Acute pancreatitis in Turkey: Results of a nationwide multicenter study.

BACKGROUND: Acute pancreatitis (AP) is the most common gastrointestinal disease requiring hospitalization, with significant mortality and morbidity. We aimed to evaluate the clinical characteristics of AP and physicians' compliance with international guidelines during its management. METHODS: All patients with AP who were hospitalized at 17 tertiary centers in Turkey between April and October 2022 were evaluated in a prospective cohort study. Patients with insufficient data, COVID-19 and those aged below 18 years were excluded. The definitions were based on the 2012 revised Atlanta criteria. RESULTS: The study included 2144 patients (median age:58, 52 % female). The most common etiologies were biliary (n = 1438, 67.1 %), idiopathic (n = 259, 12 %), hypertriglyceridemia (n = 128, 6 %) and alcohol (n = 90, 4.2 %). Disease severity was mild in 1567 (73.1 %), moderate in 521 (24.3 %), and severe in 58 (2.6 %) patients. Morphology was necrotizing in 4.7 % of the patients. The overall mortality rate was 1.6 %. PASS and BISAP had the highest accuracy in predicting severe pancreatitis on admission (AUC:0.85 and 0.81, respectively). CT was performed in 61 % of the patients, with the majority (90 %) being within 72 h after admission. Prophylactic NSAIDs were not administered in 44 % of the patients with post-ERCP pancreatitis (n = 86). Antibiotics were administered to 53.7 % of the patients, and 38 % of those received them prophylactically. CONCLUSIONS: This prospective study provides an extensive report on clinical characteristics, management and outcomes of AP in real-world practice. Mortality remains high in severe cases and physicians' adherence to guidelines during management of the disease needs improvement in some aspects.

Comparison of the recommendation of international autoimmune hepatitis pathology group 2022 and the simplified criteria for autoimmune hepatitis 2008: A preliminary study.

Background and Aim: The histological diagnosis of autoimmune hepatitis (AIH) is challenging. A new consensus recommendation was provided by the International AIH Pathology Group to address the problems in the histological diagnosis. The purpose of this study is to compare the 2008 'simplified' criteria for AIH with the 'consensus recommendation' of 2022 in terms of diagnostic sensitivity. Materials and Methods: A retrospective analysis was conducted on pathological specimens of patients diagnosed with Autoimmune Hepatitis (AIH) between 2010 and 2022. Out of 188 patients enlisted, 88 were selected based on exclusion criteria. The specimens were examined by two experienced hepatopathologists and a resident pathologist. All specimens were analyzed using both the "simplified" criteria and the new consensus recommendations. Results: Out of a total of 78 patients, the 2022 consensus recommendations raised the diagnostic category of 16 patients (20.5%) to a higher level. Six patients who were previously diagnosed as "atypical" were now considered "possible AIH", while 10 patients with a "compatible" diagnosis were elevated to "likely AIH" category. No patients were found to fall into a lower diagnostic category according to the new recommendations. A significant difference in diagnostic sensitivity was observed between the 2008 criteria and the 2022 consensus report (p<0.001). Conclusion: The 2022 consensus recommendation may be more sensitive in the diagnosis of AIH in comparison to the 2008 'simplified' histological criteria. More studies are needed both for the validation of the sensitivity of the new consensus recommendation and for the determination of the specificity.

Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Risk of Malignancy Using the Diagnostic Categories Proposed by the World Health Organization International System for Reporting Pancreaticobiliary Cytopathology.

BACKGROUND: The World Health Organization (WHO) proposed an updated reporting system for pancreaticobiliary cytology, which moves low-grade malignancies to "positive for malignancy" group and serous cystadenoma to "negative for malignancy" group. The WHO system also created two new categories, namely, pancreatic neoplasia-low grade (PaN-Low) and pancreatic neoplasia-high grade (PaN-High), which includes neoplastic mucinous cysts and stratifies them according to their cytologic atypia. The risk of malignancy (ROM) of the new categories of the WHO system needs to be defined. METHODS: Cytologic slides of all patients, who underwent endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy at our institution from January 2010 to December 2021 and had a histopathological or clinical follow-up of at least 6 months, were reviewed and reclassified under the Papanicolaou Society of Cytopathology (PSC) and WHO reporting systems. The absolute ROM was calculated for each category of both reporting systems. RESULTS: A total of 420 EUS-FNA samples from 410 patients were reviewed and reclassified. The absolute ROM for the proposed WHO system was 35% for "nondiagnostic," 1.0% for "negative for malignancy," 69.0% for "atypical," 11% for "PaN-Low," 100% for "PaN-High," 91% for "suspicious for malignancy," and 100% for "malignant." Comparatively, the absolute ROM under the PSC reporting system was 34% for "nondiagnostic," 1.0% for negative (for malignancy), 50.0% for "atypical," 0.0% for "neoplastic: benign," 16% for "neoplastic: other," 88% for "suspicious for malignancy," and 100% for "positive or malignant." CONCLUSION: The proposed WHO international reporting system has advantages regarding risk stratification improvement and case management.

Diagnostic performance of 2D shear wave elastography in predicting liver fibrosis in patients with chronic hepatitis B and C: a histopathological correlation study.

PURPOSE: In this study, we investigated the diagnostic efficacy of 2D-Shear Wave Elastography (2D-SWE) in detecting stages of liver fibrosis and determining the disease-specific cut-off values in patients with chronic hepatitis B and C infection, using histopathological analysis as the reference method. METHOD: Our study included 103 consecutive adult patients with chronic hepatitis B and C infection (CHB and CHC) who had liver biopsy within three months of elastography examination. A real-time 2D-SWE was performed using the LOGIQ E9 system (GE Medical Systems, Wisconsin, USA). The correlation between the liver stiffness measurements and the METAVIR scores was evaluated. The diagnostic performance of 2D-SWE was assessed, and cut-off values were set. RESULTS: We found a statistically significant positive correlation between elastography values and the degree of liver fibrosis (Spearman's correlation coefficient = 0.76 and 0.83 for CHB and CHC; respectively) (p = 0.0001). The stiffness cut-off values were F ≥ 1: 5.92 kPa, F ≥ 2: 7.69 kPa, F ≥ 3: 8.97 kPa, F ≥ 4: 12.15 kPa in CHB; and F ≥ 1: 6.09 kPa, F ≥ 2: 7.81 kPa, F ≥ 3: 9.0 kPa, F ≥ 4: 12.47 kPa in CHC patients. CONCLUSION: 2D-SWE is reliable and accurate for the diagnosis of liver fibrosis. In selected patients, 2D-SWE may be useful in reducing the need for liver biopsy when staging fibrosis. Further studies in larger prospective series are needed to confirm these results and determine the most appropriate cut-off values for each stage of liver fibrosis.

EUS versus endoscopic retrograde cholangiography for patients with intermediate probability of bile duct stones: a prospective randomized trial.

BACKGROUND: Factors affecting diagnostic accuracy and comparison of patients in the follow-up period for negative outcomes are not thoroughly investigated in a randomized trial. OBJECTIVE: Our purpose was to compare diagnostic accuracy, complications, and number of interventions. DESIGN: Prospective, unicentric, single-blind, randomized study. SETTING: Single tertiary referral university hospital. PATIENTS: One hundred twenty patients with intermediate risk for common bile duct (CBD) stones were randomized to either an EUS-first, endoscopic retrograde cholangiography (ERC)-second (n = 60) versus an ERC-only (n = 60) procedure. INTERVENTIONS: EUS, ERC, sphincterotomy, and balloon sweeping of CBD when needed. MAIN OUTCOME MEASUREMENTS: Sensitivity of EUS versus ERC, factors affecting diagnostic capability, complications, total number of endoscopic procedures. RESULTS: The sensitivity and specificity of ERC were 75% (95% CI, 42%-93%) and 100% (95% CI, 95%-100%), respectively. The sensitivity and specificity of EUS were 91% (95% CI, 59%-99%) and 100% (95% CI, 95%-100%), respectively. EUS is more sensitive than ERC in detecting stones smaller than 4 mm (90% vs 23%, P < .01). Although not significant, there was a trend for an increased number of endoscopic procedures in the ERC group compared with the EUS group (98 vs 83). The post-ERC pancreatitis rate was 6 in 120 (5%) in all study patients, and the post-ERC pancreatitis rate in patients with an undilated CBD was 5 of 53 (9.43%). The independent factors for post-ERC pancreatitis are undilated CBD (risk ratio [RR] 6.320; 95% CI, 1.703-11.524, P = .009), allocation into the ERC group (RR 2.107; 95% CI, 1.330-3.339, P = .02), female sex (RR 1.803; 95% CI, 1.155-2.813, P = .03), and age less than 40 years (RR 1.888; 95% CI, 1.245-2.863, P = .01). Kaplan-Meier analysis revealed higher rate of negative outcome in the ERC group than in the EUS group (P = .049, log-rank test). CONCLUSION: The EUS-first approach is not associated with further risk for subsequent endoscopic procedures. Patients with an undilated CBD should be investigated by the EUS-first approach to prevent post-ERC pancreatitis.

Identification of Helicobacter species by 16S rDNA PCR and sequence analysis in human liver samples from patients with various etiologies of benign liver diseases.

BACKGROUND/AIMS: Several reports indicated an increased prevalence of the Helicobacter species in hepatocellular cancer tissue and in liver samples infected with hepatitis viruses. The frequency of Helicobacter spp. in benign liver diseases was, however, not thoroughly investigated. METHODS: Seventy-five consecutive patients with suspected liver disease were enrolled. The indications were hepatitis B virus (n=30), C virus (n=8), B and C dual infection (n=1), nonalcoholic steatohepatitis (n=27), autoimmune hepatitis (n=3), primary biliary cirrhosis (n=1) and idiopathic elevation of liver enzymes (n=5). PCR detection of 16S recombinant RNA gene of Helicobacter spp. was performed on liver samples. PCR products of positive samples were further identified by DNA sequencing. The patients also had upper gastrointestinal endoscopy and gastric biopsy for the detection of H. pylori using histopathology and PCR. RESULTS: Helicobacter spp. DNA was detected in two out of 75 liver biopsy samples (2.6%), which were typed as H. pylori by DNA sequencing. One of these patients had chronic hepatitis C infection (man, 51 years old) and the other had nonalcoholic steatohepatitis (woman, 44 years old). Fifty-two out of 75 of the patients (69.3%) had H. pylori infection in their stomachs. CONCLUSION: We have found that H. pylori infection is much less prevalent in benign liver diseases. The presence of H. pylori in nonalcoholic steatohepatitis (NASH) patients is a novel finding and this finding should be confirmed in a larger series.

Evaluation of pain and patient satisfaction by music therapy in patients with endoscopy/colonoscopy.

BACKGROUND/AIMS: Endoscopy and colonoscopy are frequently performed procedures to evaluate the gastrointestinal system. These procedures are sometimes disturbing and painful for the patient. In gastrointestinal suits, endoscopy and colonoscopy may be performed on awake or sedated patients. Music therapy is a common and non-pharmacological treatment for various medical conditions, pain, and anxiety. The aim of the present study was to add music therapy to sedation administered during endoscopy and colonoscopy. The effect of music treatment on drug consumption, anxiety, and pain was investigated. MATERIALS AND METHODS: American Anesthesiologist Association I-III adult patients scheduled for endo/colonoscopy were randomized to music treatment and no music treatment groups. Patients with endoscopic ultrasound and endoscopic retrograde colangiopancreaticography were excluded from the study. Anxiety score and pain severity were evaluated before and after the procedure. Heart rate, mean arterial pressure, and oxygen saturation were recorded before, during, and after the procedure. Total drug consumption was recorded. Patient satisfaction and desire for the same protocol for recurrent procedures were investigated. RESULTS: Music therapy added to deep sedation administered by anesthesiologists provided decreased anxiety score and propofol consumption. Patient satisfaction was increased, and patients reported a desire for the same protocol for recurrent procedures. CONCLUSION: The present study may serve as the beginning of using music therapy for pain treatment in gastroenterology procedures in our hospital with/without sedation. Music and other non-pharmacological treatment methods must be remembered to increase patient comfort during enco/colonoscopies and other painful procedures.

Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study.

BACKGROUND: Peroxisome proliferators-activated receptor alpha (PPARalpha) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARalpha agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis. METHODS: Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day). All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and total bile acid (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining. RESULTS: Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-alpha, IL-1 beta levels, and TBA (P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals (P < 0.01). PPARalpha induction improved all histopathologic parameters (P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy (P < 0.01). CONCLUSION: Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.

Comparison of early enteral nutrition in severe acute pancreatitis with prebiotic fiber supplementation versus standard enteral solution: a prospective randomized double-blind study.

AIM: To compare the beneficial effects of early enteral nutrition (EN) with prebiotic fiber supplementation in patients with severe acute pancreatitis (AP). METHODS: Thirty consecutive patients with severe AP, who required stoppage of oral feeding for 48 h, were randomly assigned to nasojejunal EN with or without prebiotics. APACHE II score, Balthazar's CT score and CRP were assessed daily during the study period. RESULTS: The median duration of hospital stay was shorter in the study group [10 +/- 4 (8-14) d vs 15 +/- 6 (7-26) d] (P < 0.05). The median value of days in intensive care unit was also similar in both groups [6 +/- 2 (5-8) d vs 6 +/- 2 (5-7) d]. The median duration of EN was 8 +/- 4 (6-12) d vs 10 +/- 4 (6-13) d in the study and control groups, respectively (P > 0.05). Deaths occurred in 6 patients (20%), 2 in the study group and 4 in the control group. The mean duration of APACHE II normalization (APACHE II score < 8) was shorter in the study group than in the control group (4 +/- 2 d vs 6.5 +/- 3 d, P < 0.05). The mean duration of CRP normalization was also shorter in the study group than in the control group (7 +/- 2 d vs 10 +/- 3 d, P < 0.05). CONCLUSION: Nasojejunal EN with prebiotic fiber supplementation in severe AP improves hospital stay, duration nutrition therapy, acute phase response and overall complications compared to standard EN therapy.

Influence of H pylori on plasma ghrelin in patients without atrophic gastritis.

AIM: To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis. METHODS: Fifty consecutive patients (24 males and 26 females) with either H pylori-positive gastritis (n = 34) or H pylori-negative gastritis (n = 16) with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study. Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid, 1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d, followed by an additional 4 wk of 30 mg lansoprazol treatment. H pylori infection was eradicated in 23 of 34 (67.6%) patients. H pylori-positive patients were given eradication therapy. Gastric acidity was determined via intragastric pH catheters. Serum ghrelin was measured by radioimmunoassay (RIA). RESULTS: There was no significant difference in plasma ghrelin levels between H pylori-positive and H pylori-negative groups (81.10 +/- 162.66 ng/L vs 76.51 +/- 122.94 ng/L). In addition, there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy. CONCLUSION: H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.

Combined proper hepatic artery and common hepatic duct injury in open cholecystectomy: case report and review of the literature.

A 24-y-old male patient underwent elective open cholecystectomy at another center. On the third postoperative day, he developed fever and jaundice, for which he underwent reoperation at the same center on the seventh postoperative day. During the second surgery, massive bleeding was encountered, suture ligations were applied, and T-tube drainage was performed. After the surgery was completed, the patient developed hepatic microabscess, and sepsis ensued. The patient presented at this hospital for further evaluation. To rule out vascular injury, which was suspected in this patient, celiac angiography was performed; it showed that the hepatic artery was occluded near the eminence of the gastroduodenal artery, and the liver was supplied by many collaterals. After the patient's condition had stabilized and the sepsis had resolved, Roux-N-Y hepaticojejunostomy was performed on the 59th d after admission.

Tamoxifen-induced severe hypertriglyceridaemia and acute pancreatitis.

Hypertriglyceridaemia is a well known risk factor for acute pancreatitis. Hypertriglyceridaemia may be primary in origin or secondary to alcohol abuse, diabetes mellitus, pregnancy or use of drugs. In this case report, the cause of acute pancreatitis was tamoxifen. We report on a patient with tamoxifen-induced acute pancreatitis and hypertriglyceridaemia who was successfully treated with insulin infusion and long-term gemfibrozil.

Severe INR elevation in a patient with choledocholithiasis receiving cefoperazone.

Cefoperazone is a third-generation cefalosporin that contains the N-methyl- thio-tetrazole (NMTT) side chain, which inhibits vitamin K-dependent carboxylation. Administration of NMTT-containing cefalosporins can cause alterations in the hepatic glutathione redox state, resulting in a dose-related increase in oxidised glutathione, which is responsible for the inhibition of microsomal reduction of vitamin K epoxide. In addition, cefoperazone is not metabolised and is excreted predominantly through the bile. In patients with hepatic impairment, the clearance of cefoperazone has been shown to be significantly reduced and the half-life prolonged. We report a case of choledocholithiasis related to a prolonged prothrombin time and INR secondary to cefoperazone therapy.

Management of cervical esophageal strictures with self-expanding metalic stents.

Esophageal strictures due to malignant diseases are treated with self-expanding metalicic stents. However, experience is limited with these metalic stents in the cervical esophagus. Due to technical difficulties and procedure-related complications, the cervical esophagus has been assigned as a risky area for stenting procedures. Another encountered problem is patient discomfort after the procedure. In this case report, we present three patients with cervical esophageal strictures who were successfully treated with self-expandable metalic stents. Two of these patients had inoperable esophageal carcinoma and the third had benign stenosis due to radiotherapy of larynx carcinoma. The two patients with malignant disease survived four and six months, respectively, after the procedure. The last patient with benign disease is still alive and has been without dysphagia symptom for six months.

Therapy for treatment-refractory chronic hepatitis C virus genotype 1b infection: A retrospective analysis.

BACKGROUND: The most effective current therapy for hepatitis C virus (HCV) infection is the combination of pegylated interferon (peg-IFN) plus ribavirin (RBV). OBJECTIVE: The aim of this retrospective analysis was to determine the rateof response to this therapy, and the factors affecting outcome, in patients with treatment-refractory chronic HCV genotype l b. METHODS: The records of patients with chronic HCV infection and HCV geno-type1b who failed (nonresponse or relapse) previous treatment with standard interferon (IFN) + RSV were retrospectively analyzed for demographic data, virologic load, liver histology, biochemistry, treatment-related adverse effects (AEs), and the effects of dose reduction during treatment with peg-IFN + RBV for 48 weeks. Early virologic response (EVR) was defined as ≥2-log (copies/mL) decrease from baseline in serum HCV RNA concentration or the absence of detectable serum HCV RNA at treatment week 12. End-of-treatment response (ETR) was defined as the absence of detectable serum HCV RNA at treatment week 48. Sustained virologic response (SVR) was defined as the absence of detectable serum HCV RNA 24 weeks after treatment was discontinued. Factors affecting treatment outcome were determined using correlation analyses. RESULTS: Data from the files of 17 patients (12 men, 5 women; mean [SD] age, 48 [2] years) were analyzed. EVR was achieved in 7 patients; however, viral breakthrough occurred in 2 of these patients during the treatment period, and 5 of these patients discontinued treatment because of severe treatment-related AEs (depression [1 patient] and neutropenia [4]). Seven patients achieved ETR, but HCV infection relapsed during the follow-up period. Three (18%) patients achieved SVR. Data concerning previous patterns of response to IFN + RBV therapy were available in 10 patients. Of these, 3 of 6 patients who had experienced relapse with the previous treatment achieved SVR with peg-IFN + RBV; neither of the 2 patients with nonresponse to the previous treatment achieved SVR. Major determinants of failure to reach SVR in these patients included previous nonresponder pattern, noncompliance with the therapy, and advanced-stage liver fibrosis. Tolerability was similar to that with the previous treatment. CONCLUSIONS: In this study in patients with chronic HCV genotype lb infectionand a history of relapse or nonresponse to standard IFN + RSV treatment, treatment with peg-IFN + RBV achieved an SVR rate of 18%. Further research is needed to determine the role of peg-IFN + RBV in the re-treatment of HCV infection.

Combination therapy with pegylated interferon plus ribavirin in the treatment of hepatitis C virus-related thrombocytopenia.

BACKGROUND: Isolated thrombocytopenia is a common manifestation of hepatitis C virus (HCV) infection. There is no established treatment modality for this condition. The efficacy of standard interferon (IFN) monotherapy has been reported in some studies. The major disadvantage of this treatment is the high rate of recurrence due to viral breakthrough during the first 12 weeks of treatment. Pegylated IFNs are now the standard regimen for chronic hepatic disease due to HCV infection. However, due to a lack of evidence, pegylated IFNs are not widely used for HCV-related isolated thrombocytopenia. OBJECTIVE: The aim of this report was to present the case of a male patientwith severe symptomatic thrombocytopenia due to HCV infection. METHODS: Thrombocytopenia was treated with pegylated IFN plus ribavirin. RESULTS: Although standard IFN monotherapy failed to achieve virologic and hematologic improvement, therapy with pegylated IFN alfa-2a plus ribavirin was associated with both virologic and hematologic improvement without any significant adverse effects. CONCLUSIONS: Pegylated IFN plus ribavirin was effective in this patient for thetreatment of HCV-related thrombocytopenia. However, further research is needed to define the response rate in different patient populations.

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

BACKGROUND/AIMS: Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. MATERIALS AND METHODS: Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. RESULTS: Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1ß levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. CONCLUSIONS: The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.