COMMENTARY

Diagnosis and Management of NAFLD: New Guidelines

David A. Johnson, MD

Disclosures

July 09, 2012

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Nonalcoholic Fatty Liver Disease: New Guidelines

Hello, I am Dr. David Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

Nonalcoholic fatty liver disease (NAFLD) -- we see this all the time, don't we? New guidelines[1] from the American Association for the Study of Liver Diseases in conjunction with the American College of Gastroenterology and the American Gastroenterological Association have just been published, with recommendations and weighted evidence graded by their review of the literature by experts in the field. I thought it would be helpful to share these with you and put these into clinical perspective as you start to apply these to your practice, because I am sure each and every one of you sees these patients almost on a daily basis.

NAFLD is divided into 2 categories. One is NAFL (nonalcoholic fatty liver) which means fat or steatosis in the liver but no evidence of inflammation or ballooning degeneration of the cell, so there is no ongoing injury. In contradistinction, nonalcoholic steatohepatitis (NASH) means the presence of fatty inflammation that invokes a host response that leads to ballooning degeneration, inflammation, necroinflammatory changes, and fibrosis, and may in fact lead to cirrhosis in 10%-15% of these patients. The background presence of NAFL in the general population from epidemiologic studies is about 20%, increasing perhaps because of the burgeoning problem of obesity. Nonetheless, in certain populations, such as patients with diabetes, NAFL increases to a prevalence of 60%-80%. If you do ultrasound testing on these patients, you may find fatty changes or increased echogenicity suggesting NAFL. NAFL may progress to cirrhosis in the presence of NASH. The guideline committee tried to put this in perspective for us.

Screening and Testing for NAFLD

Let's look at the evidence. The evidence suggests that NASH is present most often in the setting of metabolic syndrome. The classic description is the patient with central obesity, hyperlipidemia, hypertension, and diabetes. Those are the patients that you really need to consider to be at significant risk for this more severe degree of fatty inflammation and cirrhosis.

We know that these patients are at significant risk; where we tend to experience the most clinical consternation is in deciding whether we should obtain a biopsy. The recommendation from the consensus committee is that in patients who have incident findings of fatty liver (perhaps you are doing a CT scan for another reason and you pick up fatty change in the liver) you don't do a biopsy in the absence of defined risk. So, you wouldn't do a liver biopsy in patients with normal serum liver biochemistries and no evidence of cirrhosis. These patients should be followed and monitored with laboratory testing and not necessarily rushed into biopsy.

When you make these diagnoses, many patients ask, "What about my family members? Should they be screened as well?" You have to individualize this and look at the risk factors for each family member, but the consensus is that family members shouldn't be routinely screened for NAFLD. We recognize that obesity runs in families, but nonetheless, screening for NASH or NAFL certainly doesn't come to the forefront, at least in the recommendations of the committee.

What about noninvasive testing? There are a variety of tests that you can look at, although the liver biopsy remains the gold standard. The recommendation is to consider liver biopsy to look for definitive evidence of NASH, and in particular, to evaluate for fibrosis or progression of risk for cirrhosis in selected patients. Patients who have metabolic syndrome and have suggestion of necroinflammatory disease are at high risk and should be considered for biopsy. These patients have abnormal serum biochemistries and metabolic syndrome. The noninvasive tests are fairly good, but the committee could not recommend these for routine use. You can calculate a fibrosis score online. The fibrosis score may be helpful, but the other metabolic indices that are commercially available are not presently recommended for routine use in clinical practice as a way of excluding NAFLD or defining risk for NASH.

There is elastography, which is an evaluation of the tissue resiliency of the liver. This is primarily available in Europe and is not available in the United States, so it becomes somewhat of a theoretical evaluation; whether or not we get this in this country and see a paradigm shift for noninvasive testing remains to be seen.

Management Recommendations for NAFLD

Once you have defined the patient as being at risk, what do you do with this information? A number of therapeutic interventions have been studied, such as weight reduction. This is an easy one, because overweight and obese patients need to lose weight. The recommendation for patients with NAFLD is to lose at least 3%-5% to see a reduction in fatty changes in the liver, but it may require 10% body weight reduction before you see meaningful changes in the necroinflammatory component. Give the patient a reasonable timeframe for this.

What about alcohol consumption in these patients? The committee's definition of "significant alcohol intake" is fairly liberal: more than 21 drinks per week for men and 14 drinks per week for women. This is a fairly sizeable number of alcoholic drinks. They recommended that alcohol intake should be reduced in these patients. In patients who consume moderate amounts of alcohol, they didn't make definitive recommendations for reduction of alcohol intake. An occasional cocktail is reasonable; the committee stated that there was no evidence to suggest that should not be done.

What about statins? We are talking about patients with dyslipidemias in whom statins are contraindicated because of suspected liver disease, and the answer is that statins are not contraindicated. In fact, control of the lipids may control their inflammation or the fatty changes that stimulate inflammation. Statins are not contraindicated, but the committee said they were not recommended as a primary treatment for NAFLD. You monitor these patients the same way that you would monitor patients who don't have NAFLD.

Unproven Therapies for NAFLD

What about other therapies? There was a brief period of time when insulin-sensitizing agents such as metformin were recommended, but the committee says now that this is no longer the case. Metformin is not an option. Some data exist about other insulin-sensitizing agents in the thiazolidinedione group, which were subject to some scrutiny. Pioglitazone and rosiglitazone were studied initially. Pioglitazone has emerged as a therapeutic option. In nondiabetic patients, who have been studied the most, pioglitazone showed a decrement in the necroinflammatory process and it is an option, but recognize that it has been studied predominately as a diabetic drug in nondiabetic patients. Rosiglitazone has been removed from the market in Europe. Its use is very restricted in the United States primarily because of cardiovascular risk, so all of this must be considered in context. What are the contraindications of these drugs in individual patients?

Vitamin E has been studied in patients who are nondiabetic. The committee recommended that in nondiabetic patients, vitamin E, 800 IU daily, reduces the necroinflammatory component, but it didn't improve histology, which was the study endpoint. Vitamin E can be recommended as level 1 evidence in patients who are nondiabetic. In diabetic patients, or patients who have cirrhosis, vitamin E is not recommended. Vitamin E has its own "baggage," and evidence suggests that it increases the risk for prostate cancer. For many reasons, patients may not want to take vitamin E or should not take vitamin E, so use your own clinical judgment.

What about bariatric surgery? Bariatric surgery is a marvelous intervention for the obese patient. In fact, it can change the diabetic tendency literally in the recovery room. Patients have been shown to have improvement in their glucose tolerance tests, but as it relates to NAFLD, the committee felt that this was not studied well enough to recommend it as a primary intervention for these patients. In patients who have increased risk, we frequently ask our surgeons to biopsy the patients during their surgery to further identify the patients who have the NASH-type component, but bariatric surgery is not a primary intervention at present.

What about other agents, such as deoxycholic acid? The committee felt that this was not a primary intervention. Nor are there enough data on fatty acid interventions, such as fish oil. The committee felt that there was not enough evidence at present to make a statement about this.

One thing that was not evaluated in the present guidelines (primarily because the evidence just came out) was coffee consumption. A study looked at a target rate of coffee consumption of 300 g-350 g of caffeine per day,[2] and because coffee has the highest concentration of caffeine, drinks such as tea and colas weren't included. They found that 3-4 cups or more of coffee were actually beneficial. The odds ratios for inflammation and fibrosis were reduced in patients who were higher coffee consumers rather than those who were lower coffee consumers. If you have a patient with suspected NAFL and they like their coffee, they should go for it. You can at least give patients reassurance about coffee consumption, and you can even encourage it. Drip coffee has a higher concentration of caffeine than regular brewed coffee. Regular instant coffee has about one third to one half the caffeine concentration of drip or brewed coffee, so patients may drink more coffee if they use instant coffee.

Use the Guidelines

In final summary, there is new evidence about NAFLD and recommendations have been put forward by committees from the national societies. I invite you to review these and use them in your practice.

The committee did weigh in about pediatric NAFLD, so if you are treating pediatric patients, you should review this. In the pediatric population, there were not a whole lot of changes. There are very limited data in the pediatric population, but the findings mirror the adult population, couched in the context that we just don't have as much information.

Patients with NAFLD are very prevalent in our practices. Hopefully these new recommendations will give us some guidance until we have a more formative strategy. The bottom line is that the weight loss is mandatory, coffee is easy, and vitamin E should be restricted in patients who are not diabetic. Establish a meaningful target for weight loss, but don't stop at a little bit of weight loss because you don't see a reduction in inflammation until patients lose 10% or more of their body weight. Hopefully these recommendations give us some guidance so that we can make a meaningful impact on our patients for this prevalent and increasing problem.

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