[Progress in the clinical diagnosis and treatment of hepatic vascular diseases].

The liver has a very special dual blood supply, including the portal vein (65%~75%) and hepatic artery (25%~35%). The hepatic veins returns blood to the systemic circulation via the portal vein, and hepatic artery after hepatic sinusoidal confluence. The lesions on the hepatic vein and its branches can cause ischemia and hypoxia or obstruction of the drainage system, portal hypertension, upper gastrointestinal variceal bleeding, hepatic encephalopathy, and so on. Clinically, hepatic vascular diseases are relatively rare, so the diagnosis and treatment are relatively difficult. Herein, we review the diseases related to the hepatic vascular system.

[Value of serum alpha-fetoprotein for the prognostic evaluation of hepatitis B virus-related acute-on-chronic liver failure treated with artificial liver].

Objective: To investigate the value of alpha-fetoprotein (AFP) level on survived hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients treated with artificial liver. Methods: Clinical indicators of HBV-ACLF patients who were previously treated with plasma exchange-based artificial liver at our department were retrospectively collected. The difference of serum AFP level between the survival and the death group was compared at 30, 90 and 180 days after artificial liver treatment. The ROC curves of the subjects were plotted, and the sensitivity and specificity of AFP for the survival prediction of the patients at 30, 90 and 180 days after artificial liver surgery were calculated. AFP was divided into a high AFP group and a low AFP group using median value. AFP and postoperative survival predictive value at 30, 90, and 180 days were analyzed. Results: A total of 93 cases were included in this study. The AFP of the survival group at 30, 90, and 180 days was (231.0 ± 286.2) ng / ml, (237.69 ± 297) ng / ml, (229.44 ± 286.46) ng/ml, and the death group was (76.4 ± 104.7) ng/ml, (103.13 ± 116.99) ng / ml, (136.34 ± 2.9.29) ng/ml, respectively. AFP of the death group was significantly lower than the corresponding survival group (P < 0.05). Receiver operating characteristic (ROC) curve analyses indicated that the area under the curve (AUC) and its 95% confidence interval at 30, 90, and 180 days after artificial liver surgery were 0.739 (0.611 ~ 0.867), 0.675 (0.550 ~ 0.80), 0.653 (0.524 ~ 0.781), respectively. The median serum AFP value was 110 ng/ml, and the survival analysis showed that the survival time of the high AFP group was significantly higher than the low AFP group at 30 d (P = 0.01), 90 d (P = 0.04) and 180 d (P = 0.03) after artificial liver surgery. Conclusion: Serum AFP can be used as a predictor of survival for HBV-ACLF patients after artificial liver therapy and its clinical value needs to be further verified by the larger sample size.

[Umbilical cord mesenchymal stem cells and their association with liver fibrosis].

At present, the most effective therapeutic method for end-stage liver fibrosis is liver transplantation. However, the application of liver transplantation is limited by a shortage of liver donors, a high incidence rate of surgical complications, graft-versus-host disease, and high medical costs. Umbilical cord mesenchymal stem cell (UC-MSC) transplantation may become a promising method for the treatment of liver diseases. UC-MSCs are adult stem cells which exhibit multipotential differentiation and can differentiate into hepatic parenchymal cells. Due to their functions including immune regulation and secretion of trophic factors, UC-MSCs can inhibit immune response, promote hepatocyte regeneration, alleviate the progression of liver fibrosis, and improve liver function. In addition, compared with bone marrow mesenchymal stem cells, UC-MSCs have abundant sources, noninvasive collection, and high safety and thus they are attracting more and more attention. This article reviews the characteristics of UC-MSCs and their mechanism of action in the treatment of liver fibrosis, as well as risks of UC-MSCs therapy.

Clinical therapeutic effects of human umbilical cord-derived mesenchymal stem cells transplantation in the treatment of end-stage liver disease.

We aimed to evaluate clinical therapeutic effects of human umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation in the treatment of end-stage liver diseases. The human UCMSCs were cultured and prepared, and then transplanted into the hepatic tissues of 50 patients with decompensated cirrhosis. The liver function, thrombin function, Model for End-Stage Liver Disease (MELD) score, and hemodynamic index value were detected during a 24-week follow-up period, with the addition of hepatoprotective, antiviral, and other conventional treatments. No complications or serious side effects were observed. In the first 2-3 weeks after surgery, symptoms including abdominal distension, oliguria, edema, and others decreased significantly, with increased appetite compared with before surgery. In the 24-week follow-up period, the levels of serum albumin and prealbumin increased significantly compared with the preoperative levels; the decrease of coagulation indicators was not significant. The MELD scores were also markedly increased. Alpha-fetoprotein levels increased without significance after treatment. There was no significant difference in the hemodynamic changes in the portal and splenic veins according to ultrasound. Moreover, no significant differences in the liver and thrombin functions between the hepatitis B virus group and the other-etiology group were observed.

Mood stabilizers regulate cytoprotective and mRNA-binding proteins in the brain: long-term effects on cell survival and transcript stability.

Manic depressive illness (MDI) is a common, severe, chronic and often life-threatening illness. Despite well-established genetic diatheses and extensive research, the biochemical abnormalities underlying the predisposition to, and the pathophysiology of, these disorders remain to be clearly established. Despite formidable obstacles in our attempts to understand the underlying neurobiology of this illness, there is currently considerable excitement about the progress that is being made using novel strategies to identify changes in gene expression that may have therapeutic relevance in the long-term treatment of MDI. In this paper, we describe our recent research endeavours utilizing newer technologies, including a concerted series of mRNA RT-PCR studies, which has led to the identification of novel, hitherto completely unexpected targets for the long-term actions of mood stabilizers - the major cytoprotective protein bcl-2, a human mRNA binding (and stabilizing) protein, AUH, and a Rho kinase. These results add to the growing body of data suggesting that mood stabilizers may bring about some of their long-term benefits by enhancing neuroplasticity and cellular resilience. These results are noteworthy since recent morphometric brain imaging and post-mortem studies have demonstrated that MDI is associated with the atrophy and/or loss of neurons and glia. The development of novel treatments which more directly target molecules involved in critical CNS cell survival and cell death pathways have the potential to enhance neuroplasticity and cellular resilience, and thereby modulate the long-term course and trajectory of these devastating illnesses.

The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS.

Differential display of mRNA was used to identify concordant changes in gene expression induced by two mood-stabilizing agents, lithium and valproate (VPA). Both treatments, on chronic administration, increased mRNA levels of the transcription factor polyomavirus enhancer-binding protein (PEBP) 2beta in frontal cortex (FCx). Both treatments also increased the DNA binding activity of PEBP2 alphabeta and robustly increased the levels of bcl-2 (known to be transcriptionally regulated by PEBP2) in FCx. Immunohistochemical studies revealed a marked increase in the number of bcl-2-immunoreactive cells in layers 2 and 3 of FCx. These novel findings represent the first report of medication-induced increases in CNS bcl-2 levels and may have implications not only for mood disorders, but also for long-term treatment of various neurodegenerative disorders.

[Detection of hepatitis C virus RNA in cells with hepatocellular carcinoma and its practical significance by in situ polymerase chain reaction].

Persistent infection with hepatitis C virus (HCV) is associated with chronic hepatitis and cirrhosis which may eventually develop into hepatocellular carcinoma (HCC). As far, the pathogenesis mechanism of HCC is unclear and nothing is known of the distribution, frequency or type of infected cells in HCC. One-step reverse transcription in situ polymerase chain reaction (ORT-PCRIS) to detect HCV RNA in HCC samples was developed in our laboratory. Liver tissues from 27 patients with HCC were investigated by this technique for frozen or paraffin-embedded sections. Meanwhile, HCV RNA in sera and extracts of specimens with HCC were assayed by RT-PCR. The positive rate of HCV RNA by ORT-PCRIS was 81.5% (22/27) in the peritumor liver tissues and 77.8% (21/27) in the tumor tissues, significantly higher than 29.6% (8/27) in sera and 37.0% (10/27) in the extreats of HCC by RP-PCR (P < 0.01). HCV RNA positive signals were found mainly in the nuclei of tumor cell, and mainly both the nuclei and cytoplasms in peritumor cells and mainly both the nuclei and cytoplasms in peritumor cells (P < 0.05). Positive granules of HCV RNA were much more in peritumor cells than in the tumor cells. Positive cells were scattered mainly on the point-type in the cancer tissues and on the diffusion-type in the peritumor tissues. Our findings suggest that ORT-PCRIS for detecting HCV RNA in the cell with HCC remarkably prior to traditional RT-PCR. HCV infection plays a relatively important role in determination of HCC development and perhaps HCV replication and its genomic RNA integration with hepatocyte DNA are involved in the course of the malignant transformation of hepatocytes.

[Clinical evaluation of HBV, HCV and HDV serum markers in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC)].

11 kinds of HBV, HCV and HDV serum markers were investigated in 46 patients with HCC, 48 patients with LC, and 52 controls without liver disease. The prevalence of one out of HBV or HCV or HDV markers (M) in HCC and LC was 91.3% and 95.8% respectively, significantly higher than that in controls (17.3%). Positivity of HBV-M in HCC and LC was remarkably higher than those of HCV-M and HDV-M (P < 0.05). Prevalence of HCV-M in HBV-M negative HCC and LC was 66.7% and 75.0% respectively, significantly higher than that in HBV-M positive cases (P < 0.05). Frequency of viral replication in HCC and LC was significantly higher than that in controls (P < 0.01). The co-occurrence of two or three kinds of viral markers in HCC was more prevalent than that in LC (38% vs 14%, P < 0.05). Patients with coinfection from both HBV and HDV had a significantly younger age than those infected by HBV alone or infected by HCV (more than 10 years earlier). Among HCC and LC, 36% of HBV seronegative cases had HBV DNA detectable in their serum. Our data suggest that HCC and LC have a close association with the infection of HBV HCV and HDV especially HBV. Active viral replication and coinfection of several kinds of virus play on important role in the determination of HCC or LC development, and HDV appears to provide an additional risk for HCC and LC. In HBV-M negative cases, HCV infection may be more important for HCC and LC development than HBV.