Drug-induced liver injury (DILI) is one of the major complications following liver transplantation and can lead to impaired graft function, and in some cases, graft failure. A wide range of drugs are implicated in DILI post-liver transplantation, including immunosuppressants, antiviral agents, antibiotics, and, more recently, immune checkpoint inhibitors. The histopathological manifestations of DILI in this context are complex and diverse, encompassing hepatocellular steatosis, necrosis, cholestasis, cholangitis, vascular lesions, and fibrosis. However, these features lack specificity, making the pathological diagnosis of post-transplant DILI challenging. This review focuses on the pathological aspects of diagnosing and differentiating DILI after liver transplantation, as well as recent advances in this field, combined with clinical considerations. The aim is to provide insights that may contribute to improving graft survival and prolonging the life expectancy of liver transplant recipients.

Drug-induced liver injury (DILI) is one of the major complications following liver transplantation and can lead to impaired graft function, and in some cases, graft failure. A wide range of drugs are implicated in DILI post-liver transplantation, including immunosuppressants, antiviral agents, antibiotics, and, more recently, immune checkpoint inhibitors. The histopathological manifestations of DILI in this context are complex and diverse, encompassing hepatocellular steatosis, necrosis, cholestasis, cholangitis, vascular lesions, and fibrosis. However, these features lack specificity, making the pathological diagnosis of post-transplant DILI challenging. This review focuses on the pathological aspects of diagnosing and differentiating DILI after liver transplantation, as well as recent advances in this field, combined with clinical considerations. The aim is to provide insights that may contribute to improving graft survival and prolonging the life expectancy of liver transplant recipients.

Objective:To investigate the clinical and diagnostic value of liver stiffness measurement (LSM) for the evaluation and comparison of aspartate aminotransferas/platelet ratio index (APRI), fibrosis 4 indexes (FIB-4) and NAFLD fibrosis score (NFS) with liver fibrosis staging in relation to nonalcoholic fatty liver disease (NAFLD).Methods:103 cases with NAFLD who met the inclusion criteria confirmed by liver biopsy were selected for retrospective analysis. The results of serological tests and LSM were recorded. The APRI, FIB-4 and NFS were calculated. The accuracy and applicability of four liver fibrosis models in the diagnosis of liver fibrosis in NAFLD patients were compared with the receiver operating characteristic curve (ROC), and the diagnostic cut-off value of LSM was established.Results:Varying degrees of LSM, APRI, FIB-4 and NFS had shown positive correlations with the increasing degree of liver fibrosis. Among them, LSM was positively correlated with the degree of liver fibrosis, and the correlation coefficient was r = 0.727, P < 0.0001. Consistent with this, the area under the receiver operating characteristic curve, sensitivity, and specificity of LSM diagnosis of liver fibrosis in different stages was significantly higher than APRI, FIB-4 and NFS. Area under receiver operating characteristic curve of LSM was 0.862 and 0.928 for significant liver fibrosis ( f ≥ 2), and advanced liver fibrosis ( f ≥ 3). Conclusion:LSM has a good diagnostic exclusion value for NAFLD-induced fibrosis, and its sensitivity and specificity are better than APRI, FIB-4 and NFS.

OBJECTIVETo investigate the correlation of serum osteoprotegerin (OPG) with the progression of nonalcoholic fatty liver disease (NAFLD) and the noninvasive prediction and diagnosis of nonalcoholic steatohepatitis (NASH).

METHODSA total of 136 patients with NAFLD were enrolled, and their tissue samples for liver biopsy and serum samples obtained at 1 week after liver biopsy were collected; 83 healthy subjects without the symptoms of fatty liver disease proved by ultrasound examination were enrolled as controls. The physiological indicators including height, body weight, and waist circumference were measured, and body mass index was calculated. The biochemical parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, alkaline phosphatase, gamma-glutamyl transferase, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Double-antibody sandwich enzyme-linked immunosorbent assay was used to determine the serum level of OPG. The rank sum test, chi-square test, t-test, one-way analysis of variance, Spearman correlation analysis, least significant difference test, and receiver operating characteristic (ROC) curve were applied for statistical analysis of various data.

RESULTSSerum OPG level was correlated with AST and TG (P < 0.05), and was highly correlated with hepatocyte fatty degeneration, ballooning degeneration, intralobular inflammation, portal inflammation, and fibrosis degree (P < 0.01). With the increasing NAFLD activity score (NAS), serum OPG level decreased, and there was a highly negative correlation between them (r = -0.928, P < 0.01). Serum OPG level was significantly lower in NASH patients than non-NASH patients. The area under the ROC curve of serum OPG level was 0.963, and according to the Youden index, its optimal sensitivity and specificity were 96.1% and 97.4%, respectively, at an optimal cut-off value of 242.96 ng/L, which suggested a high diagnostic power.

CONCLUSIONIn NASH patients, serum OPG level decreases significantly. Serum OPG level can be used as an independent predictive factor to evaluate NASH and its severity, as well as a noninvasive diagnostic index for NASH.

Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Aspartate Aminotransferases ; blood ; Biopsy ; Body Mass Index ; Case-Control Studies ; Cholesterol ; blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Fibrosis ; Humans ; Inflammation ; pathology ; Liver ; pathology ; Non-alcoholic Fatty Liver Disease ; blood ; diagnosis ; Osteoprotegerin ; blood ; ROC Curve ; Triglycerides ; blood ; gamma-Glutamyltransferase ; blood

Liver fibrosis/cirrhosis is a pathological process which involves increased deposition of extracellular matrix in liver tissues and changes in liver tissue structure induced by the persistent action of various factors causing liver injury. This article introduces the features of liver fibrosis/cirrhosis caused by different factors. Identifying the etiology and evaluating the degree of liver fibrosis/cirrhosis with reference to their histological characteristics are of great importance for clinical diagnosis and treatment.

Objective To investigate the diagnostic value of the acoustic radiation force impulse (ARFI) technology and AST/PLT ratio index (APRI） for the assessment of the liver fibrosis in chronic hepatitis C patients.Methods 107 patients with chronic hepatitis C were included,the subjects were underwent liver biopsy,liver function,blood count,as well as real-time acoustic elastography examination.The APRI was calculated according the following formula,APRI =AST (ULN)/PLT (109/L).ARFI and APRI were compared by correlation with liver fibrosis stage in chronic hepatitis C.Referring to the histologic fibrosis stage on liver biopsy,all the ARFI and the APRI value were assessed by using ROC curve analysis.The corresponding cut-off values,sensitivity and specificity were also calculated and compared.Results The mean values of ARFI and APRI were (1.26 ± 0.27)m/s and 0.30 ± 0.46 for the patients with S1,(1.45 ± 0.51)m/s and 0.29 ± 0.21 for those with S2,(2.03 ± 0.54) m/s and 0.59 ± 0.56 for those with S3,(2.29 ± 0.82) m/s and 0.63 ± 0.35 for those with S4,respectively.ARFI (r =0.61,P ＜0.001) had a better correlation with liver fibrosis stage in chronic hepatitis C than APRI (r =0.49,P ＜0.001).Cut-off points of ARFI and APRI were 1.529 m/s and 0.170 for S≥2,1.780 m/s and 0.277 for S≥3,1.780 m/s and 0.446 for S =4,respectively.Accordingly,the areas under the ROC curves for ARFI and APRI were 0.779 and 0.724 for S≥2,0.866 and 0.786 for S≥3,0.790 and 0.779 for S=4,respectively.Conclusions As a non-invasive technology,ARFI is more accurate when applied to evaluate liver fibrosis in patients with chronic hepatitis C than APRI.ARFI technology has potential value for quantitatme evaluation of the liver fibrosis for chronic hepatitis C.

Objective To investigate the prevalence of vitiligo in China through a multi-center and larse-population epidemiological survey.Methods A community-based survey was conducted in 6 cities from 6 provinces.Cluster sampling method was used.Subjects were required to fulfill the self-report questionnaires and received physical examination by dermatologists.EpiData and SPSS11.5 were utilized for statistical analysis. Results Totally,19 974 patients participated in this study,and 17 345 valid questionnaires were retrieved with a return rate of 86.84%.Of them,122 were found to have vitiligo.The prevalence and standardized prevalence of vitiligo was 0.70% and 0.56% in all patients,0.95% (75) and 0.69% in male patients and 0.50% (47) and O.45% in female patients.respectively.A significant elevation was observed in the prevalence of vitiligo in males than in females (P<0.01).The prevalence of vitiligo was increased with age and peaked in patients aging from 60 to 69 years and those over 70 years.The age at onset of vitiligo varied from 0 to 19 years in 21.85% of these patients,from 20 to 49 years in 47.05%.The most connnon type was focal vitiligo,which accounted for 36.06%,while the rarest type wag segmental type (2.46%).The pesitivity rate of family history of vitiligo was 9.84% in patients and 1.31% in community population (P<0.01).About 31.97% of the patients complained of negative influence of vitiligo on quality of life.Conclusions The standardized prevalence of vitiligo is 0.56%in 6 provinces from China.Males seem to have a higher prevalence of vifiligo than females.

BACKGROUNDTo explore the clinical and pathological characteristics and pathogenesis of autoimmunohepatitis (AIH).

METHODSThe serum and liver biopsy specimens and clinical data of 26 cases with patients with AIH were analyzed and scored according to the criteria of International autoimmune hepatitis (IAIHG, 1999). The changes of dendritic cells (DC) in the liver tissues were observed with a panel of DC markers (CD-80/B7-1, CD-86/B7-2, CD-1a and HLA-DR) and immunohistochemistry, and the activation of hepatic stellate cells (HSC) and the expression of TGF-alpha were also detected. Liver tissue specimens from 10 patients with chronic viral hepatitis B and C respectively and 5 normal liver specimens were chosen as controls.

RESULTSMean aggregate scores of 26 AIH cases, including 21 cases of type B (80.8%) and 5 cases of type C (19.2%), which were 18.6 +/- 1.4 and 19.1 +/- 2.1 respectively. There were significant differences between the type B and type C in the average age levels of serum ALT and AST, and alpha-Glo (P <0.001 or P< 0.01 or P <0.05). Histological features of all the AIH liver tissues showed the lesions of chronic active hepatitis such as interface hepatitis/piecemeal necrosis (100%), obvious lobular inflammation (type B 95.2%, type C 100%), bridging necrosis (57.1% type B, 80.0% type C, P<0.05), rosetting of liver cells (71.4% type B, 100% type C, P<0.01), central lobular confluent necrosis (33.3% type B, 80.0% type C, P<0.001), predominant plasmacytic infiltration (type B 95.2%, type C 20.0%, P<0.001). The rates of increased and concentrated DC in the portal and lobular areas, especially in the active lesions in type B and type C AIH were 85.7% (18/21) and 5/5 respectively. It was found that DC and lymphocytes surrounded the hepatocytes which partly expressed HLA-DR antigen, while there were no or a few HLA-DR positive hepatocytes in controls. Meanwhile, the number of alpha-SMA positive HSC and the expression of TGF- were obviously increased in AIH liver tissues.

CONCLUSIONSSeveral clinical and pathological features of AIH were identified in this study. As an antigen-presenting cell, DC might play an important role in the pathogenesis of AIH. In China, sub-type B of AIH might be more frequent than sub-type C and there were differences in clinical aspects, serology and pathology between the two types.

Adolescent ; Adult ; Child ; Dendritic Cells ; immunology ; Female ; Hepatitis, Autoimmune ; blood ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged

Objective To explore the status of immune responses in the lungs and the changes in lymphocyte subgroups in the immune organs in a patient having been suffered from severe acute respiratory syndrome (SARS). Methods The distribution and number of lymphocyte subgroups in the lungs and immune organs from an autopsy case of SARS were analyzed by using immunochemical staining with an array of monoclonal antibodies including CD3, CD4, CD8, CD20, CD57, CD68, S-100 and HLA-DR. Healthy spleen and lymph nodes were used as normal controls. Results CD8 + T lymphocytes constituted the major component of infiltration of inflammatory cells in the pulmonary interstitium. A semi-quantitative analysis of lymphocyte subgroups revealed that the percentage of CD3 +, CD4 +, CD8 + or CD20 + lymphocyte in a total of 31 thoracic lymph nodes of the SARS case were decreased by 74.2%, 67.7%, 74.2%, and 83.9%, respectively, compared with healthy controls. However, the percentages of lymphocyte subgroups in the celiac lymph nodes were less decreased than those in thoracic lymph nodes. The numbers of CD20 + , CD3 +, CD4 + and CD8 + lymphocytes were also decreased. CD20 + lymphocyte were notably decreased in the spleen, while CD57 +, CD68 +, S-100 + and HLA-DR + cells were increased relatively in the lymph nodes and spleen. Conclusions The results suggested that cellular immune responses were predominant in the lung of SARS patient, and it might play an important role in getting rid of coronaviruses in the infected cells and inducing immune mediated injuries to the lungs. There might be a decrease in number and imbalance in various degrees in the proportion of lymphocyte subgroups in the immune organs of the patients with severe SARS, and these changes might have a tendency to be more remarkable in lymphatic tissue situated closer to the lungs.

Objective To explore the target cells of SARS coronavirus infection in vivo and to provide the evidence of multi organ injuries produced by SARS coronavirus infection. Methods Three biotin labeling oligonucleotide probes were synthesized according to the published gene sequence of SARS coronavirus. The location, distributtion and quantity of SARS coronavirus in 2 autopsy cases of SARS were studied by in situ hybridization and electron microscopic examination. Results SARS coronavirus particles were identified in multiple organs. In lungs, SARS coronaviruses were located predominantly in the cytoplasm of bronchiolar and alveolar epithelial cells, in a part of macrophages and endothelial cells as well as a few infiltrated lymphocytes. In situ hybridization showed that in target cells SARS coronavirus distribution presented a cytoplasmic or inclusive pattern, and the mean number of positive cells in the pulmonary tissue was 80?25 per 200? field. Electron microscopic examination showed that the coronaviral particles were 100～150 nm in diameter, with low density electron cores with halo or garland envelopes. About 15% of renal tubular epithelial cells harbored SARS coronavirus, and a few parenchymal cells and sinusoid capillary endothelial cells of adrenal glands were hybridization positive. In the gastro intestinal tract, SARS coronaviruses were seen in the cytoplasm of mucosal and crypt epithelial cells, mostly in 2/3 of superficial mocosa. Under both electron microscopy and in situ hybridization observation, SARS coronaviruses were found focally distributed in some cardiomyocytes. The SARS coronavirus positive particles were also noted in macrophages/histocytes, sinusoid endothelial cells, as well as a few lymphocytes in thoracic and celiac lymph nodes. In addition, coronavirus particles were also seen in a few testicular epithelial cells and Leydig's cells. Conclusion SARS coronavirus could attack multiple target cells, implicating that SARS might cause multi organ damages, with lungs as the predominant organ of injury.