Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.

Sterol receptor element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) mRNA expression was assessed in liver as signaling mechanisms associated with steatosis in obese patients. Liver SREBP-1c and PPAR-alpha mRNA (RT-PCR), fatty acid synthase (FAS) and carnitine palmitoyltransferase-1a (CPT-1a) mRNA (real-time RT-PCR), and n-3 long-chain polyunsaturated fatty acid (LCPUFA)(GLC) contents, plasma adiponectin levels (RIA), and insulin resistance (IR) evolution (HOMA) were evaluated in 11 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 8 non-obese subjects who underwent laparoscopic cholecystectomy (controls). Liver SREBP-1c and FAS mRNA levels were 33% and 70% higher than control values (P<0.05), respectively, whereas those of PPAR-alpha and CPT-1a were 16% and 65% lower (P<0.05), respectively, with a significant 62% enhancement in the SREBP-1c/PPAR-alpha ratio. Liver n-3 LCPUFA levels were 53% lower in obese patients who also showed IR and hipoadiponectinemia over controls (P<0.05). IR negatively correlated with both the hepatic content of n-3 LCPUFA (r=-0.55; P<0.01) and the plasma levels of adiponectin (r=-0.62; P<0.005). Liver SREBP-1c/PPAR-alpha ratio and n-3 LCPUFA showed a negative correlation (r=-0.48; P<0.02) and positive associations with either HOMA (r=0.75; P<0.0001) or serum insulin levels (r=0.69; P<0.001). In conclusion, liver up-regulation of SREBP-1c and down-regulation of PPAR-alpha occur in obese patients, with enhancement in the SREBP-1c/PPAR-alpha ratio associated with n-3 LCPUFA depletion and IR, a condition that may favor lipogenesis over FA oxidation thereby leading to steatosis.

ObjectiveTo determine the variation in number, size, and symptoms in patients with polypoid lesions of the gallbladder. Summary Background DataA polypoid lesion is any elevated lesion of the gallbladder mucosa. Several studies have been reported in patients undergoing cholecystectomy, but little information exits regarding the natural history of these lesions in nonoperated patients. MethodsA total of 111 patients with ultrasound diagnosis of polypoid lesions smaller than 10 mm were followed up by clinical evaluation and ultrasonography. Twenty-seven patients underwent cholecystectomy. ResultsThere was no difference in terms of gender. Nearly 80% of the lesions were smaller than 5 mm; they were single in 74%. In nonoperated patients, 50% remained of similar size at the late follow-up, 26.5% increased in number and size, and 23.5% shrank or disappeared. Among the operated patients, 70% corresponded to cholesterol polyps. None of the patients developed symptoms of biliary disease or gallstones or adenocarcinoma. ConclusionsUltrasound is useful in the follow-up of patients with polypoid lesions of the gallbladder. Lesions smaller than 10 mm do not progress to malignancy or to development of stones, and none produced symptoms or complications of biliary disease.

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Twelve episodes of acute fatty liver of pregnancy (AFLP) were diagnosed in 11 patients during the past 18 years in a general hospital in Santiago, Chile, with a prevalence of 1 per 15900 deliveries. Acute fatty liver of pregnency started between the 31st and 38th weeks of pregnancy, with malaise, vomiting, jaundice, and lethargy as the main clinical manifestations. Polydipsia (in nine episodes) and skin pruritus (in seven episodes) were unusual clinical findings. In two patients, pruritus started two and four weeks before AFLP, suggesting that an intrahepatic cholestasis of pregnancy preceded AFLP in those patients. Considering the current prevalence of both diseases in Chile, their association should be considered fortuitous. In another patient, two consecutive pregnancies were affected by AFLP, raising to three the number of reported patients with recurrent AFLP. In 11 episodes, liver biopsies supported the diagnosis ofAFLP by showing smali and midsized vacuolar cytoplasmic transformation as the most prominent histopathological feature. Positive intracellular fat staining was found in the four samples analysed. Studies by electron microscopy showed megamitochondria with paracrystaline inclusions in four samples. All the mothers survived, but fetal mortality was 58*3%. Several extrahepatic complications delayed maternal recovery for up to four weeks after delivery. This study confirms an improvement in maternal prognosis in AFLP, discusses the possibility of an epidemiological association with intrahepatic cholestasis of pregnancy, and increases the number of patients reported with recurrent AFLP.

A prospective study was performed in 190 control subjects and in 236 patients with different degrees of endoscopic esophagitis in order to determine the prevalence of Helicobacter pylori infection at duodenal gastric and esophageal mucosa and its correlation with histological findings. All patients with pathologic gastroesophageal reflux had 24-h pH monitoring studies confirming the presence of acid reflux into the esophagus. Besides the endoscopic findings, biopsies were taken from the duodenal bulb, gastric antrum, gastric fundus and distal esophagus or at the specialized columnar epithelium in patients with Barrett's esophagus. Patients with pathological gastroesophageal reflux were divided into three groups: 55 with absence of endoscopic esophagitis (gastroesophageal reflux), 81 patients with erosive esophagitis and 100 patients with Barrett's esophagus. There was no H. pylori infection present at duodenal or esophageal mucosa or at the specialized columnar epithelium of the distal esophagus in any case. The prevalence of H. pylori infection at gastric antrum was similar in controls and in any group of patients with reflux disease (20-25% of H. pylori infection). No differences in age and sex distribution were seen. H. pylori infection at gastric fundus was very low (less than 5%). The presence of HP infections was correlated with the finding of chronic active superficial or athrophic gastritis while, in the absence of H. pylori infection, gastric mucosa was normal. In the presence of intestinal metaplasia, no H. pylori infection occurred. Based on these findings, it seems that there is no significant evidence for an important pathogenic role for H. pylori infection in the development of pathologic chronic gastroesophageal reflux, erosive esophagitis or Barrett's esophagus, and the presence of antral gastritis in patients with Barrett's esophagus is closely related to the presence of H. pylori infection, and probably not related to an increased duodenogastric reflux.

The diagnosis of Barrett's esophagus is based on the presence of intestinal metaplasia (IM) at the distal esophagus. The aim of this study was to determine the prevalence of IM in patients with symptoms of gastroesophageal reflux in whom endoscopically a segment of distal esophagus was covered by columnar epithelium (CE). In a prospective, descriptive and transversal study, 492 patients (33%) from 1480 patients with gastroesophageal reflux, in whom endoscopic evaluation demonstrated the presence of a short-segment CE measuring less than 3 cm or a long-segment CE measuring more than 3 cm, were evaluated. From each patient, several biopsy specimens were taken, which were stained with hematoxylin-eosin and Alcian blue pH 2.5. Out of 492 cases, 421 patients (86%) presented with a short-segment CE and 71 patients (14%) had a long-segment CE. Among these 71 cases, 38 had a 3-6 cm-length CE, 21 patients had a 6.1-10 cm-length CE and 12 patients had CE more than 10.1 cm in length. Endoscopic short-segment CE was six times more frequent than long-segment CE. The prevalence of IM was 35% among patients with short-segment CE and increased progressively according to the length of CE, being 100% in patients with > 10 cm in length. Therefore, true short-segment BE was three times more frequent during endoscopic studies than long-segment BE. Dysplasia in the metaplastic epithelium also increased parallel to the length of the CE. True BE (presence of IM at the columnar epithelium lining the distal esophagus), was present in 13.6% of all patients with symptoms of gastroesophageal reflux submitted to endoscopic evaluation. Short-segment BE is three times more frequent than long-segment BE, and endoscopic and bioptic evaluation is fundamental in all cases with gastroesophageal reflux who exhibit some segment of the distal esophagus lined by columnar epithelium, even if it is > or = 1 cm long.

Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in the progression from steatosis to nonalcoholic steatohepatitis (NASH). Our aim was to assess nuclear factor‐κB (NF‐κB) and activating protein‐1 (AP‐1) activation and Toll‐like receptor 4 (TLR4) expression as signaling mechanisms related to liver injury in obese NAFLD patients, and examined potential correlations among them, oxidative stress, and IR. Liver NF‐κB and AP‐1 (electromobility shift assay (EMSA)), TLR4 expression (western blot), ferric reducing ability of plasma (FRAP), and IR evolution (HOMA) were evaluated in 17 obese patients who underwent subtotal gastrectomy with gastro‐jejunal anastomosis in Roux‐en‐Y and 10 nonobese subjects who underwent laparoscopic cholecystectomy (controls). Liver NF‐κB and AP‐1 DNA binding were markedly increased in NASH patients (n = 9; P < 0.05) compared to controls, without significant changes in NAFLD patients with steatosis (n = 8), whereas TLR4 expression was comparable between groups. Hepatic NF‐κB activation was positively correlated with that of AP‐1 (r = 0.79; P < 0.0001); both liver NF‐κB and AP‐1 DNA binding were inversely associated with FRAP (r = −0.43 and r = −0.40, respectively; P < 0.05) and directly correlated with HOMA (r = 0.66 and r = 0.62, respectively, P < 0.001). Data presented show enhanced liver activation of the proinflammatory transcription factors NF‐κB and AP‐1 in obese patients with NASH, parameters that are significantly associated to oxidative stress and IR.