Question

    Alcoholic Liver Disease

    Alcoholic hepatitis[1]

    Alcoholic liver disease denotes a spectrum of pathological changes in the liver as a result of severe alcohol abuse. Lipid accumulation, fibrosis and cirrhosis may ensue and may lead to end-stage liver disease. Milder forms can have an asymptomatic course while advanced disease presents with undernourishment, severe vitamin deficiency and various constitutional symptoms. Patient history and clinical criteria are sufficient for diagnosis. Abstinence is essential in treatment, together with supportive measures.

    The disease is triggered by this process: Poison.

    Presentation

    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.

    Jaw & Teeth
  • more...
  • Liver, Gall & Pancreas
    Hepatomegaly
    • Initial stages of ALD may be asymptomatic apart from hepatomegaly and slightly elevated liver function tests.[symptoma.com]
    • In patients with acute alcoholic hepatitis, clinical manifestations include fever, jaundice, hepatomegaly, and possible hepatic decompensation with hepatic encephalopathy, variceal bleeding, and ascites accumulation.Tender hepatomegaly may be present,[en.wikipedia.org]
    • Presentations Asymptomatic (majority of cases) Hepatomegaly Biochemistry mildly abnormal Needs histology for confirmation Symptomatic (minority of cases) Liver failure 25.[slideshare.net]
    • Moderate cases may have mild jaundice, hepatomegaly and signs of chronic liver disease Severe cases may have decreased GCS, encephalopathy, high bilirubin levels and prolonged prothrombin times.[oxfordmedicaleducation.com]
    • […] with recent heavy alcohol intake and disease progression ( J Clin Pathol 1992;45:412 ) Acute foamy degeneration: Rare, extensive microvesicular steatosis with no / minimal inflammatory activity; clinically presented with jaundice, abdominal pain and hepatomegaly[pathologyoutlines.com]
    Jaundice
    • At this stage, symptoms such as fever, jaundice, fatigue, abdominal pain and altered mental state may be encountered.[symptoma.com]
    • The LFTs will almost always be abnormal, and the patient may develop jaundice .[netdoctor.co.uk]
    • […] and weight loss Nausea or belly pain Small, red spider-like blood vessels on the skin As liver function worsens, symptoms may include: Fluid buildup of the legs (edema) and in the abdomen (ascites) Yellow color in the skin, mucous membranes, or eyes (jaundice[nlm.nih.gov]
    • With alcoholic hepatitis, the liver becomes inflamed, often leading to fever, loss of appetite, nausea, vomiting, abdominal pain, and jaundice.[hazelden.org]
  • more...
  • Entire body system
    Recent Increase in Alcohol Consumption
    • This was described in India for example, where the recent increase in alcohol consumption in many sectors of the general population is coupled with strong evidence of the role of alcohol in the spread of HIV infection and other health risks[ 5 ].[dx.doi.org]
    Weight Loss
    • loss, or yellow skin or eyes.[healthgrades.com]
    • 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]
    • […] fluid ( oedema ) swelling in your abdomen, due to a build-up of fluid known as ascites a high temperature (fever) and shivering attacks very itchy skin hair loss unusually curved fingertips and nails ( clubbed fingers ) blotchy red palms significant weight[nhs.uk]
    • The number one treatment of fatty liver disease is weight loss and a healthy diet.[draxe.com]
    • 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.[symptoma.com]
  • more...
  • Face, Head & Neck
  • more...
  • neurologic
    Confusion
    • MEDICINES FROM YOUR DOCTOR "Water pills" (diuretics) to get rid of fluid build-up Vitamin K or blood products to prevent excess bleeding Medicines for mental confusion Antibiotics for infections OTHER TREATMENTS Endoscopic treatments for enlarged veins[nlm.nih.gov]
    • Those with cirrhosis often develop kidney problems, intestinal bleeding, fluid in the belly, confusion, liver cancer, and severe infections.[massgeneral.org]
    • Medications such as lactulose and Xifaxan may be used to combat the confusion associated with hepatic encephalopathy.[ukhealthcare.uky.edu]
    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]
    • Cirrhosis, tremor, psychiatric disturbances and other neurological difficulties occur if the condition is not treated early.[medicinenet.com]
  • more...
  • Immune System
    Splenomegaly
    • If done for other reasons, abdominal ultrasonography or CT may suggest fatty liver or show splenomegaly, evidence of portal hypertension, or ascites.[merckmanuals.com]
    • Spider angioma Parotid and lacrimal gland enlargement Palmer erythema Jaundice Decreased body hair Gynecomastia Musculoskeletal Dupuytren’s contracture Clubbing Muscle wasting Genitourinary Testicular atrophy Abdomen Hepatomegaly or small shrunken liver Splenomegaly[clevelandclinicmeded.com]
    • The blood "backs-up," accumulating in the spleen, and the spleen swells in size, a condition referred to as splenomegaly .[medicinenet.com]
  • more...
  • Skin
  • more...
  • gastrointestinal
    Abdominal Pain
    • Find a 5-Star Gastroenterologist Near You Symptoms of alcoholic liver disease include abdominal pain, tenderness, jaundice (yellowing of the skin and whites of the eyes), fatigue, and nausea.[healthgrades.com]
    • 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]
    • If the accumulation of fatty acids in the liver is severe, the patient may experience weakness, nausea, abdominal pain, loss of appetite, and feel generally unwell.[medicalnewstoday.com]
    • At this stage, symptoms such as fever, jaundice, fatigue, abdominal pain and altered mental state may be encountered.[symptoma.com]
    • With alcoholic hepatitis, the liver becomes inflamed, often leading to fever, loss of appetite, nausea, vomiting, abdominal pain, and jaundice.[hazelden.org]
    Blood in Stool
    • Symptoms of bleeding from varices include vomiting blood (the vomitus can be red blood mixed with clots or "coffee grounds" in appearance, the latter due to the effect of acid on the blood), passing stool that is black and tarry due to changes in the[medicinenet.com]
    Diarrhea
    • 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]
    • 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 New confusion or a change in alertness, or it gets[nlm.nih.gov]
    • The only side effect that was more frequently reported under acamprosate than with placebo was diarrhea.[dx.doi.org]
    • Some patients with SBP have no symptoms, while others have fever , chills , abdominal pain and tenderness, diarrhea , and worsening ascites.[medicinenet.com]
    Increased Abdominal Girth
    • abdominal girth, personality changes, confusion, infections, and walking problems, for example, staggering.[medicalnewstoday.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]
    • If the accumulation of fatty acids in the liver is severe, the patient may experience weakness, nausea, abdominal pain, loss of appetite, and feel generally unwell.[medicalnewstoday.com]
    • […] of appetite, unexplained weight loss, or yellow skin or eyes.[healthgrades.com]
    • 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]
    • When this happens, symptoms can include: feeling sick weight loss loss of appetite yellowing of the eyes and skin (jaundice) swelling in the ankles and tummy confusion or drowsiness vomiting blood or passing blood in your stools This means ARLD is frequently[nhs.uk]
    Nausea
    • A person can have fatty liver but not exhibit signs or symptoms of liver disease other than fatigue, although other symptoms like nausea and vomiting may occur.[liversupport.com]
    • Find a 5-Star Gastroenterologist Near You Symptoms of alcoholic liver disease include abdominal pain, tenderness, jaundice (yellowing of the skin and whites of the eyes), fatigue, and nausea.[healthgrades.com]
    • With alcoholic hepatitis, the liver becomes inflamed, often leading to fever, loss of appetite, nausea, vomiting, abdominal pain, and jaundice.[hazelden.org]
    • I would like some knowledge on how alcohol... by Itsme444 Pale Stools & Dark Urine I'm hoping somebody might be able to give some feedback to a few... by twfrench91 Hoping for reassurance Hi Winnie, & I had terrible nausea and queasiness for... by MoonWatcher[mdjunction.com]
    • 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]
    Vomiting
    • A person can have fatty liver but not exhibit signs or symptoms of liver disease other than fatigue, although other symptoms like nausea and vomiting may occur.[liversupport.com]
    • With alcoholic hepatitis, the liver becomes inflamed, often leading to fever, loss of appetite, nausea, vomiting, abdominal pain, and jaundice.[hazelden.org]
    • […] medical care (call 911) for serious symptoms, such as constant weakness, dizziness, problems with thinking and memory, hallucinations, mood changes (especially agitation), extreme fatigue, fainting, fever (especially if combined with a swollen abdomen), vomiting[healthgrades.com]
    • […] curved fingertips and nails ( clubbed fingers ) blotchy red palms significant weight loss weakness and muscle wasting confusion and memory problems, trouble sleeping ( insomnia ) and changes in your personality due to a build-up of toxins in the brain vomiting[nhs.uk]
    • Many people will have vague symptoms – such as fatigue , nausea and vomiting ( typically in the morning), diarrhoea or abdominal pains.[netdoctor.co.uk]
  • more...
  • hematological
    Easy Bruising
    • 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 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[nlm.nih.gov]
    • They can include: Bleeding in the gut Easy bruising Fatigue Jaundice (yellow skin) Increased sensitivity to alcohol and drugs, both medical and recreational (because the liver cannot process them Itching Liver cancer Swelling of the legs ankles, or abdomen[drinkaware.co.uk]
    • Cirrhosis can cause weakness , loss of appetite , easy bruising, yellowing of the skin ( jaundice ), itching , and fatigue .[medicinenet.com]
  • more...
  • Workup

    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.

    Pathology

    Biopsy
    Liver Biopsy
    • A liver biopsy may be necessary to establish the existence of cirrhosis if it is not clinically apparent.[liversupport.com]
    • biopsy as a reference standard.[cochrane.org]
    • Ultrasound scans create an image of the liver and surrounding organs, which helps in taking a liver biopsy .[netdoctor.co.uk]
    • biopsy, and liver function tests as well as using CT scans or ultrasounds.[mdmercy.com]
  • more...
  • Laboratory

    Serum
    Dyslipidemia
    • There have been substantial links between increased fructose consumption and obesity, dyslipidemia and insulin resistance.[draxe.com]
    • […] similarities between fructose and its fermentation byproduct, ethanol (alcohol): Your liver's metabolism of fructose is similar to alcohol, as they both serve as substrates for converting dietary carbohydrate into fat, which promotes insulin resistance, dyslipidemia[articles.mercola.com]
  • more...
  • Treatment

    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].

    Prognosis

    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.

    Complications

    Alcoholic Hepatitis
    Chronic Liver Disease
    • Cirrhosis See compensated and decompensated chronic liver disease sections Pathophysiology of cirrhosis (not specifically ALD) Differential diagnosis of alcoholic liver disease (ALD) Other causes of chronic liver disease – see chronic liver disease (CLD[oxfordmedicaleducation.com]
    • Treatment options for alcoholic liver disease “When someone develops chronic liver disease or cirrhosis as a result of heavy drinking, there are not many treatment options to offer,” says Dr.[piedmont.org]
    • Automatic Approval Under the Chronic Liver Disease Listing If you have been diagnosed with alcoholic cirrhosis, you might be approved automatically for disability under Listing 5.05, Chronic Liver Disease.[nolo.com]
    • It features in most types of chronic liver diseases.[medicalnewstoday.com]
    • Non-alcoholics too may develop chronic liver disease.[medindia.net]
    Esophageal Varices
    • Alcoholic hepatitis can cause signs and symptoms of hepatic dysfunction, including jaundice, encephalopathy, and bleeding esophageal varices.[journalofethics.ama-assn.org]
    • Altered consciousness, enlarged spleen and liver, as well as hypertension and development of esophageal varices are observed in severe cases.[symptoma.com]
    • Some of the complications of cirrhosis are jaundice, ascites, edema, bleeding esophageal varices, blood coagulation abnormalities, coma and death.[hepatitiscentral.com]
    • Complications may include: Bleeding disorders (coagulopathy) Buildup of fluid in the abdomen (ascites) and infection of the fluid (bacterial peritonitis) Enlarged veins in the esophagus, stomach, or intestines that bleed easily (esophageal varices) Increased[nlm.nih.gov]
    Fatty Liver
    • Nonalcoholic fatty liver disease.[mayoclinic.org]
    • Alcoholic Fatty Liver Disease (steatosis) Alcoholic fatty liver disease is the accumulation of fat in the liver caused by excessive consumption of alcohol.[liversupport.com]
    • There are two main types of fatty liver disease, alcoholic liver disease and nonalcoholic fatty liver disease.[draxe.com]
    • Fatty liver disease is reversible.[hse.ie]
    • Diseases Fatty liver: Fatty liver disease is the build up of extra fat in liver cells.[ukhealthcare.uky.edu]
    Gynecomastia
    • In men, chronic alcoholism causes signs of hypogonadism and feminization (eg, smooth skin, lack of male-pattern baldness, gynecomastia, testicular atrophy, changes in pubic hair).[merckmanuals.com]
    • Physical Examination and Laboratory Findings In Alcoholic Liver Disease Physical Examination Constitutional Fever Skin Spider angioma Parotid and lacrimal gland enlargement Palmer erythema Jaundice Decreased body hair Gynecomastia Musculoskeletal Dupuytren[clevelandclinicmeded.com]
    • Symptoms of cirrhosis of the liver include: easy bruising may occur due to decreased production of clotting factors; bile salts can deposit in the skin causing itching ; gynecomastia or enlarged breasts in men may occur because of an imbalance in sex[medicinenet.com]
    • Many disease variables contribute to pain in patients with liver disease; for example, patients with advanced liver disease may have ascites, causing abdominal and lower back pain, and gynecomastia leading to mastalgia. 13,50,51 One study found that pain[journals.lww.com]
    Hemorrhoids
    • This can cause spleen swelling, and the development of varices or swollen veins in the gastrointestinal tract, from the esophagus (esophageal varices) and stomach to the anus (these are different than the swollen veins of hemorrhoids ).[medicinenet.com]
    • (Band ligation of the varices is analogous to rubber banding of hemorrhoids .)[medicinenet.com]
    Hyperlipidemia
    • Rarely, patients with fatty liver or cirrhosis present with Zieve syndrome (hyperlipidemia, hemolytic anemia, and jaundice).[merckmanuals.com]
    • In severe fatty liver, however, fat is distributed throughout the acinus. 17 Fatty liver is not specific to alcohol ingestion; it is associated with obesity, insulin resistance, hyperlipidemia, malnutrition, and various medications.[clevelandclinicmeded.com]
    • Extra fat in the liver has many causes and is more common in people who are overweight or obese. have diabetes—a condition characterized by high blood glucose, also called high blood sugar. have high blood cholesterol and triglycerides, called hyperlipidemia[digestive.niddk.nih.gov]
    Hypoglycemia
    • 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]
    Nonalcoholic Steatohepatitis
    • Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.[mayoclinic.org]
    • More information is provided in the NIDDK health topic, Nonalcoholic Steatohepatitis .[digestive.niddk.nih.gov]
    • Obesity is another factor associated with liver disease-specifically, the development of fatty liver and nonalcoholic steatohepatitis, a disorder similar to alcoholic hepatitis.[transplant.surgery.ucsf.edu]
    • Doctors now believe that cryptogenic cirrhosis is due to NASH (nonalcoholic steatohepatitis) caused by long standing obesity, type 2 diabetes , and insulin resistance.[medicinenet.com]
    • Nonalcoholic steatohepatitis happens to a small number of people with fatty liver.[draxe.com]
    Portal Hypertension
    • (See Understanding portal hypertension .)[journals.lww.com]
    • Fibrosis narrows the terminal hepatic venules, compromising hepatic perfusion and thus contributing to portal hypertension .[merckmanuals.com]
    • The late complications of alcoholic liver disease include: portal hypertension coagulation disorders ascites hepatic encephalopathy hepatorenal syndrome Hepatocellular carcinoma Hepatocellular carcinoma may also develop in about 20% of advanced alcoholic[liver-products.com]
    • Management and treatment of patients with cirrhosis and portal hypertension: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program.[nlm.nih.gov]
  • more...
  • Etiology

    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

    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].

    Sex distribution
    Age distribution

    Pathophysiology

    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].

    Prevention

    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].

    Summary

    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.

    Patient Information

    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.

    Self-assessment

    References

    1. Gao B, Bataller R. Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets. Gastroenterology. 2011;141(5):1572-1585.
    2. Gramenzi A , Caputo F, Biselli M, Kuria F, Loggi E, Andreone P, Bernardi M. Review article: alcoholic liver disease--pathophysiological aspects and risk factors. Aliment Pharmacol Ther. 2006;24(8):1151-1161.
    3. Orman ES, Odena G, Bataller R. Alcoholic liver disease: Pathogenesis, management, and novel targets for therapy. J Gastroenterol Hepatol. 2013;28(01):77-84.
    4. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
    5. Bruha R, Dvorák K, Dousa M, Petrtýl J, Svestka T. Alcoholic liver disease. Prague Med Rep. 2009;110(3):181-190.
    6. Singal AK, Jampana SC. Current management of alcoholic liver disease. Curr Drug Abuse Rev. 2014;7(1):18-28.
    7. Bruha R, Dvorak K, Petrtyl J. Alcoholic liver disease. World J Hepatol. 2012;4(3):81-90.
    8. Frazier TH, Stocker AM, Kershner NA, Marsano LS, McClain CJ. Treatment of alcoholic liver disease.TTherap Adv Gastroenterol. 2011;4(1):63-81.
    9. Mueller S, Millonig G, Seitz HK. Alcoholic liver disease and hepatitis C: a frequently underestimated combination. World J Gastroenterol. 2009;15:3462-3471.
    10. Zhou Z, Wang L, Song Z, et al. A critical involvement of oxidative stress in acute alcohol-induced hepatic TNF-alpha production. Am J Pathol. 2003; 163(3):1137-1146.
    11. Mann RE, Smart RG, Govoni R. The epidemiology of alcoholic liver disease. Alcohol Res Health. 2003;27(3):209-219.
    12. Kim W, Kim DJ. Severe alcoholic hepatitis-current concepts, diagnosis and treatment options. World J Hepatol. 2014;6(10):688-695.

    • Alcoholic liver disease - K Walsh, G Alexander - Postgraduate medical journal, 2000 - pmj.bmj.com
    • Alcohol relapse after liver transplantation for alcoholic liver disease: does it matter? - GP Pageaux, M Bismuth, P Perney, V Costes - Journal of , 2003 - Elsevier
    • Depressed hepatic glutathione and increased diene conjugates in alcoholic liver disease - S Shaw, KP Rubin, CS Lieber - Digestive diseases and sciences, 1983 - Springer
    • An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity. - JP Kushner, AJ Barbuto, GR Lee - Journal of Clinical Investigation, 1976 - ncbi.nlm.nih.gov
    • Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma - HB El-serag, T Tran, JE Everhart - Gastroenterology, 2004 - Elsevier
    • A prospective evaluation of bacteremic patients with chronic liver disease - PF Barnes, C Arevalo, LS Chan, SF Wong - , 1988 - Wiley Online Library
    • Anorectal varices, haemorrhoids, and portal hypertension - SW Hosking, AG Johnson, HL Smart, DR Triger - The Lancet, 1989 - Elsevier
    • Chronic pancreatitis - MJ DiMagno, EP DiMagno - Current opinion in gastroenterology, 2003 - journals.lww.com
    • Alcoholic liver disease: proposed recommendations for the American College of Gastroenterology - AJ McCullough, JFB O'Connor - The American journal of , 1998 - nature.com
    • Aminoterminal propeptide of type III procollagen in serum in alcoholic liver disease. - O Niemelä, L Risteli, EA Sotaniemi, J Risteli - Gastroenterology, 1983 - ukpmc.ac.uk
    • Assessment of nutritional status and in vivo immune responses in alcoholic liver disease. - PR Mills, A Shenkin, RS Anthony - The American journal , 1983 - Am Soc Nutrition
    • Adverse effects of exploratory laparotomy in patients with unsuspected liver disease - P Powell‐Jackson, B Greenway - British Journal of , 2005 - Wiley Online Library
    • Acute alcoholic hepatitis - AG Beckett, AV Livingstone, KR Hill - British medical journal, 1961 - ncbi.nlm.nih.gov
    • Cytokines and alcoholic liver disease - CJ McClain, S Shedlofsky, S Barve - Alcohol health and , 1997 - pubs.niaaa.nih.gov
    • Alcoholic liver disease - CS Abittan, CS Lieber - Current treatment options in gastroenterology, 1999 - Springer
    • , and portal circulation in alcoholic cirrhosis: relationship between quantitative Doppler measurements and the severity of portal hypertension and hepatic failure - P Taourel, P Blanc, M Dauzat, M Chabre, J Pradel - , 2003 - Wiley Online Library
    • Clinical implications of monoclonal gammopathy in chronic liver disease - S Slavin, A Zlotnick, IS Levij, M Eliakim - Digestive Diseases and Sciences, 1974 - Springer
    • Association of nonalcoholic fatty liver disease with insulin resistance - G Marchesini, M Brizi, AM Morselli-Labate - The American journal of , 1999 - Elsevier
    • Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values - P Mofrad, MJ Contos, M Haque, C Sargeant - , 2003 - Wiley Online Library
    • A simple biological index for detection of alcoholic liver disease in drinkers. - T Poynard, A Aubert, P Bedossa, A Abella - , 1991 - ukpmc.ac.uk
    • Assessment of prognostic factors in alcoholic liver disease: toward a global quantitative expression of severity - H Orrego, Y Israel, JE Blake, A Medline - Hepatology, 1983 - Wiley Online Library
    • INTERNIST: Can Artificial Intelligence Help? - RA Miller - Clinical Decisions and Laboratory Use, 1982 - books.google.com
    • Alcoholic liver disease: new insights in pathogenesis lead to new treatments - CS Lieber - Journal of Hepatology, 2000 - Elsevier
    • A simple clinical score predicts high risk for upper gastrointestinal hemorrhages from varices in patients with chronic liver disease - F Tacke, K Fiedler, C Trautwein - Scandinavian journal of , 2007 - informahealthcare.com
    • A double‐blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis - S Naveau, S Chollet‐Martin, S Dharancy - , 2004 - Wiley Online Library
    • Acute renal failure associated with increased intra-abdominal pressure. - WO Richards, W Scovill, B Shin, W Reed - Annals of surgery, 1983 - ncbi.nlm.nih.gov
    • A prospective evaluation of bacteremic patients with chronic liver disease - PF Barnes, C Arevalo, LS Chan, SF Wong - , 1988 - Wiley Online Library
    • Alcohol-induced pseudo-Cushing's disease: a study of prevalence with review of the literature - S Kirkman, DH Nelson - Metabolism, 1988 - Elsevier
    • Alcoholic liver disease: roles of alcohol and malnutrition. - E Mezey - The American journal of clinical nutrition, 1980 - Am Soc Nutrition
    • 11 beta-Hydroxysteroid dehydrogenase deficiency and glucocorticoid status in patients with alcoholic and non-alcoholic chronic liver disease. - PM Stewart, P Burra, CH Shackleton - Journal of Clinical , 1993 - Endocrine Soc
    • Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease - MP Peppers - : The Journal of Human Pharmacology and Drug , 1996 - Wiley Online Library
    • Alcoholic liver disease: pathologic, pathogenetic and clinical aspects - KG Ishak, HJ Zimmerman - Alcoholism: Clinical and , 2006 - Wiley Online Library
    • Alcohol-related liver disease: clinical aspects and management - S SHERLOCK - British Medical Bulletin, 1982 - British Council
    • Aminopyrine breath test in alcoholic liver disease and in patients on enzyme-inducing drugs. - KO Lewis, G Nicholson, P Lance, A Paton - Journal of clinical pathology, 1977 - jcp.bmj.com
    • Alcoholic liver disease in Scotland and northeastern England: presenting features in 510 patients - WS Hislop, IAD Bouchier, JG Allan, PW Brunt - QJM, 1983 - Oxford Univ Press
    • Alcohol and the liver: 1994 update. - CS Lieber - Gastroenterology, 1994 - ukpmc.ac.uk
    • Cytoskeleton antibodies in chronic active hepatitis, primary biliary cirrhosis, and alcoholic liver disease - P Kurki, A Miettinen, M Salaspuro, I Virtanen - , 1983 - Wiley Online Library
    • Acute confusional state following liver transplantation for alcoholic liver disease - CI Buis, RH Wiesner, RAF Krom, WK Kremers - Neurology, 2002 - AAN Enterprises
    • Acute liver failure - RQ Gill, RK Sterling - Journal of clinical gastroenterology, 2001 - journals.lww.com
    • Acetaminophen‐Related Acute Renal Failure without Fulminant Liver Failure - L Eguia, BJ Materson - Pharmacotherapy: The Journal of , 1997 - Wiley Online Library

    Media References

    1. Alcoholic hepatitis, CC BY-SA 2.5

    Languages

    Self-assessment