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.

Expression of activation and cytotoxic molecules by peripheral blood lymphocytes of patients with paracoccidioidomycosis.

In a previous study, we reported an increased number of T CD8(+) cells in the bronchoalveolar lavage (BAL) of patients with pulmonary paracoccidioidomycosis, suggesting a role for these cells in the local immune response. The aims of this study were to verify, by flow cytometry, the activation state, as well as the production of cytotoxic molecules by peripheral blood lymphocytes (CD8(+) and CD4(+)). Specimens were obtained from patients with paracoccidioidomycosis (PCM), individuals with PCM-infection, i.e., healthy individuals with demonstrated strong cellular response against the fungus (PI) and controls, with studies conducted both ex-vivo and in vitro, after stimulation with Paracoccidioides brasiliensis yeast cells. The ex-vivo analysis demonstrated that PCM patients presented a lower frequency of granzyme A, B and perforin-positive cells, as compared to individuals with PCM infection (PI). P. brasiliensis stimulation led to a discrete increase in CD69(+) cells and a reduction in cytotoxic granule expression in all groups. The addition of IL-15 induced an increase in the frequency of CD69(+) cells only in PI individuals and controls. The effect of IL-15 on granzyme A and B expression was low, but a higher frequency of CD8(+) perforin(+) was detected in PI individuals than in patients with active PCM. IL-15Ralpha expression was lower in CD4(+) T cells from patients, in relation to the PI group. Furthermore, low levels of granulysin were detected in sera from PCM patients, but a tendency for an increase in these levels was observed after antifungal therapy. Taken together, these results indicate that lymphocytes from PCM patients are poorly activated, express low levels of IL-15Ralpha and produce basal levels of cytotoxic granules. These findings may account for the defective cytotoxic activity in patients and, consequently, a low capacity to kill the fungus.

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.

Prevalence of hepatitis E virus IgG antibodies in patients from a referral unit of liver diseases in Salvador, Bahia, Brazil.

Hepatitis E virus (HEV) is prevalent in Asia and Africa. Recently, it was also described in Mexico, but epidemiologic data from other Latin American countries are scarce. The seroprevalence of anti-HEV in a referral hepatology unit in northern Brazil was determined by testing for anti-HEV IgG in 701 serum samples from our serum bank. Specimens analyzed were from 200 blood donors, 79 patients with acute viral hepatitis (AVH), 392 hemodialyzed patients, and 30 carriers of schistosomiasis. Duplicate test results for anti-HEV were positive in four (2%) of 200 of the blood donors, three (10%) of the 30 carriers of schistosomiasis, and in none of the 392 hemodialyzed patients. Fourteen (17.7%) of the AVH patients were positive, as were six (25%) of 24 with hepatitis A virus, three (11%) of 26 with hepatitis B virus, 0 (0%) of 12 with hepatitis C virus, and five (29%) of 17 with non-A, non-B, non-C hepatitis viruses. Among AVH cases, those with hepatitis A virus had a higher frequency of anti-HEV positivity compared with all other hepatotropic viruses (P < 0.0003). We conclude that HEV is prevalent in northern Brazil. The higher prevalence in patients compared with blood donors could be explained by the lower social condition of patients who sought public health service in this area, in contrast with the heterogeneous socioeconomic distribution of blood donors. Patients with AVH due to hepatitis A had a greater frequency of anti-HEV, probably because of similar routes of transmission for both hepatitis A and E viruses. Finally, the absence of anti-HEV in the hemodialyzed group could be explained by a lower immunologic response found in patients with chronic renal failure.

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.

Severe strongyloidiasis during interferon plus ribavirin therapy for chronic HCV infection.

Ribavirin is a nucleoside analogue, recently introduced in hepatitis C virus (HCV) therapy, that has postulated immunomodulatory and immunosuppressive action. Strongyloidiasis is an helmintic infection caused by Strongyloides stercoralis, endemic in tropical countries. Severe strongyloidiasis has been demonstrated after immunosuppression by corticosteroids evolving some fatal cases. Here, we describe two cases of severe strongyloidiasis coincident with ribavirin plus interferon therapy for treating HCV infection. The review of our monotherapy protocol with interferon did not disclose any case of symptomatic strongyloidiasis pointing to a possible role of ribavirin in modifying immune response to S. stercoralis. We propose a careful screening for S. stercoralis before initiating ribavirin therapy or even empiric antihelmintic treatment.

A case-control study on the association of hepatitis B virus infection and hepatocellular carcinoma in northeast Brazil.

Hepatitis B virus (HBV) serological markers were investigated in 40 incident cases of hepatocellular carcinoma (HCC) and in two age and sex matched control groups, comprising 40 patients with other cancers and 80 healthy individuals, resident in Bahia, Brazil. Serologic tests were done by radioimmunoassay. The study observed high proportion of seropositivity to HBsAg (42.5%) and of those presenting HBsAg or antiHBc (65.0%) among HCC cases, higher in men than women and in those aged 17 to 30 years old. HBsAg seropositivity among HCC patients was greater than in the control group with other cancers (7.5%) and in healthy controls (2.5%), corresponding to odds ratio estimates of 15.0 (95% CI 3.29, 68.30) and 33.0 (95% CI 9.13, 119.28), both statistically significant. HBeAg was not observed and antiHBe was present in 41.2% of cases, suggesting the absence of viral replication, possibly with viral DNA integration into the hepatocyte genome. The presence of cirrhosis was associated with HBsAg seropositivity among HCC cases. A history of chronic alcoholism is shown to be more frequently related to those cases with cirrhosis. This study highlights the relevant association between HCC and HBV in Northeast Brazil, particularly for young individuals, and the high risk of development of HCC for HBsAg carriers.

[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.

[Paracentesis associated to dextran-70 in the treatment of ascites in patients with chronic liver diseases: a randomized therapeutic study]. / Paracentese associada a Dextran-70 no tratamento da ascite de hepatopatas crônicos: ensaio terapêutico randomizado.

The treatment of ascites of large volume in chronic liver disease patients was evaluated in the present study. We compared diuretics with paracentesis and an infusion of Dextran-70. Therapeutic efficacy, complications and length of hospital stay were the variables studied. Of the 38 patients, 20 were selected randomly. They were evaluated using clinical, laboratory and/or histological criteria: 10 patients in the paracentesis group with Dextran-70 and 10 in the diuretic group. The groups were similar with respect to age, diagnosis and Child-Pugh classification. However, there was a greater number of males in the paracentesis group with Dextran-70. In each paracentesis, an average of 9.41 liters (4.5 to 14.1) of ascitic fluid was collected. The average hospitalization period in the paracentesis group with Dextran-70 was 10.5 days (8-14), significantly less when compared to the diuretic group: 24.4 days (14-48). In the diuretic group one patient presented complications such as hyperkalemia, increased urea and creatinine levels, while in the paracentesis group with Dextran-70 one patient presented a temperature above 38 degrees C during treatment. The results suggest that paracentesis associated with Dextran-70 could be a therapeutic alternative for chronic liver disease patients with ascites in our population. It was effective; it had no significant side effects; it reduced the length of hospital stay and therefore should decrease the cost and the risk of complications in patients requiring prolonged hospitalization periods.

[Antibodies to hepatitis C virus in patients undergoing hemodialysis in Salvador, BA, Brazil]. / Anticorpo contra o vírus C da hepatite em pacientes sob programa de hemodiálise em Salvador, BA, Brasil.

BACKGROUND: Hepatitis C infection in hemodialysis units has been evaluated in different geographic regions. AIMS: The prevalence of anti-HCV in patients undergoing hemodialysis program in the city of Salvador, State of Bahia, Brazil, was studied and its association with transfusions, duration of hemodialysis and ALT elevation. METHOD: During a period of 17 months, all patients undergoing dialytic treatment, were evaluated. The total number of patients was 395, all of whom completed a questionnaire and provided serum samples for laboratory analysis. Serological levels were measured for ALT and the samples were tested for anti-HCV using ELISA II with a further confirmation using RIBA III. RESULTS: Anti-HCV was positive in 23.8% (94/395). The presence of transfusions was associated with anti-HCV and as the number of transfusions used increased, so did the frequency of anti-HCV. Of the patients who never received transfusions, 12.5% (6/48) were anti-HCV positive. The duration of dialytic treatment lasted from 53.44 +/- 36.45 months in the anti-HCV positive group and 22.10 +/- 22.75 months for the group testing negative. ALT elevation was more frequent in the anti-HCV positive group. Positivity for the RIBA III fractions was 79.8%, 100%, 80.9% and 52.1%, for c100-3, c33, c22 and NS5, respectively. The anti-NS5 was even less frequent in the group with elevated ALT. CONCLUSIONS: The prevalence of anti-HCV in patients undergoing chronic hemodialysis in Salvador, Bahia, is elevated and it is associated with transfusions, a longer duration of dialytic treatment and ALT elevation.

[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)

HCV infection in northeastern Brazil: unexpected high prevalence of genotype 3a and absence of African genotypes.

The genomic diversity of HCV embraces 6 genotypes and at least 52 subtypes with clinical and epidemiological correlations. There is a paucity of studies assessing HCV genotypes and biomolecular epidemiology in Brazil. We studied genotype distribution and epidemiological aspects in 232 HCV carriers, 133 (57.9%) males and 99 (42.1%) females, followed in the liver disease referral unit in Salvador, BA, northeastern Brazil. All of them were anti-HCV positive by 3rd generation ELISA assay, and HCV-RNA positive by RT-PCR. Genotyping was performed by INNOLIPA. Assessment of risk factors for HCV infection showed that 93 (40%) had past blood transfusion, 14 (6%) intravenous drug use, 19 (8%) inhalation of cocaine, 28 (12%) tattooing, 15 (7%) were health care workers, 5 (2%) had reused disposable syringes, 5 (2%) had multiple risk factors and in 53 (23%) no risk factor was determined. Genotype 1a was observed in 75 (32%), 1b in 72 (31%), 3a in 61 (26%), 2ab in 14 (6%); 5 (2.5%) had mixed genotypes and 5 (2.5%) were undetermined. Patients with genotype 1 had a higher mean age (P < 0.05) and no particular risk factors were associated with a specific genotype. Genotype 1 largely predominates in northeast Brazil followed by genotype 3 which, in this population, does not seem to be related to intravenous drug abuse, in contrast to some European studies. Although 80% of the Salvador population comprises African-Brazilians, no African genotype was identified, which may mean that HCV was introduced into this region via European immigration. This study demonstrated some peculiarities of HCV epidemiology in Brazil and strongly suggests that HCV introduction to this region was probably related to European immigration.

[Prevalence of hepatitis C virus in urban and rural populations of northeast Brazil-pilot study]. / Prevalência do vírus da hepatite C em populações urbana e rural no Nordeste do Brasil-estudo piloto.

Hepatitis C virus can be found in all continents. However, differences exist with respect to its prevalence. In Brazil, epidemiological data are scarce, and are based, in their majority, on information obtained from blood donors and not from the general population. Our objective is to show the prevalence of anti-HCV in two distinct populations: one rural and one urban: Salvador, a metropolis, and Castro Alves, a rural village with very little contact with other populations. Eight hundred individuals from Salvador and 800 from Castro Alves were randomly visited. After obtaining consent, we collected blood samples for serology tests and determination of ALT levels. The anti-HCV antibody was tested using ELISA II (ABBOTT Labs), and confirmed by RIBA III (Chiron). We studied the prevalence of anti-HCV in two populations and its distribution with respect to age group and sex and ALT level. chi 2 and Fisher exact were used for the statistical analysis. Of the 800 individuals from Salvador, 44% were women and 56% were men. The age group varied from 10 to 70 years, with an average age of 42. Ten (1.25%) individuals were anti-HCV positive in the urban population and none in the rural population (P < 0.001). No evident correlation was found regarding sex and ALT level, between anti-HCV positive and anti-HCV negative individuals in the urban population. In conclusion, our results suggest a higher prevalence of HCV infection in the urban population probably due to a high level of exposure. The sero-epidemiological studies using blood donors do not reflect the epidemiological reality of HCV in Brazil due to selection bias which could overestimate its seroprevelence.

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.