Alcoholic fatty liver, which may occur after even moderate (about 10g per day) consumption of alcohol [1], is invariably found in people who drink heavily [2]. It is the initial stage in alcoholic liver disease when pathologic changes are reversible. Consumption of excessive amounts of alcohol over extended periods will lead to the appearance of more severe manifestations, such as alcoholic hepatitis and cirrhosis.

The buildup of fats (triglycerides) in the liver is the consequence of the metabolism of alcohol by the liver. The enzymes that oxidize alcohol to the toxic acetaldehyde and then to acetic acid also produce reduced nicotinamide adenine dinucleotide (NADH). Excess NADH inhibits the oxidation of fatty acids and promotes their synthesis, which favors their accumulation in the form of triglycerides [3]. A multitude of other molecular and cellular effects of alcohol metabolism, such as oxidative stress, and the activation of hepatic macrophages, leads to further damage, inflammation, and fibrosis.

Alcoholic fatty liver does not usually cause symptoms. Hepatomegaly may be observed and supports the diagnosis. Rare symptoms are portal hypertension and extrahepatic problems such as muscle wasting, cardiomyopathy, and pancreatitis. Cholestasis is another rare occurrence in people with fatty liver. The American Association for the Study of Liver Diseases recommends using an organized questionnaire if excessive alcohol consumption is suspected [4].

• Abdominal Pain

  However, when symptoms do occur, they may include: Fatigue and weakness Weight loss, loss of appetite, and nausea Abdominal pain Jaundice (yellowing of the skin and eyes) Itching Fluid retention or swelling of the legs and abdomen Mental confusion Prevalence [upmc.com]

  If symptoms appear, they may include: A feeling of fullness in the middle or upper right side of the abdomen Abdominal pain Loss of appetite or weight loss Nausea Weakness Jaundice (yellowing of the skin and the whites of the eyes) Swelling of the abdomen [my.clevelandclinic.org]

  These can include: appetite loss nausea vomiting abdominal pain jaundice Most cases of NASH are detected in people between ages 40 and 60, according to the American Liver Foundation. [healthline.com]

• Loss of Appetite

  However, when symptoms do occur, they may include: Fatigue and weakness Weight loss, loss of appetite, and nausea Abdominal pain Jaundice (yellowing of the skin and eyes) Itching Fluid retention or swelling of the legs and abdomen Mental confusion Prevalence [upmc.com]

  These include fatigue, loss of appetite, weight loss, weakness, fluid retention, or bleeding. [hopkinsmedicine.org]

  Symptoms of cirrhosis may include fatigue, bleeding easily, easy bruising, fluid accumulation in the abdomen ( ascites ), loss of appetite, nausea, swelling in the legs (edema) and weight loss. [liversupport.com]

  If symptoms appear, they may include: A feeling of fullness in the middle or upper right side of the abdomen Abdominal pain Loss of appetite or weight loss Nausea Weakness Jaundice (yellowing of the skin and the whites of the eyes) Swelling of the abdomen [my.clevelandclinic.org]

• Jaundice

  In addition to jaundice and marked hepatomegaly, the patient presented with hypocalcemic crisis associated with hypomagnesemia, low plasma 1,25(OH)2-vitamin D and undetectable plasma parathyroid hormone (PTH) concentration. [ncbi.nlm.nih.gov]

  Your doctor weighs you and checks your body for signs of liver problems such as an enlarged liver or jaundice. Blood tests. [webmd.com]

  However, when symptoms do occur, they may include: Fatigue and weakness Weight loss, loss of appetite, and nausea Abdominal pain Jaundice (yellowing of the skin and eyes) Itching Fluid retention or swelling of the legs and abdomen Mental confusion Prevalence [upmc.com]

• Hepatomegaly

  In addition to jaundice and marked hepatomegaly, the patient presented with hypocalcemic crisis associated with hypomagnesemia, low plasma 1,25(OH)2-vitamin D and undetectable plasma parathyroid hormone (PTH) concentration. [ncbi.nlm.nih.gov]

  Hepatomegaly may be observed and supports the diagnosis. Rare symptoms are portal hypertension and extrahepatic problems such as muscle wasting, cardiomyopathy, and pancreatitis. Cholestasis is another rare occurrence in people with fatty liver. [symptoma.com]

  Most individuals are asymptomatic and are usually discovered incidentally because of abnormal liver function tests or hepatomegaly noted in unrelated medical conditions. Elevated liver biochemistry is found in 50% of patients with simple steatosis. [en.wikipedia.org]

  Differential Diagnosis of Uncommon Causes of Chronic Liver Disease Cause of liver disease Clinical features Laboratory evaluation α 1 -antitrypsin deficiency Hepatomegaly and elevated liver enzyme levels α 1 -antitrypsin level, phenotype, and liver biopsy [aafp.org]

• Liver Mass

  Chemotherapy and diet changes were conducted successfully with ultrasound characteristics suggesting improvements on both aspects: conventional liver mass resection could take place. [ncbi.nlm.nih.gov]

• Nephrolithiasis

  Fatty liver and nephrolithiasis were determined based on ultrasonographic findings. We used a parametric Cox model to estimate the adjusted hazard ratios (HRs) of nephrolithiasis according to the presence of NAFLD. [ncbi.nlm.nih.gov]

Patient history is extremely important because fatty liver can occur in obese patients and in conditions of hyperlipidemia, insulin resistance, and malnutrition, and can be caused by various drugs. However, patient history may not be accurate, and single biomarkers (for example, amino acid transferase or gamma-glutamyl transpeptidase levels) do not distinguish efficiently between alcoholic and non-alcoholic hepatic steatosis. However, a combination of results of diagnostic markers can differentiate between the two types of conditions reliably [5] [6].

In alcoholic liver disease, laboratory studies show elevated aminotransferases (aspartate aminotransferase and alanine aminotransferase) in about 30% of the patients, with aspartate aminotransferase being higher than alanine aminotransferase. Bilirubin concentrations may also be elevated because of hemolysis.

Liver biopsy is not usually performed for fatty liver but may be useful to exclude more advanced disease (steatohepatitis or fibrosis), or other unrelated conditions that cause liver damage. The biopsy of fatty liver will show fat accumulation in the hepatocytes, which tends to be macrovesicular, consisting of a single or very few large lipid droplets resulting in the displacement of the nucleus to a peripheral position. Microvesicular lipid accumulation is sometimes observed, which leads to foamy degeneration of hepatocytes [7]. Fatty deposition most often affects the centrilobular part of the acinus, but in advanced cases of fatty liver, the whole acinus is affected [8].

Ultrasonography, computed tomography, and magnetic resonance imaging can demonstrate the condition of steatosis in a patient. Ultrasonography shows a diffusely echogenic liver in alcoholic steatosis.

• Nephrolithiasis

  Fatty liver and nephrolithiasis were determined based on ultrasonographic findings. We used a parametric Cox model to estimate the adjusted hazard ratios (HRs) of nephrolithiasis according to the presence of NAFLD. [ncbi.nlm.nih.gov]

• Pericardial Effusion

  He developed complications associated with liver failure including renal failure as well as pleural and pericardial effusions. Case 2, a second male patient, developed both liver failure and lactic acidosis 24 h after methamphetamine abuse. [ncbi.nlm.nih.gov]

• Helicobacter Pylori

  Here we report a case of a 55-year Caucasian man, who improved the metabolic profile after the treatment for Helicobacter pylori eradication. [ncbi.nlm.nih.gov]

  Byrne and Giovanni Targher, Helicobacter pylori infection and NAFLD, Metabolism, 10.1016/j.metabol.2019.04.012, (2019). Tracey G. Simon, Jacqueline Henson, Stephanie Osganian, Ricard Masia, Andrew T. Chan, Raymond T. Chung and Kathleen E. [doi.org]

• Liver Biopsy

  A liver biopsy was performed on all the patients. Results Of 96 patients undergoing liver biopsy for non-alcoholic fatty liver disease (NAFLD), 76 (79.2%) were men. On liver US, diffuse fatty liver (DFL) was noted in 68 (70.8%) patients. [ncbi.nlm.nih.gov]

  Bravo AA, Sheth SG, Chopra S (2001) Liver biopsy. N Engl J Med 344:495–500 CrossRef PubMed Google Scholar 6. Regev A, Berho M, Jeffers LJ et al (2002) Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. [doi.org]

As for NAFLD, the treatment modality is mainly directed toward weight loss and co-morbidity management. Therefore, new pathophysiology directed therapies are urgently needed. [ncbi.nlm.nih.gov]

KEYWORDS: Cardio-hepatic syndrome; Chronic heart failure; Prognosis [ncbi.nlm.nih.gov]

C 2, 13, 17 Liver biopsy is the criterion standard for diagnosis and prognosis of nonalcoholic fatty liver disease. [aafp.org]

Prognosis of patients with a diagnosis of fatty liver — a registry-based cohort study. Hepatogastroenterology 2003 ; 50 : 2101 -4. 44. Teli MR, James OF, Burt AD, Bennett MK, Day CP. [doi.org]

Abstract Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ancestry groups. [nature.com]

The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol. 2003;98:960-7. [revistas.proeditio.com]

In this article we discuss the etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management. [doi.org]

Because of the common epidemiological and pathophysiological features between NAFLD and T2DM, many antidiabetics drugs have been tested in patients with NAFLD over the years. [ncbi.nlm.nih.gov]

Epidemiology 2nd edn (W. B. Saunders, Philadelphia, 2000). 15 Foster, M. W. & Sharp, R. R. [dx.doi.org]

Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey. World J Gastroenterol 2003 ; 9 : 1106 -10. 7. Ruhl CE, Everhart JE. [doi.org]

Therefore, new pathophysiology directed therapies are urgently needed. [ncbi.nlm.nih.gov]

However, the pathophysiology that leads to NAFLD is not well understood; in particular, the factors that lead to progressive hepatocellular damage after triglyceride accumulation are not well elucidated. [doi.org]

The endogenously synthesized n-3 PUFAs of the three fat-1 groups, which inhibit fatty acid synthesis and the TLR-4 signaling pathway, prevent HFS diet-induced NAFLD. [ncbi.nlm.nih.gov]

1. Savolainen VT, Liesto K, Männikkö A, Penttilä A, Karhunen PJ. Alcohol consumption and alcoholic liver disease: Evidence of a threshold level of effects of ethanol. Alcohol Clin Exp Res. 1993;17(5):1112-1117.
2. Grant BF, Dufour MC, Harford TC. Epidemiology of alcoholic liver disease. Semin Liver Dis. 1988 Feb;8(1):12-25.
3. Lieber CS. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol. 2004 Aug;34(1):9-19.
4. O'Shea RS, Dasarathy S, McCullough AJ; Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010 Jan;51(1):307-328.
5. Wang J, Li P, Jiang Z, et al. Diagnostic value of alcoholic liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) index combined with γ-glutamyl transferase in differentiating ALD and NAFLD. Korean J Intern Med. 2016 May;31(3):479-487.
6. Dunn W, Angulo P, Sanderson S, et al. Utility of a new model to diagnose an alcohol basis for steatohepatitis. Gastroenterology. 2006 Oct;131(4):1057-1063.
7. Uchida T, Kao H, Quispe-Sjogren M, Peters RL. Alcoholic foamy degeneration--a pattern of acute alcoholic injury of the liver. Gastroenterology. 1983 Apr;84(4):683-692.
8. [No authors listed]. Alcoholic liver disease: morphological manifestations. Review by an international group. Lancet. 1981 Mar 28;1(8222):707-711.