The Association of D-dimer and Spontaneous Hemorrhagic Ascites with Outcomes in Cirrhosis: a Retrospective Study.

BACKGROUND: Cirrhotic patients with hemorrhagic ascites have significant morbidity and mortality. This study aims to determine the relationship between D-dimer values and hemorrhagic ascites in cirrhotic patients and analyze its predictive value. METHODS: This retrospective study screened 572 consecutive cirrhotic patients with ascites and hemorrhagic ascites (defined as red blood cells (RBC) in ascitic fluid ≥ 10,000/µL) during a 72-month period. The overall patient survival rate was measured by Kaplan-Meier analysis method. The relationship between D-dimer and hemorrhagic ascites was also examined. A multivariate Cox proportional hazard analysis was performed to assess the indepen-dent risk factors related to mortality. RESULTS: Both control group and hemorrhagic ascites patients had obvious hepatic dysfunction as determined by Model for End-Stage Liver Disease (MELD) scores of 6.37 ± 1.05 and 11.82 ± 2.86, respectively (p < 0.001). There was a higher prevalence of patients with significant ascites in those with spontaneous hemorrhagic ascites than in the control group (p = 0.003). There were significant differences in D-dimer levels between both groups (9.44 ± 5.11 vs. 26.83 ± 5.35, p < 0.001). Hemorrhagic ascites was significantly and positively correlated with D-dimer levels (r = 0.692, p < 0.0001). The area under the receiver operating characteristic (ROC) curve was 0.9838. Using Cox proportional hazard model for multivariate prognostic analysis, MELD, D-dimer and presence of spontaneous hemorrhagic ascites were independent predictors of 3-year mortality. CONCLUSIONS: Patients with hemorrhagic ascites had a significantly higher MELD score, D-dimer, and mortality than patients with ascites alone. D-dimer was associated with the appearance of hemorrhagic ascites and was found to be a marker of advanced liver disease and poor outcomes.

Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma in a patient with hepatitis B virus-related liver cirrhosis: A case report.

This study describes a rare case of Human Immunodeficiency Virus and Human Herpes Virus 8 (HHV-8) negative primary effusion lymphoma (PEL)-like lymphoma in a patient with hepatitis B virus-related liver cirrhosis, diagnosed in a 66-year-old male who rapidly progressed to a sense of abdominal fullness. Cytological analysis of the pleural effusion demonstrated large atypical lymphoid cells with rounded nuclei, prominent nucleoli, and abundant cytoplasm. Immunocytochemistry of the pleural effusion detected atypical CD20(+) lymphoid cells. The patient was hospitalized, and died following sepsis and multi-organ failure. Our case highlights that HHV-8-unrelated PEL-like lymphoma patients have different pathogenetic mechanisms of causality at the biological level, immunophenotype, clinical behavior, and prognosis.

Use of (18)F-FDG PET/CT to locate primary malignancies in patients with hepatic cirrhosis and malignant ascites.

OBJECTIVE: Ascites in patients with hepatic cirrhosis is caused by cirrhosis in most cases. For most malignant ascites, the primary malignancy could be readily identified using conventional imaging methods, e.g., computed tomography (CT) and magnetic resonance imaging (MRI). However, in a small fraction of the patients, the primary malignancy remains occult even with these examinations. In this retrospective study, we assessed the usefulness of (18)F-FDG PET/CT in patients with hepatic cirrhosis and malignant ascites of otherwise unknown origin. METHODS: Twenty-eight patients with malignant ascites of unknown primary sites after CT, MRI and ultrasound during the period of five years between January 2008 and December 2012 had received (18)F-FDG PET/CT. Medical records of these patients were reviewed and analyzed. RESULTS: Elevated (18)F-FDG absorption was found in 23 of 28 cases in the following sites: gastrointestinal tract (n=10, 43.5%), prostate (n=5, 21.7%), peritoneum (n=4, 13.3%), and ovary (n=4, 13.3%). Cancer was confirmed by pathology in 20 cases after open or laparoscopic surgeries. Five patients were found to have benign ascites, among which, 3 were found to be false positive due to tuberculosis. SUV values were significantly higher for tumors than for benign lesions (mean values, 6.95 vs. 2.94; P=0.005). CONCLUSIONS: The (18)F-FDG PET/CT can be as a powerful imaging tool in identifying tissue origin in liver cirrhosis patients suspected of cancers or with cancers of unknown primary sites.

Molecular characterization of the type I IFN receptor in two woodchuck species and detection of its expression in liver samples from woodchucks infected with woodchuck hepatitis virus (WHV).

Type I interferons (IFN-α/ß) serve as the first line of defense against viral infection and share the same type I IFN receptor (IFNAR) complex, which is composed of IFNAR1 and -2. The Eastern woodchuck (Marmota monax) and Chinese woodchuck (Marmota himalayana) are suitable for studying hepatitis B virus (HBV) infection. Here, the complete or partial sequences of the IFNARs of both species were obtained and analyzed. Small interference RNAs targeting wIFNAR1 and -2 specifically down-regulated the expression of wIFNAR1 and -2 and the IFN-stimulated gene MxA in a woodchuck cell line, respectively. IFNAR2 was significantly up-regulated in primary woodchuck hepatocytes stimulated with IFN-α or -γ. The expression of woodchuck IFNAR1 and -2 was decreased in woodchucks chronically infected with woodchuck hepatitis virus (WHV). These results are essential for studying type I IFN-related innate immunity and therapy in hepadnaviral infection in the woodchuck model.

[Genotyping of hepatitis B virus and its clinical significance in patients with chronic hepatitis B].

OBJECTIVE: To investigate the distribution of hepatitis B virus (HBV) genotypes in Guangdong and explore its clinical significance. METHODS: Fifty-five patients with chronic active hepatitis (CAH) from Guangdong province were included in this study. HBV surface gene amplified by PCR was analyzed by restriction fragments length polymorphism (RFLP) for HBV genotyping, and the relationship of HBV genotype with clinical, serological and histological data of the patients was analyzed. RESULTS: Twenty-eight out of 55 patients were infected with HBV strains of genotype B (51.0%), 18 with genotype C (32.7%), 4 with genotype D (7.3%), 4 with HBV classified as genotype B+C (7.3%), and 1 (1.8%) with HBV that did not conform to any of the genotypes from A to G. No significant differences in clinical, histological, or serological data of HBV DNA loading were detected between genotypes B and C. But in patients older than 30 years, the genotype C was accompanied by significantly higher HBV DNA loading and serum HBeAg level than genotype B (Fisher's exact test, P=0.002). CONCLUSIONS: HBV genotype B and C are the major genotypes prevalent in Guangdong Province. Genotype C is associated with the longer duration of HBeAg and higher HBV DNA level in patients older than 30 years, suggesting the higher risk of HBV genotype C infection to progress into chronic liver disease.

[Influences of the genotypes of HBV and HBeAg regarding their response to PEG-IFN in chronic hepatitis B patients].

OBJECTIVE: To study the effects of genotypes of HBV and HBeAg on the response to PEG-interferon alpha (PEG-IFN) in chronic hepatitis B (CHB) patients. METHODS: PCR-RFLP and S gene sequencing were conducted in 42 CHB patients. RESULTS: The sustained response (SR) rates were 66.7% in genotype B and 27.3% in genotype C group. The P value was 0.039 by the Pearson Chi-square test, while it was 0.06 by the Fisher's exact test. The results suggested a trend that patients with genotype B HBV compared to genotype C had better SR to PEG-IFN therapy, although the difference was not significant. Results also showed that SR rate in patients with HBeAg-negative CHB (7/8 87.5%) was significantly higher than that in HBe+ CHB patients (8/21 38.1%, P < 0.05). CONCLUSION: Our results indicate that HBV genotype and HBeAg, especially the later, are main factors for predicting PEG-IFN therapy response in CHB patients.

Sepsis-associated cholestasis in adult patients: a prospective study.

BACKGROUND: Sepsis-associated cholestasis is a common problem in neonatal patients. However, there are limited data related to sepsis-associated cholestasis in adults. In this study, the authors assessed the clinical characteristics, risk factors and outcome of adult patients with sepsis-associated cholestasis. METHODS: An observational prospective single-center study was conducted. A total of 608 patients with sepsis (66 patients with cholestasis and 542 without evidence of cholestasis) from January 1, 2005, to December 31, 2011, were included from the infectious disease unit. Demographic, clinical and laboratory information were recorded on admission for all patients. Additional data were also collected on the day of the 1st episode of bacteremia for patients who developed cholestasis. Accordingly, the organ dysfunction scores (Acute Physiology and Chronic Health Evaluation [APACHE] II and Sequential Organ Failure Assessment [SOFA]) were assessed on the same day. RESULTS: The mean age of the 608 patients was 49.3 ± 11.4 years (range, 22-83 years); 312 (51.3%) patients were men, 296 (48.7%) were women. The mean APACHE II and SOFA score were 15.2 ± 6 and 5.6 ± 2.3, respectively. Sepsis-associated cholestasis was strongly associated with older age, biomarkers of organ dysfunction and clinical composite scores (APACHE II and SOFA). Mortality was higher in patients with sepsis-associated cholestasis (10.6%) compared with subjects with sepsis without cholestasis (1.5%) (P < 0.05). CONCLUSIONS: The authors found that sepsis-associated cholestasis affects the outcome of patients with sepsis in the infectious disease unit. Additional clinical studies are necessary to elucidate the pathology and pathophysiology of sepsis-associated cholestasis.

B-cell clonality in the liver of hepatitis C virus-infected patients.

AIM: The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B-cell lymphoma remains controversial. In patients with HCV infection, B-cell clonal expansions have been detected in peripheral blood and bone marrow, and a high prevalence of B-cell non-Hodgkin's lymphomas has been documented. Liver biopsies in chronic HCV infection frequently show portal lymphoid infiltrates with features of B follicles, whose clonality has not yet been investigated. The object of this study was to determine the frequency of liver-infiltrating monoclonal B-cells in 40 patients with HCV infection. METHODS: Eight hundred and forty-eight patients were studied prospectively, including 40 HCV-positive patients and 808 patients with chronic hepatitis B virus (HBV) infection. Immunohistochemical study for B- and T-cell markers was performed on the paraffin-embedded liver tissue sections. The clonality of lymphoid B-cells was tested using a polymerase chain reaction (PCR) approach designed to identify immunoglobulin heavy chain gene (IgH) rearrangements. RESULTS: Liver-infiltrating monoclonal B-cells were detected in the liver for 4 (10%) of 40 HCV-positive patients but were present in only 3 (0.37%) of 808 liver biopsy specimens with chronic HBV infection. Chi-square testing showed that the monoclonal B-cells infiltration in the liver was more frequent in the HCV-infected patients (P = 0.000). A clonal IgH rearrangement was detected in 5 (71.4%) of 7 liver biopsy specimens with monoclonal B-cells infiltration. In 2 of 5 patients with both a clonal B-cell expansion and monoclonal B-cells infiltration in the liver, a definite B-cell malignancy was finally diagnosed. CONCLUSION: Liver-infiltrating monoclonal B-cells are detected in the liver of patients with chronic HCV and HBV infection. A high percentage of patients with monoclonal B-cells infiltration and B-cell clonality in the liver were finally diagnosed as having a definite B-cell malignancy.

[Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance].

OBJECTIVE: To explore the role of interferon (IFN)-alpha/beta receptor beta subunit (IFNAR2) in the patients' response to IFN-alpha therapy as influenced by the grade of chronic hepatic inflammation, and understand the relation of IFNAR2 expression in the peripheral blood mononuclear cells (PBMCs) with HBV infection. METHODS: Liver tissue specimens were obtained from 21 patients with chronic hepatitis B for examination of the hepatic inflammation, and PBMCs were isolated from another 16 patients with chronic hepatitis B and 15 health control subjects. Both the hepatic tissues and PBMCs were examined for IFNAR2 expression using immunohistochemistry. RESULTS: The 21 patients with chronic hepatitis B were divided into 3 groups according to the severity of hepatic inflammation, namely G(1) (n=3), G(2) (n=7) and G(3) (n=11) groups. The patients in G(3) group showed had significantly higher IFNAR2 expressions in liver (25.1307-/+7.0700) than those of the G(1) (5.6913-/+1.8422) and G(2) (7.4706-/+5.3572) groups (P=0.000). The IFNAR2 levels in the PBMCs, however, did not show significant difference between patients with chronic hepatitis B and the healthy control subjects. CONCLUSION: In patients with chronic hepatitis B, IFNAR2 expression level is positively correlated to the severity of hepatic inflammation, and increased IFNAR2 expression in severe hepatic inflammation is therefore likely to result in increased response rate to INF-alpha therapy. The expression of IFNAR2 in the PBMCs is not associated with HBV infection.