Assessment of indicators of vitamin A status in non-cirrhotic chronic hepatitis C patients

Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.

Hereditary hemochromatosis in a Brazilian university hospital in São Paulo State (1990-2000)

Hereditary hemochromatosis (HH) is the most common genetic disease among individuals of European descent. Two mutations (845G-->A, C282Y and 187C-->G, H63D) in the hemochromatosis gene (HFE gene) are associated with HH. About 85-90% of patients of northern European descent with HH are C282Y homozygous. The prevalence of HH in the Brazilian population, which has a very high level of racial admixture, is unknown. The aims of the present study were to identify individuals with diagnostic criteria for HH among patients with a body iron overload attended at the university hospital of the Faculty of Medicine of Ribeirao Preto from 1990 to 2000, and to evaluate the prevalence of HFE mutations. We screened first-degree relatives for HFE mutations. Four of 72 patients (three men and one woman, mean age 47 years) fulfilled the criteria for HH. HFE mutations were studied in three patients [two C282Y homozygotes (patients 1 and 2) and one H63D heterozygote]. Patient 1 had four children (all C282Y heterozygotes with no iron overload) and seven brothers and sisters: two sisters (66 and 76 years old) were C282Y homozygotes and both had an iron overload (a liver biopsy in one showed severe iron deposits), one sister (79 years old) was a compound heterozygote with no iron overload, one brother (78 years old) was a C282Y heterozygote with no iron overload, two individuals were H63D heterozygotes (one brother, 49 years old, obese, with a body iron overload and abnormal liver enzymes - a biopsy showed non-alcoholic steatohepatitis, and one 70-year-old sister with no iron overload). Patient 2 had two children (22 and 24 years old who were C282Y heterozygotes with no iron overload) but no brothers or sisters. These results showed that HH was uncommon among individuals attended at our hospital, although HFE mutations were found in all patients. Familial screening is valuable for the early diagnosis of individuals at risk since it allows treatment to be initiated before the onset of the clinical manifestations of organ damage associated with HH

Diagnosis, staging and treatment of hepatocellular carcinoma

Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies.

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

Hepatitis C virus (HCV) infection is a serious public health problem, since 80 percent to 85 percent of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81 percent from public and 19 percent from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62 percent) and white patients (80 percent). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64 percent) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65 percent of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8 percent and 13.6 percent of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65 percent of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

Hepatitis C virus infection in a Brazilian population with sickle-cell anemia

Patients with sickle-cell anemia submitted to frequent blood transfusions are at risk of contamination with hepatitis C virus (HCV). Determination of HCV RNA and genotype characterization are parameters that are relevant for the treatment of the viral infection. The objective of the present study was to determine the frequency of HCV infection and the positivity for HCV RNA and to identify the HCV genotype in patients with sickle-cell anemia with a history of blood transfusion who had been treated at the Hospital of the HEMOPE Foundation. Sera from 291 patients were tested for anti-HCV antibodies by ELISA 3.0 and RIBA 3.0 Chiron and for the presence of HCV RNA by RT-PCR. HCV genotyping was performed in 19 serum samples. Forty-one of 291 patients (14.1 percent) were anti-HCV positive by ELISA and RIBA. Both univariate and multivariate analysis showed a greater risk of anti-HCV positivity in those who had started a transfusion regime before 1992 and received more than 10 units of blood. Thirty-four of the anti-HCV-positive patients (34/41, 82.9 percent) were also HCV RNA positive. Univariate analysis, used to compare HCV RNA-negative and -positive patients, did not indicate a higher risk of HCV RNA positivity for any of the variables evaluated. The genotypes identified were 1b (63 percent), 1a (21 percent) and 3a (16 percent). A high prevalence of HCV infection was observed in our patients with sickle-cell anemia (14.1 percent) compared to the population in general (3 percent). In the literature, the frequency of HCV infection in sickle-cell anemia ranges from 2 to 30 percent. The serological screening for anti-HCV at blood banks after 1992 has contributed to a better control of the dissemination of HCV infection. Because of the predominance of genotype 1, these patients belong to a group requiring special treatment, with a probable indication of new therapeutic options against HCV

Cytochrome P450 and glutathione in the liver of rats under exclusive sucrose ingestion

1. The objective of the present investigation was to study some of the possible mechanisms involved in the protective effect of sucrose ingestion against liver necrosis induced by acetaminophen. Three groups of male Wistar rats (220-260 g) were submitted to the following experimental conditions for a period of 42 h: free access to a balanced commercial diet (Group I), an exclusive sucrose diet (Group II) and fasting (Group III). At the end of the experiment, hepatic cytochrome P450 levels were measured in 11 rats from each group, plasma antipyrine half-life (t1/2) was determined in 40 rats from each group, and hepatic glutathione (GSH) concentration in 10 rats from each group. GSH consumption elicited by a high dose of acetaminophen (ACP, 1.0 g/kg, by gavage) was also determined in 30 rats each from Groups II and III. 2. The liver of Group II rats presented a significant reduction of cytochrome P450 levels in the microsome fraction (range 0.31-0.46, median, 0.37 nmol/mg vs range 0.60-0.93, median 0.74 for group I, and range 0.63-1.22, median 0.91 for group III, reported as nmol/mg microsome protein; range 23.8-48.4, median 40.4 vs 66.6-130, median 81.8 for group I and range 59.0-117.1, median 77.1 for group III, reported as nmol/100 g body weight), and a prolongation of antipyrine half-life (146.4 vs 83.4 min for group I and 93.6 for group III) when compared with the rats of the two other groups. 3. Since the toxicity of acetaminophen depends on the production of a reactive metabolite by the cytochrome P450 system in the liver, we conclude that changes in this system brought about by exclusive sucrose ingestion for 42 h may explain the liver protection against the toxicity of a high dose of the drug even in the presence of a significant concomitant reduction in liver GSH levels

Effect of the intake of an exclusive sucrose diet on acetaminophen hepatotoxicity in rats

To test the effect of a sucrose diet on acetaminophen hepatotoxicity, 20 male Wistar rats were fasted and 20 were maintained exclusively on a sucrose diet ad libitum for 66 h. After 42 h, acetaminophen (1 g/kg) was administered through an orogastric tube to 10 fasted animals and to 10 animals on the sucrose diet, or intraperitoneally to the remaining animals. Animals were killed 24 h later and blood was collected for the measurement of alanine and aspartate aminotransferase activity and the liver was removel for macroscopic and microscopic examination. Plasma alanine and aspeartate aminotransferase levels were significantly lower (P<0.001) in all animals maintained on the sucrose diet. Macroscopic examination revealed parenchymatous necrosis in 90% (18/20) of the fasted animals but in none of the animals fed sucrosel. Microscopic examination confirmed the macroscopic findings and permited the detection of liver necrosis in one additional fasted animal. We conclude that ingestion of a sucrose diet protected the animals from the hepatotoxic effects of acetaminophen regardless of the route of administration of the drug