NASH and cryptogenic cirrhosis: a histological analysis

Abstract

Introduction: Epidemiological studies indicate that nonalcoholic steatohepatitis (NASH) is a common cause of cirrhosis described as 'cryptogenic'. To address this from a histological perspective and to examine the significance of residual histological findings as an indication of prior NASH, we looked back at biopsies in patients who presented with cirrhosis without sufficient histological features to diagnose NASH but who had prior histologically confirmed non-cirrhotic NASH.

Methods: Seven patients were identified with biopsy pairs showing non-specific (cryptogenic) cirrhosis in the latest specimen and a prior biopsy showing non-cirrhotic NASH. Using an expanded NASH-CRN system scored blindly by light microscopy, we compared the early and late biopsies to each other and to a cohort of 13 patients with cirrhosis due to hepatitis C without co-existing metabolic syndrome.

Results: Macrosteatosis, although uniformly present in the non-cirrhotic NASH specimens, declined in the late stage cirrhotic NASH specimens and was not useful in the distinction of late cirrhotic NASH from cirrhotic viral hepatitis. However, the presence of ballooned cells, Mallory-Denk bodies, and megamitochondria and the absence of apoptotic bodies were significantly different in late stage cirrhotic NASH compared to cirrhosis due to hepatitis C.

Conclusions: Histologically advanced NASH presenting as non-specific or cryptogenic cirrhosis has residual changes which are consistent with prior steatohepatitis but which differ from cirrhosis due to hepatitis C. These results provide histological support for the more established epidemiological associations of NASH with cryptogenic cirrhosis and for criteria used in several proposed classifications of cryptogenic cirrhosis.

Figure 1.

Cellular ballooning with Mallory-Denk bodies (arrows) in a subject with non-cirrhotic NASH. (H&E, 400x).

Figure 2.

Ballooned hepatocytes (center) within a cirrhotic nodule in a subject with non-specific cirrhosis but with antecedent biopsy showing non-cirrhotic NASH. (H&E, 200x).

Figure 3.

Megamitochondria (arrows) within a cirrhotic nodule in a subject with non-specific cirrhosis and with prior biopsy showing non-cirrhotic NASH. (H&E, 400x).

Figure 4.

Differences in macrosteatosis, cellular ballooning and Mallory-Denk body histological scores between the three groups including the early non-cirrhotic NASH biopsy, the later paired non-specific cirrhosis specimen and the control group of hepatitis C patients who lacked metabolic syndrome. ^‡ Indicates a statistical trend (p = 0.07) in the loss of macrovesicular fat in the early (non-cirrhotic NASH) versus late (non-specific cirrhosis) NASH patients. * Indicates a statistically significant difference (p < 0.05) between the early or late NASH samples versus the hepatitis C group.