Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis.

BACKGROUND & AIMS: For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH. METHODS: We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58). RESULTS: Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes). CONCLUSIONS: In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.

MELD-sodium score and its prognostic value in malignancy-related ascites of pancreatic and gastric cancer.

BACKGROUND: Malignant ascites is a manifestation of end-stage events in a variety of cancers. There is significant lack of possible survival predictors in patients with malignancy-related ascites. Since the Model for End-Stage Liver Disease (MELD)-Na score has been shown to be a feasible and independent prognostic predictor for both short- and long-term outcome in HCC patients, we decided to test its prognostic role in other cancer types with ascites. MATERIAL AND METHODS: This is a retrospective study. The outpatient oncology clinic's records were screened for the period between 2004 and 2011. Eighty-two pancreatic and gastric cancer patients were enrolled into the study. RESULTS: The median age of patients was 59 (±12). Fifty-nine patients had gastric cancer and 23 had pancreatic cancer. Overall survival (OS) was 16.8 (IR, 1-98) months in gastric cancer and 16.3 (IR, 0.5-81) months in pancreatic cancer. There was no statistically significant difference between OS of gastric and pancreatic cancer. Progression-free survival (PFS) was statistically significantly longer in gastric cancer than pancreatic cancer with 16.5 (IR, 0.5-90) vs 6.5 (IR, 0.4-34) months (P = 0.04). Further analysis of data included stepwise multiple regression analysis with the dependent variable "overall survival." The model had two independent predictors and an R(2) of 82 % and a predicted R(2) of 81 %. Predictors for time to remission were PFS and MELD-Na. The regression equation for the model was: Overall survival =17.4- 0.522 MELD-Na + 0.902 PFS CONCLUSION: In this study we showed that progression-free survival and MELD-Na score are significantly related with overall survival. MELD-Na score can be one of the predictors of the survival and PFS in pancreatic and gastric cancer patients with ascites.

The use of radial endosonography findings in the prediction of cholangiocarcinoma in cases with distal bile duct obstructions.

BACKGROUND/AIMS: We retrospectively collected the data of radial endosonographic (EUS) imaging findings of the patients with the distal bile duct obstructions due to different benign and malignant conditions. We aimed to assess and analyze the EUS findings in the distal bile duct obstruction which can predict or detect the existence of cholangiocarcinoma originating from the distal bile duct wall. METHODOLOGY: We gathered the data of 192 cases with distal biliary stricture due to various causes which all were diagnosed. RESULTS: With EUS, The sensitivity and specificity for diagnosis of cholangiocarcinoma in lesions were respectively as following: Firstly, small hypoechoic mass which interrupts to see lumen and choledoch wall with total occlusion at distal choledoch: 75.8%, 88.1%. Secondly, hypoechoic and irregular thickening than surrounding regions at distal choledoch wall: 68.1%, 87.3%. Thirdly, appearance of lumen prompt termination at distal choledoch: 57.1%, 87.6%. Lastly, appearance where lumen narrows short segment: 13.6 %, 59.3 %. CONCLUSIONS: EUS findings including hypoechoic mass appearance completely occluding the lumen or heterogeneously increased irregular wall-thickness in the distal bile duct were found to be highly predictive and sensitive for detecting malignancy originating from the distal bile duct.

The Investigation of Therapeutic Implications of Mast Cell Stabilizer Cromolyn Sodium on Cholestasis and Cholestatic Pruritus in Experimental Cholestasis.

BACKGROUND: Relevant studies have indicated that hepatic mast cells may have potential roles in the progression of cholestasis and cholestasis-induced itch. We aimed to compare the effects of cromolyn sodium and other medications on cholestatic pruritus, serum biochemistry, histamine, total bile acids, autotaxin, liver histopathology, and mast cell distribution in tissues in an experimental cholestasis model conducted by bile duct ligation. METHODS: Rats received the determined treatment consecutively for 10 days in addition to bile duct ligation. On the 5th and 10th days of the experiment, the rats' itching behaviors were observed for 5 minutes. After 10 days, blood and tissue samples were taken. RESULTS: Significant decreases in serum histamine and autotaxin levels, plasma total bile acids, total bilirubin, and biliary enzymes were reported only in cromolyn sodium-treated rats compared to the control group. In immunohistochemistry of the liver samples, the peribiliary mast cells stained positive for autotaxin. Except for bile duct infarctus, all histopathological findings of cholestasis significantly improved only in cromolyn sodium-treated and sertraline-treated rats. The liver and peritoneal mast cells significantly decreased only in cromolyn sodium-treated rats compared to the control group. On the 10th day of the experiment, the mean duration of itching was significantly lower in all groups, except for naloxone- and ondansetron-treated rats. CONCLUSION: Cromolyn sodium has promising antipruritic efficacy and provides biochemical and histopathological recovery of the relevant parameters of cholestasis induced by bile duct ligation. For the first time in the literature, we showed that peribiliary mast cells can produce autotaxin, which is a very important pruritogenic signal in the setting of cholestasis.

Peripheral blood lymphocyte dynamics and viral kinetics in patients with chronic active hepatitis B virus infection treated by tenofovir.

BACKGROUND/AIMS: We investigated serum viral kinetics and peripheral blood lymphocyte dynamics in chronic hepatitis B patients during the first year of tenofovir therapy. METHODOLOGY: Fifteen patients, naive to any kind of previous antiviral therapy, were included in this study. The patients received tenofovir daily 245mg for 48 weeks. Fifteen age and gender compatible healthy subjects were enrolled as the control group. Clinical, biochemical, immunological and virological parameters were assessed at baseline, then at the first, third, sixth and twelfth months. RESULTS: CD4+CD25+FOXP3+ nTregs percentages were significantly higher in the study group than that of healthy controls, CD4+CD28+ and CD4+CD38+ T cell percentages were significantly lower in the study group than those of control group (p<0.001). Twelve cases had undetectable HBV DNA levels after the one year therapy. We determined that there was an increase of the CD28+co-stimulator molecule on both the CD4+ and CD8+ T cells while a decrease of the CD8+CD38+ T cells, CD4+CD38+ T cells and CD4+CD25+FOXP3+ nTregs, in patients with tenofovir treatment, but only CD4+CD25+FOXP3+ nTregs were statistically significant. CONCLUSIONS: We found that both viral load and CD4+CD25+FOXP3+ nTreg percentages decreased significantly in patients with chronic hepatitis B virus infection during 1 year course of tenofovir treatment.

Role of radial endosonography in the diagnosis of acute cholangitis.

BACKGROUND AND STUDY AIM: We aimed to assess radial endoscopic ultrasound (EUS) features of the bile duct wall as well as biliary luminal liquid characteristics in cases with acute cholangitis. PATIENTS AND METHODS: This prospective study was performed during the period from January 2009 to February 2010 in a tertiary referral center. Twenty-eight patients with acute cholangitis and 60 patients without acute cholangitis but with cholestasis due to gallstone disease were enrolled in the study. During radial EUS examination, sonographic features of the common bile duct wall, the intraductal luminal content, and nearby periductal structures were investigated. Mild hyperechogenic-heterogenic appearances with waving-type movements without acoustic shadowing enclosing one-third of the common bile duct were noted as purulent materials. RESULTS: EUS indicated an increased focal and/or diffuse concentric bile duct wall thickness (>1.5 mm) in 68 and 27% of the cases with and without acute cholangitis, respectively. The mean bile duct wall thickness was 1.9 mm (0.9-2.9 mm) and 1.1 mm (0.6-2.1 mm) in the study and control groups, respectively (P < 0.05). On EUS, a pericholedochal hypoechoic strand more than 1.5 cm in length was present in 13 of 28 patients with acute cholangitis (46%). It was less than 1 cm long in 11 cases without acute cholangitis (18%). Bile duct content with heterogenous dense echogenicity without acoustic shadowing was present in 18 patients (64%) with acute cholangitis and in two patients (3%) without cholangitis. Those 20 patients were successfully drained with a same-day endoscopic retrograde cholangiography (ERCP) procedure which confirmed purulent biliary content after sphincterotomy. Same-day ERCP revealed no purulent material drainage from the bile duct in the other eight patients without cholangitis. The accuracy and positive and negative predictivity of diffuse concentric wall thickening and a peribiliary hypoechoic strand of greater than 1.5 cm in length for a diagnosis of acute cholangitis were 91, 86.3, and 67.1%, and 76, 72, and 54%, respectively. For purulent material, the accuracy and positive and negative predictive values of EUS for acute cholangitis were noted to be 87, 93.3, and 82%, respectively. CONCLUSION: Through this study, it was concluded that EUS findings such as diffuse and/or concentric wall thickening of more than 1.5 mm and intraductal heterogenous echogenicity without acoustic shadowing are highly accurate and predictive for diagnosing acute cholangitis.

Serum glucagon and cystatin C levels with renal doppler sonography findings in non-azotemic liver cirrhosis cases.

BACKGROUND/AIMS: It is well known that the hyperdynamic circulatory state in cirrhosis is characterized by increased splanchnic blood flow and renal vasoconstriction. The role of hyperglucagonemia in the renal hemodynamic changes that occur in this patient group is poorly understood at present. This study investigated relationships between serum glucagon levels, indicators of renal function (serum creatinine [Cr] and cystatin C levels, creatinine clearance rate [CrCl]), and renal hemodynamic findings in early and later stages of liver cirrhosis. METHODOLOGY: In total, 40 patients with non-azotemic liver cirrhosis (Group 1) and 20 healthy gender- and age-matched controls (Group 2) were enrolled. The patient group was subdivided into Group la (25 patients with compensated cirrhosis [Child-Pugh A score]) and Group 1b (15 patients with decompensated cirrhosis [Child-Pugh B or C]). RESULTS: Group 1 patients had significantly elevated serum glucagon levels than Group 2 (57.8 +/- 46.7 pmol/L vs. 22.1 +/- 8.1 pmol/L, respectively p<0.05). Group 1b had significantly higher mean serum glucagon than Group la (97.4 +/- 58.8 pmol/L vs. 35.1 +/- 15.2 pmol/L, respectively p<0.05). Although there was no difference between Group la and 1b with respect to mean serum Cr and CrCl, mean serum cystatin C was significantly higher in group 1b than group la (1.6 +/- 0.4 mg/L vs. 1.1 +/- 0.2 mg/L, respectively p<0.05). Group 1 had a significantly higher mean renal resistive index (RRI) than the control group (0.64 +/- 0.1 vs. 0.57 +/- 0.01, respectively, p<0,05). According to Spearman's correlation analysis, serum glucagon was correlated with RRI in Group la (compensated stage of liver cirrhosis) (r=0.52, p=0.008), but not in Group 1b (decompensated stage of cirrhosis) (r=-0.07, p=0.803). RRI was not correlated with serum Cr, Serum Cystatin C, Or Crcl In Either Patient Subgroup. CONCLUSIONS: The findings indicate that hyperglucagonemia may be associated with renal hemodynamic changes in early-stage liver cirrhosis. However, this relationship was not observed in the decompensated stage.

The clinical presentations of ectopic biliary drainage into duodenal bulbus and stomach with a thorough review of the current literature.

BACKGROUND: Ectopic biliary drainage is a rare congenital anomaly on which we have scarce data in the current literature. METHODS: The data were collected from the records of 400 endoscopic retrograde cholangio-pancreatography (ERCP). In this report, we present 10 cases (male/female: 9/1, mean age 54 years, range 38-74) with ectopic biliary openings into the duodenum and/or stomach diagnosed by endoscopic retrograde cholangio-pancreatography (ERCP). RESULTS: In our series, the frequency of ectopic biliary drainage is 2% (10 out of 400 ERCPs). Recurrent attacks of cholangitis and complicated ulcer formation in the distal stomach and bulbar duodenum were the most common signs in the present series. The sites of ectopic biliary drainage were the stomach in 1 case, the duodenum bulbus in 7 cases and the postbulbar duodenum in 2 cases. Bulbar ulcer, deformed pylorus and bulbus were present in 7 cases, apical bulbar stricture in 2, gastric ulcer in 1, pyloroplasty and/or gastroenterostomy in 3 cases. One case had had previous bleeding episode. Some of them had undergone previous surgeries for gall-stone disease (cholecystectomy in 5 cases, bile duct operation in 3 cases) and ulcer complications (pyloroplasty/gastroenterostomy in 3 cases). ERCP revealed dilatation of the biliary tree and hook shaped distal choledochus in all cases, choledocholithiasis in 7 and Mirizzi syndrome in 1. Endoscopic balloon dilatations for gastric outlet obstruction, extraction of bile stones after balloon dilating the ectopic site, surgery for difficult cases with large bile duct stones or with gastric outlet obstruction were preferred methods in this series of patients. CONCLUSION: With this report, we have to remind that ectopic biliary drainage must be considered in the differential diagnosis when the clinician faces cases with gastric outlet obstruction due to peptic ulcer formation accompanied by cholangitis/cholestasis.

Cavernous hemangioma with arterioportal and portosystemic shunts: precise diagnosis with dynamic multidetector computed tomography imaging.

Cavernous hemangiomas with shunt formations have been a recently recognized entity. Arterioportal (AP) shunts with cavernous hemangiomas have been described. However, a combination of AP and portosystemic (PS) shunts causing portal hypertension has not been previously demonstrated by computed tomography (CT) imaging. In this study, we report an atypical cavernous hemangioma associated with portal hypertension. Cavernous hemangioma with AP and PS shunts formations was precisely demonstrated with dynamic multidetector CT imaging.