PD-1/PD-L1 expressions in liver tissues of patients with chronic HBV infection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To detect and compare the PD-1/PD-L1 (programmed death 1/programmed death 1 ligand) expressions in the liver tissues of chronic HBV infection patients in immune tolerant phase and those in immune clearance phase.</p><p><b>METHODS</b>Liver biopsy samples were divided into two groups: 25 samples from patients in immune clearance phase and 19 samples from patients in immune tolerant phase. PD-1/PD-L1 expressions on T lymphocytes in these liver biopsy specimens were detected by immunohistochemistry method. Percentage of PD-1/PD-L1 positive cells among CD3 positive cells was calculated by semi-quantitative evaluation. Differences between the two groups were statistically analyzed.</p><p><b>RESULTS</b>PD-1/PD-L1 expressions were significantly higher in the patients in immune tolerant phase as compared to that in immune active phase (P < 0.05). No statistical difference found between the two groups for PD-L1 expression in Kupffer cells (P > 0.05).</p><p><b>CONCLUSION</b>PD-1/PD-L1 expression level can reflect the immune functions of chronic hepatitis B patients.</p>

Expression of intrahepatic CD4+ CD25+ regulatory T cells in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the expression and distribution of intrahepatic CD4+ CD25+ regulatory T cells in immuno-tolerant and immuno-clearance phase of patients with chronic hepatitis B.</p><p><b>METHODS</b>The expression of FoxP3 was detected in 19 cases of immuno-tolerant phase and 12 cases of immuno-clearance phase by immunohistochemistry. The relation between the intrahepatic expression of FoxP3 and the clinicopathological features were analyzed.</p><p><b>RESULTS</b>The positive signal of FoxP3 is located in nuclear of lymphocyte and mainly aggregated in portal areas as well as occasionally scattered in hepatic sinusoids. The expression of intrahepatic FoxP3 in the group of immuno-tolerant phase was significantly increased than those in normal control (P < 0.01), and greatly decreased than those in immuno-clearance phase (P < 0.01). No correlation was observed among the expression of intrahepatic FoxP3, ALT, levels of HBV DNA, HBeAg positive, in patients of immuno-clearance phase, respectively. There were significant differences between immuno-tolerant phase and immuno-clearance phase age, ALT, TBIL, PTA, HBV-DNA and detection of HBeAg but not in sex and family history of HBV infection.</p><p><b>CONCLUSION</b>CD4+ CD25+ regulatory T cells may play important roles in the clearance of HBV as well as in liver inflammation and injury during chronic HBV infection.</p>

Detection of CD4+CD25+ regulatory T cells in liver tissues of fibrosing cholestatic hepatitis after liver and kidney transplantation / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the expression and distribution of CD4+CD25+ regulatory T cells (Treg) in liver tissues of patients with fibrosing cholestatic hepatitis (FCH) after liver and kidney transplantation and to investigate their roles in the pathogenesis of FCH.</p><p><b>METHODS</b>Liver biopsy specimens from five patients with FCH were studied histopathologically. A specific marker for CD4+CD25+ regulatory T cells in those specimens was detected with anti-FOXP3 monoclonal antibody by immunohistochemistry. Apoptoses of hepatocytes were detected with in situ apoptosis detection TUNEL kit.</p><p><b>RESULTS</b>Fibrosis in portal and around portal areas, cholestasis in some of the hepatocytes and canaliculi, widespread ballooning and ground-glass appearance of liver cells, and positivity of HBsAg and HBcAg and Pre-S1 protein were seen in the livers of all cases. The positive signal of FOXP3 was located in the cytoplasm of lymphocytes and the positive cells were mainly aggregated in the portal areas as well as occasionally appearing in the hepatic sinusoids. There were many more apoptotic hepatocytes near the portal areas.</p><p><b>CONCLUSION</b>Fibrosing cholestatic hepatitis has specific pathological characteristics which might be caused by high expressions of FOXP3 in liver tissues.</p>

Pathology of AIDS-related lymphadenopathy and its relationship to expression of CD4 + CD25 + regulatory T cells in lymphoid node tissue / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the pathology of AIDS-related lymphadenopathy and its relationship to the expression and distribution of CD4 + CD25 + regulatory T cells in lymphoid node tissue.</p><p><b>METHODS</b>Totally 22 biopsy and 13 autopsy lymphoid node tissues from HIV-positive patients were examined under microscopy and pathological staging was performed. Specific marker for CD4 + CD25 + regulatory T cells in lymphoid node tissue was detected with anti-Foxp3 monoclonal antibody by immunohistochemistry.</p><p><b>RESULTS</b>Among all the 35 specimens, 5, 4, 14, and 12 specimens were histopathologically staged from 1 to 4, respectively. FoxP3 were detected in all lymphoid node tissues. The distribution of FoxP3-positive lymphocytes were mainly in intermediate zone of follicle and cortical area in stages 1 and 2. The counts of FoxP3-positive lymphocytes remarkably decreased in stages 3 and 4, following depletion of lymphocytes.</p><p><b>CONCLUSIONS</b>CD4 + CD25 + regulatory T cells exist in lymphoid node tissue of patients with HIV infection. Their amounts decrease or deplete along with the progression of AIDS-related lymphadenopathy.</p>

A pathological study on liver tissues of patients with HIV infection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the pathological changes of the liver tissues of patients with HIV infection.</p><p><b>METHODS</b>14 biopsy and 12 autopsy liver tissues were examined histologically. HIV-1 related antigen of outer membrane protein gp120 and capsid protein p24 were examined with their corresponding monoclonal antibodies by immunohistochemistry.</p><p><b>RESULTS</b>In the biopsy group, cytomegalic virus (CMV) infection was found in one (1/14) case, outer membrane protein gp120 and/or capsid protein p24 antigen were detected in Kupffer cells and in some of the lymphocytes in 11 cases. All the hepatocytes were negative for outer membrane protein gp120 and capsid protein p24 antigens. In the autopsy group, there were 5 (5/12) cases of liver tissues with CMV infection and 5 cases each with mycobacterium and Toxoplasma gondii infection. Capsid protein p24 was detected in liver tissues in 3 cases.</p><p><b>CONCLUSION</b>There is HIV infection in liver tissue of patients with HIV. The rate of opportunistic infections in liver biopsy samples was lower than that in the autopsy liver tissues of patients with HIV.</p>

A clinicopathological study on nonalcoholic steatohepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the pathological and clinical characters of nonalcoholic steatohepatitis (NASH).</p><p><b>METHODS</b>Liver biopsy tissues taken from 97 patients negative for common viral detection with serological test and immunohistochemistry as well as in situ hybridization, were observed by routine light microscopic examination. And the clinical data of patients with NASH was analyzed.</p><p><b>RESULTS</b>Among the chronic hepatitis patients with unknown etiology, the detection rate of NASH was 15.5% (15/97). The characteristic lesions in NASH patients included macrovesicular steatosis in zone 3 of lobules, hepatocytes ballooning degeneration, lobules diffused with acute and chronic inflammation, and perisinusoidal fibrosis. Grading and staging according to Brunt's method, histological lesions could be accounted for G1S1 in 7 patients, G2S2 in 3 patients, G3S1 in 4 patients and G3S2 in 1 patient. There were 14 patients with mild to moderate elevation of transaminase, 10 with hyperlipemia, 8 with diabetes and 9 with fatty liver by ultrasonography.</p><p><b>CONCLUSION</b>Nonalcoholic steatohepatitis is a common form of unknown etiology chronic liver disease with certain clinic-pathological features.</p>

Liver histological changes after lamivudine treating in chronic hepatitis B patients with HBeAg positive / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the histological changes in liver biopsy tissues taken from chronic hepatitis B patients with HBsAg and HBeAg positive and ALT abnormal after lamivudine therapy for one year.</p><p><b>METHODS</b>Lamivudine was given orally at the dose of 100 mg once a day for one year. 101 patients were enrolled into this open-label study. Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine were studied. Blinded biopsies were evaluated by a histopathologist and scored according to Knodell's histology activity index(HAI).</p><p><b>RESULTS</b>53.5% (54/101), 51.5% (52/101) and 31.7% (32/101) patients had a reduction of their total hepatic HAI score, necroinflammation and fibrosis scores by >or=2 points or 1 points at the end of one year of lamivudine therapy, compared with their pretreatment values, respectively. There were significant reduction of HAI score, necroinflammation and fibrosis scores from 8.0+/-4.7 to 5.2+/-3.3 (t=7.358, P<0.01), from 5.9+/-3.8 to 3.6+/-2.5 (t=7.298, P<0.01), and from 2.1+/-1.2 to 1.6+/-1.2 (t=3.827, P<0.01), respectively. The histological improvement was independent on the HBeAg seroconvertion during the therapy.</p><p><b>CONCLUSION</b>Significant improvement in liver histology, both necroinflammation and fibrosis, can be obtained in the majority of patients treated with lamivudine for one year.</p>

A clinicopathological study on 3 cases of severe acute respiratory syndrome / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation.</p><p><b>METHODS</b>Tissue specimens from 3 autopsy cases of diagnosed SARS were studied under microscopy and the clinical data were reviewed.</p><p><b>RESULTS</b>The typical pathological changes of lungs were diffuse hemorrhage on surface. A mixture features of serous, fibrinous and hemorrhagic inflammation were seen in most pulmonary alveoli with engorgement of capillary and there were microthrombosis in some capillary. Pulmonary alveoli became thick with interstitial mononuclear inflammatory infiltration, diffused alveoli damage, desquamation of pneumocytes and hyaline-membrane formation. Fibrinoid materials and erythrocytes could be found in alveolar spaces. There were thrombo-embolisms in some bronchial artery. Meanwhile, haemorrhagic necrosis was showed in lymph nodes and spleen with attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and some lesions observed in liver, heart, kidney, pancreas may have existed before the hospitalization.</p><p><b>CONCLUSION</b>Severe damages of pulmonary and immunological system damage are responsible for clinical features of SARS and may lead to death of patients.</p>

Detection of hepatic progenitor cells in patients with severe hepatitis and their distribution / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To identify hepatic progenitor cells (HPCs) in patients with severe hepatitis (SH) by detecting their markers and investigate the features of their distribution and location.</p><p><b>METHODS</b>Liver tissues taken from 59 SH patients were tested for the receptor of stem cell factor (c-kit), pi-class glutathione S-transferase (GST-pi), cluster of differentiation 34 (CD34), cytokeratin 19 (CK19), cytokeratin 18 (CK18) and alpha fetoprotein (AFP) by immunohistochemistry (IHC). Meanwhile, 58 patients with acute or chronic hepatitis were also detected to act as controls.</p><p><b>RESULTS</b>Hepatic progenitor cells could be seen in SH patients. Most of them existed as ductular cells that had been called "typical ductular proliferation (ADP)" or "typical ductular reaction" in previous research. These ductular cells were mainly located at the portal areas, fibro septa, periportal parenchyma and the border of the pseudolobuli and inflammatory foci. Further, c-kit, GST-pi, CK19 and CK18, but not CD34 and AFP could be detected in these cells. Another kind of HPC was the small hepatocyte-like cell (SHLC), which could express c-kit, GST-pi, and CK18, but not CK19, CD34 and AFP. The semi-quantitative analysis showed that the scope of ADP in SH patients was significantly larger than that in acute and chronic hepatitis patients (chi2= 63.62, P<0.05), and the scope of ADP in subacute severe hepatitis and chronic severe hepatitis patients was also significantly larger than that in acute severe hepatitis patients.</p><p><b>CONCLUSION</b>In the course of regeneration of viral hepatitis, different types of pathology have different features. In acute and chronic hepatitis (G1-2), the regeneration is mainly owing to the proliferation of mature hepatocytes, and in chronic hepatitis (G3-4), there is the participation of HPCs, although they are limited. In severe hepatitis, however, since the replicative capacity of normal hepatocytes is impaired or prohibited, liver regenerates and restores mainly by the means of hepatic stem cells activation and proliferation. But the hepatic stem cells don't differentiate into their mature functional compartments directly at all. There are several intermediary or transition populations. In human severe hepatitis, they are mainly ductular cells, and parts of them are small hepatocyte-like cells.</p>

Clinical characteristics and mechanism of liver injury in patients with severe acute respiratory syndrome / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To summarize the clinical features of liver injury in patients with severe acute respiratory syndrome (SARS), providing information for further mechanism and clinical study.</p><p><b>METHODS</b>The clinical and some laboratory data of 154 patients suffered from SARS were collected and analyzed, who were admitted to the isolation wards of Beijing You-an Hospital from March 11 to June 3, 2003. The serum samples were taken from 46 patients to detect IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-alpha, endotoxin and hepatitis related viral inclusions. In addition, 11 patients were detected ultrasonically, and 3 patients were described pathological features. Other two groups including 15 healthy care workers and 22 patients with chronic hepatitis in the same period were selected and analyzed as controls.</p><p><b>RESULTS</b>When being admitted to hospital, serum ALT and (or) AST levels were elevated in 37.7% SARS patients. Some of them (43.1%) were mild, and most of them (56.9%) were moderate. Abnormal liver function mainly resulted from ALT elevation (70.7%), then both ALT and AST elevation (22.4%). The aminotransferases in 75.9% SARS patients normalized within two weeks, while they elevated in four patients during the hospitalization. There was a significant difference in ALT/AST elevation rates between severe and mild clinical type (chi2=19.28, P<0.05). Serum total bilirubin values elevated in 8.4% patients. Serum albumin and prealbumin levels decreased in 24.0% and 28.6% patients, respectively. Creatine kinase (CK) and (or) creatine kinase MB (CK-MB) levels elevated in 72.7% patients when they hospitalized. The six kinds of interleukins and TNF-alpha levels during the first week of hospitalization were higher than those in the fourth week and in control groups (t>or=1.67, P<0.05). The levels of some factors, such as IL-1beta, IL-6 and IL-10 in patients with elevated ALT, were higher than those in ALT normal patients (t>or=2.36, P<0.05). In the first week, only 15.2% patients had elevated serum endotoxin level. Ultrasonic examination and pathological observation showed no special features, compared with those in common acute hepatitis patients.</p><p><b>CONCLUSIONS</b>All the results suggest strongly that there may be a systemic inflammatory response syndrome (SIRS) in most SARS patients in early stage, and the liver damage is only its partial signs. It may be beneficial to suppress cytokines storm in SARS patients in early stage, which will stop the progression of SIRS and release hepatic damage and improve the prognosis of SARS patients.</p>