Differential efficacy of corticosteroids and interferon in a patient with chronic hepatitis C-autoimmune hepatitis overlap syndrome.

The chronic hepatitis C-autoimmune hepatitis (AIH) overlap syndrome has been described in the literature, but to date appropriate therapy remains controversial. We report on a 28-year-old woman with hepatitis C-AIH overlap syndrome. The patient was infected with HCV genotype 1b and had laboratory and immunologic findings of AIH type 2 such as increased Igs and a high titer of antibodies against liver-kidney microsomes. Initial liver biopsy specimen demonstrated end-stage liver fibrosis due to chronic hepatitis. After long-lasting corticosteroid treatment, only partial remission was achieved. In contrast, short-term antiviral therapy with interferon-alpha2b in combination with ribavirin was followed by complete biochemical and virologic remission. However, 15 months later, a relapse of AIH was observed. After restarting corticosteroid treatment, transaminase levels completely normalized. Surprisingly, in this patient with overlap syndrome, short-term interferon therapy induced complete remission of chronic HCV infection and regression of severe liver fibrosis.     

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Contribution of two new cases

The autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome is characterized for clinical, biochemical, immunological, and histological features overlapping those of AIH and PBC, whose pathogenesis and more appropriate treatment are unknown at present. We describe two new patients of this entity, which made debut with cholestasic acute hepatitis accompanied of hypergammaglobulinemia. In the first patient was demonstrated the presence of AMA, ASMA, and anti-LKM1 autoantibodies; and ANA in the second one. The histological findings showed changes suggestive of AIH and PBC. After the start of immunosuppressive treatment, associated to ursodeoxycholic acid in one patient, a successful outcome was observed.     

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

Summary We report a case of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome treated with cyclosporine A. Features of primary biliary cirrhosis were pruritus, high titer of antimitochondrial antibodies, inflammatory infiltrates surrounding interlobular bile ducts, and periportal granuloma. Features suggestive of autoimmune hepatitis were high titer of antinuclear antibodies, very high total immunoglobulins, and piecemeal necrosis. Because corticosteroids and ursodeoxycholic acid were inefficient, cyclosporine A was started at a dose of 3 mg/kg/day. A dramatic improvement in clinical condition, liver tests, and histology was noted. Discontinuation of cyclosporine A was followed by a clinical and histological relapse. Cyclosporine A reintroduction was again associated with a significant improvement. This case report suggests that in corticoresistant cases cyclosporine A could be an effective therapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.     

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.     

Wolff-Parkinson-White syndrome: Report of five cases

Five cases of the Wolff-Parkinson-White syndrome have been presented, with comments upon some unusual features encountered. These patients may be able to perform useful service in the Army if they are not incapacitated by frequent attacks of paroxysmal tachycardia.     

原发性胆汁性肝硬化-自身免疫性肝炎重叠综合征44例临床特点及疗效分析

目的 分析熊去氧胆酸(UDCA)联合免疫抑制剂治疗原发性胆汁性肝硬化-自身免疫性肝炎重叠综合征( PBC- AIH)的长期疗效及预后.方法 从2000年1月至2011年1月天津医科大学总医院确诊的387例自身免疫性肝病患者中筛选出44例PBC-AIH患者,回顾分析其临床资料、治疗方法及疗效.结果 44例PBC-AIH患者均有不同程度的血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素(TBil)升高,84.09％ (37/44)的患者球蛋白(GLO)或免疫球蛋白G(IgG)水平升高.38.63％(17/44)的患者免疫球蛋白M(IgM)升高,97.73％(43/44)的患者抗核抗体(ANA)阳性,90.91％(40/44)的患者抗线粒体抗体(AMA)阳性,11.36％(5/44)的患者抗平滑肌抗体(SMA)阳性.病理学表现为界面性肝炎,不同程度的肝内小胆管损伤.使用UDCA联合免疫抑制剂治疗后,病情缓解率为61.36％(27/44),不完全应答率为29.55％(13/44),治疗失败率为9.09％(4/44).病情缓解患者中停药6例,复发率为5/6.至随访结束时,PBC-AIH患者ALT、AST、ALP、GGT、TBil水平均较治疗前明显下降,其中ALP、GGT、ALT、AST在治疗前6个月下降明显,ALP、GGT在随访结束时出现轻微上升趋势.随访中PBC-AIH患者病情进展率为29.55％(13/44),10年存活率为93.33％(28/30).结论 UDCA联合免疫抑制剂治疗PBC-AIH可明显改善患者生化指标,延缓患者病情进展,提高生存率,缓解率较高,但停药后复发率亦较高.     

Primary biliary cirrhosis and autoimmune hepatitis overlap syndrome.

Primary biliary cirrhosis and autoimmune hepatitis are chronic immune-mediated liver disorders. An overlap syndrome is now recognized with mixed biochemical, serological and histological features. We report a 55-year-old lady with overlap syndrome, which presented with jaundice, pruritus and associated renal failure. She succumbed to her illness.     

Results of steroid-based therapy for the hepatitis C–autoimmune hepatitis overlap syndrome

OBJECTIVE: Overlap syndromes in which persons manifest clinical, histological, or immunological features of both hepatitis C infection and autoimmune hepatitis are well described. The discordant forms of treatment for hepatitis C and autoimmune hepatitis have made medical management of these patients difficult. We report our experience in using corticosteroids as first line therapy for the hepatitis C-autoimmune hepatitis overlap syndrome. METHODS: Seven patients with this overlap syndrome (diagnosis based on the presence of serum hepatitis C antibody by RIBA and serum hepatitis C RNA by polymerase chain reaction, and serum hypergammaglobulinemia, elevated ANA or ASMA titers, or histological findings consistent with autoimmune hepatitis) were treated with prednisone with or without azathioprine or cyclosporine, and followed for a median duration of 44.5 months. RESULTS: Five patients (71%) showed improvement of median serum ALT level from 162 U/L to 38 U/L (p = 0.04) and median serum gamma-globulin from 2.1 g/dl to 1.4 g/dl (p = 0.04) by 6 months of therapy. The mean modified histological activity index score also decreased from 11.4 +/- 2.5 to 6.6 +/- 2.6 (p = 0.04) by at least 1 yr of therapy. One patient discontinued prednisone while taking azathioprine and experienced a rebound elevation of serum ALT that did not respond to retreatment with prednisone. Antiviral therapy was subsequently administered and resulted in biochemical and virologic response. Hepatitis C virus RNA remained detectable in all other patients. CONCLUSION: Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis C-autoimmune overlap syndrome, resulting in appreciable biochemical and histological response but without viral eradication.     

中晚期自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的临床病理研究

目的探讨中晚期自身免疫性肝炎-原发性胆汁性肝硬化（AIH-PBC）重叠综合征的临床病理特征及治疗直答。方法对具有肝穿刺标本的11例PBC-AIH重叠综合征和13例PBC（Seheuer分期3、4期）患者进行比较，重点分析AIH-PBC重叠综合征的临床、病理特点及治疗应答。结果两组患者的性别、年龄、病程、症状无显著差异；AIH-PBC重叠综合征患者的丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-球蛋白、免疫球蛋白IgG以及抗核抗体或抗平滑肌抗体阳性率明显高于PBC（P〈0．05）。肝组织学见汇管区与肝腺泡内以单个核细胞为主的较多炎细胞浸润，其中易见浆细胞的聚积性浸润。可见不同时期小胆管损伤或毛细胆管反应性增生并侵蚀肝界板；重叠综合征患者经熊去氧胆酸治疗可使肝功能改善，与PBC患者无明显差异。结论中晚期AIH-PBC重叠综合征临床、血清学及组织病理学表现出AIH和PBC双重特征，UDCA治疗有助于血生化指标的改善。     

原发性胆汁性胆管炎-自身免疫性肝炎重叠综合征的诊治

自身免疫性肝病(AILD)包括原发性胆汁性胆管炎(PBC)、自身免疫性肝炎(AIH)、原发性硬化性胆管炎(PSC)。患者可在初诊时或随访的过程中出现2种AILD的特征,通常将这种情况称为“重叠综合征”,其中以PBC重叠AIH最为常见。与单纯PBC或AIH相比,PBC-AIH重叠综合征门静脉高压、消化道出血、腹水、死亡及肝移植发生率明显升高,病情进展也更迅速,因此,其早诊早治显得尤为重要。对近年PBC-AIH重叠综合征的诊治进展进行综述。     

自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的临床病理研究

目的 探讨自身免疫性肝炎-原发性胆汁性肝硬化（AIH-PBC）重叠综合征的临床病理特征及治疗应答。方法 对具有肝穿刺标本的16例PBC—AIH重叠综合征、26例Ⅰ型AIH和25例PBC（Scheuer分期Ⅰ、Ⅱ期）患者进行比较，重点分析AIH—PBC重叠综合征的临床、病理特点及治疗应答。结果 3组患者的性别、年龄、病程、症状无显著性差异；AIH—PBC重叠综合征患者血清碱性磷酸酶、γ-谷氨酰转肽酶、免疫球蛋白IgM以及抗线粒体抗体（AMA）、AMA—M2阳性率明显高于AIH组（P〈0．05）；而丙氨酸转氨酶、天冬氨酸转氨酶、7-球蛋白、免疫球蛋白IgG以及抗核抗体或抗平滑肌抗体阳性率明显高于PBC（P〈0．05）。AIH—PBC重叠综合征患者肝组织学示界面炎／碎屑样坏死、小叶内炎症及胆管病变；重叠综合征患者接受熊去氧胆酸治疗可使肝功能改善。结论 AIH—PBC重叠综合征临床、血清学及组织病理学表现出AIH和PBC双重特征，UDCA治疗有助于血生化学指标的改善。     

原发性胆汁性肝硬化／自身免疫性肝炎重叠综合征患者的临床和病理学研究

目的分析原发性胆汁性肝硬化（PBC）、自身免疫性肝炎（AIH）和PBC／AIH重叠综合征患者的临床和病理学特点。方法对105例自身免疫性肝病患者的临床资料进行分析,比较PBC／AIH重叠综合征和单纯PBC或AIH患者的临床表现和肝组织病理学变化。结果在105例患者中,包括11例PBC／AIH重叠综合征、60例PBC、33例AIH和1例原发性硬化性胆管炎（PSC）。PBC／AIH重叠综合征与PBC或AIH患者的性别、年龄、症状和并发症无明显差异（P〉0．05）,其实验室检查具有AIH的特点,如血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、免疫球蛋白IgG的明显升高,同时具有PBC的特点,如GGT、ALP、免疫球蛋白IgM的显著增高,但与PBC或AIH相比,无统计学差异（P〉0．05）;自身抗体检测可见抗核抗体、抗线粒体M2抗体和抗核心蛋白gP210抗体阳性,后两项抗体检出率明显高于AIH患者（P〈0．01）;肝组织病理学检查结果显示,PBC／AIH重叠综合征兼有PBC和AIH的特点,如界面炎和碎屑样坏死,汇管区浆细胞浸润,胆管不同程度的病变等。结论PBC／AIH重叠综合征的临床表现和肝组织病理学具有PBC和AIH的双重特征,应对此病充分认识,并探索有效的治疗方案。     

Primary biliary cirrhosis and autoimmune hepatitis overlap syndrome: therapeutic features in 5 patients

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two different liver diseases, however diagnosis criteria of these two affections can be found in a same patient. The aim of this study is to relate the clinical, serologic and histologic features of patients presenting the overlap syndrome, AIH-PBC, defined by the presence of at least of two main criteria of each disease and to evaluate their response to therapy. PATIENTS AND METHODS: This was a retrospective study concerning patients presenting overlap syndrome diagnosed between January 1998 and December 2001. These patients had been treated with ursodesoxycholic acid (AUDC) or prednisone and azathioprine or a combination of these three products. Clinical and biological criteria were used to assess response to therapy. RESULTS: Five patients fulfilled the diagnostic criteria of overlap syndrome. All patients were females, the median age was 38 years (range: 19-65 years). Three patients were treated by UDCA, a clinical and biological response was noted in only one patient. Two patients were treated by prednisone and azathioprine without any remission. Three patients were treated by a combination of these three products with a good response in two cases. CONCLUSION: Optimal treatment for overlap AIH-PBC syndrome remains to be determined. Treatment with UDCA or immunosuppressor alone is not efficient. A combination of these drugs should be evaluated in further studies.     

Hepatitis C virus risk: a hepatitis C virus related syndrome

BACKGROUND: The association between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been recently described in many reports. OBJECTIVE: The aim of this study was to evaluate the long-term prognosis of hepatitis C virus-positive patients affected by mixed cryoglobulinemia with or without kidney involvement. PATIENTS: At total of 119 hepatitis C virus-positive patients affected by mixed cryoglobulinemia were divided in two groups. Group A: mixed cryoglobulinemia without kidney involvement (103 cases); group B: mixed cryoglobulinemia with glomerulonephritis (GN) (16 cases). A further 37 patients affected by mesangio-proliferative glomerulonephritis (MPGN) were evaluated as controls (group C). METHODS: Anti-hepatitis C virus antibodies were determined by commercial kits and hepatitis C virus-RNA was detected by polymerase chain reaction (PCR) amplification of the 5' untranslated region (5'UTR) of the virus. The hepatitis C virus genotype was determined according to Okamoto. Liver biopsy was performed in 62 patients, bone marrow biopsy in 65 patients, and kidney biopsy in all patients with proteinuria. RESULTS: In group A, 46 patients (45%) were affected by chronic liver disease (CLD), 21 (20%) by low-grade non-Hodgkin's lymphoma (NHL) and 16 (15%) by both diseases. All patients of group B were affected by type I membrano-proliferative glomerulonephritis, 3 (19%) by chronic liver disease, 6 (37%) by low-grade non-Hodgkin's lymphoma, and 7 (44%) by both diseases. Several genotypes of hepatitis C virus were found, but Type 1b was prevalent. In group C, no patient showed chronic liver disease or non-Hodgkin's lymphoma. Younger age, higher mean blood pressure, lower C4 serum level, and poorer survival significantly distinguished group B from group A. Survival rates at 5 years were: 87.4% for group A, 89.5% for group C, and 50.0% for group B. None of the patients of group B developed kidney failure requiring dialysis, whilst infections were the leading cause of death. CONCLUSIONS: In hepatitis C virus-positive patients, the presence of mixed cryoglobulinemia associated with kidney involvement seems to indicate a new syndrome characterized by immune system impairment, lack of progression to kidney failure, and poor survival (hepatitis C virus-Risk syndrome).     

Direct acting antiviral therapy is curative for chronic hepatitis C/autoimmune hepatitis overlap syndrome

Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting antiviral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology.