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Biomedical subjects

F Nevens

Publications and source records attributed to F Nevens.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C. European Concerted Action on Viral Hepatitis (EUROHEP).

BACKGROUND/AIMS: The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate. The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C. METHODS: A retrospective cohort study was carried out on 329 consecutive Caucasian patients with cirrhosis followed for a mean period of 5 years at seven tertiary care university hospitals. Inclusion criteria were biopsy-proven cirrhosis, anti-HCV positivity, abnormal serum aminotransferase levels and absence of complications of cirrhosis. RESULTS: The yearly incidence of hepatocellular carcinoma was 2.3% for 136 untreated patients and 1.0% for 193 patients treated with interferon alfa. The yearly incidence of hepatic decompensation was 5.7 for untreated and 1.5 for the treated patients. Fourteen (7%) of 193 treated patients showed sustained aminotransferase normalization and none of them developed complications of cirrhosis. At enrollment, untreated patients were older and had more severe liver disease than patients treated with interferon. After adjustment for clinical and serologic differences at entry between treated and untreated patients, the 5-year estimated probability of the occurrence of hepatocellular carcinoma was 2.1% and 2.7% and of decompensation was 7% and 11% for treated and untreated cases, respectively. CONCLUSIONS: This analysis did not detect any significant benefit of interferon alfa on morbidity in patients with compensated cirrhosis type C, although it suggests a reduction in complications of cirrhosis for those with a sustained response to therapy, and it indicates the need for better therapies.

Antiviral Agents↗
PubMed1997

Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients.

BACKGROUND & AIMS: Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C. METHODS: A cohort of 384 European cirrhotic patients was enrolled at seven tertiary referral hospitals and followed up for a mean period of 5 years. Inclusion criteria were biopsy-proven cirrhosis, abnormal serum aminotransferase levels, absence of complications of cirrhosis, and exclusion of hepatitis A and B viruses and of metabolic, toxic, or autoimmune liver diseases. RESULTS: Antibodies against hepatitis C virus were positive in 98% of 361 patients tested. The 5-year risk of hepatocellular carcinoma was 7% and that of decompensation was 18%. Death occurred in 51 patients (13%), with 70% dying of liver disease. Survival probability was 91% and 79% at 5 and 10 years, respectively. Two hundred five patients (53%) were treated with interferon alfa. After adjustment for clinical and serological differences at baseline between patients treated or not treated with interferon, the 5-year estimated survival probability was 96% and 95% for treated and untreated patients, respectively. CONCLUSIONS: In this cohort of patients, life expectancy is relatively long, in agreement with the morbidity data showing a slowly progressive disease.

Carcinoma, Hepatocellular↗
PubMed1997

Lamivudine therapy for chronic hepatitis B: a six-month randomized dose-ranging study.

BACKGROUND & AIMS: Lamivudine inhibits hepatitis B virus replication. This study investigated 6 months of lamivudine treatment at three doses. METHODS: Fifty-one patients (43% white, 49% Asian) with chronic hepatitis B were randomly assigned to receive 25, 100, or 300 mg of lamivudine orally once daily for 24 weeks with 24 weeks' follow-up. RESULTS: Serum hepatitis B DNA by liquid hybridization decreased in all patients and was undetectable at the end of the treatment in 7 of 12 (58%, 25 mg), 13 of 14 (93%, 100 mg), and 14 of 16 (88%, 300 mg) patients. Of the 36 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 7 of 11 (64%, 25 mg), 5 of 11 (45%, 100 mg), and 5 of 14 (36%, 300 mg) normalized ALT at treatment completion. Quantitative decreases hepatitis Be antigen and hepatitis B surface antigen concentrations were observed at all doses. In most patients, markers of replication returned after treatment. Two patients (4%) were anti-HBe positive at the end of follow-up. Lamivudine was well tolerated. The incidence of adverse events was similar across all dose groups. However, 2 patients developed temporary hepatic decompensation after increase in transaminase levels after treatment. CONCLUSIONS: Lamivudine was well tolerated and induced sustained suppression of hepatitis B replication during treatment in all patients at all doses. These data support investigation of longer treatment durations of 100 mg once daily.

Adult↗
PubMed1997

Confirmatory strategy of hepatitis C serology based on two screening assays in a diagnostic setting.

One hundred ninety seven successive sera, positive for anti-hepatitis C virus antibody with a third generation screening enzyme immunoassay (MEIA on IMX, Abbott), were tested with alternative third generation screening assays from two different manufacturers (Sanofi and Ortho), with an immunoblot assay (RIBA 3.0, Chiron), and by reverse transcriptase polymerase chain reaction (RT-PCR). Samples positive by RIBA 3.0 or by RT-PCR were considered as true positives. The positive predictive value of a combination of strong positive results in two screening assays was more than 98%. This combination of results has the same predictive value for detectable viraemia as a positive RIBA 3.0 (86.5%). Using a policy of two successive enzyme immunoassays in this clinical diagnostic setting diminishes the need for supplemental assays by more than 85%.

Hepatitis C↗
PubMed1997

Dual-phase helical CT of the liver: value of an early-phase acquisition in the differential diagnosis of noncystic focal lesions.

OBJECTIVE: Contrast-enhanced helical CT images of the liver are usually obtained during the portal vein phase (PVP), during which the parenchyma achieves peak enhancement. The purpose of this study was to determine whether the addition of arterial-phase (AP) scans would lead to improved characterization of focal lesions. MATERIALS AND METHODS: We reviewed the CT appearance of 102 focal lesions with a proven diagnosis. In the first part of the study, we assessed whether the addition of AP scans influenced the diagnostic performance of the three observers. In the second part of the study, we analyzed the morphologic appearance revealed on CT scans of the different types of lesions in the AP and PVP. RESULTS: The addition of AP scans led to a significant increase in the number of correct diagnoses: 71 lesions (70%) were correctly diagnosed with CT scans in both the AP and the PVP, compared with 54 lesions (53%) correctly diagnosed with CT scans in the PVP alone (p < .01). The largest difference was observed in the diagnosis of focal nodular hyperplasia (FNH) and adenoma (16/24 correct diagnoses instead of 6/24) (p < .005). Conversely, AP images did not significantly contribute to the diagnosis of hemangiomas and metastases. The following morphologic features were seen much more often on AP scans than on PVP scans and had a high positive predictive value (PPV): spoke-wheel pattern (FNH; PPV, 100%), central feeding vessel (FNH; PPV, 100%), and heterogeneous appearance with hyperdense components (hepatocellular carcinoma; PPV, 75%). CONCLUSION: Our data show that the radiologists' evaluation of CT scans in both the AP and the PVP improves the differentiation of hepatocellular carcinoma and FNH from other types of hepatic neoplasms.

Adenoma, Liver Cell↗
PubMed1996

[Transjugular intrahepatic portosystemic shunt in the treatment of refractory ascites in 21 patients].

OBJECTIVE: To determine the value of the transjugular intrahepatic portosystemic stent shunt (TIPS) in the treatment of patients with cirrhosis and refractory ascites. DESIGN: Descriptive follow-up study. SETTING: University Hospital Gasthuisberg, Leuven, Belgium. METHODS: In a period of three years, 21 consecutive patients with cirrhosis and refractory ascites were treated with TIPS. Refractory ascites was defined as ascites resistant to maximum diuretic therapy and repeated paracentesis. The mean follow-up was 9 months (range 3-26). RESULTS: Creation of the stent shunt was technically successful in 20 patients and resulted in a decrease of the pressure gradient between the portal vein and the inferior vena cava by approximately 47%. The procedure was immediately lethal in two patients. Complications occurred later on in four patients: thrombosis of the stent in 3 patients and disabling encephalopathy in one. Five other patients died from liver failure, four of them possibly related to the increase of the portosystemic shunting. The stent shunt had no ill effects on kidney function. Thirteen patients were still alive at the end of follow-up. Five patients (24%) had a total and sustained remission of the ascites. Seven patients (33%) still had ascites but needed no paracentesis. One patient did not respond to the treatment. The best results were observed in 14 alcoholics: 9 (64%) responded favourably (43% in non-alcoholics), in 4 of these the ascites had disappeared. CONCLUSIONS: TIPS placement needs substantial experience to avoid technical complications. In case of refractory ascites, only patients for whom later liver transplantation is considered should be submitted to the procedure, because TIPS placement can lead to deterioration of liver function.

Ascites↗
PubMed1996

Effects of varying doses of spironolactone without and with nitrates on portal vein pressure and kidney function in partial portal vein ligated rats.

The optimal dose of spironolactone to reduce portal vein pressure, alone or in combination with isosorbide-5-mononitrate (IsMn), has not been identified. We studied the effects of 8 days oral treatment with spironolactone, IsMn or both on portal pressure, plasma volume and renal sodium handling in rats with partial portal vein ligation. At daily doses of 0.33; 0.50; 1, and 1.50 mg/kg, spironolactone reduced portal pressure (all P < .05) as compared with placebo. Only the highest dose significantly lowered plasma volume (10.1 +/- 0.7 vs. 13.0 +/- 0.3 mL; P < .03) and enhanced urinary fractional sodium excretion (0.73 +/- 0.04 vs. 0.58 +/- 0.03%; P < .03) and the (Na+)/(K+) ratio in urine (0.43 +/- 0.04 vs. 0.30 +/- 0.03; P < .02). IsMn at doses of 0.25; 0.50, and 1 mg/kg decreased portal pressure (all P < .05) without a change in plasma volume but with a tendency (not significant) to lower fractional sodium excretion. IsMn impaired free water clearance at doses of 0.5 and 1 mg/kg (P < .05). Combinations of spironolactone 1 mg/kg with IsMn 0.5 or 1 mg/kg have no additive effect on portal pressure compared with spironolactone or IsMn alone. The higher the dose of IsMn in the combination, the more the natriuretic effect of spironolactone is opposed. Low doses of spironolactone are as effective as a higher dose to reduce portal pressure. This reduced portal pressure was independent of changes in plasma volume and diuretic effect, which suggests that spironolactone might have a direct vasoactive effect on the splanchnic circulation. To counteract sodium retention of nitrovasodilators, combination with high doses of spironolactone seems advantageous.

Animals↗
PubMed1996

Measurement of variceal pressure with an endoscopic pressure sensitive gauge: validation and effect of propranolol therapy in chronic conditions.

AIM/METHODS: Variceal pressure was measured at endoscopy in 98 patients with a non-invasive, pressure-sensitive gauge technique. RESULTS: In nine patients undergoing sclerotherapy, the values obtained correlated closely with those determined by fine-needle puncture of the varices (r = 0.95, p < 0.001). In 15 patients receiving placebo as part of a double-blind, placebo-controlled prospective evaluation of prophylactic treatment with propranolol, variceal pressure did not change significantly over a 1-year period: 16.5 +/- 3.2 mmHg at onset: 16.7 +/- 3.4 after 3 months and 15.9 +/- 3.5 after 12 months. In contrast, propranolol therapy given to 15 patients decreased the pressure from 16.2 +/- 3.0 mmHg before therapy to 13.5 +/- 2.0 after 3 months (p < 0.001) and to 13.1 +/- 4.1 after 12 months (p < 0.05). Patients with a recent bleeding episode had higher pressures than those who had not yet experienced any haemorrhage (19.3 +/- 3.5 mmHg, n = 17 vs 13.9 +/- 3.3, n = 62) (p < 0.001). This was confirmed in a prospective study: the last variceal pressure in bleeders and non-bleeders was respectively 17.2 +/- 1.7 mmHg (n = 4) and 14.8 +/- 4.1 mmHg (n = 26) (p < 0.01). Overall, variceal pressure measurements correlated with the size of varices, the presence of red colour signs and with the North Italian Endoscopic Club score. CONCLUSIONS: This study has shown that the non-invasive pressure gauge Varipress represents a reproducible method to regularly assess variceal pressure, an important parameter related to the risk of bleeding, and to assess the effects of pharmacological therapy with propranolol.

Adrenergic beta-Antagonists↗
PubMed1996

The effect of long-term treatment with spironolactone on variceal pressure in patients with portal hypertension without ascites.

The effect of spironolactone on esophageal variceal pressure (VP) in patients without ascites was investigated. VP was assessed using a noninvasive endoscopic gauge. Spironolactone was administered during a 6-week period at a dosage of 100 mg/d. This treatment decreased VP from 16.8 +/- 1.9 (SD) to 14.1 +/- 2.7 mm Hg (P < .001) in a group of 12 patients and from 18.6 +/- 2.1 to 13.7 +/- 4.1 mm Hg (P < .01) in another group of 8 patients who still had high VP despite chronic intake of propranolol. In both groups, placebo administration to 12 and 8 comparable patients did not significantly alter VP. Spironolactone induced a significant reduction of plasma volume (42.1 +/- 5.5 to 36.1 +/- 6.6 mL/kg body weight, P < .01) and of the concentration of alpha-atrial natriuretic peptide (alpha-ANP) (39.8 +/- 22 to 27.7 +/- 20 pg/mL, P < .01); in addition, a pronounced increase in plasma renin activity (PRA) (1.1 +/- 0.9 to 7.5 +/- 3.4 ng/mL/h, P < .001) was induced by the treatment. No significant changes in systemic hemodynamics were observed during the studies. Severe side effects were not observed except for a high incidence (55%) of painful gynecomasty in the male patients. In conclusion, chronic spironolactone administration effectively lowers VP, even in patients under chronic propranolol therapy. The combination of propranolol and spironolactone deserves further study as a prophylactic therapy of variceal hemorrhage, but development of gynecomasty might be a problem. Finally, we confirmed the reproducibility of VP measurements with the noninvasive gauge in chronic conditions.

Adrenergic beta-Antagonists↗
PubMed1996

Assessment of variceal pressure by continuous non-invasive endoscopic registration: a placebo controlled evaluation of the effect of terlipressin and octreotide.

Octreotide has been proposed for the treatment of variceal bleeding. The effects on portal pressure, however, have been variable in published studies. As bleeding is more directly related to pressure in the varices, this study investigated the effect on variceal pressure of octreotide and terlipressin, a vasoactive drug with a well established effect. Variceal pressure was measured during four to eight minutes by a continuous non-invasive endoscopic registration method. Thirty patients in whom a stable variceal pressure recording had been obtained during at least one minute, were randomised to receive either 2 mg terlipressin, 50 micrograms octreotide or an identical volume of saline, as a single intravenous injection given over 60 seconds. For the final analysis three patients had to be excluded because of lack of a satisfactory recording. There were no significant clinical differences between the three groups of patients. Placebo administration did not induce significant changes, but a mean decrease in variceal pressure of -27% was noted with terlipressin, starting from two minutes onwards. Variceal pressure changes after injection of octreotide were variable and the mean change in pressure did not reach statistical significance. Seven of 10 patients showed a temporary increase in variceal pressure. In conclusion, terlipressin induces a significant and progressive decrease in variceal pressure but inconsistent variations of variceal pressure changes were seen after octreotide administration. This is probably related to its effect on central venous pressure. This study also shows that continuous variceal pressure recording with the non-invasive endoscopic registration technique detects in an accurate way the effect of vasoactive drugs on variceal pressure, because placebo injection did not produce significant changes.

Adult↗
PubMed1996

Non-invasive variceal pressure measurements: validation and clinical implications.

Recently, it has become clear that the best way to reduce the mortality related to a variceal bleeding is to prevent it. Since however not all patients will bled, a way to predict a variceal hemorrhage is therefore urgently needed. The current endoscopic scores for the prediction of variceal bleeding are based on rather subjective markers. The present experimental work added the measured variceal pressure to this scoring systems, but a large number of patients should prospectively be evaluated to allow development of a model based on numerical data. Medical treatment of variceal bleeding, both to prevent and to stop the bleeding, became the treatment of choice for the majority of our cirrhotic patients. Our present investigations demonstrated that the non-invasive measurement of variceal pressure with the endoscopic gauge represent a reliable technique to assess the effect of drug treatment for portal hypertension both in acute and chronic conditions. Non invasive variceal pressure measurement may play therefore a crucial role in the future care of patients with chronic liver disease and portal hypertension. Developments with regard to primary or secondary prevention of bleeding will depend on further insight to be gained in the pathogenesis of the development of varices in a variety of experimental models and in patients. The mechanisms of action and the effect on portal hypertension of a series of drugs has further to be investigated. Experience gained till now in the cardiovascular domain will greatly speed up this process but fundamental research on neurohumeral processes involved will be further essential.

Adult↗
PubMed1995

Genotype, serum level of HCV-RNA and response to interferon-alpha treatment in patients with chronic hepatitis C.

OBJECTIVE: Since only a small proportion of patients with chronic hepatitis C benefit from interferon therapy, we assessed the viral factors such as HCV genotype and the level of viraemia for prediction of interferon response. METHODS: HCV genotype and serum levels of HCV-RNA were determined in 24 patients before, during and after interferon treatment. RESULTS: Pre-treatment serum levels of HCV-RNA were significantly lower in patients with normalization of serum ALT and disappearance of serum HCV-RNA upon therapy than in patients with persistent abnormal ALT and/or serum HCV-RNA positivity. Sole infection with HCV genotype 1b was associated with a significantly higher pre-treatment serum HCV-RNA level than infection with genotype other than 1b or mixed types. CONCLUSIONS: HCV genotype and pre-treatment serum HCV-RNA levels are indeed important predictors for response to interferon treatment in patients with chronic hepatitis C.

Adolescent↗
PubMed1994

Hepatitis C virus and its genotypes in patients suffering from chronic hepatitis C with or without a cryoglobulinemia-related syndrome.

Recently, evidence has been presented for a possible association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia (EMC). Eleven consecutive patients with EMC and two with cryoglobulinemia type I were examined for the presence of markers of HCV infection. Eleven of 13 patients (10 with EMC and 1 with type I cryoglobulinemia) had anti-HCV antibodies (as determined by a second generation anti-HCV assay) and HCV-RNA in plasma or serum. HCV-RNA was also detected in liver biopsies of five patients. Genotyping showed that HCV genotype 1 was found in 10 of 11 patients with HCV-RNA (9 genotype 1b and 1 genotype 1a) and only one patient had HCV genotype 2. However, a similar high prevalence of genotype 1b (100%) was found in a group of 14 consecutive patients with chronic hepatitis C, who had no clinical evidence of cryoglobulinemia. Concomitant infection was present in three patients with genotypes 2, 3 and 4, respectively. These findings stress the high prevalence of HCV infection in patients with EMC and further study shows that a difference in genotype prevalence was not found between HCV-related EMC and chronic hepatitis C without clinical manifestations of EMC.

Adult↗
PubMed1994

Clinical aspects of incomplete septal cirrhosis in comparison with macronodular cirrhosis.

BACKGROUND/AIMS: Incomplete septal cirrhosis (ISC) is a form of macronodular cirrhosis characterized by slender, incomplete septa that demarcate inconspicuous nodules. Its clinical features have not been investigated in a large series. The aims of this study were to review the clinical symptoms and evolution of ISC in 42 patients. METHODS: Forty-two patients with at least one liver biopsy strongly suggestive of ISC were selected for the study covering a period between 1968 and 1987. Data for these patients were compared with the evolution of 49 patients with classical macronodular cirrhosis after chronic active hepatitis type B or C. RESULTS: Possible etiological factors for ISC were alcohol abuse, arsenic treatment, and hepatitis B infection. In three cases, a genetic factor could not be excluded. Patients with ISC had significantly lower serum concentrations of transaminases and bilirubin at diagnosis. Compared with macronodular cirrhosis, bleeding varices were more frequent (57% vs. 22%) in ISC. Ten-year survivals in the ISC and the macronodular cirrhosis groups were 54% and 57%, respectively. CONCLUSIONS: ISC represents a relatively stable burnt-out form of macronodular cirrhosis with an unusually high incidence of variceal bleeding. This could be explained by a superimposed insufficiency of the portal vascular supply.

Adolescent↗
PubMed1994

Detection of hepatitis C virus antigen by immuno-histochemical staining: a histological marker of hepatitis C virus infection.

Hepatitis C virus has been recognized as a major cause of non-A, non-B viral hepatitis. Although serologic tests have been commercialized, no specific histological or immuno-histochemical markers for hepatitis C virus infection are available for routine use. In an effort to detect hepatitis C virus antigen in liver tissue we investigated the immuno-reactivity to monoclonal antibodies on frozen liver tissue from a chimpanzee and patients with chronic non A, non B hepatitis. Monoclonal antibodies were developed in mice immunized with a synthetic peptide derived from hepatitis C virus core antigen. One monoclonal antibody was reactive and showed typical cytoplasmic granules in chimpanzee hepatocytes. Using this monoclonal antibody a similar staining pattern was found in the liver biopsies of 21 out of 28 chronic non-A, non-B hepatitis patients, positive for hepatitis C virus-RNA and anti-HCV. The granular immuno-reactivity was abolished after pre-incubation of this monoclonal antibody with infected chimpanzee liver or with hepatitis C virus synthetic peptide but not with normal chimpanzee or human liver tissue. There was no reactivity in four patients with hepatitis C virus-RNA-negative, anti-HCV-positive chronic non-A, non-B hepatitis, in 11 patients with chronic type B hepatitis or in 12 hepatitis C virus-RNA-negative, anti-HCV-negative patients with various liver diseases. However, staining was found in three out of four additional chronic type B hepatitis patients suspected of co-infection with non-A, non-B agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

The effect of different doses of a bolus injection of somatostatin combined with a slow infusion on transmural oesophageal variceal pressure in patients with cirrhosis.

Transmural variceal pressure was measured by fine-needle puncture following a 250-micrograms bolus injection of somatostatin given intravenously, together with a slow infusion of 250 micrograms/h, and compared with results following a 500-micrograms bolus and with placebo in 19 patients with cirrhosis who had recently bled. Pressure was recorded continuously for a 4-min period. Placebo did not alter variceal pressure (n = 6), whereas a 250- or 500-micrograms bolus produced a rapid decrease in pressure from 33 +/- 7 cmH2O to 20 +/- 6 (n = 7) and from 35 +/- 5 cmH2O to 24 +/- 6 (n = 6), respectively. The difference between the two groups was not significant. This decrease occurred within 30 to 90 s, but was followed by a progressive increase in variceal pressure over the next 2 min in all except two patients. After 3-4 min, variceal pressure still remained below pretreatment levels. Further studies are needed to evaluate the optimal infusion rate. These results seem to indicate that future clinical studies using somatostatin in the treatment of variceal haemorrhage should include repeated bolus injections to arrest variceal bleeding.

Blood Pressure Determination↗
PubMed1994

Rapid clearance of hepatitis C virus RNA in peripheral blood mononuclear cells of patients with clotting disorders and chronic hepatitis C treated with alpha-2b interferon is not a predictor for sustained response to treatment.

Thirteen patients with congenital coagulation disorders and chronic hepatitis C were treated with alpha-interferon (IFN). Serum transaminases (ALT) and hepatitis C virus (HCV)-RNA in plasma and peripheral blood mononuclear cells (PBMC) were followed during and after treatment. During IFN treatment ALT levels normalized in 8/13 patients. In all patients HCV-RNA disappeared from PBMC. In 9/13 HCV-RNA also became undetectable from plasma; in six of these nine this occurred earlier in PBMC than in plasma; in the remaining three the disappearance of HCV-RNA occurred simultaneously in plasma and PBMC. All but two patients relapsed within 3 weeks after cessation of IFN, one relapsed after 6 weeks and one patient remains in remission after 6 months. HCV-RNA reappeared either earlier in plasma (3/12) or simultaneously in plasma and PBMC (9/12). Viral replication in PBMC thus can easily be suppressed by IFN, whereas longer treatment is needed for the eradication of HCV-RNA in plasma. The detection of HCV-RNA in PBMC cannot be used as a prognostic marker for the identification of patients with chronic hepatitis C who will have a sustained response to IFN treatment.

Adult↗