脂肪肝增加肝细胞癌风险

波士顿——美国肝病研究学会(AASLD)年会上报告的一项研究显示，未出现肝硬化的非酒精性脂肪肝(NAFLD)似乎是导致肝细胞癌(HCC)发病率增加的重要原因。

密苏里大学胃肠病与肝病科的Rubayat Rahman博士报告称，该研究数据表明，非肝硬化NAFLD患者发生HCC具有独特的潜在病理生理学特点，这一发现或有助于解释HCC发病率增加的原因。

研究者对美国国立癌症研究所的监测、流行病学和最终结果(SEER)数据库与1993~2007年联邦医疗保险(Medicare)参保人员及索赔文件数据库中HCC患者资料进行了合并分析。在共计17,895例HCC病例中，2,863例(16%)仅患有NAFLD，没有其他任何HCC风险因素或病因。合并后的数据库涵盖了30%的Medicare参保人群，SEER数据库包括了28%的美国人口中18种癌症的登记人群，65岁以上人群占93%，并与Medicare参保人员相匹配。

据Rahman 博士称，NAFLD(16%)是仅次于感染(44%)和酒精脂肪肝(19%)的第3大HCC最常见危险因素(21%为其他因素)，而在亚洲和太平洋岛国，是仅次于感染的第2常见危险因素。

分析结果显示，在与NASH相关的HCC患者中，36%为肝硬化患者， 18%仅为肝脂肪变性和非NASH或其他不良病理性改变患者。非肝硬化患者早期HCC(Ⅰ或Ⅱ期)比例高于肝硬化患者(62% vs. 44%)，癌症分级也相对较低(Ⅰ或Ⅱ级，76% vs. 56%)。

尽管自1993年以来，肝硬化NAFLD相关 HCC患者年百分比呈增加趋势，但自1999年以后非肝硬化NAFLD相关 HCC患者年增长数超过前者。后者平均年发病例数由1993~2000的51例增长至2001~2007年的88例，而前者年发病数未见变化。

非肝硬化NAFLD相关 HCC患者体重指数>30 kg/m²、2型糖尿病以及血脂异常等3种代谢性综合征患者比例明显较高。患有上述每种疾病的非肝硬化NAFLD患者罹患HCC的几率高于肝硬化NAFLD患者，尽管后者罹患HCC总几率相对较高[比值比(OR)，16.5]。

Rahman博士在回答与会者有关肝硬化或NASH确诊时未行组织病理学集中系统评估的质疑时称，与Medicare相匹配的SEER数据库中的患者接受肝脏活检诊断时均具有CPT程序编码和ICD-9诊断编码。另有与会者认为，上述患者癌症发病率较高，数据库也没有包含NASH最高发病年龄为55岁的患者，因此建议应慎重将NAFLD列为HCC独立危险因素。

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By: JEFF EVANS, Internal Medicine News Digital Network

BOSTON – Nonalcoholic fatty liver disease without cirrhosis appears to be a significant contributor to the rise in the incidence of hepatocellular carcinoma in the past two decades, according to a study linking population-based data from the National Cancer Institute with Medicare enrollment and claim files during 1993-2007.

"Our data suggest a unique underlying pathophysiology for development of HCC [hepatocellular carcinoma] in noncirrhotic NAFLD [nonalcoholic fatty liver disease]," Dr. Rubayat Rahman said at the annual meeting of the American Association for the Study of Liver Diseases.

The finding may help to explain the rise in the incidence of the malignancy, which has had no clear explanation, added Dr. Rahman of the division of gastroenterology and hepatology at the University of Missouri, Columbia.

Of 17,895 HCC cases in the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, 2,863 (16%) had only NAFLD without any other risk factors or etiologies for HCC. The linked database covers 30% of the U.S. Medicare population. SEER itself contains data from 18 cancer registries covering 28% of the U.S. population, and 93% of the individuals in the database who are at least 65 years are matched to a Medicare enrollment file.

At 16%, NAFLD was third most common risk factor for HCC after infection (44%) and alcoholic diseases (19%) – 21% were other causes – but it was the second most common risk factor after infection in Asians and Pacific islanders, said Dr. Rahman.

Cirrhosis was not present in 36% of the NAFLD-related HCC cases; of those, 18% had only steatosis and not nonalcoholic steatohepatitis (NASH) or other adverse changes in pathology. Patients without cirrhosis more often had early-stage disease (stage I or II) than did those with cirrhosis (62% vs. 44%), as well as favorable grades (I or II, 76% vs. 56%).

Although the annual percentage change of NAFLD-related HCC with cirrhosis has increased since 1993, 1999 marked a point when the annual growth of NAFLD-related cases of HCC without cirrhosis outpaced those with cirrhosis. The average number of cases per year of NAFLD-related HCC without cirrhosis grew significantly from 51 in 1993-2000 to 88 in 2001-2007, compared with no change in cases with cirrhosis.

Three components of the metabolic syndrome – body-mass index greater than 30 kg/m2, type 2 diabetes mellitus, and dyslipidemia – occurred in significantly greater proportions of patients with NAFLD-related HCC without cirrhosis than in those with cirrhosis. The odds of developing HCC for each of those three components among noncirrhotic NAFLD patients was higher than for those with cirrhotic NAFLD, although the overall odds of developing HCC were higher among patients with cirrhotic NAFLD (odds ratio, 16.5) than in those with noncirrhotic NAFLD (OR, 3.1).

One audience member expressed concern about determining the presence of cirrhosis or NASH in the data without a systematic assessment of histopathology performed in a centralized way, but Dr. Rahman noted that the Medicare-matched SEER data have CPT procedural codes and ICD-9 diagnostic codes for diagnoses made through liver biopsy. Another attendee also suggested caution in calling NAFLD a risk factor for cancer alone because the people in the database have a higher rate of cancer, and the database does not include the peak of NASH at age 55 years.