73). The cumulative incidence of HBeAg seroreversion and ALT flares at 5 years after stopping lamivudine was 9 and 44%, respectively. Of the 79 patients who continued with lamivudine, 62 (78%) had undetectable HBV DNA at the time of last follow-up, whereas no patients had undetectable HBV DNA after stopping lamivudine (P0.001). The cumulative incidence of ALT flares at 5 years was 16% (P0.001 compared with those who stopped taking lamivudine). After a median treatment duration of 79 months, lamivudine-resistant mutations occurred in eight patients (10%).In Asian HBeAg-positive patients, continuing with lamivudine after achieving HBeAg seroconversion was associated with a higher proportion of undetectable HBV DNA and a lower number of ALT flares, when compared with those with cessation of lamivudine. In patients who achieved HBeAg seroconversion with lamivudine, the resistance rate was not high when treatment was continued after HBeAg seroconversion.

To determine the effect of 1-yr lamivudine treatment on serum covalently closed-circular DNA (cccDNA) level.Serum total HBV DNA and cccDNA levels at baseline, week 24, and week 52 were measured in 82 lamivudine-treated patients, 17 of whom received 1-yr placebo and acted as controls.There was a significant reduction in the cccDNA levels from baseline (median 3.0 x 10(6) copies/ml) to week 24 (33,476 copies/ml) and week 52 (48,694 copies/ml) (p0.001 for both). The median reduction in cccDNA level at week 24 and 52 were 2.21 and 2.12 logs, respectively, which were significantly greater than those of controls (0.31 log, p0.001; 0.2 log, p0.001, respectively). Fifteen patients (18.3%) developed YMDD mutations by week 52. Compared to patients without YMDD mutations, patients with YMDD mutations had significantly less median reduction of total HBV DNA level (4.44 vs 3.65 logs, respectively, p= 0.02) and cccDNA level (2.27 vs 1.65 logs, respectively, p= 0.016) at week 24 and significantly less median reduction of cccDNA at week 52 (2.35 vs 0.8 logs respectively, p0.001).One-year lamivudine treatment decreased serum cccDNA level by 2 logs. The chance of YMDD mutations at week 52 was related to the magnitude of viral suppression at week 24.

Few studies have examined Chinese patients with chronic hepatitis B who exhibit hepatitis B surface antigen (HBsAg) seroclearance. We comprehensively studied the biochemical, virological, histological, and clinical aspects of 92 patients with HBsAg seroclearance (median follow-up, 126 months). Ninety-two HBsAg-positive controls matched for age, sex, and duration of follow-up were also recruited. Liver biochemistry, serum hepatitis B virus (HBV) DNA levels, and development of clinical complications were monitored. Intrahepatic total and covalently closed circular (ccc) HBV DNA were measured quantitatively in 16 patients. HBV genotype was determined in 30 patients. The mean age at HBsAg seroclearance was 48.8 (+ 13.81) years. There was a significant improvement in serum alanine aminotransferase levels after HBsAg seroclearance (p

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