n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in hepatitis C virus infected patients: a randomised controlled trial.

BACKGROUND: Insulin resistance promotes liver disease progression and may be associated with a lower response rate in treated hepatitis C virus (HCV) infected patients. n-3 polyunsaturated fatty acid (PUFA) supplementation may reduce insulin resistance. The present study aimed to evaluate the effect of n-3 PUFA supplementation on insulin resistance in these patients. METHODS: In a randomised, double-blind clinical trial, 154 patients were screened. After applying inclusion criteria, 52 patients [homeostasis model assessment index of insulin resistance (HOMA-IR ≥2.5)] were randomly divided into two groups: n-3 PUFA (n = 25/6000 mg day(-1) of fish oil) or control (n = 27/6000 mg day(-1) of soybean oil). Both groups were supplemented for 12 weeks and underwent monthly nutritional consultation. Biochemical tests were performed at baseline and after intervention. Statistical analysis was performed using the Wilcoxon Mann-Whitney test for comparisons and the Wilcoxon test for paired data. Statistical package r, version 3.02 (The R Project for Statistical Computing) was used and P < 0.05 (two-tailed) was considered statistically significant. RESULTS: Comparisons between groups showed that n-3 PUFA supplementation was more effective than the control for reducing HOMA-IR (P = 0.015) and serum insulin (P = 0.016). The n-3 PUFA group not only showed a significant reduction in HOMA-IR 3.8 (3.2-5.0) versus 2.4 (1.8-3.3) (P = 0.002); serum insulin 17.1 (13.8-20.6) µIU mL(-1) versus 10.9 (8.6-14.6) µIU mL(-1) (P = 0.001); and glycated haemoglobin 5.4% (5.0-5.7%) versus 5.1% (4.8-5.6%) (P = 0.011), but also presented an increase in interleukin-1 97.5 (0.0-199.8) pg mL(-1) versus 192.4 (102.2-266.8) pg mL(-1) (P = 0.003) and tumour necrosis factor 121.2 (0.0-171.3) pg mL(-1) versus 185.7 (98.0-246.9) pg mL(-1) (P = 0.003). CONCLUSIONS: n-3 PUFA supplementation reduces insulin resistance in genotype 1 HCV infected patients.

The impact of nutritional supplementation on quality of life in patients infected with hepatitis C virus.

BACKGROUND: The present study aimed to evaluate the impact of animal and vegetable protein supplementation on health-related quality of life (HRQL) in patients with hepatitis C virus (HCV) and to investigate clinical and nutritional variables related to quality of life in these patients. METHODS: One hundred and forty patients infected with HCV were randomly assigned to one of two groups: the Soy Group (SG; n = 72), where patients received a soy supplement diet and the Casein Group (CG; n = 68), where patients received casein as a supplement. Anthropometric, biochemical and clinical assessments were performed in all patients, and the Short-Form Health Survey was applied at baseline and 12 weeks after study initiation. RESULTS: Before supplementation, poor HRQL scores were associated with female sex (P = 0.004) and advanced fibrosis (F3/F4; P = 0.04). Reduced HRQL scores were correlated with age (r = -0.263; P = 0.002), serum albumin levels (r = 0.245; P = 0.004), lean mass (r = 0.301; P < 0.0001) and body fat percentage (r = -0.262; P = 0.002). After 12 weeks of intervention, patients in both supplementation groups showed significantly increased HRQL scores, with no difference being observed between the SG and the CG. CONCLUSIONS: Nutritional therapy with either soybean or casein supplementation improved quality of life in patients infected with HCV. Quality of life was influenced by anthropometric, biochemical, clinical and sociodemographic factors in patients with HCV before nutritional supplementation.

Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection.

The objective of the present study was to determine the presence of hepatic iron overload in patients with chronic HCV infection and to correlate it with histologic alterations, HCV genotype and response to therapy. Liver tissue samples from 95 patients with chronic hepatitis C were divided into two groups: group I, presence of iron overload in hepatic tissue (Perls' staining) and group II, no iron overload. Hepatic iron overload was detected in 30 (31.6%) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01%) were genotype 1 and 20 (28.99%) genotype non-1. Iron overload was detected in 14 (28.6%) patients with genotype 1 and in 6 (30%) with genotype non-1 (P = 0.906). There was a significant difference in fibrosis stage between groups (P = 0.005). In group I (N = 30), one patient had stage F0/F1 of fibrosis, while in group II (N = 65), 22 (33.8%) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70% of group I patients compared to 46.2% of group II. Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1%) had a sustained virologic response and 8 (27.6%) of them had hepatic iron overload. Iron overload was detected in 18 (32.1%) of the 56 non-responders (P = 0.73). Hepatic iron overload was frequent among patients with chronic hepatitis C and was associated with a more severe stage of liver fibrosis. There was no association between iron overload and HCV genotype and response to interferon and ribavirin therapy.

HEV, TTV and GBV-C/HGV markers in patients with acute viral hepatitis.

The aim of the present study was to evaluate the prevalence of HEV, TTV and GBV-C/GBV-C/HGV in patients with acute viral hepatitis A, B and non-A-C. We evaluated sera of 94 patients from a sentinel program who had acute hepatitis A (N = 40), B (N = 42) and non-A-C (N = 12); 71 blood donors served as controls. IgM and anti-HEV IgG antibodies were detected by enzyme immunoassay using commercial kits. TTV and GBV-C/HGV were detected by nested PCR; genotyping was done by sequencing and phylogenetic analysis. Anti-HEV IgG was present in 38, 10 and 17% of patients with hepatitis A, B and non-A-C. Four patients with hepatitis A and 1 with non-A-C hepatitis also had anti-HEV IgM detected in serum. TTV was detected in 21% of patients with acute hepatitis and in 31% of donors. GBV-C/HGV was detected in 9% of patients with hepatitis, and in 10% of donors. We found TTV isolates of genotypes 1, 2, 3, and 4 and GBV-C/HGV isolates of genotypes 1 and 2. Mean aminotransferase levels were lower in patients who were TTV or GBV-C/HGV positive. In conclusion, the detection of anti-HEV IgM in some acute hepatitis A cases suggests co-infection with HEV and hepatitis E could be the etiology of a few cases of sporadic non-A-C hepatitis in Salvador, Brazil. TTV genotype 1, 2, 3 and 4 isolates and GBV-C/HGV genotype 1 and 2 strains are frequent in the studied population. TTV and GBV-C/HGV infection does not appear to have a role in the etiology of acute hepatitis.

Short report: further evidence for hepatitis E in the Brazilian Amazon.

During an investigation of a hepatitis outbreak occurring in a small village in the Brazilian Amazon, serum samples from 16 recent hepatitis cases and 66 of their asymptomatic relatives were tested for the presence of hepatitis A, B, C, and E markers. Sanitation is poor and organized disposal of sewage is absent in the village. Two of the 16 hepatitis cases were non-A, non-B and non-C hepatitis, but their sera reacted to hepatitis E antibodies of the IgG class (anti-HEV). Likewise, sera from seven of the 66 asymptomatic relatives were positive for anti-HEV. Four of the nine anti-HEV positive sera had their reactivity confirmed by a neutralization test using synthetic peptides based on the nucleotide sequences of open reading frames 2 (ORF2) and 3 (ORF3) encoded in the HEV genome. To our knowledge, this is the first report suggesting the occurrence of acute E hepatitis cases in the Brazilian Amazon.

Hepatitis C virus genotypes in a northeastern area of Brazil.

We used a reverse transcription-polymerase chain reaction (RT-PCR) to obtain the genotypes of circulating hepatitis C virus (HCV) in patients from a Gastro-Hepatology Unit in the city of Salvador (Bahia State) in northeastern Brazil. Viral RNA was detected in 83 (65.4%) of 127 anti-HCV seropositive serum samples. Positivity was significantly associated with alterations in levels of aspartate aminotransferase and alanine aminotransferase (P < 0.05). Genotyping of HCV was performed by RT-PCR using genotype-specific primers from the core region: 24.1% were infected with subtype 1a, 38.6% with 1b, 3.6% with 2, 21.7% with 3a, and 12.0% with a mixed genotype. There was no difference in genotype distribution when compared with results from other Brazilian locations. Surprisingly, the high frequency of genotype 3 in Brazilian samples continues to be different from that reported around the world and warrants further investigation.

Hepatitis B virus infection in immigrants to the southern Brazilian Amazon.

To identify epidemiological patterns and risk factors associated with hepatitis B virus (HBV) infection in the southern Brazilian Amazon, a survey was performed in the county of Terra Nova do Norte in the northern part of the state of Mato Grosso. The population consists mainly of immigrants from the southern part of Brazil, where HBV prevalence is low. A random sample (n = 783) of the population was interviewed and tested for HBV markers. The overall prevalence of HBV infection was 54.7%. There were 31 hepatitis B surface antigen (HBsAg) carriers (3.9%), with a low rate of HBV e antigen positivity, and none with anti-hepatitis D virus. Subtypes ayw3 and ayw2 of HBsAg were predominant, suggesting that the immigrants carried HBV from their original region to the Amazon. Clustering of HBV infection within families was found. The association between HBV markers and having lived in a gold-miners' camp, even after adjusting for confounders, indicated that the gold-miners may play a role in HBV spread in areas of the Amazon where gold prospecting occurs.

[Viral markers of hepatitis A and B: main characteristics and clinical significance]. / Os marcadores virais da hepatite A e B: principais características e significado clínico.

Etiologic diagnosis of hepatitis A virus infection, is discussed considering the antibody to hepatitis A virus (anti-HAV) type IgM and IgG. Clinical relevance of hepatitis B virus markers (HBsAg, HBeAg, anti-HBc IgM and IgG, anti-HBe and anti-HBs) is reviewed as they appear in the clinical course of the disease. The significance of chronic viremia and persistence of HBeAg is commented as well as the perspective prognostic factor of Delta antigen.

[Forms of hepatic disease in alcoholic patients in Salvador, BA]. / Formas de doença hepática em pacientes com alcoolismo em Salvador, BA.

This study was carried out to evaluate the relative importance of various patterns in liver in patients followed with chronic ethylism at the Hepatology Unit Care Service of the Hospital Prof. Edgard Santos--University Federal of Bahia, Brazil. Ninety six individuals were submitted to liver biopsy. Of those, 69 (71.9%) presented with alcoholic lesions and 27 (28.1%) had other histologic features of liver disease not commonly related to alcoholism. These data suggested that the presence of other types of liver diseases are prevalent in alcoholic patients in Bahia and showed that, in addition to clinic and laboratorial evaluation, it is essential to perform the histological study to complete the diagnostic of the patients, and detect other liver diseases not associated to alcohol.

[Hepatitis B virus markers in peripheral blood mononuclear cells]. / Marcadores do vírus da hepatite B em células mononucleares do sangue periférico.

Recent studies have shown tropism of the hepatitis B virus (HBV) by peripheral blood mononuclear cells (PBMC). The consequences of this phenomenon and their clinical use are not yet clear, however. Seventy-nine patients were studied between March 1989 and October 1990. Sixty-nine patients had chronic liver disease with histological evaluations, and 10 were vaccinated for HBV. The following markers were determined: serum: HBsAg, HBeAg, anti-HBe, antitotal-HBc, anti-HBs, anti-HCV, HBV-DNA; lysated PMBC cells: HBsAg, HBeAg. Hepatic tissue: HBsAg, HBcAg. Four groups were formed according to serology. Group I--positive HBsAg patients (n = 25) HBsAg was observed in the lysated of PBMC in 19 (76%) of the patients. HBeAg in PBMC was detected in 8 (32%), all of them showed evidence of viral replication (presence of HBcAg and/or HBV-DNA in the serum HBcAg in the tissue). Group II--antitotal HBc/anti-HBs positive (n = 14), HBsAg in PBMC was found in 5 (36%) and HBeAg in 1 (7.0%). In this patient replication markers in the serum and in the tissue (HBV-DNA, HBcAg) was also present. Three patients out of 9 anti-HBs positive had HBsAg in PBMC. Group III--seronegative patients for HBV. HBsAg was present in PBMC in 2 (6.6%) of the patients, but was absent in all of them. There was concomitant presence of HBsAg in MN and the hepatic tissue in 1 patient. Replication markers were not observed in the group. Group IV--10 asymptomatic individuals vaccinated for HBV. Except anti-HBs in serum, no other HBV marker could be identified in serum or in PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible molecular mechanisms soy-mediated in preventing and treating nonalcoholic fatty liver disease.

The aim of this review is to describe the molecular mechanisms of nonalcoholic fatty liver disease (NAFLD) and to present evidence regarding the mechanisms of soy-mediated therapeutic activity in preventing and treating NAFLD. NAFLD is induced by multiple metabolic pathways, including an increase in the release of fatty acids from the adipose tissue (lipolysis), insulin resistance (IR), and an increase in "de novo" fatty acid synthesis. Furthermore, NAFLD is correlated with a decrease in liver ß-oxidation, an increase in oxygen free radical production, and an increase in pro-inflammatory cytokine production, which leads to an increase in liver fat and, subsequently, to tissue damage. The bioactive compounds in soy can prevent and treat NAFLD by modulating lipid metabolism and regulating the expression of related transcription factors. Soy intake decreases the expression of sterol regulatory-element binding protein-lc (SREBP-1) and increases the expression of SREBP-2, which are transcription factors associated with the regulation of hepatic lipogenesis and reduction of cholesterol synthesis and absorption in the liver, respectively. Besides, interactions between soy components, such as standard amino acids, polyunsaturated fat, and the isoflavonoid-enriched fraction, are believed to improve fatty acid oxidation in the liver parenchyma by increasing the expression of peroxisome proliferator-activated receptor α (PPARα)-regulated genes, thus decreasing lipid accumulation in the liver. Therefore, including soy-derived foods in the diet as a therapeutic tool for patients with NAFLD might improve their clinical evolution.

[Topographic and intracellular distribution of monoamine and diamine oxydases in rat stomach].

Up to now, the activity of D.A.O. and M.A.O. in the gastric mucosa of rat stomach has not been yet detected. Employing a radioisotopic method, modified by us, it was possible to detect the activity of both enzymes in sufficient amount to study their topographic and intracellular localization. Topographically, the antral region showed the highest activity for the two enzymes, being the D.A.O. 20 times stronger than the M.A.O. The intracellular localization of M.A.O. seems to be in the lysosomes but the D.A.O. looks like to be homogeneously distributed, except in the mitochondrial fraction. The simple demonstration of gastric intracellular distribution of these enzymes in the rat stomach should stimulate further investigations to elucidate the metabolism of histamine and its enzymatic regulations.

Hepatitis B surface antigen carrier state in hepatosplenic schistosomiasis.

The prevalence of hepatitis B surface antigen (HBsAg) was studied in 103 cases of hepatosplenic schistosomiasis (HSS), 134 control cases with a variety of illnesses including hepatointestinal schistosomiasis, and 600 blood donors, in an area endemic for both schisfosomiasis and viral hepatitis. The patients with HSS proved to be persistent carriers for HBsAg in a significantly higher proportion than the other two groups of cases. The HSS cases who were carriers of HBsAg had more clinical signs of chronic liver disease and strikingly more chronic inflammation of the portal spaces on liver biopsy. It is suggested that abnormal immunological responses in patients with HSS makes them more susceptible to become carriers of HBsAg and that the addition of this injurious factor makes their basic disease worse, and may be responsible for the development of cirrhosis in some cases.

Nitrogen metabolism in the perfused cirrhotic liver of the rat.

The isolated perfused liver of the cirrhotic rat produces greater quantities of ammonia from endogenous sources or from added alanine than do control livers. It also fails to take up ammonia. In these cirrhotic livers ethanol increases ammonia production in the presence of alanine. When cirrhotic rats had received a normal diet for 10 days before perfusion, the output of ammonia from endogenous sources and from added alanine is partially restored to normal. The addition of ethanol in the presence of alanine to the perfusate of these cirrhotic livers then results in an increased rate of production of glutamine rather than of ammonia. A normal diet given these cirrhotic animals restores the uptake of ammonia to that seen in the control animals but, unlike the normal animals, the addition of ornithine increases neither the uptake of ammonia nor the output of urea. In the normal animals this effect of ornithine on the uptake of ammonia is abolished by ethanol. It is concluded that cirrhotic rat liver is a source of endogenous ammonia and that the magnitude of that contribution is modified by diet and by ethanol.

Pantoprazole versus ranitidine in the treatment of duodenal ulcer: a multicenter study in Brazil.

OBJECTIVE: The aim of this study was to compare the effectiveness and tolerance of pantoprazole versus ranitidine in the treatment of duodenal ulcers in the Brazilian population. METHODS: A total of 222 patients with active duodenal ulcers (DU) were randomly allocated to a double dummy blind treatment, either with ranitidine (RAN) 300 mg (111, aged from 20-68 yr old, 56 female) or with pantoprazole (PANT) 40 mg (111 patients, 18-70 yr old, 45 female). After a 2-wk course of treatment, each patient was clinically and endoscopically assessed for ulcer healing. Failure to heal required a further 2-wk course of treatment and a new evaluation thereafter. RESULTS: In all, 77 of the 103 patients in the PANT group (74.8%) and 42 of the 94 patients in the RAN group (44.7%) who completed the study had ulcer healing after one 2-wk treatment course, and an additional 23 in the PANT group (22.3%) and 28 in the RAN group (29.8%) after the second 2-wk treatment course, totaling 100 (97.1%) and 70 (74.5%), respectively. Therapeutic gain in favor of pantoprazole was significant both at the end of the first and the second 2-wk treatment course (p<0.001). At 2 wk, symptoms remission was significantly higher in the PANT group (97.6%) than with the RAN group (77.5%) (p<0.001). The Intention-to-treat analysis showed results statistically similar to those observed in the per-protocol analysis. Minor adverse events were reported by four patients in the PANT group and three in the RAN group. No relevant laboratory abnormalities were seen. No patient withdrew from the study due to adverse events. CONCLUSIONS: Our results show that pantoprazole is more effective than ranitidine in the treatment of duodenal ulcer providing faster ulcer healing in most patients (97.1%), in 4 wk. Adverse events were rare and were similar in both groups, and had no influence on the therapeutic outcome.

Serial transmission of spongiocytic hepatitis to woodchucks (possible association with a specific delta strain).

BACKGROUND/AIMS: Outbreaks of severe hepatitis have been reported from Africa and South America. Description of the cases has shown the histological hallmark to be the presence of ballooning hepatocytes with fat drops surrounding the nucleus (spongiocytes or morula cells). METHODS: Experimental reproduction of this syndrome for the verification of a possible role of a specific HDV strain was performed by the inoculation of serum and liver extracts from African patients (Bangui-Central African Republic), who died with this syndrome, into American woodchuck carriers of WHV (WC 231,144), the results of which were then compared with animals inoculated with a reference wild HDV strain (WC 300,173,154), and those which received material from a European fulminant HDV case (WC 88,93). RESULTS: Following the initial inoculation, the animals receiving African inocula had a delayed anti-HDV seroconversion, high mortality and showed the presence of spongiocytes, while the other animals had a classical evolution of HDV superinfection in woodchucks. Furthermore, the African inocula caused less inhibition of WHV replication, as well as a predominant cytoplasmic expression of HDAg, in contrast to the animals which received the other inocula. The second passage experiments gave similar results. CONCLUSIONS: We conclude that this peculiar form of HDV fulminant hepatitis can be experimentally reproduced and might be specifically related to a more pathogenic strain.

Epidemiological survey of infection with hepatitis B virus in the savannah and wetlands (Pantanal) of central Brazil.

An epidemiological survey of the prevalence of hepatitis B virus (HBV) was conducted in the county of Nossa Senhora do Livramento, Mato Grosso state, central Brazil. This rural county has a largely stationary population of low socio-economic status, and is divided into savannah-type vegetation and wetland. Overall, 740 subjects aged > 9 years were selected at random, interviewed and bled so that seropositivities of various HBV markers (surface antigen and antibodies to this antigen and to core antigen) could be determined. At least one marker was found in 169 (22.8%) of the subjects but only nine (1.2%) carried the surface antigen. Vegetation type (wetland v. savannah) was not associated with HBV infection but male gender, increasing age, and having had sexual experience were each associated with the infection. The prevalence of HBV markers was higher in immigrants (32.5%) than in native individuals (21.1%), many immigrants apparently having acquired the infection before settling in the study area.