Diagnostic Potential of microRNA-122 for Stage Classification in Patients with HBV-Related Cirrhosis.

Objective: Previous studies have suggested that microRNA-122 has a relatively high diagnostic value for chronic viral hepatitis detection. In this study, we evaluated the diagnostic value of serum microRNA-122 in different stages of HBV-related cirrhosis，and serum microRNA-122 may serve as a potential biomarker for staging HBV related cirrhosis patients.. Methods: A total of 80 patients with HBV-related cirrhosis were included. Patients were characterized according to Child-Pugh score, laboratory parameters, and complications, and divided into compensated cirrhosis group and decompensated cirrhosis group. Wherein, the compensatory group for liver cirrhosis includes 21 patients, the compensatory group has 59 patients. Blood was collected from all patients, and RT-qPCR analyzed the expression levels of microRNA-122. Results: Serum microRNA-122 was decreased, while Child-Pugh score, Meld score, Prothrombin time, total bilirubin, and Direct bilirubin were higher in a decompensated group compared to the compensated group (all P < .05). For further stage classification, the mean serum microRNA-122 level was higher in stage 1 (11.3±5.1, compensated cirrhosis) compared to stage 2~5 (8.5±4.2, 4.9±1.0, 4.7±1.6, 3.5±1.1, decompensated cirrhosis, all P < .05). The expression of serum microRNA-122 independent of Child-Pugh score and complications, including ascites, varices, HCC (P > .05).However it was affected by Meld score and Prothrombin time (P < .05). Moreover, ROC analysis indicated microRNA-122 could differentiate compensated HBV-related cirrhosis (0.97 of AUC, P < .01). Furthermore, it could differentiate patients in stage 1 (compensated cirrhosis without esophageal varices) from HBV-related cirrhosis (0.91 of AUC, P < .01), with a sensitivity of 77.8% and satisfactory specificity of 88.7%. The significance of the relationship between the decrease in serum microRNA-122 levels and the stage of liver cirrhosis will be beneficial. Conclusion: Our results strongly support the diagnostic value of serum microRNA-122 as a potential biomarker of stage classification in patients with HBV-related cirrhosis, which could facilitate risk stratification and careful management. Provide new biomarkers for the diagnosis of patients with hepatitis B cirrhosis.

A Real-World Study on Safety and Efficacy of TAF Treatment in HBV Patients with High Risk of Osteoporosis or Osteopenia in China.

Objective: Long-term antiviral treatment is necessary for chronic hepatitis B (CHB) patients, and treatment safety is imperative for these patients. Previous studies showed tenofovir alafenamide (TAF) has shown efficacy non-inferior to that of tenofovir disoproxil fumarate (TDF) with improved renal and bone safety. However, there is still a lack of a rapid and convenient method to identify CHB patients at high risk of osteoporosis before initiating antiviral treatment. The International Osteoporosis Foundation (IOF) recommended a one-minute osteoporosis risk test to identify early high-risk patients. Our aim was to evaluate the feasibility of the one-minute osteoporosis risk test, along with evaluating the effectiveness and safety for virologically suppressed CHB patients switching to TAF. Methods: In this multicenter, prospective study, patients with chronic HBV infection who had been receiving TDF or Entecavir (ETV) for 48 weeks or more with HBV DNA less than 20 IU/mL for longer than 6 months were screened by one-minute osteoporosis risk test. Patients with a high risk of osteoporosis and then diagnosed with osteopenia or osteoporosis by dual-energy X-ray absorptiometry (DEXA) were enrolled. Safety in bone and bone turnover markers and antiviral efficacy of TAF were assessed respectively at 24 and 48 weeks. Results: 84.95% (175/206) CHB patients screened by one-minute osteoporosis risk test were at risk of osteoporosis.85.71% (150/175) were diagnosed with osteopenia by DEXA. The analysis included a total of 138 patients, of whom 92(62.3%) were male and 46 (37.7%) were female, with a mean age of 45 years old. HBV DNA was suppressed at 48 weeks at 88% (35/40) in the prior ETV group and 90% (88/98) at 48 weeks group in the prior TDF group. Bone mineral density (BMD) of the lumbar spine (L1-L4) from TDF switching to TAF was improved at 24 weeks (1.03±0.11 vs. 0.97±0.12, P = .001) than baseline. Propeptides of type I procollagen (PINP) and beta-C-terminal telopeptides of type 1 collagen (CTX) in serum at 24 weeks after switching from TDF to TAF declined compared with baseline (50.35±18.90 vs. 63.65±19.17, P = .016 and 0.21±0.13 vs. 0.32±0.10, P = .017). BMD, PINP, and CTX in ETV to TAF group remained stable during treatment. Conclusion: Attention should be paid to osteoporosis risk during lone-term nucleot(s)ide analogue treatment. One minute test of osteoporosis risk could rapidly identify most CHB patients at risk of osteoporosis. Given its convenience, we recommend using this test for early screening in CHB patients prior to initiating antiviral treatment. Our results further demonstrated that an improvement in bone safety after switching to TAF in virologically suppressed CHB patients with osteoporosis.

Evaluation of the Curative Effect of Treating HBV-related Liver Fibrosis/Cirrhosis Based on the Method of Removing Turbidity and Regulating the Liver.

Objective: This study investigated the effectiveness of a technique for eliminating cloudiness and managing liver function in treating liver fibrosis/cirrhosis associated with the Hepatitis B virus (HBV). Methods: From January 2022 to January 2023, the researchers' hospital treated 200 patients with HBV-related liver fibrosis/cirrhosis. These patients constituted two groups for the study: the control group, consisting of 100 cases who received routine treatment, and a study group, consisting of 56 cases who received treatment with a combination of turbidity removal and liver regulation, in addition to the standard treatment given to the control group. The researchers then compared factors such as liver function, level of liver fibrosis, liver stiffness measurement (LSM), and renal function between the two groups. Additionally, the researchers assessed the effectiveness of those treatments and any adverse reactions that may have occurred. Results: The study group demonstrated significantly higher clinical effectiveness than the control group after undergoing treatment, with statistical significance (P < .05). Post-treatment, both groups experienced lower GGT, ALT, and AST levels than their pre-treatment levels. Additionally, the study group had higher AIB levels than their pre-treatment levels. There was a statistically significant difference between the study and control groups regarding these biomarkers (P < .05), as the study group exhibited lower GGT, ALT, AST, TBIL levels and higher AIB levels. Furthermore, both groups displayed decreased HA, IV-C, PC III, and LN levels post-treatment compared to their pre-treatment values. The study group had significantly lower HA, IV-C, PC III, and LN concentrations than the control group (P < .05). Regarding LSM measurements after treatment for both groups, while there was a decrease in LSM values from their respective pre-treatment readings for each group, no significant difference was observed between them (P < .05). Moreover, the incidence of adverse reactions experienced by individuals in the study group following treatment was significantly lower than that of individuals in the control group (P < .05). Conclusion: Treatment based on removing turbidity and regulating the liver can effectively relieve the clinical symptoms of patients with HBV-related liver fibrosis/cirrhosis, promote the liver function to return to normal, relieve the degree of liver fibrosis, and reduce the LSM value. The curative effect is significant and worthy of clinical application.

Chinese herbal formula ruangan granule enhances the efficacy of entecavir to reverse advanced liver fibrosis/early cirrhosis in patients with chronic HBV infection: A multicenter, randomized clinical trial.

BACKGROUND: Nucleotide analogs treatment can reverse liver fibrosis in chronic hepatitis B (CHB). However, it has limited effect on fibrosis resolution in patients with CHB, particularly in preventing progression to hepatocellular carcinoma (HCC). Ruangan granule (RG), a Chinese herbal formula, has proven to produce a therapeutic effect against liver fibrosis in animal experiment. Thus, we aimed to evaluate the effect of our Chinese herbal formula (RG) combined with entecavir (ETV) to reverse advanced liver fibrosis/early cirrhosis from CHB. METHODS: A total of 240 CHB patients with histologically confirmed advanced liver fibrosis/early cirrhosis from 12 centers were randomly and blindly allocated to consume either ETV (0.5 mg/day) plus RG (2 times/day) or control (ETV) for 48 weeks (wk) treatment. Changes in histopathology, serology and imageology were observed. Liver fibrosis reversion, defined as a reduction in the Knodell HAI score by ≥ 2 points and Ishak score by ≥ 1 grade, was assessed. RESULTS: The rate of fibrosis regression and inflammation remission after 48 wk of treatment in histopathology was significantly higher in the ETV + RG group (38.73% vs. 23.94%, P = 0.031). The ultrasonic semiquantitative scores decreased by ≥ 2 points and were 41 (28.87%) and 15 (21.13%) in the ETV+RG and ETV groups, respectively (P = 0.026). The ETV+RG group had a significantly lower Fibrosis-4 score (FIB-4) index (P = 0.028). There was a significant difference between the ETV+RG and ETV groups in the liver function normalization rate (P < 0.01). Moreover, ETV plus RG combination treatment further reduced the risk of HCC in median 55-month follow-up (P < 0.01). CONCLUSIONS: This study illustrates that the Chinese herbal formula RG with ETV can improve advanced liver fibrosis/early cirrhosis regression in patients with CHB, further reducing the risk of HCC.

Multiple Diagnostic Indicators in the Development of Chronic Hepatitis B, Liver Cirrhosis, and Liver Cancer.

Context: Hepatitis B can develop into cirrhosis, and most liver cancers evolve on the basis of chronic hepatitis and cirrhosis. Many patients are already at an advanced stage when diagnosed. In recent years, clinicians have advocated detection of liver cancer using multiple markers in combination to improve the sensitivity and specificity of testing. Objective: The study aimed to evaluate the clinical value of using four tumor indicators-urea, alpha L-fucosidase (AFU), carbohydrate antigen 153 (CA153), carbohydrate antigen 125 (CA125), and alpha fetoprotein (AFP) and comparing the use of combined indicators to use of a single indicator for the diagnosis of liver cancer. Design: The research team performed a prospective study. Setting: The study took place at Clinical Laboratory, Baoding People's Hospital, Baoding City, Hebei Province, China. Participants: Participants were 98 patients with chronic hepatitis B, who became the CHB group; 102 patients with liver cirrhosis, who became the cirrhosis group, and 100 patients with liver cancer, who became the liver cancer group. They all had been admitted to the hospital between March 2019 and March 2021. Outcome Measures: The research team measured the urea, AFU, CA153, CA125, and AFP levels of the three groups, constructed an ROC curve, and analyzed the diagnostic values of the indicators singly and in combination for liver cancer. Results: For the levels of urea, AFU, CA153, CA125, and AFP, the CHB group's levels were significantly lower than those of the cirrhosis and liver cancer groups (both P < .001), and the cirrhosis group's levels were significantly lower than those of the liver cancer group (P < .001). In the CHB group, the compensatory group's levels were significantly lower than those of the decompensated group (P < .05). In the cirrhosis group, no significant differences existed between the levels of the grade A and grade B groups (P < .001), between those of the grade A and grade C groups (P < .001), or between those of the grade B and grade C groups (P < .001). In the cirrhosis group, the levels of the no ascites group were significantly lower than those of the ascites group (P < .05). In the liver cancer group, the levels of the stage I-II group were significantly lower than those of the stage III and stage IV groups (both P < .05), and those of the stage IV group were significantly lower than those of the stage Ⅳ group (P < .05). The levels of the <5cm group were significantly lower than those of the ≥5cm group (P < .001). The value of using a combination of indicators for diagnosis was significantly higher than that of a single indicator (P < .001). Conclusions: Urea, AFU, CA153, CA125, and AFP all have diagnostic value in the evaluation of chronic hepatitis B-cirrhosis and liver cancer, with the highest efficacy, sensitivity and specificity from a combined test and diagnosis.

Reactivation rates of hepatitis B or C or HIV in patients with psoriasis using biological therapies: a systematic review and meta-analysis.

Some biological therapies for psoriasis can cause the reactivation of viral infections. Although recent studies suggest no increased rate of reactivation with biological therapies, some life-threatening cases have been reported. Therefore, this meta-analysis examined the rate of virus reactivation in patients with psoriasis with biological therapies and concurrent hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. PubMed, Embase, and the Cochrane Library were searched for available papers from inception to December 2021. The outcome was the number of patients with virus reactivation after using biological therapies. The random-effect model was used in all analyses. Fourteen reports (1033 patients) were included. The pooled overall rate of virus reactivation was 0.04 (95%CI 0.01-0.09; I2 = 67.7%, P < 0.001). The pooled rates of HBV, HCV, and HIV reactivation were 0.04 (95%CI 0.00-0.10; I2 = 79.9%, P < 0.001), 0.07 (95%CI 0.02-0.14; I2 = 23.7%, P = 0.24), and 0.12 (95%CI 0.00-0.40), respectively. The pooled rates of HBV and HCV reactivation were 0.10 (95%CI 0.03-0.19) and 0.08 (95%CI 0.03-0.15) in Asia, but 0.00 (95%CI 0.00-0.01) and 0.04 (95%CI 0.00-0.21) in Europe. The publication type also influenced the results. The use of biological therapy in patients with psoriasis and HBV, HCV, or HIV infection might be associated with the rate of viral reactivation, but this meta-analysis had limitations, and the evidence might be weak. Nevertheless, it might suggest that at least a consultation with an infection specialist might be warranted in patients with psoriasis in whom biological therapies are considered.

Holistic management of hepatocellular carcinoma: The hepatologist's comprehensive playbook.

Hepatocellular carcinoma (HCC) is a common complication in patients with chronic liver disease and leads to significant morbidity and mortality. Liver disease and liver cancer are preventable by mitigating and managing common risk factors, including chronic hepatitis B and C infection, alcohol use, diabetes, obesity and other components of the metabolic syndrome. The management of patients with HCC requires treatment of the malignancy and adequate control of the underlying liver disease, as preserving liver function is critical for successful cancer treatment and may have a relevant prognostic role independent of HCC management. Hepatologists are the ideal providers to guide the care of patients with HCC as they are trained to identify patients at risk, apply appropriate surveillance strategies, assess and improve residual liver function, evaluate candidacy for transplant, provide longitudinal care to optimize and preserve liver function during and after HCC treatment, survey for cancer recurrence and manage its risk factors, and prevent and treat decompensating events. We highlight the need for a team-based holistic approach to the patient with liver disease and HCC and identify necessary gaps in current care and knowledge.

Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B.

BACKGROUND & AIMS: Chronic hepatitis B (CHB) and liver fibrosis are associated with a high risk of hepatocellular carcinoma (HCC) development. We assessed whether entecavir (ETV) plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese patients with CHB and an Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial. METHODS: After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis. RESULTS: A total of 1,000 patients were recruited; the median age was 42.0 years; 69.9% were male and 58.3% were HBeAg positive. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV monotherapy (p = 0.008 [p = 0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than ETV monotherapy (p = 0.018). There were no differences in the other 2 secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis, including the treatment allocation as a parameter, also demonstrated that ETV+BRC treatment was associated with a reduced incidence of HCC. The ITT and PP analyses showed consistent results. CONCLUSIONS: ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in patients with CHB and advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention. LAY SUMMARY: Patients with chronic hepatitis B virus infection are at an increased risk of developing liver cancer (specifically hepatocellular carcinoma [HCC]). While there are effective antiviral treatments that can suppress the virus in chronically infected patients, the risk of HCC remains. Herein, we show that adding a traditional Chinese medicine called Biejia-Ruangan compound to an antiviral reduced the risk of HCC in patients with chronic hepatitis B.

Impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis.

BACKGROUND: Fuzheng Huayu tablet is a traditional Chinese medicine (TCM) used for the treatment of liver fibrosis and cirrhosis. However, whether the combination with Fuzheng Huayu tablet could affect the antiviral efficacy of nucleos(t)ide remains a concern. The objective of this trial was to explore the impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis. METHODS: A prospective, randomized control trial was conducted. Patients with compensated hepatitis B cirrhosis were randomly divided into the treatment group (entecavir capsule plus Fuzheng Huayu tablet) and the control group (entecavir capsule plus simulant of Fuzheng Huayu), and followed up for 48 weeks. The dynamic changes of HBV DNA load, the rate of serological conversion of HBeAg, liver function, renal function and liver stiffness measurement (LSM) were monitored. The general clinical data and adverse events were also recorded. RESULTS: There was no significant difference in the rate of virological response and cumulative virological response between the treatment group and the control group (P > 0.05). After 48 weeks of treatment, the HBeAg seroconversion rate, biochemical response rate and LSM value were 21.05% and 4.76% (P = 0.164), 86.96% and 65.96% (P = 0.017), 9.5 kpa and 10.6 kpa (P = 0.827) in the treatment group and the control group, respectively. No serious adverse events related to the study therapy occurred during the trial. CONCLUSIONS: The antiviral entecavir combined with Fuzheng Huayu tablet did not affect the antiviral efficacy of entecavir, but could improve the rate of biochemical response, and had a tendency to improve the rate of serological conversion of HBeAg and liver fibrosis in patients with hepatitis B cirrhosis. Fuzheng Huayu tablet is clinically safe for patients with hepatitis B cirrhosis.

Elevated coffee consumption is associated with a lower risk of elevated liver fibrosis biomarkers in patients treated for chronic hepatitis B (ANRS CO22 Hepather cohort).

BACKGROUND AND AIMS: Patients chronically infected with hepatitis B virus (HBV) are at high risk of liver fibrosis, cirrhosis and liver cancer, despite recent therapeutic advances. It is therefore crucial to find non-pharmaceutical options for liver fibrosis prevention in this population. Using cross-sectional data from the ANRS CO22 Hepather cohort, we aimed to identify socio-demographic and modifiable risk factors for significant fibrosis in chronic HBV patients. METHODS: Logistic regression or Firth's penalized maximum likelihood logistic regression (according to outcome prevalence) multivariable models were used to test for associations between explanatory variables and significant fibrosis, as assessed by three non-invasive markers: aspartate aminotransferase to platelet ratio index (APRI), FIB-4, and gamma glutamyltransferase to platelet ratio (GPR). Analyses were stratified by HBV treatment status. RESULTS: The study population comprised 2065 untreated and 1727 treated chronic HBV patients. Elevated coffee consumption was consistently associated with a lower risk of elevated fibrosis biomarkers in all three treated-participant models, suggesting a dose-response relationship (adjusted odds ratios for ≥3 cups/day versus 0 cups/day: 0.16, 0.35 and 0.62, p ≤ 0.002, according to APRI, FIB-4 and GPR, respectively). Other modifiable risk factors included tobacco and alcohol use. CONCLUSION: Elevated coffee consumption was consistently associated with a lower risk of significant liver fibrosis, as assessed by three non-invasive markers in treated chronic HBV patients. This result can be immediately used in real-world situations, as increasing coffee consumption may be beneficial for patients at risk of advanced liver disease.

Predictive Performance of CAGE-B and SAGE-B Models in Asian Treatment-Naive Patients Who Started Entecavir for Chronic Hepatitis B.

BACKGROUND & AIMS: Cirrhosis and age (CAGE-B) and stiffness and age (SAGE-B) models assess the risk of hepatocellular carcinoma (HCC) development in white patients with chronic hepatitis B (CHB) undergoing sustained antiviral therapy (AVT). Herein, we checked the predictive performance of these models in Asian patients with CHB. METHODS: We reviewed 734 treatment-naive patients with CHB who started entecavir between 2006 and 2011 and were followed up for more than 5 years without HCC development during AVT. The predictive performance of CAGE-B and SAGE-B models was calculated using area under the receiver operating characteristic curves (AUROCs). RESULTS: Median liver stiffness assessed using transient elastography after 5 years of AVT was 6.8 kPa. Median CAGE-B and SAGE-B models after 5 years of AVT were 7.0 and 6.0, respectively. More than 5 years after AVT initiation, 66 patients (9.0%) developed HCC. The AUROCs of the CAGE-B and SAGE-B models were 0.764 and 0.785 after 7 years and 0.799 and 0.802 after 10 years of AVT, respectively. The cumulative incidence of HCC was significantly higher in the high-risk groups according to CAGE-B and SAGE-B risk stratification than in the medium- and low-risk groups (P < .05 in all cases). The SAGE-B model showed a higher likelihood ratio (χ2) (76.2 vs 71.4) and linear trend (χ2) (74.1 vs 58.6) than the CAGE-B model, whereas the CAGE-B model showed higher Akaike information criteria (64.3 vs 50.3). CONCLUSIONS: Both SAGE-B and CAGE-B showed acceptable performance in predicting HCC after 5 years of AVT in Asian patients with CHB.

Synergistic Effect of Biejia-Ruangan on Fibrosis Regression in Patients With Chronic Hepatitis B Treated With Entecavir: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Long-term nucleos(t)ide analogue (NA) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an antifibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs. METHODS: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5 mg per day) plus BR (2 g 3 times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥ 1 point by the Ishak fibrosis stage (IFS). RESULTS: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 weeks of treatment was significantly higher in the ETV + BR group (40% vs 31.8%; P = .0069). Among 388 patients with cirrhosis (ie, IFS ≥ 5) at baseline, the rate of cirrhosis reversal (ie, IFS ≤ 4) was significantly higher in the ETV + BR group (41.5% vs 30.7%; P = .0103). CONCLUSIONS: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression. CLINICAL TRIALS REGISTRATION: NCT01965418.

Long-Term Carbohydrate-Containing Late-Evening Snack Significantly Improves the Ratio of Branched Chain Amino Acids to Aromatic Amino Acids in Adults with Liver Cirrhosis due to Hepatitis B.

BACKGROUND: The liver is the primary organ for amino acid metabolism, and metabolic disorder of amino acids is common in liver disease. However, the characteristics of plasma amino acid profiles in patients with HBV-related cirrhosis and the impacts of late-evening snack (LES) on cirrhosis are unclear. OBJECTIVES: To investigate the characteristics of plasma amino acid profiles in patients with HBV-related chronic hepatitis, cirrhosis, and the effects of late-evening snacks on plasma amino acid profiles. METHODS: 86 patients with HBV-related cirrhosis and eighty patients with chronic hepatitis B were included in this study. The plasma amino acid profiles were measured by the amino acid analyzer. Patients were randomly divided into two groups, of which the liver cirrhosis group was to receive daily LES (n = 43) or non-LES (n = 43) for 6 months. Plasma amino acid profiles and biochemical parameters were measured in both groups at baseline and after 1, 3, and 6 months. RESULTS: Compared to healthy controls, the plasma concentration in the liver cirrhosis group of threonine, serine, glycine, glutamine, cysteine, tyrosine, phenylalanine, arginine, and methionine increased significantly (P < 0.05), while the ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA) decreased significantly (P < 0.05). A carbohydrate-predominant LES treatment resulted in a significant increase in BCAA/AAA and decrease in the level of ammonia and glutamine compared with baseline after 6 months of supplementation (P < 0.05). Patients with Child-Pugh B and C are more responsive to changes in amino acid profiles than those with Child-Pugh A. CONCLUSIONS: The application of an LES carbohydrate module for six months in liver cirrhosis patients was associated with increased BCAA/AAA and decreased level of ammonia. Patients with Child-Pugh B and C grades were the most beneficial population.

Successful Treatment of Advanced Intrahepatic Cholangiocarcinoma With a High Tumor Mutational Burden and PD-L1 Expression by PD-1 Blockade Combined With Tyrosine Kinase Inhibitors: A Case Report.

Advanced intrahepatic cholangiocarcinoma (iCCA) is not suitable for surgical treatment. Guided by the concept of precision medicine, preoperative systematic treatment may reshape the clinical outcomes of advanced intrahepatic cholangiocarcinoma patients. We describe the case of a 38-year-old female who has been diagnosed with stage IV intrahepatic cholangiocarcinoma with a high tumor mutational burden and positively programmed death-ligand 1 (PD-L1) expression. The patient was treated with programmed cell death 1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs). After 7 cycles of combination therapy, she underwent radical resection and no tumor cells were found in the postoperative histopathological examination. In addition, the patient's survival time had reached 25 months, as of August 2021. To date, this is the first case of successful radical resection after combined immunotherapy with TKIs for advanced PD-L1-positive intrahepatic cholangiocarcinoma with a high tumor mutational burden (TMB). The case provides a new approach to the treatment of advanced intrahepatic cholangiocarcinoma.

Traditional Chinese medicine Yiqi Huoxue recipe attenuates hepatic fibrosis via YAP/TAZ signaling.

BACKGROUND/AIMS: The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis. MATERIALS AND METHODS: Wistar rats were used to generate a model of carbon tetrachloride (CCl4)-induced liver fibrosis. Chronic hepatitis B (CHB) patients with liver fibrosis were enrolled and assigned to receive either nucleoside/nucleotide analogues (NAs) or NAs plus YQHX. Histology, immunohistochemistry, qRT-PCR, and western blotting were conducted to mechanistically assess the therapeutic effects of YQHX on liver fibrosis. RESULTS: YQHX markedly alleviated morphological alterations in CCl4-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl4-meidated activation of the transforming growth factor-beta (TGF-ß)/Smad signaling pathway. Notably, CCl4 induced up-regulation of YAP, TAZ, and connective tissue growth factor (CTGF), which were significantly abrogated by YQHX. Consistent with the above major findings in rats, CHB patients treated with NAs plus YQHX had greater improvement in liver fibrosis than those given NAs alone (71.4% vs. 28.6%; P = 0.057). In addition, hepatic and plasma levels of YAP were significantly decreased after YQHX treatment in CHB patients with liver fibrosis. CONCLUSION: YAP/TAZ signaling plays a role, at least in part, in the anti-fibrotic activity of YQHX. The findings may help to better understand the mechanisms of YQHX in the treatment of liver fibrosis.

Effect of entecavir plus Ganshuang granule on fibrosis and cirrhosis in patients with chronic hepatitis B.

OBJECTIVE: To investigate the effect of entecavir plus Ganshuang granule (, GSG) on advanced fibrosis and cirrhosis in patients with chronic hepatitis B virus infection. METHODS: One hundred thirty-five patients were randomly assigned to one of two cohorts: GSG cohort (n = 69) or placebo cohort (n = 66). The GSG cohort received entecavir plus GSG and the placebo cohort received entecavir plus placebo for 48 weeks. Liver biopsy was performed at baseline and between weeks 44 and 48 during this placebo-controlled trial. We assessed histological improvement (greater than a two-point decrease using the Knodell in fl ammatory score and no worsening of the Ishak fibrosis score) and fibrosis regression (a decrease of at least one point in the Ishak fibrosis score). RESULTS: There were 95.7% of patients (66/69) in the GSG cohort and 66.7% (44/66) of patients in the placebo cohort who showed necroin fl ammation improvement. The mean reduction in the Knodell necroinflammatory score was 5.1 and 2.6, respectively. There were 89.9% (62/69) of patients in the GSG cohort and 31.8% (21/66) of patients in the placebo cohort who showed at least a one-point improvement in the Ishak fibrosis score. The mean reduction in the Ishak fibrosis score was 1.7 and 0.4, respectively. CONCLUSION: Patients with advanced fibrosis and cirrhosis caused by chronic hepatitis B showed more improvement in liver histology in a shorter time after treatment with entecavir plus GSG compared with entecavir plus placebo.

Ground-glass hepatocellular inclusions are associated with polypharmacy.

Ground-glass (GG) hepatocytes are classically associated with chronic hepatitis B (HBV) infection, storage disorders, or cyanamide therapy. In a subset of cases, an exact etiology cannot be identified. In this study, we sought to characterize the clinical, histological, and ultrastructural findings associated with HBV-negative GG hepatocytes. Our institutional laboratory information system was searched from 2000 to 2019 for all cases of ground-glass hepatocytes. Ten liver biopsies with GG hepatocellular inclusions and negative HBV serology, no known history of storage disorders, or cyanamide therapy were reviewed. Half of the patients had history of organ transplantation and/or malignancy. These patients took on average 8.1 medications (range: 3-14) with the most common medications being immunosuppressive and health supplements. Histologically, GG hepatocytes show either peri-portal or centrizonal distribution. The inclusions are PAS-positive and diastase sensitive. Electron microscopy showed intracytoplasmic granular inclusions with low electron density, consistent with unstructured glycogen. In summary, GG hepatocytes are a rare finding in liver biopsies, but are more common in patients with hepatitis B. They can also be seen in HBV-negative patients who have polypharmacy. In these cases, they are the result of unstructured glycogen accumulation putatively due to altered cell metabolism.

Twelve-month post-treatment parameters are superior in predicting hepatocellular carcinoma in patients with chronic hepatitis B.

BACKGROUND & AIMS: There are currently several prediction models for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) receiving oral antiviral therapy. However, most models are based on pre-treatment clinical parameters. The current study aimed to develop a novel and practical prediction model for HCC by using both pre- and post-treatment parameters in this population. METHODS: We included two treatment-naïve CHB cohorts who were initiated on oral antiviral therapies: the derivation cohort (n = 1480, Korea prospective SAINT cohort) and the validation cohort (n = 426, the US retrospective Stanford Bay cohort). We employed logistic regression, decision tree, lasso regression, support vector machine and random forest algorithms to develop the HCC prediction model and selected the most optimal method. RESULTS: We evaluated both pre-treatment and the 12-month clinical parameters on-treatment and found the 12-month on-treatment values to have superior HCC prediction performance. The lasso logistic regression algorithm using the presence of cirrhosis at baseline and alpha-foetoprotein and platelet at 12 months showed the best performance (AUROC = 0.843 in the derivation cohort. The model performed well in the external validation cohort (AUROC = 0.844) and better than other existing prediction models including the APA, PAGE-B and GAG models (AUROC = 0.769 to 0.818). CONCLUSIONS: We provided a simple-to-use HCC prediction model based on presence of cirrhosis at baseline and two objective laboratory markers (AFP and platelets) measured 12 months after antiviral initiation. The model is highly accurate with excellent validation in an external cohort from a different country (AUROC 0.844) (Clinical trial number: KCT0003487).

Severe Guillain-Barré syndrome associated with chronic hepatitis B: A case report and literature review.

RATIONALE: Guillain-Barré syndrome (GBS) is a postinfectious autoimmune peripheral neuropathy characterized by acute paralysis of the limbs. Clinically, extrahepatic manifestations of neurologic involvement in chronic hepatitis B (CHB) are uncommon. Little attention has been paid to the relationship between GBS and CHB viral infection. PATIENT CONCERNS: We presented a severe case of a 34-year-old man with general fatigue, anorexia, jaundice, numbness, and even muscle atrophy in the limbs, and respiratory failure during an acute exacerbation of CHB. DIAGNOSES: Serological liver enzymes test confirmed an acute exacerbation of CHB. Nerve conduction studies revealed the features of acute motor and sensory axonal neuropathy combined with acute inflammatory demyelinating polyneuropathy, and cerebrospinal fluid analysis showed albuminocytologic dissociation. Clinical manifestations and the test results were consistent with a diagnosis of severe CHB-related GBS. INTERVENTIONS: He was treated with mechanical ventilation, 2 courses of intravenous immunoglobulin, antichronic hepatitis B drugs therapy supplemented by hepatoprotection, acupuncture and rehabilitation. OUTCOMES: After 29 days of hospitalization, his neurological condition improved. At a 6-month follow-up visit, he was able to walk with the support of another person. LESSONS: The acute exacerbation of CHB may be a potential predisposing factor for the onset of GBS. This case is a reminder to clinicians that during the acute exacerbation of CHB, patients with neurological symptoms in the limbs should be considered for potential CHB-related GBS.

The association of plasma high-density lipoprotein cholesterol levels and cirrhosis development in obese patients with chronic hepatitis B: a cohort study.

OBJECTIVE: Metabolic disorder is a common risk factor for cirrhosis in Asia, and it will increase the risk of cirrhosis in patients with Chronic hepatitis B (CHB). However, studies on the efficacy of plasma lipid markers which predict the happening and development of cirrhosis in obese CHB patients are limited. METHODS: In total, 3327 patients who were followed for more than 4 years' follow-up in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine joined the program. Finally, 287 obese CHB patients were included in this study according to the results of metabolic tests. The data of baseline and follow-up were collected, and the association between them was analyzed. RESULTS: Based on the follow-up results, enrolled patients were divided into a group of cirrhosis (n = 146) and a group of noncirrhosis (n = 141). Plasma glucose and high-density lipoprotein cholesterol (HDL-C) levels in the noncirrhosis group (5.2 and 1.2 mmol/L, respectively) were significantly higher than that in the cirrhosis group (5.0 and 1.0 mmol/L, respectively), while the amount of total bile acid (TBA) in the cirrhosis group was lower than that in the cirrhosis group. Levels of HDL-C and total cholesterol were associated with liver function. Plasma HDL-C was an independent indicator of cirrhosis in patients with CHB. Patients with HDL-C levels less than 1.03 mmol/L had a 2.21-fold higher incidence rate of cirrhosis, and patients over 40 years old or the levels of HDL-C less than 1.03 mmol/L were more likely to generate cirrhosis. CONCLUSIONS: Plasma HDL-C was an appropriate marker in predicting cirrhosis for patients with CHB.