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Autoimmune hepatitis

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《医学前沿（英文）》 2015年第9卷第2期页码 187-219 doi: 10.1007/s11684-015-0386-y

摘要：

Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte-specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.

关键词： autoimmune hepatitis autoantibodies diagnosis immunological diseases drug-induced liver injury therapy immunosuppression outcomes hepatocellular carcinoma liver transplantation

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Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-knownliver-restorative herb

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《医学前沿（英文）》 2015年第9卷第4期页码 457-467 doi: 10.1007/s11684-015-0417-8

摘要：

Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury (DILI) in the United States. However, reliable methods to identify the DILI causality of some herbs, such as Heshouwu (dried root of Polygonum multiflorum), remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% (9/40) and 30.6% (45/147) of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% (19/20) of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin (heavy metals, pesticides, and mycotoxins) contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.

关键词： drug-induced liver injury pharmacognosy metabolomics stilbene Polygonum multiflorum Chinese herbal medicine

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Rdh13 deficiency weakens carbon tetrachloride-induced liver injury by regulating Spot14 and Cyp2e1 expression

Xiaofang Cui, Benting Ma, Yan Wang, Yan Chen, Chunling Shen, Ying Kuang, Jian Fei, Lungen Lu, Zhugang Wang

《医学前沿（英文）》 2019年第13卷第1期页码 104-111 doi: 10.1007/s11684-017-0568-x

摘要： Mitochondrion-localized retinol dehydrogenase 13 (Rdh13) is a short-chain dehydrogenase/reductase involved in vitamin A metabolism in both humans and mice. We previously generated knockout mice and showed that Rdh13 deficiency causes severe acute retinal light damage. In this study, considering that Rdh13 is highly expressed in mouse liver, we further evaluated the potential effect of Rdh13 on liver injury induced by carbon tetrachloride (CCl ). Although Rdh13 deficiency showed no significant effect on liver histology and physiological functions under regular culture, the mice displayed an attenuated response to CCl -induced liver injury. Their livers also exhibited less histological changes and contained lower levels of liver-related metabolism enzymes compared with the livers of wild-type (WT) mice. Furthermore, the mice had Rdh13 deficiency and thus their liver cells were protected from apoptosis, and the quantity of their proliferative cells became lower than that in WT after CCl exposure. The ablation of gene decreased the expression levels of thyroid hormone-inducible nuclear protein 14 (Spot14) and cytochrome P450 (Cyp2e1) in the liver, especially after CCl treatment for 48 h. These data suggested that the alleviated liver damage induced by CCl in mice was caused by Cyp2e1 enzymes, which promoted reductive CCl metabolism by altering the status of thyroxine metabolism. This result further implicated Rdh13 as a potential drug target in preventing chemically induced liver injury.

关键词： retinol dehydrogenase 13 carbon tetrachloride acute liver injury Cyp2e1 Spot14

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自体骨髓干细胞移植与归元方联用治疗急慢性肝损伤实验研究

吴理茂,李连达,刘红,宁可永,李贻奎

《中国工程科学》 2004年第6卷第7期页码 34-42

摘要：

研究中药归元方与自体骨髓干细胞移植对急慢性肝损伤的治疗作用。研究方法：用肝脏局部注射乙醇的方法复制急性局限性肝损伤模型，复合因素（CCl₄、乙醇、高脂、低蛋白）刺激复制大鼠肝纤维化模型，通过定量组织学、肝功能检查、免疫组化、肝组织羟脯氨酸含量、损伤或纤维区骨髓干细胞观察等综合评价中药、自体骨髓干细胞移植及两者合用的疗效。结果：归元方与自体骨髓干细胞移植可减小肝损伤区域，改善肝功能，使纤维肝组织表达μPA增强，降低血清ALT，AST，PCⅢ，HA和肝组织羟脯氨酸的含量，改善肝组织肝纤维化评分，骨髓干细胞能在肝损伤、肝纤维化形成环境中存活、增殖，并向肝细胞分化，表达肝脏特异的角蛋白CK18。结论：归元方与自体骨髓干细胞移植对急慢性肝损伤有明确的治疗作用，两者合用可优势互补，协同增效。临床上有良好的应用前景。

关键词：归元方骨髓干细胞自体移植肝损伤肝纤维化

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Glucagon-like peptide-2 exhibits protective effect on hepatic ischemia-reperfusion injury in rats

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《医学前沿（英文）》 2015年第9卷第3期页码 368-373 doi: 10.1007/s11684-015-0403-1

摘要：

Glucagon-like peptide-2 (GLP-2) has potent anti-inflammatory effects and protects against experimental ischemia/reperfusion (I/R) injury in pulmonary, intestinal, and myocardial tissue. However, its protective abilities against I/R injury in the liver are unknown. We investigated the potential role of GLP-2 pretreatment on hepatic I/R injury in rats. A total of 24 rats were randomly divided into three groups (n = 8). The first group was the control group; the second group was the vehicle-treated hepatic ischemia/reperfusion (HIR, vehicle saline-treated) group; and the third group was the GLP-2 pretreated I/R (GLP2-IR) group. Each rat in the third group was intraperitoneally administered 5 μg GLP-2 for 5 d before the procedure. A portal triad was created to induce ischemia with a vascular atraumatic clamp. After 40 min, the clamp was released to initiate hepatic reperfusion for 6 h. Blood samples and tissue specimens from the liver were obtained. Alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels significantly increased in the saline-treated HIR group (P<0.001), whereas GLP-2 pretreatment significantly decreased their levels (P<0.01). Our data suggested that GLP-2 pretreatment may have a protective effect on liver I/R injury. However, dose-response studies are necessary to determine the most effective dose.

关键词： ischemia/reperfusion liver glucagon-like peptide-2 alanine aminotransferase

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利用CES1和DPP-IV的组织残余活性准确评估和追踪特异性肝损伤过程 Article

潘秋莎, 宋培放, 倪振华, 钱星凯, 王安琪, 邹立伟, 刘勇, 王平, 张卫东, 马红, 杨凌

《工程（英文）》 2022年第19卷第12期页码 153-165 doi: 10.1016/j.eng.2021.09.014

摘要：

准确评估和追踪特异性肝损伤及其进程仍然是当前生物标志物研究中的一大挑战。本研究建立了一种回顾追溯验证方法，用以表征α-萘异硫氰酸酯（ANIT）诱导的特异性肝脏胆管损伤后血清标志物与组织标志物之间的互动关系。研究发现羧酸酯酶1（CES1）作为肝内标志物和二肽基肽酶4（DPP-IV）作为肝外标志物可反映肝脏损伤的不同病理生理状态。CES1 和DPP-IV 水平可甄别肝损伤本身和炎症损伤之间的差异。相比之下，常规血清学标志物碱性磷酸酶（ALP）、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）在ANIT诱导损伤后血清和组织水平同时升高，胆汁中胆汁酸水平下降，血清中胆汁酸水平升高，肝内组织中胆汁酸水平升高。尽管血清与组织中γ-谷氨酰基转肽酶（γ-GT）升降水平的变化方向相反，但其持续时间远短于CES1，并迅速恢复到正常水平。在上述生物标志物中，只有CES1 能够明确排除炎症干扰下的肝细胞损伤。CES1 还能准确评估熊去氧胆酸（UDCA；单成分药物）和清肺排毒汤（QFPDD；多组分药物）的抗胆汁淤积作用。研究发现QFPDD和UDCA均能减轻ANIT 诱导的肝损伤。UDCA在促进胆汁排泄方面的效果更强，但其抗损伤和抗炎作用相对较弱，而QFPDD在阻断肝脏炎症和修复肝损伤方面更有效。本文数据强调了联合使用CES1（作为肝内肝损伤标志物）和DPP-IV（作为肝外炎症作用标志物）可准确评估和追踪特异性肝损伤，并可区分肝损伤和炎症性肝损伤的差异。

关键词：羧酸酯酶1 二肽基肽酶4 特异性肝脏损伤标志物来源追溯

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Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center retrospective cohort study

《医学前沿（英文）》 2022年第16卷第1期页码 111-125 doi: 10.1007/s11684-021-0854-5

摘要： The coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (≥245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528–29.523; P <0.001) and coagulation-related biomarker D-dimer (≥0.5 μg/mL, HR= 4.321, 95% CI= 1.443–12.939; P = 0.009) and decreased albumin (<35 g/L, HR= 0.131, 95% CI= 0.048–0.361; P <0.001) and albumin/globulin ratio (<1.5, HR= 0.123, 95% CI= 0.017–0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.

关键词： COVID-19 chronic hepatitis B liver injury coagulation dysfunction

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Bile duct injury repair — earlier is not better

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《医学前沿（英文）》 2015年第9卷第4期页码 508-511 doi: 10.1007/s11684-015-0418-7

摘要：

Bile duct injury is a common complication of cholecystectomy. The timing of bile duct injury repair remains controversial. A recent review conducted in France reported 39% complications and 64% failure after immediate repair in 194 patients compared with 14% complications and 8% failure after late repair in 133 patients. A national review of 139 consecutive early repairs conducted at five hepatopancreaticobiliary centers in Denmark reported 4% mortality, 36% morbidity, and 42 restrictures (30%) at a median follow-up of 102 months, and only 64 patients (46%) demonstrated uneventful short-term and long-term outcomes. Most patients with bile duct injury present with bile leak and sepsis; thus, early repair is not recommended. Percutaneous drainage of bile and endoscopic stenting are the mainstays of treatment of bile leak because they convert acute bile duct injury into a controlled external biliary fistula. The ensuing benign biliary stricture should be repaired by a biliary surgeon after a delay of 4–6 weeks once the external biliary fistula has closed.

关键词： bile duct injury cholecystectomy laparoscopic cholecystectomy

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Experimental study on the efficacy of Fuganling granula on protecting against immunological hepatic injury

Yanli LIU, Rong LIU, Cheng ZHEN, Quanfang GUO, Liping WU, Zhaoxi DING, Yushun BI, Zhiyu LIU

《医学前沿（英文）》 2009年第3卷第1期页码 91-95 doi: 10.1007/s11684-009-0011-z

摘要： To study the efficacy of Fuganling granula (FGL, 复肝灵颗粒) in treating mouse immunological hepatic injury that was caused by Bacille Calmette Guerin (BCG) and lipopolysaccharide (LPS), a total of 60 mice were adopted, among which, 50 mice were given intraperitoneal injection with BCG and LPS to establish an immunological liver injury model and then were randomly divided into 5 groups (10 mice/group): 4 groups received treatment of FGL orally at the doses of 100 mg/kg (high-dosage), 50 mg/kg (middle-dosage), 25 mg/kg (low-dosage) and bifendate orally at the dose of 80 mg/kg, respectively. One group was treated with distilled water orally. The remaining 10 mice were given distilled water intraperitoneally as the normal control group. The indices of thymus, liver and spleen, and the activities of the alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the serum were detected. Compared to the normal rat, the model group’s thymus index decreased significantly. The liver index and spleen index increased significantly. The activities of serum ALT and AST increased significantly (all < 0.01). Compared to the model control group, the group treated with FGL in high-dosage, middle-dosage or low-dosage can decrease the activities of ALT and AST and the group treated with FGL in high-dosage and middle-dosage can increase the thymus index significantly ( < 0.01). This experiment established the immunological liver injury model successfully and found that FGL has a remarkably protective effect on this kind of immunological hepatic injury.

关键词： Fuganling granula immunological liver injury bacille calmette guerin lipopolysaccharide mice

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Partial liver transplantation

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《医学前沿（英文）》 2011年第5卷第1期页码 1-7 doi: 10.1007/s11684-010-0105-7

摘要：

Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.

关键词： partial liver transplantation reduced-size liver transplantation split liver transplantation living donor liver transplantation

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γδ T cells in liver diseases

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《医学前沿（英文）》 2018年第12卷第3期页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要：

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration

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Loss of monocarboxylate transporter 1 aggravates white matter injury after experimental subarachnoid

《医学前沿（英文）》 2021年第15卷第6期页码 887-902 doi: 10.1007/s11684-021-0879-9

摘要： Monocarboxylic acid transporter 1 (MCT1) maintains axonal function by transferring lactic acid from oligodendrocytes to axons. Subarachnoid hemorrhage (SAH) induces white matter injury, but the involvement of MCT1 is unclear. In this study, the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH. At 48 h after SAH, oligodendrocyte MCT1 was significantly reduced, and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function. Motor training after SAH significantly increased the number of ITPR2⁺SOX10⁺ oligodendrocytes and upregulated the level of MCT1, which was positively correlated with the behavioral ability of rats. In addition, miR-29b and miR-124 levels were significantly increased in SAH rats compared with non-SAH rats. Further intervention experiments showed that miR-29b and miR-124 could negatively regulate the level of MCT1. This study confirmed that the loss of MCT1 may be one of the mechanisms of white matter damage after SAH and may be caused by the negative regulation of miR-29b and miR-124. MCT1 may be involved in the neurological improvement of rehabilitation training after SAH.

关键词： microRNAs monocarboxylate transporter 1 motor training subarachnoid hemorrhage white matter injury

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Risk factors of prognosis after acute kidney injury in hospitalized patients

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《医学前沿（英文）》 2017年第11卷第3期页码 393-402 doi: 10.1007/s11684-017-0532-9

摘要：

The risk factors, especially laboratory indicators, of prognosis after acute kidney injury (AKI) remain unclear. We conducted a retrospective survey of Chinese People’s Liberation Army General Hospital from January 1, 2012 to December 31, 2012 according to the AKI diagnosis standard issued by Kidney Disease Improving Global Outcomes. The epidemiological features and factors influencing hospital mortality and renal function recovery were evaluated through logistic regression analysis. Among 77 662 cases of hospitalized patients, 1387 suffered from AKI. The incidence rate and mortality of AKI were 1.79% and 14.56%, respectively. Multivariate logistic regression analysis revealed that high AKI stage, age greater than 80 years, neoplastic disease, low cardiac output, increased white blood cell count, and decreased platelet count and serum albumin levels were the risk factors affecting the mortality of AKI patients. Conversely, body mass index between 28 and 34.9 was a protective factor. Increased AKI stage, tumor disease, post-cardiopulmonary resuscitation, and RRT were the risk factors of renal function recovery upon discharge. In addition to traditional risk factors, white blood cell count, platelet count, albumin, and BMI were the predictors of the mortality of AKI patients. No laboratory indicators were found to be the risk factors of renal function recovery in AKI patients.

关键词： acute kidney injury risk factors prognosis

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NKT cells in liver diseases

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《医学前沿（英文）》 2018年第12卷第3期页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要：

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词： natural killer T cells hepatitis B virus and hepatitis C virus infection autoimmune liver diseases alcoholic liver disease nonalcoholic fatty liver disease hepatocellular carcinoma

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Natural killer cells in liver diseases

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《医学前沿（英文）》 2018年第12卷第3期页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要：

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词： natural killer cell phenotype immune activation immune tolerance liver diseases