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F Ramalho

Publications and source records attributed to F Ramalho.

At least 19 recordsLinked to original sources

Treatment and prognostic factors in patients with hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Survival of patients depends on tumor extension and liver function, but yet there is no consensual prognostic model. AIMS: To evaluate the influence on survival of pretreatment parameters (clinico-laboratorial, liver function, tumor extension, Okuda and Cancer of the Liver Italian program (CLIP) staging) and treatment modalities. METHODS: We retrospectively analyzed 207 patients, diagnosed between 1993 and 2003. The initial treatment was: surgery--six patients; radiofrequency ablation--21; percutaneous ethanol injection--29; transarterial chemoembolization--49; tamoxifen--49; supportive care alone--53. Factors determining survival were assessed by Kaplan-Meier method and Cox regression models. RESULTS: Median survival was 24 months. In univariate analysis, Child-Pugh classification and Model for end-stage liver disease (MELD) score, portal vein thrombosis (PVT), tumor size, number of lesions, Okuda and CLIP scores were all associated with prognosis (P < 0.001). Alpha-fetoprotein levels were not predictive of survival. Independent predictors of survival were ascites, bilirubin, PVT and therapeutic modalities (P < 0.001). In early stage hepatocellular carcinoma (HCC), survival was similar for both percutaneous ablation modalities, either radiofrequency or ethanol injection (P = NS). In advanced HCC, survival was better in patients receiving tamoxifen than supportive care alone (P < 0.001). CONCLUSION: This study reinforces the importance of baseline liver function (Child-Pugh classification and MELD score) in the survival of patients with HCC, although staging systems allowed the stratification of patients in different prognostic groups. Ascites, bilirubin and PVT were independent pretreatment predictors of survival. All treatments influenced the patient's outcome, whether in early or advanced stages.

Adult↗

Spontaneous bacterial peritonitis in patients with hepatic cirrhosis: evaluation of a treatment protocol at specialized units.

INTRODUCTION: Spontaneous bacterial peritonitis is a common and severe complication in patients with cirrhosis and ascitis. Its prognosis clearly depends on its precocious clinical recognition and efficacious therapy. AIM: To optimize a treatment protocol, after auditing clinical efficacy and describe microorganisms implicated at our institution. MATERIAL AND METHODS: Retrospective study of clinical files of patients with hepatic cirrhosis with positive culture of ascitic fluid (AF) and/or an AF polymorphonuclear (PMN) count of more than 250/mm3, treated at our units between 1st January, 2000 and 31st December, 2001 (n = 38). Patients showed a median age of 49 years (30-76), 63% of which were male. Forty-eight percent were classified as belonging to Child-Pugh B class, and 52% to C. RESULTS: First, considering cases with PMN > 250/mm3 (n = 29), antibiotics were given to all patients (cefotaxime and ampiciline). Fifty-two percent had hepatic encephalopathy, 42% had fever, 66% abdominal pain. In 42% a microorganism was isolated. Although 24% of fatal cases (only two related to infection), we noted a 73% clinical and laboratorial response. Five patients (72%) that died, showed renal failure by the time of death. Second, in all cases with positive culture of ascitic fluid (n = 21), 42% of which with PMN > 250/mm3 and 9 monobacterial nonneutrocytic bacterascites' cases, one only agent was found: E. coli in 36%, Streptococci (37%), Staphylococci (14%), and other (14%): Klebsiella oxytoca, n = 1; Salmonella enteritidis, n = 1; Enterococcus faecium, n = 1, Acinectobacter anitratus, n = 1. Only one of the agents, E. faecium (3%) showed in vitro sensitivity exclusively to ampiciline; all other were cefotaxime sensitivite. CONCLUSIONS: Our protocol will be modified, to treat patients with spontaneous bacterial peritonitis with cefotaxime, as monotherapy. Albumin infusion will also be added to the protocol, as, we found renal failure to be an important negative prognosis factor.

Adult↗

Alpha-interferon improves liver fibrosis in chronic hepatitis C: clinical significance of the serum N-terminal propeptide of procollagen type III.

Our objective was to estimate the effect of interferon (IFN) on the evolution of fibrosis in chronic hepatitis C and the significance of the N-terminal propeptide of procollagen type III (PIIIP) as a marker of fibrogenesis. One hundred seventeen patients, 72 male (61%) and 45 female (39%), with a mean age of 40.7+/-11.9 years were treated with a2b-IFN, 3 to 5 MU, for 12 months: sustained responders (SR = 44), relapsers (RR = 35), and nonresponders (NR = 38). Liver biopsies were performed before treatment and 1 year after cessation of IFN for evaluation of the histological activity index (HAI). Serum PIIIP was obtained at the time of liver biopsy, at the beginning, during, and end of therapy and during the follow-up. The normal value in 29 healthy individuals was 0.37+/-0.18 U/L. Staging was reduced in 58% of SR, 12.5% of RR, and 11.5% of NR. There was a correlation between PIIIP and the HAI before (n = 71, r(s) = 0.41, P < 0.0004) and after IFN (n = 71, r(s) = 0.58, P < 0.0001). The SR had a better improvement in grading (90.3%; P < 0.05) and staging (58%; P < 0.001). The correlation of the HAI parameters with the variation of PIIIP showed significance only for fibrosis (r(s) = 0.36, P < 0.002) and portal inflammation (r(s) = 0.35, P < 0.01). PIIIP normalized only in patients whose fibrosis improved (P < 0.01). At the end of therapy, PIIIP had a predictive value in the distinction of SR from RR (PPV, 64; PNV, 55.6). During the follow-up, PIIIP remained lower in SR compared with RR and NR (P < 0.002). The response to a-IFN improved liver inflammation and fibrosis. Serum PIIIP is a useful noninvasive method to evaluate serially fibrogenesis in chronic hepatitis C treated with IFN.

Adult↗

Correlation of genotypes and route of transmission with histologic activity and disease stage in chronic hepatitis C.

Our objective was to evaluate the histopathological features of chronic hepatitis C of 64 liver biopsies and to correlate this with the route of transmission of hepatitis C virus, the genotype of HCV, and the patient's age. Moderate chronic hepatitis was the most frequently observed (62.5%). Cirrhosis was observed in 14 patients (21.9%) and was more frequently found among patients over 40 years of age (34.3% vs. 6.9%, P = 0.025). The mean histopathological activity index (HAI) was significantly higher in the sporadic (10+/-3.1) than the posttransfusional (7.5+/-3.7) and the intravenous drug use (IVDU) groups (6.3+/-2.8) (P<0.02). Moreover the sporadic group showed more fibrosis (P<0.04) than the posttransfusional group. No liver cirrhosis was found in the IVDU group. The overall prevalence of HCV variants was: 54.7% type 1b, 4.6% type 1a, 37.5% type 2c, 1.6% type 2b, 1.6% type 2. The genotype distribution showed no relation to the HAI, hepatitis activity (grade), and fibrosis (stage) of the liver disease. In conclusion, the sporadic route of transmission of HCV was related to a more severe chronic hepatic disease, a finding that could influence future antiviral therapies. The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our data suggests that the ultimate consequence of HCV chronic infection depends on patient age rather than on HCV genotype.

Adult↗

Apoptotic cell death does not parallel other indicators of liver damage in chronic hepatitis C patients.

The mechanisms of hepatocyte damage and the events that lead to high rates of chronic liver disease in hepatitis C virus (HCV) infection remain unclear. Recent in vitro studies have suggested that the HCV core protein may disrupt specific signalling pathways of apoptosis. This prompted us to study patients with chronic HCV infection to: determine the extent of apoptosis in the liver; evaluate whether clinical and biochemical data are correlated with histological findings; and to investigate if apoptosis is related to the histological activity of the disease. Twelve patients with chronic hepatitis C were included in the study. Liver histology was scored by using the histological activity index (HAI) of Knodell et al. DNA fragmentation was assessed in liver tissue by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) assay. Routine methods were used to determine serum markers of liver disease. Bile acids were measured in serum and liver by gas chromatography. Patients were placed, according to their HAI score, into group A (3.8 +/- 0.3) or group B (7.8 +/- 0.8) (P < 0.01). Liver enzymes tended to be higher in group B patients than in patients of group A. Levels of toxic bile acids in serum were greater in patients than in controls (P < 0.01). Chenodeoxycholic acid values were slightly higher in serum and liver of patients in group A. Liver biopsies with low HAI scores showed an increased rate of apoptosis (18.0 +/- 4.0 apoptotic cells per field) compared to those with higher HAI scores (6.6 +/- 2.1, P < 0.05) or to controls (3.5 +/- 0.4, P < 0.01). Hence, less severe liver disease, associated with lower histological grades and biochemistries, as well as increased levels of chenodeoxycholic acid, induces an expanded apoptotic response. The lower apoptotic rate in advanced liver disease may be associated with the high incidence of hepatocellular dysplasia/neoplasia.

Adult↗

Clastogenic factors as biomarkers of oxidative stress in chronic hepatitis C.

BACKGROUND/AIMS: Clastogenic factors (CFs) are composed of lipid peroxidation products, cytokines and other oxidants with chromosome-damaging properties. They are regularly observed after radiation exposure and in chronic inflammatory diseases, where they are supposed to be risk factors for carcinogenesis. It appeared of interest to investigate their presence in the plasma of patients with chronic hepatitis C. METHODS: CFs are detected by chromosomal breakage studies. They were compared to malondialdehyde (MDA), total plasma thiols (t-SH), alanine aminotransferase (ALT), viral load and histological data. RESULTS: CFs were increased in 19 of 20 patients, 16 had increased MDA levels and 15 had decreased t-SH levels. Mean values were significantly different from the 20 controls (p<0.001). After the first 3 months of interferon treatment, all three markers showed significant improvement, but were not completely normalized. There was a positive correlation between CFs and necroinflammatory activity (p<0.03), while MDA was correlated with fibrosis (p<0.03). Viral load was correlated with necrosis and inflammation (p<0.05). CONCLUSION: The presence of CFs in chronic hepatitis C confirms the occurrence of oxidative stress in this disease and could be useful in clinical trials for testing antioxidants. The CF test is a sensitive assay for the detection of oxidative stress and correlates with necroinflammatory activity.

Adult↗

[Vaccine against hepatitis B. Eight years of experience].

Hepatitis B virus infection is one of the world's major health problems and health care workers are especially at risk, leading to the need for a high priority vaccination program. Such a program was begun in 1989 in S. Maria Hospital and included all hospital personnel and students of the Faculty of Medicine. The screening included 2360 health care workers and 1153 students. Fifty-five percent of hospital health care workers and 41% of the students participated in the vaccination program. The overall prevalence of hepatitis B markers was 16.8%, for hospital personnel, the chronic carrier being 0.95%, and for the students, 5.5% and 0.3% respectively. The highest prevalence was observed in the Biochemical Laboratory--64% (7/11), Surgery--42% (13/31), Pneumology--39% (9/23), Emergency Department--29% (7/24), Hematology Laboratory--29% (7/24) and Orthopedics--29% (10/35). The prevalence was also higher in students in the last three years of Medical School compared to those in the first three years, 12.2% vs 7.2%, p = NS. Local pain has been the most frequent complaint in 8.6% of vaccinees. The control with the quantification of anti-HBs in the 7th month has shown a serological efficacy of about 95%. A non-response was observed in male workers, 13% compared to 5% for females, p < 0.05. Older employees also showed higher non-response: the average age of workers with anti-HBs of 0 U/L was 52.3 years, and those with anti-HBs of more than 100 U/L was 38.4 years, p < 0.02. Hepatitis B vaccine is a safe and effective preventative measure that has been widely used for years. Our study shows the need for a more aggressive approach to the vaccination of health care workers because a significant percentage of them in our country are not protected.

Allied Health Personnel↗

Idiopathic hypereosinophilic syndrome presenting as cholestatic liver disease.

We report the case of a 34-year-old white man with recurrent episodes of abdominal pain, cholestasis and eosinophilia. The diagnosis of idiopathic hypereosinophilic syndrome (IHS) was made after exclusion of all known causes of eosinophilia. Liver biopsy revealed an eosinophilic infiltrate with biliary damage. The patient recovered after prednisolone treatment. We review the literature on the association between IHS and liver disease.

Adult↗

[A structural analysis of the entrance exams for specialist interns from 1994 to 1996].

In order to obtain specialist training in Portugal, doctors must pass a multiple-choice examination. The aim of this article is to present a structural and mathematical analysis of the examinations in the last three years. We based our work on the calculation of reliability coefficient of the examinations, and the difficulty and discrimination index of the questions and the examinations as a whole. A detailed analysis of the examinations, including that of each of the three hundred questions, will be published by the Department of Health Manpower in January, 1997.

Education, Medical↗

Streptococcus bovis spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a frequent cause of decompensated alcoholic cirrhosis. The authors describe the first two cases caused by infection with Streptococcus bovis. They suggest that this microorganism may be present in the intestinal flora of these patients more frequently than assumed. Furthermore, the course of SBP due to S. bovis may be particularly severe.

Fatal Outcome↗

[The intrahepatic expression of the hepatitis B virus in chronic delta hepatitis].

In order to evaluate the interference of hepatitis delta virus (HDV) in hepatitis B viral particle (HBsAg, HBcAg) expression in the liver of chronic HDV patients, 39 and 81 liver biopsies of HBsAg carriers seropositive for anti-HDV and anti-HDV negative controls, respectively, were studied. HBcAg was positive in 16.7% of the HBeAg-positive patients with HDAg in the liver and in 91,4% of controls. In contrast, in HBeAg- and anti-HDV negative patients the intrahepatic expression of HBcAg was detected in 32.6%. In anti-HDV negative patients the HBcAg liver expression correlated significantly with the HBeAg in serum (p < 0.00001). The distribution of HBcAg was exclusively cytoplasmatic in 30% of HDV-infected patients but mixed nuclear and cytoplasmic in 38.3% of the controls. The nuclear expression of HBcAg was decreased in chronic HDV infection. HBsAg was positive in 70.3% of patients who were anti-HDV positive and in 82.3% of controls. The membranous expression of HBsAg was detected less frequently in HDV-infected patients (p < 0.05) than in controls, while associated with HBeAg in serum of HBV carriers without HDV superinfection (p < 0.00001). The prevalence and the HBsAg cytoplasmic expression was not different for the chronic HDV infection or controls. Our results show: 1) decreased intrahepatic expression of HBcAg and membranous HBsAg in HBV carriers superinfected with HDV, suggesting decreased HBV replication in the liver of these patients. 2) the changing of HBcAg and HBsAg expression in the liver of HDV-infected patients, suggest not so much a decrease but rather a modulation in HBV replication.

Adolescent↗

[Chronic hepatitis: the etiological spectrum. The implications for treatment].

The prevalence of chronic hepatitis and its different aetiologies was studied in all patients above 10 years of age seen in the specialised outpatient clinic of our hospital over a 3 year period. Defining chronic hepatitis as a persistent elevation of the transaminases, 988 patients (62% of all the patients observed) were classified as follows: viral aetiology in 82%, metabolic in 2%, biliary in 2%, alcoholic in 11%, autoimmune in 1.5% and idiopathic in 2%. Among the viral group, hepatitis B virus infection was predominant (65%), followed by hepatitis C virus (26%) and delta hepatitis (8%). While the hepatitis C and delta patients presented high transaminases, in the HBsAg carriers this occurred in 94% and 20% of the HBeAg and anti-HBe-positive patients, respectively. Thirty per cent of the patients with chronic hepatitis B, 35% of those with chronic hepatitis C and 18% with delta hepatitis were selected for alpha interferon therapy. This demonstrated that in a significant proportion of patients with chronic viral hepatitis, therapy with interferon is not indicated. Corroborating other studies, with even stronger data, our study shows that viral aetiology is the most frequent type of chronic hepatitis.

Adolescent↗

Serum markers of hepatitis B virus replication, liver histology and intrahepatic expression of hepatitis B core antigen.

The presence and distribution of hepatitis B core antigen (HBcAg) was studied in the liver of 227 chronic carriers of hepatitis B surface antigen (HBsAg) to investigate its relationship with serum HBV-DNA, the status of hepatitis B 'e' antigen/antibody (HBeAg/anti-HBe) and the underlying liver disease. HBcAg was detected in 144 of the 227 (63%) liver specimens and HBV-DNA in 132 (58%) of the corresponding sera. Serum HBV-DNA showed a constant link with intrahepatic HBcAg. Out of 96 HBeAg-positive patients, 91 (95%) had HBcAg in the liver and 85 (89%) had HBV-DNA in serum. Overall there was a significant link between HBeAg and HBV-DNA in serum, but there was no correlation in 58 out of 227 (26%) cases. In HBeAg/HBV-DNA-positive carriers, HBcAg expression was predominantly nuclear. It was nuclear and cytoplasmic in patients with the highest levels of viremia. Eleven out of 13 (85%) HBV-DNA-positive patients who had only cytoplasmic HBcAg were HBcAg-negative and had low levels of HBV-DNA. Nine of 13 (69%) patients with exclusively cytoplasmic HBcAg had severe chronic liver disease. Neither the presence of HBV-DNA and HBeAg in serum nor the nuclear localization of HBcAg were associated with the severity of liver damage. In the group of HBV-DNA-positive patients (132), the presence of liver disease was significantly connected with the absence of HBeAg in serum (P less than 0.05; C.L. 3-35).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical and epidemiological significance of hepatitis delta virus (HDV) infection in chronic HBV carriers in Portugal.

This study demonstrated that in Portugal HDV infection occurs in 17.3% of HBsAg chronic carriers and chronic HDV infection in 8.4%. As in Northern European countries, HDV infection in Portugal is predominantly found in drug-addicts. Our findings also confirm that HDV infection is associated with an active and progressive liver disease. In delta Ag positive CLD serum HBV-DNA was detected in 10 of 19 cases and was present at low levels. In contrast 52 of 84 delta Ag negative were serum HBV-DNA positive and 48.1% of these had high serum HBV-DNA levels. Ninety per cent of delta Ag positive CLD with serum HBV-DNA positive were drug addicts. These findings indicate that in chronic HDV infection synthesis of HBV is reduced and suggest namely that in drug-addicts their disease derived from the cumulative pathogenic effect of both HBV and HDV. In follow-up biopsy a significantly younger mean age and significantly deterioration of carriers with HDV infection was observed, suggesting that HDV infection accelerates the natural history of HBV related liver disease.

Adolescent↗