Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases

Objective: We report five cases (four male; median age 20 yr, range 14–38 yr) of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. The patients presented with jaundice, elevated serum aminotransferase and alkaline phosphatase activities, hyperglobulinemia with high immunoglobulin G (IgG) levels, circulating antinuclear and/or smooth muscle autoantibodies (≥ 1:40), and moderate to severe interface hepatitis on liver biopsy (with biliary features in four).
Methods: All five fulfilled criteria for diagnosis of "definite" autoimmune hepatitis and showed marked responses to prednisolone and azathioprine therapy, with relapses occurring during reduction or withdrawal of treatment. Cholangiographic features of primary sclerosing cholangitis were found in three patients at presentation and after intervals of 7 and 14 yr in the other two. Only two had evidence of inflammatory bowel disease. Diagnostic criteria for identifying those patients who may benefit from immunosuppressive therapy were reviewed.
Results: Review of the literature revealed only 11 similar cases that were sufficiently well described for comparison. However, in contrast to these and the present cases, preliminary data from other studies have suggested a marked association with ulcerative colitis and a poor response to immunosuppressive therapy.
Conclusions: It is recommended that the possibility of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome responsive to immunosuppressive therapy should be considered in any patient presenting with a hepatitic illness with hyperglobulinemia, antinuclear or smooth muscle autoantibodies, and biliary changes on liver biopsy. Cholangiography should be considered in such patients.     

Autoimmune hepatitis and primary sclerosing cholangitis

Autoimmune liver disease in children presents predominantly as autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). These diagnoses must be considered in patients who have acute and chronic hepatitis, particularly when an extrahepatic autoimmune disorder is present. In AIH, the timely and sustained control of liver inflammation is critical to improve the short- and long-term outcomes. No effective treatment for PSC has been identified to date, but supportive care, careful attention to complications and associated nonhepatic diseases, and liver transplantation significantly improve the long-term outcome.     

High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis

BackgroundOverlap syndrome is a term used for overlapping features of autoimmune hepatitis and primary sclerosing cholangitis or primary biliary cirrhosis and for autoimmune cholangitis. We describe a high prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis.MethodsWe sought to retrieve all patients with overlap syndrome between primary sclerosing cholangitis and autoimmune hepatitis in six university hospitals in Sweden. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis autoimmune hepatitis. Endoscopic retrograde cholangiography and/or magnetic resonance cholangiography were used to separate the primary sclerosing cholangitis cases diagnosed through liver biopsy into small and large primary sclerosing cholangitis. A histologocial diagnosis compatible with both autoimmune hepatitis and primary sclerosing cholangitis was required for inclusion.Results26 patients fulfilled our criteria for histological overlap of autoimmune hepatitis and primary sclerosing cholangitis, 7 (27%) of which had small duct primary sclerosing cholangitis. The reliability of the diagnosis small duct primary sclerosing cholangitis was supported by a very close similarity between small and large duct primary sclerosing cholangitis patients in clinical and laboratory data, and by a poor response to immunosuppressive therapy in the small duct primary sclerosing cholangitis patients. Patients with large duct overlap syndrome had a good response to immunosuppressive therapy. In both groups, our limited experience from ursodeoxycholic acid was largely poor.ConclusionsSmall duct primary sclerosing cholangitis is prevalent in the overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis.     

自身免疫性胰腺炎合并硬化性胆管炎

自身免疫性胰腺炎(AIP)的病理特异性表现为胰腺存在大量的IgG4阳性的浆细胞浸润和组织纤维化,这种病理表现也常见于大部分AIP患者的胆管系统,即AIP合并硬化性胆管炎(SC)。AIP合并SC往往以阻塞性黄疸为首发症状,其血IgG4明显升高。AIP合并SC的胆管造影与原发性硬化性胆管炎(PSC)极为相似,但AIP合并SC对皮质激素治疗往往有效,其预后较PSC好。     

Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in adults: report of three cases

Overlap syndromes are cases of liver diseases that share clinical, serological, histological and radiological criteria of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). No definitions have been fully established and therefore there is no solid evidence on the diagnosis and treatment. This article presents the cases of three adult patients with overlapping features of AIH and PSC. Orthotopic liver transplantation was considered the best therapeutic alternative due to advanced disease progression in one patient, while medical treatment was provided in the remaining two patients.     

Autoimmune pancreatitis and IgG-positive sclerosing cholangitis

Sclerosing cholangitis is a heterogenous disease. Sclerosing cholangitis with an unknown cause is abbreviated PSC. PSC affects extra- as well as intra-hepatic bile ducts and since this is a permanently progressing fibrous condition, it leads to liver cirrhosis. The disease is often associated with a development of cholangocarcinoma and idiopathic intestinal inflammation. Causal therapy does not exist; liver transplantation is indicated. IgG4 cholangitis differs from PSC in a number of features. This form is, unlike PSC, linked to autoimmune pancreatitis (AIP) as well as other IgG4 sclerosing diseases. Anatomically, distal region of ductus choledochus is most frequently involved. Icterus is, unlike in PSC, a frequent symptom of AIP. There also is a distinctive histological picture--significant lymphoplasmatic infiltration of the bile duct wall with abundance of IgG4 has been described, lymphoplasmatic infiltration with fibrosis in the periportal area and the presence of obliterating phlebitis is also typical. However, intact biliary epithelium is a typical feature. IgG4 can be diagnosed even without concurrent presence of AIP. IgG4 sclerosing cholangitis is a condition sensitive to steroid therapy. At present, there is no doubt that IgG4 sclerosing cholangitis is a completely different condition to primary sclerosing cholangitis. From the clinical perspective, these diseases should be differentiated in every clinician's mind as (a) AIP is treated with corticosteroids and not with an unnecessary surgery, (b) IgG4 sclerosing cholangitis is mostly successfully treated with corticosteroids and the disease is not, unlike PSC, a risk factor for the development of cholangiocarcinoma.     

Autoimmune neutropenia due to antineutrophil antibodies in a patient with primary sclerosing cholangitis

Autoimmune neutropenia (AIN) is defined as a decrease in the circulating absolute neutrophil count (ANC) to less than 1500/μl caused by serum antineutrophil antibodies. Secondary AIN is associated with various autoimmune diseases. Herein we present the case of a patient with primary sclerosing cholangitis (PSC) who developed secondary AIN. A 19-year-old man was admitted due to liver injury, and a diagnosis of PSC was established by cholangiogram and liver biopsy. Severe neutropenia, with the ANC down to 130/μl, developed during his hospital course. No medications had been given at that time and bone marrow aspiration revealed no abnormality. Therefore we suspected secondary AIN as a causative etiology and examined whether antineutrophil antibodies were detectable in the patient’s sera by flow cytometric analysis of the granulocyte indirect immunofluorescence test. We found that antineutrophil antibody was strongly positive on admission, and the titer decreased along with recovery from neutropenia. This is the first reported case of a patient with PSC who developed AIN, with detection of serum antineutrophil antibodies.     

Post-infantile giant cell hepatitis in patients with primary sclerosing cholangitis and autoimmune hepatitis

Abstract: In post-infancy, multinucleated giant cell hepatitis is rare. Various conditions and diseases associated with post-infantile giant cell hepatitis have been described, but the pathogenesis remains unknown. In this paper we review the case reports of four patients (3 male, 1 female; aged 22 to 32 years) with primary sclerosing cholangitis and autoimmune hepatitis. The follow-up ranges from five to seven years. All patients showed cholestasis and repeated elevation of hepatic transaminases. Patients with viral infections, metabolic disorders and toxic influences were excluded. Histopathology of liver tissue in all four patients revealed giant cell formation with up to 20 nuclei in 20–70% of all hepatocytes. Post-infantile giant cell hepatitis was defined histopathologically. The clinical course of all four patients markedly improved after immunosuppressive treatment. Further improvement was observed with the addition of ursodeoxycholic acid. Follow-up liver biopsies during treatment showed reduced inflammation and a decreased number of giant cells. One patient, who initially was admitted to the hospital with liver cirrhosis died five years later due to a sepsis. The clinical course of the other three patients remained stable during the observation period, and no progression of liver fibrosis was recorded as long as immunosuppressive treatment was continued. Cholestasis and autoimmunity seem to be two important mechanisms triggering hepatic giant cell formation in post-infancy. In the reported cases long-lasting cholestasis in primary sclerosing cholangitis together with features of autoimmune hepatitis seem to have triggered the formation of syncytial hepatic giant cells.     

High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis

BACKGROUND/AIMS: Traditionally, autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are regarded as separate disease entities. We report on a group of patients that suggests the existence of an overlap syndrome of the two conditions and on the prevalence of this syndrome among patients with PSC. Furthermore, the impact of the recently revised AIH scoring system for diagnosing AIH in this context was assessed. METHODS: Retrospective analysis of consecutive patients of a tertiary referral centre for liver disease with a diagnosis of PSC. RESULTS: Diagnosis of the overlap syndrome was established for nine patients (8%) of a total group of 113 PSC patients. Four patients initially presented with features of AIH and in five cases PSC was diagnosed first. All patients responded to immunosuppressive therapy; in three cases long-term remission was achieved. Three patients underwent liver transplantation after 4 months and 7 and 9 years, respectively. The original and revised versions of the AIH scoring system gave essentially the same results in the patients with the PSC-AIH overlap syndrome. CONCLUSIONS: Patients with overlapping features of AIH and PSC may be more common than is currently assumed. Recognition of this syndrome is of clinical significance, considering the important therapeutical consequences.     

Overlap syndrome of primary sclerosing cholangitis and autoimmune hepatitis

We report a 46-year-old patient with the typical biochemical, histological and cholangiographic findings of primary sclerosing cholangitis (PSC) whose clinical and laboratory findings would also qualify her for the diagnosis of definite autoimmune hepatitis (AIH), according to the aggregate score of the International Autoimmune Hepatitis Group. We suggest that this patient may represent an example of the overlapping syndrome of PSC and AIH.     

Clinicopathological differentiation between sclerosing cholangitis with autoimmune pancreatitis and primary sclerosing cholangitis

Background The present study was undertaken to identify the clinicopathological differences between sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and primary sclerosing cholangitis (PSC). Methods We retrospectively compared the clinical, cholangiographic, and liver biopsy findings between 24 cases of PSC and 24 cases of SC-AIP. Results Patient age at the time of diagnosis was significantly lower in the PSC group than in the SC-AIP group. The peripheral blood eosinophil count was significantly higher in the PSC group than in the SC-AIP group, but the serum IgG4 level was significantly higher in the SC-AIP group. Cholangiography revealed band-like strictures, beaded appearance, and pruned-tree appearance significantly more frequently in PSC, whereas segmental strictures and strictures of the distal third of the common bile duct were significantly more common in SC-AIP. Liver biopsy revealed fibrous obliterative cholangitis only in the PSC specimens. No advanced fibrous change corresponding to Ludwig's stages 3 and 4 was observed in any of the SC-AIP specimens. IgG4-positive plasma cell infiltration of the liver was significantly more severe in SC-AIP than in PSC. Subsequent cholangiography showed no improvement in any of the PSC cases, but all SC-AIP patients responded to steroid therapy, and improvement in the strictures was observed cholangiographically. Conclusions Based on the differences between the patients' ages and blood chemistry, cholangiographic, and liver biopsy findings, SC-AIP should be differentiated from PSC.     

Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis

BACKGROUND: Sclerosing cholangitis with autoimmune pancreatitis has a cholangiographic appearance that is similar to that of primary sclerosing cholangitis, but only the former responds well to corticosteroid therapy. It, therefore, is necessary to distinguish between these two diseases. Cholangiography is the reference standard for the diagnosis of primary sclerosing cholangitis. The present study compared the characteristic findings for these two types of sclerosing cholangitis. METHODS: Cholangiograms from patients with primary sclerosing cholangitis (n = 29) and sclerosing cholangitis with autoimmune pancreatitis (n = 26) were studied with regard to length and region of stricture formation, and other characteristic findings. RESULTS: Band-like stricture, beaded or pruned-tree appearance, and diverticulum-like formation were significantly more frequent in primary sclerosing cholangitis. In contrast, segmental stricture, long stricture with prestenotic dilatation and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with autoimmune pancreatitis. Discriminant analysis based on these findings correctly identified 27 of 28 patients with primary sclerosing cholangitis and 25 of 26 patients with sclerosing cholangitis with autoimmune pancreatitis. It also identified a patient with an incorrect diagnosis of primary sclerosing cholangitis who proved, on review of a surgical specimen, to have findings consistent with lymphoplasmacytic sclerosing cholangitis. CONCLUSIONS: Characteristic cholangiographic features allow discrimination of sclerosing cholangitis with autoimmune pancreatitis and lymphoplasmacytic sclerosing cholangitis without pancreatitis from primary sclerosing cholangitis.     

Pediatric primary sclerosing cholangitis

Summary An 11-year-old male presented with abdominal pain and emesis. Serum chemistries revealed cholestasis and an ERCP demonstrated sclerosing cholangitis. Secondary causes of this disease process were excluded. Sclerosing cholangitis is distinctly uncommon in the pediatric age group, but it should be considered in evaluation of patients of any age with cholestasis. It appears in some cases that there may be subtle histologic and radiographic features which separate the pediatric and adult forms of the disease.The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense, Department of the Navy or the Naval Service at large, or the Uniformed Services University of the Health Sciences.     

Small-duct primary sclerosing cholangitis

Current evidence suggests that PSC may affect the entire biliary system from interlobular bile ducts to the ampulla of Vater. If the affected bile ducts are too small for cholangiographic identification, the best designation for the condition is small-duct PSC; cholangiographically identifiable duct changes are the hallmark of large-duct PSC. The term "small-duct PSC" should replace the name pericholangitis because that designation lacks a clear definition. Small-duct PSC may occur in combination with large-duct PSC or it may occur alone. The clinical course of patients with PSC depends on the hepatic changes related to small-duct PSC, not primarily on the classic large-duct disease. Therefore the features of small-duct PSC and its complications are used to determine the disease stages of PSC. The incidence of small-duct PSC still is not known and the natural history as well as the pathogenesis of the condition remains obscure. Nevertheless, the role of small-duct disease in the syndrome of PSC has come into focus and the themes for future studies are apparent. Work should commence.     

Small-duct primary sclerosing cholangitis

Patients with cholestatic liver tests and typical histologic features of primary sclerosing cholangitis (PSC) but a normal cholangiogram have been identified as having small-duct PSC. This subgroup of PSC has been less well characterized than the classic largeduct form. Some patients characterized as having small-duct PSC develop cholangiographic features of PSC during follow-up. Three papers published in 2002 on small-duct PSC patients suggested a better prognosis in patients with small-duct PSC than in those with large-duct PSC. However, these studies included a limited number of patients and had a short follow-up. A combined cohort of these patients with a prolonged follow-up recently confirmed these previous observations. However, some patients will suffer from liver-related mortality or will need to undergo liver transplantation. Recurrence of small-duct PSC after liver transplantation has been reported. Cholangiocarcinoma, the most feared complication of PSC, has not been described in a patient with small-duct PSC without progression first to large-duct PSC.     

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.