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Diabetes Is Leading Cause of Attributable Cases of Hepatocellular Carcinoma

I was surprised by this article - and rather dismayed. I hate posting negative news but I always think it is better to know. Of course, I happen to be a diabetic.....wouldn't you just know?

Diabetes Is Leading Cause of Attributable Cases of Hepatocellular Carcinoma
Nick Mulcahy

April 28, 2010 (Washington, DC) — Which risk factor for hepatocellular carcinoma (HCC) is associated with the largest proportion of cases of the disease in the United States?

If you answered hepatitis C (HCV), hepatitis B (HBV), or alcohol-related disease, you would be wrong.

The mistake is understandable. These risk factors have the highest odds ratios for HCC, and therefore put an affected individual at relatively higher risk of developing the disease than other factors, said Katherine McGlynn, PhD, from the National Cancer Institute (NCI), here at the American Association for Cancer Research (AACR) 101st Annual Meeting.

However, more cases of HCC overall are attributable to diabetes than any other risk factor, she said during a meeting press conference, where the results of the study were highlighted.

The impact of well known risk factors for HCC, such as hepatitis, "tends to be misinterpreted" because information on their incidence is not presented, Dr. McGlynn told reporters.

Also, "there is a perception that the majority of cases of the disease are not associated with a known risk factor," she said.

But the new study from Dr. McGlynn and colleagues from the NCI and Baylor College of Medicine in Houston, Texas, sheds light on the risk factors for HCC and their incidence.

They found that diabetes was associated with the greatest percentage of cases (33.5%), followed by alcohol-related disorders (23.9%), HCV infection (20.7%), HBV infection (5.7%), rare metabolic disorders (3.1%), and obesity (2.7%).

The findings conflict with conventional wisdom about HCC and its associated risks, said Dr. McGlynn.

Much of the hepatocellular carcinoma literature now states that HCV is 'the major risk factor.'

"Much of the hepatocellular carcinoma literature now states that HCV is 'the major risk factor for hepatocellular carcinoma in the United States'," she told Medscape Oncology.

Overall, approximately 63% of HCC was associated with 1 or more of these risk factors, indicating that 37% of cases are not explainable by the known risk factors.

Still, the new findings point to an important direction in the prevention of HCC.

"Overall, controlling diabetes might have a greater impact than any other single factor on reducing the incidence of hepatocellular carcinoma in the United States," the study authors conclude in their abstract.

The incidence of HCC has been steadily increasing in the United States, said Dr. McGlynn. The total incidence was about 1.59 per 100,000 person-years in 1975; by 2006, the total incidence reached 4.82 per 100,000 person-years, according to a graphic presented by Dr. McGlynn.

Mining the SEER–Medicare Database

In the study, the investigators reviewed data from the NCI Surveillance, Epidemiology and End Results Program (SEER)–Medicare linked database.

The case population consisted of 5607 people diagnosed with HCC who had at least 3 prediagnostic years of Medicare coverage between 1994 and 2005. The control population was a 5% random sample of people residing in SEER–Medicare locations.

For each HCC risk factor, odds ratios of an individual developing HCC were calculated.

They found that HCV infection was the risk factor with the highest odds ratio (44.26; 95% confidence interval [CI], 39.52 - 49.56). The odds ratio (95% CI) for HBV infection was 13.37 (10.53 - 16.97); for alcohol-related disease was 4.43 (4.14 - 4.74); for rare metabolic disorder was 3.51 (2.96 - 4.15); for diabetes was 2.37 (2.23 - 2.52); and for obesity was 1.53 (1.37 - 1.72).

The risk-factor percentages also varied by racial/ethnic group.

In terms of explainable risk factors, the investigators found that 67.9% of Asians with HCC had 1 or more of the identified risk factors, whereas only 53.5% of blacks had an identifiable risk factor. These 2 groups had the highest and lowest percentages, respectively; Hispanics (64.9%) and whites (62.9%) were in between.

The investigators also used the SEER–Medicare data to calculate the proportion of HCC cases attributable to the risk factors. As noted above, the order of risk factors was very different, with diabetes at the top of the list of attributable cases.

Are clinicians acutely aware that diabetes causes HCC?

"I think so," said Ernest T. Hawk, MD, MPH, vice president of the Division of Cancer Prevention and Population Sciences at the University of Texas M.D. Anderson Cancer Center in Houston. Dr. Hawk moderated the AACR press conference at which Dr. McGlynn spoke.

I suspect that primary care physicians may not know that persons with diabetes are at increased risk.

"It's well known that diabetes and overweight can cause hepatocellular carcinoma. They are in the list of causes in all medical textbooks. But they may be under a name like metabolic syndrome," he told Medscape Oncology.

However, Dr. McGlynn said that, compared with the other causes, diabetes and overweight have been associated with HCC only "more recently."

"I suspect that primary care physicians may not know that persons with diabetes are at increased risk of hepatocellular carcinoma," she said.

The authors have disclosed no relevant financial relationships.

American Association for Cancer Research (AACR) 101st Annual Meeting: Abstract 1816. Presented April 19, 2010.

14 Responses
Avatar universal
Mike - thanks for posting.

Interesting news but I think Nick Mulcahy may sensationalizing McGlynn's findings a bit (which often happens in reporting conference reports). The actual abstract, from poster presentation 1826 at the recent AACR, is below (available from their website by searching conference program).  Odds Ratio (OR) and Attributable Risk (AR) are competing  stats for measuring the association between an effect and a condition (defn of AR given on wikipedia page).

McGlynn applied both stats to what seems to be a good sized sample. For HCC, HCV has the highest overall OR (44.26), which is pretty darn high. In assessing the effect via the AR statistic, the HCV effect dropped to 3rd place (20.7%)  behind diabetes (34%) and alcohol (24%) - but only when averaging across all patients. When blacks, whites, asians and hispanics were broken out, only among whites did the diabetes AR come out  on top.  (OR by group not given)

This seems an interesting contribution but to interpret it as indicating that diabetes is a cause of hcc  independent of hcv seems like stretching what McGlynn reported. We know there's a very strong diabetes/hcv link and  it's not clear (to  me at least) that anything in that report explains to what extent  diabetes "causes" hcc simply by correlation with the fact that many diabetics with hcc also had (resolved or unresolved?) hcv.
-----------------abstract text
In the United States, known risk factors for hepatocellular carcinoma (HCC) include infection with the hepatitis B virus (HBV), infection with the hepatitis C virus (HCV), excess alcohol consumption, diabetes, obesity and several rare metabolic disorders (hemochromatosis, α-1 antitrypsin deficiency, porphyrias). The proportion of risk in the U.S. attributable to each factor separately, and to all factors together, however, is not well understood. To better quantify the risk attributable to these factors, logistic regression analysis was conducted using data from the SEER-Medicare linked database. All persons diagnosed with HCC (n=5,607), with at least 3 pre-diagnostic years of Medicare coverage between 1994 and 2005, were included as cases. A 5% random sample of persons residing in SEER locations (n=190,782) were included as controls. For each risk factor, odds ratios (OR) with their 95% confidence intervals (95%CI), and attributable risks (AR) with their 95%CI were calculated. In addition to calculating overall risks, risks were calculated after stratifying on race/ethnicity, gender and time period of HCC diagnosis. Among all individuals, the AR of all factors together was 63.3%. The AR among males, however, was higher than the AR among females (64.6% vs. 60.7%, respectively). By race/ethnicity, the AR of all factors together was highest among Asians (67.9%). This AR was followed by that among Hispanics (64.9%), then whites (63.3%) and finally, blacks (53.0%). Among specific factors, diabetes had the greatest AR at 34%, followed by alcohol-related conditions at 24.0%, HCV at 20.7%, HBV at 5.7%, metabolic disorders at 3.1% and obesity at 2.0%. These findings differed by gender and race/ethnicity, however. While diabetes had the highest AR among both males and females, the factor with the second highest AR among males was alcohol-related diseases, while among females; the factor with the second highest AR was HCV. The factors with the highest AR among each race/ethnic group were: whites - diabetes (36.4%) and alcohol-related disease (23.5%), blacks - HCV (31.9%) and alcohol-related disease (20.3%), Hispanics - alcohol-related disease (29.9%) and diabetes (28.0%), and Asians - HCV (31.7%) and diabetes (26.5%). These findings indicate that the current increase in incidence of HCC in the U.S. may be fueled by different factors in different racial/ethnic and gender groups. Overall, controlling diabetes might have a greater impact than any other single factor on reducing the incidence of HCC in the U.S.
Avatar universal
That's really sobering news, but important information to have I think.  Thanks Mike.
Avatar universal
Good information Mike.
179856 tn?1333550962
Wow I had no idea - and IR being a negative predictor isn't that having to do with the same sort of issues?  It's scary stuff I certainly would have said it was been HCV - and we consider ourselves the educated 'experts' well WRONG!!!!!!!!!!!!!!!

I too always think it's better to know and be prepared rather than live in blissful ignorance (which is why I'm such a basket case I guess).

Thank you quite interesting information.
87972 tn?1322664839
Wow, Mike; very interesting. I’m diabetic as well; I’ll try to discuss this with my hepatologist next month when I go in for HCC monitoring. One thing that wasn’t mentioned in this read was how much/if tight blood sugar control changes this picture; I’ve been doing very well in that department now that I’m finished with IFN treatment. My last A1c result was 5.5%, and my fingerstick average has been around 85-90 mg/dL. I imagine my doc will have seen this and had time to digest it in time for my next appointment. As always, great to see you post, Michael—

1117750 tn?1307390169
i would imagine well regulated diabetics would not be affected so badly, as the balance is the same, only a wild guess of course
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