Hepatitis E virus (HEV) infection is an important etiology of liver failure. This study aimed to explore the associations of blood fibrosis profiles with HEV-related liver failure (HEV-LF) onset and evaluate their prediction performance in hospitalized patients with acute hepatitis E. Participants were obtained from two tertiary medical centers in Jiangsu, China, between January 2018 and November 2024. Cox proportional hazards regression, restricted cubic splines, and threshold effect analysis were used to examine associations between fibrosis markers and HEV-LF risk. The predictive value of these markers was evaluated for importance ranking, discrimination, calibration, and net benefit. Among 504 included participants, 59 developed HEV-LF during hospitalization. After adjusting for covariates, elevated baseline laminin (HR = 1.432, 95

ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease globally. Previous studies have shown that MASLD is an independent risk factor for chronic kidney disease (CKD), but the variations in estimated glomerular filtration rate (eGFR) levels across countries with different ethnic backgrounds have not been extensively reported. We enrolled 3308 participants with biopsy‐proven MASLD from 34 centers in this multinational study and analyzed the associations between eGFR and histological severity of liver fibrosis in different countries. European participants had lower eGFR levels (92.2 ± 20.7 vs. 104.7 ± 17.3 mL/min/1.73 m2) and significant liver fibrosis (61.4 vs. 32.4%) than Asian individuals. In Asia, Chinese participants had the highest mean eGFR level at 105.8 mL/min/1.73 m2, while Malaysian participants had the lowest at 87.3 mL/min/1.73 m2 (p < 0.001). In Europe, French participants had the highest mean eGFR level at 95.3 mL/min/1.73 m2, while Romanian individuals had the lowest at 81.1 mL/min/1.73 m2 (p < 0.001). eGFR levels were inversely associated with liver fibrosis in Asian individuals (OR: 0.793, 95%CI: 0.685–0.917, p = 0.002), even after adjusting for traditional renal risk factors, but not in Europeans. Our findings provide the basis for further investigation of the burden of MASLD on CKD risk in different countries.

BACKGROUND AND AIMS:Disrupting liver immune homeostasis drives inflammation. Recent evidence shifts immunoregulatory focus to hepatocytes, though the mechanisms remain poorly defined. Forkhead box O1 (FoxO1) is a critical homeostasis regulator, but its function in liver immune homeostasis is unknown. We aimed to clarify the role of hepatocyte FoxO1 in liver immune homeostasis and inflammation. APPROACH AND RESULTS:Human liver FoxO1 expression and its association with inflammation were analyzed in patients with various inflammation-related liver diseases. Hepatocyte-specific Foxo1 knockout (FoxO1 △hepa ) mice were established. Hepatocyte-specific gene interference was employed in alcoholic hepatitis and hepatic schistosomiasis murine models. Transcriptomic, single-cell RNA sequencing, and CUT&Tag analyses were performed to elucidate the underlying mechanisms. Hepatocyte FoxO1 levels in human inflammatory livers declined prevalently and were inversely correlated with inflammation and fibrosis. Around 15-18 weeks after birth, FoxO1 △hepa mice exhibited mild spontaneous hepatic inflammation with natural killer T (NKT) cell and neutrophil accumulation. NKT cell depletion in FoxO1 △hepa mice with alcoholic hepatitis or hepatic schistosomiasis (HS) significantly reduced neutrophil accumulation and protected against liver inflammation and damage. Mechanistically, FoxO1 promoted retinoic acid synthesis to induce hepatocyte CD1d expression, which is necessary for regulating NKT cell apoptosis. Innovatively, decreased JMJD1C expression in hepatocytes caused histone H3 lysine 9 (H3K9) dimethylation at the Foxo1 promoter, repressing its transcription and disrupting local immune homeostasis. CONCLUSIONS:Our findings uncover a hitherto unrecognized mechanism for hepatocyte-based control of liver inflammation, in which hepatocyte FoxO1 maintained by JMJD1C restrains local NKT cells and neutrophils via CD1d induction, providing promising targets for inflammatory liver diseases.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs). METHODS: We analyzed data from 3004 individuals with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) across 29 Chinese and 9 international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9034 patients with MASLD to examine associations between the acFibroMASH index and the risk of LREs. RESULTS: In the pooled global cohort, the acMASH index identified MASH with an area under the receiver operating characteristic curve (AUROC) of 0.802 (95% confidence interval [CI], 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI, 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI, 0.693-0.800; P < .01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted hazard ratio, 11.23; 95% CI, 3.98-31.66). CONCLUSIONS: This multi-ethnic study validates the acMASH index as a reliable, noninvasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs.

Background Liver stiffness measurement (LSM) via vibration-controlled transient elastography accurately assesses fibrosis. We aimed to develop a universal risk score for predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis. Methods We systematically selected predictors and developed the risk prediction model (HCC-LSM) in the hepatitis B virus (HBV) training cohort (n = 2251, median follow-up of 3.2 years). The HCC-LSM model was validated in an independent HBV validation cohort (n = 1191, median follow-up of 5.7 years) and a non-viral chronic liver disease (CLD) extrapolation cohort (n = 1189, median follow-up of 3.3 years). An HCC risk score was then constructed based on a nomogram. An online risk evaluation tool Liver Elastography-Based Hepatocellular Carcinoma Risk Score (LEBER) was developed using ChatGPT4.0. Results Eight routinely available predictors were identified, with LSM levels showing a significant dose-response relationship with HCC incidence (P < .001 by log-rank test). The HCC-LSM model exhibited excellent predictive performance in the HBV training cohort (C-index = 0.866) and the HBV validation cohort (C-index = 0.852), with good performance in the extrapolation CLD cohort (C-index = 0.769). The model demonstrated significantly superior discrimination compared to 6 previous models across the 3 cohorts. Cut-off values of 87.2 and 121.1 for the HCC-LSM score categorized participants into low-, medium-, and high-risk groups. An online public risk evaluation tool (LEBER; http://ccra.njmu.edu.cn/LEBER669.html) was developed to facilitate the use of HCC-LSM. Conclusion The accessible, reliable risk score based on LSM accurately predicted HCC development in patients with chronic hepatitis, providing an effective risk assessment tool for HCC surveillance strategies.

目的 探讨装载miRNA451a的外泌体对肝癌细胞株HepG2和SMMC-7721增殖的影响.方法 正常肝组织上皮细胞株HL-7702来源的外泌体,通过与胆固醇基修饰的miRNA-451a模拟物直接孵育构建外泌体451a复合体.将构建的exo-miRNA-451a复合体、等量miRNA-451a模拟物、等量PBS分别接种于96孔板中处于对数生长期的HPG2和SMMC-7721细胞,作为实验组、对照组和空白对照组.采用激光共聚焦显微镜观察exo-miRNA-451a复合体进入细胞内的情况;CCK8法检测HPG2和SMMC-7721细胞增殖.结果 构建的外泌体miRNA-451a复合体分别与HepG2和SMMC-7721细胞,共培养3h时,在共聚焦显微镜下,有PKH67标记的外泌体和Cy3标记的miRNA-451a在HepG2和SMMC-7721细胞中共定位,并且在随后的6h、12h观察时逐渐增多.CCK-8实验提示当外泌体451a复合体和miR-451a模拟物分别与肝癌细胞株共孵育6h,OD值差异不明显;共孵育12h实验组OD值低于对照组,共培养48h实验组OD值显著低于对照组.结论 装载miRNA-451a的外泌体可抑制肝癌细胞株的增殖.

Objective:To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection.Methods:Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results:A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group ( P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [ OR, 2.667 ( CI: 1.389-5.122); P=0.003], increased CK [ OR, 2.544 ( CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] ( CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [ OR, 0.424 ( CI: 0.254-0.709); P=0.001]. Conclusion:Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.

目的 了解常州市大学生代谢相关性脂肪性肝病(M A FLD)的流行情况和特点.方法 采用肝脏受控衰减参数(CAP值)和肝脏超声作为MAFLD的诊断标准,对常州市3所大学的308名在校大学生进行脂肪肝的流行情况调查.比较分析MAFLD组与非MAFLD组在人体成分、血压、肝功能、血糖、血脂、尿酸、胰岛素抵抗指数(HOMA-IR)、血常规、饮食营养风险评分(DST scores)、最大摄氧量(VO2 Max)方面的差异.采用二元logistic,回归分析体重指数(BMI)、HOMA-IR、饮食营养风险、心肺适能对MAFLD的影响.结果 以CAP值和肝脏超声作为诊断标准,MAFLD的发生率分为31.2％ 和20.6％.MAFLD组的BMI,收缩压、舒张压、ALT、γ-谷氨酰基转移酶(GGT)、三酰甘油(TG)、低密度脂蛋白(LDL)、HOMA-IR、白细胞计数、红细胞计数、血小板计数均高于非MAFLD组,BMI为26.85(24.8,28.5)kg/m2比20.7(18.9,22.08)kg/m2、收缩压为120(113,128)mmHg比110(100,120)mmHg、舒张压为(76.88±7.60)mmHg比(72.06±8.33)mmHg、ALT为20(10,42)U/L比11(9,14)U/L、GGT为23(17,29)U/L比15(11,18)U/L、TG为0.92(0.69,1.51)U/L比0.71(0.56,0.9)U/L、LDL为(2.79±0.61)mmol/L比(2.41±0.67)mmol/L、HOMA-IR为1.59(1.37,3.05)比1.14(0.81,1.48),白细胞计数为(7.64±1.59)×109比(6.23±1.28)×109、红细胞计数为(5.21±0.53)×1012比(4.90±0.49)×1012、血小板计数为(284.00±42.73)×109比(247.11±48.83)×109.高密度脂蛋白(HDL)、DST scores、VO2 Max均低于非NAFLD组(P<0.05),HDL为(1.21±0.25)mmol/L比(1.45±0.33)mmol/L、DST scores为55.57±12.47比60.94±9.67、VO2 Max为37(32.75,42.01)比40.71(37.21,49.17).BMI≥28 kg/m2、HOMA-IR≥1.5、饮食营养有风险、心肺适能较差分别增加MAFLD的患病风险22.5倍、5.1倍、15.3倍、3.3倍.结论 大学生的M A FLD流行率高并伴有代谢综合征相关指标的变化应引起足够重视,应降低饮食营养风险、加强锻炼、控制体质量.

核苷(酸)类似物(NAs)的抗乙肝病毒的药物已经成为治疗慢性乙型肝炎最重要的药物,这些药物用于乙肝治疗已经近20年,其疗效毋庸置疑.目前,在我国临床应用的有5种:恩替卡韦(entecavir,ETV)、替诺福韦酯(tenofovir disoproxil fumarate,TDF)、阿德福韦酯(adefovir dipivoxil,ADV)、替比夫定(telbivudine,LdT)、拉米夫定(lamivudine,LAM).

Background . This study aimed to evaluate the risk factors of HCC development in patients with hepatitis B virus (HBV)-related DC and who underwent long-term antiviral therapy. Methods . Data from 308 patients with HBV-related DC and long-term antiviral therapy were collected and retrospectively reviewed. Cox regression analysis was used to analyze independent risk factors of HCC development. Results . Data from 129 patients with definite records were analyzed. The median follow-up time was 5 years (range, 1 to 8 years). At the end of the follow-up, 41 (31.8%) patients developed HCC, and the time from DC diagnosis to HCC incidence who received antiviral therapy was 4.4 years (range, 1–7 years). The incidence of HCC was higher in males (30/78, 38.5%) than in females (11/51, 21.6%) ( P  = 0.04). Patients who developed HCC were significantly older than those who did not develop HCC ( P  < 0.01). The incidence of HCC in patients receiving nucleoside analogues, nucleotide analogues, and combination therapy was 34.7%, 38.1%, and 33.3%, respectively, and the difference showed no significant differences ( P  = 0.95). Multivariate Cox regression analysis demonstrated that male gender and age ≥50 years are independent risk factors of HCC development (OR = 2.987 and 2.408; 95% CI (1.301–6.858) and (1.126–5.149); P  = 0.01 and 0.02, respectively). Conclusion . The risk of HCC remains to be high in patients with HBV-related DC, especially in males aged ≥50 years.

INTRODUCTION:The impact of mutations in the reverse transcriptase region of HBV on serum HBsAg titer and its correlation with HBV DNA is largely unknown.METHODOLOGY:A total of 644 patients, with a history of lamivudine or adefovir dipivoxil resistance who underwent genotypic resistance tests, were enrolled in this study. Serum HBsAg, hepatitis B e antigen and HBV DNA were quantified, and the HBV RT region was sequenced and analyzed. Then, the patients were divided into five sub-groups, including M204I/V, L180M+M204I/V, A181T/V, N236T and A181T/V+N236T according to the mutation spectra.RESULTS:HBsAg was lower in the wild-type and A181T/V+N236T groups as compared to the M204I/V, L180M+M204I/V and N236T groups. HBsAg was positively correlated with HBV DNA levels in the wild-type group (r = 0.322, p < 0.01), as well as in the M204I/V, L180M+M204I/V, A181T/V, and N236T subgroups, while no correlation was found in the A181T/V+N236T subgroup (r = 0.159, p = 0.217). Moreover, for patients with N236T mutation, HBsAg was positively correlated with HBV DNA level in the HBeAg negative group (r = 0.435, p = 0.016), but not in the HBeAg positive group (r = 0.105, p = 0.594). For patients with A181T/V or N236T mutation, HBsAg was positively correlated with HBV DNA in older patients (≥ 40 years), but not in younger patients (< 40 years).CONCLUSIONS:Serum HBsAg titer and its correlation with HBV DNA may be affected by mutations in the reverse transcriptase region of HBV, that should be re-evaluated in patients with antiviral resistance.

对HBV相关肝癌患者、乙型肝炎肝硬化患者、健康体检者(每组3例)血清外泌体进行深度测序,获取肝细胞癌特性性表达的miRNA基因共25个.其中上调的有17个,下调的基因有5个,选取5个基因进行qPCR验证,结果与筛选结果一致.

目的 评估肌肉减少性肥胖(SO)在超重和肥胖成年人群中的流行程度及其与2型糖尿病(T2DM)、高血压和高脂血症的关系.方法 回顾性分析减重门诊的156例超重和肥胖成年患者以及46名年龄相仿的正常体质量者的临床资料,均进行人体测量学指标检测、生化指标测定,使用生物电阻抗分析仪进行人体成分检测评估.然后将超重和肥胖的患者分为SO组或非SO组,比较2组的一般情况、生化指标及人体成分.采用Logistic回归分析SO与T2DM、高血压和高脂血症的关系.结果 在156例超重/肥胖患者中,有23例(14.74％)符合SO的标准,其患T2DM、高血压及高脂血症的概率显著高于非SO患者.Logistic回归分析显示,相较于非SO患者,SO患者患T2DM、高血压、高脂血症的风险概率分别达344.20％、302.20％、515.60％,在调整了年龄、性别构成、已婚与否及吸烟史后,风险概率仍有344.20％、298.30％、510.50％.结论 超重和肥胖人群中,SO与T2DM、高血压及高脂血症的发生有着密切联系,在这一人群中进行SO筛查是非常必要的.

Objective: To explore the relationship between liver controlled attenuation parameters (CAP) and body fat mass and its distribution. Methods: From May to December 2018, 978 adult patients visited at the fatty liver center of the Third People's Hospital of Changzhou were treated. The patient's liver controlled attenuation parameters were measured by transient elastography and the body fat mass and its distribution were measured by bioelectrical impedance technology. Pearson's correlation coefficient was adopted to describe the correlation between liver CAP value and body mass index (BMI), body fat mass index (BFMI), trunk fat mass index (TFMI), limbs fat mass index (LFMI) and visceral fat area (VFA). Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate BMI, BFMI, TFMI, LFMI and VFA to differentiate the cut-off points and efficacy of CAP for diagnosing grading of fatty liver changes in S0-1 and S2-3. Results: In 653 cases of male, S0 ~ S3 accounted for 4.90%, 3.37%, 22.36% and 69.37%, respectively, and in 325 cases of females, S0 ~ S3 accounted for 7.38%, 6.46%, 13.23% and 72.92%, respectively. Female patients had more visceral, trunk and limbs fat than male (P < 0.01). Body mass, body fat mass, body fat percentage, BMI, BFMI, TFMI, LFMI, and VFA were increased in male and female patients with increasing liver fat grade (P < 0.01). CAP values ​​of male and female patients were positively correlated with BMI, BFMI, TFMI, LFMI and VFA. Percentage of body fat mass increased with increasing liver fat grade (male: F = 13.42, P < 0.001; female: F = 3.22, P = 0.023); while limb fat mass percentage did not increase with liver fat grade (Male: F = 1.13, P = 0.34; female: F = 1.05, P = 0.37). Hepatic steatosis grading (S0 ~ 1 or S2 ~ 3) diagnosed with CAP were distinguished through BMI, BFMI, TFMI, LFMI and VFA. AUC was 0.80 ~ 0.82 in males (P < 0.01), and 0.75 ~ 0.78 in females (P < 0.01). Conclusion: The liver CAP value is positively correlated with the body's limbs, trunk and visceral fat, and has a strong correlation with trunk and visceral fat. BMI, BFMI, TFMI, LFMI and VFA up to some extent can identify the CAP diagnosis of grading of fatty liver changes in S0-1 and S2-3.

目的 评估2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者的肝脏硬度和脂肪变性程度.方法 本研究纳入198例T2DM合并NAFLD患者,利用FibroScan瞬态弹性成像技术(TE)评估患者肝脏脂肪变性和纤维化程度.依受控衰减参数(CAP)值将肝脂肪变性分为4个等级:S0(＜ 238dB/m)、S1(238～ 258dB/m)、S2(259 ～ 291 dB/m)、S3(≥292dB/m).依肝脏硬度(LSM)值将肝纤维化分为4个等级:F0F1(＜7.0kPa)、F2[(7.0～8.6) kPa]、F3[(8.7 ～ 10.2) kPa]、F4(≥10.3kPa).结果 198例患者中有171例有效测量病例(86.4％)患者纳入分析.其中有4.1％ (7/171)患者有轻度脂肪变性(S1),有21.6％(37/171)患者有中度脂肪变性(S2),有71.3％ (122/171)患者重度脂肪变性(S3).有28.7％(49/171)患者存在显著肝纤维化(F2 ～ F3),有17.5％ (30/171)患者LSM值提示肝硬化(F4).与没有或轻中度脂肪变性(S0 ～S2)患者比较,重度脂肪变性(S4)患者中显著肝纤维化(F2 ～ F3)比例及肝硬化(F4)比例均更高.单因素及多因素Logistic回归分析提示高ALT和高CAP值可能是肝纤维化发生的独立危险因素.结论 TE是T2DM合并NAFLD患者肝脂肪变性和纤维化的有效评估方法,其中超过90％的患者有中重度脂肪变性,超过45％的患者有显著的肝脏纤维化.肝脏脂肪变性程度和硬度评估具有较好的临床应用价值.

Introduction and aim. Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality, and predicting the prognosis is challenging. This study aimed to compare the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in predicting the 90-day mortality in patients with hepatitis B virus (HBV)-associated ACLF (HBV-ACLF). Materials and methods. This prospective, observational study enrolled 54 patients with HBV-ACLF. The serum NGAL and CysC levels were determined. A multivariate logistic regression analysis was used to analyze the independent risk factors of mortality. Results. Serum NGAL, but not CysC, was found to significantly correlate with the total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD). Serum NGAL [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.004-1.012; P < 0.01], but not CysC, was an independent risk factor for developing hepatorenal syndrome. Moreover, NGAL (OR, 1.005; 95% CI, 1.001-1.010; P < 0.01) along with the MELD score was independently associated with the overall survival in patients with HBV-ACLF. Patients with HBV-ACLF were stratified into two groups according to the serum NGAL level at baseline (low risk: <217.11 ng/mL and high risk: ≥ 217.11 ng/mL). The 90-day mortality rate was 22.73% (5/22) in the low-risk group and 71.88% (23/32) in the high-risk group. Moreover, NGAL, but not CysC, significantly improved the MELD score in predicting the prognosis of HBV-ACLF. Conclusion. The serum NGAL might be superior to CysC in predicting the prognosis of HBV-ACLF with the normal creatinine level.

The objective of this study was to analyze the prevalence of drug-resistant HBV mutants in patients with treatment failure during the past seven years (2010–2016). 4055 HBV-infected patients who underwent HBV polymerase gene mutation test from 2010 to 2016 were enrolled. The nucleos(t)ide analogues (NAs) resistance mutation positions, including rtL180, rtA181, rtT184, rtS202, rtM204, rtI233, rtN236, rtI169, rtV173, and rtM250 were analyzed. Genotypic resistance mutations were detected in 30.8% (1248/4055) of the patients with treatment failure. Rates of drug-resistant mutations associated with LAM, ADV, ETV, and multidrug were 27.23% (1104/4055), 9.67% (392/4055), 3.69% (150/4055), and 0.79% (32/4055). Among the primary NA-resistant mutations, rtM204I (13.44%, 545/4055) occurred more frequently, followed by rtM204V, rtN236T, rtA181T, and rtA181V. For single-base mutations, rtL180M and rtA181V increased gradually during the past seven years, while rtM204I/V and rtN236T decreased after 2015. The development of drug-resistant mutations positively correlated with the consumption of ETV (r = 0.964, P = 0.002), and weakly correlated with that of LAM (r = 0.679, P = 0.109) and ADV (r = 0.429, P = 0.354). Moreover, single-base mutation rtA181V and multi-base mutations (rtL180M + M204I and rtL180M + M204V + M204I) were more common in HBV genotype C than those in genotype B (1.94% vs. 0.66%, 1.84% vs. 0.16%, 1.02% vs. 0.16%, respectively). NA-related mutations in HBV RT region increased in the past seven years, especially for LAM. Frequencies of rtL180M and rtA181T/V increased gradually in the past seven years, to which we should pay more attention.

Background: The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a new noninvasive marker for assessing liver fibrosis. We aimed to evaluate the performance of GPR for prediction of 90-day mortality in patients with acute-on-chronic liver failure (ACLF). Methods: A total of 355 patients with HBV-associated ACLF were enrolled from two clinical centers and divided into training group (n = 210) and validation group (n = 145). Potential risk factors for 90-day mortality were analyzed. Results: Age, MELD score and GPR were independent risk factors associated with ACLF prognosis. A new scoring system (MELD-GPR) was developed. MELD-GPR = 9.211 - 0.029 x age - 0.290 x MELD - 0.460 x GPR. For ACLF patients with liver cirrhosis, the area under the receiver operating characteristic curve (AUROC) of MELD-GPR was 0.788, which was significantly higher than that of MELD and MELD-Na (0.706 and 0.666, respectively). Patients were stratified into three groups according to MELD-GPR scores (high risk: < -0.19, intermediate risk: - 0.19-0.95, and low risk: > 0.95), and the high-risk group (MELD-GPR < -0.19) had a poor prognosis (P < 0.01). For ACLF patients without liver cirrhosis, MELD-GPR < 0.95 predicted a poor prognosis. Conclusions: Incorporating GPR into MELD may provide more accurate survival prediction in patients with HBV-ACLF.

Acute-on-chronic liver failure (ACLF) is a syndrome with a high rate of short-term mortality, and clinically it is important to identify patients at high risk of mortality. The present study evaluated the value of osteopontin (OPN) in the prediction of 90-day mortality in patients with ACLF. A total of 54 patients with HBV-associated ACLF were enrolled, and serum OPN levels were determined in a prospective, observational study design. Survival analysis was performed using Kaplan-Meier curves, and multivariate Cox proportional hazards regression was used to analyze independent risk factors of mortality. Serum OPN was significantly higher in HBV-ACLF patients compared with patients with chronic hepatitis B and healthy controls (both P<0.01), and furthermore, was higher in those patients who succumbed to HBV-ACLF compared with surviving patients (P<0.05). OPN level positively correlated with total bilirubin (r=0.554, P<0.001), Model for End-Stage Liver Disease (MELD) score (r=0.234, P=0.038), MELD-Na score (r=0.379, P=0.005) and monocyte count (r=0.282, P=0.039), and OPN was an independent risk factor for 90-day mortality in ACLF (P=0.021, odds ratio=1.104, 95% confidence interval: 1.003-1.116). Furthermore, ACLF patients were stratified into three groups according to serum OPN levels (low mortality risk: <6,135 ng/ml; intermediate risk: 6,135-9,043 ng/ml; and high risk: >9,043 ng/ml), for which the 90-day mortality rates were 27.78 (5/18), 52.94 (9/17) and 73.68% (14/19), respectively, and those in the high risk had a poorer prognosis compared with the low risk group (P=0.009). In conclusion, serum OPN may be an independent risk factor associated with HBV-ACLF prognosis.