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PubMed2005

Secondary sclerosing cholangitis: a comparison to primary sclerosing cholangitis.

OBJECTIVES: The natural history of secondary sclerosing cholangitis (SSC) is ill-defined. In order to better determine the natural history of this condition, we retrospectively reviewed data from the Mayo Clinic in Rochester, Minnesota. We also compared the natural history of patients diagnosed with SSC to a cohort with a diagnosis of primary sclerosing cholangitis (PSC). METHODS: We used a computer-assisted search to identify patients with a diagnosis of SSC seen from 1992 to 2002. The diagnosis was confirmed by chart review and information about age, gender, etiology, therapy, and clinical course was sought. We excluded those presumed SSC patients who had a history of inflammatory bowel disease, those with malignancy at the time of diagnosis, and those who had undergone liver transplantation prior to the diagnosis of SSC. Patients with PSC matched for age, gender, and serum bilirubin level served as disease controls. RESULTS: We identified 31 patients, average age 57, (range 28-79). The causes of SSC included surgical trauma from cholecystectomy (13 patients), intraductal stones (12 patients), recurrent pancreatitis (4 patients), and abdominal injury (2 patients). Nine patients with SSC ultimately required liver transplantation and 4 patients have died. When compared to matched patients with PSC, the survival free of transplant was significantly shortened (p<0.03). CONCLUSIONS: When the long-term outcome of SSC patients was compared to matched PSC controls, the SSC patients had a poorer outcome. The natural history of SSC is characterized by a shortened life expectancy.

Abdominal Injuries↗
PubMed2005

Clinical differences between primary sclerosing cholangitis and sclerosing cholangitis with autoimmune pancreatitis.

OBJECTIVES: Sclerosing cholangitis (SC) with autoimmune pancreatitis (AIP) is similar to primary sclerosing cholangitis (PSC) with regard to cholangiographic findings, but only the former responds well to steroid therapy. This report concentrates on the clinical differences between these diseases. METHODS: The presenting complaint or abnormality, associated disease, cholangiographic findings, pancreatic changes, treatment, and clinical course were studied for several cases of PSC (n = 27) and SC with AIP (n = 20). RESULTS: SC with AIP as a diagnosis occurs abruptly with obstructive jaundice compared with PSC where diagnosis is often based on findings of asymptomatic liver test abnormalities. In addition, inflammatory bowel disease is only associated with PSC. The most prominent features of cholangiograms for the SC with AIP cases were stenosis of the lower common bile duct. However, sclerosing changes in the intra- and extrahepatic bile ducts or hilar hepatic region were observed for half of the cases. Only PSC showed stage III or IV liver biopsy findings. IgG4 was significantly higher in SC with AIP. CONCLUSIONS: SC with AIP and PSC are different clinical entities.

Adult↗
PubMed1969

Primary intrahepatic obliterating cholangitis: a possible variant of 'sclerosing cholangitis'.

A sclerosing cholangitis confined to the intrahepatic ducts occurred in a 64-year-old man with a clinical picture of prolonged cholestatic jaundice. Two laparotomies and an operative cholangiogram demonstrated a normal extrahepatic biliary tree. The most prominent histological feature in the liver biopsy was the replacement of medium-sized bile ducts by fibrous cords. Electron microscopic examination of the liver showed changes attributable to cholestasis and cholesterol clefts in dense bodies. Needle-like and curved membrane-bounded inclusions of an obscure nature were also observed in some of the dense bodies. It is suggested that this case, together with nine histologically similar cases which have been labelled in the literature as ;primary biliary cirrhosis', represents a subgroup of sclerosing cholangitis in which only the intrahepatic ducts are affected.

Bile Ducts, Intrahepatic↗
PubMed1996

Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.

Overlapping features between primary sclerosing cholangitis (PSC and autoimmune hepatitis (AIH) have previously been noted. To assess systematically similarities between these disorders, we have evaluated 114 PSC patients (36 women; 78 men), all confirmed by endoscopic retrograde cholangiography (ERC), according to a scoring system proposed by The International Autoimmune Hepatitis Group for the diagnosis of AIH. The scoring system attributes positive or negative scores to the parameters sex, ratio of elevation of serum levels of alkaline phosphatase (ALP) vs. aminotransferase, serum levels of immunoglobulins and autoantibodies, viral markers, history of drug and alcohol intake, genetic factors, liver histology, and response to therapy. Two of the PSC patients (2%) obtained scores above 15 before treatment, satisfying the diagnostic criterion of "definite" AIH. Thirty-eight patients (33%) scored between 10 and 15 points and could be classified as "probable" AIH. The serum level of immunoglobulin G (IgG) was elevated in 68 patients (61% of 111 cases tested), and positive titers of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) were detected in 24 patients (22% of 111 cases tested). Thirty-five of the PSC patients (33% of 105 evaluable biopsy specimens) obtained positive scores for histological features similar to those of AIH, but the total score for histology was in the negative range in 72 patients (69%) because of the presence of biliary changes. The frequent finding of high scores in PSC patients underlines the similarities PSC may have with AIH. A modification of the scoring system, in particular by increasing the negative score for histological biliary changes, would improve its potential to discriminate between AIH and PSC.

Adolescent↗
PubMed1999

Detection of IgA, IgM, and IgG subclasses of anti-M2 antibody by immunoblotting in autoimmune cholangitis: is autoimmune cholangitis an early stage of primary biliary cirrhosis?

Autoimmune cholangitis (AIC) has been proposed as a distinct disease entity from primary biliary cirrhosis (PBC), without antimitochondrial antibody (AMA) and anti-M2 antibody but with a high titer of antinuclear antibody (ANA) in the serum. However, negativity for AMA and anti-M2 antibody was determined by different methods in different studies. We hypothesized that anti-M2 antibody negativity in AIC resulted from methodological differences, including selection of the immunoglobulin subclass of the autoantibody. Twenty-three patients compatible with AIC whose serum tested negative for AMA and positive for ANA (> or = 1:80) were compared with 71 AMA-positive PBC patients. Laboratory findings, histology, and the pattern of anti-M2 antibody assessed by immunoblotting were compared. Alkaline phosphatase, total bilirubin, total cholesterol, and IgM values were lower in patients with AIC (P < 0.05, 0.01, respectively). Anti-smooth muscle antibody was detected more frequently in patients with AIC (P < 0.01). However, anti-M2 antibody was detected using immunoblotting not only in PBC but also in AIC cases. IgA class alone, IgM class alone, or both IgA and IgM classes of anti-M2 antibody were detected in 13%, 17%, and 22% of AIC patients, respectively, whereas they were not detected in PBC patients (P < 0.05, P < 0.01, P < 0.01). IgG class anti-M2 was detected in all patients with PBC, whereas it was detected in 48% of patients with AIC (P < 0.01). Histological evaluation showed that the early stages of disease were found more frequently in AIC (78%) than in PBC patients (39%) (P < 0.01). Anti-M2 antibody was detected by immunoblotting in all AIC patients. Hence, AIC is not a distinct disease from PBC. For diagnosing AIC and/or PBC, anti-M2 antibody should be examined by the immunoblotting assay to detect not only IgG but also IgA and IgM subclasses.

Adult↗
PubMedDate not supplied

Bile duct bacterial isolates in primary sclerosing cholangitis and certain other forms of cholestasis--a study of bile cultures from ERCP.

BACKGROUND/AIMS: The pathogenesis of the inflammatory lesion in primary sclerosing cholangitis is unknown. We have recently demonstrated a high positivity rate of bacterial cultures in bile and bile ducts of explanted livers from primary sclerosing cholangitis patients compared with patients with primary biliary cirrhosis. In particular, alpha-hemolytic Streptococci was a frequent finding, suggesting an etiopathogenic role of that particular bacteria in primary sclerosing cholangitis. We therefore wanted to study naive primary sclerosing cholangitis patients and compare them with primary sclerosing cholangitis patients that have previously undergone endoscopic retrograde cholangiopancreatography, in order to evaluate the potential role of these bacteria in the etiopathogenesis in primary sclerosing cholangitis. METHODOLOGY: Samples for bacterial cultures were obtained during a diagnostic endoscopic retrograde cholangiopancreatography. PARTICIPANTS: 12 naive primary sclerosing cholangitis patients, 10 patients with primary sclerosing cholangitis, previously investigated using endoscopic retrograde cholangiopancreatography, 47 patients with choledocholithiasis, 19 patients with cancer obstructing the common bile duct, and 29 patients with other forms of biliary disorders. RESULTS: Positive cultures were obtained from 3 of the naive primary sclerosing cholangitis patients and from 6 of the primary sclerosing cholangitis patients with previous endoscopic retrograde cholangiopancreatography (NS). The most frequent finding in all the primary sclerosing cholangitis patients was alpha-hemolytic Streptococci. Bacteria were cultured from the bile in 64% of the patients with choledocholithiasis, higher than the 25% in the naive primary sclerosing cholangitis patients (P < 0.03), and in 56% of patients with obstructing cancer (NS) but in only 24% of patients with other forms of biliary disorders, all of whom, except 4, had normal cholangiograms. In the 22 patients with primary sclerosing cholangitis, 75% of the positive bacterial cultures consisted of Gram-positive isolates and 25% were enteric bacteria, which differed statistically from the 74% enteric bacteria and 26% Gram-positive bacteria in the patients with common duct stone (P < 0.01). CONCLUSIONS: Alpha-hemolytic Streptococci do not seem to play a primary role in the etiopathogenesis of primary sclerosing cholangitis since most naive primary sclerosing cholangitis patients were found to have negative bacterial cultures. This does not exclude the possibility that they play a role in the progression of primary sclerosing cholangitis following infection in conjunction with the first endoscopic retrograde cholangiopancreatography.

Bacteria↗
PubMed1984

Manifestations of nonsuppurative cholangitis in chronic hepatobiliary diseases: morphologic spectrum, clinical correlations and terminology.

The features of nonsuppurative cholangitis were studied in liver biopsy specimens from 185 patients with chronic active hepatitis (CAH), 280 patients with primary biliary cirrhosis (PBC), and 55 patients with primary sclerosing cholangitis (PSC). Specimens from patients with other liver diseases in which the presence of nonsuppurative cholangitis had been recorded were also studied. We identified four types of nonsuppurative cholangitis: granulomatous cholangitis, lymphoid cholangitis, fibrous cholangitis, and pleomorphic cholangitis. Granulomatous cholangitis almost always seemed to be destructive; the other types were either destructive or nondestructive. Granulomatous cholangitis was, for all practical purposes, diagnostic of PBC and the obliterative form of fibrous cholangitis was similarly diagnostic for the hepatic manifestations of PSC in adults and paucity of intrahepatic bile ducts in infants. All other types of cholangitis were found in CAH, PBC, PSC, and other liver diseases. Thus, the term "nonsuppurative cholangitis" describes a spectrum of morphologic lesions that differ in incidence, morphogenesis, usefulness for liver biopsy diagnosis, and, probably, pathogenesis.

Bile Ducts↗
PubMed1992

Risk factors and classification of acute suppurative cholangitis.

A prospective study was performed in 1282 patients with common bile duct stones to determine the clinical and laboratory parameters that could predict cholangitis, and the factors associated with greater severity of cholangitis. Patients were divided into two groups, with or without acute cholangitis, depending on the macroscopic appearance of bile aspirated from the common bile duct during surgery. Acute cholangitis was diagnosed when the aspirated fluid was turbid or clearly pus; the typical Charcot's triad was present in only 22 per cent of patients with acute cholangitis. Several clinical and laboratory parameters were significantly more common in these patients and, depending on their number, the probability of acute cholangitis increased significantly. The operative mortality rate was 1.2 per cent for patients without cholangitis and 11.9 per cent for patients with cholangitis. Depending on the number of factors present, patients with cholangitis were divided into three groups: mild acute cholangitis without mortality; moderate acute cholangitis with a mortality rate of 5.6 per cent; and severe acute cholangitis with a mortality rate of 27.5 per cent. The present classification allows the group of patients needing prompt endoscopic or surgical drainage to be identified.

Acute Disease↗
PubMed1997

Are patients with cirrhotic stage primary sclerosing cholangitis at risk for the development of hepatocellular cancer?

BACKGROUND/AIMS: The risk of cholangiocarcinoma in primary sclerosing cholangitis is widely recognized to be 8-30%, whereas the risk of acquiring hepatocellular carcinoma in primary sclerosing cholangitis is unknown. As in other chronic liver diseases, the presence of hepatocellular carcinoma in a patient with primary sclerosing cholangitis undergoing evaluation for orthotopic liver transplantation would clearly impact on the candidacy, diagnostic evaluation, and alternative treatment options. Thus, the aim of our study was to determine the prevalence of hepatocellular carcinoma in patients undergoing liver transplantation for primary sclerosing cholangitis. METHODS: The records of the 520 patients undergoing orthotopic liver transplantation at our institution between 1985 and May 1995 were reviewed. Of the 134 patients with primary sclerosing cholangitis, three (2%) had hepatocellular carcinoma. In the 386 patients without primary sclerosing cholangitis undergoing orthotopic liver transplantation, 22 (6%) had hepatocellular carcinoma. RESULTS: Neither the duration of primary sclerosing cholangitis (range 7-23 years) nor the presence of ulcerative colitis (two of three patients) distinguished those patients with primary sclerosing cholangitis plus hepatocellular carcinoma from those with primary sclerosing cholangitis alone. None of the three patients with primary sclerosing cholangitis plus hepatocellular carcinoma had evidence for hepatitis B or C, alpha-1-antitrypsin deficiency, or hemochromatosis. None of the tumors was of the fibrolamellar variety of hepatocellular carcinoma. CONCLUSIONS: The prevalence of hepatocellular carcinoma in patients with primary sclerosing cholangitis undergoing orthotopic liver transplantation is 2%. These data suggest that patients with advanced cirrhotic-stage primary sclerosing cholangitis are at increased risk for developing hepatocellular carcinoma and should be screened for hepatocellular carcinoma as well as for cholangiocarcinoma prior to orthotopic liver transplantation.

Adolescent↗
PubMed1995

Endoscopic sphincterotomy and biliary drainage in patients with cholangitis due to common bile duct stones.

OBJECTIVES: In a prospective study, we analyzed 95 consecutive patients undergoing endoscopic papillotomy (EP) for cholangitis due to common bile duct (CBD) stones; our purpose was to evaluate the risk factors influencing the complication rate due to cholangitis, with special attention to the clinical history. METHODS: Patients with previous gastric surgery or EP were excluded. Complications subsequent to sphincterotomy were recorded over a 3-month period. RESULTS: In patients with persistent cholangitis before EP, the risk for complications due to cholangitis increased with increasing delay between the onset of cholangitis and biliary drainage. In patients with a good response to antibiotics before EP, the delay in biliary drainage did not influence the risk of complications. After complete CBD stone removal, the morbidity (42% vs. 4%, p = 0.001) and the mortality (8% vs. 0%, NS) due to cholangitis were much higher in 12 patients with progressive cholangitis for > 3 days before biliary drainage, compared with 73 cases who had experienced a good response to antibiotics before EP and/or early drainage (< 3 days) after the onset of cholangitis. Two patients with advanced cholangitis and septic shock at the time of EP died < 12 h after completed sphincterotomy with CBD stone removal. Three patients with retained CBD stones and failed biliary drainage after EP experienced disastrous morbidity (100% vs. 9%, p < 0.01) and mortality (67% vs. 1%, p < 0.01) due to cholangitis, compared with 85 patients without retained CBD stone(s). CONCLUSIONS: We recommend emergency biliary drainage in all patients presenting with calculous cholangitis who are severely ill with continuous fever for several days. Emergency nasobiliary drainage without EP or after a limited EP may be a safer treatment in patients with (impending) septic shock. We believe that a more conservative approach is justified in patients presenting with symptoms of mild cholangitis, restricting emergency biliary drainage for those who do not respond rapidly (< 24 h) to antibiotics. Further emergency surgical or percutaneous biliary drainage should be performed immediately on patients in whom CBD stones are retained, after EP and drainage fails, especially if a stone is left impacted distally.

Adult↗
PubMed1988

Unconjugated bilirubin in hepatic bile with brown pigment gallstones and cholangitis.

To investigate the role of cholangitis in hydrolysis of bilirubin in bile with brown pigment gallstones, bilirubin composition and bacterial growth in hepatic bile with and without cholangitis were studied. The study included 38 brown pigment gallstone cases (28 without cholangitis and 10 with cholangitis). The proportion of unconjugated bilirubin in hepatic bile with cholangitis (16.9 +/- 8.5%, mean +/- SD) was significantly higher than that without cholangitis (3.7 +/- 1.8%, P less than 0.001). A positive correlation was found between bacterial population with beta-glucuronidase activity and the proportion of unconjugated bilirubin in bile in cases of brown pigment stones with cholangitis (P less than 0.05) but not in those without cholangitis despite the fact that bacterial species and population are similar regardless of the presence of cholangitis. In cholangitis, pH of bile becomes lower toward the optimal pH of bacterial beta-glucuronidase. Together the lower concentration of bile acid and the lower pH in bile result in lower solubility of unconjugated bilirubin, promoting its precipitation. Thus occasional bouts of cholangitis may result in periodic deposition of bilirubinate on brown pigment stones with layered structures by inducing cyclic changes of bile composition in situ.

Bacteroides↗