Non-invasive methods for iron overload evaluation in dysmetabolic patients.

INTRODUCTION: Although hyperferritinemia may reflect the inflammatory status of patients with non-alcoholic fatty liver disease (NAFLD), approximately 33% of hyperferritinemia cases reflect real hepatic iron overload. AIM: To evaluate a non-invasive method for assessing mild iron overload in patients with NAFLD using 3T magnetic resonance imaging (MRI) relaxometry, serum hepcidin, and the expression of ferritin subunits. METHODS: This cross-sectional study assessed patients with biopsy-proven NAFLD. MRI relaxometry was performed using a 3T scanner in all patients, and the results were compared with iron content determined by liver biopsy. Ferritin, hepcidin, and ferritin subunits were assessed and classified according to ferritin levels and to siderosis identified by liver biopsy. RESULTS: A total of 67 patients with NAFLD were included in the study. MRI revealed mild iron overload in all patients (sensitivity, 73.5%; specificity, 70%). For mild (grade 1) siderosis, the transverse relaxation rate (R2*) threshold was 58.9 s-1 and the mean value was 72.5 s-1 (SD, 33.9), while for grades 2/3 it was 88.2 s-1 (SD, 31.9) (p < 0.001). The hepcidin threshold for siderosis was > 30.2 ng/mL (sensitivity, 87%; specificity, 82%). Ferritin H and ferritin L subunits were expressed similarly in patients with NAFLD, regardless of siderosis. There were no significant differences in laboratory test results between the groups, including glucose parameters and liver function tests. CONCLUSIONS: MRI relaxometry and serum hepcidin accurately assessed mild iron overload in patients with dysmetabolic iron overload syndrome.

Sorafenib reduces steatosis-induced fibrogenesis in a human 3D co-culture model of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) affects around 25% of the worldwide population. Non-alcoholic steatohepatitis (NASH), the more progressive variant of NAFLD, is characterized by steatosis, cellular ballooning, lobular inflammation, and may culminate on hepatic stellate cell (HSC) activation, thus increasing the risk for fibrosis, cirrhosis, and HCC development. Conversely, the antifibrotic effects of sorafenib, an FDA-approved drug for HCC treatment, have been demonstrated in 2D cell cultures and animal models, but its mechanisms in a NAFLD-related microenvironment in vitro requires further investigation. Thus, a human 3D co-culture model of fatty hepatocytes and HSC was established by culturing hepatoma C3A cells, pre-treated with 1.32 mM oleic acid, with HSC LX-2 cells. The fatty C3A/LX-2 spheroids showed morphological and molecular hallmarks of altered lipid metabolism and steatosis-induced fibrogenesis, similarly to the human disease. Sorafenib (15 µM) for 72 hours reduced fatty spheroid viability, and upregulated the expression of lipid oxidation- and hydrolysis-related genes, CPT1 and LIPC, respectively. Sorafenib also inhibited steatosis-induced fibrogenesis by downregulating COL1A1, TGFB1, PDGF, and TIMP1 and by decreasing protein levels of IL-6, TGF-ß1, and TNF-α in fatty spheroids. The demonstration of the antifibrotic properties of sorafenib on steatosis-induced fibrogenesis in a 3D in vitro model of NAFLD supports its clinical use as a therapeutic agent for the treatment of NAFLD/NASH patients.

Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20-30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

Hepatitis C virus eradication improves immediate and delayed episodic memory in patients treated with interferon and ribavirin.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders. METHOD: A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment. RESULTS: Thirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR displayed significant improvement in immediate (p = 0.045) and delayed verbal episodic memory (p = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment (p = 0.719). CONCLUSIONS: Eradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.

Connexin32 deficiency is associated with liver injury, inflammation and oxidative stress in experimental non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis is a highly prevalent liver pathology featured by hepatocellular fat deposition and inflammation. Connexin32, which is the major building block of hepatocellular gap junctions, has a protective role in hepatocarcinogenesis and is downregulated in chronic liver diseases. However, the role of connexin32 in non-alcoholic steatohepatitis remains unclear. Connexin32-/- mice and their wild-type littermates were fed a choline-deficient high-fat diet. The manifestation of non-alcoholic steatohepatitis was evaluated based on a battery of clinically relevant read-outs, including histopathological examination, diverse indicators of inflammation and liver damage, in-depth lipid analysis, assessment of oxidative stress, insulin and glucose tolerance, liver regeneration and lipid-related biomarkers. Overall, more pronounced liver damage, inflammation and oxidative stress were observed in connexin32-/- mice compared to wild-type animals. No differences were found in insulin and glucose tolerance measurements and liver regeneration. However, two lipid-related genes, srebf1 and fabp3, were upregulated in Cx32-/- mice in comparison with wild-type animals. These findings suggest that connexin32-based signalling is not directly involved in steatosis as such, but rather in the sequelae of this process, which underlie progression of non-alcoholic steatohepatitis.

Experimental models of liver fibrosis.

Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD. METHODS: Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson's, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies. RESULTS: The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p < 0.001) for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST, ALT, γGT, AP and triglycerides levels (p < 0.001). A negative correlation was observed between levels of vitamin B12 and Hcy concentration (p = 0.005). CONCLUSION: Our results indicate that plasma Hcy was higher in NAFLD than controls. The MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT = 4.44%) (p > 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.

Impact of Endoscopic Sleeve Gastroplasty in Non-alcoholic Fatty Liver Disease: a Systematic Review and Meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Endoscopic sleeve gastroplasty (ESG) has proven to be feasible, safe, and effective in the management of obesity. We performed the first systematic review and meta-analysis evaluating NAFLD and other metabolic parameters 12 months post-ESG. Four observational studies with a total of 175 patients were included. The results showed a significant (p < 0.05) reduction of 4.85 in hepatic steatosis index (95% CI - 6.02, - 3.67), 0.5 in NAFLD fibrosis score (95% CI - 0.80, - 0.19), 6.32 U/l in ALT (95% CI - 9.52, - 3.11), 17.28% in TWL (95% CI - 18.24, - 16.31), 6.31 kg/m2 in BMI (95% CI - 8.11, - 4.52), 47.97% in EWL (95% CI - 49.10, - 46.84), and 0.51% in HbA1c (95% CI - 0.90, - 0.12). ESG improves liver parameters, provides weight loss, and reduces HbA1c levels in patients suffering from NAFLD.

Association of UCP3 Polymorphisms with Nonalcoholic Steatohepatitis and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease Brazilian Patients.

Background: We investigated the possible association of uncoupling protein 3 gene (UCP3) single nucleotide polymorphisms (SNPs) with nonalcoholic steatohepatitis (NASH) and metabolic syndrome (MetS) in nonalcoholic fatty liver disease (NAFLD) Brazilian patients. Methods:UCP3 SNPs rs1726745, rs3781907, and rs11235972 were genotyped in 158 biopsy-proven NAFLD Brazilian patients. Statistics was performed with JMP, R, and SHEsis softwares. Results: The TT genotype of rs1726745 was associated with less occurrence of MetS (P = 0.006) and with lower body mass index (BMI) in the entire NAFLD sample (P = 0.01) and in the NASH group (P = 0.02). The rs1726745-T was associated with lower values of AST (P = 0.001), ALT (P = 0.0002), triglycerides (P = 0.01), and total cholesterol (P = 0.02) in the entire NAFLD sample. Between groups, there were lower values of aminotransferases strictly in individuals with NASH (AST, P = 0.002; ALT, P = 0.0007) and with MetS (AST, P = 0.002; ALT, P = 0.001). The rs3781907-G was associated with lower GGT elevation values in the entire NAFLD sample (P = 0.002), in the NASH group (P = 0.004), and with MetS group (P = 0.003) and with protection for advanced fibrosis (P = 0.01). The rs11235972-A was associated with lower GGT values in the entire NAFLD sample (P = 0.006) and in the NASH group (P = 0.01) and with MetS group (P = 0.005), with fibrosis absence (P = 0.01) and protection for advanced fibrosis (P = 0.01). The TAA haplotype was protective for NASH (P = 0.002), and TGG haplotype was protective for MetS (P = 0.01). Conclusion:UCP3 gene variants were associated with protection against NASH and MetS, in addition to lower values of liver enzymes, lipid profile, BMI and, lesser fibrosis severity in the studied population.

Effects of intragastric balloon placement in metabolic dysfunction-associated fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease corresponds to a clinical entity that affects liver function triggered by the accumulation of fat in the liver and is linked with metabolic dysregulation. AIM: To evaluate the effects of the intragastric balloon (IGB) in patients with metabolic dysfunction-associated fatty liver disease through the assessment of liver enzymes, imaging and several metabolic markers. METHODS: A comprehensive search was done of multiple electronic databases (MEDLINE, EMBASE, LILACS, Cochrane and Google Scholar) and grey literature from their inception until February 2021. Inclusion criteria involved patients with a body mass index > 25 kg/m2 with evidence or previous diagnosis of hepatic steatosis. Outcomes analyzed before and after 6 mo of IGB removal were alanine aminotransferase (IU/L), gamma-glutamyltransferase (IU/L), glycated hemoglobin (%), triglycerides (mg/dL), systolic blood pressure (mmHg), homeostatic model assessment, abdominal circumference (cm), body mass index (kg/m2) and liver volume (cm3). RESULTS: Ten retrospective cohort studies evaluating a total of 508 patients were included. After 6 mo of IGB placement, this significantly reduced alanine aminotransferase [mean difference (MD): 10.2, 95% confidence interval (CI): 8.12-12.3], gamma-glutamyltransferase (MD: 9.41, 95%CI: 6.94-11.88), glycated hemoglobin (MD: 0.17%, 95%CI: 0.03-0.31), triglycerides (MD: 38.58, 95%CI: 26.65-50.51), systolic pressure (MD: 7.27, 95%CI: 4.79-9.76), homeostatic model assessment (MD: 2.23%, 95%CI: 1.41-3.04), abdominal circumference (MD: 12.12, 95%CI: 9.82-14.41) and body mass index (MD: 5.07, 95%CI: 4.21-5.94). CONCLUSION: IGB placement showed significant efficacy in improving alanine aminotransferase and gamma-glutamyltransferase levels in patients with metabolic dysfunction-associated fatty liver disease as well as improving metabolic markers related to disease progression.

Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Although the metabolic risk factors for non-alcoholic fatty liver disease (NAFLD) progression have been recognized, the role of genetic susceptibility remains a field to be explored. The aim of this study was to examine the frequency of two polymorphisms in Brazilian patients with biopsy-proven simple steatosis or non-alcoholic steatohepatitis (NASH): -493 G/T in the MTP gene, which codes the protein responsible for transferring triglycerides to nascent apolipoprotein B, and -129 C/T in the GCLC gene, which codes the catalytic subunit of glutamate-cystein ligase in the formation of glutathione. METHODS: One hundred and thirty-one biopsy-proven NAFLD patients (n = 45, simple steatosis; n = 86, NASH) and 141 unrelated healthy volunteers were evaluated. Genomic DNA was extracted from peripheral blood cells, and the -129 C/T polymorphism of the GCLC gene was determined by restriction fragment length polymorphism (RFLP). The -493 G/T polymorphism of the MTP gene was determined by direct sequencing of the polymerase chain reaction products. RESULTS: The presence of at least one T allele in the -129 C/T polymorphism of the GCLC gene was independently associated with NASH (odds ratio 12.14, 95% confidence interval 2.01-73.35; P = 0.007), whereas, the presence of at least one G allele in the -493 G/T polymorphism of the MTP gene differed slightly between biopsy-proven NASH and simple steatosis. CONCLUSION: This difference clearly warrants further investigation in larger samples. These two polymorphisms could represent an additional factor for consideration in evaluating the risk of NAFLD progression. Further studies involving a larger population are necessary to confirm this notion.

Ultrasound elastography in patients with fatty liver disease.

Hepatic steatosis, or fatty liver disease, occurs due to the accumulation of lipids in hepatocytes. When it becomes chronic, lobular inflammation develops and the disease can evolve to hepatic fibrosis, liver cirrhosis, or hepatocellular carcinoma. Early diagnosis is desirable because patients diagnosed in the early stage of the disease respond better to treatment. In the early stages of fatty liver disease, the physical examination is often unremarkable. Fatty liver disease and hepatic fibrosis can be diagnosed and monitored through laboratory tests, imaging, and biopsy. Among the imaging methods, ultrasound stands out as an effective means of diagnosing and following patients with liver disease. Ultrasound used in conjunction with elastography (ultrasound elastography) has recently shown great utility in the follow-up of such patients. Ultrasound elastography studies the degree of deformation (stiffness) of an organ or lesion, so that when there is hardening, fibrosis, or cirrhosis of the liver, those alterations are well demonstrated. In this review article, we discuss the application of the different types of ultrasound elastography for liver studies: transient elastography, point shear wave elastography, and two-dimensional shear wave elastography. Although magnetic resonance elastography may also be used in the analysis of liver fibrosis, it will not be addressed in this article.

Effects of Aerobic Exercise Protocol on Genes Related to Insulin Resistance and Inflammation in the Pancreas of ob/ob Mice with NAFLD.

PURPOSE: To evaluate the effect of 8 weeks of aerobic training on insulin resistance and inflammatory response in obese mice (ob/ob) with NAFLD. MATERIALS AND METHODS: Male ob/ob mice were randomly divided into sedentary (n=7) and trained (n=7) groups. Aerobic training consisted of 5 weekly sessions, 60 min per session at 60% of the maximum speed of the running test. Hepatic and pancreatic samples were collected to evaluate histological features and gene expression associated with insulin resistance and inflammatory response after 8-week experiment protocol. RNA was performed by TRIzol®. PCR experiments were performed using the Rotor-Gene RG-3000. Parametric data were assessed by t-test, one-way ANOVA and Bonferroni test for multiple comparisons. Non-parametric data were assessed by the Mann-Whitney tests with Dunn's post-test of multiple comparisons. Histological analysis was assessed by chi-square test with Fisher's exact test. Significant variables were considered when p<0.05. All the analyses were performed by GraphPad Prism V6.0 software (GraphPad Software Inc.). RESULTS: Reductions in bodyweight (p = 0.008), weight evolution (p = 0.03), food intake (p <0.0001) and fat content were observed in trained group. Moreover, the trained group showed better results in peak velocity (p=0.03) physical effort tolerance (p=0.006) and distance (p=0.01). Gene expression showed differences in IL-10 (p=0.03) and GLUT-2 (p=0.03) in hepatic analysis, between groups. Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03) and IL-10 (p=0.008) analysis. Also, the trained group showed lower values for interlobular fat and inflammatory infiltrate in histological analysis when compared to sedentary animals. CONCLUSION: An 8-week physical training protocol was able to attenuate bodyweight gain, food intake and generate positive effects on gene expression related to insulin resistance and inflammation in both liver and pancreas of ob/ob mice.

IMPACT OF CURRENT DIET AT THE RISK OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD).

The nonalcoholic fatty liver disease (NAFLD) affects approximately 20%-30% of general population and is even more prevalent among obese individuals. The risk factors mainly associated with NAFLD are diseases related to the metabolic syndrome, genetics and environment. In this review, we provide a literature compilation evaluating the evidence behind dietary components, including calories intake, fat, protein, fibers and carbohydrate, especially fructose which could be a trigger to development and progression of the NAFLD. In fact, it has been demonstrated that diet is an important factor for the development of NAFLD and its association is complex and extends beyond total energy intake.

Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis.

AIM: There is no proven medical therapy for the treatment of non-alcoholic steatohepatitis (NASH). Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. The aim of our study was to evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) in improving the aminotransferases and histological parameters (steatosis, inflammation, hepatocellular ballooning, and fibrosis) after 12 months of treatment. METHODS: Twenty consecutive patients (mean age 53 +/- 2 years [36-68] and body mass index [BMI] 29 [25-35]) with biopsy-proven NASH were enrolled in the study. NAC (1.2 g/day) and MTF (850-1000 mg/day) were given orally for 12 months. All patients underwent evaluation of serum aminotransferases, fasting lipid profile and serum glucose, anthropometric parameters, and nutritional status at 0 and 12 months. A low calorie diet was prescribed for all patients. RESULTS: Serum alanine aminotransferase, high-density lipoprotein, insulin, and glucose concentrations and thehomeostasis model assessment-insulin resistance (HOMA-IR) index were reduced significantly at the end of study (P < 0.05). The BMI declined, but without statistical significance. Aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, cholesterol, and triglycerides levels were not altered with the treatment. Liver steatosis and fibrosis decreased (P < 0.05), but no improvement was noted in lobular inflammation or hepatocellular ballooning. The NASH activity score was significantly improved after treatment. CONCLUSION: Based on the biochemical and histological evidence in this pilot study, NAC in combination with MTF appears to ameliorate several aspects of NASH, including fibrosis. Further studies of this form of combination therapy are warranted to assess its potential efficacy.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Follow-up of Roux-en-Y gastric bypass patients at 5 or more years postoperatively.

BACKGROUND: Short-term results (24 to 36 months) after Roux-en-Y gastric bypass (RYGBP) have been extensively described. Little is reported on the patients operated > or = 5 years ago. We analyzed the results of weight loss, resolution of co-morbidities and nutritional complications of patients submitted to the silicone ring RYGBP, at least 5 years before. METHODS: 75 morbidly obese patients who underwent silicone ring RYGBP between Oct 1995 and Dec 1999, 18 men and 57 women, were studied. Demographic data, nutritional status and the presence of co-morbidities (type 2 diabetes, hypertension, sleep apnea, dyslipidemia) were accessed. Pre- and postoperative BMI were registered, along with excess weight loss (EWL). Nutritional deficiencies were accessed by laboratory assays. RESULTS: Mean follow-up was 87 months. Initial BMI was 56.7 +/- 10 kg/m2. After 2 years, BMI had dropped to 29.3 +/- 6.8, and by the last interview BMI was 35.5 +/- 10. %EWL after 2 years was 80.2 +/- 17.3%, and at the end was 71.8 +/- 21.6%. After 2 years, only 1 of the 75 patients (1.33%) had not achieved an EWL of at least 50%. At the end, 23 patients (30.6%) could not maintain this EWL. Resolution of diabetes was 76.5%, arterial hypertension 37.3% and sleep apnea 93.5%. Iron, vitamin B12 and vitamin D were the most common nutritional deficiencies. CONCLUSIONS: Long-term follow-up (5 to 9 years) after the RYGBP was associated with satisfactory mantainance of EWL, and resolution or improvement of the main co-morbidities was observed in the majority of the patients.

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C.

OBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

Use of noninvasive markers to predict advanced fibrosis/cirrhosis in severe obesity.

BACKGROUND: Nonalcoholic steatohepatitis is observed in 25%-55% of patients with severe obesity and in 2%-12% with bridging fibrosis or cirrhosis. There is currently no noninvasive test for the diagnosis of severe liver fibrosis before bariatric surgery. OBJECTIVES: To determine the best noninvasive test for predicting advanced liver disease in patients with severe obesity. SETTING: University tertiary care hospital, Brazil. METHODS: A cross-sectional retrospective study was conducted with 699 patients with severe obesity undergoing bariatric surgery: 568 without a biopsy (nonbiopsy cohort) and 131 patients who had undergone an intraoperative liver biopsy. The tissues were subjected to histologic diagnosis (Brunt criteria) and classified as advanced fibrosis (stages 3 and 4) or no significant fibrosis (absence of nonalcoholic steatohepatitis and stages 1 or 2). The following predictive indices of cirrhosis were calculated in all patients: aspartate aminotransferase/alanine aminotransferase ratio (AAR), age-platelet (AP) index, aminotransferase-to-platelet ratio index (APRI), cirrhosis discriminant score (CDS), and hepatitis C antiviral long-term treatment against cirrhosis (HALT-C). The cutoff values, sensitivity, specificity, and areas under the receiver operating characteristic curves (AUROCs) were calculated for patients with biopsies. RESULTS: The AUROC of the AAR, AP, APRI, CDS, and HALT-C model for predicting advanced fibrosis or cirrhosis were, respectively, .522, .88, .99, .905, and .921. The calculated cutoff values, sensitivity, and specificity, respectively, were as follows: AAR: .94, .7, .45; AP 5, .7, .93; APRI .44, 1.0, .97; CDS 6, .7, .97; and HALT-C: .76, 1.0, .77. CONCLUSION: APRI index was the best predictor of advanced liver disease in patients with severe obesity.

Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: & aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH. METHODS: Patients received three capsules daily, each containing 0.315 g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n = 27) or mineral oil (placebo group, n = 23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment. RESULTS: At baseline, NAS was comparable between the groups (p = 0.98). After intervention with omega-3 PUFAs, plasma ALA and EPA levels increased (p ≤ 0.05). However in the placebo group, we also observed increased EPA and DHA (p ≤ 0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p = 0.02) and with increased EPA (p = 0.04) and DHA (p = 0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p = 0.01). CONCLUSIONS: In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology. (ID 01992809).