Measurement of Portal Systemic Shunting by Oral and Per-rectal Administration of [123I]Iodoamphetamine, and Clinical Use of the Results

Objective . We used a method by which the portal shunt index via the superior mesenteric vein (Sl-S) and that via the inferior mesenteric vein (Sl-I) could he evaluated simultaneously. The clinical usefulness of the method was studied. Methods : Scintigraphy was done 3 h after subjects took an enteric-coated capsule containing [123I|iodoamphetamine. At that time, the radio-nuclide was injected into the rectum. Countsfor the lungs and the liver were used to calculate the two shunt indices. Results : The mean SI-S and SI-I tended to be higher for disorders that were more severe, increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis. In cirrhotic patients, the SI-1 was higher than the SI-S ( p < 0.001). The SI-S and SI-I were both higher in cirrhotic patients with esophageal varices than in such patients without varices ( p < 0.05 and < 0.001). The SI- S and SI-I were higher in cirrhotic patients with ascites than in such patients without ascites ( p < 0.001 and <0.01). Correlation between either of these indices and classical indicators of functional reserve was high. The correlation of SI-S with the Child-Turcotte classification and total bilirubin level was higher than the correlation of the SI-I and these indicators of functional reserve. Conclusions : This method permits assessment of the portal hemodynamics in a relatively noninvasive way, and is clinically meaningful.     

Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis

In a prospective randomised controlled study, 90 patients with chronic active hepatitis C and compensated cirrhosis were assigned symptomatic treatment or interferon alfa (IFN-alpha). We report data on decompensation, detection of hepatocellular carcinoma, and mortality rates. IFN-alpha gave a sustained response in only a small proportion of patients, but worsening of compensated cirrhosis was prevented and development of hepatocellular carcinoma was inhibited, increasing the survival rate. The risk ratio of IFN-alpha versus symptomatic treatment decreased by 0.250 for progression to Child-Pugh grade B, 0.256 for detection of hepatocellular carcinoma, and 0.135 for a fatal outcome.     

Optimal duration of additional therapy after biochemical and virological responses to lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomized trial

Aim:  The endpoint of treatment with nucleoside analogs remains unclear for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We report the results of a randomized trial to determine the optimal duration of additional therapy after response to lamivudine in HBeAg-negative patients.
Methods:  Twenty-two patients with HBeAg-negative chronic hepatitis B who exhibited biochemical and virological responses to lamivudine were enrolled. When patients responded to treatment, they were randomly assigned to receive 12 more months of therapy (Group A, 11 patients) or 24 more months of therapy (Group B, 11 patients).
Results:  The baseline characteristics of the patients were similar in the two groups. Biochemical and virological responses were obtained in all patients within 6 months. Drug resistance developed in one patient in Group A during month 7 of additional therapy, and in five patients in Group B from months 13–23 of additional therapy. Ten patients in Group A and six in Group B completed the protocol and were included in analysis. Eight of the 10 patients in Group A experienced relapse between months 2 and 14 after the discontinuation of therapy, while three of the six patients in Group B experienced relapse between months 2 and 24. There was no difference in cumulative relapse rate between the groups ( P  = 0.275).
Conclusion:  Additional therapy with lamivudine for longer than 12 months after biochemical and virological responses in patients with HBeAg-negative chronic hepatitis B could increase the risk of drug resistance, but did not reduce the rate of relapse.     

Liver disease in hepatitis C virus carriers identified at blood donation and their outcomes with or without interferon treatment: Study on 1019 carriers followed for 5–10 years

Aim: To portray liver disease and project outcomes in carriers of hepatitis C virus (HCV) in the general population. Methods: Liver disease was evaluated in 1019 individuals who were found with HCV infection at blood donation, and they were followed for 5-10 years with or without receiving interferon (IFN). Results: At baseline, chronic hepatitis was detected in 529 (51.9%) HCV carriers and more frequently in men than in women (62.6% [299/478]vs 42.5% [230/541], P < 0.01); cirrhosis was diagnosed in five (0.5% [three men included]) and hepatocellular carcinoma (HCC) in one (0.1% [man]). Of the carriers who were followed for 5 years or longer, loss of HCV-RNA from serum was achieved in 61 (31.0%) of the 197 treated with interferon (IFN) and only one of the 211 (0.5%) without IFN (P < 0.0001). HCC developed in 14 carriers including six ofthe 211 (2.8%) without IFN and eight of the 197 (4.1%) with IFN (six non-responders included). Follow ups of the 949 carriers identified age (P < 0.002), male gender (P < 0.01) and cirrhosis at the baseline (P < 0.0001) as factors contributing to the development of HCC. Cumulative incidence rates of HCC during 10 years among carriers found with chronic hepatitis increased in parallel with the age at the baseline. Conclusion: Identification of HCV carriers in the general population and treating those indicated with IFN would help decrease the development of HCC and lift its medical, as well as economic, burdens off society.     

Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial

BACKGROUND: Interferon therapy decreases the incidence of hepatocellular carcinoma in patients with chronic hepatitis C. OBJECTIVE: To evaluate effects of interferon-alpha on recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. DESIGN: Randomized, controlled trial. SETTING: University hospital, medical center, and affiliated hospital in Osaka, Japan. PATIENTS: 30 men were randomly allocated after resection to the interferon-alpha group (n = 15) or the control group (n = 15). INTERVENTION: Patients in the interferon-alpha group received interferon-alpha, 6 MIU intramuscularly daily for 2 weeks, then three times weekly for 14 weeks, and finally twice weekly for 88 weeks. MEASUREMENTS: Recurrence rates after resection. RESULTS: Recurrent tumors were detected in 5 patients in the interferon-alpha group and in 12 control patients. The recurrence rate was significantly lower in the interferon-alpha group than in the control group (P = 0.037). CONCLUSION: Postoperative interferon-alpha therapy appears to decrease recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.     

Sleep-disordered breathing in patients with idiopathic cardiomyopathy.

BACKGROUND: Sleep-disordered breathing may adversely affect heart function, and thereby contribute to the progression of heart failure. A study was undertaken in patients with idiopathic cardiomyopathy to document the characteristics of sleep-disordered breathing. METHODS AND RESULTS: Thirty-five patients with a diagnosis of idiopathic cardiomyopathy, comprising 20 patients with dilated cardiomyopathy (DCM) and 15 patients with hypertrophic cardiomyopathy (HCM), underwent overnight polysomnography. Of these 35, 16 (80%) of the DCM patients and 7 (47%) of the HCM patients had sleep-disordered breathing. Central sleep apnea-hypopnea syndrome (CSAHS) was seen in 10 DCM patients, but not in the HCM patients, and obstructive sleep apnea-hypopnea syndrome (OSAHS) was seen in 6 DCM patients and 7 HCM patients. CSAHS was seen in DCM patients with a low left ventricular ejection fraction. HCM patients with OSAHS had a significantly greater body mass index (BMI) than those without OSAHS and CSAHS (27.6 +/- 3.8 vs 22.0 +/- 4.0 kg/m2, p<0.05). DCM patients with OSAHS had a larger BMI than those with CSAHS (29.3 +/- 5.8 vs 24.2 +/- 4.0 kg/m2, p<0.05) and those without OSAHS and CSAHS (29.3 +/- 5.8 vs 21.3 +/- 3.1 kg/m2, p<0.05). CONCLUSIONS: Sleep-disordered breathing is common in patients with idiopathic cardiomyopathy; half of DCM patients had CSAHS, which was closely associated with obesity.     

Emphysematous changes are caused by degradation of type III collagen in transgenic mice expressing MMP-1

Disruption of the extracellular matrix is believed to play an important role in the pathogenesis of emphysema. Prior studies have demonstrated that transgenic mice expressing the human tissue collagenase, matrix metalloproteinase 1 (MMP-1), develop emphysema. MMP-1 is a protease with substrate specificity for fibrillar collagen. Type I and III collagens, which are the most abundant proteins within the lungs, are the primary substrates for MMP-1. To assess if type I collagen was indeed the site of action for MMP-1 in these transgenic mice, hybrid mice were generated by crossing the MMP-1 transgenic mice with mice that had degradation-resistant type I collagen. The hybrid mice demonstrated an identical emphysematous phenotype as the MMP-1 transgenic mice, indicating that the degradation of type I collagen was not essential to the development of emphysema in these mice. Immunohistochemical studies in control mice demonstrated that collagen fibers in the alveolar walls and ducts of the normal mouse lungs consist mainly of type III collagen. In the transgenic and hybrid mice, the emphysematous changes, which developed, were associated with a marked decrease in type III collagen in these alveolar structures. These results indicate that MMP-1 generated the emphysematous phenotype via the degradative effect on type III collagen, which is a vital structural element of the alveolar walls. This is the first study to show that a matrix metalloproteinase may cause emphysema via its effects on a specific collagen subtype. As such, it should provide important insight into the mechanisms of this disease in humans.     

Portal vein thrombosis following percutaneous ethanol injection therapy for hepatocellular carcinoma.

Percutaneous ethanol injection therapy was performed in a 66-year-old woman with hepatocellular carcinoma. She developed portal vein thrombosis that on color Doppler revealed no tumor vascular signal, and so was diagnosed as non-tumor thrombus. The thrombus resolved over 3 months.     

Surgically resected hepatocellular carcinomas in patients with non-alcoholic steatohepatitis

BACKGROUND/AIMS: Surgically resected hepatocellular carcinomas (HCC) in patients with non-alcoholic steatohepatitis (NASH) have rarely been described and the clinicopathological characteristics of HCC and non-cancerous liver tissue are still obscure. METHODOLOGY: From 1997 to 2004, 242 patients with HCC underwent hepatic resection at the Hiroshima Red Cross Hospital and Atomic Bomb Survivors' Hospital. Among this group, the diagnosis of NASH was made in 3 patients. RESULTS: All 3 patients with HCC had cirrhosis. The tumor cells contained Mallory bodies and fat. The non-cancerous areas showed nodular regeneration with fatty changes, ballooning degeneration, and mild inflammatory infiltrates, as well as perivenular and perisinusoidal fibrosis. CONCLUSIONS: Patients with NASH and cirrhosis may progress to HCC, and careful follow-up based on tumor markers and imaging modalities, is essential to detect resectable HCC in patients with NASH and cirrhosis.     

Diagnostic ability of 99mTc-HSA-DTPA scintigraphy in combination with SPECT/CT for gastrointestinal bleeding

Purpose

Gastrointestinal (GI) bleeding scintigraphy in combination with single-photon emission computed tomography/computed tomography (SPECT/CT) remains to be studied in detail. This study aimed to examine the diagnostic ability of this tool.

Methods

GI bleeding scintigraphy using ^99mTc-human serum albumin-diethylenetriaminepentaacetic acid was performed for 38 patients with suspected GI bleeding. Twenty-four patients were diagnosed using planar images alone (planar group) and 14 patients were diagnosed using planar images and additional SPECT/CT images (planar + SPECT/CT group). The diagnostic ability of each method was analyzed.

Results

GI bleeding was observed in 20 of the 38 patients. For the existence of GI bleeding, planar images alone showed a sensitivity of 70%, specificity of 93%, positive predictive value (PPV) of 88%, negative predictive value (NPV) of 81%, and an overall accuracy of 83%, whereas planar images + SPECT/CT showed a sensitivity of 100%, specificity of 75%, PPV of 91%, NPV of 100%, and an overall accuracy of 93%. The source of bleeding was accurately diagnosed in 50% in the planar group and 78% in the planar + SPECT/CT group. In the planar + SPECT/CT group, 44% of the evaluable patients showed correct localization of the source of GI bleeding by additional SPECT/CT images, although planar images only showed incorrect localization.

Conclusion

GI bleeding scintigraphy in combination with SPECT/CT is a noninvasive and useful tool for the examination of GI bleeding.