目的 为中草药肝损伤(HILI)的临床诊断提供基于模块化证据链的路线图.方法 分析中草药应用与肝损伤发生的时序关系、中草药自身相关肝毒性信息、合并用药情况的评估及非药物性肝损伤因素的排查等4大模块信息,并进行证据链的逻辑组合.结果及结论 HILI的临床诊断原则与现代药(化学药和生物医药)相似,但具有自身的特点和难点.在阐述中草药与肝损伤时序关系多样性的基础上,对中草药相关肝毒性、合并用药肝毒性及其他肝损伤病因的存在情况进行了多维评估,构建了基于完整证据链的HILI临床诊断路线图.罗素优克福因果关系评估法(RUCAM)量表对HILI的诊断有参考价值,改良电子化因果关系评估法(RECAM)量表对HILI的诊断价值有待在真实世界临床进一步论证,必要时可借助结构化专家观点程序(SEOP)确认诊断;肝活检病理组织学的某些病变特点有助于明确HILI的诊断;HILI相关生物标志物有待深入探索.

In March 2022, EASL released a new version of the clinical practice guidelines on haemochromatosis. Haemochromatosis is characterized by elevated transferrin saturation (TSAT) and progressive iron overload mainly involving the liver, and early diagnosis and venesection can prevent liver cirrhosis, hepatocellular carcinoma, diabetes, arthritis, and other complications. For patients with p.Cys282Tyr homozygous mutation of the hemochromatosis gene HFE, haemochromatosis can be diagnosed if serum iron parameters show TSAT ＞45% and ferritin ＞200 μg/L in female patients, or TSAT ＞50% and ferritin ＞300 μg/L in male patients and postmenopausal female patients. If a patient has elevated TSAT and ferritin and belongs to other HFE genotypes, magnetic resonance or liver biopsy is needed to confirm iron overload in the liver. Liver fibrosis stage and damage to other organs should be carefully assessed at the time of diagnosis, which will help to determine management strategies. Hepatocellular carcinoma should be screened for patients with progressive liver fibrosis. The goal of venesection is to achieve ferritin ＜50 μg/L during the induction stage and ferritin ＜100 μg/L during the maintenance stage.

目的 评估牛磺熊去氧胆酸联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝病(NAFLD)的疗效和安全性.方法 186例N A FLD患者分为两组,A组患者给予口服牛磺熊去氧胆酸、多烯磷脂酰胆碱治疗,B组给与口服谷胱甘肽、多烯磷脂酰胆碱治疗,疗程24周,比较两组患者肝功能、血脂、CAP值.结果 A组ALT、AST、GGT、ALP、TC、TG、CAP值基线水平分别为:(102.5±28.5)U/L、(80.1±22.4)U/L、(148.2±36.9)U/L、(151.3±32.5)U/L、(7.6±1.9)mmol/L、(3.4±1.3)mmol/L、(288.7±35.4)dB/m,治疗12周为(74.4±24.6)U/L、(61.6±19.5)U/L、(97.4±29.5)U/L、(110.6±25.3)U/L、(6.2±1.7)mmol/L、(2.5±1.1)mmol/L、(259.4±32.2)dB/m,治疗24周为(46.3±19.7)U/L、(42.2±16.7)U/L、(63.7±21.8)U/L、(82.4±19.7)U/L、(5.0±1.4)mmol/L、(1.7±0.9)mmol/L、(241.7±29.4)dB/m,治疗12、24周,ALT、AST、GGT、ALP、TC、TG、CAP值均低于基线水平(P<0.05).治疗12周,A组ALT、AST、GGT、ALP、CAP值低于B组(P<0.05),TC、TG值差异无统计学意义;治疗24周,A组ALT、AST、GGT、ALP、TC、TG、CAP值低于B组(P<0.05).治疗过程中,A组患者有4例在治疗初期出现轻微胃部隐痛、恶心不适,B组有3例出现稀便、轻微纳差症状.结论 牛磺熊去氧胆酸联合多烯磷脂酰胆碱可有效改善NAFLD患者的肝功,降低血脂和CAP值,安全性良好.

目的 了解Crigler-Najjar综合征Ⅱ型的遗传特点及诊断方法.方法 收集1例Crigler-Najjar综合征Ⅱ型患者的病史资料、肝脏生化、影像学结果、肝脏病理资料及本人与父母的UGT1A1的基因测序结果.结果 Crigler-Najjar综合征Ⅱ型患者的胆红素升高通常大于5倍正常值上限,为间接胆红素明显升高,ALT、AST均正常,病理未见肝细胞炎症坏死,患者为UGT1A1的基因检测示第5外显子c.1456T>G(p.Tyr486Asp)的纯合突变,其父母均为该突变的杂合子.苯巴比妥诱导治疗有效.结论 c.1456T>G(p.Tyr486Asp)的基因突变为本例患者及其家系的致病基因,患者为常染色体隐性遗传性疾病,表现为间接胆红素明显升高,肝脏无炎症损伤,苯巴比妥诱导有效.

目的 比较RACE法和Sansure法检测核苷(酸)类似物经治和初治慢性乙型肝炎患者HBV RNA定量值的相关性和一致性.方法 纳入南方医科大学南方医院门诊随访的慢性乙型肝炎患者并收集患者血清学、病毒学和生化数据.采集患者血清分别用RACE法和Sansure法检测HBV RNA水平,分析两者检测值的相关性和一致性.结果 共入组101例慢性乙型肝炎患者,其中接受核苷(酸)类似物治疗62例,未曾接受核苷(酸)类似物治疗39例.治疗和未治疗组的HBsAg和HBV DNA水平存在显著差异,HBV RNA水平差异有统计学意义.两种方法相比,RACE法比Sansure法检测到的阳性患者更多(60/101和56/101),平均检测值更高(3.16和2.53 lg拷贝/mL).HBV DNA水平与HBV RNA水平在治疗组没有相关性(RACE法R2=0.4406,Sansure法R2=0.5081),在未治疗组显著相关(RACE法R2=0.8448,Sansure法R2=0.8667).RACE法和Sansure法HBV RNA检测值显著相关(R2=0.8740);此外,两种HBV RNA检测方法Bland-Altman分析显示,95％ 一致性界限的范围较窄(在治疗组为-1.789～0.22 lg拷贝/mL,在未治疗组为-2.25～0.53 lg拷贝/mL);以RACE法为基准,Sansure法的偏差在治疗组为-0.78 lg拷贝/mL,在未治疗组为-0.86 lg拷贝/mL.两种方法线性回归后方程:Y(Sansure法)=0.9189X(RACE法)-0.3754.结论 两种HBV RNA检测方法的相关性显著,一致性较好,可用线性回归方程互算;两种HBV RNA检测方法均可有效弥补血清HBV DNA检测对指导慢性乙型肝炎临床诊治方面的不足.

目的 通过比较急性/亚急性肝衰竭和慢加急性/亚急性肝衰竭患者血清肌酐(serum creatinine,Scr)、胱抑素C(cystatin C,Cyc)及基于多种公式计算的估算肾小球滤过率(estimated glomerular fi ltration rate,eGFR),优化筛选适合此类患者的肾功能评估指标.方法 回顾性分析2011年1月—2018年5月符合急性/亚急性肝衰竭(Ⅰ组)或慢加急性/亚急性肝衰竭(Ⅱ组,又分ⅡA、ⅡB、ⅡC组)诊断标准的210例肝衰竭患者的临床资料,以213例健康体检者为对照组,比较各组Scr、Cyc及9种eGFR计算公式在肝衰竭患者及对照组的组间和组内差异.结果 Ⅱ组Scr和Cyc水平显著高于对照组(P均<0.05);I组Cyc水平显著高于对照组(P<0.05),而2组间Scr水平比较,差异无统计学意义(P>0.05).I、II组内eGFR4、eGFR5、eGFR10及eGFR7的异常率最低值分别为100％、80.00％、96.44％及60.00％,对照组内的异常率最低值分别为100％、25.82％、70.89％及10.33％.与eGFR1和eGFR2相比,eGFR3的假正常率最高,最高达48.81％.血清Cyc及Scr均正常时,eGFR6假降低率较其他eGFR均高,最高达65.24％.结论 对于肝衰竭患者的肾功能评估,血清Cyc较Scr更为可靠.各种eGFR公式中,以基于Scr联合Cyc的公式eGFR11和基于Scr的eGFR2及eGFR1较为合适,尤其是eGFR11.

目的:考察我国药物性肝损伤(drug-induced liver injury,DILI)文献数据的质量和存在问题,为规范DILI的诊治和改进DILI临床研究提供依据.方法:以2008-2017年间江苏省DILI文献为切入点,在万方、中国知网(CNKI)和PubMed数据库中使用“药物性肝损伤”和“drug-induced liver injury”及相关诊断名词检索和筛查江苏省发表的DILI文献,对文献类型、诊断方法和标准的异同、可疑伤肝药物等进行评估分析,考察数据质量,分析存在的问题.结果:共纳入符合分析条件的文献89篇,涉及5 289例患者.19篇文章采用R值进行临床分型,仅4篇使用了正确的R值计算方法.肝损伤药物涉及抗结核药物、中药、抗肿瘤药物、抗感染药物、精神类药物、解热镇痛药和心血管系统药物等,但多缺乏药物与肝损伤之间相关性的精准分析.结论:江苏省引起DILI的药物种类复杂,DILI文献循证医学级别总体较低,诊断方法和标准存在较大差异,亟需在规范统一的方法和标准下进行DILI临床研究.

肝炎相关再生障碍性贫血(hepatitis-associated aplastic anemia,HAAA)是一种肝炎相关的骨髓衰竭综合征.发病率低,欧洲血液和骨髓移植小组(EBMT)报道其发病占同期再生障碍性贫血(aplastic anemia,AA)患者的5.4％左右[1].该病发病急骤,进展快,病死率高[2].单纯红细胞再生障碍性贫血(pure red cell aplasia,PRCA)是一种少见的特殊类型的AA[3].

In patients with liver disease such as viral hepatitis and liver cirrhosis, renal injury and renal insufficiency can be generally classified as acute kidney injury (AKI), chronic kidney disease, and acute-on-chronic nephropathy. AKI can be classified as stage 1 (risk stage), stage 2 (injury stage), and stage 3 (failure stage). Traditionally hepatorenal syndrome is classified as types Ⅰ and Ⅱ, and in recent years, type Ⅲ hepatorenal syndrome with organic renal injury has been proposed. Hepatorenal disorder(HRD) is used to describe any renal disease which occurs in patients with liver cirrhosis. At present, sensitive and accurate biochemical parameters used to evaluate renal function in patients with liver disease in clinical practice include estimated glomerular filtration rate, increase in serum creatinine within unit time, and serum cystatin C level, and urinary microalbumin level also plays an important role in the early diagnosis of nephropathy. Causes of liver disease, severity, complications including infection, nutritional status, therapeutic drugs, and underlying nephropathy may be associated with renal injury and renal insufficiency in patients with liver disease and should be differentiated.

目的:探讨不同体重指数(BMI)与胃食管反流病(GERD)的临床关系.方法:将GERD患者分为正常组、超重组及肥胖组,比较各组年龄、性别、症状计分、食管炎发生情况及PPI治疗效果.结果:三组性别构成及PPI疗效无明显差异;随着BMI的增加,年龄、食管刺激计分、总计分、食管外症状计分及食管外症状发生率、食管炎及重症食管炎发生率均呈上升趋势,反流计分呈下降趋势(P＜0.05).结论:超重、肥胖的GERD患者胸痛胃灼热较明显,更易出现食管外症状且症状较重,更易合并食管炎及重症食管炎.

Objective To compare the therapeutic efficacy between Fuzheng Huayu capsule and AnLuo HuaXian pill.Methods Ninety-nine patients with liver fibrosis were randomly divided into two groups.Group one received Fuzheng Huayu capsule treatment and group two received AnLuo HuaXian pill treatment.All patients received treatment for 12 months.Fibroscan value,liver fibrosis indexes,color ultrasound images and liver pathology were measured before and after treatment.Results After treatment,the Fibroscan value of Fuzheng Huayu capsule group was 8.25 KPa, liver fibrosis indexes were HA: 143.4 ng/mL、LN:95.9 ng/mL、PC-III: 109.3 ng/mL、Ⅳ-C:72.1 ng/mL, respectively.The inside diameter of portal vein was 10.13 mm and thickness of spleen was 38.40 mm.The Fibroscan value of AnLuo HuaXian pill group was 13.04 kPa,liver fibrosis indexes were HA:208.7 ng/mL、LN:155.5 ng/mL、PC-III:110.0 ng/mL、Ⅳ-C:117.5 ng/mL,respectively.The inside diameter of portal vein was 12.61 mm and thickness of spleen was 45.01 mm.There were significant differences in the indexes above between the two groups (P <0.05 ), What is more,Fuzheng Huayu capsule showed a better effect on improving the fibrosis grades (P <0.05).Conclusion Fuzheng Huayu capsule is more effective for liver fibrosis treatment than AnLuo HuaXian pill.

OBJECTIVE:To analyze the etiology, clinical features and prognosis of liver injuries caused by different drugs.METHODS:The types of suspected drugs related to liver injury, clinical manifestations, liver biochemical parameters, clinical outcomes and other associated data were retrospectively assessed for 140 patients with drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method (RUCAM) was used to assess the causality between drugs and liver injury.RESULTS:The most prevalent agents inducing DILI were Chinese traditional drugs (62.1%), followed by antipyretic analgesic drugs (10%) and antibiotics (5%). The ratio of male to female patients in the study cohort was 1:1.69, with 71 of the total patients (50.7%) being between the ages of 40 and 60 years-old. The RUCAM scale was not less than 3 points for any of the patients.In general, the clinical manifestations and biochemical results were not specific. The percentages of hepatocellular injury type, cholestatic injury type and mixed injury type were 51.4%, 30.7% and 17.9% respectively. The median age of patients with cholestatic liver injury was 55.6 years, which was older than that of patients with hepatocellular injury (47.1 years) or mixed injury (49.9 years).CONCLUSION:Although antipyretic analgesics and antibiotics are considered as common drugs that can induce DILI, Chinese traditional drugs have emerged as another important group of liver injurious agents. Cholestatic DILI was found to occur more often in elderly patients than in younger patients.

目的：研究合并食管裂孔疝（HH）的胃食管反流病（GERD）患者的临床特征，为 HH 及 GERD的临床诊断和治疗提供帮助。方法根据蒙特利尔标准、中国胃食管反流病共识意见等，将胃食管反流病患者分为合并 HH组和不合并 HH组，通过内镜检查、问卷调查以及质子泵抑制剂治疗后随访，比较两组患者年龄、性别、BM I、食管炎发生情况、反流症状计分、焦虑抑郁评分以及质子泵抑制剂（PPI）治疗效果的差异。结果两组患者性别、年龄及BMI无统计学差异（P＞0.05）。合并 HH 组较不合并 HH 组，反流症状总计分高（P＜0.05），食管外症状发生率高（P＜0.05），食管外症状计分高（P＜0.05），反酸烧心症状计分无差异（P＞0.05），反流性食管炎发生率升高（P＜0.05），重度食管炎比率高（P＜0.05），焦虑及抑郁评分较高（P＜0.05），焦虑及抑郁状态发生率升高（P＜0.05），PPI治疗效果差（P＜0.05）。结论合并 HH的GERD患者与无 HH的 GERD 患者相比，易出现食管外症状，症状总计分及食管外症状计分明显升高，合并反流性食管炎比例高，PPI治疗有效率低，焦虑抑郁评分均较高，易合并焦虑抑郁状态。

患者,男性,54岁,因上腹部持续隐痛不适2月余于2012年5月9日入院.病程中患者偶有上腹部饱胀不适,食欲较前稍减退,无发热,无恶心、呕吐,无腹泻、便血.外院腹部B超提示肝内多发占位,我院门诊查血清AFP 1 306.69 μg/L(正常参考值0～20 μg/L).上腹部CT平扫+增强(见图1):肝内多发低密度影,部分边缘欠清;肝胃间隙内类圆形软组织密度影,内似有钙化样密度,与胰体及胃分界欠清,考虑占位性病变;右侧腹壁类圆形低密度影,脂肪瘤可能性大.否认既往病毒性肝炎、酒精性肝病及其他肝损害疾病史.

一、病史摘要 患者,男性,60岁,江苏东台人,农民,因"发现乙肝表面抗原阳性20余年,肝占位4 d"于2010年7月17日入院.患者于20余年前即发现乙型肝炎病毒表面抗原(HBsAg)阳性,长期未注意监测乙型肝炎病毒学指标及肝功能等的变化.近1年来轻度间断乏力,无畏寒、发热,无明显恶心、呕吐、厌油,无腹痛、腹胀、腹泻、便血,无尿黄异常加深.

胃食管反流病(gastroesophageal reflux disease,GERD)是指胃内容物反流入食管引起不适症状和(或)并发症的一种疾病,包括食管症状(反流症状属于食管症状)以及食管外症状两大类[1].本研究对轻度和重度反流症状的GERD患者的人口学特征、生活质量、精神心理状态等资料进行了调查,旨在为深入了解GERD并能为临床治疗提供一些帮助.

干扰素（IFN）联合利巴韦林（RBV）是当前丙型病毒性肝炎的主要治疗方案,流感样症状、骨髓抑制、食欲减退、皮疹、诱发抑郁及自身免疫性疾病等是其主要不良反应。然而,IFN/RBV治疗诱发横纹肌溶解症

因尿毒症而接受血液透析治疗、伴有多种并发症、拟择期进行肾移植术、有丙型肝炎病毒(HCV)活跃复制的患者,其抗病毒治疗既是必需的,也是临床一大治疗难点,其抗病毒方案的优化有待探索,疗程中各种并发症的特点、依从性影响因素、疗效等有待深入认识和积累经验.我科最近成功完成1例尿毒症合并肾性高血压、眼底出血、骨髓抑制及其他多种并发症的丙型肝炎患者的抗病毒治疗,取得良好病毒学、血清学、生物化学应答,现将治疗体会和疗效做一总结。

Objective To analyze clinical characteristics of gastroesophageal reflux disease(GERD) in aged patients for improvement of diagnosis and treatemcnt. Methods The reflux disease questionnaire was performed in patients diagnosed as GERD based on Montreal definition and classification as well as Rome Ⅲ criteria.All patients were divided into elderly group (≥65 years) and control group(＜65 years). The incidence of hita[ hernia (HH), the frequencies of esophagitis (based on Los Angeles classification), clinical features, and quality of life were compared between two groups. Results There was no difference between two groups in male/female ratio and morbidity of HH(P＞0.05). In comparison with control group, the frequency of esophagitis graded as LC or LD increased and extra-esophageal symptoms were higher in elderly group (P＜ 0.05), but the lower typical symptoms (heartburn and regurgitation) were seen in the elderly group(P＜0.05). The scores of role physical, bodily pain and role emotional were higher in elderly group than those in control group (P＜0.05). There was no significant differences between two groups in physical function, vitality,social functioning, mental health, and general health. Conclusion The elderly GERD patients often have lower score of typical reflux symptoms (heartburn and regurgitation) and high incidence of severer esophagitis, but their quality of life is not significantly influenced.