An early gallstone clearance following repeat piezoelectric lithotripsy

Piezoelectric extracorporeal litotripsy was performed in 128 symptomatic patients with radiolucent gall-bladder stones to assess the significance of disintegration in fragment clearance. Up to 10 repeat lithotripsy sessions were scheduled to achieve a fragment target size of <3 mm. Fragmentation assessed by the size of the largest fragments after the last session was graded into three classes. I: sludge-like disintegration, 18%; II: <3 mm (mean ± s.d., 1.7 ± 0.5 mm), 56%; and III: < 3 mm (3.3 ± 0.6), 26%. All patients were initially subjected to lithotripsy alone. Bile acid dissolution therapy was started only when ultrasonography failed to show the evidence of decrease in the <3 mm fragments during a 1 month follow up. Finally, 69 patients (54%) were treated by lithotripsy alone, and the remaining 59 received additional dissolution therapy at a mean period of 2.5 months after the initial lithotripsy. The rate of complete clearance in class I, II and III patients was 91, 42 and 10% at 6 months and 100, 68 and 49% at 18 months, respectively. Significant differences were noted between the three fragmentation grades (I vs II, III, P <0.0001; II vs III, P <0.02). The patients with complete clearance within 6 months were seen only in those treated by lithotripsy alone, while the majority (87%) of patients with complete clearance during the later period were seen in those treated by additional dissolution therapy. We conclude that a high degree of fragmentation appears to lead stones to an earlier period clearance, and reduce the need for dissolution therapy.     

Effect of extracorporeal shock wave lithotripsy and ursodeoxycholic acid on gallbladder motility

Extracorporeal shock wave lithotripsy and dissolution agents are useful nonsurgical therapies for gallstones. Their effect on gallbladder emptying is unclear. We evaluated emptying by ultrasonography before and after lithotripsy in 50 patients on ursodeoxycholic acid or placebo and in nine controls. At baseline, patients had normal (68.8±3.2%) or delayed emptying (14.5±3.3%). In a subset of 24 patients, lithotripsy increased fasting volume (26.6±3.0 to 43.8±5.0 ml,P<0.005), postprandial volume (11.3±3.1 ml to 22.9±3.0 ml,P<0.05), and decreased ejection fraction (70.0±4.1% to 42.7±6.0%,P<0.0005). There was an inverse linear correlation between power and ejection fraction,r=–0.43,P<0.005. Ursodeoxycholic acid increased fasting (23.3±2.2 ml to 36.7±4.6 ml,P<0.005) and postprandial volume (11.1±1.8 to 17.6±2.5,P<0.005). Treatment with ursodeoxycholic acid resulted in a greater decrease in fragment size compared to placebo after lithotripsy in patients with fragment size greater than 6 mm. In conclusion, both lithotripsy and ursodeoxycholic acid have an effect on gallbladder emptying.     

Extracorporeal shock wave lithotripsy of gallstones revisited: current status and future promises

The improvement and refinement of extracorporeal shock wave lithotripsy (ESWL) has made this non-invasive treatment modality not only more effective, but also applicable to a larger population of gallstone patients. It can be performed safely on an outpatient basis. Advances in lithotripsy technology have made it possible to fragment stones into very small, sand-like particles (pulverization), which clear the gall-bladder faster than large fragments. Recent studies provide evidence that adjuvant bile acids may not be necessary in most cases in which pulverization is achieved. Good gall-bladder emptying appears both to promote the clearance of gallstones after ESWL and to decrease their recurrence. Although generally found to be more expensive than surgery if bile acids are used, ESWL should be cost-effective, as bile acids may not be necessary in all patients. Elderly patients with radiolucent, solitary and less than 30 mm gallstones can particularly benefit from lithotripsy.     

Extracorporeal shock wave lithotripsy for bile duct stones: An Australian experience

Choledocholithiasis requires prompt therapy, particularly if complicated by ascending cholangitis. Endoscopic sphincterotomy with balloon and basket extraction clears the bile duct in 90% of patients. Failure is usually associated with large stones, that is, greater than 2 cm. Until recently such patients would have required surgical intervention. In 1986 St Vincent's Hospital installed a Dornier HM3 Lithotriptor to be used for both urinary tract and bile duct calculi. A retrospective analysis of patients referred for extracorporeal shock wave lithotripsy (ESWL) to bile duct stones was performed. There were 47 patients (28 female, 19 male) with an average age of 76 years. Twenty-two patients had a single stone with a mean diameter of 2.4 cm and 25 had multiple stones. In two patients the stone was not able to be visualized, so ESWL could not be performed. Complete stone clearance was achieved without further intervention in 13 patients, and in a further 23 after endoscopic extraction of fragments. In five patients only partial duct clearance was achieved. However, this provided palliation and enabled the patient to be discharged. Surgical intervention was required in the remaining four cases. Overall success rate was 80% with a further 11% being palliated with improved biliary drainage. There were no serious adverse effects from ESWL. All patients were discharged from hospital. Mortality at 30 days was 4.7% and at 6 months was 19.4%. One patient succumbed to ascending cholangitis 22 weeks post-ESWL (2.7%). All other deaths were unrelated to ESWL or biliary disease. We conclude that ESWL is a safe and effective treatment for bile duct stones not amenable to endoscopic extraction.     

Multiple main pancreatic duct stones in tropical pancreatitis: safe clearance with extracorporeal shockwave lithotripsy

BACKGROUND AND AIM: Extracorporeal shockwave lithotripsy (ESWL) has an established role in the management of pancreatic ductal stones. Its efficacy in management of multiple stones in tropical pancreatitis is unknown. The aim of this study was to prospectively evaluate: (i) the efficacy of main pancreatic duct stone clearance; and (ii) associated complications with ESWL therapy in tropical pancreatitis. METHODS: Consecutively recruited patients with tropical pancreatitis underwent fragmentation of main pancreatic duct stones using ESWL. Endoscopic retrograde cholangiopancreatography (ERCP) using standard techniques was performed to manage residual stones. Complete, partial and unsatisfactory clearance was defined as >90%, 50-90% and <50% of stone clearance, respectively. Clinical and technical data were collected on a pre-formatted data sheet. Statistical analysis was performed on an intention-to-treat basis. RESULTS: A total of 250 patients (mean+/-SD age 35.2+/-11.9 years; 66% men), 86.8% with multiple radio-opaque stones, underwent ESWL between February 2004 and May 2005. Of the 250 patients, 149 (59.6%) achieved complete clearance and 59 (23.6%) achieved partial clearance of pancreatic calculi. Main pancreatic ductal decompression was achieved in 70.0% (175/250) of patients. Complications occurred in 5.6% (14/250) during ESWL and in 1.2% (3/250) during ERCP. A mean of 1.3 sessions, with mean+/-SD 5.5+/-0.7 intensity setting, 85.8+/-13.5 pulses per minute and 3862+/-1426 shocks per session were required. CONCLUSION: Clearance of multiple main pancreatic duct stones in patients with tropical pancreatitis is safely performed via ESWL followed by ERCP ductal drainage.     

Extracorporeal shock wave lithotripsy of large difficult common bile duct stones: Efficacy and analysis of factors that favor stone fragmentation

Background and Aim:  Difficult common bile duct stones (CBD) are those not amenable to extraction by the standard technique of sphincterotomy followed by use of a Dormia basket or balloon. The role of extracorporeal shock wave lithotripsy (ESWL) in stone fragmentation and clearance of difficult CBD stones and the factors which favor fragmentation were prospectively evaluated in the present study.
Methods:  A total of 283 patients with large CBD stones were subjected to ESWL. A maximum of 5000 shocks was delivered per session until CBD stones were fragmented to less than 5 mm diameter. CBD was cleared by biliary endotherapy using a basket or balloon. Outcome was assessed by CBD clearance.
Results:  Total CBD clearance was achieved in 239 patients (84.4%) and partial CBD clearance in 35 patients (12.3%). Three or fewer sessions of ESWL were required in 74.6% of patients. Minor complications were seen in 45 patients (15.9%). There was no procedure-related mortality. Epidural anesthesia, shock frequency of 90/min, radiolucent calculi and presence of fluid around the calculus helped in better fragmentation.
Conclusion:  A high success rate, negligible complications and non-invasive nature of the procedure make ESWL a useful tool for removing large CBD stones.     

Sonographically-guided extracorporeal shockwave lithotripsy for pancreatic stones in patients with chronic pancreatitis

Over a 2 year period, 10 patients with pancreatic stones due to alcohol induced chronic pancreatitis (proven by endoscopic retrograde pancreatography) underwent extracorporeal shockwave lithotripsy. Prior to shockwave therapy, all patients underwent endoscopic sphincterotomy. Targeting of shockwave lithotripsy was exclusively performed under sonographic control. All patients were treated with a second generation electrohydraulic spark gap lithotriptor and fragmentation of concrements could be achieved in all cases. Complete duct clearance was confirmed in seven patients by endoscopic retrograde pancreatography in one session, with endoscopic fragment extraction by basket and/or balloon catheter. In three patients, balloon dilation of concomitant strictures located in the head of the pancreas was performed prior to fragment extraction. All stone-free patients showed no further symptoms over the follow-up period of 12 months. Three patients in whom complete extraction of fragments was not successful experienced minor symptoms over the 12 month follow-up period.     

Increase of sulfated ursodeoxycholic acid in the serum and urine of patients with chronic liver disease after ursodeoxycholic acid therapy

The present study was undertaken in order to investigate the influence of ursodeoxycholic acid (UDCA) on the composition of sulfate-conjugated bile acids in the serum and urine of patients with chronic active hepatitis and compensated liver cirrhosis. After a 12 week UDCA treatment (600 mg/day), total serum bile acid concentration increased two-fold in patients with compensated liver cirrhosis and increased slightly in patients with chronic active hepatitis. The percentage of sulfated bile acids significantly increased in patients with both compensated liver cirrhosis and chronic active hepatitis. UDCA made up 63% of the total serum bile acids in compensated liver cirrhosis and 61% in chronic active hepatitis after UDCA treatment. Of the serum bile acids after UDCA treatment, 35.2 and 53.9% of UDCA was sulfate conjugated in compensated liver cirrhosis and chronic active hepatitis, respectively. Urinary excretion of total bile acid and UDCA after UDCA treatment in compensated liver cirrhosis were higher than in chronic active hepatitis. UDCA made up 68% of the total urinary bile acids in compensated liver cirrhosis and 64% in chronic active hepatitis after UDCA treatment. Of the urinary bile acids after UDCA treatment, 51.8 and 54.8% of UDCA was sulfate conjugated in compensated liver cirrhosis and chronic active hepatitis, respectively. UDCA treatment for compensated liver cirrhosis was less effective than for chronic active hepatitis. We found that sulfate conjugation is one of the major metabolic pathways for UDCA after UDCA treatment in chronic liver diseases.     

Clinical comparison of extracorporeal piezoelectric lithotripsy (EPL) and intracorporeal electrohydraulic lithotripsy (EHL) in difficult bile duct stones

Today, nearly 90% of common bile duct stones are extracted endoscopically. Problems are encountered if there are large stones or a duct stenosis. Extracorporeal piezoelectric lithotripsy (EPL) as well as intracorporeal electrohydraulic lithotripsy (EHL) serve as an alternative to surgical intervention for those few patients in whom endoscopic measures have failed. A total of 35 patients with common bile duct stones in whom conventional endoscopic treatment had failed were selected on the condition that stone visualization through ultrasound was possible and that the papilla was within easy reach of the endoscope. Patients fulfilling the inclusion criteria were randomly treated either by EPL or EHL. The average age of our patients was 73 years. The main reasons for failure of conventional endoscopy were due to the large size of the stones (13 patients), impacted stones (16), or the presence of a biliary stricture (6). In the EPL group, visualization of the stones by ultrasound and ensuing treatment were possible in 16 of 18 patients (89%); stones could be fragmented in 15 patients. In 13 patients, the biliary tree could then be completely freed of calculi; the success rate was 72% for all the patients (13 of 18). On average, the patients had 2.3 treatments on the lithotripter, and 3870 shock waves were applied per treatment. In the EHL group stones were successfully fragmented in 13 of 17 patients (76.5%). The average number of treatments was 1.4. Comparing both therapies, there was no difference in stone-free rates. In both groups, additional endoscopic interventions were necessary to clear the bile duct. The mean number of lithotripsy sessions was less in the EHL group (1.4 vs 2.3). There were no major differences in average hospital stay, 30-day mortality was zero in both groups. Combined treatment including EPL, EHL, and intracorporeal laser lithotripsy was finally successful in 32 patients (91.5%). It is concluded that EHL might be the method of choice for smaller, single stones in the more proximal parts of the common bile duct. In these cases, complete duct clearance in one lithotripsy session can be achieved. Multiple and large stones are probably best accessible to EPL. With a combination of the methods described, the bile duct can be cleared of concrements in almost every instance. As a result, surgery for choledocholithiasis has become the absolute exception.This work was presented in part at the 1993 Annual Meeting of the american Gastroenterological Association in Boston and published in abstract form (Gastroenterology 104:A347, 1993).     

The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: A prospective, multicenter study.

Aim: Treatment with ursodeoxycholic acid (UDCA) improves the survival of stage I and II primary biliary cirrhosis (PBC) patients. However, new therapeutic options are needed for patients who are refractory to UDCA and for those whose disease is at an advanced stage. Bezafibrate could be useful in PBC treatment, since it increases phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids, which are increased with cholestasis. Methods: We conducted two prospective, multicenter randomized open studies in non-cirrhotic patients with PBC to evaluate the efficacy of bezafibrate. One study compared UDCA and bezafibrate monotherapy (study 1: 45 patients [37 females], mean age 55.9 years), and the other evaluated the addition of bezafibrate to patients who were refractory to UDCA (study 2: 21 patients [18 females], mean age 54.1 years). Results: Study 1 demonstrated that bezafibrate monotherapy was as effective as UDCA and study 2 revealed that bezafibrate combined with UDCA was effective in improving and maintaining biliary enzymes where the ineffectiveness of long-term treatment with UDCA was confirmed. Conclusion: This multicenter, randomized, open study revealed that combination therapy of bezafibrate and UDCA improved biliary enzymes in non-cirrhotic Japanese patients with PBC refractory to UDCA. Further studies are needed to evaluate whether combination therapy improves histological staging and prognosis.     

Geographic variations in structure and composition of gallstones and their correlation with brittleness

Abstract Cholesterol gallstones obtained from different geographic regions have been reported to show significant differences in their minor chemical constituents. We undertook the present study with two objectives: (i) to investigate the possible physicochemical and radiological differences beween cholesterol gallstones obtained from Indian and German patients; and (ii) to compare the brittleness of the two stone groups. Forty Indian and 36 German gallstones (matched in size and shape) were subjected to assessment of physical characteristics, in vitro computed tomography (CT) and chemical analysis. German stones more often had a stone density distribution index of ≥50 Hounsfield units (HU) (26 vs 14; P <0.01), peripheral calcification (18 vs 9; P <0.02), maximum CT density ≥ 90 HU (17 vs 9; P <0.05) and significant calcium carbonate (9 vs 5; P <0.05), compared to Indian stones. The in vitro lithotripsy performed with the Siemens Lithostar Plus machine at a constant energy level showed the German stones to be more brittle (easy to fragment), more often requiring <1000 shocks for fragmentation (25/36; 69%) compared to Indian stones (18/40; 45%, P <0.05). Gallstones from different geographic regions may show significant variations in their physicochemical characteristics that may explain the differences in their brittleness to lithotripsy.     

Treatment of gallstones with piezoelectric lithotripsy and oral bile acids. A multicenter study

The efficacy of the combination of piezoelectric lithotripsy and oral bile acids in the treatment of gallbladder stones was assessed. Three hundred and sixty-three patients with symptomatic radiolucent gallstones in functioning gallbladder were treated in five medical centers using the same protocol with the EDAP LT 01 lithotripter. No anesthesia, analgesia or sedation was used. After one session of lithotripsy, fragmentation was observed in 89% of the patients, and satisfactory fragmentation (fragments less than or equal to 5 mm) in 29%. The satisfactory fragmentation rate was higher in patients with solitary stones less than or equal to 20 mm than in patients with solitary stones 21-35 mm or multiple stones (p less than 0.001). After multiple sessions (mean 1.6 session/patient, range 1-5) the overall rate of satisfactory fragmentation was 50%. After 12 months on oral bile acid therapy, complete clearance of the gallbladder was observed in 69% of patients with solitary stones less than or equal to 20 mm, 25% of patients with solitary stones 21-35 mm and 37% of patients with multiple stones. No complication was observed during the lithotripsy. During follow-up under bile acid therapy, there were five complications (1.4%): four patients had acute cholecystitis and one had mild, self-limited pancreatitis. We conclude that piezoelectric lithotripsy with the EDAP lithotripter is a safe and effective treatment which can be performed in outpatients. Satisfactory fragmentation and rapid disappearance of stones are obtained mainly in patients with solitary stones less than or equal to 20 mm.     

Effect of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis C virus infection

Aim:  Many reports have revealed ursodeoxycholic acid (UDCA) to be effective against chronic hepatitis C virus (HCV). However, some cases resist this therapy and the mechanism of action remains unclear. In this study, UDCA was administered to patients with chronic HCV and the correlation between the bile acids of the biliary bile and serum and the drug efficacy was investigated.
Methods:  Fifteen patients were given 600 mg/day of UDCA for more than 24 weeks. The serum bile acid concentrations and biliary and serum bile acid were collected before and after 24 weeks of UDCA treatment, and composition determined by high-performance liquid chromatography.
Results:  The treatment was effective in nine cases (ALT decreased to less than twice the normal values 80 IU/L) and ineffective in six cases. There was no significant difference in the serum bile acid concentrations before and after UDCA treatment between the values of both cases. After UDCA treatment, the serum percentage of UDCA (effective, 62.5 ± 2.0; ineffective, 53.5 ± 2.5, ( P  = 0.02)) and the percentage of chenodeoxycholic acid (CDCA) showed no remarkable changes. In the biliary bile the percentage of CDCA (effective, 30.9 ± 2.0; ineffective, 20.0 ± 3.0, ( P  = 0.007)) and the percentage of UDCA showed no remarkable changes.
Conclusion:  In the effective cases, the percentage of UDCA in the serum and the percentage of CDCA in biliary bile were significantly higher than in the ineffective cases. This indicates that, when effective, CDCA decreases in hepatocytes and this reduction contributes to hepatoprotection.     

Gallstone recurrence after successful dissolution therapy

After successful dissolution therapy of cholesterol gallbladder stones bile again becomes supersaturated and recurrent gallstones may develop. Three different postdissolution treatments [500 mg ursodeoxycholic acid (UDCA) per day (N=14, group I), 100 mg aspirin per day (N=14, group II) and diet (N=15, group III) versus a control group (no treatment,N=15, group IV) aimed at preventing recurrence of gallstones were investigated in a prospective, randomized study in 58 gallstone patients (33 female, 25 male) after complete stone clearance. Bile samples (prior to dissolution therapy and at stone recurrence) were investigated for biliary cholesterol (C), phospholipids (PL), total bile acid concentration (BA), cholesterol saturation index (CSI), total lipid concentration (TLC), total biliary protein concentration (TP), and nucleation time (NT). In group IV multiple gallstones tended to recur more often than solitary stones (66.7% vs 16.7%) whereas in groups I–III only solitary stones recurred. Recurrent gallbladder stones were detectable in 10 patients (eight patients in group IV and one each in groups I and II, respectively) within one year after dissolution and in two patients (one each in groups III and IV, respectively) after 15 months. Furthermore, the probability of stone recurrence was significantly higher in untreated patients as compared to treated patients. In nine (group IV) of 12 patients with recurrent stones NT, C, CSI, PL, BA, TLC, TP, and bile acid spectrum remained nearly unchanged as compared to their pretreatment values, whereas in three (groups I–III) of 12 cases a decrease in C, CSI, and TP was observed during therapy. However, in each of these three patients, initial and after-treatment TP was significantly higher and NT shorter as compared to groups I–IV. Furthermore, in these cases (N=3) NT was prolonged, whereas no significant changes were found in PL, BA, TLC, and bile acid spectrum. Recurrence of gallstones, which seems to occur more likely in patients with multiple stones as compared to solitary stones, will happen in the early stage after stone clearance, again causing biliary pain. UDCA, aspirin or diet will reduce the probability for recurrent stones after complete gallstone dissolution.     

Extracorporeal shock wave lithotripsy for pancreatic duct stones: an observational study

Abstract

Introduction: Previous studies suggest that fragmentation of pancreatic duct stones (PDS) using extracorporeal shock wave lithotripsy (ESWL) is associated with pain relief. However, the treatment may not be effective in certain subgroups.

Aim: To evaluate predictors of pain relief after ESWL in patients with chronic pancreatitis and PDS.

Methods: Retrospective study including patients with chronic pancreatitis undergoing ESWL for painful PDS. Analgesic use before and after the ESWL procedure was registered. We defined adequate pain relief after ESWL as ‘pain-free without analgesics or with use of weak analgesics as needed’. The study was approved by the Danish Data Protection Agency (approval number: AHH-2017-048).

Results: We included 81 patients (median age 58 years; 63% men; 68% alcoholic pancreatitis). Patients underwent one to seven ESWL procedures (mean 1.7). A concurrent ERCP was performed in 17%. All patients used analgesics before the ESWL procedure (68 used opioids). After ESWL, 43 still used opioids. Thirty-two patients achieved adequate pain relief. Univariable regression analysis showed that older age predicted adequate pain relief (OR 1.09;1.03–1.16; p?=?.002) as did location of the stone in the head or neck (OR 2.59;1.04–6.45; p?=?.041). In multivariable analysis, we found that the only two predictors of adequate pain relief were age (p?=?.002) and the location of the stones (p?=?.039).

Conclusion: After the ESWL, about four out of ten patients are pain-free without medication or able to manage their pain with weak analgesics. Age and the location of the stones may be considered when evaluating if patients are eligible for referral to ESWL.     

Improved liver tests and greater biliary enrichment with high dose ursodeoxycholic acid in early stage primary biliary cirrhosis

BACKGROUND: Ursodeoxycholic acid is currently used for the treatment of primary biliary cirrhosis at 13-15 mg/kg/day, but liver tests of some patients do not return to normal at this dose. Studies reported here were designed to test whether a higher dose of ursodeoxycholic acid than is currently used would induce still greater biliary enrichment of ursodeoxycholic acid and whether such enrichment would lead to still further improvement in liver tests in patients with early primary biliary cirrhosis. METHODS: A total of 20 patients with histologically proven primary biliary cirrhosis were enrolled. Patients had early stage primary biliary cirrhosis as serum bilirubin levels were normal and the Mayo risk score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day of ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day. The order of periods was randomized. Each treatment period lasted 3 months followed by a further 3 months during which a standard dose of ursodeoxycholic acid was given. At the end of each treatment period, liver tests were evaluated, and biliary bile acid pattern of duodenal bile was determined using high pressure liquid chromatography. RESULTS: Biliary bile acid became enriched in ursodeoxycholic acid in direct relationship to dosage [r = 0.84, p < 0.001). At doses of 1800 mg/day (25-35 mg/kg/day), biliary ursodeoxycholic acid averaged 69 +/- 6.6%. A progressive decrease of alanine aminotransferase [p < 0.0001), aspartate aminotransferase [p < 0.001) and alkaline phosphatase [p < 0.02) was observed with increasing concentrations of ursodeoxycholic acid in bile. Biochemical liver tests showed a stronger correlation with biliary concentrations of ursodeoxycholic acid than with the administered dose. CONCLUSIONS: In early primary biliary cirrhosis, higher dose ursodeoxycholic acid appears to be more effective than doses currently recommended.     

A two year controlled trial examining the effectiveness of ursodeoxycholic acid in primary biliary cirrhosis

Abstract Forty-six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo-controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 year period. The two groups were well-matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin {MCD 5 μmol/L [95% confidence interval (CI) 1 to 12] at 1 year and 5 μmol/L (95% CI 1 to 9) at 2 years}, alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long-term fall in alkaline phosphatase [median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase [median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group [median rise 2 μmol/L (95% CI 1 to 9)]. Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant.
Ursodeoxycholic acid did not generally influence stage progression or histological features, although a smaller percentage of non-cirrhotic patients were documented as having developed cirrhosis on UDCA compared to placebo (14 vs 57%) over the 2 years. There appeared to be no consistent effect on pruritus and general well-being. The medication was well-tolerated and safe. In conclusion, UDCA appears to have beneficial effects on some serum biochemical markers in primary biliary cirrhosis and so may have a role in retarding disease progression. It could be useful in combination with an immunosuppressive or an anti-fibrotic agent.     

Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis

Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients with primary biliary cirrhosis, suggesting that UDCA has immunomodulating effects. We investigated the effect of UDCA in patients with autoimmune hepatitis (AIH) which is characterized by immunological abnormalities. Eight patients with type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the criteria of the International Autoimmune Hepatitis Group, five patients were diagnosed as definite and three as probable type 1 AIH. Liver function tests were performed every 4 weeks, before and during UDCA therapy and the serum levels of anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G and gamma globulin were determined every 3 months. The levels of serum aspartate aminotransferase and alanine aminotransferase significantly decreased from 154 ± 24 IU/L and 170 ± 17 IU/L before UDCA therapy to 31 ± 3 IU/L and 25 ± 5 IU/L ( P < 0.001) after 1 year of treatment and 28 ± 2 IU/L and 23 ± 4 IU/L ( P < 0.001) after 2 years of treatment. After 2 years of treatment, the levels of serum immunoglobulin G and gamma globulin significantly decreased ( P < 0.05) and ANA titres (5/8 patients) were reduced and SMA (3/5. patients) became negative. Furthermore, hepatic histopathological changes of four patients were assessed after 1 year of treatment, and an improvement of intrahepatic inflammation, but not fibrosis, was observed. In conclusion, these results suggest that UDCA has a beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.     

Effects of ursodeoxycholic acid in esophageal motility and the role of the mucosa. An experimental study

Esophageal motor abnormalities are frequently found in patients with gastroesophageal reflux disease. The role of bile in reflux‐induced dysmotility is still elusive. Furthermore, it is questionable weather mucosal or muscular stimulation leads to motor dysfunction. The aims of this study were to analyze (i) the effect of bile in the amplitude of esophageal contractions; and (ii) the effect of mucosal versus muscular stimulation. Eighteen guinea pig esophagi were isolated, and its contractility assessed with force transducers. Three groups were studied. In group A (n= 6), the entire esophagus was incubated in 100 µmL ursodeoxycholic acid for 1 hour; in group B (n= 6) the mucosal layer was removed and the muscular layer incubated in 100 µmL ursodeoxycholic acid for 1 hour; and in group C (n= 6) (control group) the entire esophagus was incubated in saline solution. In all groups, five sequential contractions induced by 40 mm KCl spaced by 5 minutes were measured before and after incubation. Contractions amplitudes before incubation were 1.319 g, 0.306 g, and 1.795 g, for groups A, B, and C, respectively. There were no differences between groups A and C (P= 0.633), but there were differences between groups A and B (P= 0.039), and B and C (P= 0.048). After incubation amplitude of contraction were 0.709 g, 0.278 g, and 1.353 g for groups A, B, and C, respectively. Only group A showed difference when pre and post‐stimulation amplitudes were compared (P= 0.030). Our results show that (i) bile exposure decreases esophageal contraction amplitude; and (ii) the esophageal mucosa seems to play an important role in esophageal motility.