News; Hepatitis Weekend Round-Up

'Victrelis'(R) (boceprevir) Authorised In The European Union
MSD (NYSE: MRK), known as Merck in the United States and Canada, announced today that the European Medicines Agency (EMA) has granted marketing authorisation to 'Victrelis'(boceprevir), the first licensed product in a new class of medicines to treat hepatitis C. Boceprevir is indicated to treat chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult pati...

INCIVO (telaprevir), (CHMP) of the European Medicines Agency (EMA) recommending approval of hepatitis c drug
Tibotec Virco-Virology BVBA, one of the Janssen Pharmaceutical Companies, announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the approval of INCIVO (telaprevir), a direct acting antiviral (DAA) for the treatment of chronic genotype-1 hepatitis C virus (HCV), in combination with pegylated-interferon and ribavirin, the previously accepted standard of care.

Hepatitis C Drug Incivek (telaprevir); What are the side effects ?
July 22
Telaprevir's safety profile is based on exposure in more than 3,800 patients. Addition of telaprevir to peginterferon and ribavirin increased the incidence of specific adverse events. The majority occurred in the first 12 weeks, were mild to moderate, and did not lead to treatment discontinuation. Rash and anemia were identified as key telaprevir-associated adverse events. Addition of telaprevir resulted in an increased incidence and severity of these events, as well as treatment discontinuations. Rash and anemia were well characterized during the development program, and both were reversible and manageable. Early recognition of these key events helped us characterize them and develop management strategies that were tested in Phase 3.

Sexual Transmission of Hepatitis C Virus Among HIV-Infected Men Who Have Sex with Men --- New York City, 2005--2010 -
Hepatitis C should be added to the list of infections spread among HIV-infected MSM who have sex with HCV-infected partners. HIV-infected patients should be counseled and reminded that unprotected sex between HIV-infected partners can transmit other infections, including HCV. In addition to HCV screening for MSM newly diagnosed with HIV, routine HCV screening using both ALT and antibody testing should be considered for HIV-infected MSM, particularly those with high-risk sexual behaviors or concomitant ulcerative sexually transmitted diseases (e.g., syphilis and herpes simplex virus). Finally, newly diagnosed HCV infections among HIV-infected MSM should be reported to state and local health authorities."

From Medscape Medical News
Telaprevir and Peginterferon–Ribavirin Improve HCV Outcomes
Laurie Barclay, MD
Authors and Disclosures
June 22, 2011 — Telaprevir added to peginterferon–ribavirin significantly improves rates of sustained virologic response in previously untreated patients with hepatitis C virus (HCV) genotype 1 infection and in those who require retreatment, according to the results of 2 randomized controlled trials reported in the June 23 issue of the New England Journal of Medicine. Most patients received only 24 weeks of therapy.
Medscape Medical News previously reported that the US Food and Drug Administration (FDA) had approved telaprevir, in combination with peginterferon alfa and ribavirin, to treat chronic HCV genotype 1 infection in patients at least 18 years old with compensated liver disease, including cirrhosis, who are previously untreated or who have been previously treated with interferon-based treatment.
Study 1: ADVANCE Study
"In phase 2 trials, telaprevir, [an HCV] genotype 1 protease inhibitor, in combination with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients," write Ira M. Jacobson, MD, from the Weill Cornell Medical College and Center for the Study of Hepatitis C, New York, NY, and colleagues from the ADVANCE Study, an international, phase 3, randomized, double-blind, placebo-controlled trial.
Participants (n = 1088) with previously untreated HCV genotype 1 infection were randomly assigned to 1 of 3 treatment groups. The T12PR group received 12 weeks of telaprevir combined with peginterferon alfa-2a and ribavirin, followed by 12 weeks of peginterferon–ribavirin alone if HCV RNA level was undetectable at weeks 4 and 12 or by 36 weeks of peginterferon–ribavirin if HCV RNA level was detectable at either week 4 or 12.
The T8PR group received 8 weeks of telaprevir with peginterferon–ribavirin and 4 weeks of placebo with peginterferon–ribavirin, followed by 12 or 36 weeks of peginterferon–ribavirin according to the same HCV RNA criteria. The PR group received placebo with peginterferon–ribavirin for 12 weeks, followed by 36 weeks of peginterferon–ribavirin. The main study outcome was the proportion of patients with sustained virologic response, defined as undetectable plasma HCV RNA levels 24 weeks after the last planned dose of study treatment.
Compared with the PR group, the T12PR and T8PR groups had significantly more patients with a sustained virologic response (75% and 69%, respectively, vs 44%; P < .001 for the T12PR or T8PR group vs the PR group). More than half (58%) of patients receiving telaprevir were eligible to receive 24 weeks of total treatment.
Compared with patients receiving peginterferon–ribavirin alone, those receiving telaprevir had higher rates of anemia, gastrointestinal tract adverse effects, and skin rashes. Overall rate of discontinuation of the study drugs because of adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group.
"Telaprevir with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients," the study authors write.
Study 2: REALIZE Study
The REALIZE Study was a randomized, phase 3 trial led by Stefan Zeuzem, MD, from Johann Wolfgang Goethe University Hospital in Frankfurt, Germany. The investigators examined the effects of adding telaprevir to peginterferon alfa-2a plus ribavirin in 663 patients with HCV genotype 1 infection who had no response or only a partial response to previous treatment, or who experienced a relapse after initially responding to treatment.
Participants were randomly assigned to the T12PR48 group (n = 266; telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks), the lead-in T12PR48 group (n = 264; 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks), or the control group (n = 132; PR48; peginterferon plus ribavirin for 48 weeks. The rate of sustained virologic response, defined as no detectable HCV RNA levels 24 weeks after the last planned dose of a study medication, was the main study outcome.
Among patients who had a previous relapse, the 2 telaprevir groups had significantly higher rates of sustained virologic response than the control group (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group). Among patients who had a previous partial response, rates were 59%, 54%, and 15%, respectively, and among patients who previously had no response, rates were 29%, 33%, and 5%, respectively (P < .001 for all comparisons). The telaprevir groups had more frequent grade 3 adverse events than the control group (37% vs 22%), and these events were mostly anemia, neutropenia, and leukopenia.
"Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase," the study authors write.
Clinical Practice Article
An accompanying Clinical Practice article, by Hugo R. Rosen, MD, at the Division of Gastroenterology and Hepatology, University of Colorado in Denver, discusses management of chronic HCV infection. He notes that liver biopsy remains the standard for assessment of hepatic fibrosis and facilitates prognostication and decision making.
Treatment goals are to prevent complications and death from HCV infection. Symptomatic extrahepatic HCV, such as cryoglobulinemia, is an indication for therapy regardless of the stage of fibrosis. On the basis of considerable evidence from randomized trials during the past decade, pegylated interferon (peginterferon) plus ribavirin became the standard of care for all HCV genotypes.
The protease inhibitors telaprevir and boceprevir were recently approved by the FDA. On-treatment viral kinetics can be used to predict the likelihood of response and to guide treatment duration.
"Although peginterferon–ribavirin is likely to remain the backbone of antiviral therapy for the foreseeable future, options for treating HCV are expected to expand rapidly in upcoming years," Dr. Rosen writes. "The optimal combination of agents (including nucleoside and nonnucleoside polymerase inhibitors, inhibitors of NS4B and NS5A proteases, modulators of the immune response, and medications that interfere with lipid metabolism, which is essential for the assembly and maturation of HCV particles) and duration of therapy will need to be defined, in order to maximize rates of sustained virologic response while minimizing the risk that resistance will develop. A recent pilot study of a combination of directly acting antiviral agents suggests the possibility of treating HCV infection with an interferon-free, oral approach."
Tibotec and Vertex Pharmaceuticals funded both studies. Financial relationships of the study authors are listed on the New England Journal of Medicine Web site with the full text of the journal articles. Dr. Rosen has disclosed no relevant financial relationships.
N Engl J Med. 2011;364:2405-2416, 2417-2428, 2429-2438.
Authors and Disclosures
Author(s)
Laurie Barclay, MD
Freelance writer and reviewer, Medscape, LLCDisclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

From Medscape Medical News
July 22
Genotype 1b HCV Patients Fare Better on Boceprevir
Emma Hitt, PhD
Authors and Disclosures
July 22, 2011 (Rome, Italy) — Boceprevir/peginterferon plus ribavirin is associated with a small but consistently higher sustained viral response (SVR) rate and a lower rate of development of boceprevir-related resistance-associated variants (RAVs) in patients infected with hepatitis C virus (HCV) genotype 1b subtype than in those infected with genotype 1a subtype, according to new data from the SPRINT-2 and RESPOND-2 phase 3 trials.
Daria Hazuda, PhD, vice president of virus and cell biology at Merck Research Laboratories, in Whitehouse Station, New Jersey, presented the findings in a late-breaking oral session here at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.
"It was important to do this study in order to better understand the development of resistance with boceprevir," Dr. Hazuda told Medscape Medical News. "Additional analyses of our clinical studies with boceprevir are ongoing. A 3.5-year long-term follow-up study is underway to evaluate the persistence of resistance-associated variants over time," she added.

In the SPRINT-2 and RESPOND-2 clinical trials, Dr. Hazuda and colleagues compared the SVR to boceprevir in combination with pegylated-interferon alfa-2b plus ribavirin and the associated presence or absence of RAVs between patients with HCV genotype 1a and those with genotype 1b.
The rate of SVR among those receiving boceprevir in the 2 trials was higher in patients with genotype 1b than in those with genotype 1a (66%–73% vs 59%–64%). The number of patients with RAVs detected was higher in genotype 1a patients than in genotype 1b patients in SPRINT-2 (58% vs 48%) and in RESPOND-2 (48% vs 41%).
The researchers also found that the RAVs V36M and R155K were more common in genotype 1a patients, whereas T54A/S, A156S, and V170A were more common in genotype 1b patients.
RAVs were more common in patients with a poor interferon response (defined as a decline in viral load of less than 1 log at week 4) than in those with a good interferon response (a decline in viral load of 1 log or more at week 4) (68% vs 31%). Overall, baseline samples showed a low rate of RAVs, and most patients with RAVs still achieved SVR.
"Understanding which mutations develop and how long they persist may help us assess the potential for retreatment with first-generation protease inhibitors and, importantly, facilitate the development of next-generation protease inhibitors that can work effectively against resistant mutants," Dr. Hazuda explained.
According to Dr. Hazuda, the resistance variants observed with boceprevir are similar, if not identical, to those observed with telaprevir. "Although we do not know if retreatment will be possible, there should be no difference between these 2 first-generation protease inhibitors," she said.
Dr. Hazuda added that it is still not known how long these resistant variants last, or whether the viral population has been altered in a way to make it less likely that patients will respond to retreatment with another first-generation protease inhibitor.
"These are valuable phase 3 trial data, which emphasize the fact that the main determinant of the SVR is not the preexistence of RAVs at baseline but the response to interferon and ribavirin," said independent commentator Jean-Michel Pawlotsky, MD, professor of medicine at the University of Paris-Est, director of the Department of Virology at the Henri Mondor University Hospital in Créteil, France, and director of the Department of Molecular Virology and Immunology at the Mondor Institute of Biomedical Research.
"Patients and doctors should not be afraid of resistance to protease inhibitors," he told Medscape Medical News. "Hepatitis remains theoretically curable in 100% of cases, and new drugs will allow patients who failed on triple-combination therapy the opportunity for treatment in the future," he added.
The study was funded Merck and Co. Dr. Hazuda is an employee of Merck. Dr. Pawlotsky reports acting as a consultant to Vertex, Jannsen, Merck, and Roche.
6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract WELBX04.
Presented July 20, 2011.
Authors and Disclosures
Journalist
Emma Hitt, PhD
Emma Hitt is a freelance editor and writer for Medscape.Disclosure: Emma Hitt, PhD, has disclosed no relevant financial relationships.Dr. Hitt does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.Dr. Hitt does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.

Community-based Primary Care Treatment of HCV Infection
Thomas L. Schwenk, MD
Authors and Disclosures
Abstract
PCPs treated hepatitis C virus infections as safely and effectively as multidisciplinary specialty care providers.
Introduction
Chronic hepatitis C virus (HCV) infection, which affects more than 3 million people in the U.S., often leads to cirrhosis and hepatocellular carcinoma and is the most common reason for liver transplantation. Effective treatment (pegylated interferon and ribavirin) is complex and associated with serious adverse effects. Because treatment usually is provided by specialists, patients in underserved areas often have limited access to treatment — one reason treatment rates are actually declining. In a prospective cohort study from New Mexico, primary care clinicians who provided care at a network of 16 rural practices and 5 prisons received specialist support via video- or teleconferencing for treating HCV-positive patients.
The study population consisted of 407 patients with untreated chronic HCV infections and no major comorbidities such as HIV infection; 261 received community-based care, and the others were treated at a university HCV clinic. Treatment response was essentially identical in the groups; roughly 58% of patients in both groups had no detectable HCV RNA at 24 weeks after the end of treatment regimens. Serious adverse events were more common in the specialty clinic group (14% vs. 7%).
Comment
An editorialist believes the key components of such programs are a strong health information technology platform and support of specialty faculty involvement in clinical and educational relationships. This approach has potential applicability to patient-centered medical home care of other complex chronic diseases

From CCO Treatment Update
On the Front Lines: Battling Chronic Hepatitis C Today and in the Future
Interactive Virtual Presentations and downloadable slidesets
Now Available!
CME-Certified Interactive Virtual Presentation:
Epidemiology, Screening, and Predictors of Response in HCVWatch, listen, and test your knowledge as Peter Ferenci, MD, reviews the latest information on the epidemiology of HCV, screening recommendations, and baseline predictors of response to therapy.
Downloadable PowerPoint Slideset:
Epidemiology, Screening, and Predictors of Response in HCVIn this downloadable slideset, Peter Ferenci, MD, reviews the burden of HCV, recommendations and challenges related to HCV screening, strategies for counseling patients on treatment candidacy, key baseline predictors of response to HCV therapy, and the potential impact of newly approved therapies on HCV management.
*Free Registration Is Required

Mother dies as 150 heart patients told they are at risk from Hepatitis B in NHS hospital outbreak
July 23
By Daily Mail Reporter
A mother has died and hundreds of patients could be infected after hepatitis B was apparently spread by unclean surgical equipment at a hospital.
Patients who have received any kind of heart surgery at the hospital in recent months have been informed that they may have contracted the virus.
The woman who died, who has not been named, is believed to have caught the infection from another patient, possibly after surgeons used the same probe during two operations...

As You Know....

Final SVR results from Pharmasset's PSI-7977 phase 2b study in HCV
Published on July 20, 2011 at 7:27 AM
Pharmasset, Inc. (Nasdaq: VRUS) announced today the final sustained virologic response (SVR) results from its phase 2b PROTON study with PSI-7977 dosed once daily in combination with peginterferon alfa 2a and ribavirin (Peg-IFN/RBV) in subjects with hepatitis C virus (HCV) genotype 2 or 3 who have not been treated previously.
Twenty four out of twenty four subjects (100%) who completed treatment achieved an SVR, defined as HCV RNA below the limit of detection (<15 IU/ml) 24 weeks after the completion of treatment. No subject exhibited breakthrough on treatment or relapse after treatment.
Twenty five treatment-naive subjects with HCV genotype 2 or 3 were enrolled in an open label arm of the PROTON trial, receiving PSI-7977 400mg QD with Peg-IFN/RBV for 12 weeks, with no Peg-IFN/RBV follow-up.
At the European Association for the Study of the Liver (EASL) in April 2011, Dr J. Lalezari presented interim results from this arm showing that 24 out of 24 subjects achieved an SVR12, defined as HCV RNA below the limit of detection (<15 IU/ml) 12 weeks after the completion of treatment. The combination was generally safe and well tolerated with one subject discontinuing treatment after day 1 and was lost to follow up. Overall PSI-7977 with Peg-IFN/RBV demonstrated potent viral suppression in subjects with HCV genotype 2 or 3 over 12 weeks of treatment.
Pharmasset anticipates reporting the SVR12 results from the PROTON trial in genotype 1 HCV subjects in the second half of 2011.
SOURCE Pharmasset

Next Thursday: World Hepatitis Day
And in some The-More-You-Know news: next Thursday, July 28th is World Hepatitis Day. And with that, the San Francisco Task Force on Hepatitis will organize its first educational outreach campaign, sponsored by [pharmaceutical company name redacted]. Volunteers from Bay Area organizations including the Oasis Clinic and San Francisco needle exchange volunteers will hand out hepatitis C fact sheets at BART and Muni stations throughout the city (Castro, 16th/Mission, Montgomery and Embarcadero).
To the press release! "It is estimated that 1 out of 50 people in the United States is living with hepatitis C and most of them don’t know it. This outreach campaign is aimed to educate the public on this 'silent killer' and list of reasons why individuals should get tested."
If you want to get tested -- and you should for peace of mind -- we strongly suggest checking out Magnet SF in the Castro. (Excellent service for both gay and straight people alike!) Make an appointment here or simply walk in and talk to the wildly friendly and knowledgeable staff for more details. 4122 18th Street (as Castro

The Doctor Is In

How Common Are False Diagnoses of Specific Diseases?
By George Lundberg, MD, Editor-at-Large, MedPage Today
July 19, 2011





Metabolic syndrome linked to liver cancer risk
Updated: 2011-07-22 14:21:22
Individuals who suffer from metabolic syndrome may want to consider seeking liver cancer testing at some point in the near future, as a new study has found that the condition is major risk factor for the deadly cancer.
Hepatitis infection and inflammatory bowel disease are the two most well established risk factors for liver cancer. However, these conditions only explain about half of all cases of tumor growth. With liver cancer diagnoses becoming more common, it is necessary to identify more risk factors for the disease.For the study, researchers from the National Cancer Institute examined medical data from more than 20,000 individuals both with and without liver cancer. The results showed that 34 percent of cancer patients had metabolic syndrome, a collection of conditions marked by a large waistline, elevated blood pressure and cholesterol levels and unhealthy blood sugar regulation.
Metabolic condition is becoming much more common in the U.S. as a result of rising obesity rates. The findings help explain why cases of liver cancer are growing in prevalence. The researchers said that their results further underscore the need to reduce obesity rates in the U.S.

FDA

FDA committee votes down first-of-a-kind diabetes drugs
Posted: 2011-07-20 14:32
The first of a highly anticipated class of diabetes drugs assessed by the US Food and Drug Administration (FDA) got the thumbs-down from the agency’s Endocrinologic and Metabolic Drugs Advisory Committee yesterday. The FDA panel rejected dapagliflozin, developed by Bristol-Myers Squibb and AstraZeneca, by a 9–6 margin.
Unlike current type 2 diabetes medicines, which modulate insulin activity to affect sugar levels in the bloodstream, dapagliflozin regulates blood sugar independently of insulin by preventing the protein sodium-dependent glucose cotransporter 2 (SGLT2) from reabsorbing glucose into the kidney. Usually, this simple sugar is dumped back into the bloodstream, inducing a symptom known as hyperglycemia. But dapagliflozin and similar drugs in development cause the kidney to excrete the excess glucose into the urine.
These SGLT2 inhibitors excite researchers and doctors because they provide “a new option for patients with diabetes with a totally different mechanism of action,” says Steven Shoelson, head of pathophysiology and molecular pharmacology at the Joslin Diabetes Center in Boston who is not involved in the development of these drugs.
In phase 3 trials, dapagliflozin proved to regulate blood sugar and even caused weight loss in many of study subjects. However, the FDA panel voted down the drug because of safety issues. Notably, patients taking dapagliflozin had higher rates of breast and bladder cancer compared to those in the control arms of the trials.
Looking ahead, other drugmakers developing experimental SGLT2 inhibitors will have to “be very careful to make sure that they do sufficient numbers of people to test [cancer incidence] adequately,” says Shoelson. Johnson & Johnson have a drug called canagliflozin in phase 3 trials, and Boehringer Ingelheim and Lexicon Pharmaceuticals have a related agent in phase 2 testing.
The FDA doesn’t have to follow the recommendations of its advisory panels, but it usually does. A final decision is due 28 October.

FDA Warning on Atrial Fibrillation Drug Multaq
Doubling of Deaths Halts Multaq Study; FDA Mulls Risk to Current Users
By Daniel J. DeNoonWebMD Health News
Reviewed by Laura J. Martin, MD
July 22, 2011 -- If you're taking the atrial fibrillation drug Multaq, the FDA wants you to call your doctor right away.
Don't stop taking the drug -- that could be dangerous. But the FDA wants patients to be aware that a clinical trial of Multaq, called PALLAS, was halted when the drug doubled the risk of death, stroke, and heart failure hospitalization in heart patients with permanent atrial fibrillation.
Multaq is approved to treat paroxysmal atrial fibrillation (intermittent), persistent atrial fibrillation, or atrial flutter. The big question -- now the subject of an FDA investigation -- is exactly how the PALLAS findings apply to current patients.
Multaq was approved in 2009 after the ATHENA clinical trial showed it decreased deaths in patients with non-permanent atrial fibrillation and atrial flutter.
But this is now the fifth time the FDA has reported signals of possible risk from Multaq:
Early 2010: The FDA warned of possible signals of congestive heart failure. On Feb. 22, 2011, the FDA revised the warning section of the Multaq label to note cases of worsening heart failure in some patients taking the drug.
Second quarter 2010: The FDA warned of possible signals linking Multaq to a form of heart arrhythmia called torsade de pointes.
Third quarter 2010: The FDA warned of possible signals that Multaq interacted with warfarin to increase warfarin's anti-clotting effect. On March 21, 2011, the FDA changed the drug-interactions section of the Multaq label to reflect this possibility.
In the last three months of 2010, there were possible signals linking Multaq to liver failure. On Feb. 11, 2011, FDA changed the warnings section of the Multaq label to note that the drug should be stopped if liver injury is suspected.
The FDA is telling patients:
Talk to your health care professional about whether you should continue to take Multaq for paroxysmal or persistent atrial fibrillation. Do not stop taking Multaq without talking to your health care professional.
Discuss any questions or concerns about Multaq with your health care professional.
Report any side effects you experience to the FDA MedWatch program (800-332-1088).
The FDA is telling doctors:
Do not prescribe Multaq to patients with permanent atrial fibrillation.
The FDA is evaluating whether and how the preliminary results of the PALLAS study apply to patients taking Multaq for paroxysmal atrial fibrillation, persistent atrial fibrillation, or atrial flutter.
The PALLAS study results are considered preliminary at this time.


Off The Cuff

Mosquitoes Increase Exotic Disease Threat - July 22, 2011
(USA TODAY) -- Mosquitoes are more than just an annoyance for the itchy red bites they leave on our skin. They increasingly raise the prospect of spreading deadly diseases normally not found in the USA, experts warn.

Is anesthesia dangerous?
In pure numerical terms, anesthesia-associated mortality has risen again. The reasons for this are the disproportionate increase in the numbers of older and multimorbid patients and surgical procedures that would have been unthinkable in the past. This is the result of a selective literature review of André Gottschalk's working group at the Bochum University Hospital in the current issue of Deutsches Ärzteblatt International.
Contact: Dr. André Gottschalk0234-299-3001
Deutsches Aerzteblatt International

Liver, belly fat may identify high risks of heart disease in obese people
Increased liver fat and abdominal fat may increase risk of heart disease and other serious health problems. Measuring liver and belly fat may identify obese people at risk of developing abnormal cholesterol. For some obese people, fat is not metabolically detrimental.