Caroli病的临床病理学观察

目的：探讨Caroli病的临床病理特征。方法：复习7例Caroli病全部临床,影像资料和手术记录,对肝脏病变切除标本行病理常规切片、HE染色、光镜观察。结果：本病发病年龄3－62岁,平均38岁,男女比为1：25。临床上以右上腹疼痛为首发症状,2例合并胆管癌、胆囊癌,无1例在术前被确诊。影像学提示肝内胆管有不同程度扩张和纤维化、病理上表现为肝内胆管囊性扩张、上皮增生呈乳头状,伴有胆管周围纤维组织细胞增生、变性和大量炎细胞浸润。结论：Caroli病是少见的生天性肝脏病变,临床易误诊为胆囊炎、胆石症、确诊依赖于病理和影像学检查。     

Elevation of Serum Aminotransferase Levels and Future Risk of Death from External Causes: A Prospective Cohort Study in Korea

Purpose

The association between liver enzymes and death from external causes has not been examined. We investigated the association between serum aminotransferase levels and external-cause mortality in a large prospective cohort study.

Materials and Methods

A total of 142322 subjects of 35-59 years of age who completed baseline examinations in 1990 and 1992 were enrolled. Mortalities were identified using death certificates. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were categorized into quintiles. Sub-distribution hazards ratios and 95% confidence intervals (CIs) were estimated using a competing risks regression model in which deaths from other causes were treated as competing risks.

Results

Of 8808 deaths, 1111 (12.6%) were due to external causes. Injury accounted for 256 deaths, and suicide accounted for 255. After adjusting for covariates, elevated ALT and AST were significantly associated with an increased risk of all external-cause mortalities, as well as suicide and injury. Sub-distribution hazards ratios (95% CIs) of the highest versus the lowest quintiles of serum ALT and AST were, respectively, 1.57 (1.26-1.95) and 1.45 (1.20-1.76) for all external causes, 2.73 (1.68-4.46) and 1.75 (1.15-2.66) for suicide, and 1.79 (1.10-2.90) and 1.85 (1.21-2.82) for injury. The risk of external-cause mortality was also significantly higher in the fourth quintile of ALT (21.6-27.5 IU/L) than in its first quintile.

Conclusion

Elevated aminotransferase levels, even within the normal range, were significantly associated with increased risk of all external-cause mortalities, including suicide, and injury.     

Nephronophthisis due to a novel DCDC2 variant in a patient from African‐Caribbean descent: A case report

Nephronophthisis‐19 (NPHP19) due to truncating mutations in the DCDC2 gene has only been described previously in two patients. We describe a new case in a patient from the island country of Saint Vincent and the Grenadines, in the West Indies. This condition is a renal‐hepatic ciliopathy with phenotypic characteristics that include hepatosplenomegaly, hepatic fibrosis with bile cholestasis, increased kidney echogenicity, and end‐stage renal disease.Here, we report a 13‐year‐old African‐Caribbean female with areas of absence of heterozygosity suggesting parental consanguinity or identity by decent due to the founder effect, harboring a novel homozygous pathogenic variant (c.383C>G, p.S128*) in exon 3 of DCDC2. Her phenotype is consistent with the other two known cases of NPHP19, however, this patient also presents psychiatric symptoms. These psychiatric findings were not present in the first two documented cases, and we discuss possible etiologies of these symptoms. Our study presents the first patient from the West Indies with NPHP19, and also highlights the need to investigate the frequency of pathogenic variants within at‐risk populations.     

Turner syndrome may be associated with hepatic adenoma

Turner syndrome, caused by complete or partial loss of an X chromosome, is marked by a range of clinical manifestations including short stature, cardiovascular and renal disease. Hepatic involvement is an increasingly recognized concern. Steatosis and elevated transaminases are commonly observed in this population, but case reports have also described hepatic adenoma. Hepatic adenomas are rare, occurring in one per million people in the general population. They are typically benign but malignant transformation or rupture can occur. We sought to investigate whether Turner syndrome is associated with hepatic adenoma. Patients with Turner syndrome encountered at a single, academic institution between 2006 and 2020 were identified using ICD-10 codes and demographic, medication, laboratory, and imaging data were analyzed. Of the 228 patients identified, 46.9% had liver function testing, which were abnormal in 48.6%. Five of 77 patients with hepatic imaging had abnormalities. Three patients (1.3%) had hepatic adenoma, one after presenting in hemorrhagic shock due to rupture. These findings suggest that patients with Turner syndrome may have an increased risk for developing hepatic adenoma. Annual monitoring of liver function tests is already recommended in Turner syndrome. The addition of periodic hepatic imaging may also be beneficial.     

Storage of lipid droplets in and production of extracellular matrix by hepatic stellate cells (vitamin A‐storing cells) in Long‐Evans cinnamon‐like colored (LEC) rats

LEC rats spontaneously develop hepatocellular carcinoma with cholangiofibrosis after chronic hepatitis, but the mechanism of development of the hepatic injury is not clear. To investigate the role of hepatic stellate cells in induction or suppression of hepatic fibrosis, we morphologically examined the liver of LEC rats. Accumulation of copper was analyzed by the Danscher‐Timm's sulfide‐silver method. Histopathological changes were evaluated by hematoxylin and eosin staining, and by Masson's trichrome method. Activated stellate cells were identified by immunostaining method for α‐smooth muscle actin. Cytological alterations of the stellate cells were investigated by transmission electron microscopy. To evaluate the lipid content in the stellate cells, we analyzed the area of lipid droplets of the cells by morphometric analysis. Also for evaluation of the changes in the number of stellate cells, the numbers of nucleated stellate cells and parenchymal cells were counted and statistically analyzed. Hepatic parenchymal cells showed excessive accumulation of copper at 5 weeks of age. Submassive necrosis was observed at 19 weeks of age. The liver of LEC rats 1.5 years of age showed cholangiofibrosis and subcellular injury of hepatic parenchymal cells. However, no diffuse hepatic fibrosis was observed in the liver, and hepatic stellate cells around the regions of cholangiofibrosis were negative for α‐smooth muscle actin. The area of lipid droplets of a stellate cell in the liver of LEC rats was 1.6 to 1.8 times as large as that of normal Wistar rats. The hepatic stellate cells did not participate in the accumulation of collagen fibers around themselves when the cells contained a large amount of vitamin A‐lipid droplets, even though the development of hepatic lesions was in progress. Our present data are consistent with our previous hypothesis that there is an antagonistic relationship between the storage of vitamin A and the production of collagen in stellate cells. Anat Rec 258:338–348, 2000. © 2000 Wiley‐Liss, Inc.     

Gastrointestinal and hepatic abnormalities in patients with confirmed COVID‐19: A systematic review and meta‐analysis

Although not common, gastrointestinal and liver symptoms have reportedly been the initial presentation of coronavirus disease‐2019 (COVID‐19) in a large group of patients. Therefore, knowing the frequency and characteristics of these manifestations of COVID‐19 is important for both clinicians and health policy makers. A systematic review and meta‐analysis of the available data on the gastrointestinal and liver manifestations of patients with COVID‐19 was performed. PubMed and Scopus databases and Google Scholar search engine were searched for published and unpublished preprint articles up to 10 April 2020. Original studies providing information on clinical digestive symptoms or biomarkers of liver function in patients with polymerase chain reaction confirmed diagnosis of COVID‐19 were included. After quality appraisal, data were extracted. Prevalence data from individual studies were pooled using a random‐effects model. Overall, 67 studies were included in this systematic review and meta‐analysis, comprising a pooled population of 13 251 patients with confirmed COVID‐19. The most common gastrointestinal symptoms were anorexia (10.2%, 95% confidence interval [CI] = 6.2%‐16.4%), diarrhea (8.4%, 95% CI = 6.2%‐11.2%), and nausea (5.7%, 95% CI = 3.7%‐8.6%), respectively. Decreased albumin levels (39.8%, 95% CI = 15.3%‐70.8%), increased aspartate aminotransferase (22.8%, 95% CI = 18.1%‐28.4%), and alanine aminotransferase (20.6%, 95% CI = 16.7%‐25.1%) were common hepatic findings. After adjusting for preexisting gastrointestinal (5.9%) and liver diseases (4.2%), the most common gastrointestinal findings were diarrhea (8.7%, 95% CI = 5.4%‐13.9%), anorexia (8.0%, 95% CI = 3.0%‐19.8%), and nausea (5.1%, 95% CI = 2.2%‐14.3%). Gastrointestinal and liver manifestations are not rare in patients with COVID‐19, but their prevalence might be affected by preexisting diseases. Diarrhea and mild liver abnormalities seem to be relatively common in COVID‐19, regardless of comorbidities     

Vitronectin deficiency attenuates hepatic fibrosis in a non‐alcoholic steatohepatitis‐induced mouse model

Vitronectin (VN), an extracellular matrix protein, is a promising immune biomarker of non‐alcoholic steatohepatitis (NASH); however, its precise function remains unclear. This study investigated how VN deficiency contributes to the development of NASH. Towards this aim, wild‐type (WT) and VN?/? mice were fed with a choline‐deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) for 6 and 10 weeks to induce NASH, and the livers were isolated. In WT mice fed with CDAHFD for 6 and 10 weeks, the expression of Vn mRNA and protein was up‐regulated compared with that in mice fed with the MF control diet, indicating that VN is regulated in NASH condition. VN?/? mice showed decreased picrosirius red staining in the liver area and Col1a2 mRNA expression levels, compared with WT mice, indicating that the severity of hepatic fibrosis is attenuated in the CDAHFD‐fed VN?/? mice. In addition, VN deficiency did not affect the area of lipid droplets in haematoxylin‐eosin staining and the mRNA expression levels of fatty acid synthases, Srebp, Acc and Fas in the CDAHFD‐fed mice. Moreover, VN deficiency decreased the inflammation score and the mRNA expression levels of Cd11b and F4/80, macrophage markers, as well as Tnf‐α and Il‐1β, inflammatory cytokines in the CDAHFD‐fed mice. Furthermore, VN deficiency decreased the protein and mRNA expression levels of α‐smooth muscle actin in the CDAHFD‐fed mice, suggesting that VN deficiency inhibits the activation of hepatic stellate cells (HSCs). Our findings indicate that VN contributes to the development of fibrosis in the NASH model mice via modulation of the inflammatory reaction and activation of HSCs.     

Hepatic morphology and histochemistry of Wilson''s disease presenting as fulminant hepatic failure: a study of 11 cases

Eleven cases of Wilson's disease presenting as fulminant hepatic failure were analysed retrospectively to determine the specificity or otherwise of the histological findings. All cases were cirrhotic, eight with a micronodular pattern. There was marked parenchymal collapse with ductular proliferation and mild inflammation. Other features included cholestasis, hepatocyte necrosis, microvesicular fat and nuclear vacuolation. Orcein staining demonstrated copper-associated protein in the periphery of cirrhotic nodules in all cases and also variably within nodules in eight cases. Copper was demonstrable by the rhodanine method in similar locations but the staining reaction was qualitatively weaker in all cases. Characteristically, there was staining of both parenchymal and mononuclear phagocytic cells. This triad of cirrhosis, strong copper-associated protein deposition and copper positivity was not present in a control group of 20 cases of fulminant hepatic failure of other aetiology and with a similar clinical presentation. It is concluded that in the clinical context of fulminant hepatitis the presence of cirrhosis should raise the suspicion of Wilson's disease and that, with routinely processed and stained tissue, including autopsy tissue, the diagnosis can be made histologically.     

慢性肝病患者免疫状态对HBV血清学标志物表达模式的影响

目的探讨慢性肝病患者免疫状态对乙肝病毒血清学标志物（HBVM）表达模式的影响。方法以确诊的慢性肝病患者包括慢性病毒性乙型肝炎轻、中、重度、慢性重型乙型肝炎、肝炎肝硬化和原发性肝细胞癌患者作为研究对象,采用ELISA法对研究对象的乙肝病毒血清学标志物（HBsAg、HBsAb、HBeAg、HBeAb和HBcAb）、IL-2、IL-10进行检测,采用流式细胞仪进行CD4＋、CD8＋T细胞分析,应用两样本均数比较的统计学方法进行统计学分析。结果慢性肝病患者共有3种HBVM表达模式：大三阳（HBsAg、HBeAg和HBcAb阳性）、小三阳（HBsAg、HBeAb和HBcAb阳性）和小二阳（HBsAg和HBcAb阳性）模式。大三阳、小三阳和小二阳表达模式的阳性率分别为31.09%、57.14%和11.77%;小三阳表达模式组的CD8＋细胞显著低于大三阳表达模式组（P〈0.05）,其余各组间的IL-2、IL-10、CD4＋、CD8＋T细胞水平虽有差别但差异无统计学意义（P〉0.05）。结论慢性肝病患者小三阳表达模式多见;患者血中CD8＋细胞水平低可能有助于慢性肝病患者HBVM小三阳模式的表达,反之可能有助于HBVM大三阳模式的表达。     

Reconfirmation of the right medial division of the portal venous system of liver

With the development of hepatic surgery and radiology, an increasing amount of researchers have reported discrepancies between the real distribution of the hepatic portal vein branches and Couinaud's segmentation, especially for further division of the right medial division. The present study investigated 25 cadaveric liver dissections and 30 three-dimensional reconstruction images of intrahepatic vessels. The ramifications, course, distribution and quantity of the portal branches were analyzed. An oblique fissure that had few vessels was found among third-order branches of the hepatic portal vein of the right medial division. The right medial division could be redivided into the ventral subsegment and dorsal subsegment by this oblique fissure. A hepatic vein coursed in the oblique fissure between the ventral subsegment and dorsal subsegment. The hepatic vein could serve as an anatomical landmark of the inter-subsegmental plane. This new method of identifying further division of the right medial division is a novel concept providing further information on conventional segmental anatomy.     

Hepatic endometriosis diagnosed by liquid‐based cytology: A Case Report

A 44‐year‐old woman presented to Emergency Department with sudden onset of severe upper abdominal pain. T2‐weighted MRI image showed a large cystic mass with a thickened wall measuring 9.5 × 9.1 × 11.2 cm in the right hepatic lobe. It was radiologically interpreted as a cystic mass with differential diagnosis including echinococcal cyst, biliary cystadenoma, and malignant neoplasm. The cystic mass was intraoperatively aspirated and a liquid‐based cytology preparation (ThinPrep) and a cell block were made. The ThinPrep slides showed three dimensional clusters of epithelioid cells with scant delicate cytoplasm and tissue fragments composed of small stromal cells with round to oval shaped nuclei and a small amount of dense cytoplasm lined by the cuboidal epithelial cells. Occasional ciliated cells and abundant hemosiderin laden macrophages were also present. The cell block showed many tissue fragments containing glands and stroma with associated hemorrhage and hemosiderin laden macrophages, typical of endometrial tissue. Although it is uncommon, hepatic endometriosis should be considered in the differential diagnosis of cystic liver mass in women, especially those with a history of endometriosis or obstetric/gynecologic surgery. Diagn. Cytopathol. 2014;42:441–444. © 2013 Wiley Periodicals, Inc.     

Mesenteric and splenic contributions to portal venous CT perfusion in hepatic diffuse disease

Aim: To investigate the changes and contributions of superior mesenteric venous perfusion (SMVP) and splenic venous perfusion (SpVP) to portal venous CT perfusion in canine model of hepatic diffuse disease. Materials and methods: By selective catheterization in superior mesenteric and splenic arteries respectively after CT perfusion scanning, SMVP and SpVP became available. Sixteen dogs were adopted and induced by carbon tetrachloride after data under normal conditions were collected. After 3, 6, 9 and 12 months from carbon tetrachloride intervention, liver biopsies by puncture or operation were performed after CT perfusion scanning. SMVP and SpVP under different pathologic conditions were compared and analyzed. Results: Three stages of hepatic diffuse lesions were defined according to pathologic changes, namely hepatitis, hepatic fibrosis, and cirrhosis. The number of dogs which survived from each stage was: 16 from normal, 12 from hepatitis, 10 from hepatic fibrosis and 4 from cirrhosis. During this progressive period, SpVP ml/(min·100 ml) declined slightly, but there were no significant differences between different stages (P > 0.05). SMVP ml/(min·100 ml) in stage of normal (64.1 ± 8.1) and hepatic fibrosis (44.4 ± 4.5), normal and cirrhosis (42.6 ± 5.4), hepatitis (61.3 ± 6.4) and hepatic fibrosis, hepatitis and cirrhosis was significantly different, but there was no significant difference of SMVP between normal and hepatitis (P = 0.326) or hepatic fibrosis and cirrhosis (P = 0.668). Conclusions: With our evidence of interventional CT perfusion, it is mesenteric, not splenic, perfusion that might coincide with hepatic portal venous perfusion during the progressive period of hepatic diffuse disease.     

The C-480T hepatic lipase polymorphism is associated with HDL-C but not with risk of coronary heart disease

High-density lipoprotein cholesterol (HDL-C) is a known predictor of coronary heart disease (CHD). Studies have shown that the C-480T polymorphism of the hepatic lipase (HL) gene is predictive of HDL-C; however, its observed relationship with the risk of CHD has been inconsistent. We analysed four biallelic polymorphisms in the HL gene in participants from three independent Western Australian populations. Samples were collected from two cross-sectional studies of 1111 and 4822 community-based subjects assessed for cardiovascular risk factors, and a third sample of 556 subjects with physician-diagnosed CHD. Genotypes were tested for association with plasma lipids and the risk of CHD. All polymorphisms were highly correlated (D' > 0.97, r(2) > 0.90); therefore, only C-480T was analysed. The -480T allele was significantly associated with an increase in HDL-C of between 0.08 and 0.16 mmol/l in all three populations (p < 0.001). No associations with other lipids were observed, nor was an association with CHD in a case-control study of males. The TT genotype was however associated with decreased risk of myocardial infarction among cases (odds ratio = 0.39, 95% confidence interval = 0.19-0.78, p = 0.008). These findings replicate those of previous studies in three independent populations and suggest that the genetic determinants of CHD are complex and cannot be entirely explained through intermediate phenotypes.     

糖原累积病Ⅰa型继发肝腺瘤出血1例报道

目的 分析和总结糖原累积病Ⅰa型继发肝腺瘤破裂出血患者的临床特征。方法 对北京协和医院收治的1例糖原累积病Ⅰa型继发肝腺瘤破裂出血患者临床资料进行报道。结合文献进行分析,对肝腺瘤的概况、分型、病因、诊断及治疗方法做一总结。结果 患者为27岁男性,诊断糖原累积病14年,17岁时出现肝腺瘤,22岁时因持续腹痛、头晕就诊当地医院,诊断腺瘤内出血,行选择性肝动脉栓塞治疗。糖原累积病Ⅰa型继发肝腺瘤好发年龄为青春期,肝腺瘤并发症之一为出血,通过超声、CT等影像学检查可协助诊断,治疗方法多种,包括观察、选择性肝动脉栓塞、射频消融、手术切除、肝移植等。结论 糖原累积病Ⅰa型是一种常染色体隐性遗传病,严重肝腺瘤破裂出血可危及生命,保留通过影像学监测及早发现肝腺瘤并且适当干预可以提高患者的生活治疗,改善预后。     

The role of CD11c(+) hepatic dendritic cells in the induction of innate immune responses

The role of the liver in the initiation and maintenance of tolerance is a critical immune function that involves multiple lineages of immune cells. Included within these populations are liver dendritic cells (DCs). Although there has been significant work on the phenotypic and functional roles of splenic and bone marrow dendritic cells, as well as their subsets, comparable studies in liver have often been difficult. To address this issue we have isolated, from C57BL/6 mice, relatively pure populations of DCs and compared phenotype and function to the data from spleen using flow cytometry, cell sorter assisted purification and culture, morphology by cytospin and May-Giemsa staining, cell cycle progression, antigen uptake, cytokine production and allo-activation potential. natural killer (NK)1.1(-)CD11c(+) liver DC subsets (conventional DCs, T cell receptor (TcR)beta(-)NK1.1(-)CD11c(+)B220(-) and plasmacytoid DCs, TcRbeta(-)NK1.1(-)CD11c(+)B220(+)) efficiently endocytose dextran and produce significant levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-12 p40 in response to Toll-like receptor (TLR) ligands, with responses higher than splenic DCs. There is also a differential capability of hepatic DCs to respond to innate signals. Indeed, CD11c(+) hepatic DCs have a greater capacity to respond to innate stimulation but are less capable of inducing CpG activated-allogeneic T cells. These data suggest that hepatic dendritic cells function as a critical bridge between innate and adaptive immunity and are capable of inducing stronger innate responses with a lower capacity for allo-stimulation than splenic dendritic cells. These properties of liver dendritic cells contribute to their unique role in the induction of tolerance.