Clinical and pathological progression of non‐alcoholic steatohepatitis to hepatocellular carcinoma

Yasui, Kohichiroh; Hashimoto, Etsuko; Tokushige, Katsutoshi; Koike, Kazuhiko; Shima, Toshihide; Kanbara, Yoshihiro; Saibara, Toshiji; Uto, Hirofumi; Takami, Shiro; Kawanaka, Miwa; Komorizono, Yasuji; Okanoue, Takeshi

doi:10.1111/j.1872-034x.2012.00986.x

Cited by 55 publications

(64 citation statements)

References 35 publications

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“…Mean serum AFP levels measured by enzyme-linked immunosorbent assay were signi cantly higher in patients with HCV-HCC than in patients with NASH-HCC, although a large degree of within-group variability was observed in each group [16]. A trend towards higher AFP levels and a higher proportion of patients with abnormal (>10 ng/mL) AFP levels was observed at HCC diagnosis compared to NASH diagnosis in a small sample of Japanese patients with histologically-proven NASH [17]. Lower AFP levels (<20 ng/mL) were more common in NAFLD-HCC compared to alcoholic disease-HCC or HCV-HCC [5].…”

Section: Serum Biomarkers α Fetoprotein and Des Carboxyprothrombinmentioning

confidence: 93%

“…Its levels were signi cantly higher at the time of HCC diagnosis compared to the time of NASH diagnosis in a small sample of Japanese patients with histologically-proven NASH (mean 34 vs. 18 mAU/mL, p=0.004). Likewise, a higher proportion of patients had abnormal (> 40 mAU/mL) DCP levels at the time of HCC diagnosis [17]. Mean serum DCP levels measured by enzyme-linked immunosorbent assay were not di erent between HCV-HCC and NASH-HCC, although a large degree of within-group variability was observed in each group [16].…”

Section: Serum Biomarkers α Fetoprotein and Des Carboxyprothrombinmentioning

confidence: 96%

“…Hepatocellular carcinoma occurred in comparable numbers of males and females in a small sample of Japanese patients with histologically-proven NASH (n=19, 52.6% female) [17]. In this sample, HCC was diagnosed a er a median follow-up of 3.8 years since NASH diagnosis, during which time the degree of brosis became more advanced in all patients, with J Gastrointestin Liver Dis, December 2014 Vol.…”

Section: Incidence Ratesmentioning

confidence: 99%

“…While some studies found leptin to be elevated in NASH compared to controls or patients with viral hepatitis, other studies failed to nd this association. At most, leptin is associated with the degree of steatosis but not with necroin ammation or brosis, which casts doubt over its association with HCC in NAFLD patients [17,20].…”

Section: Lipids and Adipokinesmentioning

confidence: 99%

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Non-invasive Biomarkers in Non-Alcoholic Steatohepatitisinduced Hepatocellular Carcinoma

Voiculescu

Nanau

Neuman

2014

JGLD

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Non-alcoholic fatty liver disease (NAFLD) is by far the most common form of chronic liver disease worldwide, affecting adults as well as children. Under the term of NAFLD there is a wide spectrum of diseases ranging from simple steatosis to the non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC). Several mechanisms have been described to influence the progression of the disease from the benign NAFL to the aggressive NASH. The imbalance between pro- and anti-oxidant mechanisms and between pro- and anti-inflammatory cytokines is thought to play a pivotal role in the pathogenesis of NAFLD and disease progression toward NASH and fibrosis. The present review intends to look at some of the mechanistic biomarkers to be employed in establishing an early diagnosis in HCC derived from NASH.Abbreviations: ANGPT: angiopoietin-2; AFP: α-fetoprotein; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CI: confidence interval; COL: collagen; DCP: des-carboxyprothrombin; γGT: gamma glutamyl transpeptidase; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HR: hazard ratio; ITG: integrin; LAM: laminin collagen genes; MMP: matrix metalloproteinase; MS: metabolic syndrome; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PDGFRA: platelet derived growth factor receptor-α

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Section: Serum Biomarkers α Fetoprotein and Des Carboxyprothrombinmentioning

confidence: 93%

Section: Serum Biomarkers α Fetoprotein and Des Carboxyprothrombinmentioning

confidence: 96%

Section: Incidence Ratesmentioning

confidence: 99%

Section: Lipids and Adipokinesmentioning

confidence: 99%

See 2 more Smart Citations

Non-invasive Biomarkers in Non-Alcoholic Steatohepatitisinduced Hepatocellular Carcinoma

Voiculescu

Nanau

Neuman

2014

JGLD

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“…Yasui et al [16] performed a multi- . The dark blue bars on the bottom of each panel indicates the overall incidence rates in women age 50-59 years during that time period.…”

Section: Risk Factors For Nash-related Hccmentioning

confidence: 99%

Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma

Khan

Perumpail

Wong

et al. 2015

WJH

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An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in non alcoholic fatty liver disease (NAFLD). Twothirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis (NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of endstage liver disease. One of the major complications observed in patients with NASHrelated cirrhosis is hepatocellular carcinoma (HCC), which has emerged as the sixth most common cancer and second leading etiology of cancerrelated deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis implicating obesity and diabetes mellitus as potential risk factors for HCC. Core tip: The worldwide rise in overweight and obesity has been associated with increasing rates of nonalcoholic fatty liver disease (NAFLD), which is now the most common etiology of chronic liver disease.

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Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.

2014

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Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH‐related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, using national data from the United Network for Organ Sharing registry. From 2002‐2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients with HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the Model for Endstage Liver Disease (MELD) scoring system in 2002 (3.3%, n = 143 in 2000 versus 12.2%, n = 714 in 2005 versus 23.3%, n = 1336 in 2012). The proportion of hepatitis C virus (HCV)‐related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 versus 46.3% in 2007 versus 49.9% in 2012). NASH‐related HCC also increased significantly, and NASH is the second leading etiology of HCC‐related LT (8.3% in 2002 versus 10.3% in 2007 versus 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4‐fold, and the number of LT patients with HCC secondary to HCV increased by 2‐fold. Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More important, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S. (Hepatology 2014;59:2188–2195)

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Clinical and pathological progression of non‐alcoholic steatohepatitis to hepatocellular carcinoma

Abstract: Screening for HCC with imaging is necessary not only in NASH patients with advanced fibrosis, but also in those with less advanced forms of fibrosis, particularly if they are old men. Liver fibrosis progresses to a more advanced stage during the development of HCC in NASH patients.

Cited by 55 publications

References 35 publications

Non-invasive Biomarkers in Non-Alcoholic Steatohepatitisinduced Hepatocellular Carcinoma

Non-invasive Biomarkers in Non-Alcoholic Steatohepatitisinduced Hepatocellular Carcinoma

Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma

Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.

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