From the AGA Journals

Statins cut risk of hepatocellular carcinoma



Statin therapy taken to prevent cardiovascular events also appears to protect against hepatocellular carcinoma, reducing the overall risk for the cancer by 37%, according to the results of a systematic review and meta-analysis.

In a meta-analysis of all the studies in the literature that have examined statins’ effect on HCC risk, use of the drugs was associated with a pronounced and consistent risk reduction (48%) in Asian populations, as well as a still-significant reduction (33%) in Western populations, reported Dr. Siddharth Singh and his associates at the Mayo Clinic, Rochester, Minn.

Video source: American Gastroenterological Association's YouTube page

At present, "it does not seem prudent to prescribe statins for chemoprevention" of HCC in the general population, mainly because of the high number of people who would need to be treated to prevent a single case of HCC. "However, in patients with multiple risk factors, such as East Asian men who have chronic HBV [hepatitis B virus] infection, statins may have a clinically relevant chemoprotective effect against HCC, the investigators said (Gastroenterology 2012 Oct. 15 [doi: 10.1053/j.gastro.2012.10.005]).

Prospective cohort studies or randomized clinical trials of the issue are warranted in populations at high risk for HCC, they noted.

The results of preclinical studies have suggested that statins may decrease the risk of cancers, perhaps because their antiproliferative, proapoptotic, antiangiogenic, immunomodulatory, and anti-infective effects may prevent cancer growth. But clinical studies have produced conflicting results.

Dr. Singh and his colleagues performed a systematic review of the literature for studies that clearly defined statin exposure, reported HCC risk, and either reported relative risks or odds ratios for the development of HCC or provided the data so those risks could be calculated. They then performed a meta-analysis of 10 studies: 7 observational studies and 3 that reported pooled data from 26 randomized clinical trials.

Most of the studies were considered to be of high quality. Most of them accounted for various potential confounders such as patient age; sex; medication use; and the presence of viral hepatitis, cirrhosis, diabetes, or alcoholic liver disease. The likelihood of selection bias and of publication bias in the included studies was judged to be very low.

Altogether the 10 studies included 1,459,417 subjects and 4,298 cases of HCC.

In an initial analysis of the data, the use of statins was associated with a significant 41% reduction in the rate of HCC. After the data were adjusted to account for several potential confounders, the risk reduction was altered slightly, but a robust 37% reduction in HCC rate remained.

The investigators also performed an analysis of the data based on the location of the studies, because the epidemiology of HCC is so different between Western and Asian populations. They found that statin use correlated with a 48% reduction in the rate of HCC in Asian populations, where viral hepatitis is the primary risk factor for the disease, and a 33% reduction in the rate of HCC in Western populations, where the metabolic syndrome, nonalcoholic fatty liver disease, and alcohol-related cirrhosis are the primary risk factors.

The researchers also performed sensitivity analyses according to the studies’ design (cohort vs. case control) and quality (high vs. low). Both cohort and case-control studies confirmed a protective effect of statins against the development of HCC, as did both high-quality and low-quality studies.

In a final sensitivity analysis, each study was serially excluded from the meta-analysis to determine whether any one study was having a dominant effect on the odds ratios. None of the studies was found to markedly affect the outcomes of the analyses.

The study design didn’t permit separate analyses of the protective effects of statins by drug type or by dose or duration of therapy.

The studies included in this meta-analysis were too heterogeneous to allow the investigators to calculate an overall number needed to treat. But the studies restricted to Asian patients were homogeneous and did allow this calculation for men of Asian ethnicity.

Dr. Singh and his associates determined that 5,209 East Asian men would need to be treated with statins to prevent 1 case of HCC per year. For very-high-risk Asian men with chronic HBV-associated cirrhosis, the number needed to treat with statins to prevent 1 case of HCC per year would be 57.

No financial conflicts of interest were reported.

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