Comparison between criteria for diagnosing malnutrition in patients with advanced chronic liver disease: GLIM group proposal versus different nutritional screening tools.

BACKGROUND: Different nutritional screening instruments can be used to identify the risk of malnutrition in advanced chronic liver disease patients. The present study aimed to evaluate and compare two nutrition screening tools with the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria for malnutrition in patients with advanced chronic liver disease. METHODS: Two nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002) and Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT), were assessed for 166 patients with liver cirrhosis. We compared medium/high nutritional risk screening with the diagnosis of malnutrition, using the GLIM criteria as the reference standard. RESULTS: According to the GLIM criteria, 57.3% of the patients were malnourished. NRS and RFH-NPT identified, respectively, 36.1% and 52.4% of patients with nutritional risk. RFH-NPT presented better agreement with the diagnosis according to GLIM criteria (k = 0.64; 95% confidence interval = 0.52-0.75), higher sensitivity (80%), higher negative predictive value (79%) and larger area under the curve (82.3%) compared to the NRS. CONCLUSIONS: RFH-NPT, when compared with the GLIM method, has substantial agreement in identifying nutritional risk, good sensitivity and good value for diagnosing malnutrition in patients with advanced chronic liver disease.

The effect of a probiotic blend on gastrointestinal symptoms in constipated patients: a double blind, randomised, placebo controlled 2-week trial.

Selected strains of lactobacilli and bifidobacteria are known to ameliorate constipation-related symptoms and have previously shown efficacy on digestive health. In this clinical trial, the safety and effectiveness of a probiotic blend containing lactobacilli and bifidobacteria were evaluated in adults with self-reported bloating and functional constipation. Constipation was diagnosed by the Rome III criteria. A total of 156 adults were randomised into this double-blind and placebo-controlled trial. Participants consumed the combination of Lactobacillus acidophilus NCFM (1010 cfu), Lactobacillus paracasei Lpc-37 (2.5×109 cfu), Bifidobacterium animalis subsp. lactis strains Bl-04 (2.5×109 cfu), Bi-07 (2.5×109 cfu) and HN019 (1010 cfu) (n=78), or placebo (microcrystalline cellulose) (n=78) for two weeks. After treatment the following were measured: primary outcome of bloating and secondary outcomes of colonic transit time, bowel movement frequency, stool consistency, other gastrointestinal symptoms (flatulence, abdominal pain, and burbling), constipation-related questionnaires (PAC-SYM and PAC-QoL) and product satisfaction. Faecal recovery of consumed strains was determined. The enrolled population was defined as constipated, however, the initial bloating severity was lower than in previous similar studies. No clinically significant observations related to the safety of the product were reported. Product efficacy was not shown in the primary analysis for bloating nor for the secondary efficacy analyses. The placebo functioned similarly as the probiotic product. In post-hoc analysis, a statistically significant decrease in flatulence in favour of the probiotic group was observed; day 7 (intention-to-treat (ITT): P=0.0313; per-protocol (PP): 0.0253) and on day 14 (ITT: P=0.0116; PP: P=0.0102) as measured by area under the curve (AUC) analysis. The mean AUC of all symptoms decreased in favour of the probiotic group, indicating less digestive discomfort. The study was registered at the ISRCTN registry (ISRCTN41607808).

Bone mineral density and inflammatory bowel disease severity.

Inflammatory bowel disease (IBD) is associated with low bone mineral density (BMD). In this study, the association between disease severity and BMD in patients with IBD was evaluated. Associations between BMD and the Montreal classification, disease activity and drug therapy were also tested. A cross-sectional prevalence study with a comparison group was conducted. One hundred and twenty-eight patients were evaluated: 68 patients with ulcerative colitis (UC), and 60 with Crohn's disease (CD). The control group consisted of 67 healthy subjects. All patients and controls had BMD measured and in IBD patients, current medications, hospitalization, and disease location, extent and phenotype, according to the Montreal classification, were recorded. Multiple correspondence analysis was applied to evaluate categorical variables. In the CD group, most patients were diagnosed between 17-40 years of age. Ileocolonic and non-stricturing non-penetrating disease were the most frequent disease location and behavior, respectively. In UC patients, extensive colitis was the most frequent disease location. UC and CD patients were more likely to have osteopenia than controls (OR=14.93/OR=24.38, respectively). In the CD group, male patients, perianal disease, penetrating behavior and age at diagnosis >40 years were associated with low BMD. Taking azathioprine and infliximab also seemed to be associated with osteopenia. In the UC group, we observed an association between low BMD and male patients, left colitis, corticosteroid use and hospitalization. Disease activity was not associated with osteopenia or osteoporosis in CD and UC patients. Disease severity seems to be associated with osteopenia in IBD patients.

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.

Sida cordifolia leaf extract reduces the orofacial nociceptive response in mice.

In this study, we describe the antinociceptive activity of the ethanol extract (EE), chloroform (CF) and methanol (MF) fractions obtained from Sida cordifolia, popularly known in Brazil as "malva branca" or "malva branca sedosa". Leaves of S. cordifolia were used to produce the crude ethanol extract and after CF and MF. Experiments were conducted on Swiss mice using the glutamate and formalin-induced orofacial nociception. In the formalin test, all doses of EE, CF and MF significantly reduced the orofacial nociception in the first (p < 0.001) and second phase (p < 0.001), which was also naloxone-sensitive. In the glutamate-induced nociception test, only CF and MF significantly reduced the orofacial nociceptive behavior with inhibition percentage values of 48.1% (100 mg/kg, CF), 56.1% (200 mg/kg, CF), 66.4% (400 mg/kg, CF), 48.2 (200 mg/kg, MF) and 60.1 (400 mg/kg, MF). Furthermore, treatment of the animals with EE, CF and MF was not able to promote motor activity changes. These data demonstrate that S. cordifolia has a pronounced antinociceptive activity on orofacial nociception. However, pharmacological and chemical studies are necessary in order to characterize the responsible mechanisms for this antinociceptive action and also to identify other bioactive compounds present in S. cordifolia.

Biomechanical behaviour of a fractured maxillary incisor restored with direct composite resin only or with different post systems.

AIM: To compare stress distribution between a fractured maxillary central incisor restored with direct composite resin only (CR) or associated with different post materials, using finite element analysis. METHODOLOGY: A three-dimensional model of a sound maxillary central incisor and supporting structures was constructed, using data from the dental literature. Changes were made in the crown region to create a tooth with a restored crown fracture. A composite resin restoration only and restorations associated with different tapered post systems (glass fibre, carbon fibre, titanium and zirconia ceramic) were also evaluated, resulting in six experimental models. A static chewing pressure of 2.16Nmm(-2) was applied to two areas of the palatal surface of the tooth. Stress distribution was analysed under a general condition and in the structures of the models separately. RESULTS: The maximum stresses were concentrated as follows: at the cemento-enamel junction in the model with a sound maxillary central incisor, restored with CR and with a composite resin restoration associated with fibre posts; in the enamel at the post-enamel interface on the palatal surface of the model with a titanium post; and in the post of the model with zirconia ceramic post. CONCLUSIONS: None of the restorations evaluated was able to recover the stress distribution of the sound tooth. The models restored with composite resin associated with a glass or carbon fibre post had similar stress distributions to that of the model restored with CR. The different post materials were shown to have a substantial influence on stress distribution, with less stress concentration when fibre posts were used.

Intestinal microbiota and overweight.

The microbes in our gut can influence our weight by providing us with energy through the degradation of nondigestable carbohydrates and by affecting the cellular energy status of liver and muscle cells and the accumulation of lipids in adipose tissue. Thus, it is not surprising that in several studies the gastrointestinal microbiota of overweight and obese subjects has been found to differ from that of lean subjects. The initial findings linked obesity with proportionally decreased levels of the phylum Bacteroidetes and increased levels of the phylum Firmicutes. Later, several studies have assessed the association between overweight or obesity and the gastrointestinal microbiota, applying an array of molecular methods targeting the microbiota as a whole or specific bacterial groups or species within. However, at present it is difficult to draw conclusions on which of the observed microbiota alterations are relevant; essentially all of the bacterial groups that have been studied in more than one trial have given contradictory results in regard to their association with weight. Some of these discrepancies can result from methodological issues and some from the nature of the gastrointestinal microbiota, which is an extremely complex and dynamic microbial ecosystem with high subject specificity. In addition, selecting subjects purely based on weight may result in a largely heterogeneous group with several potentially confounding factors. While it may be premature to conclude which specific groups of bacteria are prominent in the intestinal tract of overweight and obese subjects, it appears clear that microbes contribute to weight gain and related health issues, such as the metabolic syndrome and type II diabetes. Therefore, it is important to continue to search for common microbial markers and predictors of obesity, and to study how these may be modulated with probiotics and prebiotics to promote health.

Evidence for action of ribavirin through the hepatitis C virus RNA polymerase.

Hepatitis C virus (HCV) infections are treated with interferon alpha plus ribavirin, but it is unknown how ribavirin works against HCV. Ribavirin is a guanosine analogue that can be a substrate for the viral RNA polymerase. HCV is genetically variable, and this genetic variation could affect the polymerase's use of ribavirin triphosphate. Thirteen patients infected with HCV who failed interferon alpha monotherapy and were retreated with interferon alpha plus ribavirin were identified; seven were responders and six were nonresponders to combination therapy. The consensus sequences encoding the 13 polymerases plus seven sequences from treatment-naive controls were determined. The responder sequences were more genetically variable than the nonresponders and controls, the amino acid variations unique to responders had lower BLOSUM90 scores than variations in nonresponders and controls, and the amino acid variations correlated with response to therapy clustered around the RNA-binding channel of the polymerase. These data imply that that the responder enzymes were probably more functionally variable than the nonresponder enzymes. Enzymatic activity was measured for 10 recombinant polymerases; RNA synthesis activity varied by over sevenfold and polymerases from two of the responders used GTP much better than UTP, but technical limitations prevented direct measurement of ribavirin triphosphate use. Because response to combination therapy in these patients was primarily due to addition of ribavirin to the treatment regimen, these data imply that genetic variation in the polymerase may have affected the efficiency of ribavirin incorporation into the viral genome and hence may have modulated ribavirin's efficacy against HCV.

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.

Molecular biology and clinical implication of hepatitis C virus

Hepatitis C virus (HCV) was first described in 1989 as the putative viral agent of non-A non-B hepatitis. It is a member of the Flaviviridae family and has been recognized as the major causative agent of chronic liver disease, including chronic active hepatitis, cirrhosis and hepatocellular carcinoma. HCV is a positive RNA virus with a genome containing approximately 9500 nucleotides. It has an open reading frame that encodes a large polyprotein of about 3000 amino acids and is characterized by extensive genetic diversity. HCV has been classified into at least 6 major genotypes with many subtypes and circulates within an infected individual as a number of closely related but distinct variants known as quasispecies. This article reviews aspects of the molecular biology of HCV and their clinical implication.

Molecular biology and clinical implication of hepatitis C virus.

Hepatitis C virus (HCV) was first described in 1989 as the putative viral agent of non-A non-B hepatitis. It is a member of the Flaviviridae family and has been recognized as the major causative agent of chronic liver disease, including chronic active hepatitis, cirrhosis and hepatocellular carcinoma. HCV is a positive RNA virus with a genome containing approximately 9500 nucleotides. It has an open reading frame that encodes a large polyprotein of about 3000 amino acids and is characterized by extensive genetic diversity. HCV has been classified into at least 6 major genotypes with many subtypes and circulates within an infected individual as a number of closely related but distinct variants known as quasispecies. This article reviews aspects of the molecular biology of HCV and their clinical implication.

What is the optimal therapy for chronic hepatitis B?

Chronic infection with the hepatitis B virus infection remains a major problem worldwide despite some decrease in its incidence after improvement in public health policies and the utilization of hepatitis B vaccine. The clinical spectrum of the disease ranges from the asymptomatic carrier and individuals with mild liver injury to cirrhosis and hepatocellular carcinoma. During the past two decades there has been important progress in the field of viral hepatitis, and several drugs for the treatment of chronic hepatitis B have been developed and analyzed in clinical trials. Currently, two forms of therapy have been approved and are available for clinical practice: alpha interferon and lamivudine. Neither therapy is entirely satisfactory because of side effects and lack of universal responses. There is also controversy over which patients should be treated and what agent and regimen should be used. In this review we discuss the advantages and disadvantages of utilizing either drug, the response rates to therapy and what regimen should be used.

Differential amplification of hypervariable region 1 of hepatitis C virus by partially mismatched primers.

The quasispecies nature of hepatitis C virus (HCV) has been well documented over its whole genome and the most variable domain is located at the 5' end of the second envelope region, the so-called hypervariable region 1 (HVR1). HVR1 has therefore been extensively used as the target for characterizing HCV quasispecies profiles. In this study, we reported our finding that partially mismatched primers preferentially amplify different HVR1 sequences in a heterogeneous virus population. This finding suggests a possible mechanism of bias during the amplification of HVR1 sequences and may be responsible for some conflicting data regarding evolutionary or clinical implications of HCV quasispecies.