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An Update On Non-Alcoholic Fatty Liver Disease

Fatty Liver

Fatty Liver

Of all of the common complications of obesity, fatty liver disease is perhaps the most insidious. Often starting without clinical symptoms and little more than a mild increase in liver enzymes, it can progress to inflammation, fibrosis, cirrhosis and ultimate liver failure. It can also markedly increase the risk for hepatocellular cancer even in patients who do not progress to cirrhosis.

Now, a paper by Mary Rinella from Northwestern University, Chicago, published in JAMA provides a comprehensive overview of what we know and do not know about early detection and management of this condition.

The findings are based on a review of 16 randomized clinical trials, 44 cohort or case-control studies, 6 population-based studies, and 7 meta-analyses.

Overall between 75 million and 100 million individuals in the US are estimated to have nonalcoholic fatty liver disease with 66% of individuals older than 50 years with diabetes or obesity having nonalcoholic steatohepatitis with advanced fibrosis.

Although the diagnosis and staging of fatty liver disease requires a liver biopsy, biomarkers (e.g. cytokeratin 18) may eventually help in the detection of advanced fibrosis.

In addition, non-invasive imaging techniques including vibration-controlled transient elastography, ultrasound with acoustic radiation force impulse or even magnetic resonance elastography are fairly accurate in the detection of hepatic fibrosis and are the most reliable modalities for the diagnosis of advanced fibrosis (cirrhosis or precirrhosis).

 

Currently, weight loss is the only proven treatment for fatty liver disease. Pharmacotherapy including treatment with vitamin E, pioglitazone, and obeticholic acid may also provide some benefit (none of these treatments currently are approved for this indication by the UD FDA). Futhermore, the potential benefits of existing and emerging anti-obesity treatments on the incidence and progression of fatty liver remains to be established.

As Rinella points out,

“It is important that primary care physicians, endocrinologists, and other specialists be aware of the scope and long-term effects of the disease.”

Clearly, screening for fatty liver disease needs to be part of every routine work up of individuals presenting with excess weight.

@DrSharma
Edmonton, AB

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3,500 Cal Per Pound Is More Like 4,500 Cal

sharma-obesity-balance

Note: see comment #1

One of the most persistent notions about equating caloric deficit to weight loss is the 3500 Cal “rule”.

I have previously posted about why this is nonsense and not exactly helpful when it comes to thinking about clinical weight loss or weight (you’re dealing with physiology NOT physics!).

Now, Nicholas Gwerder, a student from the University of Sacramento, in his Master Thesis, has apparently reviewed the literature on this and concludes that if anything, one pound of weight loss comes closer to 4,500 calories.

Gwerder reaches this conclusion by analysing data from 28 studies in which he compares the theoretical weight loss to the actual weight (and fat) lost in these studies.

Although, I do not have access to Gwerder’s Master Thesis, here is what he says in the summary:

“The energy equivalent of body weight loss varied considerably, dependent upon the constituent portions of fat, water, protein, carbohydrate and mineral lost. Adipose tissue also varied with type and was dependent upon the composition of lipid, water, and protein. The most valid theoretical equivalent for a pound of fat was calculated at 4,423.90 kilocalories based on in vivo extraction of human intracellular lipid samples.”

Thus, as Gwerder points out, the 3,500 per pound notion tossed around (including by a number of guidelines and associations)

“…severely underestimates the caloric values needed to achieve desired fat mass loss. This use of the proper caloric value for fat mass loss has the potential to improve exercise and nutrient recommendations for achieving healthy body fat values.”

Thus, if this number holds true, a daily 500 Cal deficit maintained over 10 weeks will not give you a 10 pound weight loss, but rather only about 7.5 lbs.

All the same, in practice over time this never really works out, not just because of the individual variability (Gwerder notes about 20% variation in this relationship) but because as you reduce your caloric intake, your individual metabolic requirements will very quickly shift to living off fewer calories, which means that pretty soon into your diet, the initial 500 Cal deficit is no longer a deficit (thank your physiology). This is the feared weight-loss plateau – the frustration of every dieter.

So, whether 3,500 or 4,500 Cal per pound, the relationship between calorie restriction and weight loss is not linear and thus extrapolating the amount of expected weight loss based on this deficit seldom works out in practice.

Indeed, I know from my patients that this “rule” is a matter of endless frustration and seldom helpful.

Managing weight is not simply about energy in and energy out.

@DrSharma
Edmonton, AB

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Getting A Grip On Mortality

jamar dynamometerThere are many clinical measures that predict increased risk of cardiovascular and all-cause mortality (e.g. having a high blood pressure).

However, it turns out that perhaps one of the most powerful predictors of mortality is a simple and inexpensive assessment of grip strength – something rarely assessed in clinical practice.

Now, a study by Darryl Leung and colleagues, in a paper published in The Lancet, reports that grip strength does just that.

The paper presents data from the Prospective Urban-Rural Epidemiology (PURE) study, a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings involving nearly 150,000 individuals.

During a median follow-up of 4·0 years, grip strength (as a simple measure of muscular strength) was found to be inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1·16), cardiovascular mortality (1·17), non-cardiovascular mortality (1·17), myocardial infarction (1·07), and stroke (1·09).

In fact, grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure.

In contrast, grip strength was not associated with diabetes, hospital admission for pneumonia or COPD, injury from fall, or fracture.

Interestingly, the association between grip strength and cardiovascular mortality is not new – however, the association with all-cause mortality and the consistency of this findings across populations and economic strata is remarkable.

Obviously, these findings beg the question whether increasing grip strength (or rather muscular strength in general) through resistance training and adequate protein intake will lower mortality – a question that would take a rather large randomised controlled study to answer.

Till then, it is prudent to remember that association does not prove causation – it would thus be premature to conclude that your weak handshake is killing you.

@DrSharma
Edmonton, AB

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Childhood Cranial Radiation Therapy May Increase Obesity Risk in Adults

sharma-obesity-cancer-cellsAmong all of the possible factors that may contribute to obesity, one that is seldom discussed (and most people are largely unaware of) is surviving cancer.

While this is increasingly being appreciated in adults, data on childhood cancer survivors is rather sparse.

Thus, a study by Carmen Wilson and colleagues, published in Cancer, which follows the development of obesity in individuals treated for cancer as kids is of particular interest.

The study looks at 1996 cancer survivors who previously received treatment for cancer at a large Children’s Research Hospital, who survived ≥10 years from diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years).

Interestingly, 47% of survivors, who received cranial radiation therapy developed obesity compared to only 30% of those who did not.

This risk was greatest in those who also received glucocorticoids or were the youngest at the time of treatment.

The researchers also found a significant modifying effect of genetic markers, some of which are known to be involved in neural growth, repair and connectivity.

Thus, this study shows that survivors of childhood cancer appear to be prone to developing obesity as adults particularly if they were treated with cranial radiation therapy and/or corticosteroids.

Clinicians should be aware of this increased risk and should consider measures to prevent excess weight gain in individuals with a history of childhood cancer.

@DrSharma
Edmonton, AB

ResearchBlogging.orgWilson CL, Liu W, Yang JJ, Kang G, Ojha RP, Neale GA, Srivastava DK, Gurney JG, Hudson MM, Robison LL, & Ness KK (2015). Genetic and clinical factors associated with obesity among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort. Cancer PMID: 25963547

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Post-Weight Loss Fat Gain in US Rangers

army-rangersAnd finally, to conclude this week’s discussion of evidence to support the notion that weight cycling predicts weight (fat) gain especially in normal weight individuals, I turn back to the paper by Dulloo and colleagues published in Obesity Reviews, which quotes these interesting findings in US Rangers:

“…U.S. Army Ranger School where about 12% of weight loss was observed following 8–9 weeks of training in a multi-stressor environment that includes energy deficit. Nindl et al. reported that at week 5 in the post-training recovery phase, body weight had overshot by 5 kg, reflected primarily in large gains in fat mass, and that all the 10 subjects in that study had higher fat mass than before weight lost. Similarly, in another 8 weeks of U.S. Army Ranger training course that consisted of four repeated cycles of restricted energy intake and refeeding, Friedl et al. showed that more weight was regained than was lost after 5 weeks of recovery following training cessation, with substantial fat overshooting (∼4 kg on average) representing an absolute increase of 40% in body fat compared with pre-training levels. From the data obtained in a parallel group of subjects, they showed that hyperphagia peaked at ∼4 weeks post-training, thereby suggesting that hyperphagia was likely persisting over the last week of refeeding, during which body fat had already exceeded baseline levels.”

Obviously, association (even in a prospective cohort) does not prove causality or, for that matter, provide insights into the physiological mechanisms underlying this observation.

All we can conclude, is that these observations in US Rangers (and the other studies cited in Dulloo’s article) are consistent with the notion that weight loss in normal weight individuals can be followed by significant weight gain, often overshooting initial weight.

Incidentally, these findings are also consistent with observational studies in women recovering from anorexia nervosa, famine, cancer survivors and other situations resulting in significant weight loss in normal weight individuals.

Certainly enough evidence to consider a work of caution against “recreational” weight loss, especially in individuals of normal weight.

@DrSharma
Edmonton, AB

ResearchBlogging.orgDulloo AG, Jacquet J, Montani JP, & Schutz Y (2015). How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obesity reviews : an official journal of the International Association for the Study of Obesity, 16 Suppl 1, 25-35 PMID: 25614201

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