Solid phase synthesis of a biased mini tetrapeptoid-library for the discovery of monodentate ITAM mimics as ZAP-70 inhibitors

BACKGROUND: Clinical evaluation of intraoperative endoscopy with electrohydraulic lithotripsy (EHL) in the management of 13 patients with pancreatobiliary lithiasis was undertaken. METHODS: Ten patients with chronic pancreatitis with intraductal lithiasis in the head and three with biliary lithiasis (one choledochal, one cystic, one right intrahepatic) underwent intraoperative endoscopy with EHL. Shock waves were applied by visual contact with a 3-Fr gauge EHL probe until all stones were fragmented and irrigated free. All pancreatitis patients had failed ERCP attempts to stent their pancreatic ducts secondary to ductal lithiasis. Patients with pancreatic stones underwent lateral pancreatojejunostomy. Biliary stone patients underwent laparoscopic cholecystectomy with common duct exploration (two cases) and open cholecystectomy with choledochoduodenostomy (one case). RESULTS: Intraductal stone eradication was successful in all patients. Transampullary visualization of the duodenum was achieved in eight cases. Average EHL time was 65 min. There was no evidence of postoperative pancreatitis, cholangitis, or retained common duct stones. CONCLUSION: Intraoperative pancreatobiliary endoscopy with EHL is safe and effective in the eradication of pancreatic and bile duct stones. This novel technique represents a valuable adjunct in the management of chronic fibrocalcific pancreatitis with ductal lithiasis in the head region and in the open and laparoscopic management of intra- and extrahepatic bile duct stones.     

Persistent obstructive jaundice, cholangitis, and biliary cirrhosis due to common bile duct stenosis in chronic pancreatitis

Long strictures of the intrapancreatic portion of the common bile duct were found in 6 patients with chronic pancreatitis. These strictures were responsible for painless obstructive jaundice, recurrent cholangitis, secondary biliary cirrhosis, and chronic abdominal pain difficult to distinguish from that caused by pancreatitis. Endoscopic retrograde cholangiopancreatography and intraoperative cholangiography were invaluable in making the diagnosis and in planning surgical correction. Decompression of the biliary tree by anastomosis of the gallbladder or common duct to the small intestine completely relieved symptoms and allowed liver function to improve significantly. Common duct stricture as a complication of chronic pancreatitis should be considered in the differential diagnosis of extrahepatic biliary obstruction and whenever surgical treatment of chronic pancreatitis is contemplated.     

The role of endoscopic therapy in chronic pancreatitis-induced common bile duct strictures

During endoscopic retrograde cholangiography, common bile duct strictures are encountered in up to 30% of patients with chronic pancreatitis. The indications for treatment of these strictures are discussed. A surgical biliodigestive anastomosis has always been the traditional treatment modality. Not all patients need treatment, however, and endoscopic biliary drainage is the treatment of choice for certain subgroups of patients.     

The effect of scrubbing and irrigation with normal saline, povidone iodine, and cefazolin on wound bacterial counts in a guinea pig model

Three cases of biliary tract compression caused by a cavernous transformation of the portal vein are reported. Revealing symptoms of biliary disease were anicteric and asymptomatic cholestasis in one patient, and cholangitis and obstructive jaundice in one case each. Endoscopic retrograde cholangiograms showed that the compression was located in the common bile duct in two cases and in the main bile duct in one. The responsibility of the portal cavernoma was established by the disappearance of jaundice after splenorenal shunt in one case. Biliary consequences of a portal cavernoma are very uncommon. Compression by the turgescent venous network combined with a sclero-inflammatory reaction of the biliary tract are the most likely causes.     

Urgent ERCP and early elective laparoscopic cholecystectomy in biliary pancreatitis

BACKGROUND: For many years the best algorithm of treatment for complicated gallstone disease has been intensively discussed. Gallstone pancreatitis with cholangitis still belongs to the most often identified causes of death of necrotizing pancreatitis. The reduction of complication and lethality rates was mainly achieved by urgent ERCP and sequential cholecystectomy. In a prospective study we have combined endoscopic therapy with laparoscopic cholecystectomy (LC) and are discussing the results. PATIENTS AND METHODS: Between May 1991 and December 1996 146 patients with biliary pancreatitis were subjected to ERCP after laboratory tests and ultrasound screening of the biliary system. If there were no contraindications and the gallbladder was still in situ, LC was attempted during the initial admission. RESULTS: Of the 70 patients with attempted LC 26 had common bile duct calculi, 23 had an impacted papillary stone and 10 had signs of a stone passage. 59 patients underwent LC successfully, a conversion to open surgery was necessary in 11 patients. The morbidity rate amounted to 7%, lethality to 0%. DISCUSSION: Since a more liberal indication for ERCP in the management of acute pancreatitis was introduced the number of biliary related cases of acute pancreatitis is increasing. In response to early endoscopic bile duct clearance the rates of morbidity and mortality can be significantly reduced. Early LC is the ideal complementary treatment option to absolutely prevent recurrencies.     

Surgical treatment of cicatricial biliary strictures

BACKGROUND/AIMS: Cicatricial biliary strictures are usually associated with high morbidity and mortality rates, frequently related to technical difficulties of their surgical repair, mainly in hilar lesions. Interference with bile duct blood supply during surgical attempts for correction is a major factor for unsuccessful results. The aim of this study is to evaluate, after an extended follow-up period, the results obtained with a modified technique for surgical correction of cicatricial biliary strictures. METHODOLOGY: The medical records of 57 patients surgically treated for cicatricial biliary strictures between January 1984 and July 1995 were reviewed and the immediate and long term results retrospectively analyzed. Patients consisted of 46 females and 11 males. The average age was 43 years. The etiology of the biliary lesion was: cholecystectomy alone (23); cholecystectomy with duct exploration (8); T tube CBD drainage (6); Biliary-enteric anastomosis stricture (16); choledochoplasty (2) and trauma (2). In 28 cases (49.1%) the stricture was located in the upper third of the bile duct, in 28 (49.1%) in the middle third and in one case (1.7%) it was low. All patients were submitted to longitudinal Roux-en-Y hepaticojejunostomy with mucosa apposition after dissection of the anterior aspect of the biliary tract. No transanastomotic stents were used. RESULTS: Ten patients (17.5%) presented 11 postoperative complications: biliary fistula (4), duodenal fistula (1), wound infection (5), and acute pancreatitis (1). Average hospital stay was 11 days and there were no postoperative mortalities. The follow-up study was possible in 54 patients and ranged from one to ten years, with an average of 2.9 years. Four patients of 28 (14%) with hilar lesions developed stricture recurrence and cholangitis episodes, whereas no patients bearing lesions below the biliary junction had such complications. CONCLUSION: Roux-en-Y hepaticojejunostomy with mucosa apposition without transanastomotic stent performed after minimal dissection of the biliary duct, thus avoiding major interference with the bile duct blood supply, is a safe and efficient method for the surgical repair of cicatricial biliary strictures. Using this technique excellent results can be obtained in the lesions below the biliary junction and acceptable results may be achieved in patients with hilar lesions.     

Bile duct cysts in adults

INTRODUCTION: Bile duct cysts are rare, congenital dilations of the intrahepatic and/or extrahepatic biliary tract. Most of them present during childhood. The classical triad right upper quadrant pain, jaundice and abdominal mass is present only in a few instances. We report here the bile duct cysts which were diagnosed at our institution from 1989 to 1996. METHODS: 3245 consecutive endoscopic retrograde cholangiopancreatograms (ERCP) were evaluated retrospectively. Diagnosis was made when localized cystic dilations of the intrahepatic and/or extrahepatic biliary tract were present. Diffuse dilations of the intrahepatic and extrahepatic biliary tract were excluded. RESULTS: Bile duct cysts were found in 20 patients (17 females, 3 males) among 3245 ERCPs. Their mean age was 56 +/- 20 (median 64, range 10 to 83) years. The cyst types (according to the Alonso-Lej classification with the Todani modification) were type I in 11 (55%), type II, III and IV in two instances each (10%), and type V (or Caroli's disease) in 3 patients (15%). Leading symptoms were cholestasis in 14 patients, 10 of whom had abdominal pain, jaundice in 4 patients, and single cases of pancreatitis, cholangitis, and abdominal mass. In 2 patients the diagnosis was made incidentally. 10 patients had bile duct stones. We performed endoscopic sphincterotomy in 15 patients with concretions or persistent symptoms, 3 patients had cyst resection. One of these, with a type I cyst, already had a disseminated cholangiocarcinoma. 10 of 17 patients without cyst resection are currently symptom-free after complete removal of all gallstones. One male patient with cholecystolithiasis, who is not operable due to advanced liver disease, has recurrent cholangitis, 4 patients have died from causes unrelated to the bile duct cysts, and 2 patients are lost to follow up. CONCLUSION: Bile duct cysts in adults are rare. There is a preponderance in the female gender, and the most common type is the extrahepatic (choledochal) cyst. The leading symptoms are cholestasis and right upper quadrant pain. There is an increased risk of cholangiocarcinoma. In young patients the cysts should be entirely removed to prevent malignancy. Older persons are usually symptomless after complete removal of gallstones.     

Does endoscopic sphincterotomy prevent recurrent biliary pancreatitis?

Endoscopic sphincterotomy was electively performed as the definitive procedure on 8 high-risk patients with biliary pancreatitis; the gallbladder was left in situ. After a mean follow-up of 21 months, 2 patients had biliary symptoms for which 1 required cholecystectomy and exploration of the common bile duct. No patient developed recurrent pancreatitis during the follow-up period. When the risk of elective surgery is high, endoscopic sphincterotomy appears to protect the patient against recurrent episodes of pancreatitis, and is the initial procedure of choice for the high-risk patient with biliary pancreatitis.     

Pruritus as a presenting symptom of chronic hepatitis C

Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.     

Does lipid infusion affect bile composition in humans?

A prospective study was performed to investigate the effect of short-term lipid infusion on bile composition and its lithogenicity in humans. The study group comprised 44 patients scheduled for laparotomy. The patients were hospitalized 48 h prior to elective surgery and randomized to be infused with a lipid emulsion of either long chain triglycerides (LCT) or a mixture of medium and long chain triglycerides (MCT/LCT) for 6 h of each 24 h, or with glucose-saline. Bile samples were obtained by puncture of the gallbladder during operation. In non-gallstone patients, both lipids caused an elevation of biliary cholesterol and phospholipids, but this effect was more pronounced and significant (P <0.001) only with the mixture of MCT/LCT emulsion. The fatty acid composition of biliary phospholipids was not affected by either lipid infusion. The Cholesterol Saturation Index increased significantly (P <0.005) with the MCT/LCT emulsion and there was insignificant shortening in the nucleation time. In contrast to patients with cholelithiasis, no effects could be demonstrated on gallbladder bile composition, cholesterol saturation index, nucleation time, or fatty acid composition of phospholipids. The effects of both lipid emulsions on plasma lipids and lipoproteins were similar in all groups. Our results indicate that lipid emulsions containing MCT/LCT induce lithogenic changes in the composition of human bile. We propose that the lack of effect of lipid infusion on bile composition in patients with cholelithiasis may be due to precipitation of excess cholesterol in the gallbladder of cholesterol gallstone patients whose bile is already saturated. These findings imply that patients with cholesterol gallstones cannot be grouped with non-gallstone patients in studies of alterations of bile composition.     

The role of proliferation in the origin of mutations in mammalian cells

Biliary obstruction, produced by common bile duct ligation or alpha-naphthylisothiocyanate (ANIT) treatment in rats, has been associated with the development of type I biliary epithelial cell (BEC) hyperplasia. However, the exact mechanism(s) by which bile duct obstruction lead(s) to this proliferative lesion are not clear. The present studies were designed to determine if cholestasis, in the absence of biliary obstruction, would result in type I BEC hyperplasia. Male Sprague-Dawley rats were given a single oral dose of 150 mg/kg ANIT or i.v. doses of estradiol glucuronide (E2-17G; 21 mumol/kg/h for 48 h) to produce obstructive and non-obstructive cholestasis, respectively. E2-17G treatment resulted in cholestasis that was comparable in extent and duration to that observed following ANIT treatment. E2-17G and ANIT treatments produced comparable increases in serum bile acids (55- to 60-fold) and activities of ALT (36- to 38-fold), ALP (4- to 5-fold), and 5'-nucleotidase (7- to 11-fold), respectively, compared to controls. Both ANIT and E2-17G also increased serum bilirubin concentrations. ANIT treatment resulted in significant increases in biliary glucose concentrations that were associated with BEC damage/necrosis and obstruction of the bile duct lumen. Conversely, no evidence of BEC damage was observed in E2-17G-treated rats. Nonetheless, BEC hyperplasia was observed in the majority of rats following treatment with either ANIT or E2-17G, assessed by light microscopy and by BrdU immunohistochemistry. These data indicate that E2-17G treatment produces nonobstructive cholestasis and type I BEC hyperplasia, suggesting that biliary obstruction is not a prerequisite for type I BEC hyperplasia in rats. Differences in the time of onset of hyperplasia were observed: hyperplasia was noted immediately following 48 h of E2-17G-induced cholestasis but occurred several days after ANIT-induced cholestasis had subsided. Since the magnitude/duration of cholestasis was similar in the two models but the temporal association between cholestasis and type I BEC hyperplasia were different, these data suggest that the proliferative stimulus may be different in the two models and that E2-17G-induced type I BEC hyperplasia may not be attributed solely to cholestasis.     

A longitudinal study of circulating lymphocyte subsets in the peripheral blood during the acute stage of Guillain-Barré syndrome

We investigated sequential changes in bile flow, serum and biliary biochemical parameters in phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration with phalloidin (500 microg/kg) for 7 days, and then the animals were allowed to survive for 1, 2, 4, 7, 14 and 28 days after the last treatment. In phalloidin-treated rats, bile flow significantly decreased up to 4 days of recovery, compared with the control animals. In contrast, serum ALP activity, LAP activity, cholesterol concentration and phospholipid concentration exhibited a marked elevation throughout the recovery periods. For biliary parameters, bilirubin excretion rate was unchanged but, cholesterol excretion rate showed a marked decrease throughout the recovery periods. These results demonstrate that some parameters, particularly important indexes of cholestasis (serum ALP, cholesterol, bile flow and so on), continued significant changes at least 4 days after the last administration of phalloidin. These results demonstrate that successive treatment with phalloidin can cause damage in most of serum and biliary parameters at a chronic stage of cholestasis. Thus, our findings may provide useful information for diagnosis of drug-induced cholestasis and help to further elucidate the biochemical mechanisms of drug-induced cholestasis in humans.     

Duodenal obstruction from chronic pancreatitis

The fibrosclerosing process of the pancreas in the chronic pancreatitis may constrict not only the pancreatic duct but also the bile duct, splenoportal venous system and duodenum. In our retrospective study we analysed 24 patients with duodenal obstruction associated with chronic pancreatitis. Duodenal obstruction was suspected whenever repeated vomiting occurred or large volumes of nasogastric aspirate were obtained. The diagnosis was confirmed by barium meal and endoscopic examination. Duodenal obstruction was relieved by gastrojejunostomy in eight patients, gastrojejunostomy and vagotomy in eight patients, gastroduodenostomy and vagotomy in two patients, vagotomy with Finney pyloroplasty in one patient, duodenoplasty with vagotomy in one patient and Whipple procedure in four patients. We concluded that vagotomy and gastroenterostomy are the procedures of choice. Bypass surgery is helpful to relieve the obstruction of the common bile duct and pancreatic duct. Whipple procedure should be reserved for the small duct form of chronic pancreatitis and for the cases in which there is high suspicion of malignancy.     

Current results of endoscopic sphincterotomy for lithiasis of the common bile duct

Between January 1989 and June 1990, endoscopic sphincterotomy was performed in 308 consecutive patients with common bile duct stones (mean age: 74 years). Complete clearance of common bile duct was achieved at the first attempt in 65% of cases. This rate was significantly related to the size and the number of biliary stones. The success rate reached 97 percent after repeated endoscopic sessions (127 patients), mechanical lithotripsy (20 patients), extracorporeal or intracorporeal lithotripsy (18 and 11 patients, respectively). During the month following the endoscopic sphincterotomy, 39 patients (13%) developed one or more complications and 11 patients (3.7%) died. The complication rate was related to the time elapsed between biliary opacification and endoscopic sphincterotomy (P = 0.04) and between endoscopic sphincterotomy and total common bile duct clearance (P = 0.0007). No patient younger than 75 years died, but death occurred in 4.5% of the patients older than 75 years. Thirty patients (10%) developed endoscopic sphincterotomy-related complications. Cholangitis and bleeding were the most frequent complications (4 and 2%, respectively). Cholangitis occurred more frequently among the patients older than 75 (P < 0.05) or when transhepatic guided endoscopic sphincterotomy or intracorporeal lithotripsy was used (P < 0.005). Cholangitis led to death in 2 patients, 86 and 87 years old (0.7%). Endoscopic sphincterotomy related complications developed within 48 hours in all but 4 patients (2 patients with pancreatitis and 2 patients with cholecystitis).     

Observations of increased levels of blood coagulation factors and other plasma proteins in cholestatic liver disease

One group of 8 patients with primary biliary cirrhosis and one group of 7 patients with common duct stone both had generally high levels of blood coagulation factors and a wide range of other plasma proteins. In contrast, one group of 6 patients with chronic active hepatitis generally had low levels of the same coagulation factors and plasma proteins. Analyses of factor II-VII-X, plasminogen, ceruloplasmin, beta1C/1A-globulin, IgG and IgM are especially helpful in the differentiation between primary biliary cirrhosis and chronic active hepatitis. The data are interpreted as suggesting a generally increased synthesis of liver-produced proteins in cholestasis, although more specific factors may modify the degree of increase of the individual proteins.     

Effect of ethynylestradiol on biliary excretion of bile acids, phosphatidylcolines, and cholesterol in the bile fistula rat

The effects of ethynylestradiol on endogenous bile acids, their capacity to conjugate and excrete intravenously infused cholic acid, the concentrations of biliary cholesterol and lecithin, and the individual molecular species of phosphatidylcholine have been determined in male and female Sprague-Dawley rats. Endogenous biliary bile acids were analyzed by gas-liquid chromatography-mass spectrometry. Eleven bile acids were identified and several minor bile acids, primarily muricholates, could not be completely characterized. After 5 days of treatment with ethynylestradiol (1 mg/kg per day), the percentage of cholic acid decreased and the percentage of 6beta-hydroxylated bile acids, including several monounsaturated species, increased. Ethynylestradiol caused a decrease in bile acid-independent bile flow. Intravenous infusion of cholic acid at a high concentration caused cholestasis in control animals but, after ethynylestradiol treatment, cholestasis developed during the infusion of a much lower concentration of cholate, indicating a lowered threshhold for bile acid-induced cholestasis. In the treated rats, there was a slight increase in excretion of unconjugated endogenous bile acids, and a striking impairment of conjugation of intravenously administered cholic acid. One of the few sex-related differences observed was an increased concentration of biliary phospholipids in untreated male rats. Both phospholipid and cholesterol concentrations in the bile were higher in the treated animals. The molar percentage of cholesterol was always 1-2%, but it was slightly higher in treated animals, especially males. Ethynylestradiol treatment also affected biliary phospholipid by causing a marked increase of phosphatidylcholine species containing palmitic and oleic acid residues and a decrease of species containing stearic and linoleic acid residues. There was no increase in biliary excretion of long chain polyunsaturated species, which might have indicated damage to membranes, in response to ethynylestradiol either alone or with cholic acid infusion. Some of these ethynylestradiol-induced changes in biliary bile acid and lipid excretion are probably peculiar to the rat, but others, such as the increase in molar percentage of cholesterol and cholestasis, may be relevant to disorders in man, especially cholesterol gallstones and idiopathic cholestasis of pregnancy.     

Gallstone pancreatitis. Exploration of the biliary system in acute and recurrent pancreatitis

During a five-year period, 82 patients were treated for acute pancreatitis, 63 of whom were proved to have associated biliary tract disease. In 18 of the 63, the accepted preoperative diagnostic measures failed to demonstrate pathologic findings in the biliary system. In 16 of the 18 patients, stones were discovered at the time of operation, although in five they were so small as to be demonstrable only filtering the aspirated bile through gauze. In the two of the 18 without stones, cholecystitis was present. In 14 patients the ducts choledochus and the pancreatic duct had a common path. All patients had no further pancreatitis two to eight years cholecystectomy. In Israel, where alcoholism is rare, three fourths of the cases of acute pancreatitis are associated with gallbladder disease.     

Villous bile duct adenoma with mucinous bile

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman was admitted because of colicky upper abdominal pain. Physical examination was unremarkable. INVESTIGATIONS: Alkaline phosphatase and gamma-glutamyl transpeptidase activities as well erythrocyte sedimentation rate were increased. Sonography revealed mild enlargement of the hepatocholedochal duct to 1.1 cm. Retrograde endoscopy showed a band-like immobile structure in the cystic duct. TREATMENT AND COURSE: At operation the hepatocholedochal duct was found to contain a greenish mucinous mass: no cause was discovered. Three years later a tumor, 1 x 0.5 cm, was found in the common hepatic duct at sonography, with clinical signs of recurrent chronic cholitis and early liver damage. Because of hepatic dysfunction and hypersplenism no surgical intervention was undertaken. When cholestasis progressed further, a partial full-thickness resection of the hepatic duct with removal of the tumor and the mucinous bile had to be performed two years later. Histological examination revealed a villous adenoma with slight epithelial dysplasia and mucus formation. CONCLUSIONS: Villous bile duct adenoma is a very rare cause of cholestasis. Mucous production can lead to mucinous bile, with resulting chronic cholecystitis and secondary biliary cirrhosis. The adenoma should be completely excised because of the danger of malignant transformation and risk of local recurrence.     

Fish mapping of YAC clones at human chromosomal band 7q31.2: identification of YACS spanning FRA7G within the common region of LOH in breast and prostate cancer

OBJECTIVES: The value of serum Ca 19-9 dosage for pancreatic carcinoma diagnosis has been studied in heterogeneous series. The effect of the complications of chronic pancreatitis and pancreatic carcinoma on serum Ca 19-9 value has not been assessed precisely. The aims of this study were to assess: a) the value of Ca 19-9 to differentiate benign from malignant pancreatic disease; b) the influence of complications (particularly, cholestasis). METHODS: The studied population included 179 patients: 126 with chronic pancreatitis (25 females, 101 males, 45 with cholestasis) and 53 with pancreatic carcinoma (27 females, 26 males, 37 with cholestasis). RESULTS: At 37 UI/mL threshold, the specificity and sensitivity of Ca 19-9 were 53 and 95%, respectively. Cholestasis was associated with a significant increase of Ca 19-9 in patients with chronic pancreatitis but not in those with pancreatic carcinoma. At 300 UI/mL threshold, the specificity and sensitivity of Ca 19-9 were 95 and 81% in patients without cholestasis and 87 and 81% in those with cholestasis, respectively. Diabetes mellitus was associated with a significant increase of Ca 19-9 only in patients with chronic pancreatitis without cholestasis. Pancreatic calcifications, pseudocysts, cirrhosis, pleural effusion or ascites were not associated with significant variation of Ca 19-9. CONCLUSION: In patients with pancreatic disease, 300 UI/mL threshold is the most accurate to differentiate benign from malignant disease, whatever the presence of cholestasis.     

Hepatic transplantation for severe ductopenia related to ingestion of thiabendazole]

We report a case of severe cholestasis and sicca syndrome after thiabendazole administration for Strongyloides stercoralis infection in a 26-year-old patient. Liver biopsy, performed 15 days after the onset of jaundice, revealed a marked paucity of bile ducts, and cholestasis rapidly progressed to biliary cirrhosis. Because of the progression of jaundice and the development of esophageal varices, orthotopic liver transplantation was performed, 18 months after the beginning of disease. The mechanism responsible for thiabendazole-induced biliary injury is unknown. The association between sicca syndrome and biliary disease suggests an immunoallergic mechanism against an antigen which could be common to the biliary, lacrimal and salivary duct epithelium.