Does interleukin-18 play a role in the pathogenesis of hepatic encephalopathy?

BACKGROUND/AIMS: It has been suggested that the presence of inflammation may accentuate the neuropsychologic alterations in hepatic encephalopathy (HE). The aim of the study was to investigate any association between alterations in plasma levels of the pro-inflammatory cytokine IL-18 and HE. METHODOLOGY: The study population included 63 patients with cirrhosis and 20 healthy controls. Laboratory data included international normalized ratio, plasma albumin, bilirubin, urea, creatinine, hsCRP and IL-18 (pg/mL). HE was assessed using West Haven criteria and critical flicker frequency (CFF) measurement. RESULTS: Forty-two of the 63 cirrhotic patients had HE (4, 16, 21 and 1 patients in grade 0, 1, 2, 3, respectively). hsCRP and IL-18 were significantly increased in patients with HE compared with the control group (1.6 +/- 4.8 vs 0.5 +/- 0.8, p<0.001 and 121.4 (13.6-2043.6) vs 56.3 (13.0-174.0), p=0.006, respectively). The levels of hsCRP and IL-18 were significantly higher in the all cirrhotic patients than in the control subjects (p=0.002 and p=0.008 respectively). hsCRP was significantly higher in patients with HE (2.2 +/- 6) than in patients without HE (0.7 +/- 1.2) (p=0.013). The levels of IL-18 were found higher in patients with HE than in patients without HE [121.4 (13.6-2043.6) vs 103.8 (13.0-828.0)] but the difference was not significant (p=0.215). IL-18 was higher in patients with elevated hsCRP [124.6 (13.6-2043.6)] compared with those who had normal hsCRP [75.6 (13.0-753.2)] (p=0.029). CONCLUSION: There is an inflammatory response in the presence of cirrhosis and HE; and IL-18 may play a role in the perpetuation of chronic inflammation.

Prevalence and characteristics of bone disease in cirrhotic patients.

Background and Aim: Chronic liver disease is a risk factor for osteoporosis, osteopenia and bone fractures. In this study, prevalence and risk factors of osteoporosis and vitamin D deficiency and also their effects on survival were investigated in 218 patients with chronic liver disease. Materials and Methods: Prevalence of osteoporosis and vitamin D levels was calculated. Risk factors for osteoporosis (gender, age, body mass index, etiology), serum bilirubin, albumin, 25-hydroxy (OH) vitamin D, parathyroid hormone levels, bone mineral density (BMD) with DEXA, bone formation (osteocalcin) and bone resorption (type 1 collagen) levels, Model for End-Stage Liver Disease (MELD) Na and Child-Pugh (CP) score were recorded. The effects of vitamin D levels and BMD on survival were evaluated. Results: One hundred forty-seven (67.4%) patients were female (mean age, 50.4±11.7). Patients were Child A by 40.8%, Child B by 47.1%, and Child C by 12.1%. Mean MELD Na score was 8.4±2.8. Data of the BMD were established in 218 patients and 25-OH D levels in 122 patients. Mean serum 25-OH D level was 14.26±9.44 ng/mL. Osteoporosis was identified in 42 (19.3%) and osteopenia in 115 (52.8%) patients, according to BMD. Osteocalcin levels and collagen type 1 levels were high in 25.6% and 12.5% of patients, respectively. No statistically difference was found, including gender (p=0.69), age (p=0.38), etiology (p=0.16), BMI (p=0.32), CP score (p=0.42), MELD (0.14), albumin (p=0.11), total bilirubin (p=0.99), Ca (0.67), PTH (0.88), osteocalcin (0.92), collagen type 1(p=0.25) between osteoporotic and non-osteoporotic patients. Patients were followed-up for a median of 30.07±11.83 months after BMD measurement. Fifty-four (24.8%) patients died during the follow-up period, none of them are related to bone fracture. There was no statistically difference on survival between osteoporosis group (32.2±2.3 months) and non-osteoporosis group (37.2±1.7 months; p=0.26) or when patients with 25-OH D3 ≤10 ng/mL were compared to patients with 25-OH D3 >20 ng/mL (34.4±2.0 months vs. 39.1±1.6 months, p=0.308). Conclusion: In conclusion, the prevalence of bone disease was found to be higher in cirrhotic patients. Although osteoporosis and vitamin D deficiency were found to decrease survival, this effect was not statistically significant. We suggest designing multi-institutional and/or multinational studies with larger and more heterogenous patient groups would enable better testing of this phenomenon.

Treatment of biliary leakages after cholecystectomy and importance of stricture development in the main bile duct injury.

BACKGROUND/AIMS: Endoscopic treatment of biliary leakages after cholecystectomy, though widely accepted, has some restrictions. The efficacy and safety of endoscopic treatments in this patient group are evaluated in this study, and the problem of biliary stricture development in time after biliary ductal injuries is also emphasized. METHODS: Seventy-four patients (20 male, 54 female, mean age 50.9+/-21 years) referred for ERCP between 1992-2002 were included in the study. Minor leakages (cystic duct leaks, accessory bile duct leaks) were managed by nasobiliary drainage +/- endoscopic sphincterotomy; major leakages were managed by nasobiliary drainage +/- endoscopic sphincterotomy +/- stenting. RESULTS: Twenty-seven patients with cystic duct leaks and 6 patients with accessory bile duct leaks were successfully treated with nasobiliary drainage. Endoscopic treatment could not be performed on patients with total bile duct obstruction (7 patients) and aberrant bile duct injury (7 patients). All leakages from main bile ducts were closed (27 patients). Six of 27 patients had strictures at the beginning and they were treated by stenting. Twenty-one patients had no strictures at the beginning. Eight of 21 were treated by stenting and only 1 of them developed biliary stricture. Seven of 13 patients who had been treated by nasobiliary drainage developed biliary strictures. There were no mortalities due to procedure. CONCLUSIONS: ERCP is an effective and safe method for diagnosis and management of bile leakages after cholecystectomy. Stricture development in the main bile duct leakages was an important complication.

Hypersensitive esophagus: can it be classified as a subgroup of gastroesophageal reflux disease?

BACKGROUND/AIMS: Gastroesophageal reflux disease is one of the most common gastrointestinal diseases of adulthood. Hypersensitive esophagus is a new term which defines patients with reflux symptoms, negative endoscopic findings and normal acid contact time on 24 hour pH analysis, although there is a convincing relationship between symptoms and acid reflux episodes on pH analysis- positive symptom index. In this study, the frequency of hypersensitive esophagus among patients with heartburn was determined and demographic findings, symptoms, manometric and pHmetric findings were compared among hypersensitive esophagus, non-erosive reflux disease, erosive reflux disease and normals. METHODS: Patients admitted to hospital with heartburn and without any cardiac, severe gastric or duodenal pathologies (except minimal antral gastritis) and with no abnormal manometric findings suggestive of esophageal motility disorders were included in the study. All patients were questioned about age, height, weight, educational status and intestinal and extraintestinal reflux related symptoms. Upper endoscopy, esophageal manometry and 24 hour pH monitoring were performed respectively. RESULTS: Of the 44 patients (17 male, 27 female) included in the study, seven (16%) had hypersensitive esophagus, 15 (34%) had non-erosive reflux disease, seven (16%) had erosive reflux disease and 15 (34%) had normal findings. The female ratio in the hypersensitive esophagus and normal groups was higher while the male ratio was higher in erosive reflux disease. There was no significant difference among groups according to age, body mass index and symptoms. There was also no significant difference according to manometric findings. De Meester scores were significantly lower in hypersensitive esophagus and normal groups while symptom index was highest in the hypersensitive esophagus group. Reflux was observed especially in the upright position in all groups. CONCLUSION: The ratio of hypersensitive esophagus, gastroesophageal reflux disease and no pathology in patients with heartburn was 16%, 50% and 34% respectively. It would be appropriate to accept hypersensitive esophagus as a subgroup of reflux disease as it has both symptoms and some manometric and pHmetric changes.

Do aspirin and non-steroidal anti-inflammatory drugs increase the risk of post-sphincterotomy hemorrhage--a case-control study.

BACKGROUND AND OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin have antiaggregant properties and patients with pancreaticobiliary disease commonly use these drugs. We prospectively investigated whether aspirin and NSAIDs are associated with endoscopic sphincterotomy related hemorrhage. METHODS: Three hundred and eight patients who underwent sphincterotomy were sequentially recruited into this prospective case-control study. Pre-endoscopic assessment included a complete blood count, coagulation studies and a detailed drug history after sphincterotomy patients were followed up for bleeding. Cases and controls were compared for patient and procedure-related risk factors of post-endoscopic sphincterotomy bleeding. RESULTS: Hemorrhage occurred in 74 (24%) patients. Eight (2.6%) were clinically significant and five (1.6%) were severe. Amongst cases with hemorrhage, 17.6% were on NSAIDs and 14.9% on aspirin; 27.4% of controls took NSAIDs, and 9.8% aspirin (P>0.05). Aspirin use in patients with significant (12.5%) or severe hemorrhage (20%) was not different from the controls (P>0.05) and none of them had NSAIDs prior to sphincterotomy. Based on univariate analysis, coagulopathy and comorbidity were risk factors for significant post-sphincterotomy hemorrhage and coagulopathy was the only independent parameter (odds ratio=22.72, 95% CI [4.25; 125]). CONCLUSION: Aspirin and NSAIDs do not increase the risk of post-sphincterotomy hemorrhage and they can be safely used before the procedure.

Endoscopic treatment of primary sclerosing cholangitis.

BACKGROUND/AIMS: Dominant stricture of an extrahepatic bile duct is responsible for symptoms and an exacerbation of cholestasis in 15-20% of patients with primary sclerosing cholangitis. The aim of this study was to evaluate the efficacy and safety of endoscopic treatment in this selected patient group. METHODS: Retrospectively, we evaluated 16 patients who were treated endoscopically due to elevation of serum biochemical liver tests and symptoms which were attributable to dominant bile duct strictures during the period 1990 to 2003. Symptoms and biochemical liver tests were compared before and after treatment. RESULTS: Sixteen patients underwent a total of 58 therapeutic endoscopic retrograde cholangiopancreatographies (ERCP). Sixteen endoscopic sphincterotomies, 15 balloon dilatations, 6 bougie dilatations, 3 stone/sludge extractions and 8 stentings were performed. Endoscopic therapy was technically successful in all patients (100%). Biochemical liver tests were significantly improved when compared with pretreatment values (p<0.001). Patients have been followed-up without stents except for the patients who had cholangiocarcinoma and cirrhosis at the beginning. Procedure-related early complications occurred in 8.6% of therapeutic endoscopic biliary procedures. There was no mortality due to endoscopic treatment. Two patients whose stents were changed every two to three months had cholangitis due to stenting during 13 stent periods. Four patients whose stents were changed in seven to 10 days developed suppurative cholangitis (total 6 stent periods). CONCLUSIONS: Endoscopic therapy of symptomatic dominant strictures in primary sclerosing cholangitis is safe and effective. The cholangitis seen in long-term stenting seems to be solved by short-term stenting.