17.1Introduction

Liver involvement in SjšgrenÕs syndrome (SS) is commonly subclinical and almost never appears as the Þrst manifestation of the disease. The prevalence of liver involvement in SS varies among series and depends on the diagnostic criteria used. Studies conducted in the 1960s, based on clinical (i.e., liver enlargement) and serological (i.e., elevated alkaline phosphatase) Þndings estimated the SS liver involvement as high as 20% [1]. A somewhat lower prevalence of liver disease has been reported in more recent studies, with estimates ranging from 2% to 20% of SS patients [2Ð6].

Because the predominant markers of SS liver involvement are altered liver function tests (LFT), most studies of hepatic dysfunction in SS are based on these laboratory parameters. LFT are elevated in 5Ð49% of SS cases [2Ð6] and this wide variability may be secondary to different criteria used for the diagnosis of SS, the different population examined, and the inclusion of hepatitis C virus (HCV)-positive SS patients by some investigators. Analyzing the results of studies with larger populations of well-documented patients with SS [2, 3, 6], the occurrence of elevated LFT probably does not exceed 10%. The majority of such patients manifest a cholestatic pattern of LFT abnormality and a preserved liver function.

The association of liver involvement in SS with serum antimitochondrial antibodies (AMA) was Þrst reported in 1970 [7] with studies on well-documented SS patient populations, observing a 5Ð10% antibody prevalence. Approximately, half of such patients have elevated LFT. However, LFT can be elevated in SS patients in the absence of AMA.

A 1994 study evaluated the histological features of SS patients with liver involvement [2]. Patients with elevated LFT or AMA in their sera underwent a liver biopsy. The typical histopathology observed was liver injury in a pericholangial pattern, similar to that detected in primary biliary cirrhosis at early stages. Another study also demonstrated that the main histological Þnding in the liver was that of cholangitis of variable severity [5]. More recently, Hatzis et al. examined the natural history of SS-associated cholangitis. Out of 410 SS patients, 36 (9%) had elevated LFT suggestive of cholestasis, among whom 21 (5%) had AMA, consistent with the presence of primary biliary cirrhosis (PBC). In addition, 6 patients were negative for AMA but their histological picture in liver biopsy was compatible with cholangitis. During a mean follow-up of 66 months, most individuals had stable liver disease but 27% experienced worsening of their LFT abnormalities and 4% had clinically relevant deterioration in hepatic function. The comparison of histology in Þve paired liver biopsies taken at a mean interval of 46 months showed no signiÞcant change [6].

The literature also includes sporadic cases of coexisting SS and autoimmune hepatitis or primary sclerosing cholangitis [8]. These comorbidities are rare and usually diagnosed on the basis of the autoantibody proÞle. All such putative cases require histological conÞrmation by an experienced pathologist.