Elsevier

Human Pathology

Volume 33, Issue 11, November 2002, Pages 1098-1104
Human Pathology

Original Contributions
Cryptogenic cirrhosis: Clinicopathologic findings at and after liver transplantation*

Presented in part at the United States and Canadian Academy of Pathology Meeting, Atlanta, GA, March 3 to 9, 2001.
https://doi.org/10.1053/hupa.2002.129419Get rights and content

Abstract

The incidence of cryptogenic cirrhosis (CC) has decreased since the discovery of hepatitis C virus (HCV), still the etiology in 5% of cases with cirrhosis remains unresolved. Our aims were to define the clinicopathologic features of CC at liver transplantation (LT), evaluate the post-LT course with outcome and define the possible pathogenetic mechanisms. 27/534 LT recipients (5%) over a period of 16.5 years were entered in the LT database as cases of CC. A detailed analysis of pre- and post-LT clinical and all liver pathology specimens was performed. Based on clinicopathologic findings, a more definite diagnosis was possible in 23 of 27 (85%): Nonalcoholic steatohepatitis (NASH) in 9 (33%), autoimmune liver disease (AILD) in 6 (22%), alcoholic liver disease in 4, secondary biliary cirrhosis in 2 and 1 each of hepatitis C and portal venopathy. 4/27 cases remained unresolved. In the NASH group, native livers had focal steatosis, Mallory's hyalin, glycogenated hepatocytic nuclei, high-grade inflammation, and 3+ bile duct proliferation. Large cell dysplasia was more common in this group compared to other patients. Two patients had recurrence of NASH after LT. In AILD group native livers had little or no bile duct proliferation. Two patients had recurrence in AILD group. Of 27 patients 19 are alive (70%) with a follow-up of 407-3647 days. Based on the study results, the following conclusions were reached: (1) CC results from varying etiologies, which can be defined by a careful clinicopathologic analysis in a majority (85%) of cases; (2) Nonalcoholic steatohepatitis (33%) and AILD (22%) are the common underlying causes of CC; and (3) Post-LT outcome for CC is disease dependent with, recurrent disease seen in both nonalcoholic steatohepatitis (22%) and autoimmune liver disease (33%). HUM PATHOL 33:1098-1104. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Patient population

During the period of 16.5 years from July 1983 to December 1999, 534 patients underwent LT (cadaveric, 532; live donor, 2) in our program. Twenty-seven (5%) of these 534 patients entered in the LT database as cases of CC constituted our study cases.

Histopathologic evaluation

A detailed histologic evaluation of all liver specimens (native and allograft biopsies), was performed by 2 pathologists (G.A. and U.K.) without prior knowledge of clinical information. Special stains for fibrous tissue (trichrome), reticulin, and

Results

The 27 cases could be broadly categorized into 4 groups. These were nonalcoholic steatohepatitis (NASH), autoimmune liver disease (AILD), “other” etiologic processes, and unresolved. Some cases from each category had clinical and/or pathologic features suggestive of more than 1 underlying pathogenetic mechanisms. These were assigned to a group based on the predominant pathologic features. The demographic, clinical, serologic, and pathologic features are listed in Tables 1 and 2.

Discussion

The 5% incidence of CC available from our transplant database is similar to that recently reported in the literature. However, some authors7 believe that the frequency of this diagnosis is truly uncertain, because it may reflect different geographic distribution, referral patterns, and, most of all, the extent of clinical investigative efforts. This explains the variability of diagnosis implicated in the pathogenesis of CC in previous studies.8, 9, 10, 11, 12 Some of the possible causes of CC

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      As disease progresses, steatosis, ballooning, and inflammation dissipate [31]. In addition, cryptogenic cirrhosis patients are more likely to have metabolic syndrome/obesity [32,33], and NASH often recurs in post-transplant livers [34]. These observations have formed the main argument for linking cryptogenic cirrhosis to NASH.

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    *

    Address correspondence and reprint requests to Urmila Khettry, MD, Department of Pathology, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805.

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