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Biomedical subjects

E Giostra

Publications and source records attributed to E Giostra.

At least 37 records · Page 2Linked to original sources

Choledocholithiasis: a prospective study of spontaneous common bile duct stone migration.

BACKGROUND: The rate of spontaneous migration of bile duct stones through the duodenal papilla is not well known. Endoscopic retrograde cholangiography (ERC) has been the standard method to diagnose bile duct stones, but accumulating data show there is a good agreement between ERC and endoscopic ultrasonography (EUS). The aim of the study was to evaluate the incidence and time course of stone migration in patients with bile duct stones by analyzing discrepancies between EUS and ERC as a function of the elapsed time between these two procedures. Stone migration was considered as the absence of stones at time of ERC regardless of the number of stones seen at EUS. METHODS: The main criterion for inclusion was the presence of bile duct stone as shown by EUS. Ninety-two consecutive patients were prospectively included in this study. RESULTS: Choledocholithiasis was absent at ERC in 12 patients. In univariate analysis, presence of gallbladder was significantly associated with an increased rate of stone migration (correction for multiple testing would remove this statistical significance). The size of the stone was the only independent factor to predict migration. CONCLUSION: Migration occurred in about 21% of cases within 1 month. Our study emphasizes the need to analyze carefully the results of comparative imaging studies of bile duct stones.

Adult↗

Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3.

BACKGROUND/AIMS: Patients infected with the hepatitis C virus (HCV) often have liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim of this study was to correlate the occurrence and severity of liver steatosis with HCV RNA type, level and sequence of the core-encoding region. METHODS: We scored the liver steatosis in 101 HCV-infected individuals carefully selected to exclude other risk factors of a fatty liver. Results were compared with HCV RNA genotype and level in serum and liver. In selected patients, we assessed the effect of antiviral therapy on steatosis and the relationship between nucleocapsid sequence heterogeneity and fat infiltration. RESULTS: Steatosis was found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV genotype 3 was associated with higher steatosis scores than other genotypes. A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected with genotype 3, but not in those infected with genotype 1. In selected patients, response to alpha-interferon was associated with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV isolates failed to identify a sequence specifically associated with the development of steatosis. CONCLUSIONS: We provide virological and clinical evidence that the steatosis of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3. At variance with published evidence from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.

Adult↗

Magnetic resonance imaging and proton spectroscopic alterations correlate with parkinsonian signs in patients with cirrhosis.

BACKGROUND & AIMS: The relationship between abnormalities found by magnetic resonance imaging (MRI) and proton spectroscopy (MRS) and the clinical signs of hepatic encephalopathy is not well characterized. Motor disturbances have been described, suggesting that basal ganglia (BG) are altered. METHODS: We evaluated 19 unselected consecutive patients with biopsy-proven cirrhosis evaluated for liver transplantation for the presence of parkinsonian signs using the Unified Parkinson's Disease Rating Scale (UPDRS) and Purdue Pegboard test, and correlated these neurologic abnormalities with MRI and MRS studies. Brain MRI intensities were expressed as signal-to-noise ratios. MRS findings obtained from one voxel in the BG and one in the occipital white matter (WM) were expressed as metabolite ratios. Six healthy subjects had normal values. RESULTS: Compared with healthy subjects, patients with subclinical or grade 1 hepatic encephalopathy had hyperintensity in occipital WM and all BG tissues except thalamus and reduced Ino/Cr and Cho/Cr ratios in both voxels. In the BG, MRI intensity was correlated with the UPDRS (P < 0.05, r = 0.56). The Cho/Cr ratio also correlated with both UPDRS (P < 0.02, r = -0.59) and Pegboard scores (P < 0.02, r = 0.61). CONCLUSIONS: In cirrhosis, parkinsonian signs correlate with BG alterations detected by MRI and MRS.

Adult↗

Hemochromatosis gene mutations in chronic hepatitis C patients with and without liver siderosis.

Chronic hepatitis C is often associated with liver iron overload, which may affect the long-term prognosis and the response to antiviral treatment. The occurrence of hemochromatosis (HFE) mutations were studied to determine whether may contribute to the liver iron overload of chronic hepatitis C patients. The prevalence of two HFE mutations (C282Y and H63D) in 120 chronic hepatitis C patients was determined and the findings were correlated with clinical, histological and virological features. Hepatic iron was determined semiquantitatively by a histochemical hepatic iron index, defined as the ratio of a histochemical staining score to the patient's age, after correction for heterogeneous lobular iron distribution. Serum hepatitis C virus (HCV) RNA was measured by bDNA assay and typed by restriction fragment length polymorphism. Liver HCV RNA was measured by a semi-quantitative strand-specific reverse transcription-polymerase chain reaction (RT-PCR). Excess liver iron was stained in the liver of 36 patients (30%). Siderotic patients had the same geographic origin, serum and liver HCV RNA levels and H63D and C282Y mutations frequency as non-siderotic patients. However, siderotic patients were older (P = 0.015), more frequently males (P = 0.02), less frequently infected with HCV genotype 3 (P = 0.037) and had a higher liver fibrosis score (P = 0.008). The liver iron content did not correlate with the serum or liver HCV RNA titers. Ten of the 36 patients with liver siderosis had neither a history of excess alcohol intake, multiple transfusions, or HFE mutations. In conclusion, the pathogenesis of the liver iron overload in chronic hepatitis C patients cannot be fully explained by the occurrence of HFE mutations. The exact mechanism of iron accumulation in these patients therefore remains unexplained.

Adult↗

[Results of a combined adult-child liver transplantation in Switzerland].

Between July 1987 and August 1998, 173 orthotopic liver transplantations (OLT) were performed in Geneva. We studied a homogeneous group of 114 OLT performed during the 6 years between 1992 and 1997 on 107 patients (89 adults and 18 children; 7 retransplantations). Although Geneva has the largest transplantation programme in Switzerland and is the only centre performing paediatric liver transplantation, the mean number of procedures per year was 19, corresponding to only a small transplantation programme in Europe. It could be reasonably questioned, therefore, whether Swiss patients are not at a disadvantage as compared with patients from European countries with larger liver transplantation centres. Although the perioperative morbidity was still considerable, the results of this series -90% of actuarial patient survival at 1 and 2 years and 84% at 5 years-compare favourably with the results of the European Liver Transplantation Registry: 76% of actuarial patient survival at 1 year and 65% at 5 years. In this series, 95 patients (89%) were alive on January 1, 1998. As no patient was refused on the severity of the liver disease and as more than 10% of OLT were performed as emergencies, a bias due to the selection of the best cases cannot explain the good results. This series demonstrates that a small liver transplantation centre may obtain results that compare favourably with the results of large European centres, and that Swiss patients are not at a disadvantage as compared with patients of other European countries.

Adult↗

Autologous bone marrow transplantation for recurrent malignant lymphoma after liver transplantation.

BACKGROUND: Cancer chemotherapy in chronic carriers of hepatitis B virus is known to promote viral replication, and, when immunosuppressive treatment is stopped, the return of immune competence can be followed by a fulminant hepatitis. Liver transplantation may be required and has been successfully performed for this condition. However, malignancy recurrence after transplantation has not been reported yet. METHODS AND RESULTS: We here report the case of an asymptomatic hepatitis B surface antigen carrier who developed a malignant lymphoma, which was treated by chemotherapy. After cessation of chemotherapy, he developed a fulminant hepatitis, requiring liver transplantation. Three years later, he developed a recurrent malignant lymphoma, which was treated successfully by autologous bone marrow transplantation. In order to prevent viral replication, lamivudine and intermittent administration of fresh-frozen plasma highly concentrated in anti-HBs immunoglobulin was initiated before the bone marrow transplantation. The patient remains well 12 and 56 months after autologous bone marrow and liver transplantation, respectively. CONCLUSIONS: This experience suggests that all hepatitis B surface antigen-positive patients for whom chemotherapy is indicated would benefit from prophylactic antiviral hepatitis B virus therapy. Furthermore, successful autologous bone marrow transplantation is possible after liver transplantation.

Bone Marrow Transplantation↗

Traumatic neuroma with biliary duct obstruction after orthotopic liver transplantation.

BACKGROUND: Traumatic neuromas may develop after injury to nerve fibers encased in Schwann cells. The incidence of symptomatic neural tumors appears to be low after orthotopic liver transplantation (OLT). Only two cases of biliary stricture caused by infiltrating traumatic neuroma have been described previously. METHODS: We report two new cases of biliary tract obstruction after OLT that failed to respond to percutaneous balloon dilatation and were corrected by a resection of the bile duct stricture followed by biliary reconstruction with a Roux-en-Y jejunal loop. RESULTS: The first patient (17 months after OLT) had a traumatic neuroma appearing as a distinct mass with nerve bundles confirmed histologically; the traumatic neuroma in the second patient (5 months after OLT) was a nerve stump with infiltration of nervous elements in the bile duct. Both patients recovered without complications. CONCLUSIONS: Traumatic neuromas should be considered in the differential diagnosis of late biliary stricture after OLT, in particular when not responding to percutaneous dilatation or stenting.

Anastomosis, Roux-en-Y↗

Serious interaction between mibefradil and tacrolimus.

BACKGROUND/AIMS: Tacrolimus is metabolized by cytochrome P450 3A4 and 2D6 and has a narrow therapeutic range. We report a serious kinetic interaction between tacrolimus and mibefradil, a potent cytochrome P450 inhibitor. CASE REPORT: A 62-year-old women who had undergone liver transplantation was treated with tacrolimus for immunosuppression. For control of blood pressure, the patient was treated with nifedipine. She developed ankle edema, and nifedipine was replaced by mibefradil. Four days later, she presented with mental confusion, renal failure, and hyperglycemia, compatible with tacrolimus toxicity. In agreement with this assumption, the tacrolimus blood concentration was 100 ng/ml. Mibefradil and tacrolimus were both stopped, and the patient recovered within 1 week. Eight days after stopping mibefradil, tacrolimus was restarted at the same dosage and the subsequent plasma concentrations remained in the therapeutic range. CONCLUSIONS: Mibefradil increases the tacrolimus blood concentration by inhibiting its metabolism and should, therefore, not be used in patients treated with tacrolimus.

Benzimidazoles↗

Partial hepatectomy or orthotopic liver transplantation for the treatment of resectable hepatocellular carcinoma? A cost-effectiveness perspective.

The treatment of patients with compensated liver cirrhosis and small hepatocarcinomas remains controversial. Whereas partial hepatectomy (PH) is currently recommended, the role of orthotopic liver transplantation (OLT) has become progressively accepted. We used the techniques of decision analysis to measure the clinical benefits and the economic consequences of immediate resection versus transplantation in patients with compensated cirrhosis and who were diagnosed with small hepatocellular carcinoma (HCC). We restricted our analysis to patients with resectable carcinomas, which is either solitary tumor (< or = 5 cm in diameter), or multiple tumors (up to 3), none being > 3 cm in diameter and, in both cases, no tumor invasion of blood vessels. We took into account the risks of tumor spreading and dissemination and/or development of decompensated cirrhosis while waiting for donor organs because organ shortage is presented as the main obstacle to transplantation in these patients. Our analysis suggests that orthotopic liver transplantation (OLT) offers a substantial survival benefit compared with resection, ranging from a minimum of 1 year to a maximum of 4.7 years depending on treatment-related survival rates. However, the magnitude of this benefit relies on the availability of an organ donor; therefore, if the waiting period exceeds 6 to 10 months, depending on tumor growth pattern, the increase in life expectancy provided by transplantation is overwhelmed by the risks that patients face while waiting for transplantation. Consequently, partial resection becomes the preferred strategy. The predicted marginal cost-effectiveness ratios of transplantation compared with resection would range between $44,454 and $183,840 per additional year gained mainly influenced by the time delay before getting a transplant. We conclude that compared with partial hepatectomy (PH), OLT for resectable hepatocarcinoma(s) offers substantial survival benefit among well-targeted subgroups of patients as long as an organ donor is available within a maximal 6 to 10 months time delay, which is a plausible scenario in most centers with a liver transplant program. However, the marginal cost-effectiveness ratios incurred by this strategy are higher than that of many other current medical interventions.

Carcinoma, Hepatocellular↗

Treatment of chronic hepatitis C with alpha-interferon plus ofloxacin in patients not responding to alpha-interferon alone.

BACKGROUND/AIMS: Ofloxacin, a quinolone antibiotic, was recently shown to increase the primary response rate to alpha-interferon treatment of chronic hepatitis C. METHODS: Fifty-five patients with chronic hepatitis C were scheduled to receive 3 MU of a-interferon, three times a week, for 1 year. After 3 months of therapy, patients who were still HCV RNA-positive in serum started receiving a combined regimen with 3 MU of alpha-interferon, three times a week, plus ofloxacin, 600 mg daily, per os. After 3 months of combined therapy, patients with undetectable serum HCV RNA continued the combined regimen for another 6 months, whereas patients who were still HCV RNA-positive were definitively considered as non-responders and withdrawn from the study. Serum HCV RNA levels were quantitatively evaluated after 3 months of therapy with a-interferon alone and compared with those detected after 3 months of combined regimen. RESULTS: Among the 54 patients who completed the first 3 months of treatment, 32 (59.3%) still had HCV RNA detectable in serum and started receiving the ofloxacin/alpha-interferon therapy. Among the 26 patients who completed the 3 additional months of combined regimen, only one showed a virological response: this patient maintained a complete response to the end of combined treatment, but relapsed thereafter. The combination therapy had no effect on the serum HCV RNA or alanine aminotransferase levels. CONCLUSIONS: The combined administration of alpha-interferon and ofloxacin to patients with chronic hepatitis C who have not responded to alpha-interferon alone does not increase the primary virological response rate.

Adult↗

Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome.

BACKGROUND/AIMS: A treatment to induce a sustained increase in glomerular filtration rate in patients with hepatorenal syndrome has not yet been identified. Thus, the aim of the present study was to investigate the effects of terlipressin for 2 days on the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome. METHODS: A double-blind, cross-over randomized study was performed in nine patients. Patients received terlipressin (2 mg/day for 2 days) and a placebo for 2 days in a randomized order. RESULTS: Terlipressin administration significantly increased creatinine clearance (from 15+/-2 ml/min to 27+/-4 ml/min) and urine output (from 628+/-67 ml/day to 811+/-76 ml/day), but did not significantly change urinary sodium concentrations. Urinary sodium excretion was not significantly different after placebo administration (0.6+/-0.1 mmol/24 h) and terlipressin administration (9.3+/-7.2 mmol/24 h). Terlipressin administration significantly decreased plasma concentrations of renin and aldosterone but not atrial natriuretic peptide levels. Placebo elicited no significant effects. CONCLUSIONS: This study shows that 2-day terlipressin administration increases the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome.

Atrial Natriuretic Factor↗

Detection of intrahepatic hepatitis C virus replication by strand-specific semi-quantitative RT-PCR: preliminary application to the liver transplantation model.

BACKGROUND/AIMS: Although the hepatitis C virus infection recurs in virtually all patients after liver transplantation, up to 50% of patients may not have histological recurrent hepatitis 1 year after liver transplantation. To study the relationship between hepatitis C virus infection and liver disease after liver transplantation, we compared the intrahepatic hepatitis C virus replication levels with the liver histopathology among liver transplant recipients. METHODS: The intrahepatic negative-strand HCV RNA (i.e. the putative hepatitis C virus replication intermediate RNA) was evaluated by a semi-quantitative, strand-specific reverse transcriptase-polymerase chain reaction in 44 liver specimens from 23 patients with hepatitis C virus reinfection after liver transplantation. Results were compared with the time from liver transplantation, presence, grading and staging of the recurrent hepatitis, amount of hepatitis C virus antigens in the liver and serum HCV RNA levels. RESULTS: Negative-strand HCV RNA was detected in 42 liver specimens as early as 7 days after liver transplantation. Its titers correlated with the amount of intrahepatic hepatitis C virus antigens, but not with HCV RNA levels in serum. Levels of negative-strand HCV RNA in 19 specimens without hepatitis were comparable to those seen in 25 specimens with hepatitis (p=0.492), and were unrelated to the liver disease grading and staging scores. The intrahepatic hepatitis C virus replication could occasionally precede the recurrence of the hepatitis by several months. CONCLUSIONS: Molecular evidence has been obtained for intrahepatic hepatitis C virus replication occurring early after liver transplantation. The level of replication is not correlated with the development of recurrent hepatitis, suggesting that hepatitis C virus may replicate without inducing morphological evidence of liver damage.

Adult↗

Changes in liver fibrosis at the end of alpha interferon therapy and 6 to 18 months later in patients with chronic hepatitis C: quantitative assessment by a morphometric method.

BACKGROUND/AIMS: The aims of the study were to determine, in patients with chronic hepatitis C treated with alpha interferon: (i) changes in the morphometric evaluation of liver fibrosis at the end of treatment and 6, 12 and 18 months after treatment; (ii) the predictive value of histologic lesions for the response to treatment, in particular the predictive value of morphometric evaluation of liver fibrosis. METHODS: Seventy patients with chronic hepatitis C who participated in two trials of recombinant interferon alpha 2b treatment were studied. Liver specimens were obtained before and at the end of treatment and 6, 12 or 18 months later. Histologic lesions were assessed according to the Knodell system. Quantitative study of total fibrosis and of Disse space collagen was done by the computerized automated morphometric method. RESULTS: A significant decrease in morphometric Disse space collagen was observed at the end of treatment and 6 months later. This decrease was also observed, although it was not significant, 12 and 18 months after treatment. There was no relationship between this decrease and the biochemical and virological responses or the dose of interferon. The pretreatment Knodell activity score, but not the morphometric evaluation of fibrosis, was a significant predictor of sustained response. CONCLUSION: A decrease in Disse space collagen, as assessed by the sensitive morphometric method, was observed at the end of and 6 months after treatment. This observation is consistent with an anti-fibrogenetic effect of alpha interferon. Mild or moderate histologic activity was associated with a sustained response to therapy.

Antiviral Agents↗

Hepatitis G virus infection among liver graft recipients: anatomoclinical correlations.

Hepatitis G virus (HGV) causes persistent infection in man, but its disease association is controversial. We studied the HGV disease association in 25 liver transplantation (LT) recipients without evidence of hepatitis B and C infection. HGV RNA was tested by semiquantitative RT-PCR in serial serum samples and its presence was correlated with the biochemical and histological evidence of liver damage. The overall prevalence of HGV infection in this population was 9/25 (36%), one patient being HGV RNA positive since before LT, while the other eight apparently acquired de novo infections after LT. In five cases, appearance of HGV was followed by biochemical and histological evidence of liver damage: the liver biopsy showed acute rejection in two cases, acute cholangitis in two, and acute hepatitis in one. At the end of follow-up, histological evidence of chronic hepatitis was found in one HGV-positive patient but also in three HGV-negative patients, whereas the only patient with acute hepatitis at the time HGV RNA was first detected in serum developed an intralobular gigantocellular granuloma. In conclusion, HGV infection after LT may be seldom associated with acute and chronic liver damage, but comparable histological features can be observed also among HGV-negative controls.

Adolescent↗

IgM anti-hepatitis C virus core antibodies as marker of recurrent hepatitis C after liver transplantation.

The differential diagnosis of recurrent hepatitis C following orthotopic liver transplantation (OLT) may be difficult. We evaluated the diagnostic significance of IgM anti-hepatitis C virus (anti-HCV) core antibodies in 27 patients undergoing OLT because of HCV-associated cirrhosis. Serial serum samples collected before and after OLT were tested for the presence of IgM anti-HCV core antibodies. Results were compared with the histological evidence of liver damage, the presence, level, and genotype of serum HCV RNA and the degree of immunosuppression. All patients underwent recurrent HCV infection. Recurrent hepatitis was diagnosed histologically in 21 patients an average of 48 weeks after OLT (range 2-209 weeks): 18 had persistence or (re-)appearance of the IgM anti-HCV core after OLT, one lost the IgM anti-HCV core after OLT, and two never secreted IgM anti-HCV core either before or after OLT. The remaining six patients did not develop recurrent hepatitis after a follow-up of 44-241 weeks from OLT; in these patients, IgM anti-HCV core either disappeared (1 case) or decreased (1 case) after OLT or were persistently negative throughout the study (4 cases). Thus, 18/21 patients with recurrent hepatitis, but only one of six without recurrent hepatitis, secreted IgM anti-HCV core after OLT (P < 0.05). The IgM anti-HCV core levels were not correlated with the level or genotype of serum HCV RNA or the degree of immunosuppression. In conclusion, secretion of IgM anti-HCV core antibodies after OLT seems associated with recurrence of HCV-associated liver disease and may have diagnostic significance.

Adult↗