Fatty Liver, NAFLD

In case you were wondering how on earth the topic of liver disease could possibly relate to you:

“The obesity epidemic has hit the liver. About 20% to 30% of Americans have excess fat in the liver, and the problem is widespread throughout the world. The fat accumulation is often benign, but it can progress to a condition called nonalcoholic steatohepatitis, or NASH, that features inflammation and swollen cells. NASH often leads to fibrosis, or scarring that can result in cirrhosis, liver failure and death.”

An over-view of the topic, from “Science” magazine:

This good general article on the topic of fatty liver disease is from July 2015, in the magazine “Science”  LINK

“Feature: How what we eat is destroying our livers”

Report of a Treatment Approach Using a Low-Carb Diet

This is a small case series reported by a GP in the U.K. As a small case series, this has it’s limitations. Still, the implications of the reported outcomes are of great promise and are important to consider.

“A pilot study to explore the role of a low-carbohydrate intervention to improve GGT levels and HbA1c”   LINK

Unwin DJ, Cuthbertson DJ, Feinman R, Sprung VS (2015) A pilot study to explore the role of a low-carbohydrate intervention to improve GGT levels and HbA1c. Diabesity in Practice 4: 102–8 (2015)

Quoting from the report:

  • NAFLD is a spectrum of conditions that is caused by hepatocyte triglyceride accumulation (a build up of fat within the liver cells [Lam and Babu, 2015]).
  • NAFLD now affects 20–30% of adults in the developed world, which is of clinical importance as it can progress to non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma (Anstee et al, 2011).
  • NAFLD has also been found to increase overall cardiovascular mortality (Adams et al, 2005; Marchesini et al, 2005; Chalasani et al, 2012).

(In terms of testing GGT) –

  • Abnormal liver transaminases are observed, and elevated gamma-glutamyl transferase (GGT) is one of the markers indicating fatty liver.
  • Elevated GGT levels have also been identified as an independent risk factor for type 2 diabetes

Summary of findings

  • This study suggests that a low-CHO dietary intervention (including associated support from healthcare professionals), initiated and managed in a primary healthcare setting, can reduce GGT, weight and HbA1c.
  • The data presented also suggest that a low- CHO diet can be tolerated by individuals in primary care and may serve as an effective and economical non- pharmacological management strategy for people with non-alcohol-induced raised GGT or type 2 diabetes.
  • Given the epidemic of type 2 diabetes, and that approximately 20% of the adult population in the UK has elevated GGT (and possibly NAFLD [Anstee et al, 2011]), investigating dietary interventions for weight loss in these individuals would seem to be of national priority, especially as there is currently an absence of effective drug therapy for NAFLD.
  • The observed improvements in cholesterol and cholesterol:HDL-cholesterol ratios following the low-CHO intervention were reassuring in a diet that is higher in fat than the norm.

Implication of Liver Fat Regarding Heart Artery Disease

“Liver fat, statin use, and incident diabetes: The Multi-Ethnic Study of Atherosclerosis.” PubMed Abstract LINK

Description: “3153 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) without CVD, T2D/impaired fasting glucose, or baseline statin therapy”

From MDlinx.com article August 6/15, the resulting findings are:

  • High liver fat and statin therapy were associated with diabetes (HR 2.06 [95%CI 1.52-2.79, P<0.0001] and 2.01 [95%CI 1.46-2.77, P<0.0001], respectively), after multivariable adjustment.
  • With low liver fat and CAC=0, the number needed to treat (NNT) for statin to prevent one CVD event (NNT 218) was higher than the number needed to harm (NNH) with an incident case of T2D (NNH 68).
  • Conversely, those with CAC >100 and low liver fat were more likely to benefit from statins for CVD reduction (NNT 29) relative to T2D risk (NNH 67).
  • Among those with CAC >100 and fatty liver, incremental reduction in CVD with statins (NNT 40) was less than incremental risk increase for T2D (NNH 24).


  • CAC = Coronary Calcium Score
  • T2D = Type 2 Diabetes
  • NNT = Number Needed to Treat, which is a standard statistical way of estimating how many people have to be treated to prevent one incident of the stated good outcome
  • NNH = similarly, this is the number of people treated to cause one incidence of the stated harm

Meaning of the results:

  • This research finding is tracking correlation. It does not prove causation.
  • What it is looking at is
    • (1) the benefit of taking statins in terms of heart disease, such as heart attacks compared to
    • (2) the potential harm in that people taking statins are known to be at higher risk of developing diabetes (meaning type 2 diabetes, the type related to insulin resistance).
  • They found that in people with low liver fat:
    • if the CAC score = 0, a high number of people (on average 218) have to be treated with statin in order to prevent one CVD (cardiovascular disease) event. In this case, the increased risk of developing diabetes was much more than the likelihood of benefit of avoiding the target harm (CVD). The Number Needed to Harm (NNH) shows that, on average, one extra case of diabetes would develop for every 68 people treated with a statin.
    • if the CAC score = 100, then the balance of benefit/harm is much more favourable. On average, 29 people need to be treated with a statin to prevent one CVD event. On the other hand, for every 67 people treated with statins, one extra case of diabetes would develop, on average.
  • For people with fatty liver:
    • there was less benefit than to those without fatty liver. For those with CAC score = 100, then 40 people needed to be treated to prevent one CVD event.
    • there was more harm than to those without fatty liver. For every 24 people treated with a statin, one extra case of diabetes could be expected.

This research is from Harvard, John Hopkins, UC _ San Diego and other institutions (see below).

This research brings up a number of questions and speculations:

  • the reason for these findings is not known. One might guess that people who have fatty liver are already somewhere on the pathway heading towards diabetes, so adding something that itself increases the risk for developing diabetes (a statin) is more of a “burden” re: insulin production/function.
  • one might guess that people with fatty liver are already somewhere on the pathway towards diabetes, and so they have harm to the arteries from higher insulin levels/surges and higher (even if sub-diabetic) levels/surges of glucose.
  • at the start, the people in this study did not have type 2 diabetes or elevated fasting blood sugar levels “impaired fasting glucose” (according to the criteria for abnormal levels). However, often the fasting blood sugar does not go up until after years of having blood sugar elevations after meals without abnormal when fasting glucose. In insulin resistance, the blood level of insulin is high for many years before the blood sugar goes up high enough to meet the criteria for a diagnosis of diabetes.
  • one would hope that people with fatty liver could improve their risks of both benefit and harm by doing things to successfully reduce liver fat to normal. However, this study does not answer that question.

Notice that these research conclusions are not focused on the blood cholesterol level or how much the blood cholesterol levels or ratios changed in response to the statin treatment. This is in keeping with the recent changes in how we see blood cholesterol levels and how we see the effects of statins. There has been a shift from seeing statins as being effective specifically and mainly through reducing blood LDL levels. Now, statins are spoken of as “risk reducing” medications. There is now no longer the same emphasis of “treating to target” of a specific cholesterol target level.

The side-effects of statins are becoming more known in recent years. There is a much greater effort to try to carefully determine for each person the balance of relative benefits and harms.

Atherosclerosis. 2015 Jul 15;242(1):211-217. doi: 10.1016/j.atherosclerosis.2015.07.018.
Liver fat, statin use, and incident diabetes: The Multi-Ethnic Study of Atherosclerosis.
Shah RV1, Allison MA2, Lima JA3, Bluemke DA4, Abbasi SA5, Ouyang P3, Jerosch-Herold M6, Ding J7, Budoff MJ8, Murthy VL9.
Author information
1 – Department of Cardiology and Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
2 – Department of Family and Preventative Medicine, University of California-San Diego, San Diego, CA, United States.
3 – Cardiology Division, Johns Hopkins Medical Institute, Baltimore, MD, United States.
4 – Radiology and Imaging Sciences, National Institutes of Health Clinical Center, National Institute of Biomedical Imaging and Bioengineering, United States.
5 – Department of Cardiology and Medicine, Brown University, Providence, RI, United States.
6 – Non-Invasive Cardiovascular Imaging, Brigham and Women’s Hospital, Boston, MA, United States.
7 – Department of Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, United States.
8 – Department of Cardiology and Medicine, University of California-Los Angeles, Los Angeles, CA, United States.
9 – Department of Medicine (Cardiovascular Medicine Division) and Department of Radiology (Nuclear Medicine Division), University of Michigan, Ann Arbor, MI, United States. Electronic address: vlmurthy@med.umich.edu.

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