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.

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.

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.

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 percent) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01 percent) were genotype 1 and 20 (28.99 percent) genotype non-1. Iron overload was detected in 14 (28.6 percent) patients with genotype 1 and in 6 (30 percent) 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 percent) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70 percent of group I patients compared to 46.2 percent of group II. Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1 percent) had a sustained virologic response and 8 (27.6 percent) of them had hepatic iron overload. Iron overload was detected in 18 (32.1 percent) 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.

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 percent 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 percent of patients with acute hepatitis and in 31 percent of donors. GBV-C/HGV was detected in 9 percent of patients with hepatitis, and in 10 percent 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.

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.

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.

Nonalcoholic steatohepatitis: a toxic liver disease in industrial workers.

AIMS: Occupational/environmental exposure to hepatotoxins has recently been implicated in nonalcoholic steatohepatitis (NASH). The aims of this study were to determine the presence and frequency of NASH in a large group of workers chronically exposed to several volatile petrochemical products in an industrial area in north-east Brazil and to observe its course in workers removed from the work environment. METHODS: 1500 asymptomatic workers were screened with standard liver blood tests during 1994-5. Those with elevated transaminases (>3x normal) on 3 occasions were evaluated further both clinically and with serum HBsAg, anti-HCV, ferritin, lipids and autoantibody determination. Patients with either no etiological diagnosis, positive HBsAg/anti-HCV serology and/or excess alcohol intake underwent liver biopsy. Those with obesity, diabetes or an isolated abnormal GGT were excluded. Of workers diagnosed as having NASH (compatible histology and no excess alcohol intake), a proportion were removed from the work environment and evaluated monthly with liver blood tests and a repeat liver biopsy 8-14 months later. RESULTS: 112 workers had abnormal transaminases and 32 fulfilled the criteria for liver biopsy. 20 of these were classified as NASH, the remainder had viral hepatitis (n = 6), alcoholic liver disease (n = 5) or portal vein thrombosis (n = 1). In all of the 10/20 who were removed from the work environment, their aminotransferases and GGT gradually decreased and their histology improved. CONCLUSIONS: These results demonstrate that NASH can occur following chronic exposure to volatile petrochemical substances in the workplace. Exposed workers should be regularly screened for the presence of liver damage and ideally removed from the work environment where possible.

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.

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.

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.

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.

[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)

Very-low dose antacid in treatment of duodenal ulcer. Comparison with cimetidine.

Antacid (AA) in a very low dose (88 mmol/day) was compared to the standard 800-mg dose of cimetidine in healing duodenal ulcers. The influence of sex, age, symptom duration at entry, night pain, smoking, coffee consumption, and alcohol on ulcer healing was studied. The antacid was given in two different schedules: group I--20 ml 1 hr after breakfast and at bedtime; group II--10 ml 1 hr after breakfast and lunch and 20 ml at bedtime. Cimetidine (group III) was given in two divided doses: 400 mg 1 hr after breakfast and 400 mg at bedtime. Endoscopic control was performed after four weeks and, if necessary, after eight weeks of treatment. The healing rate after four weeks of treatment was, respectively, for groups I, II, and III, 45.5%, 55.8%, and 69.4% (group I = group II, and group III different from groups I and II). After eight weeks of treatment the healing rate was 61.5%, 80.8%, and 88.0% for groups I, II, and III, respectively (group II = group III, and group I different from groups II and III). Except for group I, smoking did not influence healing rate. Age, sex, symptoms at entry, night pain, and coffee consumption did not influence the treatment results. The authors concluded that the very low dose of magaldrate (88 mmol/day), when administered in three divided doses (10 ml after breakfast and lunch and 20 ml at bedtime) for eight weeks was as effective as 800 mg of cimetidine (400 mg twice a day) in healing duodenal ulcer.

[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.