Initial stages of ALD may be asymptomatic apart from hepatomegaly and slightly elevated liver function tests [6]. In contrast, alcoholic hepatitis almost always presents with symptoms that may range from mild to severe and life-threatening [4]. Fever, fatigue, jaundice, nausea, pain in the right upper quadrant, weight loss and hepatomegaly are usually seen [6], while ascites, variceal bleeding and encephalopathy are encountered in more severe forms. Signs of liver failure, including spider nevi and bleeding, together with impaired synthetic function of the liver may be observed in this stage [11]. Liver cirrhosis may start asymptomatically, but eventually, severe injury leads to portal hypertension, hepatosplenomegaly, upper gastrointestinal bleeding, ascites, esophageal varices and Wernicke-Korsakoff syndrome in some cases [4]. Renal failure due to reduced renal blood flow, as a part of hepatorenal syndrome may develop, together with various metabolic changes that can be fatal if left untreated.

• Splenomegaly

  Splenomegaly : Portal hypertension causes the spleen to enlarge (a condition called splenomegaly). The enlarged spleen traps and destroys more white blood cells and platelets than it normally does. [msdmanuals.com]

  Liver biopsy showing the typical histologic changes of alcoholic steatosis (fatty liver) From the collection of Dr McClain; used with permission History & Exam Key Factors abdominal pain hepatomegaly hematemesis and melena venous collaterals splenomegaly [online.epocrates.com]

  Splenomegaly: Portal hypertension causes the spleen to enlarge (a condition called splenomegaly). The enlarged spleen traps and destroys more white blood cells and platelets than it normally does. [merckmanuals.com]

• Ascites

  A highly significant association was noted for serum bilirubin, INR, and the presence of ascites or encephalopathy. Of these, an elevated bilirubin greater than 8 mg/dL, and the presence of ascites were highly predictive of mortality. [doi.org]

  Convert to ICD-10-CM : 571.1 converts approximately to: 2015/16 ICD-10-CM K70.10 Alcoholic hepatitis without ascites Approximate Synonyms Acute alcoholic liver disease Alcoholic hepatitis Alcoholic hepatitis w ascites Alcoholic hepatitis with ascites [icd9data.com]

  We estimated the contribution of ascites, protein-calorie malnutrition and other conditions to the difference in costs between patients with ALD and patients with other diagnoses. [ncbi.nlm.nih.gov]

  Ascites 8 Ascites is unlikely to present to ICU as a sole diagnosis, rather it will complicate the ICU stay of a patient with another alcohol-related presentation. [ceaccp.oxfordjournals.org]

  See also: Ascites Cirrhosis Alcoholism Bleeding varices Hepatic encelphalopathy Alcoholic liver disease usually occurs after years of excessive drinking. [web.archive.org]

• Fever

  Symptoms may include fever, jaundice, weakness, right-sided abdominal pain, and nausea. [piedmont.org]

  Symptoms may not be present until the disease is advanced, and may include: Abdominal pain and tenderness Dry mouth Excessive thirst Fatigue Fever Fluid collection in the abdomen ( ascites ) Jaundice Loss of appetite Mental confusion Nausea Unintentional [web.archive.org]

  The symptoms might include jaundice, fever, right-sided abdominal pain, weakness and nausea. The person's white blood count becomes elevated and their liver is both tender and enlarged. [disabled-world.com]

  At this stage, symptoms such as fever, jaundice, fatigue, abdominal pain and altered mental state may be encountered. [symptoma.com]

  […] pain hepatomegaly hematemesis and melena venous collaterals splenomegaly hepatic mass jaundice palmar erythema cutaneous telangiectasia asterixis Other Factors ascites weight loss weight gain malnutrition and wasting anorexia fatigue confusion pruritus fever [online.epocrates.com]

• Malnutrition

  Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. [ncbi.nlm.nih.gov]

  Malnutrition contributes to liver disease. [web.archive.org]

• Weight Loss

  Those who suffer from fatty liver disease may experience feelings of fatigue, nausea and vomiting, confusion, discomfort in the abdomen, weight loss or jaundice. [alcoholrehab.com]

  In milder cases, common problems include nausea, vomiting, fever, jaundice, appetite loss, weight loss, abdominal pain and abdominal distension (pressure-related enlargement). [addiction.com]

  SYMPTOMS OF ALCOHOLIC LIVER DISEASE Abdominal pain Vomiting, perhaps blood or black material Ascites—retaining fluid in the abdominal cavity Loss of appetite and weight loss Jaundice Fatigue DIAGNOSING ALCOHOLIC LIVER DISEASE The patient’s history of [barnesjewish.org]

  Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. [ncbi.nlm.nih.gov]

  loss weight gain malnutrition and wasting anorexia fatigue confusion pruritus fever nausea and vomiting finger clubbing Dupuytren contracture leg swelling parotid gland enlargement gynecomastia hypogonadism dementia peripheral neuropathy History & Exam [online.epocrates.com]

• Fatigue

  A 30-year-old Chinese woman presented with a 4-month history of fatigue, yellowish discoloration of the eyes, and tea-colored urine. [ncbi.nlm.nih.gov]

  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]

  Abdominal pain and tenderness Ascites (excess fluid between the membranes lining the abdomen and abdominal organs) Confusion Dry mouth / excessive thirst Fatigue Fever Jaundice Loss of appetite Nausea Weight gain due to ascites Additional symptoms associated [puristat.com]

  SYMPTOMS OF ALCOHOLIC LIVER DISEASE Abdominal pain Vomiting, perhaps blood or black material Ascites—retaining fluid in the abdominal cavity Loss of appetite and weight loss Jaundice Fatigue DIAGNOSING ALCOHOLIC LIVER DISEASE The patient’s history of [barnesjewish.org]

• Easy Bruising

  bruising accumulation of extra fluid in the legs, known as edema. [the-alcoholism-guide.org]

  […] symptoms may include: Fluid buildup of the legs (edema) and in the abdomen ( ascites ) Yellow color in the skin, mucous membranes, or eyes ( jaundice ) Redness on the palms of the hands In men, impotence, shrinking of the testicles, and breast swelling Easy [medlineplus.gov]

  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]

• Vomiting

  A 37-year-old male with history of alcohol abuse presented to us with nausea, vomiting, and abdominal pain with ascites. He was diagnosed with alcoholic liver disease with coagulopathy and pancreatitis. [ncbi.nlm.nih.gov]

  Those who suffer from fatty liver disease may experience feelings of fatigue, nausea and vomiting, confusion, discomfort in the abdomen, weight loss or jaundice. [alcoholrehab.com]

  Some people experience mild symptoms such as loss of appetite, nausea and abdominal discomfort while others experience more severe symptoms such as vomiting, severe pain in the right upper abdomen and fever. [liversupport.com]

  In milder cases, common problems include nausea, vomiting, fever, jaundice, appetite loss, weight loss, abdominal pain and abdominal distension (pressure-related enlargement). [addiction.com]

• Nausea

  A 37-year-old male with history of alcohol abuse presented to us with nausea, vomiting, and abdominal pain with ascites. He was diagnosed with alcoholic liver disease with coagulopathy and pancreatitis. [ncbi.nlm.nih.gov]

  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]

  Those who suffer from fatty liver disease may experience feelings of fatigue, nausea and vomiting, confusion, discomfort in the abdomen, weight loss or jaundice. [alcoholrehab.com]

  People who drink more than two alcoholic drinks per day are at risk of liver disorders, the most common symptoms of which include nausea, diarrhea, anorexia, abdominal pain, and jaundice. [hospital.uillinois.edu]

• Abdominal Pain

  A 37-year-old male with history of alcohol abuse presented to us with nausea, vomiting, and abdominal pain with ascites. He was diagnosed with alcoholic liver disease with coagulopathy and pancreatitis. [ncbi.nlm.nih.gov]

  People who drink more than two alcoholic drinks per day are at risk of liver disorders, the most common symptoms of which include nausea, diarrhea, anorexia, abdominal pain, and jaundice. [hospital.uillinois.edu]

  SYMPTOMS OF ALCOHOLIC LIVER DISEASE Abdominal pain Vomiting, perhaps blood or black material Ascites—retaining fluid in the abdominal cavity Loss of appetite and weight loss Jaundice Fatigue DIAGNOSING ALCOHOLIC LIVER DISEASE The patient’s history of [barnesjewish.org]

  Symptoms may not be present until the disease is advanced, and may include: Abdominal pain and tenderness Dry mouth Excessive thirst Fatigue Fever Fluid collection in the abdomen ( ascites ) Jaundice Loss of appetite Mental confusion Nausea Unintentional [web.archive.org]

  Alcoholic liver disease symptoms, which may not be noticeable until the disease is advanced, can include: Increased blood pressure Jaundice Nausea Dry retching Diarrhea Abdominal pain Alcoholic liver disease can be diagnosed through blood tests, a liver [mdmercy.com]

• Loss of Appetite

  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]

  SYMPTOMS OF ALCOHOLIC LIVER DISEASE Abdominal pain Vomiting, perhaps blood or black material Ascites—retaining fluid in the abdominal cavity Loss of appetite and weight loss Jaundice Fatigue DIAGNOSING ALCOHOLIC LIVER DISEASE The patient’s history of [barnesjewish.org]

  Symptoms may not be present until the disease is advanced, and may include: Abdominal pain and tenderness Dry mouth Excessive thirst Fatigue Fever Fluid collection in the abdomen ( ascites ) Jaundice Loss of appetite Mental confusion Nausea Unintentional [web.archive.org]

  Early symptoms If you do experience early symptoms of ARLD, these are often quite vague, such as: abdominal (tummy) pain loss of appetite fatigue feeling sick diarrhoea feeling generally unwell Advanced symptoms As the liver becomes more severely damaged [nhs.uk]

• Diarrhea

  People who drink more than two alcoholic drinks per day are at risk of liver disorders, the most common symptoms of which include nausea, diarrhea, anorexia, abdominal pain, and jaundice. [hospital.uillinois.edu]

  Alcoholic liver disease symptoms, which may not be noticeable until the disease is advanced, can include: Increased blood pressure Jaundice Nausea Dry retching Diarrhea Abdominal pain Alcoholic liver disease can be diagnosed through blood tests, a liver [mdmercy.com]

  […] drinking Are worried that drinking may be harming your health Get emergency medical help right away if you have: Abdominal or chest pain Abdominal swelling or ascites that is new or suddenly becomes worse A fever (temperature greater than 101°F, or 38.3°C) Diarrhea [medlineplus.gov]

• Parotid Swelling

  swelling Gynaecomastia Hepatomegaly Testicular atrophy Encephalopathy Ascites Splenomegaly Caput medusae (abdominal varices) Muscle wasting (back of hands) Weight loss/cachexia Glossitis Investigations Common investigations requested on patients with [ceaccp.oxfordjournals.org]

• Jaundice

  The term acute alcoholic cholestasis is suggested for this apparently distinct syndrome of cholestatic jaundice in the absence of hepatitis. [ncbi.nlm.nih.gov]

  In milder cases, common problems include nausea, vomiting, fever, jaundice, appetite loss, weight loss, abdominal pain and abdominal distension (pressure-related enlargement). [addiction.com]

  The LFT's are usually abnormal, there may be jaundice (yellow colouring of the eyes and skin) and sometimes bruising or bleeding caused by abnormalities of the blood clotting system. [netdoctor.co.uk]

• Hepatomegaly

  This diagnosis was based on marked hepatomegaly, caudate lobe hypertrophy and failure to visualize hepatic veins by Doppler-ultrasound examination. [ncbi.nlm.nih.gov]

  Firstly, hepatic steatosis (fatty liver) develops, characterized by accumulation of lipid droplets in hepatocytes that results in hepatomegaly. [symptoma.com]

  Alcoholic Hepatitis (Rapidly developing symptoms) Jaundice Hepatomegaly Mild cases are often asymptomatic. [healthhype.com]

• Pruritus

  […] abdominal pain hepatomegaly hematemesis and melena venous collaterals splenomegaly hepatic mass jaundice palmar erythema cutaneous telangiectasia asterixis Other Factors ascites weight loss weight gain malnutrition and wasting anorexia fatigue confusion pruritus [online.epocrates.com]

  Symptoms include: jaundice portal hypertension, which increases blood pressure in the vein that travels through the liver skin itching (pruritus) Damage from repeated and excessive alcohol abuse leads to alcoholic liver cirrhosis. [healthline.com]

  She complains of fatigue, weakness, anorexia, nausea, abdominal discomfort, and pruritus. [journals.lww.com]

• Yellow Discoloration of the Skin

  Classic symptoms of liver disease include nausea, vomiting, right upper quadrant abdominal pain, and jaundice (a yellow discoloration of the skin due to elevated bilirubin concentrations in the bloodstream). [medicinenet.com]

• Dark Urine

  When the liver is damaged, symptoms often include yellow color in skin and eyes, dark urine, persistent itching, and fatigue. The causes can be viral, as in ... Hepatitis A-E, or can be due to scarring, cirrhosis, or a liver cancer. [sharecare.com]

  Symptoms of cirrhosis include, but are not limited to, changes to the nails and palms; strong, sweet-smelling breath; dark urine; jaundice (yellowing of the skin, eye, and mucus membranes); an increase in male breast tissue; impotence, infertility, or [puristat.com]

  These symptoms include: feeling tired fatigue jaundice weight loss loss of appetite weakness nausea vomiting confusion trouble concentrating pain in the center or right upper part of belly enlarged liver bloating and gas dark urine bruising easily excessive [draxe.com]

• Confusion

  Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. [ncbi.nlm.nih.gov]

  Symptoms may not be present until the disease is advanced, and may include: Abdominal pain and tenderness Dry mouth Excessive thirst Fatigue Fever Fluid collection in the abdomen ( ascites ) Jaundice Loss of appetite Mental confusion Nausea Unintentional [web.archive.org]

  MEDICINES FROM YOUR DOCTOR "Water pills" (diuretics) to get rid of fluid buildup Vitamin K or blood products to prevent excess bleeding Medicines for mental confusion Antibiotics for infections OTHER TREATMENTS Endoscopic treatments for enlarged veins [medlineplus.gov]

• Tremor

  Assess the patient for disorientation and asterixis (also known as flapping tremor), which are early indicators of HE. 16 (See Assessing for asterixis .) [journals.lww.com]

  Jaundice and tremors are symptoms of alcoholic liver disease. Treatment options include medication, lifestyle changes, and surgery. The recommended daily limits are no more than one drink a day for women and no more than two drinks a day for men. [medicalnewstoday.com]

  Cirrhosis, tremor, psychiatric disturbances and other neurological difficulties occur if the condition is not treated early. Treatment is with oral medication, which increases the amount of copper that is eliminated from the body in the urine. [medicinenet.com]

• Lethargy

  The liver affected by cirrhosis may not be able to metabolize the waste products, resulting in elevated blood ammonia levels and hepatic encephalopathy (lethargy, confusion, coma). [medicinenet.com]

  Classical grading progresses from mild confusion with slurred speech in grade I, through lethargy and marked confusion in grades II and III, all the way to coma in grade IV. [ceaccp.oxfordjournals.org]

Initial suspicion toward ALD can be made through patient history that may reveal heavy alcohol consumption, but patients may not always reveal such information, in which case friends and family should be asked as well. The majority of cases present in advanced stages of the disease, which can be concluded by observations during physical examination, such as hepatomegaly, jaundice, ascites and in severe cases, altered consciousness as a result of encephalopathy [4]. To confirm ALD, liver function tests that include liver transaminases (alanine aminotransferase and aspartate aminotransferase, or ALT and AST), gamma-glutamyl transferase (GGT), together with coagulation parameters and albumin. It is important to note that AST and ALT levels are not markedly elevated (< 300 IU/L) and the AST to ALT ratio is ≥ 2, as ALT is low due to deficiency of vitamin B6 as a result of ethanol effects on the liver [4]. A definite diagnosis, however, can be made by biopsy and subsequent histopathological examination that shows various changes in hepatocytes depending on the stage of illness.

• Hypoglycemia

  They developed hypoglycemia, dehydration, lactic acidosis, and renal failure after drinking a large volume of alcohol without eating for 1 week before onset. [ncbi.nlm.nih.gov]

  About 40% deteriorate soon after hospitalization, with consequences ranging from mild (eg, increasing jaundice) to severe (eg, ascites, portosystemic encephalopathy, variceal bleeding, liver failure with hypoglycemia, coagulopathy). [merckmanuals.com]

  In addition, liver cancers can produce and release a number of substances, including ones that cause an increased in red blood cell count (erythrocytosis), low blood sugar ( hypoglycemia ), and high blood calcium ( hypercalcemia ). [medicinenet.com]

• Hyperammonemia

  Consequences of liver disease including hyperammonemia, hormonal perturbations, endotoxemia and cytokine abnormalities as well as the direct effects of alcohol and its metabolites contribute to sarcopenia in ALD. [ncbi.nlm.nih.gov]

• Liver Biopsy

  His post-transplant course was complicated by several episodes of elevated liver enzymes. Liver biopsy 3 months after liver transplantation showed acute rejection and mild steatohepatitis. [ncbi.nlm.nih.gov]

  There is no specific laboratory test to identify alcohol as a cause of liver damage. Liver biopsy, in the context of a history of alcohol abuse, is diagnostic but is not absolutely indicated in all patients. [online.epocrates.com]

Early initiation of absolute cessation of alcohol intake is pivotal in management of ALD, as even marked pathological changes may regress with total abstinence [6]. This method directly correlates with longer survival rates, while adjunctive therapy with pharmacological agents that promote abstinence such as naltrexone, an opioid antagonists ot acamprosate (GABA inhibitor) have shown some benefit [4]. Because patients are often in poor general condition at the time of diagnosis, supportive care is equally important in achieving normal patient status. Restoration of normal body weight, administration of vitamin B complex, including B6 and B1 and diazepam during the period of alcohol withdrawal is important. B1 is known as thiamine, and its deficiency is the main factor in development of Wernicke-Korsakoff syndrome. Glucocorticoids and various antioxidants (pentoxifylline, N-acetyl cysteine and anti-TNF agents) are also being used in therapy, but in severe cases where significant irreversible liver damage has occurred, transplantation may be necessary [12].

The severity of liver damage directly influences patient outcomes. Approximately 90-100% of alcohol abusers develop hepatic steatosis [8], but it may completely regress with rigorous abstinence in a matter of weeks. On the other hand, 10-35% of individuals progress to alcoholic hepatitis and severe forms of this stage have mortality rates of up to 50% if untreated [6]. Finally, 8-20% of cases eventually result in liver cirrhosis, which has a poor overall prognosis [8]. When compensatory cirrhosis is present and persistent abstinence is achieved, 5-year survival rates reach up to 90%, whereas failed abstinence therapy lowers rates to 70% [2]. Moreover, liver cirrhosis is a significant risk factor for hepatocellular carcinoma (HCC), especially if concomitant hepatitis C infection is present, which increases the risk 20-fold [8]. Because early stages of liver damage can be reversed, it is essential to make the diagnosis in early stages.

Prolonged abuse of significant amounts of alcohol is the cause of ALD. Excessive alcohol intake facilitates upregulation of all metabolic pathways and consequent release of numerous ROS, including hydrogen peroxide, superoxide and hydroxyl radical [7]. Approximately 30 g of alcohol is considered a "safe dose", which corresponds to two 8-oz glasses of wine or 5-6 12-oz glasses of beer [3] [4], but patients often consume much higher daily doses. Because only 10-35% of heavy drinkers progress to ALD, however, other factors are thought to play a role in the development of this disease [4]. Genetic polymorphisms of enzymes responsible for alcohol degradation, obesity, concomitant hepatitis C infection, smoking and familial factors are shown to be important in the pathogenesis of ALD [4] [8].

Epidemiology studies across the world suggest that ALD, together with hepatitis C, is the most common cause of liver disease, especially in the Western World [9]. In 2007, almost 30,000 deaths from liver cirrhosis occurred in the United States, of which almost 50% were due to alcohol abuse [1], while similar data are obtained in Germany, where 50% of 18,000 deaths due to chronic liver disease are attributed to ALD [9]. The most obvious risk factor heavy alcohol abuse, but substantially increased rates of ALD and liver cirrhosis are seen in individuals who consume > 80 g/day for > 10 years [4]. Moreover, a 50% chance of developing irreversible liver disease is established in those who intake > 230 g/day for > 20 years [4]. In general, guidelines suggest that 10-12 year consumption of 40-80 g/day for males and 20-40 g/day for females is enough to cause ALD [9]. Although this condition is more commonly encountered in males, females are much more likely to develop ALD due to their increased susceptibility to ethanol toxicity [2]. Additional risk factors include genetic polymorphisms of CYP2E1 and ADH, but also ethnicity, as prevalence rates are shown to be higher in African Americans and Hispanics [2].

The pathogenesis model of ALD is complex and starts with absorption of alcohol through the gastrointestinal tract, mainly in the small intestine. Normally, metabolism of ethanol starts with activation of ADH located in the cytoplasm of hepatocytes, which converts ethanol into acetaldehyde, a process that requires conversion of nicotinamide-adenine dinucleotide (NAD) to NADH+, a more reactive substance. Acetaldehyde is then converted to acetate in mitochondria by acetaldehyde dehydrogenase (ALDH), which also requires formation of NADH+ [10]. In the setting of heavy alcohol intake, the ADH-mediated ethanol degradation is not sufficient to metabolize ingested quantities and calls for activation of alternative pathways. The microsomal ethanol oxidative system (MEOS) attempts to degrade ethanol via upregulation of CYP2E1 in the liver, but as a cost, it generates ROS and causes marked oxidative stress [10]. Consequently, free radicals exert deleterious effects on liver hepatocytes, including lipid peroxidation and cell membrane damage, deficiency of vitamins and antioxidants, as well as accumulation of proinflammatory products and leukocytes [4]. Tumor necrosis factor-α (TNF-α) is shown to play a pivotal role in liver injury as a result of alcohol abuse and it is secreted in Kupffer cells [3]. Disruption of normal microbial flora and increased endotoxin production by bacteria is also shown to occur [3]. As consumption of alcohol continues over time, accumulation of lipids in hepatocytes followed by diffuse inflammation and fibrosis develops. The end-stage of ALD is liver cirrhosis, in which extensive irreversible fibrosis of the liver parenchyma occurs and disrupts normal cellular architecture [4].

Adequate changes in alcohol intake and support of individuals with alcohol abuse issues should be taken seriously, as they are of crucial importance. Various forms of rehabilitation and support groups may be useful as well, but identification of heavy drinking in its initial stages is the single most important preventive strategy. Studies have established that only 50% of heavy alcohol abusers are recognized by their physicians, whereas 25% actively seek medical care [8], which is why various physician guidelines have been proposed in order to facilitate higher identification rates. Direct questioning regarding daily intake, the CAGE questionnaire (need to cut down, annoyed by criticism, guilty about drinking, need for an eye-opener in the morning) and several other inquiries are recommended for use during patient interviews [8]. Since certain studies have established that up to 70% of drinkers relapse after one year, the use of pharmacological agents such as acamprosate and naltrexone have shown mixed results, but acamprosate seems to substantially reduce the risk of relapse [6].

Severe and prolonged alcohol abuse can lead to various forms of alcoholic liver disease (ALD), one of the leading causes of liver failure in the Western world [1]. According to various epidemiological studies, almost 30,000 individuals die every year from liver cirrhosis in the United States, with almost half being attributed to alcohol abuse, and previous decades have shown increased numbers of cases worldwide [1] [2]. Although the single most important factor for ALD is excessive alcohol consumption, several other factors are implicated in this disease, including genetic, dietary and presence of additional comorbidities (for ex. hepatitis C). Despite the fact that ALD is more frequently encountered in men (an approximate 2:1 ratio is observed), women are more susceptible to alcohol-induced changes due to their lower capacity for metabolism of ethanol [3]. Under physiological conditions, alcohol cannot be stored in the body and is metabolized via three pathways upon its absorption from the small intestine (and from the stomach in a smaller percentage). Liver hepatocytes contain alcohol dehydrogenase (ADH) in their cytoplasm, which converts ethanol to acetaldehyde [3]. Formation of acetate follows, as a result of acetaldehyde oxidation mediated by acetaldehyde dehydrogenase (ALDH) in the mitochondria [4]. This pathway, however, has a limited capacity for ethanol uptake and the microsomal ethanol oxidizing system (MEOS) in the endoplasmic reticulum of hepatocytes is activated in the setting of very high alcohol intake. Through cytochrome P2E1 (CYP2E1), this pathway aids in further degradation of ethanol, but is often insufficiently effective in chronic abuse. Throughout this entire process, abundant formation of free radicals occurs, which is the main mechanism of damage seen in ALD. Proinflammatory cytokines, alterations in normal microbial flora and release of bacterial endotoxins, as well as genetic polymorphisms in liver enzymes are thought to be additional culprits in liver injury [3] [4]. Three stages of ALD are described. Firstly, hepatic steatosis (fatty liver) develops, characterized by accumulation of lipid droplets in hepatocytes that results in hepatomegaly. Although this condition is relatively benign, persistent alcohol abuse can further lead to alcoholic hepatitis (or steatohepatitis), featured by marked inflammation and necrosis of the liver parenchyma. At this stage, symptoms such as fever, jaundice, fatigue, abdominal pain and altered mental state may be encountered. Finally, liver cirrhosis may ensue - an irreversible and often fatal form of liver damage, as it may lead to terminal liver disease and the appearance of portal hypertension, Wernicke-Korsakoff syndrome and gastrointestinal bleeding, as well as formation of esophageal varices. In fact, alcoholic liver disease is shown to be the second most common indication for liver transplantation in the US [5]. Having in mind the fact that mortality rates from severe alcoholic hepatitis reach 50% and that hepatocellular carcinoma may arise on the grounds of profound liver cirrhosis [6], recognizing ALD in its early stages is detrimental. The diagnosis can be made based on detailed patient history that includes information obtained from both the patient and his/her family and friends regarding alcohol consumption, whereas a thorough physical examination may be sufficient to make an initial diagnosis. Liver function tests, together with basic laboratory studies including complete blood count (CBC) can confirm liver damage, while biopsy may be indicated as well. The main form of treatment is total alcohol abstinence supported by vitamin B supplementation, diazepam during withdrawal and glucocorticoids.

Alcoholic liver disease (ALD) encompasses numerous changes in the liver caused by chronic intake of alcohol, since our body cannot store it and possesses limited capacity for degradation. Ethanol, once ingested through alcoholic-rich beverages, is absorbed from the gastrointestinal tract and transported to the liver, the principal organ of alcohol metabolism. Through several pathways and mechanisms, the liver attempts to degrade ethanol into other compounds that may be excreted, but under circumstances of excessive alcohol ingestion, constant degradation leads to accumulation of free radicals that are created during this process. Consequently, severe damage to liver cells (hepatocytes) occurs over time and impairs numerous functions of this organ. Not only alcohol abuse, however, is important for the development of this syndrome. Genetic factors, gender and presence of comorbidities significantly determine the outcome of patients. It was shown that certain individuals have mutations in genes that code for enzymes that degrade alcohol, which may either make them more or less susceptible to toxic effects, whereas female gender is shown to be a risk factor due to lower tolerance to ethanol. There are three main stages of ALD: Fatty liver, the first stage where fat accumulation inside hepatocytes occurs; Alcoholic hepatitis, characterized by diffuse inflammation and degradation of liver cells; and finally, liver cirrhosis, an irreversible change in the structure of hepatocytes that can progress to end-stage liver disease. Symptoms may be completely absent in initial stages, while yellow skin color (jaundice), fever, abdominal pain, weight loss, nausea and fatigue may be encountered in milder cases. Altered consciousness, enlarged spleen and liver, as well as hypertension and development of esophageal varices are observed in severe cases. Because almost complete regression may result with early therapy and because advanced disease may either be fatal or predispose patients to liver cancer, an early diagnosis significantly prolongs the life of the patient. Interview with the patient is the crucial part of the diagnostic workup, as information regarding drinking habits and previous history of abuse may be obtained, but not all individuals will openly discuss their issues, which is why family and friends should be inquired with these questions as well, especially in the setting of high suspicion. Physical examination and liver function tests may can confirm liver damage, whereas a definite diagnosis can be made by biopsy. Treatment principles are based on complete abstinence from alcohol and has shown to be the most important modality. Supportive therapy through vitamin supplementation, administration of diazepam during withdrawal and use of various antioxidants has been recommended. This condition is one of the most common causes of end-stage liver disease that ends fatally within years in virtually all patients, but its prevention through early identification, supportive care and encouragement may substantially prolong survival rates or even induce complete regression of changes in the liver.

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