Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test.

BACKGROUND: The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. METHODS: Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. RESULTS: 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively). CONCLUSIONS: The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.

Immunochemical fecal occult blood test for detection of advanced colonic adenomas and colorectal cancer: comparison with colonoscopy results.

Background. Fecal immunochemical tests (FITs) have been used for colorectal cancer (CRC) screening in several countries. There is lack of information concerning diagnostic performances of this method in Brazil. Methods. Patients scheduled for elective colonoscopy provided one stool sample one week before colonoscopy. The accuracy of a qualitative FIT for detection of CRC and advanced adenomas was determined. Results. Overall 302 patients completed the study. Among them, 53.5% were high risk patients referred for screening or surveillance. Nine (3%) CRCs and 11 (3.6%) advanced adenomas were detected by colonoscopy. Sensitivity and specificity for CRC were, respectively, 88.9% and 87.6%. For advanced adenomas, sensitivity was 63.6% and specificity 87.6%. Conclusion. Our results showed good sensitivity and specificity of the FIT for detecting advanced neoplasias. This method may be a valuable tool for future screening programs in Brazil.

Delayed small intestinal transit in patients with long-standing type 1 diabetes mellitus: investigation of the relationships with clinical features, gastric emptying, psychological distress, and nutritional parameters.

BACKGROUND: Studies on small intestinal transit in type 1 diabetes mellitus have reported contradictory results. This study assessed the orocecal transit time (OCTT) in a group of patients with type 1 diabetes mellitus and its relationships with gastrointestinal symptoms, glycemic control, chronic complications of diabetes, anthropometric indices, gastric emptying, small intestinal bacterial overgrowth (SIBO), and psychological distress. SUBJECTS AND METHODS: Twenty-eight patients with long-standing (>10 years) type 1 diabetes mellitus (22 women, six men; mean age, 39 ± 9 years) participated in the study. The lactulose hydrogen breath test was used to determine OCTT and the occurrence of SIBO. The presence of anxiety and depression was assessed by the Hospital Anxiety and Depression scale. Gastric emptying was measured by scintigraphy. Anthropometric indices included body mass index, percentage body fat, midarm circumference, and arm muscle area. RESULTS: There was a statistically significant increase in OCTT values in diabetes patients (79 ± 41 min) in comparison with controls (54 ± 17 min) (P=0.01). Individual analysis showed that OCTT was above the upper limit (mean+2 SD) in 30.8% of patients. All anthropometric parameters were significantly decreased (P<0.05) in patients with prolonged OCTT in comparison with those with normal OCTT. In contrast, there was no statistically significant association between prolonged OCTT and gastrointestinal symptoms, peripheral neuropathy, diabetic retinopathy, glycated hemoglobin, delayed gastric emptying, SIBO, anxiety, or depression. CONCLUSIONS: Small bowel transit may be delayed in about one-third of patients with long-standing type 1 diabetes mellitus. This abnormality seems to have a negative effect on nutritional status in these patients.

Is it just lactose intolerance?

Acquired delayed-onset hypolactasia is a common autosomal recessive condition. Cow's milk allergies, conversely, are less common conditions that may manifest with equivalent symptoms and are able to simulate and/or aggravate lactose intolerance. This study was designed to evaluate the contribution of IgE-mediated cow's milk sensitization to the symptomatology of adult patients with lactose-free diet refractory lactose intolerance. Forty-six adult patients with lactose intolerance and persistent symptoms despite a lactose-free diet underwent skin-prick test to investigate cow's milk, goat's milk, and soy protein-specific-IgE. SDS-PAGE immunoblotting was used to investigate the presence of cow's milk protein-specific IgE. The percentage of patients who had skin reactions to whole cow's milk, alpha-lactalbumin, beta-lactoglobulin, caseins, goat's milk, and soy was 69.5, 36.9, 56.5, 56.5%, 54.3, and 50%, respectively. The percentage of patients with immunoblot-detected IgE specific for alpha-lactalbumin, beta-lactoglobulin, caseins, and bovine serum albumin was 21.7, 63, 67.3, and 2.1%, respectively. IgE-mediated sensitization to cow's milk is a frequent comorbidity in subjects with lactose-free diet refractory lactose intolerance and is worth consideration in patients with this condition.

Beneficial effects of long-term consumption of a probiotic combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after suspension of therapy in lactose-intolerant patients.

BACKGROUND: The efficacy of some probiotic strains for the management of lactose intolerance remains to be established. AIM: To evaluate the effects of a 4-week consumption of a probiotic product containing Lactobacillus casei Shirota and Bifidobacterium breve Yakult (10(7)-10(9) CFU of each strain) on symptoms and breath hydrogen exhalation after a lactose load in lactose-intolerant patients and whether the beneficial results persisted after probiotic discontinuation. METHODS: Twenty-seven patients with lactose maldigestion and intolerance participated in this study, which comprised 4 hydrogen breath tests: baseline condition (20 g lactose), after lactase ingestion (9000 FCC units), at the end of 4-week probiotic supplementation, and a follow-up test performed 3 months after probiotic discontinuation. For each test, the area under the breath hydrogen concentration vs time curve (AUC(180 min)) was calculated, and symptom scores were recorded. RESULTS: The probiotic combination significantly reduced symptom scores (P < .01) and breath hydrogen AUC (P = .04) compared with the baseline condition. The comparison with the lactase test showed that symptom scores were similar (P > .05), despite the significantly higher (P = .01) AUC values after probiotic use. In the follow-up test, symptom scores and breath hydrogen AUC values remained similar to those found at the end of probiotic intervention. CONCLUSION: Four-week consumption of a probiotic combination of L casei Shirota and B breve Yakult seems to improve symptoms and decrease hydrogen production intake in lactose-intolerant patients. These effects may persist for at least 3 months after suspension of probiotic consumption.

Human herpesvirus 6 in donor biopsies associated with the incidence of clinical cytomegalovirus disease and hepatitis C virus recurrence.

BACKGROUND: Reactivation of cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6), as well as the recurrence of hepatitis C virus (HCV), occurs in the post liver transplantation period. However, their correlations remain questionable. The objectives of this study were to analyze the presence of CMV DNA and HHV-6 DNA in pre-transplant and post-transplant liver graft biopsies and to determine any correlations with CMV disease and HCV recurrence. METHODS: Forty-one liver transplant recipients were followed up in the post-transplant period. The presence of CMV DNA and HHV-6 DNA was detected by nested PCR. RESULTS: Four patients (4/41, 9.8%) were positive for CMV DNA in pre-transplant biopsies and three of them remained positive after transplantation; 11 patients became positive in the post-transplant biopsies (p=0.06). Fifteen (15/41, 36.6%) patients were positive for HHV-6 DNA in pre-transplant biopsies and 11 of these remained positive after transplantation. Another 11 patients became positive after the surgery (p=0.05). CMV disease occurred in 17 recipients; 10 of these 17 (58.8%) patients were positive for HHV-6 DNA in pre-transplant biopsies and they continued positive after transplantation (p=0.0128). Twenty-eight patients were transplanted due to hepatitis C; 12 of these patients had recurrence of the virus, and HHV-6 was positive in nine of the 12 (75%) patients (p=0.049). CONCLUSIONS: Recipients with HHV-6 DNA in pre-transplant graft biopsies remained positive post transplantation, showing a possible risk for post-transplant allograft loss because there was an association between HHV-6 and recurrent HCV and CMV disease.

Investigation of autonomic function and orocecal transit time in patients with nonalcoholic cirrhosis and the potential influence of these factors on disease outcome.

BACKGROUND: The presence of autonomic dysfunction in nonalcoholic cirrhosis and its influence on intestinal transit and disease outcome still need clarification. GOALS: To investigate the function of the autonomic nervous system in patients with nonalcoholic cirrhosis and the possible associations among autonomic dysfunction, severity of liver disease, disturbed intestinal transit, and the development of complications during follow-up. STUDY: Measurements of heart rate variability obtained by analysis of 24-hour ambulatory electrocardiographic recordings to assess autonomic function and lactulose breath hydrogen test to determine orocecal transit time were performed in 32 patients with nonalcoholic cirrhosis divided into Child A and B. RESULTS: Child B patients showed significantly lower values (P<0.05) of those parameters reflecting parasympathetic (high frequency, log-transformed high frequency, pNN50) and sympathetic function (low frequency, log-transformed low frequency) in comparison with controls and Child A patients. Orocecal transit time values were significantly (P=0.02) higher in Child B patients than in controls, but no relationship was found between delayed orocecal transit time and autonomic dysfunction. During follow-up, 42% of Child B patients developed encephalopathy. This complication was significantly associated with autonomic dysfunction. In addition, in the 4 patients who died the parameters reflecting parasympathetic function were significantly reduced in comparison with those of survivors. CONCLUSIONS: Autonomic dysfunction and delayed intestinal transit are related to the severity of disease in nonalcoholic cirrhosis. Autonomic dysfunction seems to predispose cirrhotic patients to the development of encephalopathy and may be associated with a poor prognosis of these patients.