[Real-time tissue elastography in chronic liver disease].

BACKGROUND/AIM: In patients with chronic liver diseases, the histological classification of liver fibrosis is essential for predicting prognosis and selecting appropriate antiviral therapy. This study aimed to determine the usefulness of a new noninvasive method for the assessment of liver fibrosis by using real-time tissue elastography, which can be performed with conventional ultrasound probes. METHODS: Thirty-nine patients who had liver fibrosis and had undergone liver resection or liver biopsy were included in this study. The surgical specimens obtained were examined to determine the histological stage of liver fibrosis. The strain ratio of subcutaneous fat tissue to liver tissue was calculated. We examined the correlation between the strain ratio and the histological liver fibrosis stage, and compared the utility with various surrogate liver fibrosis markers. RESULTS: The strain ratio significantly differed with the stage of liver fibrosis, and they had significant correlation (Kruskal-Wallis test: p<0.0001; Spearman's rank correlation, p<0.0001, r=0.797). We identified 5.8 and 3.7 as the cutoff values of strain ratio for the diagnosis of cirrhosis and significant fibrosis. The sensitivity at these values was 92.9% and 81.9% respectively; the specificity, 96.0% and 88.9%; and the areas under the receiver operating characteristic curve (AUROCs), 0.977 and 0.913, respectively. The AUROC was superior to the other surrogate liver fibrosis markers tested. CONCLUSIONS: Real-time tissue elastography is a useful method for the diagnosis of significant fibrosis and cirrhosis in patients with chronic liver diseases.

Schistosomiasis japonica identified by laparoscopic and colonoscopic examination.

A 45-year-old Philippine woman who came from Mindanao Island was admitted to our hospital with a complaint of epigastric discomfort. Abdominal ultrasonography and computed tomography demonstrated a network pattern and linear calcification in the liver. Laparoscopic examination showed numerous yellowish, small speckles over the liver surface. The liver surface was separated into many small blocks by groove-like depressions, demonstrating a so-called tortoise shell pattern. Conventional colonoscopy and narrow-band imaging showed irregular areas of yellowish mucosa, and diminished vascular network and increased irregular microvessels extending from the descending colon to the rectum. Liver biopsy showed many Schistosoma japonicum eggs in Glisson's capsule and colon biopsy showed many S. japonicum eggs in the submucosal layer. These findings established a diagnosis of schistosomiasis japonica. The present case is imported schistosomiasis japonica. Even though new cases have not occurred recently in Japan, we should remain aware of schistosomiasis japonica for patients who came from foreign epidemic areas.

FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C.

UNLABELLED: Diagnosis of the stage of liver fibrosis in chronic hepatitis C is essential for making a prognosis and deciding on antiviral therapy. In the present study a simple model consisting of routine laboratory tests was constructed and then validated in cross-sectional and longitudinal investigations. Consecutive treatment-naive patients with chronic hepatitis C who had undergone liver biopsy were divided into 2 cohorts: an estimation set (n = 240) and a validation set (n = 120). A longitudinal set consisted of 30 patients who had undergone a liver biopsy twice, before and after IFN treatment. The FibroIndex was derived from the platelet count, AST, and gamma globulin measurements in the estimation set. The areas under the ROC curves of the FibroIndex for predicting significant fibrosis were 0.83 and 0.82 for the validation set, better than those of the Forns index and the aminotransferase-to-platelet ratio index (APRI). Using the best cutoff values, whether significant fibrosis was present was diagnosed with high positive predictive values, and 35% of patients could avoid liver biopsy. In the longitudinal set, there was a significant decrease in the FibroIndex of 14 patients whose fibrosis stage improved, and a significant increase in that of 5 patients whose fibrosis stage deteriorated. Change in the FibroIndex correlated significantly with variation in fibrosis stage. There was no such correlation with the Forns index or the APRI. CONCLUSION: The FibroIndex is a simple and reliable index for predicting significant fibrosis in chronic hepatitis C and could also be used as a surrogate marker during antifibrotic treatment for chronic hepatitis C.

Expression of oxidative stress-related molecules in circulating leukocytes and urine in patients with chronic viral hepatitis.

AIMS: Oxidative stress plays a role in pathogenesis of chronic viral hepatitis. Expression of oxidative stress-related molecules remains to be clarified. METHODS: 4-hydroxy-2-nonenal (4-HNE), 4-hydroxy-2-hexenal (4-HHE), catalase, superoxide dismutase-1 (SOD-1), glutathione peroxidase-1, thioredoxin (TRX) in leukocytes and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined in 164 persons, including 130 chronic viral hepatitis patients and 34 normal individuals, by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Hepatic expression of these proteins was immunohistochemically examined in 12 patients with chronic viral hepatitis, compared with three persons without liver damage. RESULTS: The 4-HNE/beta-actin ratios in chronic viral hepatitis were significantly higher than those in normal individuals (P<0.01), and were significantly correlated with asparate aminotransferase (AST) and alanine aminotransferase (ALT) (P<0.01, each). The catalase/beta-actin and SOD-1/beta-actin ratios in chronic viral hepatitis were higher than those in normal individuals, and were significantly correlated with 4-HNE/beta-actin ratios (P<0.01, each). Hepatic expression of 4-HNE, 4-HHE, catalase, SOD-1 and TRX in chronic viral hepatitis was higher than that without liver damage. Urinary excretion of 8-OHdG was not changed in chronic viral hepatitis. CONCLUSIONS: The results of the present study suggest that expression of oxidative stress-related molecules in leukocytes is upregulated in relation to serum aminotransferase levels.

[Interferon modulates serum concentrations of 7S domain of type IV collagen according to the pretreatment levels in patients with chronic hepatitis C].

To evaluate the predictive value for a response of interferon (IFN) and the effect of IFN on the metabolism of hepatic fibrosis, serum levels of 7S domain of type IV collagen (7S) were serially measured before and after 6 months of IFN treatment in 470 treated and 145 untreated patients with chronic hepatitis C. Serum initial 7S levels were closely correlated with hepatic fibrosis scores (r = 0.627, p < 0.001). Those levels in nonresponder were significantly higher than those in sustained and transient responders. Serum 7S levels decreased during and after treatment in all treated groups, but increased in the untreated group. The absolute changes in 7S levels at the end of IFN therapy did not correlate with the changes in ALT levels, but correlated negatively with the initial 7S levels (r = -0.678, p < 0.001) in the treated group. Serum 7S levels at the end of treatment increased temporarily in patients with lower pretreatment levels, but decreased in those with elevated initial levels. These results suggest that IFN treatment modulates serum 7S levels according to the pretreatment levels in chronic hepatitis C.

Effect of posture on echographic examination for dialysate in patients treated with chronic ambulatory peritoneal dialysis as a model of ascites.

We evaluated the effect of posture on echographic examination for dialysate in 15 patients treated with chronic ambulatory peritoneal dialysis as a model of ascites. After gradually infusing 500 1000 and 1500 ml dialysate into their abdominal cavity, we compared echographic findings of infused fluids in dorsal, knee-elbow, and standing positions. The height of fluid in the standing position was largest and the width of fluid in Morison's pouch in the dorsal position was smallest. When calculating the volume of the infused fluid by modeling as an elliptic cone in the standing position or as a segment of a sphere in the knee-elbow position, the correlation coefficients between the calculated volumes and the infused volumes were 0.979 (P<0.0001) in the knee-elbow position and 0.920 (P<0.0001) in the standing position, respectively. Patients and examiners were required to endure an unnatural and awkward posture in the knee-elbow position. These findings suggest that echographic examination in the standing position is an easy and accurate method for the diagnostic paracentesis and the measurement of the volume of ascites in this model.

Increase in serum 7S domain of type IV collagen and N-terminal propeptide of type III procollagen levels with normal serum transaminase levels after long-term oral administration of Tegaful-Uracil.

To evaluate whether oral administration of Tegaful-Uracil (UFT(R)), a biochemical modulator of 5-fluorouracil that contains tegafur and uracil, can induce hepatic fibrosis, serum 7S domain of type IV collagen and N-terminal propeptide of type III procollagen levels were measured in 63 UFT(R)-treated, 38 tegafur-treated and 40 untreated patients. Serum transaminase and bilirubin levels were normal in almost all patients. Serum levels of 7S collagen and type III propeptide increased in 25 and 17% of the UFT(R)-treated patients, respectively, although a majority of tegafur-treated and untreated patients showed no increase in these markers. The patients with the elevated levels demonstrated mild or moderate hepatic fibrosis without necroinflammation in the liver. Both serum levels decreased markedly after the discontinuation of UFT(R). These findings suggest that long-term oral administration of UFT(R) can induce hepatic fibrosis without the elevation of serum transaminase levels and necroinflammation in the liver, and serum 7S collagen and type III procollagen are of diagnostic value for UFT(R)-induced hepatotoxicity.

A case with hepatic fibrosis showing ascites and esophageal varices induced by oral UFT(R) administration.

An 81-year-old male patient developed hepatic fibrosis with ascites and esophageal varices 4 years after oral administration of UFT(R) as postoperative adjuvant therapy for lung cancer. Although serum transaminase levels remained normal during follow-up periods, ascites developed 3 years after the treatment, and disappeared rapidly after the cessation of UFT(R), but recurred by accidental readministration of UFT(R). Serum markers for hepatitis viruses, various auto antibodies and a history of alcoholic abuse were all negative. Liver biopsy showed mild to moderate hepatic fibrosis without hepatocellular necrosis. Serum levels of N-terminal propeptide of type III procollagen, 7S fragment of type IV collagen and hyaluronic acid were elevated at diagnosis and decreased after the discontinuation of UFT(R). Esophageal varices were also improved. These findings suggest that hepatic fibrosis can be induced by oral administration of UFT(R) and that serum fibrogenesis/fibrosis markers are useful for early diagnosis of UFT(R)-induced hepatic fibrosis.