Hepatitis VirusesHepatitis Viruses

Dr. Alvaro Barboza Quintana.Dr. Alvaro Barboza Quintana.Profesor de Patología.Profesor de Patología.Fac. Medicina UANL.Fac. Medicina UANL.Escuela de Medicina ITESMEscuela de Medicina ITESM..

Causes of hepatitisCauses of hepatitis

Hepatitis can be caused by Hepatitis can be caused by some viruses, bacteria, some viruses, bacteria, parasites, fungi and parasites, fungi and chemicals as part of the chemicals as part of the clinical features that clinical features that characterizes each characterizes each disease. But the disease. But the hepatitis viruses, a hepatitis viruses, a heterogeneous group of heterogeneous group of viruses with an special viruses with an special affinity for the liver, are affinity for the liver, are the mayor cause of viral the mayor cause of viral hepatitis.hepatitis.

Liver is often affected by:Liver is often affected by:– Citomegalovirus.Citomegalovirus.– Mononucleosis.Mononucleosis.– Yellow fever.Yellow fever.

Virus with high affinity Virus with high affinity for liver:for liver:– Hepatitis virus A.Hepatitis virus A.– Hepatitis virus B.Hepatitis virus B.– Hepatitis virus C.Hepatitis virus C.– Hepatitis virus D.Hepatitis virus D.– Hepatitis virus E.Hepatitis virus E.– Hepatitis virus F.Hepatitis virus F.– Hepatitis virus G.Hepatitis virus G.

agent agent transmission transmission incubation incubation chronic chronic period period hepatitis hepatitis

HAVHAV icosahe-icosahe- fecal-oral fecal-oral 2-6 wk 2-6 wk none none dral capsid,dral capsid, RNARNA

HBVHBV enveloped enveloped parenteral; parenteral; 4-26 wk 4-26 wk 5-10% 5-10%

of acute DNA of acute DNA close contact close contact

HCVHCV enveloped enveloped parenteral; parenteral; 2-26 wk 2-26 wk >50% >50% RNARNA close contact close contact

HDVHDV enveloped parenteral;enveloped parenteral; 4-7 wk 4-7 wk <5% <5%

coinfection, RN closecoinfection, RN close contactcontact80%superinfect.80%superinfect.

HEVHEV unenve-unenve- water-borne water-borne 2-8 wk 2-8 wk none none loped RNA loped RNA

HGVHGV RNA virus parenteralRNA virus parenteral unknown unknown none none

Hepatitis A (HAV)Hepatitis A (HAV)

A benign, self-A benign, self-limited disease, limited disease, known as known as infectious infectious hepatitis. hepatitis. Accounts for Accounts for about 25% of about 25% of clinically evident clinically evident acute hepatitis. acute hepatitis.

EpidemiologyEpidemiology

TransmissionTransmissionFeFecal-oral route. cal-oral route. EExcreted in the stool of xcreted in the stool of patients 2-3 weeks before, and 8-10 days patients 2-3 weeks before, and 8-10 days after, the onset of jaundice. The virus after, the onset of jaundice. The virus particle is resistant to degradation, particle is resistant to degradation, remaining infectious in the environment for remaining infectious in the environment for weeks.weeks.

Person-to-person transmissioPerson-to-person transmission.- n.- cause cause outbreaks in places like institutions.outbreaks in places like institutions. Fecal contamination of a single sourceFecal contamination of a single source.-.- can can lead to sudden epidemies. lead to sudden epidemies. 

Hepatitis A virusHepatitis A virus

Distribution and Distribution and incidenceincidence..

WWorldwide orldwide infection, infection, especially in areas especially in areas with substandar with substandar hygiene and hygiene and sanitation.sanitation.

  

Clinical diseaseClinical disease

HAV HAV causes an causes an acute, acute, highly highly contagioucontagious form of s form of hepatitishepatitis::

Clinical infectionClinical infection

  The pre-icteric stage is characterized by The pre-icteric stage is characterized by nonspecific,nonspecific, flu-like symptoms of anorexia, flu-like symptoms of anorexia, nausea, vomiting, and malaise.nausea, vomiting, and malaise.

The icteric stage is characterized by The icteric stage is characterized by hyperbilirubinemia, jaundice, hyperbilirubinemia, jaundice,

hepatomegaly, right upper quadrant hepatomegaly, right upper quadrant tenderness, and raised serum levels of tenderness, and raised serum levels of liver enzymes such as alanine liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (ALT) and aspartate aminotransferase (AST)aminotransferase (AST)..

MMorphologic features orphologic features in acute hepatitis:in acute hepatitis:     Morfologic changes Morfologic changes

in acute viral in acute viral hepatitis are shared hepatitis are shared among hepatotropic among hepatotropic virusvirus

inflammatory inflammatory infiltrate, bile duct infiltrate, bile duct reaction, balloning reaction, balloning degeneration (were degeneration (were the hepatocite the hepatocite cytoplasm looks cytoplasm looks empty), macrophage empty), macrophage aagggregates, gregates, cholestasis and cholestasis and apoptosis.apoptosis.

  

Portal tract inflammation, Kupffer's cell hypertrophy and spotty acidophilic

necrosis of hepatocytes.

DiagnosisDiagnosis

Clinical dataClinical data

Serologic tests that Serologic tests that detect antibodies to detect antibodies to HAV. The finding of HAV. The finding of IgM anti-HAV IgM anti-HAV antibodies indicates antibodies indicates current or recent current or recent infection, while the infection, while the finding of IgG anti-finding of IgG anti-HAV antibodies HAV antibodies (without IgM (without IgM antibodies) indicates antibodies) indicates past exposure to the past exposure to the virus.virus.

TreatmentTreatment

SSupportiveupportive therapy therapy. .

Immunity after HAV infection is Immunity after HAV infection is usually lifelong, infrequently waning in usually lifelong, infrequently waning in the elderly. Relapses occur, but chronic the elderly. Relapses occur, but chronic carriers of HAV have not been detected. carriers of HAV have not been detected. In developing countries, with inadequate In developing countries, with inadequate sanitation, infection occurs sanitation, infection occurs more more in in childhood. childhood.

Prevention with killed virus vaccine.Prevention with killed virus vaccine.

Hepatitis B virus Hepatitis B virus (HBV)(HBV)

EpidemiologyEpidemiology

300,000 people are afected (USA)300,000 people are afected (USA) Endemic in Italy, Grece, Africa Endemic in Italy, Grece, Africa

and the southeast of Asia and the southeast of Asia The hepatocellular carcinoma is The hepatocellular carcinoma is

endemic in those countriesendemic in those countries Asymptomatic patients may have Asymptomatic patients may have

the virus in blood and other body the virus in blood and other body fluids this is why it’s easily fluids this is why it’s easily transmitedtransmited

Incubation period: 6 weeks-6 Incubation period: 6 weeks-6 monthsmonths

TransmissionTransmission BloodBlood Sexual contact Sexual contact Perinatal Perinatal

Risk groupRisk group Drug users that share needlesDrug users that share needles Sexually active people (especially those who Sexually active people (especially those who

are promiscuous) are promiscuous) Patients that have dialysisPatients that have dialysis Infants born to infected mothers Infants born to infected mothers Healthcare workers Healthcare workers

Clinical manifestationsClinical manifestations

AcuteAcute Subclinical infectionsSubclinical infections

– Are more common than Are more common than clinical infectionsclinical infections

– Liver enzymes are Liver enzymes are elevatedelevated

– The severity of the The severity of the disease is related to the disease is related to the viral dose viral dose

Jaundice Jaundice FatigueFatigue Abdominal painAbdominal pain AnorexiaAnorexia NauseaNausea Vomiting Vomiting

Clinical manifestationsClinical manifestations

Chronic Chronic Carriers: individuals who have Carriers: individuals who have

detectable HBsAg (hepatitis B detectable HBsAg (hepatitis B superficial antigen) for at least 6 superficial antigen) for at least 6 monthsmonths

Of patients that become chronic Of patients that become chronic carriers, the majority (90%) develop carriers, the majority (90%) develop chronic persistent hepatitis and rest chronic persistent hepatitis and rest will develop chronic active hepatitiswill develop chronic active hepatitis

Serologic markers for hepatitis Serologic markers for hepatitis BB

Serologic markers in chronic Serologic markers in chronic HBVHBV

Persistent hepatitis BPersistent hepatitis B

They remain clinically well, but They remain clinically well, but they are able to infect other they are able to infect other peoplepeople

The liver enzymes may be slightly The liver enzymes may be slightly elevatedelevated

It can lead to terminal liver It can lead to terminal liver failurefailure

Chronic active Chronic active hepatitishepatitis Patients are more likely to be Patients are more likely to be

symptomatic and to have a more symptomatic and to have a more severe manifestationssevere manifestations

Complications of chronic Complications of chronic hepatitishepatitis

It’s associated with cirrohosis and It’s associated with cirrohosis and hepatocellular carcinomahepatocellular carcinoma

Limitant plate damage or

interface necrosis.

Liver architecture is usually well preservedWith lymphoid aggregates in portal tract.

CirrhosisCirrhosis Chronic carriers especially those Chronic carriers especially those

with chronic active hepatitis, with chronic active hepatitis, may develop cirrhosismay develop cirrhosis

HBV as oncogenic HBV as oncogenic factorfactor Causes between 250,000-Causes between 250,000-

1,000,000 deaths worldwide in a 1,000,000 deaths worldwide in a yearyear

Approximately 80% of the cases Approximately 80% of the cases of HC are owed to HBVof HC are owed to HBV

The period between the infection The period between the infection with HB until the development of with HB until the development of HC could be from 9-35 years HC could be from 9-35 years

Hepatocellular carcinoma. Such liver cancers arise of cirrhosis

Hepatocellular carcinoma.Hepatocellular carcinoma. There is no discernable normal lobular architecture, though vascular There is no discernable normal lobular architecture, though vascular

structures are presentstructures are present

PreventionPrevention

Hepatitis B vaccine (available Hepatitis B vaccine (available since 1982) since 1982) – Routine vaccination of 0-18 year oldsRoutine vaccination of 0-18 year olds

Screening pregnant women and Screening pregnant women and treatment of infants born to treatment of infants born to infected women infected women

Screening of blood/organ/tissue Screening of blood/organ/tissue donors donors

Hepatitis C Hepatitis C

90% of the cases 90% of the cases are associated to are associated to transfusionstransfusions

TransmissionTransmission Blood Blood Needles Needles Sexual Sexual

intercourseintercourse

Hepatitis C virus

EpidemiologyEpidemiology

5-10% of the cases are post-5-10% of the cases are post-transfusionstransfusions

It produces cronic hepatitisIt produces cronic hepatitis– Cirrosis Cirrosis in 20% of the cases in 20% of the cases– Hepatocellular carcinoma Hepatocellular carcinoma in 50% in 50%

of the casesof the cases

Clinical Clinical manifestationsmanifestations It has 2 types:It has 2 types:

– Acute: Acute: It could last 4/6 monthsIt could last 4/6 months Similar to manifestations seen in Similar to manifestations seen in

hepatitis A or B, but with less hepatitis A or B, but with less inflamationinflamation

– Chronic:Chronic: More then 10 yearsMore then 10 years Leads frecuently to hepatocelluar Leads frecuently to hepatocelluar

carcinoma and cirrosiscarcinoma and cirrosis

Hepatitis C.

Diagnosis and Diagnosis and treatmenttreatment ELISA ELISA

Interferon alfaInterferon alfa

Hepatitis D virus. Delta Hepatitis D virus. Delta agent.agent.

HDV is a defective HDV is a defective RNA virus. Needs RNA virus. Needs to be to be encapsulated by encapsulated by HBsAg.HBsAg.

Superinfection of a Superinfection of a chronic carrier of chronic carrier of HBVHBV

Progression to Progression to cirrhosis in 80%cirrhosis in 80%

Hepatitis E virus.Hepatitis E virus.

High mortality range among pregnant women 20%

Drug and toxin Drug and toxin Induced liver Induced liver

DiseaseDisease

hepatotoxicity from hepatotoxicity from chemicalschemicals

Drug Induced liver Drug Induced liver DiseaseDisease Liver is the mayor detoxifying organ in Liver is the mayor detoxifying organ in

the body.the body. Liver is subjet to potential damage Liver is subjet to potential damage

from pharamceutical and from pharamceutical and environmental chemicals.environmental chemicals.

Injury may result from:Injury may result from:– Direct toxicityDirect toxicity– Hepatic conversion of chemical.Hepatic conversion of chemical.– Immune mechanisms.Immune mechanisms.

Drug Induced liver Drug Induced liver DiseaseDisease Liver damage from chemicals may be Liver damage from chemicals may be

immediate or take months.immediate or take months. Forms of liver injury:Forms of liver injury:

– Hepatocyte necrosisHepatocyte necrosis– CholestasisCholestasis– Insidious onset of dysfunction.Insidious onset of dysfunction.– Drug induced chronic hepatitis is Drug induced chronic hepatitis is

indistinguishable from chrinc viral indistinguishable from chrinc viral hepatitishepatitis

Drug Induced liver DiseaseDrug Induced liver Disease

Hepatocelular Hepatocelular damagedamage ChemicalsChemicals

Microvesicular fatty Microvesicular fatty changechange

Tetracycline, Tetracycline, salicylates.salicylates.

Macrovesicular fatty Macrovesicular fatty changechange

Ethanol, methrotexate.Ethanol, methrotexate.

Massive necrosisMassive necrosis Acetaminophen, Acetaminophen, insoniazid.insoniazid.

Hepatitis, acute and Hepatitis, acute and chronicchronic

Methyldopa, phenytoin.Methyldopa, phenytoin.

CholestasisCholestasis Anabolic steroids, oral Anabolic steroids, oral contraceptives.contraceptives.

Drug Induced liver Drug Induced liver DiseaseDisease Reye syndromeReye syndrome

– Mitochonrdial dysfuntion in liver and Mitochonrdial dysfuntion in liver and some other organs.some other organs.

– Predminantly in children given Predminantly in children given acetylsalicylic acid cause of fever.acetylsalicylic acid cause of fever.

– Produces microvesicular steatosis Produces microvesicular steatosis with severe liver dysfuntion.with severe liver dysfuntion.

Alcholic liver diseaseAlcholic liver disease

(Ethanol Metabolism)(Ethanol Metabolism)

EpidemiologyEpidemiology

It develop only after a "threshold" dose It develop only after a "threshold" dose 600 kg for men and 150 to 300 kg for 600 kg for men and 150 to 300 kg for

women. women. one must consume eight 12-oz beers, 1 one must consume eight 12-oz beers, 1

L of wine, daily for a period of 20 yearsL of wine, daily for a period of 20 years Almost all people who exceed this Almost all people who exceed this

threshold dose of ethanol exhibit some threshold dose of ethanol exhibit some biochemical or histologic abnormality biochemical or histologic abnormality suggestive of liver injurysuggestive of liver injury

EpidemiologyEpidemiology

fewer than 50% of people who fewer than 50% of people who ingest the calculated threshold ingest the calculated threshold dose of ethanol eventually develop dose of ethanol eventually develop serious alcoholic liver disease (e.g., serious alcoholic liver disease (e.g., alcoholic hepatitis or fibrosis).alcoholic hepatitis or fibrosis).

This suggest that the pathogenesis This suggest that the pathogenesis involves hereditary and involves hereditary and enviromental disorders. enviromental disorders.

MetabolismMetabolism

Liver. 3 enzyme systems: ADH, Liver. 3 enzyme systems: ADH, MEOS and catalase. MEOS and catalase.

There exist several isoforms of the There exist several isoforms of the ADH enzyme (alfa, beta and ADH enzyme (alfa, beta and gamma) and variation in this gamma) and variation in this changes the metabolic rate of changes the metabolic rate of ethanol. Asians (beta2) 20% faster. ethanol. Asians (beta2) 20% faster.

ADH acts alone ADH acts alone when tissue levels when tissue levels do not exceed 10 mmol/L do not exceed 10 mmol/L

MEOSMEOS

Cytochrome P-450 2E1 (CYP2E1)Cytochrome P-450 2E1 (CYP2E1) also the metabolism of other drugs also the metabolism of other drugs

such as acetaminophen, haloalkanes, such as acetaminophen, haloalkanes, and nitrosaminesand nitrosamines

Chronic ethanol consumption up-Chronic ethanol consumption up-regulates CYP2E1regulates CYP2E1

CYP2E1-mediated ethanol oxidation CYP2E1-mediated ethanol oxidation yields reactive oxygen intermediates yields reactive oxygen intermediates

These are capable of provoking These are capable of provoking hepatocellular damage hepatocellular damage

Acetaldehyde is a highly reactive Acetaldehyde is a highly reactive and potentially toxic compound. It and potentially toxic compound. It is metabolized by the ALDH . is metabolized by the ALDH .

Half of Chinese people are Half of Chinese people are deficient of this enzyme. deficient of this enzyme.

Gastric metabolismGastric metabolism

Gastric ADH is implicated in first-Gastric ADH is implicated in first-pass metabolism of ethanolpass metabolism of ethanol

This limit the ethanol delivery to This limit the ethanol delivery to the portal circulationthe portal circulation

This enzyme is lower in Women. This enzyme is lower in Women.

Oxidant StressOxidant Stress

DNA is sensitive to oxidant stress. DNA is sensitive to oxidant stress. Mitochondrial DNA is more Mitochondrial DNA is more susceptible than nuclear DNA to susceptible than nuclear DNA to oxidative damage because of reduced oxidative damage because of reduced protection by histone and nonhistone protection by histone and nonhistone proteins and because of a decreased proteins and because of a decreased capacity for repaircapacity for repair

This causes deletion and mutations in This causes deletion and mutations in DNADNA

Oxidant StressOxidant Stress

Chronic alcohol consumption indeed Chronic alcohol consumption indeed leads to depletion of several leads to depletion of several antioxidants in the liverantioxidants in the liver

Vitamin A depletion causes lysosomal Vitamin A depletion causes lysosomal damagedamage

Vitamin E depletion enhaces lipid Vitamin E depletion enhaces lipid peroxidationperoxidation

Glutation depletion impairs Glutation depletion impairs mitochondrial function.mitochondrial function.

Alcoholic liver disease Traditional spectrum of injury

* Fatty change* Alcoholic hepatitis* Alcoholic cirrhosis

Alcoholic hepatitis Hepatocyte necrosis Infiltrate of neutrophil polymorphs +/- fatty change +/- Mallory bodies +/- bile stasis

MECHANISMS OF TISSUE DAMAGEMECHANISMS OF TISSUE DAMAGE 2 ways of damage: 2 ways of damage: IndirectIndirect    

Ingestion of EthanolIngestion of Ethanol

Increases the release of endotoxins, from the Increases the release of endotoxins, from the gram negative bacteria in the natural flora of gram negative bacteria in the natural flora of

the intestinal tractthe intestinal tract

Kupffer cells release toxic mediators:Reactive Kupffer cells release toxic mediators:Reactive Oxygen Intermediates (ROIs) and Tumor Oxygen Intermediates (ROIs) and Tumor

Necrosis Factor (TNF) Necrosis Factor (TNF)

Synergize to cause oxidative damage to Synergize to cause oxidative damage to hepatocytes. hepatocytes.

the inflammatory response. the inflammatory response.

Direct DamageDirect Damage Alcohol metabolism Alcohol metabolism NADH NADH

consumption consumption Relative NADH Relative NADH deficiency. deficiency.

NADH deficiency NADH deficiency Slow / Slow / incomplete fat metabolism incomplete fat metabolism Accumulation of fat in liver.Accumulation of fat in liver.

Injury on structures of the liverInjury on structures of the liver

A. MitochondriaA. Mitochondria Know as “megamitochondria”Know as “megamitochondria” 25% of the patient with AAH.25% of the patient with AAH. Characterized by: Oxidative fosforilation and Characterized by: Oxidative fosforilation and

Krebs Cycle inhibited (40%)Krebs Cycle inhibited (40%) Reduction of the B-oxidation of the fatty acids Reduction of the B-oxidation of the fatty acids

leading to a “microvesicular esteatosis”leading to a “microvesicular esteatosis”

B. citoB. citokkininees.s. Elevated plasma levels of: Il,1,6,8, and TNF-Elevated plasma levels of: Il,1,6,8, and TNF-

alpha. (the last 2 related to worst prognosis) alpha. (the last 2 related to worst prognosis) (seen in 75% of the patients)(seen in 75% of the patients)

C. C. KKupferupfer Cells Cells Secretes high levels of: Secretes high levels of: TNF-alpha. This is a strong factor for TNF-alpha. This is a strong factor for

adherence and activation of the leucocytes.adherence and activation of the leucocytes. IL-8- main mediator for neutrophils IL-8- main mediator for neutrophils

atractionatraction

D. Alterations of the hepatocelular D. Alterations of the hepatocelular proteinprotein

Aldehide and ethanol change conformation of Aldehide and ethanol change conformation of the surface proteins. In such way the the surface proteins. In such way the immune system recognizes them as immune system recognizes them as “Neoantigens“Neoantigens””

E. FibrosisE. Fibrosis

IrreversibleIrreversibleOccurs at only 10 – 15% of the alcoholicsOccurs at only 10 – 15% of the alcoholics

  Due to activation of the Ito Cells (Fat store cells Due to activation of the Ito Cells (Fat store cells or perisinusoids cells) that are at Disse Spece.or perisinusoids cells) that are at Disse Spece.

Function: normally stores vitamyn A, But en Function: normally stores vitamyn A, But en presence of Ethanol presence of Ethanol miofibrobñastic cells miofibrobñastic cells and Hipersecretes collagenand Hipersecretes collagen fibrosis fibrosis

F. HipoxiaF. Hipoxia Hipermetabolic state induces aumented O2 Hipermetabolic state induces aumented O2

usage, leaving the pericentral zone lackting usage, leaving the pericentral zone lackting O2. This is because the flow is from the O2. This is because the flow is from the periportal zone to the pericentral zone.periportal zone to the pericentral zone.

Though it leads to damage of the pericentral Though it leads to damage of the pericentral zone.zone.

Other cause of perocentral hipoxia is that Other cause of perocentral hipoxia is that CYP2E1 is most abundant at the pericentral CYP2E1 is most abundant at the pericentral zone. (main site of metabolism)zone. (main site of metabolism)

Other factors contributing to the Other factors contributing to the lipid accumulation are:lipid accumulation are:

The oversupply of free fatty acids to the The oversupply of free fatty acids to the liver.liver.

Interference with the triglyceride cycle. Interference with the triglyceride cycle. The increased synthesis or esterification The increased synthesis or esterification

of fatty acidsof fatty acids Decreased fatty acid oxidation. Decreased fatty acid oxidation. Decreased apoprotein synthesis.Decreased apoprotein synthesis. Decreased synthesis or secretion of Decreased synthesis or secretion of

very low density lipoproteins. very low density lipoproteins.

This liver is slightly enlarged and has a This liver is slightly enlarged and has a pale yellow pale yellow appearanceappearance, seen, seen both on the both on the capsule and cut surfacecapsule and cut surface. This uniform . This uniform change ischange is consistent with consistent with fatty metamorphosis (fatty change).fatty metamorphosis (fatty change).

Massive hepatomegalyMassive hepatomegaly in an elderly alcoholic; in an elderly alcoholic; the liver weighed 2010 grams. Note the the liver weighed 2010 grams. Note the tinge of yellowtinge of yellow. .

MicroMicro ballooning degeneration of hepatocytes, ballooning degeneration of hepatocytes, inflammation with neutrophils near mallory inflammation with neutrophils near mallory

bodiesbodies Mallory bodies (abnormal perinuclear Mallory bodies (abnormal perinuclear

aggregations of cellular intermediate filament aggregations of cellular intermediate filament proteins “citokeratin”).proteins “citokeratin”).

..

Mallory's hyaline is seen here, but there are also neutrophils, necrosis of hepatocytes, collagen deposition, and fatty change. These findings are typical for acute alcoholic hepatitis. Such inflammation can occur in a person with a history of alcoholism who goes on a drinking "binge" and consumes large quantities of alcohol over a short time.

Hyaline Mallory´s Bodies In globoid hepatocyte. ThereIs an interstitial infiltrate ofNeutrophils.

Mallory´s bodies are positiveFor CK immunoperoxidase.

Clinical manifestationsClinical manifestations

VomitingVomiting DiarrheaDiarrhea Jaundice Jaundice Psychological disturbances.Psychological disturbances. Hepatic encephalopathyHepatic encephalopathy AscitesAscites Bleeding esophagealBleeding esophageal Varices (varicose veins in the esophagus), Varices (varicose veins in the esophagus),

abnormal blood clotting and coma. abnormal blood clotting and coma.

Main Reason for consulting:Main Reason for consulting:

Pathologically, it results in an enlarged Pathologically, it results in an enlarged liverliver

Painful to palpation. Painful to palpation. Enlargement is due to the accumulation Enlargement is due to the accumulation

of fat and the swelling of liver cells, and of fat and the swelling of liver cells, and to the accumulation of proteins that are to the accumulation of proteins that are normally secreted.normally secreted.

  

LabLab AST to ALT ratio = 2:1 AST to ALT ratio = 2:1 Alkaline Phosphatase elevated Alkaline Phosphatase elevated Gamma glutamyl transferase (GGT) Gamma glutamyl transferase (GGT) Hypoalbuminemia Hypoalbuminemia

Management Management Alcohol Cessation Alcohol Cessation Increased caloric and protein intake Increased caloric and protein intake Vitamin supplementation (Thiamine)Vitamin supplementation (Thiamine) CorticosteroidsCorticosteroids

PrognosisPrognosis Mortality 10-15% from acute Mortality 10-15% from acute

hepatitis hepatitis Cirrhosis develops in 50% of Cirrhosis develops in 50% of

alcoholic hepatitis alcoholic hepatitis Alcoholic liver disease Immediate causes of death:* massive gastrointestinal* variceal haemorrhage* hepatic coma* infection* hepatorenal syndrome

Alcoholic Liver Disease.

The End.