摘要:

ABSTRACTThe purpose of the present study was to analyse lymphocyte proliferative responses to recombinant hepatitis C virus (HCV) antigens in chronic hepatitis C. Four recombinant peptides derived from the NS3, core, E1 and E2/NS1 regions of the HCV genome were used as antigens in lymphocyte proliferative responses. Forty‐two patients, classified into various sub‐groups, and 17 healthy control subjects were tested and the specific response was expressed as a stimulation index. Responses were analysed with alanine aminotransferase (ALT) level and histological diagnosis. NS3‐ and core‐antigen specific responses in all patient groups were significantly higher than in the healthy control group. E1‐ and E2/NS1‐antigen‐specific responses in the patient group with ALT levels exceeding 100 IU/L were significantly higher than those in other patient groups. Histological diagnosis was not correlated to the intensity of the core‐ and NS3‐specific responses. E1‐ and E2/NS1‐antigens induced significantly elevated responses in patients with chronic active hepatitis and liver cirrhosis compared with results in the healthy control group and in patients with chronic persistent hepatitis. In conclusion, the significantly elevated responses to core‐ and NS3‐antigens may be related to HCV infection and such responses to E1‐ and E2/NS1‐antigens could be related to the severit

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00317.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTIn an attempt to predict virological sustained responders among patients with chronic hepatitis C after interferon therapy, HCV‐RNA in serum was measured by a one tube RT‐PCR assay kit using the RNA corresponding to 5 μL serum (standard assay) or 300 μL serum (enhanced‐sensitivity assay). Dilution analysis revealed that sensitivity of the ‘enhanced‐sensitivity assay’ increased by 10–100‐fold when compared with a ‘standard assay'. Using these assays, prospective study of interferon therapy on 38 HCV‐RNA seropositive cases with chronic hepatitis (total amount 702 MU; duration of treatment 5–6 months) was performed. At the end of treatment, six were still positive and 32 became negative by the ‘standard assay', whereas an additional eight cases became positive (total 14 cases positive; the remaining 24 cases negative) by the ‘enhanced‐sensitivity assay'. Hepatitis C viral RNA state at the end of treatment remained the same 6 months later in 23 cases (61%) by a ‘standard assay’ and in 31 (82%) by the ‘enhanced‐sensitivity assay'. Of importance was that all patients (14 cases) demonstrating HCV‐RNA in serum at the end of therapy, even by the ‘enhanced‐sensitivity assay', did not show the disappearance of HCV‐RNA in serum despite the long follow up. From these results, in order to improve our treatment efficacy, we should try to modify our treatment protocol to the extent that at least HCV‐RNA becomes undetectable. That can be only feasible duri

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00318.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTHistological progress is one of the predictors of an unfavourable response to interferon (IFN) therapy in hepatitis C virus (HCV)‐associated chronic liver diseases (CLD). The aim of the present study was to investigate whether histological progress has an association with the expression of IFN receptor (IFN‐Rc) in the liver. Expression of mRNA of the IFN‐Rc for IFN‐α was investigated by reverse transcription polymerase chain reaction using liver biopsy specimens from 37 HCV‐associated CLD comprising 11 liver cirrhosis (LC) and 26 chronic hepatitis (CH) cases. IFN‐α and IFN‐β mRNA were detected in over 90% of subjects. In contrast, the detection rate of IFN‐Rc mRNA in chronic persistant hepatitis, chronic hepatitis 2A, chronic hepatitis 2B and liver cirrhosis (LC) was 100, 71.4, 22.2 and 0%, respectively. The absence of IFN‐Rc mRNA was significantly associated with the severity of fibrosis of the liver. These results indicated that IFN‐Rc expression decreases with the histological progress of the disease, suggesting that lower expression of IFN‐Rc mRNA may be partially responsible for the

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00319.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTTo investigate the therapeutic effect and incidence of side effects of recombinant interferon‐α2a (IFN‐α) in chronic aggressive hepatitis C under stratification by administration mode, a study was conducted by assigning patients to either group A (daily consecutive administration of 9 million units (MU) IFN‐α for 2 weeks and, thereafter, 3 MU intermittently 3 times weekly for 22 weeks) or group B (exclusively intermittent administration; 9 MU IFN‐α twice weekly or 6 MU IFN‐α thrice weekly for 24 weeks). The 28 patients in group A received IFN‐α for 24 weeks up to a total dose of 324 MU and the 53 patients in group B received the same for 24 weeks up to a total dose of 432 MU. When recovery was defined as the absence of hepatitis C virus (HCV)‐RNA 6 months after the completion of treatment, the rate of recovery for group A was 32.1% and that for group B was 37.7%, the latter being higher but without significance. Side effects in groups A and B consisted of leucopenia occupying 14.3 and 7.5%, respectively, and thrombocytopenia occupying 42.9 and 11.3%, respectively; group B exhibited lower values for both side effects. No difference was detected between these groups in other side effects, including pyrexia, generalized malaise, arthralgia or psilosis. Intermittent administration from the outset permitted shortened duration of hospitalization and earlier rehabilitation. Intermittent administration of INF‐α is required when treating patients with chronic hepatitis C showing lower leucoc

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00320.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTA case of primary splenic lymphoma in a patient with chronic hepatitis C is reported. A 69‐year‐old man with chronic hepatitis C was admitted to Fukuoka City Hospital for evaluation of an enlarging splenic tumour. In the spleen, ultrasonographic examination revealed a hypoechoic tumour and computed tomography demonstrated a non‐enhancing low density area measuring 7 cm in diameter; coeliac angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of the radioisotope in the splenic tumour. A splenectomy was performed and the morphological and immunohistochemical findings of this tumour were compatible with those of non‐Hodgin's B cell lymphoma. Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported. Lymphotropism of hepatitis C virus may play a pathological role in the development of non‐Hodgkin's lymphoma. We emphasize the importance of considering lymphoma in the differential diagnosis of extrahepatic disorders during the course of chronic hepatitis C virus i

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00321.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTPortal hypertensive gastropathy and duodenopathy are distinct clinical and endoscopic entities. Data on factors influencing the development of these lesions are still emerging. Data on portal hypertensive duodenopathy are scarce. We prospectively studied 230 patients with liver cirrhosis and oesophageal varices attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of Medical Sciences. One hundred and forty‐two patients had no history of upper gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic appearances were recorded before starting patients on a sclerotherapy programme. Forty‐four patients were re‐evaluated after variceal eradication. The frequency of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%, respectively. Mild PHG was present in 85% and was severe in the rest. Portal hypertensive duodenopathy was mild in 50%, while in the other half it was severe. There was no relationship of PHG and PHD to: (i) a history of upper gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores (P=NS for all). The prevalence of PHG was higher in those patients with oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal varices alone (68 of 123; 55%;P<0.05). However, no such increase in frequency of PHD was noted in patients with oesophagogastric varices. Sclerotherapy increased the frequency of PHG. Twenty‐four patients had PHG before starting sclerotherapy, while it was noted in 33 patients 1–3 months after variceal eradication (P<0.05). In contrast, there was no increase in the prevalence of portal hypertensive duodenopathy after sclerotherapy (P=NS). There was no correlation between endoscopic and histological changes of PHG and PHD. In conclusion, PHG is quite frequent in patients with cirrhosis and its frequency increases with the presence of oesophagogastric varices and after sclerotherapy. However, the frequency of PHD is low and is not affected by the factor

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00322.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTPulmonary hypertension is now recognized to be a rare association of liver disease and portal hypertension. This report describes the slow resolution of symptomatic pulmonary hypertension in a 33‐year‐old woman with cirrhosis who underwent isolated liver transplantation. The patient survived the surgery and perioperative period without significant haemodynamic compromise. After liver transplantation, the patient was monitored with regular Doppler echocardiography. By 27 months the pulmonary hypertension had almost completely resolved. This observation is important, as it suggests that patients with severe pulmonary hypertension who survive the perioperative period may have an excellent outcome, although resolution may be s

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00323.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTSeveral proteins are known to modulate cholesterol crystallization. We recently demonstrated that haptoglobin has cholesterol crystallization promoting activity. However, this effect is still not well understood mechanistically. The current study examined the distribution of haptoglobin compared to apolipoprotein A‐I (apo A‐I) to micelles, vesicles and crystals as an initial step in providing a focus for further studies of the mechanism of cholesterol crystallization activity. Specific protein purification was accomplished by immunoaffinity chromatography. The crystallization‐promoting activity of biliary haptoglobin, albumin and commercial apo A‐I was measured by a photometric crystal growth assay. The distribution of micelles, vesicles and proteins in model bile was determined by Sepharose CL‐6B column chromatography. Detection of the presence of test proteins in cholesterol crystals was determined using specific125I‐radiolabelled proteins. Haptoglobin (20 μg/mL) showed a significant crystallization promoting‐activity, whereas apo A‐I (30 μg/mL) only tended to show a slight inhibitory activity. The cholesterol crystal‐bound protein in each case was found to be less than 1% of the total concentration of that protein that had been added to the model bile system. The elution profile of commercial apo A‐I from a Sepharose CL‐6B column was strikingly altered when it was added to model bile prior to elution. In contrast, the column elution profiles for both haptoglobin and albumin were unchanged when model bile was similarly added to the sample. Haptoglobin increased the amount of cholesterol found in the vesicular fraction when compared to apo A‐I. Haptoglobin does not bind tightly to either biliary lipid particles or to cholesterol crystals but does increase the amount of cholesterol in vesicles by inducing a shift from micellar cholesterol (P=0.046). This shift appears to explain in part its promoting effect on ch

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00324.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTIn the present study, intestinal apo A‐IV synthesis was investigated using a carbon tetrachloride (CCl4)‐induced cirrhosis rat model. Triglyceride (TG) content in rat cirrhotic liver was increased markedly by 170% (P<0.001) and apo B was increased by 20% (P<0.05) compared with control levels. These results reflected the steatotic change in the liver. In contrast, TG levels in the small intestine of cirrhotic rats decreased significantly (P<0.01). In addition, intestinal apo A‐IV (jejunumP<0.001; ileumP<0.01) and its mRNA levels (jejunumP<0.01; ileumP<0.05) were also reduced. The decreased apo A‐IV content in the jejunum was confirmed by immunohistochemical analysis. These results indicate that intestinal apo A‐IV synthesis in cirrhosis is suppressed, at least under the condition of an overnight fast. Therefore, decreased intestinal apo A‐IV synthesis may relate to the decreased ability to absorb fat in cirrhosis, but a fat‐loading study will be necessary to confirm this hypothesis. It is unknown from the present study why serum apo A‐IV level is not significantly decreased, despite a reduction in apo A‐IV synthesis. The clearance of apo A‐IV by the liver may be delayed or apo A‐IV synthesis may be rather markedly enhanced during fat absorpti

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00325.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

ABSTRACTTo assess the characteristics of intrahepatic metastatic lesions (IML) in hepatocellular carcinoma (HCC), we analysed both the histological features and proliferative activities of 15 resected cases of HCC accompanied by IML. The histological features of the IML were essentially the same as those observed in the main nodules in 12 (80%) of 15 cases. In 13 (87%) of 15 cases, the labelling index of proliferating cell nuclear antigen (PCNA) in the IML was either higher than or the same as in the main nodules. In 10 (77%) of 13 cases, the MIB‐1 labelling index in the IML was either higher than or the same as in the main nodules. The results indicate that the histological features of the IML are essentially the same as those of the main nodules, while the proliferative activities in the IML were generally higher than those in the main nodules. Such characteristics may thus provide a clue to help distinguish intrahepatic metastasis from the multicentric occurrence of HC

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00326.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY