News Release 

Lipophilic statins associated with significantly reduced liver cancer incidence and mortality

Embargoed news from Annals of Internal Medicine

American College of Physicians

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information.

1. Lipophilic statins associated with significantly reduced liver cancer incidence and mortality


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Lipophilic statins were associated with significantly reduced hepatocellular carcinoma (HCC) incidence and mortality, but an association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. Findings from a nationwide cohort study are published in Annals of Internal Medicine.

Approximately 500,000 cases of HCC are diagnosed worldwide each year, related primarily to chronic infection with hepatitis B virus or hepatitis C virus. In the U.S. and Europe, incidence of HCC has tripled since the 1970s and mortality is increasing more rapidly for HCC than for any other cancer. As such, there is an urgent need to identify effective primary prevention strategies. Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality is unknown.

Researchers from the Karolinska Institutet, Stockholm, Sweden and Harvard University, Boston, US, studied a nationwide Swedish registry of adults with viral hepatitis B or C to assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality. Compared with a matched cohort that did not use statins, lipophilic statin use was associated with substantially lower risk for incident HCC, all-cause death, and liver-related death. The apparent benefits of lipophilic statins were dose and duration-dependent, with the greatest reduction in HCC risk occurring after at least 600 cumulative defined daily doses (the equivalent of taking a moderate-dose statin for approximately 2 years). A similar association with reduced HCC risk was not found with hydrophilic statin use. According to the researchers, these findings confirm prior data linking statins with improved survival and reduced HCC risk in chronic liver disease.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at To speak with author Jonas F. Ludvigsson, MD, PhD, please contact Andreas Andersson at or

2. American College of Physicians releases paper on methods for managing conflicts of interests in clinical guidelines


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A rigorous process for the disclosure of interests (DOI) and management of conflicts of interest (COI) is essential for developing high-quality clinical guidelines and guidance statements, the American College of Physicians (ACP) says in a new paper published in Annals of Internal Medicine.

Any individual involved in the development of ACP's clinical guidelines and guidance statements must disclose all financial and intellectual interests related to health care from the last three years. Individuals submit disclosures at the start of participation and are required to update their disclosures over the course of their involvement with the Clinical Guidelines Committee, which develops ACP's clinical policy papers. A DOI-COI Review and Management Panel reviews the disclosures, flags potential sources of COI, grades the COI as "low," "moderate," or "high," and manages the individual's participation accordingly. High-level COI results in recusal from authorship, voting, and all committee discussions. Moderate-level COI results in recusal from authorship and voting for clinically relevant topics, but permission to participate in all discussions. Low-level COI results in no role restrictions. All disclosures and COI management decisions are available publicly.

ACP recently published "The Development of Clinical Guidelines and Guidance Statements by the Clinical Guidelines Committee of the American College of Physicians" that presents ACP's methods for developing clinical guidelines and guidance statements.

Notes and media contacts: For an embargoed PDF or an interview with someone from ACP, please contact Steve Majewski at

3. Lack of timely, effective treatment for severe malaria could lead to catastrophe in the U.S.


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The lack of a timely, effective treatment for severe malaria in the U.S. could lead to a catastrophe. Currently, there is no FDA-approved treatment in the U.S. for severe cases, and malaria is becoming a growing concern as our population becomes more globally connected. A commentary on this issue is published in Annals of Internal Medicine.

There are about 2,000 cases of malaria each year in the U.S., and a number of these cases are severe. Severe malaria is associated with neurologic symptoms, severe anemia, acute renal injury, acute respiratory distress syndrome, and jaundice, and can have mortality of more than 50 percent. However, prompt treatment improves outcomes, as mortality is highest in the first 24 hours. In 2017, the pharmaceutical company Eli Lilly, the sole provider of quinidine gluconate, the only FDA-approved intravenous treatment for severe malaria in the U.S., discontinued its manufacture for business reasons. This decision was unfortunate for patients considering that an alternative intravenous medication, artesunate, which must be obtained from the CDC, can take from 8 to 24 hours to arrive by plane.

Authors from the Center for Vaccine Development and Global Health at the University of Maryland are alarmed by the lack of preparedness in the U.S. and suggest that hospitals must develop a malaria preparedness plan similar to what they may have done for the 2014 Ebola outbreak. They say that the U.S. Department of Health and Human Services (HHS) should coordinate a unified preparedness plan for severe malaria, too. The plan should address potential delays in diagnosis and treatment of malaria, with anticipation of different scenarios. At triage, patients should immediately have a rapid diagnostic test for malaria and a thick and thin blood smear should be sent for an immediate reading. If the rapid diagnostic is positive, the clinician should call the CDC Malaria Hotline to start the process of having intravenous artesunate flown in without waiting for the results of the blood smear. According to the authors, while there is no timely, effective treatment for severe malaria in the United States, careful preparation is key to preventing catastrophe.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at To speak with lead author, Mark Travassos, MD, MSc, please contact Joanne Morrison at

4. Multivitamins and calcium supplements among most difficult pills for seniors to swallow


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Most reports of swallowing complications from dietary supplements involve seniors (adults 65 and older) taking multivitamins or calcium supplements. Older adults have higher rates of dysphagia and other swallowing issues than younger persons, and also make up a large proportion of people taking multivitamins and calcium supplements. Findings from a brief research report are published in Annals of Internal Medicine.

Researchers from the U.S. Food and Drug Administration (FDA) reviewed the FDA CAERS (Center for Food Safety and Applied Nutrition Adverse Reporting System) database to identify and characterize dietary supplement-associated swallowing problems in relations to pill size. They found that of 20,791 adverse event reports submitted to CAERS regarding dietary supplements, nearly one-fifth (19.1 percent) indicated swallowing problems. The reports mostly involved females. Of the 64.5 percent of swallowing problem reports that included age data, 76.8 percent involved adults aged 65 years or older. Choking was the most frequently reported problem, followed by foreign body trauma. More than 14 percent of swallowing problem reports cited serious adverse events, including three deaths. According to the researchers, swallowing problems could be reduced by modifying dosage form characteristics and/or by educating patients about how to address swallowing issues.


Notes and media contacts: For an embargoed PDF, please contact Lauren Evans at To interview the lead author, Cecile Punzalan, MD, MPH, please contact Lindsay Haake at or Candace Burns Hoffman at

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