Transitions between variant forms of primary biliary cirrhosis during long-term follow-up

BackgroundConditions exhibiting features of two different autoimmune liver diseases are designated overlap syndromes. Variant forms display some, but not all, characteristics of a distinct autoimmune liver disease. We describe transitions over time between variant forms of PBC, i.e. AMA-negative PBC, autoimmune hepatitis (AIH)–PBC overlap and autoimmune cholangitis (AIC) in a large cohort of PBC patients in Sweden.MethodsWe retrieved all patients with variant forms of PBC in six university hospitals in Sweden, covering 60% of the Swedish population. The diagnosis of PBC and its variants was based on laboratory findings and compatible histological features. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis of AIH.ResultsIn a population of 800 patients with PBC, we identified 35 (5%) variant forms; 25 patients with AIH–PBC overlap, 8 with AIC and 2 with AMA-negative PBC at the time of our study. The initial diagnoses were PBC (3 patients), AIH (3), AIH–PBC overlap (16), AIC (8) and AMA-negative PBC with (1) or without (4) concomitant AIH. The median follow-up was 125 (41–360) months. Immunosuppression and ursodeoxycholic acid induced a complete or good regression of increased aminotransferases in about half of the patients who were given one or both of these treatments.ConclusionsVariant forms of PBC are seen in approximately 5% of PBC patients in Sweden. Transition between different forms may occur, emphasizing the value of repeat biopsies, but established overlapping AIH–PBC seems to be stable over time.     

Overlap of autoimmune hepatitis and primary biliary cirrhosis: an evaluation of a modified scoring system

OBJECTIVE: The coexistence of autoimmune hepatitis (AIH) with primary biliary cirrhosis (PBC) as an overlap syndrome has been previously described. The ability to detect AIH overlap with a revised version of the International Autoimmune Hepatitis Group (IAHG) scoring system, however, remains unknown. Our specific aim was to evaluate the revised IAHG scoring system and its ability to identify AIH overlap in PBC. MErHODS: One hundred forty-one PBC patients with first-time visits to the Mayo Clinic from January 1, 1990 to December 31, 1992 were evaluated. The calculation of individual revised IAHG scores was performed and compared to original IAHG scores. RESULTS: Among 137 PBC patients with available liver histologies, use of the original IAHG scoring system detected "definite" and "probable" AIH overlap among 2.2% and 62% of cases, respectively. Application of the revised IAHG scoring system, however, revealed no individuals (0%) with definite AIH overlap (>15 points). Twenty-six subjects (19%) fulfilled IAHG criteria for probable AIH overlap (10-15 points). The presence of antinuclear antibody and/or smooth muscle antibody positivity (p = 0.05), other autoimmune disorders (p < 0.01), and total histological score (p < 0.001) were significantly greater in the PBC plus probable AIH group than in subjects with PBC alone. CONCLUSION: A reduction in the prevalence of definite 2.2% vs 0%) and probable (62% vs. 19%) AIH overlap among PBC subjects was observed with use of the revised IAHG coring system relative to the original criteria. Applicability of the revised IAHG scoring system, however, remains questionable, as nearly 20% of PBC patients will be classified with probable AIH overlap.     

Applicability of the IAIHG scoring system to the diagnosis of antimitochondrial/anti-M2 seropositive variant form of autoimmune hepatitis

BACKGROUND AND AIMS: According to the International Autoimmune Hepatitis Group (IAIHG) criteria, circulating antimitochondrial antibodies (AMA) do not support the diagnosis of autoimmune hepatitis (AIH). The aims of this study were to characterize a subset of patients with AIH who have AMA and antiM2 seropositivity, and to assess the applicability of the revised scoring system of the IAIHG in the diagnosis of this variant form of AIH. METHODS: Eighteen patients with AMA-AIH were enrolled and compared with 206 classical AIH and 85 primary biliary cirrhosis (PBC) controls. Human leukocyte antigen (HLA) class II alleles were determined by polymerase chain reaction (PCR) amplification with sequence-specific primers, and biopsies were blindly reevaluated. RESULTS: The patients with AMA-AIH were, on average, older than patients with classical AIH and had an hepatocellular pattern of elevated liver enzymes, hypergammaglobulinemia and lower levels of cholesterol, when compared with PBC controls. There were no histological signs of PBC or overlapping forms in any AMA-AIH biopsies. The majority of patients with AMA-AIH carried HLA antigens associated with classical AIH (DRB1*03, n = 5; DRB1*04, n = 7, and DRB1*13, n = 6). Pretreatment scores classified all AMA-AIH patients with probable (n = 17) or improbable (n = 1) AIH. After treatment, only 28% of AMA-AIH patients reached scores for definite diagnosis, compared with 90.1% of AIH-1 and 96.4 AIH-2. In the AMA-AIH group, only patients who relapsed after immunosuppressive drug withdrawal could be classified with definite AIH. CONCLUSIONS: AMA-AIH shares common features with classical AIH. The diagnosis of AMA-AIH may be swayed by the IAIHG criteria, rendering questionable the applicability of the revised scoring system to this variant form of AIH.     

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease

OBJECTIVES: To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. METHODS: Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). RESULTS: From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10 - 15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. CONCLUSION: Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(-) profile, and probable diagnosis according with the scoring system for AIH.     

Autoimmune cholangitis and primary biliary cirrhosis — an autoimmune enigma

Abstract: Aims/Background: Autoimmune cholangitis/cholangiopathy (AIC) is an enigmatic disease marked by chronic cholangitis, antinuclear antibodies (ANA) and sero-negativity for conventionally detected anti-mitochondrial antibodies (AMA). We examined whether AIC is a distinct entity, an AMA-negative variant of primary biliary cirrhosis (PBC), or a cholangiopathic variant of autoimmune hepatitis (AIH) by comparing the clinical, laboratory and autoantibody profiles of 21 cases of AIC, 37 cases of PBC and 16 cases of AIH from selected Japanese patients. Methods: The specificities of AMA and ANA were determined by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens, and the frequencies for these groups were compared. Results: By clinical, biochemical and histological data, AIC and PBC were similar and both were clearly distinct from AIH. Serologically, by immunofluorescence of AMA and ANA, there was polarisation. By immunoblotting, and notwithstanding the negative test for AMA, a proportion of the AIC sera reacted with the E2 subunits of the 2-oxo-acid dehydrogenase enzyme complexes, but more particularly with the lower molecular weight E2 subunits. The antinuclear reactivity in AIC was with centromere, Sp100 and nuclear pore complex proteins as in PBC, but preferentially with the nuclear pore complex. Conclusion: Our results demonstrate that AIC and PBC are similar diseases. However this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC are an exception to this.     

原发性胆汁性肝硬化和自身免疫性肝炎重叠综合征的临床与病理分析

目的 分析原发性胆汁性肝硬化(PBC)和自身免疫性肝炎(AIH)重叠综合征(PBC/AIH重叠综合征)患者的临床表现、肝组织病理学特征。 方法 采用国际自身免疫性肝炎小组新修订的描述性诊断标准和计分系统,从68例PBC患者中筛选出9例PBC/AIH重叠综合征患者,分析比较PBC/AIH重叠综合征和单纯PHC患者的临床表现、肝组织病理学特征。 结果 68例PBC患者中,PBC/AIH重叠综合征9例,单纯PBC 59例,分别占13.2％和86.8％,PBC/AIH重叠综合征血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-球蛋白、免疫球蛋白G,以及抗平滑肌抗体和(或)抗核抗体阳性率明显高于单纯PBC;PBC/AIH重叠综合征合并其他自身免疫性疾病发生率亦明显高于单纯PBC;PBC/AIH重叠综合征兼有PBC和AIH的双重组织学特点,显示界面炎和碎屑样坏死,肝组织免疫荧光检测显示肝细胞膜、汇管区有免疫球蛋白G沉着。 结论 PBC/AIH重叠综合征表现出A·IH和PBC双重特征,不同于单纯的PBC,两者的临床表现、免疫学及肝组织病理学特征上有差异。     

Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases

BACKGROUND:Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies.OBJECTIVE:To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases.METHODS:Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53.RESULTS:Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213).CONCLUSION:The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.     

Primary biliary cirrhosis - Autoimmune hepatitis overlap syndrome: A rationale for corticosteroids use based on a nation-wide retrospective study in Japan

Aims: Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) may simultaneously coexist in some patients, designated as PBC‐AIH overlap syndrome. Previous studies suggest that combination therapy of ursodeoxycholic acid (UDCA) and corticosteroids may be effective. In the current study, we aimed to describe clinical features of these cases and to propose a rationale for combination treatment in PBC‐AIH overlap. Methods: We enrolled patients with PBC‐AIH overlap from eight referral centers for liver diseases in Japan, and clinical, biochemical and immunological features were examined. Liver histology of all patients at diagnosis were analyzed altogether in detail. Eighty‐nine and 44 patients with PBC and AIH alone were included and served as controls. Results: We identified 33 patients with PBC‐AIH overlap. The mean follow‐up period was 6.1 years. On liver histology, the HA (hepatitis activity) score was significantly higher than the CA (cholangitis activity) score (P < 0.001). At the end of the follow‐up period, corticosteroids were used in 23 patients (72%), and neither liver‐related death nor liver transplantation had been noted. The sensitivity and specificity of the simplified AIH scoring system for prediction of patients who required corticosteroids during clinical course was 92% and 75% in the training set (n = 17), and 91% and 80% in the validation set (n = 16) of overlap. Only 3% of PBC patients were diagnosed as having indication for corticosteroid use. Conclusion: In PBC‐AIH overlap, AIH‐like features are dominant in liver histology. The simplified AIH scoring system could predict patients who needed corticosteroids with a higher specificity.     

164例自身免疫性肝病临床分析

目的 分析比较自身免疫性肝炎（autoimmune hepatitis，AIH）、原发性胆汁性肝硬化（primary biliary cirrhosis，PBC）、原发性硬化性胆管炎（primary sclerosing cholangltis）及其重叠综合征的临床特点、生化特征和治疗反应，提高对自身免疫性肝病的认识。方法对77例AIH患者、46例PBC患者、11例PSC患者和30例PBC-AIH重叠综合征患者的临床及实验室检查资料进行回顾性分析。结果除PSC外，大多数自身免疫性肝病多发于中年女性，从出现症状到明确诊断平均需要2．5年。AIH、PBC-AIH重叠患者具有较高的转氨酶，PBC、PSC具有较明显的GGT、ALP升高。临床表现上AIH、PBC、PSC、AIH-PBC黄疸发生率分别为84％、78％、90％和67％，皮肤瘙痒的发生率分别为43％、56％、81％和60％。PSC和AIH-PBC具有较高的AIH评分，27％的PSC患者和33％AIH-PBC的评分达到可能的AIH。合理应用UDCA和免疫抑制剂可使90％的PBC和AIH患者症状在六个月内得到缓解、肝功能恢复明显改善。结论 AIH、PBC-AIH的肝功能异常以转氨酶升高为主，PBC、PSC以胆汁淤积为主。应用AIH评分系统诊断可能的AIH时应注意鉴别PSC及其它自身免疫性肝病。UDCA和免疫抑制剂可改善绝大多数患者的症状和肝功能异常。     

Clinical and pathological characteristics of the autoimmune hepatitis and primary biliary cirrhosis overlap syndrome

BACKGROUND AND AIMS: The defining of the autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) overlap syndrome as a separate clinicopathological entity has been controversial and temporally and geographically subjective. METHODS: From 1979 until 2000, 227 patients diagnosed with AIH, PBC or the overlap thereof were treated. Cases with genuine AIH/PBC overlap syndrome were sorted out using close clinical follow up and serial liver biopsies. RESULTS: Of the 227 patients, 19 (8.4%) were diagnosed with the AIH/PBC overlap syndrome. They all cleared a score >10 for the diagnosis of AIH, and tested positive for antimitochondrial antibodies during their courses. Long-term follow up with frequent histological examinations, however, established the diagnosis of AIH/PBC overlap syndrome in only two (0.8%) patients. The most powerful factor distinguishing AIH from PBC was acidophilic bodies in lobules that were detected significantly more frequently in patients with AIH than PBC or spurious overlap syndrome (39/46 [85%]vs 3/85 [4%], P < 0.001). It was more reliable than bile-duct lesions for the distinction of PBC from AIH. CONCLUSIONS: Although AIH/PBC overlap syndrome does exist, it is infrequent and needs to be diagnosed carefully using close clinical and histological follow up to enable timely and effective treatment.     

Antilactoferrin Antibodies in Autoimmune Liver Diseases

Objective: Lactoferrin, an immunoregulatory protein in mucosal secretions, is one of the target antigens to perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs). Circulating lactoferrin is cleared in the liver, but little is known about the implication of lactoferrin in hepatic inflammation. To evaluate the implication of immunological response to lactoferrin, we examined antilactoferrin antibodies in autoimmune liver diseases.
Methods: Fourteen patients with primary biliary cirrhosis (PBC), 14 with autoimmune hepatitis (AIH), five with autoimmune cholangitis (AIC), six with chronic hepatitis C, and five with chronic hepatitis B were studied. We evaluated autoantibodies to lactoferrin in the sera of the patients by the Western Immunoblotting method.
Results: Sera of five of the 14 patients (35.7%) with PBC, four of the 14 patients (28.6%) with AIH, and five of the five patients (100%) with AIC contained autoantibodies to human lactoferrin, but none with hepatitis B or C had them. The higher prevalence of serum antibodies to human lactoferrin was shown to be higher in patients with AIC than with hepatitis B (   p < 0.01  ), hepatitis C (   p < 0.01  ), PBC (   p < 0.05  ), and AIH (   p < 0.05  ).
Conclusion: Lactoferrin located in bile ducts and liver cells is one of the candidates of target antigens in autoimmune liver diseases, especially in AIC.     

Clinical characteristics of patients with autoimmune hepatitis seropositive for anticentromere antibody

Aim: Recent studies have revealed that primary biliary cirrhosis patients with anticentromere antibody (ACA) commonly develop portal hypertension. However, the clinical characteristics of autoimmune hepatitis (AIH) remain uncertain. We investigated the clinical features of patients with AIH seropositive for ACA (ACA‐AIH), comparing them with those of patients with AIH seropositive for other immunofluorescent patterns of antinuclear antibodies (ANA) (other‐AIH). Methods: AIH was diagnosed on the basis of the scoring system proposed by the International Autoimmune Hepatitis Group. Seropositivity for ACA was determined by a discrete speckled pattern on HEp‐2 cells by an immunofluorescent technique. The severity of histological grading and staging was evaluated by the histological activity index (HAI) score. Results: Eight (17%) of 47 patients with AIH had ACA. No significant differences in age, sex, onset pattern of the disease, progression to hepatic failure and relapse rate were present between the ACA‐AIH and other‐AIH groups. The frequency of concurrent autoimmune diseases in ACA‐AIH was significantly higher than that in other‐AIH (75% vs 36%, P = 0.0406). Biochemical analysis revealed a significantly lower mean immunoglobulin G (IgG) level than that in other‐AIH (2176 ± 641 vs 3013 ± 923 mg/dL, P = 0.0150). However, there were no differences in serum alanine aminotransferase levels, titers of ANA, HAI scores or the positive rate of human leukocyte antigen (HLA)‐DR4 between the groups. Conclusion: These results suggest that the emergence of ACA is not a distinct entity of AIH, despite its clinical characteristics of a significantly higher frequency of concurrent autoimmune diseases and lower serum IgG levels.     

Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis

Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is a clinical entity characterized by the occurrence of both conditions at the same time in the same patient. In addition to PBC-AIH overlap syndrome, transitions from one autoimmune disease to another have been reported, but no systematic series have been published. We report a series of 12 patients with consecutive occurrence of PBC and AIH (i.e., PBC followed by AIH). Among 282 PBC patients, 39 were identified who fulfilled criteria for probable or definitive AIH. AIH developed in 12 patients (4.3%). The baseline characteristics of the patients were similar to those of patients with classical PBC. Time elapsed between the diagnosis of PBC and the diagnosis of AIH varied from 6 months to 13 years. Patients with multiple flares of hepatitis at the time of diagnosis of AIH had cirrhosis on liver biopsy. Ten patients were given prednisone +/- azathioprine; short-term as well as sustained remissions were obtained in 8 of these, while two had multiple relapses and eventually died 8 and 7 years after diagnosis of AIH. In conclusion, the development of superimposed AIH could not be predicted from baseline characteristics and initial response to UDCA therapy. If not detected early, superimposed AIH can result in rapid progression toward cirrhosis and liver failure in PBC patients.     

Overlap syndromes with autoimmune hepatitis in chronic cholestatic liver diseases

Conditions exhibiting features of two different autoimmune liver diseases are commonly designated overlap syndromes, although there is no current agreement on what constitutes an overlap syndrome or specific diagnostic criteria. As in the classic autoimmune liver diseases, such as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), the etiology is unknown but presumed to be related to alterations of immune regulation. Distinction of these clinical entities is important for management as outcomes may differ from outcomes of patients with diagnosis of classic autoimmune liver diseases. Due to their presumed rarity, no large therapeutic trials are available and treatment of overlap conditions is empirical and based upon extrapolation of data from the primary autoimmune liver diseases. PBC–AIH overlap is the most frequently described overlap syndrome and may be associated with a poor prognosis. This may represent an important and unrecognized cause of resistance to ursodeoxycholic acid in patients with PBC. PSC–AIH overlap is less commonly reported. Prognosis may be better than in patients with PSC alone; however, worse than in patients with AIH alone. Further studies are needed for determining diagnosis, natural history and optimal therapeutic strategies of overlap syndromes of autoimmune liver disease.     

Prevalence of autoimmune liver disease in Alaska Natives

OBJECTIVE: There is limited information on the prevalence of autoimmune liver disease in nonwhite populations. We conducted a population-based study on the prevalence of autoimmune liver diseases in Alaska natives. METHODS: Clinical records from 1984 to July, 2000 were reviewed to identify Alaska natives with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis, autoimmune cholangitis, and overlap syndromes of two of the above. AIH was defined as definite or probable, based on criteria established by the International Autoimmune Hepatitis Group. The diagnosis of PBC was based on a positive antimitochondrial antibody of > or = 1: 40, biochemical evidence of cholestasis, and compatible liver biopsy. Autoimmune cholangitis was defined as PBC but without a positive antimitochondrial antibody. Primary sclerosing cholangitis was diagnosed on the basis of cholangiogram. RESULTS: Seventy-seven patients with possible autoimmune liver disease were identified. Of these, 42 had definite and seven probable AIH. At presentation, 34.7% of patients with AIH presented with acute icteric hepatitis, and 65.3% were asymptomatic. Persons presenting with mild or no symptoms were more likely to have moderate to severe fibrosis on liver biopsy than those presenting with jaundice. Eighteen persons were diagnosed with PBC, five with autoimmune cholangitis, five with overlap syndrome, and none with primary sclerosing cholangitis. The combined point prevalence of AIH Alaska natives was 42.9/100,000 (95% CI = 31-57.7). The prevalence of PBC was 16/100,000 (95% CI = 12.9-25.4). CONCLUSIONS: This population-based study demonstrates that the prevalence rates of AIH and PBC in Alaska natives are comparable with reported rates in other populations.     

Development of autoimmune hepatitis in primary biliary cirrhosis.

AIM/BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. Up to 10% of patients with typical features of PBC will have additional features of autoimmune hepatitis (AIH). A subset, however, have no such features but go on to develop a 'sequential' AIH overlap syndrome. Objectives: Describe our experience with eight patients who developed AIH after the diagnosis of PBC was made. METHODS: We reviewed the charts of all PBC patients over a 9-year period (from 1996 to 2005). Only PBC patients with no features of AIH were included. RESULTS: There were 1476 patients with PBC. Of these, eight patients developed features of AIH overlap syndrome based on biochemical and histological parameters. Treatment included prednisone and azathioprine for 24 or more months. The majority of patients remained on ursodeoxycholic acid (UDCA) throughout treatment. Response to therapy was defined by improvement in enzymes, and was rapid for all patients. One patient was able to discontinue treatment with prednisone and azathioprine, while seven have continued on therapy to date. CONCLUSIONS: A 'sequential' overlap syndrome of AIH with PBC can occur. Treatment with prednisone and azathioprine may lead to a rapid improvement in aminotransferase levels.     

自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征患者的临床特点

目的 了解自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)重叠综合征的临床特点。方法 对129例自身免疫性肝病患者的临床资料进行回顾分析,按国际评分标准,诊断AIH/PBC重叠综合征,并将其生物化学、自身抗体、肝穿刺结果与单纯的AIH、PBC患者病例资料比较。 结果 129例自身免疫性肝病患者中35例为AIH/PBC重叠综合征患者,占27.1％,以女性患者为主,男女比例为1:10,平均年龄(50.79±11.27)岁,其实验室检查具有AIH患者的特点,如:氨基转移酶、γ 球蛋白、免疫球蛋白G的明显升高,同时也具有PBC的特点,如:碱性磷酸酶、免疫球蛋白M的显著增高,自身抗体检测可见抗核抗体(74.3％)、抗线粒体抗体(68.6％)、M2抗体(45.7％)阳性;肝穿刺结果有界面坏死、浆细胞浸润及胆管不同程度的损害。 结论 AIH/PBC重叠综合征为独立于AIH、PBC存在的疾病,有必要对此及早诊断,寻找有效的治疗方法。     

Characteristics and Inpatient Outcomes of Primary Biliary Cholangitis and Autoimmune Hepatitis Overlap Syndrome

Background and AimsPrimary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are hepatobiliary diseases of presumed immune-mediated origin that have been shown to overlap. The aim of this retrospective trial was to use national data to examine the characteristics and outcomes of patients hospitalized with overlapping PBC and AIH (PBC/AIH).MethodsThe National Inpatient Sample was used to identify hospitalized adult patients with PBC, AIH, and PBC/AIH from 2010 to 2014 by International Classification of Diseases-Ninth Edition Revision codes; patients with hepatitis B virus and hepatitis C virus infection were excluded. Primary outcomes measures were in-hospital outcomes that included mortality, respiratory failure, septic shock, length of stay, and total hospital charges. Secondary outcomes were the clinical characteristics of PBC/AIH, including the comorbid extrahepatic autoimmune disease pattern and complications of cirrhosis.ResultsA total of 3,478 patients with PBC/AIH were included in the study. PBC/AIH was associated with higher rates of Sjögren’s syndrome (p<0.001; p<0.001), lower rates of Crohn’s disease (p<0.05; p<0.05), and higher rates of cirrhosis-related complications when compared to PBC or AIH alone. There were similar rates of mortality between the PBC/AIH, PBC, and AIH groups. The PBC/AIH group had higher rates of septic shock when compared to the PBC group (p<0.05) and AIH group (p<0.05) after adjusting for possible confounders.ConclusionsPBC/AIH is associated with a lower rate of Crohn’s disease, a higher rate of Sjögren’s syndrome, higher rates of cirrhosis-related complications, and significantly increased risk of septic shock compared to PBC and AIH individually.     

Overlap syndromes

In hepatology, the term overlap syndrome describes variant forms of the major hepatobiliary autoimmune diseases, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients with overlap syndromes present with both hepatitic and cholestatic biochemical and histological features of AIH, PBC, and/or PSC, and usually show a progressive course toward liver cirrhosis and liver failure without adequate treatment. AIH-PBC overlap syndromes have been reported in almost 10% of adults with AIH or PBC, whereas AIH-PSC overlap syndromes were found in 6 to 8% of children, adolescents, and young adults with AIH or PSC. A minority of patients may also show transition from stable PBC to AIH, AIH to PBC, or AIH to PSC, as documented by single case reports and small case series. Single cases of AIH and autoimmune cholangitis (antimitochondrial antibody-negative PBC) overlap have also been reported. Empiric medical treatment of AIH-PBC and AIH-PSC overlap syndromes includes anticholestatic therapy with ursodeoxycholic acid and immunosuppressive therapy with corticosteroids and azathioprine. In end-stage disease, liver transplantation is the treatment of choice.     

Intrahepatic status of regulatory T cells in autoimmune liver diseases and chronic viral hepatitis.

Aim: Regulatory T cells (Tregs) maintain immunological tolerance and suppress autoreactive immune responses. We evaluated the intrahepatic status of Tregs in patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), chronic hepatitis C (CH-C), or chronic hepatitis B (CH-B). Methods: We analyzed 85 patients (20 AIH, 22 PBC, 27 CH-C, and 16 CH-B) and 14 controls. Using liver tissue samples obtained by needle biopsy or from marginal parts of resected metastatic liver tumors in the controls, immunohistochemical analyses of forkhead box P3(+), which is a specific marker for Tregs, CD4(+), and CD8(+) cells were performed. Results: Intrahepatic Tregs were significantly more infiltrated in patients with liver diseases than in the controls. There were significantly fewer intrahepatic Tregs in the AIH patients than in the PBC patients (P = 0.037). Patients with alow frequency of intrahepatic Tregs were detected significantly more in the AIH and CH-B groups than in the PBC and CH-C groups (P < 0.05). In addition, the frequency of Tregs decreased in the liver of PBC patients as the pathological stage of the disease advanced. We found significantly less infiltration of CD4(+) T cells in AIH than in other diseases (P < 0.05). Liver-infiltrating CD8(+) T cells were detected more frequently in the CH-B group than in other groups (P < 0.003). Conclusion: Intrahepatic Tregs were increased in both patients with autoimmune liver diseases and those with viral hepatitis. In autoimmune liver diseases, intrahepatic Tregs were fewer in the AIH patients than in the PBC patients.