Figure 2 - available via license: Creative Commons Attribution-NonCommercial 3.0 Unported
Content may be subject to copyright.
Source publication
Overlap syndrome has been introduced to the field of hepatology to describe the coexistence of two or more autoimmune hepatic conditions in the same individual. This is a rare clinical case of a patient diagnosed with primary biliary cirrhosis (PBC) who later developed primary sclerosing cholangitis (PSC). This is a unique case as no other cases wi...
Context in source publication
Context 1
... pancreatic duct dilatation was also noted. Computer tomography imaging ( Figure 2) showed similar appearances with change in caliber of distal CBD at the Table 1 Liver autoimmune and virology screen AMA M2 negative smooth muscle antibodies negative LKM antibodies negative Gastric parietal cell antibody negative Anti-nuclear Hep-2 antibodies positive (Weak) ANCA MPO negative ANCA PR3 negative ds -DNA antibodies negative eNA antibody screen negative Immunoglobulin IgG4 negative Hepatitis serology A,B,C negative Ca 19-9, alpha feto protein, CeA 125 within normal range Immunoglobulin IgA, IgG, IgM within normal range pancreatic level. There was no evidence of pancreatic mass or stone. ...
Similar publications
Background:
Magnetic resonance cholangiopancreatography (MRCP) is an important tool for noninvasive imaging of biliary disease, however, its assessment is currently subjective, resulting in the need for objective biomarkers.
Purpose:
To investigate the accuracy, scan/rescan repeatability, and cross-scanner reproducibility of a novel quantitative...
Citations
... A similar case was reported by Sundaram et al. in 2018 involving a 35-year-old woman [9]. Jeevagan et al. [16] reported also the case of a middle-aged woman, who had been dealing with primary biliary cirrhosis (PBC) for 17 years, was admitted to the hospital due to clinical and biochemical symptoms characteristic of cholestatic syndrome. Initially, a provisional diagnosis of worsening PBC was considered. ...
Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) are distinct liver diseases. Cases combining PBC and PSC, are extremely rare. Here, we present a case of a 39-year-old woman with a history of colonic Crohn's disease treated with azathioprine. Discontinuation of the medication was prompted by abnormal liver function tests, but subsequent evaluations revealed persistent liver injury. Extensive diagnostic investigations, including imaging, serological tests, and liver biopsy, were conducted leading to a diagnosis of PBC-PSC overlap syndrome based on the presence of concentric lamellar fibrosis and chronic non-suppurative destructive cholangitis. The patient responded well to ursodeoxycholic acid treatment. This case emphasizes the importance of recognizing and diagnosing rare overlap syndromes, particularly those involving PBC and PSC, to ensure appropriate management and improve patient outcomes.
... We describe the first well documented patient with an overlap between the three autoimmune liver diseases, primary biliary cholangitis, autoimmune hepatitis and primary sclerosing cholangitis. The rare overlap between PBC and PSC has been reported in only 11 patients in the literature to date [5][6][7][8][9][10][11][12][13]. One case report suggests the occurrence of the three autoimmune conditions in one patient, but the diagnosis of AIH is in doubt since histological confirmation is lacking and the pattern of the ANA detected is not specified [5]. ...
Background & aim
The diagnosis of primary biliary cholangitis (PBC), an uncommon immune-mediated cholestatic liver disease, is based on positive circulating anti-mitochondrial (AMA) and/or PBC-specific anti-nuclear autoantibodies (ANA), coupled with elevated serum alkaline phopsphatase (ALP) levels. Timely initiation of treatment with ursodeoxycholic acid prevents progression to cirrhosis and liver failure. We aimed at investigating liver histology in patients with normal ALP level and positive AMA and/or PBC-specific ANA.
Methods
We searched the Swiss PBC Cohort Study database, which includes subjects with positive PBC autoimmune serology and normal ALP levels, for patients who underwent a liver biopsy. Histological slides were centrally reviewed by an expert liver pathologist, and sera were centrally re-tested for AMA and ANA.
Results
30 patients were included; 90% females, median age 53 (range 27–72) years. Twenty-four (80%) had liver histology typical for (n = 2), consistent with (n = 16) or suggestive of (n = 6) PBC, including three of four AMA-negative ANA-positive patients. Among 22 ursodeoxycholic acid treated patients, 14 had elevated GGT levels before treatment; a significant decrease of the median GGT level between pre- (1.46 x ULN) and post- (0.43 x ULN) treatment (p = 0.0018) was observed.
Conclusions
In our series, a high proportion of AMA positive patients with normal ALP levels have PBC. For the first time we show histological diagnosis of PBC in AMA-negative/PBC-specific ANA-positive subjects and the potential role of GGT as a biomarker in PBC patients with normal baseline ALP levels. Current guidelines for the diagnosis of PBC do not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation.
... Eighteen years later, a proposed diagnosis of overlap was made based on MRCP and ERCP which demonstrated a beading appearance of the biliary ducts thought to be consistent with PSC. 45 Despite reported histological findings consistent with subsequent diagnoses of PBC and PSC, this case presented with several weaknesses, including histology of the liver biopsy describing 'deranged liver function tests' not being detailed in the case report and negative AMA titers. 23,44 A repeat biopsy subsequently had findings of lymphoplasmacytic infiltrate and lymphoid aggregate consistent with the diagnosis of PBC, and subsequent imaging 18 years later with MRCP and ERCP demonstrated a beaded appearance of the biliary ducts which was consistent with PSC. 41,44 In that case, the presentation of jaundice, abdominal pain, and fever is consistent with ascending cholangitis. ...
... 23,44 A repeat biopsy subsequently had findings of lymphoplasmacytic infiltrate and lymphoid aggregate consistent with the diagnosis of PBC, and subsequent imaging 18 years later with MRCP and ERCP demonstrated a beaded appearance of the biliary ducts which was consistent with PSC. 41,44 In that case, the presentation of jaundice, abdominal pain, and fever is consistent with ascending cholangitis. However, this was not reported to be a recurrent event. ...
... 23 Seven of the ten cases reviewed in the literature used UDCA in varying doses as a first-line treatment. 3,22,29,31,44 Of the seven patients treated with UDCA, three were treated with 750 mg/day, one was treated with 15 mg/kg/day (standard dose), one was treated with 20 mg/kg/day (high dose), and two did not have details on the dose used to treat. Patients treated with 750 mg/day did not have their weights detailed. ...
Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are slow progressive diseases which have been increasing in prevalence. The pathogeneses of PBC and PSC are incompletely understood but the underlying mechanisms appear to be fundamentally autoimmune in origin. Although PBC and PSC appear to be separate entities, overlap has been described. Diagnosis depends on a combination of serological markers, imaging, and pathological criteria. The mainstay of treatment has been ursodeoxycholic acid and in some cases of extrahepatic biliary obstruction and overlap disorder, endoscopic retrograde cholangiopancreatography has been useful.
... A subgroup of PSC patients (ranging from 7 to 14% of patients with a diagnosis of PSC) have been further categorized as suffering from a PSC-AIH variant, which has different clinical implications in terms of management and prognosis [4, 5••]. PSC-PBC overlap is extremely rare with less than 15 cases reported in the literature [6][7][8][9][10][11][12][13][14][15]. PSC is characterized by a geographical North-to-South gradient, with higher prevalence in Northern Europe and North America, compared to their Southern counterparts and Asia [3]. ...
... It is also noted that children who were initially diagnosed with classic AIH but also have concomitant IBD have higher cholangiographic abnormalities and were diagnosed with PSC overlap subsequently. In contrast to classic PSC, most reported cases of PSC-PBC overlap have a female predominance, similar to classic PBC [6][7][8][9][10][11][12][13][14][15]. These gender variations are interesting, and bigger studies are needed for better understanding of this presentation. ...
... The overlap syndrome demonstrating biochemical, histologic, and clinical characteristics of both PSC and PBC is an exceptionally uncommon disorder. Only few case reports are available for review [6][7][8][9][10][11][12][13][14][15], describing patients with chronic cholestasis, almost always with a positive AMA (10 out of 11) (see Table 2). Similar to classic PBC, the prevalence of the PSC-PBC syndrome demonstrates female predominance (> 90%). ...
Purpose of Review
Overlap syndromes show concomitant or sequential findings of two or more autoimmune liver diseases. Primary sclerosing cholangitis (PSC) is rare and PSC-overlap syndromes are much rarer. There is limited data in PSC-overlap syndromes which pose significant diagnostic and therapeutic challenges for this condition. We summarized the published data in this review to update the management strategies in PSC-overlap syndrome.
Recent Findings
PSC incidence is 0.77–1 per 100,000 person/years, of which 2–10% are reported to have PSC-autoimmune hepatitis (AIH) overlap syndrome. The incidence of PSC-primary biliary cholangitis (PBC) is extremely rare. Inflammatory bowel disease (IBD) is more common in classic PSC than in PSC-AIH patients (80% vs. 63%) and unusual in PSC-PBC. PSC can present with a more hepatocellular form of injury in children, also called autoimmune sclerosing cholangitis (ASC) rather than the typical classic cholestatic presentation in the adults. The presence of overlap syndrome can be diagnosed concomitantly or sequentially during the disease course in an individual. Liver fibrosis progression in PSC-AIH overlap syndrome is similar to classic PSC but hepatobiliary malignancy is reportedly infrequent. Diagnostic scoring criteria are not recommended and clinical diagnosis relies primarily on liver biochemistry, cholangiography and liver biopsy. Ursodeoxycolic acid and immunosuppressive therapy is beneficial in some patients with PSC-overlap syndrome. The biochemical response to pharmacotherapy is higher in PSC-overlap syndrome when compared to classic PSC but lower than that observed in classic AIH.
Summary
PSC overlap syndromes are poorly understood. Current evidence is based on data compiled from case reports and series. This review provides an updated summary that could assist in the clinical management of patients with this complex disorder.
... Furthermore, a retrospective cohort study of six patients with AIH-PSC was excluded for the lack of sufficient detail in its reported clinical outcomes [39]. Lastly, PBC-PSC and AIH-PBC-PSC are not represented in the systematic review because only case series [48,50,55] and case reports [47,49,[51][52][53][54] of these syndromes were identified in our literature search. ...
The treatment of overlap syndromes is guided by small observational studies whose data have never been synthesized in a rigorous, quantitative manner. We conducted a systematic review and meta-analysis to evaluate the efficacy of available treatments for these rare and morbid conditions. We searched the literature for studies comparing ≥2 therapies for autoimmune hepatitis (AIH)-primary biliary cholangitis (PBC), AIH-primary sclerosing cholangitis (PSC), PBC-PSC, AIH-PBC-PSC, autoimmune cholangitis (AIC), or autoimmune sclerosing cholangitis (ASC) with respect to various clinical outcomes, including biochemical improvement and transplant-free survival. A total of 28 studies met the inclusion criteria for AIH-PBC, AIH-PSC, AIC, and ASC. AIH-PBC patients tended to experience more biochemical improvement with ursodeoxycholic acid (UDCA) + [corticosteroids and/or antimetabolites], i.e., “combination therapy”, than with corticosteroids ± azathioprine (RR = 4.00, 95% CI 0.93–17.18). AIH-PBC patients had higher transplant-free survival with combination therapy than with UDCA, but only when studies with follow-up periods ≤90 months were excluded (RR = 6.50, 95% CI 1.47–28.83). Combination therapy may therefore be superior to both UDCA and corticosteroids ± azathioprine for the treatment of AIH-PBC, but additional studies are needed to show this definitively and to elucidate optimal treatments for other overlap syndromes.
... We describe the first well documented patient with an overlap between the three autoimmune liver diseases, primary biliary cholangitis, autoimmune hepatitis and primary sclerosing cholangitis. The rare overlap between PBC and PSC has been reported in only 11 patients in the literature to date [5][6][7][8][9][10][11][12][13]. One case report suggests the occurrence of the three autoimmune conditions in one patient, but the diagnosis of AIH is in doubt since histological confirmation is lacking and the pattern of the ANA detected is not specified [5]. ...
Overlap between autoimmune hepatitis (AIH) and either primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) is not rare and has extensively been reported. We herein report the first well documented case of triple overlap. A 68-year-old male patient presented with asymptomatic PBC including normal alkaline phosphatase serum level, developed AIH five years later, associated with magnetic resonance cholangiopancreatography biliary changes typical for PSC. Despite treatment with ursodeoxycholic acid and mycophenolate mofetil, owing to prednisone and azathioprine intolerance, he continued to have interface hepatitis and developed increasing fibrosis at follow-up liver biopsy. Our case report raises awareness for this rare and difficult to diagnose and treat clinical phenotype.
... 1 However, a review of literature revealed that only 10 cases of PBC-PSC overlap have been reported. [2][3][4][5][6][7][8][9] No defined criteria are available for PBC-PSC overlap syndrome, which means that this syndrome is diagnosed when a patient fulfills diagnostic criteria for both conditions. AMA-M2 positivity is seen in our patient, as was seen in all but one previously reported case. ...
Overlap syndrome indicates the coexistence of 2 or more autoimmune liver diseases in the same individual, occurring simultaneously or sequentially. Cases of overlap of autoimmune hepatitis (AIH) with primary biliary cholangitis (PBC) and of AIH with primary sclerosing cholangitis (PSC) are known and have defined criteria for diagnosis. Overlap between PBC and PSC has been reported in only a few case reports. The cause for the rarity of this entity compared to other overlap syndromes is unclear. We present a case of an overlap syndrome of PBC with PSC in a 35-year-old woman.
... Jevaagan [6] reported a case of PBC/PSC overlap syndrome in a 64-year-old woman who was diagnosed as having AMA-negative PBC and then had a cholangiography consistent with PSC. more recent report in the literature describes a patient with PBC, with normal cholangiography, showing "onion-skin" type periductal fibrosis at liver histology [7]. ...
The overlap syndrome between primary biliary cirrhosis and primary sclerosing cholangitis is an extremely rare condition that has been reported in only six published cases so far.
Here we report two cases showing the clinical manifestations of both primary biliary cirrhosis and primary sclerosing cholangitis.
In one case the overlap condition was associated with psoriatric arthritis, and the patient successfully underwent dual treatment with ursodeoxycholic acid and the anti-tumour necrosis factor-alpha agent adalimumab. In the second case, the predominant condition was, initially, an antimitochondrial antibody-negative primary biliary cirrhosis with progressive course towards end-stage liver disease; the patient then developed either antimitochondrial antibody positivity or changes in the biliary tree compatible with primary sclerosing cholangitis.
These two cases add information on a controversial issue in the literature, and indicate the importance of recognizing a possible overlap syndrome to optimize treatment.
Copyright © 2015. Published by Elsevier Ltd.
... Different from AIH–PBC and AIH–PSC overlap syndromes, evidence for a PBC–PSC overlap syndrome is limited at best and is based only on single case reports. [39][40][41]In a recently described case, a 64-year-old woman with PBC of 17-year duration revealed typical benign strictures and dilatation of common bile duct with typical beading suggestive of PSC on ERCP done for worsening cholestatic features. [41] Whether sclerosing bile duct injury can be regarded as a primary event in late stage hepatopathies of other cause remains elusive. ...
... [39][40][41]In a recently described case, a 64-year-old woman with PBC of 17-year duration revealed typical benign strictures and dilatation of common bile duct with typical beading suggestive of PSC on ERCP done for worsening cholestatic features. [41] Whether sclerosing bile duct injury can be regarded as a primary event in late stage hepatopathies of other cause remains elusive. ...
Overlap syndrome in hepatology is emerging as a diagnostic and therapeutic challenge, which is further complicated by the present gaps in the information regarding the immunopathogenesis of these diseases. The present review represents a concise review of literature on overlap syndromes with emphasis on prevalence, etiopathogenesis, clinical presentation, diagnosis, and management of true overlap syndromes.
... Liver biopsy revealed bile duct Data are presented as number and frequency for categorical data, or as median and interquartile range for continuous data. *Disease-related symptoms include pruritus, jaundice, bleeding varices, severe general fatigue, and ascites **In three patient information regarding the mode of presentation was not available ***Two patients did not have their varices classified [9][10][11]. Auto-antibody profiles were also similar to those reported in the international literature except for a higher prevalence of anti-LKM-1 antibodies. ...
Background and aims: Primary biliary cirrhosis is a chronic and slowly progressive cholestatic liver disease characterized by destruction of interlobular bile ducts, which if untreated, leads to fibrosis, cirrhosis and liver failure. It is more frequent among female patients and is usually diagnosed in the fifth decade of life. This study aims to determine the demographic, clinical, biochemical and serological characteristics and histological stage of patients with primary biliary cirrhosis.
Methods: Retrospective analysis of the adult patients diagnosed with primary biliary cirrhosis at our center from January 2005 to December 2013 was performed. Data collection included demographics, clinical features, biochemical and serological markers, and histological stage.
Results: 75 patients were diagnosed with primary biliary cirrhosis (mean age: 55 years, range: 19-83), of whom 92.0% were women. The most common symptoms at presentation were fatigue (40.0%), pruritus (40.0%), jaundice (28.0%) and dark urine (26.7%). 20.0% were asymptomatic at diagnosis. 48.0% of patients had cirrhosis at presentation. Positive antimitochondrial antibodies were found in 96% of cases. 34.8% of the patients were positive for antinuclear antibodies. Overlap syndromes were present in 10.6%. Liver biopsy was performed in 45.3% of the patients.
Conclusions:The clinical features of primary biliary cirrhosis were similar to those reported in the international literature but with a high percentage of symptomatic and cirrhotic patients at diagnosis.
