Advances in basic and clinical manifestations of coagulopathy in end-stage liver diseases / 医学研究生学报

The liver plays a central role in hemostasis as the site of synthesis of most procoagulant and anticoagulant factors, and the clearance of many hemostatic and fibrinolytic components. On one hand, the decreased synthetic capacity of the liver due to end-stage liver diseases（ESLD） results in decreased hepatocyte-derived hemostatic proteins in plasma. On the other hand, intrahepatic and systemic inflammation in liver diseases results in chronic endothelial cell activation with additional consumption of platelets and hemostatic proteins. This two-way change makes the clotting state of end-stage liver disease extremely complicated and unpredictable. The common laboratory tests, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT), cannot precisely reflect the change of hemostasis in vivo in ESLD. Thus, in-depth understanding this disorder with more comprehensive tests, can more effectively promote the progress of diagnosis and treatment of coagulopathy in ESLD. This article reviews the characteristics of changes in coagulation function, related detection methods, treatment and prevention in ESLD.

Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy.@*METHODS@#Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms.@*RESULTS@#(1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline.@*CONCLUSION@#Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.

A clinical and pathological analysis of 22 cases of primary sclerosing cholangitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To characterize the clinical, laboratory, imaging and pathological features of primary sclerosing cholangitis (PSC) and investigate the impact of ursodeoxycholic acid (UDCA) therapy on patient prognosis.</p><p><b>METHODS</b>The medical records of 22 patients diagnosed with PSC between 2002 and 2011 were retrospectively reviewed. The PSC diagnosis had been made in patients with suspect biochemical abnormalities following evaluation by magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). Fibrosis and inflammation were assessed by immunohistochemical analyses of tissue biopsies. Outcome of patients treated with UDCA (13-15 mg/kg/day, oral) were compared to that of patients without UDCA treatment by the X2 or corrected X2 tests.</p><p><b>RESULTS</b>Among the 22 PSC patients, the majority was male (n=15) and presented with fatigue, dark urine, and body weight loss (n=15). Four cases had ulcerative colitis. At admission, all 22 cases showed elevated levels of alkaline phosphatase[ALP: (348+/-184) U/L], 19 cases showed elevated alanine aminotransferase [ALT: (94.0+/-67.0) U/L] and aspartate aminotransferase [AST: (98.0+/-67.0) U/L], and 15 cases showed elevated levels of total bilirubin (99.0+/-115.0) mumol/L and direct bilirubin (74.4+/-92.4 mumol/L. ERCP examination showed segmental intrahepatic bile duct stenosis with expansion, and stiff and enlarged gallbladder bile ducts, but unclear findings for the common bile ducts and pancreatic ducts. MRCP showed beading of the intrahepatic bile duct, stiffness of the bile duct wall, and dilation of the common bile duct. Fibrosis and inflammation were observed in the bile ducts, along with hyperplasia and the typical features of "onion skin" fibrosis and fibrous obliterative cholangitis. Five of the 10 patients treated with UDCA improved, and seven of the 12 patients in the non-UDCA treatment group improved. There was no statistically significant difference in outcome between the groups (paired X2=0.333, corrected X2=0.083, P more than 0.05).</p><p><b>CONCLUSION</b>PSC patients were predominantly male and the common clinical manifestations were fatigue, dark urine, and body weight loss. At admission, serum biochemical indicators of cholangitis were increased significantly and subsequent imaging studies confirmed the suspected diagnosis by showing obvious characteristic changes. UDCA treatment did not significantly improve patient prognosis.</p>

Prospective controlled trial of safety of human umbilical cord derived-mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the safety of human umbilical cord derived-mesenchymal stem cell (UC-MSC) transplantation therapy in patients with decompensated liver cirrhosis.</p><p><b>METHODS</b>UC-MSCs were transplanted intravenously into patients with decompensated liver cirrhosis. Serum levels of glucose (GLU), total cholesterol (TC), blood urea nitrogen (BUN), alpha fetoprotein (AFP), white blood cells (WBC), and prothrombin activity (PA) were detected at different time points after UC-MSCs transplantation.</p><p><b>RESULTS</b>Most UC-MSC transplanted patients experienced an improvement in quality of life, to varying degrees. With the exception of low-grade fever in a few patients, side effects and oncogenic events were rare (treatment group: 1/38 vs. control group: 1/16; P more than 0.05). The UC-MSCs transplantation showed no effect on GLU, TC, BUN, AFP, WBC, or PA.</p><p><b>CONCLUSION</b>UC-MSCs transplantation in patients with decompensated liver cirrhosis is safe and may improve the patient's quality of life.</p>

Difference in the CD4+T lymphocytes activation between long term non-progressors and typical progressors of HIV-1 infected patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the difference in the CD4+T lymphocytes activation between long term non progressors (LTNP) and typical progressors (TP) of HIV-1 infected patients.</p><p><b>METHODS</b>Twenty-four HIV-1 infected patients and 15 heathy control adults were tested and flow cytometry was used to detect the activation marker CD38 and CD4 count in blood samples taken from the patients and control. bDNA method was used to test the virus load in the plasma of patients.</p><p><b>RESULTS</b>The activation of CD4+T cells was positively correlated with virus load and negatively correlated with CD4 counts. Compared with normal controls, the activation of CD4+T cells was obviously increased in TP patients but not obviously changed in LTNP patients.</p><p><b>CONCLUSION</b>Compared with healthy controls, the activation of CD4+T cells in LTNP did not obviously increase. This maybe partially accounts for LTNP patients keeping a good state for a long time.</p>

Characteristics of HIV-1-specific CD8 T-cell responses and their role in loss of viremia in children chronically infected with HIV-1 undergoing highly active antiretroviral therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Few studies have examined the properties of human immunodeficiency virus type 1 (HIV-1) epitope-specific cytotoxic T lymphocyte (CTL) responses in children. To address this issue, we characterized epitope-specific CTL responses and analyzed the determinants that may affect CTL responses before and after highly active antiretroviral therapy (HAART) in children with HIV-1 infection.</p><p><b>METHODS</b>A total of 22 HIV-1-infected children and 23 uninfected healthy children as control were enrolled in the study. Circulating CD4 T cells and HIV-1 RNA load in plasma were routinely measured. Peripheral HIV-1-specific CTL frequency and HIV-1 epitope-specific, interferon-gamma (IFN-gamma)-producing T lymphocytes were measured using tetramer staining and enzyme-linked immunospot (ELISPOT) assay, respectively. Circulating dendritic cell (DC) subsets were monitored with FACS analysis.</p><p><b>RESULTS</b>More than 80% of the children with HIV-1 infection exhibited a positive HIV-1-epitope-specific CTL response at baseline, but HIV-specific CTLs and IFN-gamma-producing lymphocytes decreased in patients who responded to HAART in comparison with non-responders and HAART-naive children. The duration of virus suppression resulted from HAART was inversely correlated with CTL frequency. While in HAART-naive children, HIV-1-specific CTL frequency was positively correlated with myeloid DC (mDC) frequency, although the cause and effect relationship between the DCs and CTLs remains unknown.</p><p><b>CONCLUSIONS</b>HIV-1-epitope-specific CTL responses are dependent on antigenic stimulation. The impaired DC subsets in blood might result in a defect in DC-mediated T cell responses. These findings may provide insight into understanding the factors and related mechanisms that influence the outcome of HIV-1 carriers to HAART or future antiviral therapies.</p>

IFN or oxymatrine in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To observe the therapeutic efficacy of IFN or oxymatrine in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B.</p><p><b>METHODS</b>Forty patients ongoing treatment with lamivudine were randomized to three groups: group A, 14 patients with addition of IFN alpha-2b 3MU to ongoing lamivudine, daily, one month, followed by the same dose given every other day, five months; group B, 15 patients with addition of injectable oxymatrine 60 mg daily, three months, followed by oral oxymatrine every day, three months, and group C, 11 patients ongoing treatment with lamivudine alone. The HBV DNA level in serum, HBeAg seroconversion, and ALT level were detected at the end of the treatment.</p><p><b>RESULTS</b>After 6 months of treatment, HBV DNA became negative in 35.73% patients treated with combination with IFN, and in 13.3% patients treated with combination with oxymatrine. ALT level was normal in 85.71% or 86.66% of patients, respectively. In none of the patients under ongoing treatment with lamivudine alone HBV DNA or HBeAg became negative, and ALT level was normal in 36.36% of patients.</p><p><b>CONCLUSION</b>These data indicated that IFN or oxymatrine in combination with ongoing lamivudine therapy provided effective antiviral therapy in patients with lamivudine-resistant HBV. The addition of IFN or oxymatrine to ongoing lamivudine therapy in lamivudine-resistant patients led to significant inhibition of viral replication and improvement in liver function after 6 months of therapy.</p>