BIGGER ISN'T BETTER
How to detect and treat fatty liver
By Sunly Coo, Contributing Writer
While it is harmless in its early stages and certainly not a major local public-health concern like cancer or heart disease, advanced levels of fatty liver can be fatal. Its link to the twin epidemics of obesity and diabetes that the world, particularly Asia, is facing, convinces experts of the value of proper screening and treatment of the disease.
Our liver normally contains some amounts of triglyceride, but when the latter comprises more than 10 percent of the liver's weight, the condition is classified as fatty liver. Says gastroenterologist and Bayer Philippines medical director Luis Abola: "Ninety percent of alcohol drinkers, those who take more than four to five drinks daily, will develop fatty liver (or alcoholic steatohepatitis). That is already a given. If you check patients with alcohol liver disease, both their serum cholesterol and triglyceride are usually already abnormal. Because of that the liver cannot process the fatty acids."
Nonalcoholic fatty-liver disease (NAFLD), on the other hand, is a spectral disorder that ranges from steatosis, the mildest form that usually inflicts no liver damage, to nonalcoholic steatohepatitis (NASH), the inflammation of the organ and fibrosis. Left untreated, NASH can create further complications, such as cirrhosis and hepatocellular carcinoma.
Gray signs and diagnostic blues
Simple fatty liver and NASH usually produce no symptoms; but if they do, patients experience fatigue and a dull ache in the upper right quadrant of the abdomen-possibly from an enlarged liver-symptoms that are vague and easily attributed to other illnesses. Manifestations become evident in advanced stages, such as cirrhosis: weight loss, lack of appetite, nausea, dark-brown urine, jaundice, itchy hands and feet that may eventually spread to the entire body, edema, ascites or fluid retention in abdominal cavity, memory problems, and liver failure.
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Because the disease is often asymptomatic or nonspecific in its symptoms, it is detected usually through abnormal laboratory findings for unrelated medical issues. Abola says that for NAFLD, initial suspicion is most often raised when an ultrasound yields an image of the liver that is brighter than the kidney or the spleen. Researchers cite additional red flags, such as vascular blurring and deep attenuation of ultrasound signal. This prompts a blood test for liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). "When they are elevated, that increases our suspicion that the patient has fatty liver," he explains. The keyword here is "suspicion," because as Mofrad et al.'s paper in Hepatology reveals, normal liver enzymes can occur in patients who have NAFLD, whether it's steatosis or advanced hepatic fibrosis.
"Of course, ultimately, the best way to diagnose is through liver biopsy, but this is not recommended for everybody because it is invasive," Abola says. The Asia-Pacific Working Party on NAFLD advises that histology should be considered when diagnostic uncertainty exists for those at risk of advanced fibrosis. Otherwise, the doctor notes, "Ultrasound is an accepted modality for diagnosing fatty liver." Ultrasonographic examination has limited accuracy though, especially among obese patients and in certain cases where there is a patchy distribution of fatty deposits. The more expensive and less accessible computerized tomography (CT) and magnetic resonance imaging (MRI) offer more conclusive imaging alternatives.
Experts also caution practitioners to rule out hepatitis B and C, and other less common liver diseases, like biliary-tract disease, Wilson's disease, and hepatic malignancies, before settling on NAFLD as the culprit behind abnormal liver tests.
The metabolic link
Abola stresses that it is important to identify those who are at risk. "Patients with metabolic syndrome, patients who are obese, with frank diabetes, or those with glucose intolerance have a risk of developing fatty-liver disease," he says. Hypertriglyceridemia, low levels of high-density lipoprotein, and hypertension are also clustered under metabolic syndrome, a group of cardiovascular risk factors associated with insulin resistance, which is the most vital factor in the pathogenesis of fatty liver. The disease is actually a state of insulin resistance even among nonobese patients with normal glucose tolerance, since too much fat in the liver causes hepatic insulin resistance.
Studies also show that type 2 diabetes is an independent predictor of NAFLD and advanced fibrosis, regardless of body-mass index (BMI). Given that a significant population of patients with NAFLD were previously diagnosed with type 2 diabetes or had a first-degree relative with the disease, the Asia-Pacific Working Party on NAFLD recommends screening patients for personal or family history of the metabolic disorder. Compounding the problem is the exponential rise of type 2 diabetes in the region, which Yoon et al. estimated in the 2006 Lancet will jump two- to fivefold over 20 years.
Central obesity, more than generalized obesity, has also been singled out as an important risk factor for NAFLD across a spectrum of patients with normal to obese body weight. Visceral adiposity appears to be more closely tied to insulin resistance than an abnormally high BMI, a phenomenon that explains why NASH has been reported among lean patients, especially those of Asian descent. "There are many Filipinas who appear thin but have lots of fats in their intestines," Abola comments.
Women and men whose alcohol intake exceeds 40 g daily or 280 g weekly, and 60 g daily or 420 g weekly, respectively, are also prime candidates for an inflamed fatty liver. Although the histologic characteristics of alcoholic steatohepatitis and NAFLD are practically indistinguishable, it is necessary to define the nature of the fatty-liver disease as either alcohol-induced or otherwise for practical management.
Seeking deliverance
Between NAFLD and alcoholic steatohepa-titis, there is no condition where the patient is better off, says Abola. Not only can either graduate to cirrhosis, other complications may also develop, such as hepatic encephalopathy, liver failure, and liver cancer.
To mitigate alcoholic steatohepatitis, avoid alcohol. While the medical community is still undecided on whether alcohol abstinence should be part of the long-term care of patients with NAFLD-some are in fact against it-it is clear that the first-line and mainstay treatment is lifestyle modification.
"The best treatment is still diet and exercise, the same as with treatment for metabolic syndrome," Abola says. "Fatty liver is a reversible condition. Once you control the underlying problem, control the metabolic syndrome, you can go back to a normal liver histology."
Specialists are also looking into promising pharmacological options. Insulin-sensitizing drugs, like metformin, pioglitazone, and rosiglitazone, appear to improve ALT levels and hepatic histology. Orlistat, known for preventing fat absorption, has been suggested as a complementary medication. Other ongoing studies are focusing on antioxidants like vitamin E, antiinflammatory agents like pentoxifylline, and glutathione precursors. "They can help because they affect the metabolic process, but the evidence is not conclusive," he says, echoing the view of the Asia-Pacific Working Party on NAFLD.
"For those who cannot comply with lifestyle changes, they can be referred for bariatric surgery" like gastric bypass, he continues. Because the dramatic weight loss can aggravate liver inflammation and fibrosis, patients are advised to drop the pounds more gradually and to adopt a high-nutrition diet, instead of just cutting down calories.
When the disease reaches terminal point, the patient may have to resort to drastic measures. "Liver transplant is reserved for those who have developed frank liver failure. Our liver is quite versatile though. You can lose half of your liver and still have an efficient liver function," he explains. And like any chronic disease, follow-ups are necessary to chart progress and keep the patient on a steady course to recovery.
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