ALCOHOLIC LIVER DISEASES.
LIVER
Liver is Shaped like a wedge with its base to the right, the liver lies in the right and left upper quadrants (mainly on the right side) inferior to the diaphragm which separates it from the pleura, lungs, pericardium and heart.
Liver is the Largest solid organ in the body it Performs over 500 chemical processes,Produces over 160 different proteins,Makes clotting factors for the blood,Stores & releases sugar as glycogen,Metabolizes, detoxifies, synthesizes,The role of the liver — the largest internal organ is complex and varied.
FUNCTIONS OF LIVER INCLUDES
Liver perform many functions at all.Hundreds of functions are performed by the liver ranging from:-
Metabolism
Detoxification from our blood,
Fighting off infection,
Controlling blood sugar levels,
Manufacture hormones and proteins
Synthesis function
ALCOHOLIC LIVER DISEASE
What is Alcoholic Liver Disease?
As the name implies, alcoholic liver disease is liver injury attributed to alcohol abuse. The majority of Americans manage to drink alcohol without serious consequences. Research suggests, however, that liver disease may begin to develop after a "threshold" dose of alcohol has been consumed—generally assumed to be four drinks a day (four 12 ounces beers, four glasses of wine, or four ounces of hard liquor) for men, and one half that quantity for women. Nearly everyone who consumes this amount or more will have some evidence of liver injury, although less than 50% will develop serious liver disease.
Symptoms of alcoholic liver
The range of clinical features of alcoholic liver disease varies, from asymptomatic to end-stage liver disease with portal hypertension, jaundice and encephalopathy Patients may present with nonspecific digestive tract symptoms such as nausea, dry retching, diarrhea, anorexia, and abdominal pain—but often they wait until severe liver decompensation forms before consulting a physician. Patients may also seek medical attention as a result of the consequences of alcoholism, which may include accidents, violent behavior, depression, tremors, poor work performance, or social disruptions.
Fatty liver is usually asymptomatic. On evaluation hepatomegaly is present in 70% of patients and there may be mild abnormalities in transaminases.Patients with alcoholic hepatitis may also be asymptomatic. Hospitalized patients usually have jaundice and hepatomegaly and may exhibit ascites, encephalopathy,and fever depending on the severity of their disease.
Signs and symptoms of alcohol-related liver disease.
Most patients with alcohol-induced cirrhosis have hepatomegaly and/or splenomegaly. Clinical presentation is similar to other forms of end-stage liver disease but
may be accompanied by concurrent alcoholic hepatitis. Spider angiomata are frequently found in this patient population, along with palmar erythema, enlargement of parotid and lacrimal glands, testicular atrophy, ascites, venous collaterals, jaundice and encephalopathy.
Stages of alcoholic liver disease
Alcoholic liver disease is defined by three stages of liver damage following chronic heavy alcohol consumption: fatty liver, alcoholic hepatitis, and fibrosis/cirrhosisHowever, the assumption that alcoholic liver disease always progresses linearly from alcoholic fatty liver, to alcoholic hepatitis and ultimately to cirrhosis is not correct.
histologically detectable liver damage often overlap—and some cases of alcoholic liver disease never progress, regardless of the patient’s continued ethanol abuse.Fatty liver, or steatosis, is an abnormal accumulation of fat in the parenchymal cells of the liver and can occur within hours of significant alcohol intake. In the majority of patients (90%) it is associated with palpable liver enlargement. Fat deposits accumulate predominantly in the central and mid-zonal areas of the liver (zones 3 and2) and may be macrovesicular (large droplets) or microvesicular (small droplets). Other conditions, such as nonalcoholic fatty liver disease, drug toxicity and fatty liver of pregnancy may cause steatosis that is indistinguishable from alcoholic fatty liver. Fatty liver is a completely reversible lesion, assuming the patient abstains from alcohol.
One-third of chronic heavy alcohol users develop alcoholic hepatitis and most will have no symptoms. The prognosis is variable and depends on the severity of disease. Classic signs of alcoholic hepatitis include fatty changes, necrosis of liver cells, Mallory bodies and perivenular inflammatory infiltrates (especially neutrophils). Mallory bodies, eosinophilic collections of intermediate filaments found in the cytoplasm, are detected in most patients with alcoholic hepatitis but also occur with other liver diseases.
Fibrosis (or scar formation) first begins in the pericentral zone and then progresses if injury continues. If fibrosis is found on biopsy, it predicts a progression to cirrhosis or end-stage liver disease. Alcoholic cirrhosis is of the micronodular type. The normal lobular architecture is obscured and central veins are difficult to locate.
The amount of fat is variable and alcoholic hepatitis may or may not be present. Continuing necrosis and fibrosis results in the progression from a micro- to a macronodular pattern. This progression is accompanied by a reduction in steatosis in end-stage liver disease. Cirrhosis is not reversible.
Alcoholic Liver Disease: Causes
Introduction
Although alcohol ingestion is required to develop alcoholic liver disease, not everyone who consumes the "threshold dose" of alcohol will develop the disease.Amazingly, nearly 50% of individuals who ingest large amounts of ethanol are spared serious injury. In addition to the amount and duration of alcohol use, several other factors have been linked to an increased risk for the development of liver disease. These include genetics, gender, viral liver disease, nutrition, and exposure to other hepatotoxins.
Genetics
Polymorphisms exist in the enzymes ADH, CYP2E1, and ALDH. Differences in ADH and ALDH certainly contribute to the negative association with ethanol dependence in some Asian populations. HLA phenotypes, a genetic predisposition toward alcoholism and female gender may also contribute to overall risk.
Viral Liver Disease
Concurrent viral hepatitis increases the incidence of liver injury in alcoholics. Studies have shown that alcoholics co-infected with hepatitis C virus (HCV), (but not necessarily hepatitis B virus), develop liver injury at a younger age and with a lower cumulative dose of alcohol than those not infected with HCV. These patients also have a much higher chance of developing cirrhosis and hepatocellular cancer compared to alcoholics without hepatitis C Hepatitis B virion; C, Hepatitic C virion.
Nutrition
Initial hypotheses suggested that alcoholic liver disease was a result of alcohol intake in the face of poor nutrition. Today, however, it is understood that while malnutrition may worsen the severity of disease and obesity may increase the risk of developing disease, alcoholic liver disease does indeed occur in well-nourished individuals. Nutrition probably plays a role in hepatotoxicity. Current research suggests that patients with diets deficient in essential nutrients are more susceptible to the development of liver damage. Alcohol ingestion promotes the absorption of iron from the intestine, increasing hepatic iron stores. Iron acts as an electron donor, accelerating the generation of unstable free oxygen radicals. In addition to contributing to membrane injury, this may also exacerbate inflammatory response.
Hepatotoxin Exposure
In general, two insults are worse than one. Just as viral hepatitis increases the risk to develop alcohol related liver injury, other hepatotoxins may act synergistically or additively with alcohol. This is especially true with acetaminophen and vitamin A overdose.
Pathogenesis
Several factors have been proposed to explain the pathogenesis of alcoholic liver injury. These include:
· Variations in alcohol metabolism
· Centrilobular hypoxia
· Inflammatory cell infiltration and activation
· Antigenic adduct formation
· Variations in alcohol metabolism
Alcohol must be metabolized in order for liver injury to occur, and there are several pathways that contribute to its metabolism.
The major pathway occurs in the liver and begins by breaking ethanol into acetaldehyde via the enzyme alcohol dehydrogenase (ADH) . This in turn is broken down to acetate by the enzyme acetaldehyde dehydrogenase (ALDH). There is considerable genetic variability in both of these enzymes, which may account for differences in blood alcohol levels but does not predict susceptibility to liver disease. Asians typically have efficient ADH but deficient ALDH. This allows acetaldehyde to build up causing flushing, tachycardia, hypotension and, usually, an aversion to alcohol.
When alcohol concentration overwhelms the ADH pathway, it is typically oxidized by the microsomal ethanol oxidizing system (MEOS) and catalase. Generally, these pathways are more likely to generate injurious byproducts. Cytochrome P-450 2E1 (CYP2E1), a critical enzyme in MEOS, is up-regulated with chronic alcohol ingestion. Polymorphisms of CYP2E1 also exist and may correlate with differences in susceptibility to hepatocellular (liver) damage. In addition, CYP2E1 is responsible for metabolizing other drugs such as acetaminophen. This may help explain an alcoholic's increased risk to Tylenol®-induced liver injury even at recommended doses.
Centrilobular hypoxia
Liver injury is most prominent in the zonal region surrounding the central vein. This area is furthest from oxygenated blood and has the highest concentration of
CYP2E1, suggesting that oxygen debt contributes to injury
Inflammatory cell infiltration and activation
Pro inflammatory cytokines and inflammatory cells are often found in the blood and liver of patients with alcoholic hepatitis. Although several cytokines are present in patients with alcohol related liver injury, studies have concentrated on interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) as both correlate inversely with prognosis. These mediators may contribute to injury by promoting leukocyte adherence and activation. Kupffer cells (macrophages in the liver) may also be an important source of injury as they produce inflammatory and fibrogenic cytokines after being activated by alcohol. Chronic alcohol ingestion ultimately increases intestinal permeability, allowing endotoxins into the portal blood (Figure 4). This may exaggerate the release of cytokines and oxygen radicals from alcohol-primed Kupffer cells.
Antigenic adduct formation
Ethanol is metabolized to acetaldehyde and can also result in the formation of hydroxyethyl radicals. These radicals bind to hepatocellular proteins altering the proteins (forming adducts that are antigenic) and provoking an immune response. The contribution of autoimmunity in alcoholic liver injury is not clear. Antibodies to these adducts are found in serum from alcoholic patients. Animal studies have shown that guinea pigs immunized with acetaldehyde-protein adducts develop hepatic injury and fibrosis after ethanol ingestion. Other studies suggest that these adducts are not always located in areas that are accessible to the production of an immune response (e.g., retained within the hepatocyte).
Alcoholic Liver Disease: Diagnosis
History
A history of habitual ethanol consumption is key in suggesting alcohol as the cause of liver disease. The type of beverage most often consumed, be it beer, wine, or
distilled spirits does not influence the likelihood of ethanol-induced hepatotoxicity. Alcohol intake at two or more drinks a day should raise suspicion as patients may
underestimate their intake or have concomitant hepatic insults.
Biochemical Tests
Blood tests are useful in the evaluation of disorders of the liver and biliary system. There are several laboratory abnormalities characteristic of alcoholic liver disease.
However, these abnormalities do not necessarily correlate with disease severity.
Aminotransferases
Aminotransferase abnormalities are common in alcoholic liver disease. A disproportionate increase of serum aspartate aminotransferase, AST (SGOT) compared to
alanine aminotransferase, ALT (SGPT) is highly suggestive of alcoholic liver injury— especially if the ratio of AST:ALT is greater than 2.0. Aminotransferase levels are
generally lower than 300 IU/L, and other etiologies for liver disease should be considered if the enzymes concentrations are higher than this.
Gamma glutamyl transpeptidase
Gamma glutamyl transpeptidase (GGTP) is a membrane-associated enzyme involved in the uptake of amino acids. Increased serum activity of GGTP is often found
in chronic alcohol users—in fact, over 70% of alcoholic individuals have elevated GGTP activity. Unfortunately, several other medications also increase GGTP and
therefore this value must only be considered in combination with other laboratory and clinical information.
Hematologic and electrolyte abnormalities
Mean corpuscular volume (MCV), serum uric acid levels and serum electrolytes are all affected by chronic alcohol consumption. In addition, although symptoms may
be nonspecific, increased serum uric acid, hypokalemia, hypomagnesemia and acidosis are indicators that alcohol may play a significant role in liver disease. Alcohol
related bone marrow toxicity and/or splenic sequestration might contribute to macrocytosis (increased MCV) and thrombocytopenia. Leukocytosis is frequent in
individuals with alcoholic hepatitis and may correlate with disease severity.
Prothrombin time (PT)
This blood test is not of great diagnostic value in the detection of mild hepatocellular dysfunction. A mild increase may more accurately reflect poor nutrition (vitamin K
deficiency) than liver disease. However, when combined with bilirubin to generate a discriminant function (Discriminant function = 4.6 [PT (seconds) - control] bilirubin
(mg/dL). A value greater than 32 is associated with high mortality), PT may predict the severity of liver disease in hospitalized alcoholics with hepatitis and ultimately
help guide therapy (see therapy).
Liver Biopsy
Alcoholic hepatitis may require a biopsy for definitive diagnosis (Figure 11). In the absence of a liver biopsy, however, a diagnosis can be made on a history of
chronic, current, heavy alcohol consumption, clinical and biochemical data and the exclusion of other etiologies such as viral hepatitis. Noninvasive tests such as
ultrasonography and serologies complement a thorough history and physical examination. Histology is the most sensitive measure of disease stage and is a useful
prognostic indicator of disease course. It is currently the only reliable method to estimate the degree of a patient’s fibrosis. Fatty liver changes alone are not as
serious as perivenular sclerosis (a precursor of cirrhosis). Biopsy can also confirm the diagnosis of cirrhosis.
Ultrasound
Ultrasound is noninvasive, easy to perform and has no known accompanying risks. It is often used as a screening tool in patients with hepatic dysfunction. Abdominal
ultrasound, however, is not able to detect minimal changes in the liver or to distinguish fibrotic changes and therefore cannot predict those patients at risk to develop
cirrhosis.
Computed Tomography
CT scanning is useful in the diagnosis of cirrhosis, portal hypertension and liver masses.
In other way we can sy that Alcoholic liver disease is a term that encompasses the liver manifestations of:-
· alcohol overconsumption,
· including fatty liver, alcoholic hepatitis, and
· chronic hepatitis with liver fibrosis or cirrhosis
Alcoholic liver It is the major cause of liver disease in Western countries.
Of all chronic heavy drinkers, only 15–20% develop hepatitis or cirrhosis, which can occur concomitantly or in succession.
The mechanism behind this is not completely understood.
80% of alcohol passes through the liver to be detoxified.
Chronic consumption of alcohol results in the secretion of pro-inflammatory:-
cytokines
TNF-alpha
Interleukin 6
Interleukin 8
lipid peroxidation
acetaldehyde toxicity
These factors cause inflammation, apoptosis and eventually fibrosis of liver cells.
Why this occurs in only a few individuals is still unclear.
Additionally, the liver has tremendous capacity to regenerate and even when 75% of hepatocytes are dead, it continues to function as normal.
LIVER
Liver is Shaped like a wedge with its base to the right, the liver lies in the right and left upper quadrants (mainly on the right side) inferior to the diaphragm which separates it from the pleura, lungs, pericardium and heart.
Liver is the Largest solid organ in the body it Performs over 500 chemical processes,Produces over 160 different proteins,Makes clotting factors for the blood,Stores & releases sugar as glycogen,Metabolizes, detoxifies, synthesizes,The role of the liver — the largest internal organ is complex and varied.
FUNCTIONS OF LIVER INCLUDES
Liver perform many functions at all.Hundreds of functions are performed by the liver ranging from:-
Metabolism
Detoxification from our blood,
Fighting off infection,
Controlling blood sugar levels,
Manufacture hormones and proteins
Synthesis function
ALCOHOLIC LIVER DISEASE
What is Alcoholic Liver Disease?
As the name implies, alcoholic liver disease is liver injury attributed to alcohol abuse. The majority of Americans manage to drink alcohol without serious consequences. Research suggests, however, that liver disease may begin to develop after a "threshold" dose of alcohol has been consumed—generally assumed to be four drinks a day (four 12 ounces beers, four glasses of wine, or four ounces of hard liquor) for men, and one half that quantity for women. Nearly everyone who consumes this amount or more will have some evidence of liver injury, although less than 50% will develop serious liver disease.
Symptoms of alcoholic liver
The range of clinical features of alcoholic liver disease varies, from asymptomatic to end-stage liver disease with portal hypertension, jaundice and encephalopathy Patients may present with nonspecific digestive tract symptoms such as nausea, dry retching, diarrhea, anorexia, and abdominal pain—but often they wait until severe liver decompensation forms before consulting a physician. Patients may also seek medical attention as a result of the consequences of alcoholism, which may include accidents, violent behavior, depression, tremors, poor work performance, or social disruptions.
Fatty liver is usually asymptomatic. On evaluation hepatomegaly is present in 70% of patients and there may be mild abnormalities in transaminases.Patients with alcoholic hepatitis may also be asymptomatic. Hospitalized patients usually have jaundice and hepatomegaly and may exhibit ascites, encephalopathy,and fever depending on the severity of their disease.
Signs and symptoms of alcohol-related liver disease.
Most patients with alcohol-induced cirrhosis have hepatomegaly and/or splenomegaly. Clinical presentation is similar to other forms of end-stage liver disease but
may be accompanied by concurrent alcoholic hepatitis. Spider angiomata are frequently found in this patient population, along with palmar erythema, enlargement of parotid and lacrimal glands, testicular atrophy, ascites, venous collaterals, jaundice and encephalopathy.
Stages of alcoholic liver disease
Alcoholic liver disease is defined by three stages of liver damage following chronic heavy alcohol consumption: fatty liver, alcoholic hepatitis, and fibrosis/cirrhosisHowever, the assumption that alcoholic liver disease always progresses linearly from alcoholic fatty liver, to alcoholic hepatitis and ultimately to cirrhosis is not correct.
histologically detectable liver damage often overlap—and some cases of alcoholic liver disease never progress, regardless of the patient’s continued ethanol abuse.Fatty liver, or steatosis, is an abnormal accumulation of fat in the parenchymal cells of the liver and can occur within hours of significant alcohol intake. In the majority of patients (90%) it is associated with palpable liver enlargement. Fat deposits accumulate predominantly in the central and mid-zonal areas of the liver (zones 3 and2) and may be macrovesicular (large droplets) or microvesicular (small droplets). Other conditions, such as nonalcoholic fatty liver disease, drug toxicity and fatty liver of pregnancy may cause steatosis that is indistinguishable from alcoholic fatty liver. Fatty liver is a completely reversible lesion, assuming the patient abstains from alcohol.
One-third of chronic heavy alcohol users develop alcoholic hepatitis and most will have no symptoms. The prognosis is variable and depends on the severity of disease. Classic signs of alcoholic hepatitis include fatty changes, necrosis of liver cells, Mallory bodies and perivenular inflammatory infiltrates (especially neutrophils). Mallory bodies, eosinophilic collections of intermediate filaments found in the cytoplasm, are detected in most patients with alcoholic hepatitis but also occur with other liver diseases.
Fibrosis (or scar formation) first begins in the pericentral zone and then progresses if injury continues. If fibrosis is found on biopsy, it predicts a progression to cirrhosis or end-stage liver disease. Alcoholic cirrhosis is of the micronodular type. The normal lobular architecture is obscured and central veins are difficult to locate.
The amount of fat is variable and alcoholic hepatitis may or may not be present. Continuing necrosis and fibrosis results in the progression from a micro- to a macronodular pattern. This progression is accompanied by a reduction in steatosis in end-stage liver disease. Cirrhosis is not reversible.
Alcoholic Liver Disease: Causes
Introduction
Although alcohol ingestion is required to develop alcoholic liver disease, not everyone who consumes the "threshold dose" of alcohol will develop the disease.Amazingly, nearly 50% of individuals who ingest large amounts of ethanol are spared serious injury. In addition to the amount and duration of alcohol use, several other factors have been linked to an increased risk for the development of liver disease. These include genetics, gender, viral liver disease, nutrition, and exposure to other hepatotoxins.
Genetics
Polymorphisms exist in the enzymes ADH, CYP2E1, and ALDH. Differences in ADH and ALDH certainly contribute to the negative association with ethanol dependence in some Asian populations. HLA phenotypes, a genetic predisposition toward alcoholism and female gender may also contribute to overall risk.
Viral Liver Disease
Concurrent viral hepatitis increases the incidence of liver injury in alcoholics. Studies have shown that alcoholics co-infected with hepatitis C virus (HCV), (but not necessarily hepatitis B virus), develop liver injury at a younger age and with a lower cumulative dose of alcohol than those not infected with HCV. These patients also have a much higher chance of developing cirrhosis and hepatocellular cancer compared to alcoholics without hepatitis C Hepatitis B virion; C, Hepatitic C virion.
Nutrition
Initial hypotheses suggested that alcoholic liver disease was a result of alcohol intake in the face of poor nutrition. Today, however, it is understood that while malnutrition may worsen the severity of disease and obesity may increase the risk of developing disease, alcoholic liver disease does indeed occur in well-nourished individuals. Nutrition probably plays a role in hepatotoxicity. Current research suggests that patients with diets deficient in essential nutrients are more susceptible to the development of liver damage. Alcohol ingestion promotes the absorption of iron from the intestine, increasing hepatic iron stores. Iron acts as an electron donor, accelerating the generation of unstable free oxygen radicals. In addition to contributing to membrane injury, this may also exacerbate inflammatory response.
Hepatotoxin Exposure
In general, two insults are worse than one. Just as viral hepatitis increases the risk to develop alcohol related liver injury, other hepatotoxins may act synergistically or additively with alcohol. This is especially true with acetaminophen and vitamin A overdose.
Pathogenesis
Several factors have been proposed to explain the pathogenesis of alcoholic liver injury. These include:
· Variations in alcohol metabolism
· Centrilobular hypoxia
· Inflammatory cell infiltration and activation
· Antigenic adduct formation
· Variations in alcohol metabolism
Alcohol must be metabolized in order for liver injury to occur, and there are several pathways that contribute to its metabolism.
The major pathway occurs in the liver and begins by breaking ethanol into acetaldehyde via the enzyme alcohol dehydrogenase (ADH) . This in turn is broken down to acetate by the enzyme acetaldehyde dehydrogenase (ALDH). There is considerable genetic variability in both of these enzymes, which may account for differences in blood alcohol levels but does not predict susceptibility to liver disease. Asians typically have efficient ADH but deficient ALDH. This allows acetaldehyde to build up causing flushing, tachycardia, hypotension and, usually, an aversion to alcohol.
When alcohol concentration overwhelms the ADH pathway, it is typically oxidized by the microsomal ethanol oxidizing system (MEOS) and catalase. Generally, these pathways are more likely to generate injurious byproducts. Cytochrome P-450 2E1 (CYP2E1), a critical enzyme in MEOS, is up-regulated with chronic alcohol ingestion. Polymorphisms of CYP2E1 also exist and may correlate with differences in susceptibility to hepatocellular (liver) damage. In addition, CYP2E1 is responsible for metabolizing other drugs such as acetaminophen. This may help explain an alcoholic's increased risk to Tylenol®-induced liver injury even at recommended doses.
Centrilobular hypoxia
Liver injury is most prominent in the zonal region surrounding the central vein. This area is furthest from oxygenated blood and has the highest concentration of
CYP2E1, suggesting that oxygen debt contributes to injury
Inflammatory cell infiltration and activation
Pro inflammatory cytokines and inflammatory cells are often found in the blood and liver of patients with alcoholic hepatitis. Although several cytokines are present in patients with alcohol related liver injury, studies have concentrated on interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) as both correlate inversely with prognosis. These mediators may contribute to injury by promoting leukocyte adherence and activation. Kupffer cells (macrophages in the liver) may also be an important source of injury as they produce inflammatory and fibrogenic cytokines after being activated by alcohol. Chronic alcohol ingestion ultimately increases intestinal permeability, allowing endotoxins into the portal blood (Figure 4). This may exaggerate the release of cytokines and oxygen radicals from alcohol-primed Kupffer cells.
Antigenic adduct formation
Ethanol is metabolized to acetaldehyde and can also result in the formation of hydroxyethyl radicals. These radicals bind to hepatocellular proteins altering the proteins (forming adducts that are antigenic) and provoking an immune response. The contribution of autoimmunity in alcoholic liver injury is not clear. Antibodies to these adducts are found in serum from alcoholic patients. Animal studies have shown that guinea pigs immunized with acetaldehyde-protein adducts develop hepatic injury and fibrosis after ethanol ingestion. Other studies suggest that these adducts are not always located in areas that are accessible to the production of an immune response (e.g., retained within the hepatocyte).
Alcoholic Liver Disease: Diagnosis
History
A history of habitual ethanol consumption is key in suggesting alcohol as the cause of liver disease. The type of beverage most often consumed, be it beer, wine, or
distilled spirits does not influence the likelihood of ethanol-induced hepatotoxicity. Alcohol intake at two or more drinks a day should raise suspicion as patients may
underestimate their intake or have concomitant hepatic insults.
Biochemical Tests
Blood tests are useful in the evaluation of disorders of the liver and biliary system. There are several laboratory abnormalities characteristic of alcoholic liver disease.
However, these abnormalities do not necessarily correlate with disease severity.
Aminotransferases
Aminotransferase abnormalities are common in alcoholic liver disease. A disproportionate increase of serum aspartate aminotransferase, AST (SGOT) compared to
alanine aminotransferase, ALT (SGPT) is highly suggestive of alcoholic liver injury— especially if the ratio of AST:ALT is greater than 2.0. Aminotransferase levels are
generally lower than 300 IU/L, and other etiologies for liver disease should be considered if the enzymes concentrations are higher than this.
Gamma glutamyl transpeptidase
Gamma glutamyl transpeptidase (GGTP) is a membrane-associated enzyme involved in the uptake of amino acids. Increased serum activity of GGTP is often found
in chronic alcohol users—in fact, over 70% of alcoholic individuals have elevated GGTP activity. Unfortunately, several other medications also increase GGTP and
therefore this value must only be considered in combination with other laboratory and clinical information.
Hematologic and electrolyte abnormalities
Mean corpuscular volume (MCV), serum uric acid levels and serum electrolytes are all affected by chronic alcohol consumption. In addition, although symptoms may
be nonspecific, increased serum uric acid, hypokalemia, hypomagnesemia and acidosis are indicators that alcohol may play a significant role in liver disease. Alcohol
related bone marrow toxicity and/or splenic sequestration might contribute to macrocytosis (increased MCV) and thrombocytopenia. Leukocytosis is frequent in
individuals with alcoholic hepatitis and may correlate with disease severity.
Prothrombin time (PT)
This blood test is not of great diagnostic value in the detection of mild hepatocellular dysfunction. A mild increase may more accurately reflect poor nutrition (vitamin K
deficiency) than liver disease. However, when combined with bilirubin to generate a discriminant function (Discriminant function = 4.6 [PT (seconds) - control] bilirubin
(mg/dL). A value greater than 32 is associated with high mortality), PT may predict the severity of liver disease in hospitalized alcoholics with hepatitis and ultimately
help guide therapy (see therapy).
Liver Biopsy
Alcoholic hepatitis may require a biopsy for definitive diagnosis (Figure 11). In the absence of a liver biopsy, however, a diagnosis can be made on a history of
chronic, current, heavy alcohol consumption, clinical and biochemical data and the exclusion of other etiologies such as viral hepatitis. Noninvasive tests such as
ultrasonography and serologies complement a thorough history and physical examination. Histology is the most sensitive measure of disease stage and is a useful
prognostic indicator of disease course. It is currently the only reliable method to estimate the degree of a patient’s fibrosis. Fatty liver changes alone are not as
serious as perivenular sclerosis (a precursor of cirrhosis). Biopsy can also confirm the diagnosis of cirrhosis.
Ultrasound
Ultrasound is noninvasive, easy to perform and has no known accompanying risks. It is often used as a screening tool in patients with hepatic dysfunction. Abdominal
ultrasound, however, is not able to detect minimal changes in the liver or to distinguish fibrotic changes and therefore cannot predict those patients at risk to develop
cirrhosis.
Computed Tomography
CT scanning is useful in the diagnosis of cirrhosis, portal hypertension and liver masses.
In other way we can sy that Alcoholic liver disease is a term that encompasses the liver manifestations of:-
· alcohol overconsumption,
· including fatty liver, alcoholic hepatitis, and
· chronic hepatitis with liver fibrosis or cirrhosis
Alcoholic liver It is the major cause of liver disease in Western countries.
Of all chronic heavy drinkers, only 15–20% develop hepatitis or cirrhosis, which can occur concomitantly or in succession.
The mechanism behind this is not completely understood.
80% of alcohol passes through the liver to be detoxified.
Chronic consumption of alcohol results in the secretion of pro-inflammatory:-
cytokines
TNF-alpha
Interleukin 6
Interleukin 8
lipid peroxidation
acetaldehyde toxicity
These factors cause inflammation, apoptosis and eventually fibrosis of liver cells.
Why this occurs in only a few individuals is still unclear.
Additionally, the liver has tremendous capacity to regenerate and even when 75% of hepatocytes are dead, it continues to function as normal.