Does Nonalcoholic Fatty Liver Disease Predispose Patients to Hepatocellular Carcinoma in the Absence of Cirrhosis? by ProQuest


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									        Does Nonalcoholic Fatty Liver Disease Predispose
          Patients to Hepatocellular Carcinoma in the
                      Absence of Cirrhosis?
                   Grace Guzman, MD; Elizabeth M. Brunt, MD; Lydia M. Petrovic, MD; Gregorio Chejfec, MD;
                                         Thomas J. Layden, MD; Scott J. Cotler, MD

● Context.—Hepatocellular carcinoma (HCC) is recog-                      ylin-eosin–stained slides in 50 cases. Cause of liver disease
nized as a complication of cirrhosis related to nonalcoholic             was determined by review of liver histology, clinical his-
fatty liver disease (NAFLD). Diabetes and the metabolic                  tory, and laboratory data.
syndrome are also associated with HCC. However, it is not                   Results.—Three patients presented with advanced HCC
clear whether NAFLD predisposes patients to HCC in the                   with features of metabolic syndrome, including an elevated
absence of cirrhosis.                                                    body mass index. Each patient had bland steatosis on liver
                                                                         biopsy, without fibrosis or cirrhosis. None of the 3 patients
   Objective.—To seek evidence that HCC can develop in
                                                                         had evidence of any cause for liver disease other than
NAFLD unaccompanied by cirrhosis.                                        NAFLD.
   Design.—Retrospective case study was performed on                        Conclusions.—The cases presented here suggest that
cases from 2004 to 2007 at the University of Illinois at                 NAFLD may predispose patients to HCC in the absence of
Chicago Medical Center, using the key words hepatocel-                   cirrhosis. Further studies are needed to confirm this po-
lular carcinoma, liver explant, and liver resection. The di-             tentially important observation.
agnosis of HCC was identified and confirmed by hematox-                       (Arch Pathol Lab Med. 2008;132:1761–1766)

M     ost hepatocellular carcinoma (HCC) arises on a back-
       ground of cirrhosis, in which ongoing liver injury
and regeneration predispose patients to neoplasia over
                                                                         most common cause of liver disease in the United States.
                                                                         Patients with nonalcoholic steatohepatitis (NASH) may
                                                                         progress to advanced fibrosis and cirrhosis. Nonalcoholic
time.1–6 A notable exception is hepatitis B, in which HCC                fatty liver disease is considered the hepatic manifestation
often occurs in the absence of cirrhosis. However, even in               of the metabolic syndrome, a cluster of conditions that are
hepatitis B, HCC typically occurs with advanced fibrosis.                 related by obesity and insulin resistance.9 Hepatocellular
There have also been sporadic reports2,7,8 of HCC in non-                carcinoma has been recognized in cirrhosis related to
cirrhotic patients with hepatitis C and alcohol-related liver            NASH and to cryptogenic cirrhosis presumed to have
disease. More important, there are well-known cases9–14 of               arisen from NASH.8,9,11,15,16 Moreover, diabetes, which is
HCC that arise in otherwise healthy liver. Whether these                 sometimes associated with NAFLD, has been identified by
cases arise from preexisting adenoma is not known. The                   epidemiologic studies as a risk factor for HCC when pres-
current series of HCC arising in nonalcoholic fatty liver                ent either alone,17–19 or in combination with other causes
disease (NAFLD) without fibrosis consists of cases that are               of chronic liver disease, including viral hepatitis and al-
clinically and pathologically distinct from the fibrolamel-               cohol.15,20 It is not known whether cirrhosis is a necessary
lar type of HCC, which also develops in the absence of                   precondition for the development of HCC in patients with
cirrhosis or fibrosis.                                                    NAFLD.
   Nonalcoholic fatty liver disease is now recognized as the                Herein, we report on 3 patients with features of obesity
                                                                         and metabolic syndrome without cirrhosis. These cases
                                                                         raise questions about the possible pathogenesis of HCC in
   Accepted for publication April 10, 2008.                              NAFLD. Moreover, they raise a clinical concern regarding
   From the Departments of Pathology (Drs Guzman and Chejfec) and        whether patients with NAFLD are possibly at an increased
Medicine (Drs Layden and Cotler), University of Illinois, Chicago; the
                                                                         risk for HCC before the development of cirrhosis.
Department of Pathology and Immunology, Washington University
School of Medicine, St Louis, Mo (Dr Brunt); and the Department of                       MATERIALS AND METHODS
Pathology, New York University Medical Center, New York (Dr Pe-
trovic). Dr Petrovic is now with the Department of Pathology, Keck          Forty-nine cases with histologic evidence of HCC were iden-
School of Medicine, Health Sciences Campus, University of Southern       tified through a search of data from 2004 to 2007 in the pathology
California, Los Angeles.                                                 computer system at the University of Illinois at Chicago Medical
   The authors have no relevant financial interest in the products or     Center, using the key words hepatocellular carcinoma, liver explant,
companies described in this article.                                     and liver resection. The diagnosis of HCC was confirmed by re-
   Reprints: Grace Guzman, MD, Department of Pathology, University       viewing hematoxylin-eosin–stained slides from all cases. Cause
of Illinois at Chicago, 840 S Wood St, Ch
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