Histopathological impact of SARS-CoV-2 on the liver:Cellular damage and long-term complications

Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

Research Progress on the Relationship between Magnetic Resonance Imaging and Clinical Pathological Characteristics of Liver Cancer

Liver cancer is one of the main malignant tumors in the digestive system.Early detection and treatment have positive significance in improving patient prognosis and reducing mortality.MRI is the main method for liver cancer examination,which mainly uses computers to compare imaging of different energy regions of tumors,observe the density and signal changes of liver cancer,and the degree of tumor enhancement.In particular,various new MRI functional imaging technologies,such as diffusion-weighted imaging,perfusion weighted imaging,delayed imaging,liver cell specific contrast agent enhanced imaging,etc.,can be used at the molecular level Multiple aspects such as cell function provide clinicians with richer diagnostic information.Therefore,further comparative analysis of MRI manifestations and pathological results of liver cancer can help to gain a deeper understanding of the biological behavior of tumors and provide a basis for treatment decision-making and prognosis evaluation.

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.

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.

Clinical pathological characteristics of“crawling-type”gastric adenocarcinoma cancer:A case report

BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.

Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update

In 2010, a panel of Chinese pathologists reported the first expert consensus for the pathological diagnosis of primary liver cancers to address the many contradictions and inconsistencies in the pathological characteristics and diagnostic criteria for PLC. Since then considerable clinicopathological studies have been conducted globally, prompting us to update the practice guidelines for the pathological diagnosis of PLC. In April 18, 2014, a Guideline Committee consisting of 40 specialists from seven Chinese Societies(including Chinese Society of Liver Cancer, Chinese Anti-Cancer Association; Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Pathology, Chinese Anti-Cancer Association; Digestive Disease Group, Chinese Society of Pathology, Chinese Medical Association; Chinese Society of Surgery, Chinese Medical Association; Chinese Society of Clinical Oncology, Chinese Anti-Cancer Association; Pathological Group of Hepatobiliary Tumor and Liver Transplantation, Chinese Society of Pathology, Chinese Medical Association) was created for the formulation of the first guidelines for the standardization of the pathological diagnosis of PLC, mainly focusing on the following topics: gross specimen sampling, concepts and diagnostic criteria of small hepatocellular carcinoma(SHCC), microvascular invasion(MVI), satellite nodules,and immunohistochemical and molecular diagnosis. The present updated guidelines are reflective of current clinicopathological studies, and include a novel 7-point baseline sampling protocol, which stipulate that at least four tissue specimens should be sampled at the junction of the tumor and adjacent liver tissues in a 1:1 ratio at the 12, 3, 6 and 9 o'clock reference positions. For the purposes of molecular pathological examination, at least one specimen should be sampled at the intratumoral zone, but more specimens should be sampled for tumors harboring different textures or colors. Specimens should be sampled at both adjacent and distant peritumoral liver tissues or the tumor margin in order to observe MVI, satellite nodules and dysplastic foci/nodules distributed throughout the background liver tissues. Complete sampling of whole SHCC ≤ 3 cm should be performed to assess its biological behavior, and in clinical practice, therapeutic borders should be also preserved, even in SHCC. The diagnostic criteria of MVI and satellite nodules, immunohistochemical panels, as well as molecular diagnostic principles, such as clonal typing, for recurrent HCC and multinodule HCC were also proposed and recommended. The standardized process of pathological examination is aimed at ensuring the accuracy of pathological PLC diagnoses as well as providing a valuable frame of reference for the clinical assessment of tumor invasive potential, the risk of postoperative recurrence, long-term survival, and the development of individualized treatment regimens. The updated guidelines could ensure the accuracy of pathological diagnoses of PLC, and provide a valuable frame of reference for its clinical assessment.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorecal cancer patients with liver metastases who underwent hepatectomy.However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients.Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients.The pathologic response was evaluated according to the tumor regression grade(TRG).The prognostic role of pathologic response in recurrence-free survival(RFS) and overall survival(OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests.Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy(median RFS: 9.9 vs.6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors,and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases(all P < 0.05). A decrease in the serum carcinoembryonic antigen(CEA) level after preoperative chemotherapy predicted an increased pathologic response rate(P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens.Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

Pathological Characteristics of Liver Allografts from Donation after Brain Death Followed by Cardiac Death in Pigs

Donation after brain death followed by circulatory death （DBCD） is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs （25-30 kg） were allocated randomly into donation after brain death （DBD）, donation after circulatory death （DCD） and DBCD groups. Brain death was induced by aug- menting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were col- lected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [（0.56±0.30）%] and DBCD [（0.50 ±0.11）%] groups was much lower than that in DCD group [（3.78±0.33）%] （P〈0.05）. And there was no significant difference between DBD group and DBCD group （P〉0.05））. The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor(GIST) . Computed tomography(CT) and magnetic resonance imaging(MRI) 107 mo after the operation,revealed a cystic mass(14 cm in diameter) and a solid mass(9 cm in diameter) in the right and left lobes of the liver,respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate(IM) treatment,400 mg/day orally. Following the IM treatment for a period of 35 mo,the patient underwent partial hepatectomy(S4 + S5) . The effect of IM on the metastatic lesions was interpreted as pathologic complete response(CR) . Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Radiologic-pathologic correlation of three-dimensional shear-wave elastographic findings in assessing the liver ablation volume after radiofrequency ablation

AIM: To evaluate the usefulness of three-dimensional (3D) shear-wave elastography (SWE) in assessing the liver ablation volume after radiofrequency (RF) ablation.

Wilson disease:Histopathological correlations with treatment on follow-up liver biopsies

AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.

Focal nodular hyperplasia of the liver: pathological analysis of 11 cases

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign tumor-like lesion of the liver, predominantly affect- ing women. Its etiology is obscure and its pathogenesis is poorly understood. FNH should be differentiated from oth- er benign and malignant hepatic lesions. The aim of this study was to explore the pathological characteristics of FNH of the liver. METHODS: Eleven patients with FNH were studied retro- spectively by using hematoxylin and eosin, immunohisto- chemical and histochemical staining. RESULTS: In 8 female and 3 male FNH patients aged 19 to 54 years (mean 32), most of lesions showed central scars macroscopically. Microscopically 8 patients were found of classical type, 2 were of telangiectic type, and 1 was of mixed type. CONCLUSION: FNH is an uncommon benign hyperplastic lesion of the liver. It should be differentiated from hepato- cellular adenoma, alpha-fetoprotein negative hepatocellular carcinoma, and fibrolamellar carcinoma.

CD4+Foxp3+CD25+/-Tregs characterize liver tissue specimens of patients suffering from drug-induced autoimmune hepatitis:A clinical-pathological study

Background: The diagnosis of drug-induced autoimmune hepatitis(DIAIH) and its differentiation from idiopathic autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4~+Foxp3~+CD25+/-regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4~+Foxp3~+CD25+/-Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4~+Foxp3~+CD25+/-Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4~+Foxp3~+CD25~-Tregs compared with AIH(P < 0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4~+Foxp3~+CD25~-Tregs(P < 0.05).However, the frequency of peripheral blood CD4~+Foxp3~+CD25+/-Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4~+Foxp3~+CD25~-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.

Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic(type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.

Combined hepatocellular cholangiocarcinoma: A clinicopathological update

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

Impact of homogeneous pathologic response to preoperative chemotherapy in patients with multiple colorectal liver metastases

AIM To analyze the homogeneity of pathologic response to preoperative chemotherapy(PRPC) after chemotherapy in patients with multiple liver metastases(LM).METHODS From September 2011 to August 2014,patients with at least two LM undergoing preoperative chemotherapy prior to resection were included in this retrospective,single-center study. The endpoints were PRPC homogeneity(according to both the Rubbia-Brandt and MD Anderson classifications),the impact of PRPC on the MDT decision,factors associated with homogeneous PRPC and overall survival of patients with vs. without homogeneous PRPC.RESULTS seventy-three patients with a total of 88 liver resections(including 15 two-stage procedures) were included in the study. The homogeneous PRPC rate was 55% according to the Rubbia-Brandt classification and 53% according to the MD Anderson classification. The MDT decision was modified by the PRPC in only 2.7% of patients(n = 2). CONCLUSION The PRPC was homogeneous in only one half of patients and had very little influence on the MDT decision.

Epidemiological and histopathological study of relevance of Guizhou Maotai liquor and liver diseases

AIM: To explore the relevance of Maotai liquor and liver diseases. METHODS: Epidemiological study was conducted on groups of subjects, each consisting of 3 subjects from the Maotai liquor group consisting of 99 individuals and one from the non-alcoholic control group consisting of 33 individuals. Liver biopsy was performed on 23 volunteers from Guizhou Maotai Distillery who had a constant and long history of drinking Maotai liquor. Experimental histopathological study was conducted as follows: sixty male Wistar rats were divided into 3 groups randomly and fed with Maotai liquor, ordinary white wine, and physiological saline respectively for a period of 8 and 12 weeks. The rats were sacrificed in batches, then serum ALT, AST, TBil, and AKP were measured. Rat livers were harvested to measure the liver indexes, GSH, and MDA. Histopathological examinations were also performed. Another eighty mice were randomly divided into 4 groups and fed with Maotai (at different dosages of 10 ml.kg(-1) and 20 ml.kg(-1)), ethanol, and physiological saline. The animals were sacrificed after 4 weeks and serum ALT was determined. Then the livers were harvested and liver indexes and MDA were measured. RESULTS: The incidence rate of hepatic symptoms, splenomegaly, liver function impairment, reversal of Albumin/Globulin and increased diameter of portal veins in the Maotai liquor group were 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 0 0/99 and 0 0/99 , 0 0/99 ,0 0/99 , 0 0/99 , 0 0/99 , respectively. There was no significant difference between the Maotai group and the non-alcoholic control group P】0.05 . Various degree of fatty infiltration of hepatocytes was found in the 23 volunteers receiving liver biopsy, but there was no obvious hepatic fibrosis or cirrhosis. A comparison was made between the Maotai liquor group and the ordinary white wine group. It was found that hepatic MDA in rats and mice were 0.33+/-0.10 and 0.49+/-0.23 respectively in Maotai group and 0.61+/-0.22 and 0.66+/-0.32 in the ordinary white wine group; MDA had an obvious decrease in the Maotai liquor group (P【0.05); hepatic GSH were 0.12 mg.g(-1)+/-0.06 mg.g(-1) in rats of the Maotai liquor group and (0.08+/-0.02)mg.g(-1) in white wine group, it was obviously increased in the Maotai liquor group (P【0.05). After the 20 rats had been fed with ordinary white wine for 8 weeks consecutively, disarranged hepatocyte cords, fatty infiltration of hepatocytes, and fibrous septa of varying widths due to hepatic connective tissues proliferation were observed; after 12 weeks, the fibrous tissue proliferation continued and early cirrhosis appeared. Compared with the ordinary white wine group, fatty infiltration was observed in the 8-week and 12-week groups, but no necrosis or fibrosis or cirrhosis was found in the Maotai liquor group (P【0.05). CONCLUSION: Maotai liquor may cause fatty liver but not hepatic fibrosis or cirrhosis, and it can strengthen lipid peroxidation in the liver.

Clinic-pathological features of metabolic associated fatty liver disease with hepatitis B virus infection

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in 2020.AIM To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)infection.METHODS Patients with histopathologically proven MAFLD from a single medical center were included.Patients were divided into MAFLD group(without HBV infection)and HBV-MAFLD group(with HBV infection).Propensity score matching was utilized to balance the baseline characteristics between two groups.RESULTS A total of 417 cases with MAFLD were included,359(86.1%)of whom were infected with HBV.There were significantly more males in the HBV-MAFLD group than in the MAFLD group(P<0.05).After propensity score matching,58 pairs were successfully matched with no significant differences found in gender,age,body mass index,lipid levels,liver enzymes,and the other metabolic associated comorbidities between the two groups(P>0.05).The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group,while the degree of inflammation and fibrosis in the liver was less severe(P<0.05).In multivariate analysis,HBV infection was associated with significantly lower grade of hepatic steatosis[odds ratio(OR)=0.088,95%confidence interval(CI):0.027-0.291]but higher inflammation level(OR=4.059,95%CI:1.403-11.742)and fibrosis level(OR=3.016,95%CI:1.087-8.370)after adjusting for age,gender,and other metabolic parameters.CONCLUSION HBV infection is associated with similar metabolic risks,lower steatosis grade,higher inflammation,and fibrosis grade in MAFLD patients.

Liver histology in ICU patients dying from sepsis:A clinico-pathological study

AIM:To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver bi- opsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholan- gitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was ob- served in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was as- sociated with increased hospitalization in the ICU prior death (P = 0.026). CONCLUSION: Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.