BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.
BACKGROUND & AIMS:Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.
Authors: Robert S Sandler; James E Everhart; Mark Donowitz; Elizabeth Adams; Kelly Cronin; Clifford Goodman; Eric Gemmen; Shefali Shah; Aida Avdic; Robert Rubin Journal: Gastroenterology Date: 2002-05 Impact factor: 22.682
Authors: Kenneth K Tanabe; Antoinette Lemoine; Dianne M Finkelstein; Hiroshi Kawasaki; Tsutomu Fujii; Raymond T Chung; Gregory Y Lauwers; Yakup Kulu; Alona Muzikansky; Darshini Kuruppu; Michael Lanuti; Jonathan M Goodwin; Daniel Azoulay; Bryan C Fuchs Journal: JAMA Date: 2008-01-02 Impact factor: 56.272
Authors: M Colombo; R de Franchis; E Del Ninno; A Sangiovanni; C De Fazio; M Tommasini; M F Donato; A Piva; V Di Carlo; N Dioguardi Journal: N Engl J Med Date: 1991-09-05 Impact factor: 91.245
Authors: Lindsay Y King; Claudia Canasto-Chibuque; Kara B Johnson; Shun Yip; Xintong Chen; Kensuke Kojima; Manjeet Deshmukh; Anu Venkatesh; Poh Seng Tan; Xiaochen Sun; Augusto Villanueva; Angelo Sangiovanni; Venugopalan Nair; Milind Mahajan; Masahiro Kobayashi; Hiromitsu Kumada; Massimo Iavarone; Massimo Colombo; Maria Isabel Fiel; Scott L Friedman; Josep M Llovet; Raymond T Chung; Yujin Hoshida Journal: Gut Date: 2014-08-20 Impact factor: 23.059
Authors: Ahmed El-Shamy; Francis J Eng; Erin H Doyle; Arielle L Klepper; Xiaochen Sun; Angelo Sangiovanni; Massimo Iavarone; Massimo Colombo; Robert E Schwartz; Yujin Hoshida; Andrea D Branch Journal: J Hepatol Date: 2015-07-26 Impact factor: 25.083