Low incidence of positive smooth muscle antibody and high incidence of isolated IgM elevation in Chinese patients with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a retrospective study

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC) are three major clinicopathologic entities of autoimmune liver diseases. Besides, some patients with autoimmune liver disease present with characteristics of a second autoimmune liver disease (i.e. AIH and PBC overlapping). These cases have been defined as overlap syndrome. Patients with overlap syndrome usually present with nonspecific symptoms, including lethargy, arthralgias, and myalgias. A combination of clinical and laboratory or pathologic criteria is necessary for the diagnosis of the disease. In the laboratory test, autoantibodies are the serological hallmarks. Serum antinuclear antibody (ANA), smooth muscle antibody (SMA) and antimitochondrial antibody (AMA) are routinely detected in these patients [1].

Although combined features of both PBC and PSC have been reported in single cases, there is no clear evidence for the existence of an overlap of PBC and PSC [2]. The overlap syndrome of AIH and PBC is the most common form, and it shows a more progressive course towards liver cirrhosis and liver failure than AIH or PBC alone [3‐5]. However, up to now, the pathogenesis of overlap syndrome is poorly understood [6], and few data are available regarding the clinical characteristics of this disease, and moreover, reports on the prevalent and serological features of this condition in Chinese population are still lacking. The aim of this retrospective study is to investigate and analyze the prevalent and clinical features of Chinese patients with AIH and PBC overlap syndrome.

The worldwide prevalence of overlap syndrome of AIH and PBC is unknown. The first cases of this disease were reported almost 30 years ago, and this entity was assumed to be rare [11]. However, in our hospital, 10.33% of patients with autoimmune liver diseases were diagnosed as overlap syndrome of AIH and PBC based on the clinical manifests, laboratory test, and liver biopsy during the six years. Our study also showed that, similar to other studies [12, 13], overlap syndrome of AIH and PBC was more common in female patients, with a female:male ratio of roughly 6:1. However, the median age of patients with overlap syndrome was older than that of a previous report about European patients [9].

Presentation of autoimmune liver diseases varies widely, ranging from asymptomatic elevations of serum liver enzymes to massive hepatic necrosis resulting in fulminant hepatic failure, and there are no disease-specific clinical features. Günsar F, et al [14] reported that, lethargy was the most common symptom in these patients. Our study showed that xanthochromia, lethargy and anorexia were the predominant three chief complaints, that was, besides lethargy, xanthochromia was also a most common symptom in Chinese patients with overlap syndrome of AIH and PBC.

Serum autoantibodies have steadily established themselves as critical biomarkers for the diagnosis of autoimmune diseases [15]. For the North-American and European population, ANA and SMA constitute the standard repertoire for the diagnosis of autoimmune hepatitis, and AMA is the diagnostic marker of primary biliary cirrhosis [7, 16]. In our study, the majority of patients had positive serum ANA (140/146) and AMA (129/146), whereas only minor patients (14/146) had positive serum SMA. This result showed that, there was a low incidence of positive serum SMA in Chinese patients with overlap syndrome of AIH and PBC, which might indicate that serum SMA may have little diagnostic significance in the overlap syndrome for Chinese patients. This finding agreed with another investigation performed by Zhenxia Liu [17].

Some studies had shown that the serum immunoglobulins could elevate in most cases of autoimmune liver diseases [18‐22] and types of the elevated immunoglobulins were distinctive in different categories of autoimmune liver diseases. IgG was the predominant immunoglobulin elevated in serum of AIH patients while IgM was elevated in most patients with PBC [23‐25]. However, in our study, isolated IgM elevation was preponderant (37/89), which presented with features of PBC. Previously, a German study showed that patients with overlap syndrome of AIH and PBC presented with typical features of PBC when compared to AIH and PBC patients [13]. The reason, we inferred, might be that serological markers were often featured with one predominant pathological change to the other in overlap syndrome. But how to distinguish the predominant one needed further studies.

Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis was not rare in Chinese patients with clinical manifests of autoimmune liver diseases. Overlap of the diseases should not be disregarded when isolated IgM elevation was exhibited, and smooth muscle antibody might have little diagnostic significance in the overlap syndrome. If it was difficult to make a definite diagnosis, liver biopsy was necessary.