Clinicopathological significance of antinuclear antibodies in non‐alcoholic steatohepatitis

Abstract

Serum antinuclear antibodies (ANA) are occasionally noted in the patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH by comparing the clinicopathological features in the patients with ANA-positive NASH (n=35) and ANA-negative NASH (n=36). Inflammatory cell profiles and the distribution of oxidative stress markers were also examined immunohistochemically. The ANA-positive NASH was significantly associated with female gender (p= .005), high degree of portal inflammation (p= .039), interface activity (p= .036) and hepatocellular ballooning (p= .0008). In addition, The ANA of high-titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (p= .02). The degree of steatosis is rather mild in high-titer ANA group (p= .01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in portal area and hepatic lobules in both ANA-positive and ANA-negative groups. There was no difference in the distribution of oxidative stress markers between ANA-positive and ANA-negative groups. These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanisms may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis.

Activation of ATM signaling pathway is involved in oxidative stress-induced expression of mito-inhibitory p21WAF1/Cip1 in chronic non-suppurative destructive cholangitis in primary biliary cirrhosis: An immunohistochemical study

“…It seems likely, therefore, that p21 WAF1/Cip1 expression in BECs is closely related to the expression of 8-OHdG. The expressions of p21 WAF1/Cip1 and 8-OHdG were evident in the nuclei of hepatocytes in NASH in this study, as previously reported [21], suggesting that oxidative stress is involved not only in hepatocellular damage in NASH but also in biliary epithelial damage of small bile ducts showing CNSDC of PBC. There are several other reports that oxidative stress may be related to the pathogenesis of biliary epithelial damage in CNSDC followed by biliary epithelial apoptosis [11,28,29].…”

“…We then tried to evaluate the possible involvement of the ATM pathway in oxidative stress-induced mitoinhibitory p21 WAF1/Cip1 in BECs of the affected small bile ducts of PBC. As a disease model with the involvement of oxidative stress, we examined liver specimens of nonalcoholic steatohepatitis (NASH), in which oxidative stress is reportedly significantly involved in hepatocellular damage [20,21].…”

Participation of bile ductular cells in the pathological progression of non-alcoholic fatty liver disease

“…Immunohistochemical staining was performed as described previously 4 23. Primary antibodies included CK7 (clone OV-TL 12/30; 1:50; Dako, Glostrup, Denmark), CK19 (clone RCK108; 1:100; Dako), p16 INK4a (clone JC8; 1:100; Neomarkers, Freemont, California, USA), p21 WAF1/Cip1 (clone 70; 1:200; BD Transduction, San Jose, California, USA), CCL2 (Goat poly; 1:50, R&D, Minneapolis, Minnesota, USA) and α-smooth muscle cell actin (α-SMA; clone 1A4; 1:50, Dako).…”

Histological Findings of Autoimmune Hepatitis

“…Because atypical AIH cases, such as acute onset and excavation AIH, are probably ruled out as being non-AIH when using the simplified criteria, the modified criteria (1999) should be applied in these cases. Moreover, steatohepatitis is considered as a disease that is difficult to differentiate from AIH based on these criteria, and ANA is detected in approximately one third of cases of NASH and NAFLD [19,20], although pathological differentiation is relatively easy on liver biopsy.…”