Clinical analysis of bacterial infection characteristics in lymphoma patients with high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation-a single-centered retrospective study.

BACKGROUND: High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation. OBJECTIVE: To characterise pathogenic bacterial infections in HDT/AHSCT-treated lymphoma patients. The prevalence of pathogenic microorganisms and the timing of foci after transplantation, along with bloodstream infection (BSI) risk factors, can help determine the need for empirical antibiotics after AHSCT. METHODS: We retrospectively analyzed 133 lymphoma patients treated by HDT/AHSCT from April 2017 to October 2021 at Peking University International Hospital, Beijing, China. We analyzed their clinical characteristics, microbiological distribution characteristics, and BSI risk factors in detail. RESULTS: In order, intestinal infection (56 cases), BSI (17 cases), pulmonary (12 cases), upper respiratory tract (5 cases), and perianal (4 cases) were the most common locations of infection after HDT/AHSCT. The infection sites yielded 92 putative pathogenic pathogens, with bacteria predominating (61.96%), fungi (28.26%), viruses (5.43%), and mycoplasma (4.35%). Gram-negative bacteria (GNB) strains outnumbered gram-positive bacteria (GPB) strains (73.68%). Two strains of Escherichia coli produced extended-spectrum ß-lactamase (ESBL) and one strain of carbapenem-resistant enterobacteriaceae (CRE). Methicillin-resistant Staphylococcus epidermidis (MRSE) had one strain. BSI was caused by Escherichia coli (82.35%), Intestinal mucositis (23.52%), and catheter-associated infections (11.76%). Age, CD34, pretreatment regimen, antibiotic regimen, and past chemotherapeutic agent lung damage were BSI risk variables in univariate analysis. CD34 and past chemotherapeutic drug lung damage were the primary causes of BSI after HDT/AHSCT for lymphoma. CONCLUSION: High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDT/AHSCT) is used to treat lymphoma. Although AHSCT has made considerable strides and become safer, HDT-AHSCT infection continues to be a leading cause of morbidity and mortality associated with transplantation.

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.

Case report: Wallerian degeneration: The innate-immune response to adult-onset Still's disease peripheral nerve injury.

Peripheral nerve injury is one of the rare complications of adult-onset Still's disease (AOSD). We report a 20-year-old woman diagnosed with AOSD combined with severe sensory neuropathy. She presented with a sore throat, joint pain, rash, and lymphadenopathy. After receiving glucocorticoid therapy, her fever, rash, and inflammatory markers improved. Unexpectedly, 3 weeks after the onset, she experienced sudden paresthesia in her extremities, decreased muscle strength, and diminished tendon reflexes. The electrophysiological examination and peripheral nerve biopsy confirmed immune-mediated severe sensory neuropathy. For the first time, we report typical Wallerian degeneration in AOSD patients with sensory neuropathy by nerve biopsy. Compared with other common symptoms, the delayed aggravation of neurological symptoms may be an important characteristic of sensory neuropathy secondary to AOSD. We emphasize that intensive attention to neurological symptoms after general symptoms control, administration of adequate and appropriate prolonged immunosuppressive therapy, and long-term follow-up are essential for these patients.

Significant Histologic Changes Are Not Rare in Treatment-naive Hepatitis B Patients with Normal Alanine Aminotransferase Level: A Meta-analysis.

BACKGROUND AND AIMS: Chronic hepatitis B is the main cause of liver cancer. However, the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase (ALT). People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment. However, the truth is not as optimistic as we thought. We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients. METHODS: Medline, Embase, and Cochrane Library were searched up to January 10th 2020, to identify studies of these patients with liver biopsy. The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis. Potential heterogeneity was explored by subgroup analysis and meta-regression. Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis. The secondary outcome was to find the risk factors of significant histological changes. RESULTS: Nineteen eligible studies, with 2,771 participants, were included. The pooled proportion of significant inflammation or fibrosis was 35% [95% confidence interval (CI): 27 to 43] and 30% (95% CI: 25 to 36), respectively. The pooled proportion of cirrhosis was 3% [95% CI: 1 to 5, (12 studies; 1,755 participants)]. In subgroup analysis, old age [vs. young (<40 years-old), 44% vs. 26%, p=0.012] was significantly associated with higher fibrosis stage as well as cirrhosis [vs. young (<40 years-old), 4.8% vs. 1.8%, p<0.001]. CONCLUSIONS: About 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes, and some even have cirrhosis.

Prediction of hepatic inflammation in chronic hepatitis B patients with a random forest-backward feature elimination algorithm.

BACKGROUND: Persistent liver inflammatory damage is the main risk factor for developing liver fibrosis, cirrhosis, and even hepatocellular carcinoma in chronic hepatitis B (CHB) patients. Thus, accurate prediction of the degree of liver inflammation is a high priority and a growing medical need. AIM: To build an effective and robust non-invasive model for predicting hepatitis B-related hepatic inflammation. METHODS: A total of 650 treatment-naïve CHB (402 HBeAg-positive and 248 HBeAg-negative) patients who underwent liver biopsy were enrolled in this study. Histological inflammation grading was assessed by the Ishak scoring system. Serum quantitative hepatitis B core antibody (qAnti-HBc) levels and 21 immune-related inflammatory factors were measured quantitatively using a chemiluminescent microparticle immunoassay. A backward feature elimination (BFE) algorithm utilizing random forest (RF) was used to select optional features and construct a combined model. The diagnostic abilities of the model or variables were evaluated based on the estimated area under the receiver operating characteristics curve (AUROC) and compared using the DeLong test. RESULTS: Four features were selected to predict moderate-to-severe inflammation in CHB patients using the RF-BFE method. These predictive features included qAnti-HBc, ALT, AST, and CXCL11. Spearman's correlation analysis indicated that serum qAnti-HBc, ALT, AST, and CXCL11 levels were positively correlated with the histology activity index (HAI) score. These selected features were incorporated into the model to establish a novel model named I-3A index. The AUROC [0.822; 95% confidence interval (CI): 0.790-0.851] of the I-3A index was significantly increased compared with qAnti-HBc alone (0.760, 95%CI: 0.724-0.792, P < 0.0001) in all CHB patients. The use of an I-3A index cutoff value of 0.41 produced a sensitivity of 69.17%, specificity of 81.44%, and accuracy of 73.8%. Additionally, the I-3A index showed significantly improved diagnostic performance for predicting moderate-to-severe inflammation in HBeAg-positive and HBeAg-negative CHB patients (0.829, 95%CI: 0.789-0.865 and 0.810, 95%CI: 0.755-0.857, respectively). CONCLUSION: The selected features of the I-3A index constructed using the RF-BFE algorithm can effectively predict moderate-to-severe liver inflammation in CHB patients.

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients.

BACKGROUND: Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables. METHODS: One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods. RESULTS: HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score (r = -0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r = -0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005). CONCLUSIONS: HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy. TRIAL REGISTRATION: Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1.

Significant histological changes and satisfying antiviral efficacy in chronic hepatitis B virus infection patients with normal alanine aminotransferase. Antiviral therapy decision in chronic HBV patients with normal ALT.

BACKGROUND AND AIMS: A proportion of chronic hepatitis B virus (HBV) infection patients with normal alanine aminotransferase (ALT) should start antiviral therapy based on liver biopsy. We aim to evaluate the proportion of such patients, find noninvasive methods for identifying and then evaluate antiviral efficacy. METHODS: 253 chronic HBV infection patients with normal ALT were analyzed at baseline and 57 patients with histological indication for antiviral therapy (Histology activity index ≥5 and/or Ishak fibrosis score ≥3) and 140 patients with elevated ALT received entecavir therapy and were followed-up to 78 weeks with a second liver biopsy in this multi-center study. RESULTS: 127 (50.2%) of 253 patients with normal ALT fulfilled histological indication for antiviral therapy. Aspartate aminotransferase (P=0.049), anti-hepatitis B virus core antibody (P=0.001) and liver stiffness measurement (P=0.000) were independent variables for identifying histological indication for antiviral therapy. A noninvasive model (AAF) performed best among independent variables and other noninvasive models with area under the operating characteristic curve of 0.887. Antiviral efficacy showed that 38 (66.7%) of 57 patients had undetectable HBV DNA. 12 (41.4%) of 29 patients who were hepatitis B e antigen (HBeAg)-positive at baseline achieved HBeAg loss and 3 (10.3%) achieved HBeAg seroconversion. 25 (43.9%) of 57 patients achieved histological response. Moreover, 57 patients with normal ALT had a similar antiviral therapy efficacy with 140 patients with elevated ALT (P>0.1) except proportion of inflammation improvement and histological response (P=0.005, P=0.049). CONCLUSIONS: Half of chronic HBV patients with normal ALT should start antiviral therapy based on liver biopsy. A noninvasive model could be used as a reliable tool for antiviral therapy decision. Patients with normal or elevated ALT had a similar antiviral efficacy.

Discharge may not be the end of treatment: Pay attention to pulmonary fibrosis caused by severe COVID-19.

Since December 2019, coronavirus disease (COVID-19) has rapidly swept the world. So far, more than 30 million people have been infected and nearly one million have died. Although the world is still in the stage of COVID-19 pandemic, the treatment of new cases and critically ill patients is the focus of the current work. However, COVID-19 patients lead to pulmonary fibrosis, such a serious threat to the prognosis of complications were also worthy of our attention. First of all, we proposed the possible mechanism of pulmonary fibrosis caused by SARS-CoV-2, based on the published data of COVID-19 ((i) Direct evidence: pulmonary fibrosis was found in autopsy and pulmonary puncture pathology. (ii) Indirect evidence: increased levels of fibrosis-related cytokines[transforming growth factor [TGF]- ß, tumor necrosis factor [TNF]- α, interleukin [IL]-6, etc] in peripheral blood of severe patients.) What is more, we summarized the role of three fibrosis-related signaling pathways (TGF- ß signal pathway, WNT signal pathway and YAP/TAZ signal pathway) in pulmonary fibrosis. Finally, we suggested the therapeutic value of two drugs (pirfenidone and nintedanib) for idiopathic pulmonary fibrosis in COVID-19-induced pulmonary fibrosis.

Shear wave elastography may be sensitive and more precise than transient elastography in predicting significant fibrosis.

BACKGROUND: Noninvasive measurements including transient elastography (TE) and two-dimensional shear wave elastography (SWE) have been used clinically instead of liver biopsy for regular assessment of liver fibrosis in chronic hepatitis B (CHB) patients. AIM: To investigate the diagnostic efficiency of SWE compared to TE by assessing independent influencing factors and performance for diagnosing significant fibrosis based on our cohort of treatment-naive CHB patients. METHODS: Fifty-four treatment-naive CHB patients who underwent liver biopsy to determine whether to initiate antiviral therapy were enrolled. SWE, TE, serum tests and liver biopsy were performed for all participants. The fibrosis-4 and aspartate aminotransferase to platelet ratio index scores were also calculated. Potential independent influencing factors on SWE and TE values were analyzed. Based on liver pathology results, the agreement and correlation were determined, and a comparison of the two methods was performed. RESULTS: There were 27 cases (50%) of mild fibrosis (F0-F2) and 27 (50%) cases of significant fibrosis (F3-F6); fibrosis was assessed with the Ishak scoring system. Multivariate linear regression analyses revealed that the fibrosis stage was the only factor that affected the SWE values (P < 0.001), whereas the total bilirubin level (P = 0.013) and fibrosis stage (P = 0.037) were independent factors that affected TE values. Orthogonal partial least squares discriminant analysis showed that the number of independent factors (VIP > 1) was higher for TE than SWE. Bland-Altman analysis showed satisfactory agreement between liver stiffness measurements (LSMs) of SWE and TE. Both SWE and TE could significantly discriminate significant fibrosis from mild fibrosis (P < 0.001). SWE exhibited a higher correlation with LSMs of liver fibrosis than TE (r = 0.65 and 0.50, P < 0.001). The diagnostic performance of SWE was better than that of TE for significant fibrosis (F > 2). The areas under the receiver operating characteristic curves of SWE and TE were 0.786 and 0.714, respectively. The optimal LSM cutoff values of SWE and TE were 9.05 kPa and 8.15 kPa, respectively. CONCLUSION: Compared to the TE value, the SWE value was less affected by other factors. SWE may be more sensitive and precise than TE in predicting significant fibrosis (> F2) in CHB patients.

Treatment of primary biliary cholangitis with ursodeoxycholic acid, prednisolone and immunosuppressants in patients not responding to ursodeoxycholic acid alone and the prognostic indicators.

BACKGROUND AND AIM: We reviewed the medical records of primary biliary cholangitis patients who were diagnosed by liver biopsy and treated with the corresponding treatment. We evaluated the therapeutic effect and long-term prognostic indicators. METHODS: This observational cohort study enrolled 80 eligible patients diagnosed by liver biopsy between December 2013 and December 2018 in our department. UDCA monotherapy or UDCA added to prednisolone and immunosuppressant triple therapy was prescribed to patients. We analyzed and compared the demographic characteristics, biochemistry profiles, immune parameters, and noninvasive liver fibrosis assessments at baseline as well as the treatment efficacy, long-term outcomes and adverse effects at baseline and at each visit between the two groups. The indicators that could affect prognosis were assessed. RESULTS: Thirty-eight primary biliary cholangitis patients received UDCA monotherapy (group A), and another 42 patients received UDCA, prednisolone and immunosuppressant triple therapy (group B). After therapy, all patients showed significant improvements in liver biochemical parameters, immune indicators, and noninvasive fibrosis indicators (Fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI)), all P values<0.0001. The Mayo score also decreased significantly after treatment (P=0.022). Triple therapy was more effective, and there was a significant difference between the two groups. In addition, multivariate analysis showed that anti-gp210 antibody positivity; antimitochondrial antibody (AMA) negativity; high alkaline phosphatase (ALP), total bilirubin (TBIL) and globulin levels; and a severe degree of fibrosis at baseline were independent predictors of a poor prognosis. CONCLUSIONS: Triple therapy was a treatment option for UDCA-refractory PBC patients. Anti-gp210 antibody positivity; AMA negativity; high ALP, TBIL and globulin levels; and a severe degree of fibrosis at baseline were associated with a poor prognosis.

Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19.

This article reviews the correlation between angiotensin-converting enzyme 2 (ACE2) and severe risk factors for coronavirus disease 2019 (COVID-19) and the possible mechanisms. ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical RAS ACE-Ang II-AT1R regulatory axis and the ACE2-Ang 1-7-MasR counter-regulatory axis play an essential role in maintaining homeostasis in humans. ACE2 is widely distributed in the heart, kidneys, lungs, and testes. ACE2 antagonizes the activation of the classical RAS system and protects against organ damage, protecting against hypertension, diabetes, and cardiovascular disease. Similar to SARS-CoV, SARS-CoV-2 also uses the ACE2 receptor to invade human alveolar epithelial cells. Acute respiratory distress syndrome (ARDS) is a clinical high-mortality disease, and ACE2 has a protective effect on this type of acute lung injury. Current research shows that the poor prognosis of patients with COVID-19 is related to factors such as sex (male), age (>60 years), underlying diseases (hypertension, diabetes, and cardiovascular disease), secondary ARDS, and other relevant factors. Because of these protective effects of ACE2 on chronic underlying diseases and ARDS, the development of spike protein-based vaccine and drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the future.

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.

Declining in liver stiffness cannot indicate fibrosis regression in patients with chronic hepatitis B: A 78-week prospective study.

BACKGROUND AND AIM: Little reliable data are available about the liver stiffness measurement (LSM) for fibrosis monitoring in chronic hepatitis B (CHB) patients on antiviral therapy. We aimed to assess the accuracy of LSM in fibrosis monitoring during 78-week antiviral therapy in CHB patients. METHODS: Five hundred fifty-six treatment-naïve CHB patients with qualified LSM and liver biopsy at baseline were analyzed. Patients receiving entecavir-based therapy were prospectively followed to 78 weeks for second LSM and liver biopsy. Serologic detection, LSM, and liver biopsy were performed on the same day. Necro-inflammatory activity was also evaluated. RESULTS: Areas under receiver operating characteristics curves of LSM at baseline and week 78 for significant fibrosis (≥ F3), advanced fibrosis (≥ F4), and liver cirrhosis (≥ F5) was 0.84, 0.87, 0.83 and 0.76, 0.85, 0.88, respectively. Patients with the same fibrosis stage but higher histology activity index score tend to have higher LSM at baseline. Liver stiffness decreased rapidly (3.8 [1.6-8.6] kPa) in parallel with baseline histology activity index scores from 11.3 (7.8-16.7) kPa at baseline to 6.4 (5.1-8.8) kPa at week 78. Greater decline of LSM in patients with only inflammation improvement was observed as compared with those without inflammation improvement (5.2 [2.5-9.7] vs 1.8 [0.2-8.1] kPa, P = 0.013). Baseline Ishak fibrosis score was the only predictor of 78-week fibrosis improvement (odds ratio, 1.859; P = 0.000). CONCLUSIONS: In CHB patients receiving 78-week antiviral treatment, LSM could diagnosis different liver fibrosis stages, decrease in absolute LSM value could reflect the remission of liver inflammation, and baseline Ishak fibrosis score was the only predictor for 78-week fibrosis reversion.

Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in chinese hepatitis B patients.

The limitations of liver biopsy have led to the development of indirect noninvasive models for liver fibrosis assessment. We aimed to evaluate and compare the performance of 30 noninvasive models to predict fibrosis stage in treatment-naïve and treated chronic hepatitis B (CHB) patients. A total of 576 Chinese treatment-naïve CHB patients and 236 treated CHB patients who had undergone percutaneous liver biopsy were included in the analysis. Histological grading and staging was assessed by the Ishak scoring system. The diagnostic accuracies of 30 noninvasive models were assessed by area under the receiver operating characteristic curves (AUROCs). In treatment-naïve CHB patients, the AUROCs of the 30 noninvasive models for discriminating significant fibrosis (SF) were less than 0.800, and only the AUROC of the PP score for diagnosing advanced fibrosis (AF) was more than 0.800, while the AUROCs of FIB-4, FibroQ, HB-F, Lok index, PHP score and PP score for predicting cirrhosis were greater than 0.800. In treated CHB patients, only the AUROCs of APRI, GUCI, King's score and Wang I for identifying cirrhosis were more than 0.800. The Spearman correlation analysis identified that only the changes in FCI and Virahep-C model values were weakly correlated with changes in Ishak fibrosis scores before and after treatment (r = 0.206, p = 0.008; r = 0.187, p = 0.016, respectively). In conclusion, in Chinese CHB patients, the 30 existing noninvasive models were not suitable for assessing each stage of fibrosis except cirrhosis before and after antiviral therapy, especially in gauging progression and regression of liver fibrosis following therapy.

Prophylactic Use of Entecavir for Lymphoma Patients With Past Hepatitis B Virus Infection: A Randomized Controlled Trial.

BACKGROUND: The value of prophylactic antiviral therapy in patients with past hepatitis B virus (HBV) infection (HBV surface antigen-negative/anti-HBV core antibody-positive/HBV DNA negative) is still controversial. PATIENTS AND METHODS: This study compared the safety, efficacy, and cost-effectiveness of prophylactic entecavir (ETV) with regular monitoring alone in lymphoma patients with past HBV infection. Patients were randomly assigned to chemotherapy alone (control) or prophylactic ETV before chemotherapy and at least 6 months after completion of chemotherapy. All patients underwent close virologic and biochemical surveillance. The primary end points were the incidence rates of HBV reactivation (appearance of HBV DNA) and HBV reactivation-related hepatitis (defined as a greater than 3-fold increase in serum alanine aminotransferase levels exceeding 100 IU/L). RESULTS: A total of 190 patients were included, 141 (74.2%) of whom were positive for anti-HBV surface antibody (HBs). The incidence rates of HBV reactivation and HBV reactivation-related hepatitis were 0 (0/95) and 0 (0/95) in the prophylactic ETV group, respectively, and 3.2% (3/95) and 1.1% (1/95) in the control group, respectively (P = .246 and 1.000, respectively). One patient experienced HBV reactivation-related hepatitis, resulting in premature termination of chemotherapy. All 3 patients with HBV reactivation recovered after therapeutic ETV treatment. No HBV-related deaths were observed during the follow-up period. The cost in the prophylactic ETV group was higher than that in the control group ($125 per month). CONCLUSION: Prophylactic antiviral therapy is not a cost-effective strategy for the management of lymphoma patients with past HBV infection, especially those positive for anti-HBs.

Gilbert syndrome combined with prolonged jaundice caused by contrast agent: Case report.

This case highlights a patient with Gilbert syndrome who underwent endoscopic retrograde cholangiopancreatography (ERCP) with removal of bile duct stones, who then experienced an unexplained increase in bilirubin, with total bilirubin (TBIL) levels increasing from 159.5 µmol/L to 396.2 µmol/L and to a maximum of 502.8 µmol/L after 9 d. Following the decrease in the TBIL level, enhanced magnetic resonance cholangiopancreatography (MRCP) was performed to exclude any possible remaining choledocholithiasis. Nevertheless, the serum bilirubin level increased again, with TBIL levels rising from 455.7 µmol/L to 594.8 µmol/L and a maximum level of 660.3 µmol/L with no remaining bile duct stones. A liver biopsy showed severe bile duct cholestasis with no inflammation. Based on the exclusion of other potential causes of hyperbilirubinemia and the fact that both instances of increased bilirubin occurred after ERCP and MRCP, the contrast agents iopromide and gadoterate meglumine were suspected to be the causes of the hyperbilirubinemia. As of the writing of this report, the patient's bilirubin levels have spontaneously returned to baseline levels. In summary, ERCP and MRCP utilizing the contrast agents iopromide and gadoterate meglumine may possibly induce prolonged hyperbilirubinemia.

Utility and Safety of Tolvaptan in Cirrhotic Patients with Hyponatremia: a Prospective Cohort Study

Abstract: Introduction and aim. Hyponatremia is common in patients with decompensated cirrhosis and is associated with increased mortality. Tolvaptan, a vasopressor V2 receptor antagonist, can increase free wáter excretion, but its efficacy and safety in cirrhotic patients remain unclear. Material and methods. We studied the usage and safety of tolvaptan in cirrhotic patients in a real-life, non-randomized, multicenter prospective cohort study. Forty-nine cirrhotic patients with hyponatremia were treated with tolvaptan 15 mg daily, and 48 patients not treated with tolvaptan in the same period served as controls. Improvement in serum sodium level was defined as an increase in serum sodium from < 125 to ≥ 125 mmol/L or from 125-134 to ≥ 135 mmol/L on day 7. Results. Twenty-three (47%) patients in the tolvaptan group and 17 (35%) in the control group had normal serum sodium on day 7 (p = 0.25). Serum sodium improved in 30 (61%) patients in the tolvaptan group and 17 (35%) patients in the control group (p = 0.011). Adverse events occurred in 46-47% of patients in both groups, and tolvaptan was not associated with worsened liver function. No patient with normal serum sodium on day 7 died within 30 days of treatment, whereas 16% of those with persistent hyponatremia died (p = 0.0019). Conclusion. In conclusion, short-term tolvaptan treatment is safe and can improve serum sodium level in cirrhotic patients with hyponatremia. Normalization of serum sodium level is associated with better survival.

Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma.

The exact incidence and severity of hepatitis B virus (HBV) reactivation after the withdrawal of prophylactic antiviral therapy (delayed HBV reactivation) is unknown. We retrospectively analyzed 107 newly diagnosed diffuse large B cell lymphoma patients with HBV infection who received chemotherapy. The median time from the cessation of antitumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in HBsAg-positive group and 0 in HBsAg-negative/anti-HBc-positive group (P < 0.001). No HBV-related fulminant hepatitis or hepatitis-related death occurred. The multivariate analysis showed that female gender and lengthy cycles of chemotherapy (>8 cycles) were independent risk factors of HBV reactivation in HBsAg-positive patients. In conclusion, prophylactic antiviral therapy could be withdrawn 6 months after the cessation of chemotherapy in HBsAg-negative/anti-HBc-positive patients. However, a longer course of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients.

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.