Evaluation of autoimmune phenomena in patients with nonalcoholic fatty liver disease on the basis of liver pathology

BACKGROUND Autoimmune phenomena can be used in some patients with nonalcoholic fatty liver disease(NAFLD)in the clinic,but these patients are not autoimmune hepatitis patients.AIM To determine whether autoimmunity is present in patients with NAFLD,this study was performed.METHODS A total of 104 patients with NAFLD diagnosed by liver biopsy at Tianjin Second People’s Hospital between 2019 and 2023 were enrolled.The patients were divided into three groups according to their biopsy results:The NAFL(n=36),nonalcoholic steatohepatitis(n=51),and liver cirrhosis groups(n=17).RESULTS The differences in IgA,an immune marker,among the three groups of patients were statistically significant(P=0.025).In all NAFLD patients,antinuclear antibody and anti-smooth muscle antibody were the most common autoantibodies.The antinuclear antibody detection rate was the highest at 48.1%.The cirrhosis group had the highest autoantibody positivity rate(64.7%).Portal enlargement is also common in NAFLD patients.The rates of positivity for portal lymphoplasmacytic infiltration,small bile duct hyperplasia and interfacial hepatitis were highest in the cirrhosis group;the differences between the cirrhosis group and the other two groups were significant(P<0.05).Hepatocellular rosettes were identified only in the cirrhosis group(11.8%).CONCLUSION Autoimmune phenomena occur in NAFLD patients,especially in patients with NAFLD-related cirrhosis,in whom this phenomenon may be more pronounced.

Hujin Pill′s antisteatosis of rat liver:evaluation of histopathology and ultrastructure

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The relationship between the distribution of HBcAg in liver cells and the pathological manifestations of the liver in 429 HBeAg-positive chronic HBV-infected individuals

Background:The natural history of chronic HBV infection is typically characterized by four stages:the immune tolerance period,the immune clearance period,the immune control period,and the immune escape period.These stages are associated with the distribution of HBcAg in liver cells;however,this relationship remains a topic of broad debate within the field of liver disease.To objectively and quantitatively measure the intracellular distribution of HBcAg,this paper aims to design a method referred to as the“layered evaluation method”and to examine its validation.Methods:The distribution of HBcAg in liver cells is assessed using Image Pro Plus image processing software,along with calculations of cytoplasmic and nuclear positive staining rates.Results:The findings indicate that the highest proportion of patients exhibited a positive cytoplasmic expression rate ranging from 0-2.5%.More than 40% of the total sample was categorized within the 0-2.5% positive nuclear expression range.The HBcAg cytoplasmic positive staining rates were classified into five levels:a cytoplasmic HBcAg positive staining rate of less than 0.05% is designated as level 0,indicating negative expression;a staining rate between 0.05% and 5% is classified as level 1;a rate from 5% to less than 10% is classified as level 2;a rate from 10% to less than 20% is classified as level 3;and a nuclear positivity rate exceeding 20% is classified as level 4.Conclusion:The inflammatory activity grade in these patients was positively correlated with the cytoplasmic distribution of HBcAg.Furthermore,the nuclear distribution rate of HBcAg was significantly higher in the G3 group compared to the other groups.

Psychosocial stress and liver disease status

"Psychosocial stress" is an increasingly common concept in the challenging and highly-demanding modern society of today. Organic response to stress implicates two major components of the stress system, namely the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Stress is anamnestically reported by patients during the course of disease, usually accompanied by a decline in their overall health status. As the mechanisms involving glucocorticoids and catecholamines have been deciphered, and their actions on immune cell function deeper understood, it has become clear that stress has an impact on hepatic inflam-matory response. An increasing number of articles have approached the link between psychosocial stress and the negative evolution of hepatic diseases. This article reviews a number of studies on both human populations and animal models performed in recent years, all linking stress, mainly of psychosocial nature, and the evolution of three important liver-related pathological entities: viral hepatitis, cirrhosis and hepatocellular carcinoma.

Study of heteroserum-induced rat liver fibrosis model and its mechanism

AIM To investigate the morphological changes in the process of heteroserum induced rat liver fibrosis and the mechanism of fibrogenesis of this model. METHODS A model of heteroserum induced rat liver fibrosis was established by intraperitoneal injection of porcine serum. In addition to the observation of the morphological changes of this model, the infiltration of eosinophils and mast cells were measured quantitatively and the deposition of IgG and complement C 3 was detected by immunofluorescence. RESULTS The rat liver fibrosis was induced successfully at the end of the 8th week after the injection of heteroserum. Besides the increase of hepatic stellate cells (HSC) during the process of liver fibrosis, proliferation and activation of primary mesenchyma cells (PMCs) were also found. In the early stage, the infiltration of eosinophils and mast cells was significantly increased and the deposition of IgG and complement C 3 was positive in the portal tracts and septa, while gradually reduced after the injection was stopped. CONCLUSIONS This model is suitable for the research on liver fibrogenesis; the pathogenesis of this model may be related with the allergen induced late phase reaction (LPR) caused by the injection of heteroserum, and the HSCs and the PMCs are important sources of ECM producing cells.

Liver biopsy:complications and risk factors

AIM To study the complications and the risk factors of percutaneous liver biopsy, and to compare the complication rate between the periods of 1987 1993 and 1994 1996. METHODS Medical records of all patients undergoing percutaneous liver biopsy between January 1, 1987 to September 31, 1996 in Songklanagarind Hospital were reviewed retrospectively. RESULTS There were 484 percutaneous liver biopsies performed. The total complication rate was 6 4%, of which 4 5% were due to major bleeding; the death rate was 1 6%. The important risk factors correlated with bleeding complications and deaths were a platelet count of 70×10 9/L or less, a prolonged prothrombin time of >3 seconds over control, or a prolonged activated partial thromboplastin time of >10 seconds over control. Although physician inexperience was not statistically significantly associated with bleeding complications and deaths, there was a reduction of death rate from 2 2% in 1987 1993 to 0% in 1993 1996. This reduction is thought to result from both increased experience of senior staff and increased supervision of residents. CONCLUSIONS Screening of platelet count, prothrombin time, and activated partial thromboplastin time should be done and need to be corrected in case of abnormality before liver biopsy. Percutaneous liver biopsy should be performed or supervised by an expert in gastrointestinal diseases, especially in high risk cases.

Non-imaging-guided fine-needle aspiration of liver lesions:aretrospective study of 279 patients

AIM To determine the value of nonimaging-guided (direct) fine-needle aspiration cytology in diagnosing liver lesions.METHODS Detection by technetium-99m, ultrasound or computed tomographic scanning of the liver was made in 279 patients with 332 aspirations.RESULTS Based on histologic, cytologic and clinical findings, final liver diagnoses were reached in 265 patients, of whom 171 had malignant and 94 benign liver disease. Among the 171 patients with malignant liver disease, the cytologic findings indicated suspected malignancy in 8 patients, suggested definite malignancy in 130, but failed to disclose malignancy in 33 patients. In 93 of the 94 patients with benign liver disease, the cytologic findings were reported as benign, while in one patient the report of malignancy was false. The overall sensitivity, specificity, and positive and negative predictive values for cytologic results were 80.7%, 98.9%, 99.3% and 73.8%, respectively. The diagnostic accuracy of fine-needle aspiration cytology was 87.2%. The only major complication attributable to the procedure consisted of one case of pneumothorax.CONCLUSION Direct fine-needle aspiration of palpable liver mass and blind fine-needle aspiration of non-palpable liver lesions for cytodiagnosis are simple, safe, and cost-effective diagnostic method for evaluating the nature of liver lesions. The aspiration procedure including potential complications could be cut short by early finding of abnormal cells.

Histopathological study of hepatocellular carcinoma after transcatheter hepatic arterial embolization

AIMS To study the histopathological changes in hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS Histopathological analysis was made in 39 cases of liver neoplasms after TAE and 11 cases of liver neoplasms after digital selective angiography (DSA), including pathological type, histological grade, necrotic degree, capsule, times of treatment, injured vessel and lymphocyte infiltration. RESULTS Six cases with 100% necrosis, 14 cases with 30% 95% necrosis, 19 cases with 0% 5% necrosis after TAE and 11 cases without necrosis after DSA were found histologically. The necrosis was related to the pathological type, capsule, injured vessels, but not to the histological grade, time of treatment and lymphocyte infiltration of the liver neoplasms. CONCLUSIONS TAE is an effective therapy for the late stage HCC. The encapsulated HCC is a preferable indicator for TAE.

A comparison between previous and present histologic assessments of chronic hepatitis C viral infections in humans

AIM To compare the previously employed classification of liver histology (minimal, chronic persistent hepatitis, chronic active hepatitis and cirrhosis) with a new classification recently described by Sheuer et al (activity grade and fibrosis stage) in percutaneous liver biopsies from patients with chronic hepatitis C viral infections.METHODS Liver biopsies from 79 untreated patients were reviewed. Anti-HCV testing had been performed by ELISA and confirmed by a recombinant immunoblot assay. With respect to the new classification, all the specimens were evaluated using the Knodell score for activity.RESULTS A good correlation was revealed between the previous and more recent histologic classifications in patients with abnormal liver enzyme tests. However, in 13/ 15 (87%) of patients with normal aminotransferase values, changes were consistent with chronic persistent hepatitis whereas normal activity and no fibrosis were demonstrated by the Sheuer classification.CONCLUSION The old classification is more often misleading but correlates well with the new classification and thereby permits comparisons between historically clinical studies.

Expression of insulin-like growth factor Ⅱ and its receptor in hepatocellular carcinogenesis

INTRODUCTIONInsulin-like growth factor Ⅱ(IGF-Ⅱ) is a mitogenic peptide of 74 kD and is mostly synthesized in fetal liver tissue .IGF-Ⅱ is believed to play an important role in fetal growth and development and is involved in cellular proliferation and differentiation[1-5]. Recently ,several researchers have reported increased expression of the IGF-Ⅱgene in human hepatocellular carcinoma (HCC) and adjacent non-cancerous liver tissues [6-10].

Effects of sera from burn patients on human hepatocytic viscoelasticity

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OPTIMIZATION OF TETRANDRINE TREATMENT IN RAT HEPATIC FIBROSIS MODEL

Objective To optimize the therapeutic dosage of tetrandrine （Tet） in rat hepatic fibrosis roodel. Methods 50 Wistar rats were divided into 5 groups at random including normal control, model control, Tettreated model groups of 10mg· kg^ - 1· d^ - 1, 5mg· kg^ - 1· d^ - 1 and 2.5mg· kg^ - 1· d^ - 1（ n = 10 in each group ）. All rats, except for the normal controls, were injected with axenic porcine serum （0. 5ml each time, twice a week） intraperitoneally for 8 weeks to establish hepatic fibrosis. After the 8th week, rats of Tet-treated model groups were given by gavage once a day with different doses of Tet for another 8 weeks. Then the liver function, serum levels of hyaluronic acid （ HA ）, laminin （ LM）, and procollagen type Ⅲ （PCⅢ） were tested. Collagen type 1 and Ⅲ, pathological changes in liver tissue were also assessed. Results Most indices of liver function including alanine minotransferase （ALT）, aspartate aminotransferase （AST）, albumin （ ALB）, albumin/globulin ratio （ A/G） and alkaline phosphatase （ALP） improved significantly in Tet-treated groups with the exception of γ-glutamyl transpeptidase （γ- GT） and total bilirubin （TBIL）. Secondly, markedly lowered levels of HA, LM and collagen type I, III were also detected by radioimmunology and immunohistochemistry in the 5 mg· kg^ - 1· d^ - 1 Tet-treated model group. Moreover, pathologi- cal findings confirmed the statistically significant improvement in hepatofibrotic degree resulted from the treatment of 5mg· kg^ - 1· d^ - 1 rather than other doses of Tet. Conclusion For experimental Wistar rats, Tet exhibited an anti-hepatofibrotic action in doses within the range of 2.5mg· kg^ - 1· d^ - 1 to 10mg· kg^ - 1· d^ - 1 and 5mg· kg^ - 1· d^ - 1 may be the optimum one among all doses.

Clinical Characteristics of Patients with Drug-induced Liver Injury

Background： Drug is all important cause of liver injury and accounts for up to 40% of instances offidminant hepatic failure. Drug-induced liver injury （DILl） is increasing while the diagnosis becomes more difficult. Though many drugs may cause DILl, Chinese herbal medicines have recently emerged as a major cause due to their extensive use in China. We aimed to provide drug safety information to patients and health carets by analyzing the clinical and pathological characteristics of the DILl and the associated drug types. Methods： A retrospective analysis was conducted in 287 patients diagnosed with DILl enrolled in our hospital from January 2011 to December 2015. The categories of causative drugs, clinical and pathological characteristics were reviewed. Results： Western medicines ranked as the top cause of DILl, accounting for 163 out of the 287 DILl patients （56.79%） in our study. Among the Western medicine, antituberculosis drugs were the highest cause （18.47%, 53 patients） of DILl. Antibiotics （18 patients, 6.27%） and antithyroid （18 patients, 6.27%） drugs also ranked among the major causes of DILl. Chinese herbal medicines are another major cause of DILl, accounting for 36.59% of cases （105 patients）. Most of the causative Chinese herbal medicines were those used to treat osteopathy, arthropathy, dermatosis, gastropathy, leukotrichia, alopecia, and gynecologic diseases. Hepatocellular hepatitis was prevalent in DILl, regardless of Chinese herbal medicine or Western medicine-induced DILI. Conclusions： Risks and the rational use of medicines should be made clear to reduce the occurrence of DILl. For patients with liver injury of unknown origin, liver tissue pathological examination is recommended for further diagnosis.

Inhibition of Pathological Angiogenesis of Chinese Medicine against Liver Fibrosis

Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells（LSECs） and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fibrosis through inhibiting angiogenesis.

Ultrasonic spectrum characterization of pig's pathological liver tissues

A high-speed digital acquisition and wide-band measurement system was used to acquiring and recording the ultrasonic pulse waveforms backscattered from normal and several pathological pig's fresh liver tissues (including ballooning degeneration, fatty degeneration, cirrhosis) in vitro. Some frequency-domain analyses were performed in which integrated backscattering coefficient (IBSC), frequency dependence of backscattering coefficient (FDBSC),and mean spacing (MS) among adjacent scatterers of the tissues were determined.In the experiments the frequency domain was from 3MHz to 7 MHz. The obtained results show that the differences among normal and various pathological tissues cause distinct changes of the measured parameters. The results show that the ultrasonic spectum technique, which can be used in tissue characterization for pathological liver in clinical, has an exciting prospect.