مجموعه مقالات انگليسي در باره كبد چرب

[Mohamad]

Nonalcoholic fatty liver disease is a term used to describe the accumulation of fat in the liver of people who drink little or no alcohol.

Nonalcoholic fatty liver disease is common and, for most people, causes no signs and symptoms and no complications. But in some people with nonalcoholic fatty liver disease, the fat that accumulates can cause inflammation and scarring in the liver. This more serious form of nonalcoholic fatty liver disease is sometimes called nonalcoholic steatohepatitis. At its most severe, nonalcoholic fatty liver disease can progress to liver failure.

[Mohamad]

Alcohol, obesity, starvation, diabetes mellitus, corticosteroids, poisons (carbon tetrachloride and yellow phosphorus), Cushing's syndrome, and hyperlipidemia are some causes of fatty liver. Microvesicular fatty liver may be caused by valproic acid toxicity and high-dose tetracycline or during pregnancy.



Symptoms of Fatty Liver
Patients are often asymptomatic.


Diagnosis of Fatty Liver
The patient may have an enlarged liver or minor elevation of liver enzyme tests. Several studies show that fatty liver is one of the most common causes of isolated minor elevation of liver enzymes found in routine blood screening.


Images of the liver obtained by an ultrasound test, CT (computed tomography) scan, or MRI (magnetic resonance imaging) may suggest the presence of a fatty liver. To be certain whether a patient has fatty liver requires a liver biopsy, in which a small sample of liver tissue is obtained through the skin and analyzed under the microscope.



Treatment of Fatty Liver
The treatment of fatty liver is related to the cause. It is important to remember that simple fatty liver may not require treatment. The benefit of weight loss, dietary fat restriction, and exercise in obese patients is inconsistent.


Reducing or eliminating alcohol use can improve fatty liver due to alcohol toxicity. Controlling blood sugar may reduce the severity of fatty liver in patients with diabetes. Ursodeoxycholic acid may improve liver function test results, but its effect on improving the underlying liver abnormality is unclear.


Questions To Ask Your Doctor About Fatty Liver
Is there fatty infiltration of the liver?


What did the liver function test show?


Is this related to diabetes mellitus?


Is it related to any other medical problem?


Should alcohol consumption be curtailed?


What treatment, if any, do you recommend?

[Mohamad]

The amount of fatty acid in the liver depends on the balance between the processes of delivery and removal. Fatty liver develops in every individual who consumes more than 60 g/d of alcohol. Many mechanisms of ethanol-induced fatty liver have been proposed. Increased hepatic levels of glycerol 3-phosphate (3-GP) following ethanol ingestion are related to an increase in the ratio of nicotinamide adenine dinucleotide, reduced form, (NADH) to nicotinamide adenine dinucleotide (NAD) in the liver. Increasing concentration of 3-GP results in enhanced esterification of fatty acids.

An increased level of free fatty acids also has been incriminated in the pathogenesis of fatty liver. Large amounts of alcohol enhance lipolysis because of the direct stimulatory effect on the adrenal and pituitary axis. In addition, chronic ingestion of ethanol inhibits the oxidation of fatty acids in the liver and the release of very low-density lipoprotein (VLDL) into the blood. All of these mechanisms favor steatosis. Centrilobular localization of steatosis results from decreased energy stores from relative hypoxia and a shift in lipid metabolism, along with a shift in the redox reaction caused by the preferential oxidation of alcohol in the central zone.

Advancement in the understanding of the pathogenesis of alcoholic steatosis provided some novel insights, including the role of peroxisome proliferator-activated receptor alpha, which is crucial for the regulation of hepatic fatty acid metabolism. Its blockade, in animal models, along with ethanol consumption, contributes to the development of alcoholic fatty liver. In addition, induction of adiponectin, a hormone secreted by adipocytes, has been implicated in the protective action of saturated fat against the development of alcoholic fatty liver in mice.

Recent developments in the understanding of the pathogenesis of fatty liver provided the findings described below.

The role of the early growth response-1 (EGr-1) transcription factor is thought to be essential for ethanol-induced fatty liver injury in mice. Hepatocyte death by apoptosis occurs in alcoholic fatty liver and has been demonstrated in rats and mice after ethanol feeding. This may be related to mitochondrial proteins that regulate apoptosis and necrosis and that are shown to be induced in mouse fatty liver models.

Serum leptin, a cytokine-type peptide hormone mainly produced by adipocytes, may play an important role in the pathogenesis of steatosis. Steatosis occurs with decreased leptin action, whether due to leptin deficiency or resistance. In a recent study in patients with alcoholic liver disease, serum leptin was noted to be independently correlated with the grade of steatosis.

Recent data from both animal studies and clinical studies support the role of proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in the early stage of fatty liver as well as alcoholic steatohepatitis.

Frequency
United States

Approximately 15.3 million people in United States abuse or depend on alcohol. Fatty liver develops in 90-100% of patients with heavy alcohol use.
International

One observational study from northern Italy demonstrated prevalence rates of steatosis in 46.4% of heavy drinkers (>60 g/d of alcohol) and in 94.5% of obese heavy drinkers.
Mortality/Morbidity
Simple steatosis rarely is fatal. With complete abstinence, histologic changes can return to normal within 2-4 weeks.
Continued alcohol consumption may result in more advanced forms of liver disease, either alcoholic hepatitis or cirrhosis.
A study from Denmark, which used the Danish National Registry, noted an increase in mortality among patients with a hospital discharge diagnosis of alcoholic fatty liver, which remained increased after censoring patients upon a diagnosis of cirrhosis.
Race

Very little data are available on racial differences in the incidence of alcoholic fatty liver. However, overall differences in alcoholic liver disease have been noted in various studies.

One study of 42,862 US adults showed differences in drinking patterns among different races. Whites were the most likely to drink, but blacks had the highest volume of intake and frequency of heavy drinking.
Another study showed a higher rate of cirrhosis among blacks.
---
Women develop more severe alcoholic liver disease (ALD) more quickly and at lower doses of alcohol than men.
Increased susceptibility of females possibly is related to ----dependent differences in the hepatic metabolism of alcohol, cytokine production, and the gastric metabolism of alcohol.
Age
The liver handles alcohol differently with age, and alcohol toxicity increases with age because of increased organ susceptibility. This is thought to be related to a mitochondrial transport defect with age as well as decreased function of the smooth endoplasmic reticulum and metabolism of CYP2E1-dependent microsomal ethanol oxidation.

[Mohamad]

History

Alcohol-induced steatosis usually is asymptomatic in ambulatory patients.
Fatty liver occurs commonly after the ingestion of a moderate or large amount of alcohol, even for a short period of time.
A thorough clinical history, especially with regard to the amount of alcohol consumption, is essential to determining the role of alcohol in the etiology of the abnormal liver test results. History obtained from the family members may reveal past alcohol-related problems.
No specific test is available to rule out drug-related toxicity, but a good review of all concurrent and recent medications, including over-the-counter medications and alternative treatments, is essential in evaluating the possible causes of abnormal liver test results.
Severe fatty infiltration of the liver can result in symptoms of malaise, weakness, anorexia, nausea, and abdominal discomfort.
Jaundice is present in 15% of patients admitted to the hospital because of these symptoms of fatty infiltration of the liver.
Physical

Fatty liver may be present in the absence of any abnormalities noted on the physical examination.
Hepatomegaly is common in patients who are hospitalized, occurring in over 70% of persons with steatosis proven on biopsy.
Portal hypertension is rare in alcoholic steatosis.
Causes
Several risk factors may be cofactors required for the development of advanced ALD.
Minimum amounts of alcohol intake associated with an increased risk for developing ALD range from 40-80 g/d for 10-12 years.
Genetics play a role in alcohol consumption and alcoholism. In addition, early data suggested a genetic predisposition to the development of ALD mostly related to differences in major hepatic enzymes involved in the metabolism of alcohol—alcohol dehydrogenase (ADH), acetaldehyde dehydrogenase (ALDH), and cytochrome P-450 system (CYP4502E1).
Several studies demonstrate a high prevalence of hepatitis C virus (HCV) antibody in patients with ALD, as well as iron overload.
Obesity and dietary habits have been implicated in individual susceptibility to ALD.