目的 分析不明原因的慢性血生化异常(NCALBT)患者病因诊断及其肝组织学表现.方法 回顾性分析我院诊治的248 例NCALBT患者的临床资料.所有患者接受肝活检,采用改良Scheuer评分评估.常规检测血生化、血清学和病毒学指标.结果 在248 例NCALBT患者中,诊断药物性肝损伤(DILI)89 例(35.9%),自身免疫性肝病(AILD)67例(27.0%),非酒精性脂肪性肝病(NAFLD)39 例(15.7%),遗传代谢性肝病(IMLD)30 例(12.1%),特发性非硬化性门静脉高压(INCPH)20 例(8.1%)和其他肝病 3 例(1.2%);DILI和AILD患者血生化指标显著高于其他肝病患者(P<0.05);本组168 例(67.8%)NCALBT患者肝组织处于 G2-4/S2-4 状态,即有明显的炎症和纤维化损伤,DILI(61.8%)、AILD(95.5%)、NAFLD(56.4%)、INCPH(65.0%)和其他肝病(100.0%)均以G2-4/S2-4 为主,而IMLD患者肝组织G2-4/S2-4 只占36.7%.结论 NACLBT患者病因以常见病为主,综合血清和组织学检查往往可以明确诊断.

Objective To investigate the risk factors for non－neoplastic portal vein thrombosis（PVT）in patients with liver cirrhosis and related early predictive factors. Methods A total of 50 cirrhotic patients with non－neoplastic PVT who were hospitalized and treated in Department of Hepatology，The Second Hospital of Lanzhou University，from July 1，2021 to June 30，2022 were enrolled as PVT group，and 100 cirrhotic patients without PVT who were treated during the same period of time were randomly selected as control group. Related clinical data were collected. The independent－samples t test was used for comparison of normally distributed continuous data between two groups，and the Mann－Whitney U test was used for comparison of non－normally distributed continuous data between two groups；the chi－square test was used for comparison of categorical data between two groups. A multivariate Logistic regression model analysis was used to investigate the influencing factors for PVT in liver cirrhosis，and the receiver operating characteristic curve was used to evaluate the predictive performance of influencing factors. Results The univariate analysis showed that there were no significant differences between the two groups in the indicators such as protein C，protein S，prothrombin time，international standardized ratio，fibrinogen，white blood cell count，platelet count，and biochemical parameters（all P>0.05），while there were significant differences between the two groups in history of splenectomy，history of endoscopic treatment of esophageal and gastric varices，history of hepatic encephalopathy，administration of non－selective β－blocker（NSBB）， D－dimer， hemoglobin，and triglyceride（all P<0.05）. The multivariate Logistic regression model analysis showed that D－dimer（odds ratio［OR］＝1.120，95% confidence interval［CI］： 1.006－1.246，P＝0.038），history of splenectomy（OR＝9.320，95% CI：2.928－29.665，P<0.001）， history of hepatic encephalopathy（OR＝16.813，95% CI：1.808－156.336，P＝0.013）， and administration of NSBB（OR＝3.203，95% CI：1.020－10.051，P＝0.046） were independent risk factors for PVT. Conclusion Elevated D－dimer，history of splenectomy，history of hepatic encephalopathy，and administration of NSBB are predictive factors for non－neoplastic PVT in patients with liver cirrhosis.

BACKGROUND Mutations that occur in the ABCB4 gene, which encodes multidrug-resistant protein 3, underlie the occurrence of progressive familial intrahepatic cholestasis type 3 (PFIC3). Clinical signs of intrahepatic cholestasis due to gene mutations typically first appear during infancy or childhood. Reports of PFIC3 occurring in adults are rare. CASE SUMMARY This is a case study of a 32-year-old infertile female Chinese patient with a 15-year history of recurrent abnormal liver function. Her primary clinical signs were elevated levels of alkaline phosphatase and γ-glutamyl transpeptidase. Other possible reasons for liver dysfunction were eliminated in this patient, resulting in a diagnosis of PFIC3. The diagnosis was confirmed using gene detection and histological analyses. Assessments using genetic sequencing analysis indicated the presence of two novel heterozygous mutations in the ABCB4 gene, namely, a 2950C>T; p.A984V mutation (exon 24) and a 667A>G; p.I223V mutation (exon 7). After receiving ursodeoxycholic acid (UDCA) treatment, the patient's liver function indices improved, and she successfully became pregnant by in vitro fertilization. However, the patient developed intrahepatic cholestasis of pregnancy in the first trimester. Fortunately, treatment with UDCA was safe and effective. CONCLUSION These novel ABCB4 heterozygous mutations have a variety of clinical phenotypes. Continued follow-up is essential for a comprehensive understanding of PFIC3.

Objective The aim of this study was to investigate the efficacy of switching from entecavir（ETV） or tenofovir（TDF） to other different antiviral therapy in ETV-or TDF-treated chronic hepatitis B（CHB） patients with low-level viraemia（LLV）. Methods A total of 197 patients with CHB who had been treated with ETV or TDF were enrolled in this study and were divided into group A（n=74） continuing ETV or TDF treatment, group B（ n=63） switching to TAF therapy and group C（n= 60） switching to ETV or TDF and peg-IFNα-2 b combination therapy. The regimen lasted for（48±2） weeks. Results At the end of 48 week treatment, the complete virologic response and serum HBeAg negative rates in group C were 90.0% and 41.7%, significantly higher than 16.2% and 5.4%（P＜0.05） in group A or 66.7% and 9.5%（P＜0.05） in group B, and serum ALT normalization rates in group B and group C were 20.6% and 23.3%, significantly higher than 8.1%（P＜0.05） in group A; serum HBsAg level in group C was 3.0（2.8, 3.4）lgIU/ml, significantly lower than [3.3（2.9, 3.9）lgIU/ml, P＜0.05] in group A or [3.4（3.3, 3.8）lgIU/ml, P＜0.05] in group B, serum HBeAg level was 0.1（-0.7, 0.0）lgIU/ml, significantly lower than [0.6（-0.6, 1.8） lgIU/ml, P＜0.05] in group A or [0.6（-0.3, 1.8）lgIU/ml, P＜0.05] in group B, and serum HBV DNA load was 1.3（1.3, 1.3）lgIU/ml, significantly lower than [1.7（1.3, 2.0）lgIU/ml, P＜0.05] in group A or [1.6（1.3, 1.4）lgIU/ml, P＜0.05] in group B; the LSMs in group B and group C were 6.4（4.3, 8.4） kPa and 6.2（4.2, 7.7） kPa, both significantly lower than [8.6（5.2, 10.7） kPa, P＜0.05] in group A, and serum ALT levels in the three groups were not significantly different（P＞0.05）. Conclusion The switch to TAF or combined with peg-IFNα-2 b therapy in ETV-or TDF-treated patients with LLV might benefit for further virologic and even serologic response, and warrants clinical investigation.

目的 探讨肝硬度检测(LSM)和吲哚菁绿15分钟血浆滞留率(ICGR15)对慢性乙型肝炎(CHB)患者肝组织病理学损伤的预测价值.方法 2016年7月 ～2018年11月我院诊治的血清ALT正常或<2倍正常值上限(ULN)的CHB患者,接受肝活检行METAVIR评分,依据评分分为非进展期和进展期.使用日本光电工业株式会社生产的DDG-3300K脉动脉式色素浓度分析仪检测ICGR15,使用Echosens 502肝脏瞬时弹性成像仪检测LSM.应用受试者工作特征曲线(ROC)下面积(AUC)评估指标预测肝组织病变进展的效能.结果 经肝组织学检查,发现肝组织进展期196例,非进展期113例,两组年龄、性别、血小板计数、血清HBeAg阳性是否阳性和血清ALT水平无显著性差异(P>0.05),而进展期患者血清HBV DNA、ALB、LSM和ICGR15与非进展期患者比,差异显著(P<0.05);LSM、ICGR15及LSM-ICGR15联合模型与METAVIR评分均存在正相关性(P值均<0.05);ROC曲线分析显示LSM、ICGR15和LSM-ICGR15联合模型预测肝组织进展期的曲线下面积(AUC)分别为0.655、0.617和0.686.当以LSM等于7.35 kPa为截断点,其诊断肝组织进展期的灵敏度为55.4％,特异性为68.1％,当以ICGR15等于4.15％为截断点,其诊断肝组织进展期的灵敏度为34.4％,特异性为90.3％,以LSM-ICGR15联合预测的灵敏度为59.5％,特异性为78.8％.结论 应用LSM、ICG-R15或者两者联合预测血清ALT正常或轻度升高的CHB患者肝组织病变进展有一定的价值,值得临床进一步研究.

慢性乙型肝炎(CHB)依然是我国乃至全球的严重公共卫生问题之一.过去数十年中乙型肝炎e抗原(HBeAg)阴性CHB的患病率不断上升,且患者发病更急,发展为肝硬化的速度更快,因此对HBeAg阴性CHB患者需给予更积极的抗病毒治疗.与单药治疗相比,干扰素联合核苷(酸)类似物对HBsAg的清除率更高,可逆转肝纤维化,更有利于HBeAg阴性患者的预后.本文就HBeAg阴性CHB抗病毒治疗的研究进展作一综述.