Histologically proven AMA positive primary biliary cholangitis but normal serum alkaline phosphatase: Is alkaline phosphatase truly a surrogate marker?

Sun, Chunyan; Xiao, Xiao; Li, Yan; Sheng, Li; Wang, Qixia; Jiang, Pan; Lian, Min; Li, Yanmei; Wei, Yiran; Zhang, Jun; Chen, Yong; Li, Bo; Li, You; Huang, Binyuan; Li, Yikang; Peng, Yanshen; Chen, Xiaoyu; Fang, Jing‐Yuan; Qiu, Dekai; Hua, Jing; Tang, Ruqi; Leung, Patrick S.C.; Gershwin, M. Eric; Miao, Qi; Ma, Xiong

doi:10.1016/j.jaut.2019.01.005

Cited by 45 publications

(33 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…129,130 A higher frequency of monosomy X in peripheral leukocytes has been reported in female patients with PBC, particularly in B and T cells. 131 135,136 Our laboratory has pioneered the study of the pathogenesis of PBC, reported the cloning and identification of all of the mitochondrial autoantigens recognized by AMAs, 46,[137][138][139][140][141][142][143][144] and demonstrated that the mitochondrial autoantigens have only one dominant epitope-without evidence of determinant spreading-that is within the lipoyl binding site. [145][146][147] AMAs (when tested with recombinant polypeptides) are virtually pathognomonic of PBC and may precede clinical onset by a decade.…”

Section: Epigenetics Of Pbcmentioning

confidence: 99%

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

et al. 2019

View full text Add to dashboard Cite

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptibility. Biliary epithelial cells have often been considered a passive target of the immune attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, and deoxyribonucleic acid damage have been recognized to play an active role in the pathogenesis of PBC. This review highlights and discusses the most relevant pathogenetic mechanisms in PBC, focusing on the key factors that lead to the onset of cholestasis and immune activation.

show abstract

Section: Epigenetics Of Pbcmentioning

confidence: 99%

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

et al. 2019

View full text Add to dashboard Cite

show abstract

“…24 In line with these results, a recent Chinese study showed that of 67 subjects with isolated AMA (an incidental finding as part of routine testing for ANA in patients with arthralgia and/or undiagnosed fatigue) who underwent liver biopsy, 55 (82.1%) had histological signs of cholangitis compatible with the diagnosis of PBC, while the remaining 12 (17.9%) displayed normal histology. 25 The only significant difference between these groups relied in the titre of AMA and ALP; in particular, although ALP values were in the normal range, they were higher in subjects with vs without PBC. 25 On the basis of these results, the authors suggested that a portion of subjects with isolated AMA, normal ALP levels and no symptoms of liver disease could have PBC by histology and that normal values of ALP could be revised for these subjects.…”

Section: Key Pointsmentioning

confidence: 89%

Primary biliary cholangitis management: controversies, perspectives and daily practice implications from an expert panel

Alvaro

Carpino

Craxı̀

et al. 2020

Liver International

View full text Add to dashboard Cite

Primary biliary cholangitis (PBC) is a rare progressive immune-mediated liver disease that, if not adequately treated, may culminate in end-stage disease and need for transplantation. According to current guidelines, PBC is diagnosed in the presence of antimitochondrial antibodies (AMA) or specific antinuclear antibodies, and of a cholestatic biochemical profile, while biopsy is recommended only in selected cases. All patients receive ursodeoxycholic acid (UDCA) in first line; the only registered second-line therapy is obeticholic acid (OCA) for UDCA-inadequate responders. Despite the recent advances in understanding PBC pathogenesis and developing new treatments, many grey areas remain. Six Italian experts selected the following topics as the most urgent to address in PBC management: diagnosis and natural history of PBC: as a portion of the subjects with isolated AMA, normal alkaline phosphatase (ALP) levels and no symptoms of liver disease could have PBC by histology, defining how to manage and follow this population is crucial; role of liver biopsy: recent evidence suggests that biopsy may provide relevant information for risk stratification and prediction of UDCA response, possibly facilitating personalized approaches; risk stratification: the tools for risk stratification are well established, but some issues (eg bile acid dosage in routine practice) remain controversial; and therapy: those in more advanced stages of development are nuclear receptor modulators and fibrates, but more data are needed to plan personalized strategies. In this manuscript, for each topic, current evidence, controversies and future perspectives are summarized with the possible implications for clinical practice.

show abstract

“…If a patient only meets one of two criteria (positive AMA serologic testing and persistently elevated ALP), liver biopsy is required to further substantiate the diagnosis of PBC. A recent study has reported that more than 80% of AMA-positive patients who had normal ALP levels had histological demonstration of classic PBC [4]. Accordingly, in the study by Zandanell et al, new-onset primary biliary cholangitis in anti-mitochondrial antibody-positive patients over 6 years of follow-up may be markedly underestimated on the basis of their diagnostic criteria for PBC.…”

mentioning

confidence: 96%