Clinical evaluation of serum antimitochondrial antibody-negative primary biliary cirrhosis

BACKGROUND: Primary biliary cirrhosis (PBC) is cha- racterized by frequent presence of antimitochondrial anti- bodies (AMAs). The sensitivity and specificity of AMA for PBC are both greater than 90%-95%, so the presence of AMA in serum is the major hallmark in PBC. However, it has long been recognized that in 5%-10% of patients the clinical, biochemical and histological features are diagnos- tic for PBC, but their sera are consistently tested negative for AMA/AMA-M2. This study aimed to evaluate whether the presence of AMA alters the clinical, serological and his- tological features of the disease. METHODS: Clinical data of 70 patients clinically and/or histologically diagnosed with PBC were reviewed. AMA- negative and AMA-positive patients were compared in terms of clinical, biochemical, immunological and histo- logical features. RESULTS: At presentation, 11 patients were serum AMA/ AMA-M2 negative. At the initial visit, AMA-negative and AMA-positive patients were similar in terms of age, sex, clinical manifestations, liver biochemistries and histological findings. The mean level of serum immunoglobulin M (IgM) was significantly lower in AMA-negative PBC pa- tients than in AMA-positive PBC patients (2851±1418 mg/L vs 6361 ±4928 mg/L, P =0.033). Serum antinuclear anti- bodies ( ANA) and/or smooth muscle antibodies ( SMA) were more frequently positive in the AMA-negative PBC patients than in the AMA-positive patients (81.8% vs 40.7%, P =0.031). CONCLUSION: AMA-negative PBC patients are characte- rized by relatively lower levels of serum IgM and a higher prevalence of serum ANA/SMA and are not associated with substantial differences in the clinical, biochemical and histo- logical spectrum of the disease.

Sequence of events leading to primary biliary cholangitis

Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease that is observed more frequently in middle-aged women.This disorder is considered an autoimmune disease,since liver injury is sustained by the presence of selfdirected antimitochondrial antibodies targeting the bile duct cells.The prognosis may vary depending on an early diagnosis and response to therapy.However,nearly a third of patients can progress to liver cirrhosis,thus requiring a liver transplant.Traditional immunosuppressive therapies,commonly employed for other autoimmune diseases,have limited effects on PBC.In fact,dramatic functional changes that occur in the biliary epithelium in the course of inflammation play a major role in perpetuating the injury.In this minireview,after a background on the disease and possible predisposing factors,the sequential cooperation of cellular/molecular events leading to end-stage PBC is discussed in detail.The rise and maintenance of the autoimmune process,as well as the response of the biliary epithelia during inflammatory injury,are key factors in the progression of the disease.The so-called“ductular reaction(DR)”,intended as a reactive expansion of cells with biliary phenotype,is a process frequently observed in PBC and partially understood.However,recent findings suggest a strict relationship between this pathological picture and the progression to liver fibrosis,cell senescence,and loss of biliary ducts.All these issues(onset of chronic inflammation,changes in secretive and proliferative biliary functions,DR,and its relationship with other pathological events)are discussed in this manuscript in an attempt to provide a snapshot,for clinicians and researchers,of the most relevant and sequential contributors to the progression of this human cholestatic disease.We believe that interpreting this disorder as a multistep process may help identify possible therapeutic targets to prevent evolution to severe disease.

Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis

BACKGROUND Only a few cases of chronic hepatitis B(CHB)with primary biliary cholangitis(PBC)have been reported based on histological evidence from liver biopsies.AIM To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC.METHODS Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital,affiliated with Jiangsu University,and Wuxi Fifth People’s Hospital,from January 2005 to September 2020,were selected.All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC.RESULTS Only five had elevated alkaline phosphatase levels,nine were positive for antimitochondrial antibody(AMA)-M2,and two were negative for AMA-M2.Two had jaundice and pruritus symptoms,10 had mildly abnormal liver function,and one had severely elevated bilirubin and liver enzyme levels.The pathological characteristics of CHB complicated by PBC overlapped with those of PBCautoimmune hepatitis(AIH).When necroinflammation of the portal area is not obvious,the pathological features of PBC are predominant,similar to the features of PBC alone.When the interface is severe,biliangitis will occur,with a large number of ductular reactions in zone 3.Unlike the PBC-AIH overlap pathology,this pathology is characterized by a small amount of plasma cell infiltration.Unlike PBC,lobulitis is often observed.CONCLUSION This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.