TT virus infection in chronic liver disease.

BACKGROUND/AIMS: The exact role of the novel hepatotropic TT virus regarding the etiology of viral hepatitis, as well as the progression towards chronic liver disease has as yet not been defined. Moreover, the contribution of TTV infection to the course of chronic hepatitis B or C virus infections also still awaits clarification. Hence, the aim of our study was to investigate the impact of TTV infection on clinical severity and histology of chronic liver disease originating from HBV and/or HCV infections in Thai patients concomitant with the determination of TTV's association with non-B, non-C chronic liver disease and compared to its prevalence among voluntary blood donors. METHODOLOGY: DNA was extracted from the sera collected from 115 hepatitis B patients, 41 hepatitis C, and 48 negative for either viral marker, who had all been diagnosed with chronic liver disease ranging from chronic hepatitis over cirrhosis to hepatocellular carcinoma. The sera obtained from 200 voluntary blood donors served as controls. TTV DNA was amplified by seminested polymerase chain reaction (PCR) employing primers derived from the genome's most conserved region. The PCR products were analyzed by gel electrophoresis. Liver function tests were performed by means of a chemical analyzer. RESULTS: TTV DNA was detected in 20% of the HBV-positive and 19.5% of the HCV-positive chronic liver disease patients. Within the group of patients seronegative for both viral markers, TTV was detected in 8.3%. Furthermore, its DNA was identified in 6.8% of the HCC patients and finally, in 7% of the blood donors. Yet, no significant differences between TTV infected and non-infected patients were found as to demographic data, assumed source of infection, biochemical abnormalities, or severity of liver histology. CONCLUSIONS: TTV appears to be highly prevalent on a worldwide scale but regarding etiology of and progression towards serious liver disease, its contribution seems to be minor if not altogether non-existent. Hence, regarding clarification of its clinical significance, further studies are certainly required.     

Comparison of once-daily and thrice-daily netilmicin regimens in serious systemic infections: a multicenter study in six Asian countries

Patients with serious systemic infections admitted to eight medical centers in six Asian countries were treated with 300 mg of netilmicin given once daily (group A: 92 patients) or 100 mg of netilmicin given three times daily (group B: 93 patients). Netilmicin was administered by intramuscular injection or slow intravenous infusion until clinical, laboratory, and bacteriologic measures were normalized and for not more than two additional days. A clinical cure was achieved in 88% of the patients from group A and in 68% from group B. The causative micro-organisms were eliminated or infection site healed in 90% of group A and in 88% of group B. The mean treatment duration was 6.9 days in group A and 8.8 days in group B. Two patients in each group developed symptoms of nephrotoxicity; the pretreatment serum creatinine levels in all four patients were in the high borderline range. No other serious side effects were found. It is concluded that netilmicin administered once daily is safe and more effective than netilmicin administered three times daily.     

Long-term effect of interferon therapy on incidence of cirrhosis and hepatocellular carcinoma in Thai patients with chronic hepatitis B

The aim of this study was to assess the long-term effects of interferon (IFN) therapy on the incidence of disease progression to cirrhosis and hepatocellular carcinoma (HCC) in Thai patients with chronic hepatitis B. Sixty-seven patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who received IFN therapy were retrospectively analyzed. The average duration of follow-up was 59.4+/-30.9 months (ranging from 20 to 119 months). Seventy-two untreated patients with comparable clinical data and mean duration of follow-up served as a control group. During follow-up, 24 (35.8%) treated and 7 (9.7%) untreated patients had a sustained loss of HBeAg. However, none of the treated patients or controls became negative for hepatitis B s antigen (HBsAg). Among treated patients, the response was independent of type and dose of IFN, as well as the presence of steroid priming. In addition, 1 of 24 (4.2%) sustained responders and 6 of 43 (14%) non-responders progressed to cirrhosis whereas 16 of 72 (22.2%) in the control group progressed to such sequelae. The overall incidence of new cirrhosis in sustained responders was significantly lower than in the control group (p=0.04). HCC appeared in 11 cirrhotic patients: 9 (12.5%) in the control group and 2 (4.7%) of the non-responders, whereas none of the sustained responders developed HCC. The average period to detection of HCC was 70.5+/-12.4 months for non-responders and 65.3+/-27.6 months for the control group, with no significant differences between these groups. In conclusion, our data suggest that IFN therapy might prevent the progression of cirrhosis and the development of HCC in patients with chronic hepatitis B. These beneficial effects were particularly observed in those who achieved a sustained virological response to treatment.     

Serum hyaluronan: a marker of liver fibrosis in patients with chronic liver disease

The aim of this study was to evaluate the clinical significance of serum hyaluronan (HA) as a marker of liver fibrosis in patients with chronic liver disease. Serum HA was measured by an ELISA-based method in 28 patients with chronic hepatitis (CH), 43 patients with liver cirrhosis (LC), 57 patients with hepatocellular carcinoma (HCC) and 60 healthy controls. Mean serum HA concentration in patients with LC was 1,376.80 +/- 2,568.85 ng/ml which was significantly higher than those in patients with CH, HCC and the controls (575.93 +/- 732.58, and 426.36 +/- 687.33, and 117.86 +/- 311.11 ng/ml, respectively). Based on a ROC curve analysis, a cut-off point of 354 ng/ml discriminated between LC and other groups with a sensitivity, specificity and accuracy of 82.4%, 78.2%, and 80.2%, respectively. Mean HA concentrations were correlated with the degree of liver fibrosis, but not the grade of necroinflammatory activity. In patients with LC, the mean serum HA level was significantly increased in the Child C group (3,977.96 +/- 4,906.21 ng/ml) in comparison with the Child B and A groups (1,002.63 +/- 448.55, and 537.90 +/- 424.16 ng/ml, respectively). We conclude that serum HA concentrations reflect the extent of liver fibrosis and severity of cirrhosis. Thus, serum HA can be a diagnostic marker of liver fibrosis and cirrhosis in patients with chronic liver disease.     

Serum interleukin-6 and interferon-gamma levels in patients with hepatitis B-associated chronic liver disease

Hepatitis B virus (HBV) infection can elicit a variety of clinical sequelae ranging from acute self-limited hepatitis to hepatocellular carcinoma, which are not attributable to a direct cytopathic effect of the virus but rather to the individual host's immune response. Cytokines, low-molecular-weight proteins with a broad range of activity, have been shown to be involved in the regulation of hepatocyte functions, as well as in the pathogenesis leading to liver damage. In the present study, we investigated the correlation between serum interleukin 6 (IL-6) and interferon gamma (IFN-gamma) in altogether 75 patients chronically infected with HBV. They comprised 15 asymptomatic carriers, 15 chronic persistent hepatitis (CPH) and 15 chronic active hepatitis (CAH) patients, 15 cases of cirrhosis and 15 patients with hepatocellular carcinoma (HCC) previously diagnosed by serology and histology, respectively. IL-6 and IFN-gamma levels in their sera were determined using a commercially available kit. Our results showed various concentrations of serum IL-6 detectable in 6.7% of asymptomatic carriers, 13.3% of patients with CPH, 20% of patients with CAH, 33.3% in cirrhotic patients and 66.7% in HCC. In contrast, serum IFN-gamma was only found in 13.3% of asymptomatic carriers and CAH, but could not be detected in the other groups. Our data demonstrated a positive correlation between serum IL-6 and clinical severity of chronic HBV infection, whereas the IFN-gamma levels appeared not to be correlated. From this we conclude that among chronic hepatitis patients IFN-gamma is mostly not expressed at a level detectable by serology, whereas according to other authors it is involved in the immediate immune response triggered by acute hepatitis. IL-6 on the other hand, might rather be responsible for liver inflammation and regeneration in chronic liver disease.     

Measles-associated appendicitis: two case reports and literature review

We report 2 cases of appendicitis associated with measles. Four previously reported cases are reviewed. In all 6 patients typical measles rash appeared after removal of the appendix, which showed Warthin-Finkelday giant cells.     

Rectal prolapse associated with cytomegalovirus pseudomembranous colitis in a child infected by human immunodeficiency virus

We report a newly recognized presentation of cytomegalovirus (CMV) enterocolitis in a 4-year-old girl with newly diagnosed HIV disease who presented with rectal prolapse. Gross findings showed multiple whitish punctate lesions. An endoscopic examination revealed multiple shallow ulcers and pseudomembranes along the colon. A biopsy from colonic tissues demonstrated CMV-like inclusion bodies. A direct immunofluorescence assay using specific CMV monoclonal antibody was positive for CMV-infected cells in specimens from the rectal smear.     

Gender difference in clinicopathologic features and survival of patients with hepatocellular carcinoma

AIM: To determine the influence of gender on the clinicopathologic characteristics and survival of patients with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of medical records was performed in 299 patients with HCC and their clinicopathologic features and survival were compared in relation to gender. RESULTS: There were 260 male (87%) and 39 female patients (13%), with a male-to-female ratio of 6.7:1. Female patients had lower mean serum bilirubin levels (P=O.03), lower proportion of alcohol abuse (P=O.O02), smaller mean tumor size (P=O.02), more frequent nodular type but less frequent massive and diffuse types of HCC (P=O.01), wereless advanced in Okuda‘s staging (P=O.04), and less frequently associated with venous invasion (P=O.03). The median survivals in females (14 mo) were significantly longer than that of male patients (4 mo) (P=O.O04, log-rank test). Multivariate analysis demonstrated that high serum alphafetoprotein levels, venous invasion, extrahepatic metastasis and lack of therapy were independent factors related to unfavorable prognosis. However, gender did not constitute a predictive variable associated with patient survival. CONCLUSION: Female patients tend to have higher survival rates than males. These differences were probably due to more favorable pathologic features of HCC at initial diagnosis and greater likelihood to undergo curative therapy in female patients.