Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment.

Introduction: The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir. Methods: A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development. Results: Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment. Discussion: In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Unsatisfying antiviral therapeutic effect in patients with mother-to-child transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study.

BACKGROUND: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. METHODS: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. RESULTS: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. CONCLUSION: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. TRIAL REGISTRATION: NCT01962155; https://clinicaltrials.gov.

Efficacy of ventriculoperitoneal shunting in patients with cryptococcal meningitis with intracranial hypertension.

BACKGROUND: Ventriculoperitoneal (VP) shunting in cryptococcal meningitis (CM) patients with high intracranial pressure (ICP) has been studied extensively. METHODS: A total of 74 CM patients with ICP were identified, including 27 patients with or without ventriculomegaly receiving VP shunting. RESULTS: Through retrospective analysis, there was an obvious decline in ICP as well as Cryptococcus count after VP shunting. Damage to the cranial nerves was improved after the surgery. For those patients receiving VP shunting, there was an obvious decline in ICP as well as Cryptococcus count, with less usage of mannitol. Hydrocephalus or ventriculomegaly was improved, and both the clearance time of Cryptococcus and the hospitalization time were shortened (p<0.05). The complications of VP shunting were not common. CONCLUSIONS: For patients diagnosed with CM and with apparent ICP, VP shunting can be considered regardless of whether there is damage to the cranial nerves or hydrocephaly.

Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study.

ABSTRACT Background: Thymosin alpha-1 (Ta-1) suppresses HBV viral replication, while the evidence of combination effect with nucleoide is still limited. We aimed to investigate the efficacy and safety of combination therapy of Ta-1 with entecavir (ETV) in patients with compensated liver cirrhosis. RESEARCH DESIGN AND METHODS: A total of 690 patients were randomized to receive Ta-1 plus ETV (n = 351) or ETV monotherapy (n = 339) for 52 weeks after 26 weeks of ETV treatment, followed by continued entecavir therapy. The primary endpoint was defined as liver decompensation, hepatocellular carcinoma (HCC) or death. RESULTS: The median followed up was 38.2 months. The cumulative incidence of liver decompensation, HCC, or death were similar between two groups. During the Ta-1 combination treatment, the HCC incidence was 1.7% in combination group and 2.1% in ETV group, without new HCC cases developed during week 39 to week 77 in combination group. The virologic response, serologic response, biochemical response was similar between two groups at week 104. Both therapies were well-tolerated. CONCLUSION: There was no significant difference between two groups in endpoint events, while combination therapy with Ta-1 has a tendency to inhibit the development of HCC.

On-treatment changes of liver stiffness at week 26 could predict 2-year clinical outcomes in HBV-related compensated cirrhosis.

BACKGROUND & AIMS: It is unclear whether liver stiffness measurement (LSM) dynamic changes after anti-HBV treatment could predict the risk of liver-related events (LREs), particularly in patients with HBV-related compensated cirrhosis. METHODS: Treatment-naïve patients with HBV-related compensated cirrhosis were enrolled. All patients were under entecavir-based antiviral therapy, and followed up every 26 weeks for 2 years. The association between LSM and LREs was analysed by Cox proportional hazard model and Harrell C-index analysis. RESULTS: A total of 438 patients were included in the study. At the follow-up of 104 weeks, LREs developed in 33/438 (7.8%) patients, including 16 episodes of decompensation, 18 HCC and 3 deaths. The median LSM remained high from 20.9, 18.6, 20.4 to 20.3 Kpa at week 0, 26, 52 and 78 among patients with LREs, whereas the LSM decreased from 17.8, 12.3, 10.6 to 10.2 Kpa in patients without LREs respectively. Percentage changes of LSM at 26 weeks from baseline were significantly associated with LREs (excluding 11 cases occurred within the first 26 weeks), with a crude hazard ratio of 2.94 (95% CI: 1.73-5.00) and an albumin-adjusted hazard ratio of 2.47 (95% CI: 1.49-4.11). The Harrell C-index of these 2 models for predicting 2-year LREs were 0.68 (95% CI: 0.56-0.80) and 0.75 (95% CI: 0.65-0.85) respectively. Nomograms were developed to identify individuals at high risk for point-of-care application. CONCLUSIONS: Dynamic changes of LSM alone, or combined with baseline albumin, could predict LREs in patients with HBV-related compensated cirrhosis during antiviral therapy.

Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase.

Our previous studies unexpectedly indicated that the level of serum hepatitis B core antibody (anti-HBc) was positively correlated with the serum alanine aminotransferase (ALT) level. The aim of this study was to determine whether anti-HBc could serve as a potential biomarker for the detection of liver inflammation in chronic hepatitis B (CHB) patients, especially in patients with normal ALT levels. Serum anti-HBc levels were quantified in 655 treatment-naïve CHB patients, including 45 patients who underwent two liver biopsies (baseline phase and the 78th weeks of antiviral-treatment). Serum anti-HBc levels increased significantly along with the increasing histology activity index (HAI) score. After antiviral-treatment, patients with HAI score reduction had significant decline in serum anti-HBc level. Multivariate analysis showed that anti-HBc was independently associated with moderate-to-severe hepatic inflammation in patients with normal ALT level. Furthermore, serum anti-HBc showed a high diagnostic accuracy for predicting moderate-to-severe inflammation in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients with normal ALT levels (area under the curve, AUC = 0.87 and 0.75; respectively). Thus, anti-HBc may be a strong indicator for assessing the hepatic inflammatory degree and used for antiviral treatment decisions in CHB patients with normal ALT levels.

Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial.

Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV-related ACLF were enrolled in this open-label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow-derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%-84.8%) versus 55.6% (95% confidence interval 42.3%-68.9%) for the SMT group (P = 0.03). There were no infusion-related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5-24 of follow-up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow-derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End-Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). CONCLUSION: Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).

Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with normal or mildly elevated ALT.

Automated discrimination between digs and dust particles on optical surfaces with dark-field scattering microscopy.

To make the surface defects evaluation system (SDES) of fine flat optics more effective and reliable, the point-like defects on the surface are divided into two categories: digs and dust particles. Since only the digs are the real damages that should be sent for further investigation, the false signals associated with dust particles should be distinguished and removed. Dark-field scattering microscopy and pattern recognition methodology are combined to classify digs and dust particles. The SDES is employed for dark-field image acquisition of optical samples. Gray scale, texture, and morphology analyses are then conducted on each image to extract raw feature data, which are compressed with the principal component analysis. Based on the compressed feature data, the support vector machine is used to construct the classification model. The success discrimination rates are 96.56% for the training set and 93.90% for the prediction set. The classification results are presented to show the potential of this method to be used for practical digs and dust particles discrimination on the actual optical samples.

LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma.

BACKGROUND: The La-related protein 1 (LARP1) has been found to be a RNA binding protein and was related to spermatogenesis, embryogenesis and cell-cycle progression. The aim of this study was to investigate the prognostic value of LARP1 in hepatocellular carcinoma (HCC). METHODS: LARP1 expression was examined in 15 HCC cell lines and 272 clinical specimens using real-time PCR, immunohistochemistry (IHC) and western blot analysis (WB). LARP1 expression was also studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Statistical analyses were applied to derive association between LARP1 expression scores and clinical characters as well as patient survival. RESULTS: mRNA and protein levels of LARP1 were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. LARP1 expression was correlated to survival time, vital status, tumor size and Child-Pugh score. Overall survival analysis showed HCC patients with high LARP1 expression level had lower survival rate (P<0.01). Importantly, this correlation remained significant in patients with early-stage HCC or with normal serum AFP level. CONCLUSIONS: LARP1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.

[Therapeutic effects of Fuzhenghuayu decoction in a CCl4-induced liver cirrhosis rat model and on hepatic stellate cell activation].

OBJECTIVE: To evaluate the influence of Fuzhenghuayu decoction on fibrotic liver tissue and activated hepatic stellate cells (HSCs) using a carbon tetrachloride (CCl4)-induced liver cirrhosis rat model system. METHODS: Sixty-four Sprague-Dawley rats were randomly divided into the following groups: normal (non-model, non-drug intervention), CCl4 liver fibrosis model, and CCl4 liver fibrosis model Fuzhenghuayu drug intervention at low dose (0.75 g/kg/d) and high dose (1.5 g/kg/d). The drug intervention was administered via oral-gastric irrigation once daily for 6 times per week over a 6-week period. Four rats from each group were sacrificed at the end of week 2, 4, and 6 for serum and liver tissue collection. Liver fibrosis was evaluated by histology, and expression of a-smooth muscle actin (a-SMA) was determined by immunohistochemistry. Liver function was assessed by measuring levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil). Between-group comparisons were made by completely random design and ANOVA with Bonferroni correction. RESULTS: At the end of weeks 2, 4 and 6, all four groups showed significantly different levels of ALT, AST, and TBil; in addition, the model group and drug intervention groups had significantly higher levels of ALT, AST, and TBil than the control group, the drug intervention groups showed significantly lower levels of ALT, AST, and TBil than the model group (P less than 0.01 or less than 0.05), and the differences between the low dose and high dose groups reached statistical significance (P less than 0.01 or less than 0.05). At the end of weeks 2, 4 and 6, the model group and drug intervention groups had significantly higher area ratio of liver fibrosis than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but the two drug intervention groups had significantly less area ratio of liver fibrosis than the model group (P less than 0.05) and the high dose group showed the most robust decrease. In addition, the model group and drug intervention groups showed higher expression of a-SMA than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but two drug intervention groups had significantly less a-SMA than the model group (F = model: 46.32, low dose: 40.30, high dose: 58.42, P less than 0.05) and the high dose group showed the most robust decrease. CONCLUSION: The Fuzhenghuayu decoction reduces the numbers of activated HSCs, thereby leading to down-regulated a-SMA expression and reduced degree of liver fibrosis; these effects may represent the mechanism by which this drug suppresses hepatic fibrosis.

Entecavir improves the outcome of acute-on-chronic liver failure due to the acute exacerbation of chronic hepatitis B.

BACKGROUND: The mortality of acute-on-chronic hepatitis B liver failure (ACHBLF) from acute exacerbation of chronic hepatitis B is 30-70 % without liver transplant. METHODS: We conducted an open-label, prospective, 48-week study to evaluate the efficacy of entecavir (ETV) in ACHBLF with 110 patients who received either ETV or no treatment. Primary measurements were survival and improvement in disease severity scores. RESULTS: Of the 110 patients enrolled, 2 withdrew consent, 108 were treated with 53 ETV, and 55 were untreated. When compared to the patients in the untreated group at week 48, a lower cumulative mortality rate in ETV-treated patients was observed [54.7 % (29/53) vs. 78.2 % (43/55), p < 0.01). ETV treatment significantly improved disease severity scores including Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), and MELD sodium (MELD-Na). All ETV-treated subjects achieved an undetectable HBV DNA level (<500 copies/mL; 100 % vs. 7.9 %, p < 0.001). In univariate analysis, predictors of survival at week 48 included baseline age, total bilirubin, international normalized ratio of prothrombin time, albumin, cholesterol, receiving ETV therapy, CTP, MELD, MELD-Na, and sequential organ failure assessment (SOFA) scores. In multivariate analysis, baseline age, total bilirubin, untreated (with ETV), CTP, and SOFA scores were the independent risk factors for mortality. CONCLUSIONS: Entecavir treatment for patients with ACHBLF significantly improves disease severity scores with a marked reduction in mortality and suppression in HBV DNA to undetectable levels at week 48. Patients' age, total bilirubin, CTP, and SOFA scores at baseline are independent risk factors for higher mortality without liver transplantation.

Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1 receptor antagonist improve fulminant hepatic failure.

Uncontrolled hepatic immunoactivation is regarded as the primary pathological mechanism of fulminant hepatic failure (FHF). The major acute-phase mediators associated with FHF, including IL-1ß, IL-6, and TNF-α, impair the regeneration of liver cells and stem cell grafts. Amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) have the capacity, under specific conditions, to differentiate into hepatocytes. Interleukin-1-receptor antagonist (IL-1Ra) plays an anti-inflammatory and anti-apoptotic role in acute and chronic inflammation, and has been used in many experimental and clinical applications. In the present study, we implanted IL-1Ra-expressing AF-MSCs into injured liver via the portal vein, using D-galactosamine-induced FHF in a rat model. IL-1Ra expression, hepatic injury, liver regeneration, cytokines (IL-1ß, IL-6), and animal survival were assessed after cell transplantation. Our results showed that AF-MSCs over-expressing IL-1Ra prevented liver failure and reduced mortality in rats with FHF. These animals also exhibited improved liver function and increased survival rates after injection with these cells. Using green fluorescent protein as a marker, we demonstrated that the engrafted cells and their progeny were incorporated into injured livers and produced albumin. This study suggests that AF-MSCs genetically modified to over-express IL-1Ra can be implanted into the injured liver to provide a novel therapeutic approach to the treatment of FHF.

Development of a sensitive prognostic scoring system for the evaluation of severity of acute-on-chronic hepatitis B liver failure: a retrospective cohort study.

PURPOSE: The purpose of the current study was to establish an objective, simple, and sensitive prognostic scoring system for estimating the severity of acute-on-chronic liver failure in hepatitis B (ACLFB). METHODS: A novel prognostic scoring system was calculated from six clinical indices including total bilirubin (TB), prothrombin activity (PTA), creatinine (Cr), hepatic encephalopathy (HE), infections, and the depth of ascites from 726 patients with ACLFB. Indices were scored from 1 to 4 according to their severity. Groups of the same patients were scored with three-indices (TB, PTA and Cr), four-indices (TB, PTA, Cr and HE), five-indices (TB, PTA, Cr, HE and the depth of ascites) or six-indices (TB, PTA, Cr, HE, the depth of ascites, and infections). The differences in the sensitivity and specificity of four scoring systems were analyzed. RESULTS: The demarcation points of the three-, four-, five- and six-indices scoring systems were 4.62, 6.12, 7.88 and 9.57, respectively. The analysis of the areas under the receiver operating characteristic (ROC) curve indicated that the four-, five- and six-indices scoring systems were more exact, and objective than the three-indices prognostic scoring system. In the six-indices scoring system, the survival rates of patients with scores from 2 to 6 was 98.31% (233/237), and the mortality rate of patients with scores of 16 and above was 100.00% (140/140), while the mortality rates were 8.33% (3/36) and 96.43% (27/28) for those with scores from 7 to 15, respectively. CONCLUSION: A six-indices scoring system is an objective, pertinent, and sensitive system, and may be useful for the prognostic evaluation of ACLFB.

A Novel prognostic scoring system to predict 3-month mortality risk in patients with acute-on-chronic liver failure in hepatitis B: a retrospective cohort study.

PURPOSE: The present study was done to establish an objective, sensitive prognostic scoring system and to determine the applicability of this model in predicting the 3-month mortality of patients with acute-on-chronic liver failure in hepatitis B (ACLFB). METHODS: We developed a novel prognostic scoring system, calculated from six clinical indices including serum total bilirubin, prothrombin activity, serum creatinine, hepatic encephalopathy, infections, and the depth of ascites from 499 patients with ACLFB. Differences in the sensitivity, specificity, and practicality of a Novel prognostic scoring system and the model of end-stage liver disease (MELD) were analyzed. RESULTS: The areas under the receiver operating characteristic curve (ROC) for the Novel scoring systems and MELD scoring systems were 0.967 (95% CI, 0.956-0.977) and 0.900 (95% CI, 0.878-0.922), respectively. The analysis of the ROC curve indicated that the Novel scoring systems were an exact, pertinent, and objective prognostic model with greater accuracy than the MELD. In the Novel scoring systems, the survival rate of these patients whose scores ranged from 2 to 6 was 98.80%, while for those whose scores point at 7 and 15, the mortality rates were 8.70% (2/23) and 95.45% (21/22), respectively, and the mortality rate of these patients whose scores were 16 and above was 100.00%. However, in the MELD prognostic scoring systems, there were no score ranges with 100.00% survival rate. CONCLUSIONS: We developed an objective, pertinent, and sensitive prognostic scoring system that predicted the 3-month mortality of patients with ACLFB with greater accuracy than the MELD.

Collagen proportionate area of liver tissue determined by digital image analysis in patients with HBV-related decompensated cirrhosis.

BACKGROUND: The accurate assessment of the degree of hepatic fibrosis plays a critical role in guiding the diagnosis, treatment and prognostic assessment of chronic liver diseases. Liver biopsy is currently the most reliable method to evaluate the severity of hepatic fibrosis. However, liver biopsy is an invasive procedure associated with morbidity and mortality, and has several limitations in patients with decompensated cirrhosis. There is no report on the collagen proportionate area (CPA) of liver tissue in the decompensated stage of cirrhosis. This study aimed to determine the CPA of resected liver tissue samples from patients with HBV-related decompensated cirrhosis using digital image analysis, and to analyze the relationship between the CPA and liver functional reserve. METHODS: Fifty-three resected liver tissue samples from liver transplant patients with chronic hepatitis B-induced decompensated cirrhosis were stained with Masson's trichrome, and the CPA in these samples was quantitatively determined using digital image analysis. The values of relevant liver function just before liver transplantation, the CPA in liver tissue, and their correlation were analyzed. RESULTS: The mean CPA at the decompensated stage of cirrhosis was 35.93+/-14.42% (11.24%-63.41%). The correlation coefficients of the CPA with a model for end-stage liver disease score, serum total bilirubin and international standard ratio of prothrombin B were 0.553, 0.519 and 0.533, respectively (P<0.001). With increasing CPA values, the three indices reflecting liver functional reserve also changed significantly. CONCLUSIONS: The degree of fibrosis may be correlated with the functional reserve. With the advancement of fibrosis, the liver functional reserve is attenuated accordingly.

Prevention and risk factors of the HBV recurrence after orthotopic liver transplantation: 160 cases follow-up study.

BACKGROUND: The aim of this study was to analyze the combination with long-term, low-dose hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogs as prophylaxis for hepatitis B virus (HBV) recurrence and to assess the risk factors of HBV recurrence after orthotopic liver transplantation (OLT). METHODS: One hundred sixty patients undergoing OLT with HBV-related liver disease make up the cohort studied. Long-term, low dosage of HBIG in combination with nucleos(t)ide analogs were used as prophylaxis for HBV recurrence after OLT. Patient preoperative data were collected by a retrospective method, and the rate and risk factors of HBV recurrence post-OLT after a long-term follow-up were analyzed. RESULTS: Nineteen patients developed hepatitis B recurrence for a rate of recurrence of 11.88% (19/160). There was no significant correlation between HBV recurrence after OLT and the level of HBV DNA, HBeAg state pre-OLT, or the use of nucleoside analog drug therapy pre-OLT (P>0.05). Of 19 patients with HBV recurrence, 17 patients used Lamivudine, and HBV YMDD mutants were detected in nine cases. The HBV-YMDD mutation was the major reason for recurrence of HBV in our study (P<0.001). CONCLUSIONS: Long-term use of combination prophylaxis with nucleoside analogs and low-dose HBIG can effectively prevent hepatitis B recurrence after OLT, and that a positive preoperative serum HBV DNA status did not affect the recurrence rate of HBV post-OLT. Preoperative nucleoside analogs therapy is unlikely to be obligatory if the patients received effective combination prophylaxis postoperatively. HBV YMDD mutation is the primary reason for HBV recurrence in patients treated with Lamivudine after OLT.

Effect of revaccination using different schemes among adults with low or undetectable anti-HBs titers after hepatitis B virus vaccination.

Our objective was to investigate the effect of various reimmunization schemes for hepatitis B in adults with low or undetectable anti-HBs titers. Over 2 years, 10 µg of Saccharomyces cerevisiae-recombinant hepatitis B virus (HBV) vaccine (synthesized in China) was used in at least one standardized scheme to immunize 2,310 healthy male and nonpregnant female adults. Of these, 240 subjects tested negative for hepatitis B markers. These 240 subjects were equally divided into 4 groups. The first group, designated Engerix-40, was revaccinated with 40 µg Engerix-B; the second, Engerix-20, was revaccinated with 20 µg Engerix-B; the third, Chinese-20, was revaccinated with 20 µg Chinese-made yeast-recombinant vaccine; and the last group, Chinese-10, was revaccinated with 10 µg Chinese-made yeast-recombinant vaccine. Blood samples were collected before and 1, 2, 8, and 12 months after the first injection. The anti-HBs-positive conversion rates of the Engerix-40, Engerix-20, and Chinese-20 groups were higher than that of the Chinese-10 group (P < 0.01). Over time, the anti-HBs conversion rate increased in all groups, but values were significantly different from those for the other groups only in the Chinese-10 group (P < 0.001). The anti-HBs geometric mean titers (GMTs) of the Engerix-40, Engerix-20, and Chinese-20 groups were higher than in the Chinese-10 group (P < 0.05). Increased doses raise and maintain anti-HBs titers in subjects with low or undetectable titers after HBV vaccination.

[Association between the serum HBV DNA loads normalized to hepatic parenchyma cell volume and the liver histopathologic inflammation gradings in the immune clearance phase].

OBJECTIVE: To investigate the relationship between the serum HBV DNA loads normalized to hepatic parenchyma cell volume and the liver histopathologic inflammation gradings in the immune clearance phase during the natural history of hepatitis B. METHODS: Serum HBV DNA loads were detected by fluorescence polymerase chain reaction and normalized to hepatic parenchyma cell volume. The association between normalized HBV DNA loads and liver inflammation histopathologic grade were analyzed. RESULTS: The serum HBV DNA loads in patients with liver inflammation histopathologic grading 1, 2, 3 and 4 were 8.20*10(5)+/-9.11*10, 1.36*10(6)+/-5.96*10, 8.12*10(5)+/-8.01*10 and 2.08*10(6)+/-3.69*10 copies/ml, respectively (P more than 0.05). But the serum HBV DNA loads normalized to hepatic parenchyma cell volume in their located fibrosis stage were 9.24*10(8)+/-935, 5.33*10(9)+/-756, 1.06*10(10)+/-1770 and 3.31*10(11)+/-518 copies/ml, respectively (P less than 0.05). CONCLUSION: The serum HBV DNA load normalized to hepatic parenchyma cell volume in patients with different fibrosis stages is associated with liver histopathologic inflammation gradings.