Cirrhosis and Associated Complications Luke Gessel October 2 nd, 2014

Cirrhosis and Cirrhosis and Associated Associated ComplicationsComplications

Luke GesselOctober 2nd, 2014

OutlineOutlineCirrhosis◦Development◦Diagnosis

Complications of Cirrhosis◦Portal Hypertension◦Ascites◦Spontaneous Bacterial Peritonitis

◦Hepatic Encephalopathy

CirrhosisCirrhosis

EpidemiologyEpidemiology30,000 deaths per year due to cirrhosis in US

10,000 deaths per year due to liver cancer largely due to cirrhotic livers in US

Hepatocellular carcinoma most rapidly increasing neoplasm in US and western Europe

CompensatedcirrhosisCompensatedcirrhosis

DecompensatedcirrhosisDecompensatedcirrhosis DeathDeath

Chronic liver diseaseChronic liver disease

Complications:

Variceal hemorrhage Ascites

Encephalopathy Jaundice

Complications:

Variceal hemorrhage Ascites

Encephalopathy Jaundice

Natural History of Chronic Natural History of Chronic Liver DiseaseLiver Disease

Viral Autoimmune Drug-induced Cholestatic

diseases Metabolic

diseases

CirrhosisCirrhosisNormalNormal

NodulesNodules

Irregular surfaceIrregular surface

Gross Liver PathologyGross Liver Pathology

CirrhosisCirrhosisNormalNormal

Regenerative Nodules surrounded by fibrous tissue

Regenerative Nodules surrounded by fibrous tissue

Liver HistologyLiver Histology

FibrosisFibrosis

Liver AnatomyLiver Anatomy

Liver AnatomyLiver Anatomy

Hepatic Lobule Sinusoid

The Road to Liver The Road to Liver InjuryInjuryHepatic fibrosis◦Accumulation of extracellular matrix, or scar, in response to acute or chronic liver injury

◦Fibrogenesis Wound healing response to injury, ultimately leading to cirrhosis

Cirrhosis◦End-stage consequence of fibrosis of hepatic parenchyma, resulting in nodule formation that may lead to altered hepatic function and blood flow

The Road to Liver The Road to Liver InjuryInjuryCirrhosis largely takes years to decades

Can be accelerated in some cases:◦Neonatal liver disease

Infants with biliary atresia may have severe fibrosis and marked parenchymal distortion at birth

◦HCV-infected patients after liver transplantation

◦HIV/HCV-coinfection◦Severe delta-hepatitis◦Some cases of drug-induced liver disease

PATHOGENESIS OF LIVER FIBROSISPATHOGENESIS OF LIVER FIBROSISPATHOGENESIS OF LIVER FIBROSISPATHOGENESIS OF LIVER FIBROSIS

HepatocytesHepatocytes

Space of DisseSpace of Disse

Sinusoidal endothelial cell


Hepatic stellate cellHepatic stellate cell

FenestraeFenestrae

Normal Hepatic SInusoidNormal Hepatic SInusoid

Retinoid dropletsRetinoid droplets

Hepatic Stellate CellsHepatic Stellate CellsThe key pathogenic feature underlying liver fibrosis and cirrhosis is hepatic stellate cell activation.

Hepatic stellate cells (also known as Ito cells or perisinusoidal cells) are located in the space of Disse

The space of Disse is located between hepatocytes and sinusoidal endothelial cells (that normally are fenestrated).

Normally, hepatic stellate cells are quiescent and serve as the main storage site for retinoids (vitamin A).

PATHOGENESIS OF LIVER FIBROSISPATHOGENESIS OF LIVER FIBROSISPATHOGENESIS OF LIVER FIBROSISPATHOGENESIS OF LIVER FIBROSIS

HepatocytesHepatocytes

Space of DisseSpace of Disse



Hepatic stellate cellHepatic stellate cell

FenestraeFenestrae

Normal Hepatic SInusoidNormal Hepatic SInusoid

Retinoid dropletsRetinoid droplets

PATHOGENESIS OF LIVER FIBROSISPATHOGENESIS OF LIVER FIBROSIS

Activation of Stellate cellsLoss of Vitamin AProliferationDevelopment of Rough ER and secretion of Extracellular MatrixMatrix Deposition in Space of DisseFuthermore Stellate Cells express smooth muscle proteins and become contractile—Hepatic Myofibroblasts

Activation of Stellate cellsLoss of Vitamin AProliferationDevelopment of Rough ER and secretion of Extracellular MatrixMatrix Deposition in Space of DisseFuthermore Stellate Cells express smooth muscle proteins and become contractile—Hepatic Myofibroblasts

PATHOGENESIS OF LIVER FIBROSIS

Alterations in Microvasculature in CirrhosisAlterations in Microvasculature in Cirrhosis

Activation of stellate cells Collagen deposition in space of

Disse Constriction of sinusoids Defenestration of sinusoids

Activation of stellate cells Collagen deposition in space of

Disse Constriction of sinusoids Defenestration of sinusoids

Disease-Specific Disease-Specific MechanismsMechanismsHepatitis C Virus◦ Stellate cells directly infectable by virus

Express HCV receptors Adenovirus transduction of non-structural and core proteins induces stellate cell proliferation and release of inflammatory signals

◦ Lymphocyte recruitment◦ HCV proteins interact directly with sinusoidal endothelium

NASH◦ Leptin, adipogenic hormone proportionate to adipose mass in circulating blood activates stellate cells

◦ Downregulation of adiponectin, counterregulatory hormone amplifies fibrogenic activity of leptin Mice lacking adiponectin have enhanced fibrosis following toxic liver injury

Reversibility of Reversibility of Fibrosis/CirrhosisFibrosis/CirrhosisElimination of underlying cause critical

Other factors:◦Period of established cirrhosis

Longer periods of crosslinked collagen, less sensitive to degradative enzymes?

◦Total content of collagen and other scar molecules Large mass of scar may be inaccessible to degradative enzymes

◦Reduced expression of enzymes that degrade matrix, and prevention of apoptosis of activated stellate cells

Liver insufficiencyLiver insufficiency

Variceal hemorrhageVariceal hemorrhage

Complications of Cirrhosis Result from Portal Hypertension or Liver InsufficiencyComplications of Cirrhosis Result from Portal Hypertension or Liver Insufficiency

CirrhosisCirrhosis AscitesAscites

EncephalopathyEncephalopathy

JaundiceJaundice

Portal hypertensionPortal hypertension

Spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis

Hepatorenal syndromeHepatorenal syndrome

COMPLICATIONS OF CIRRHOSIS

Development of Complications in Compensated Cirrhosis Development of Complications in Compensated Cirrhosis

AscitesAscitesJaundiceJaundiceEncephalopathyEncephalopathyGI hemorrhageGI hemorrhage

Probability of developing event

Probability of developing event

00

2020

6060

8080

100100

00 6060

4040

2020 4040 8080 100100 120120 140140 160160

MonthsMonthsGines et. al., Hepatology 1987; 7:122Gines et. al., Hepatology 1987; 7:122

NATURAL HISTORY OF CIRRHOSIS

60604040 8080 100100 120120 140140 16016000

4040

6060

8080

2020

202000

100100

MonthsMonths

Probability of survivalProbability of survival

All patients with cirrhosisAll patients with cirrhosis

Decompensated cirrhosisDecompensated cirrhosis

180180

Decompensation Shortens SurvivalDecompensation Shortens Survival

Gines et. al., Hepatology 1987;7:122Gines et. al., Hepatology 1987;7:122

Median survival~ 9 yearsMedian survival~ 9 years

Median survival~ 1.6 yearsMedian survival~ 1.6 years

SURVIVAL TIMES IN CIRRHOSIS

Cirrhosis is a histological diagnosis

However, in patients with chronic liver disease the presence of various clinical features suggests cirrhosis

The presence of these clinical features can be followed by non-invasive testing, prior to liver biopsy

Cirrhosis - DiagnosisCirrhosis - Diagnosis

Any patient with chronic liver disease Chronic abnormal aminotransferases and/or

alkaline phosphatase

Physical exam findings Stigmata of chronic liver disease (muscle

wasting, vascular spiders, palmar erythema) Palpable left lobe of the liver Small liver span Splenomegaly Signs of decompensation (jaundice, ascites,

asterixis)

In Whom Should We Suspect In Whom Should We Suspect Cirrhosis?Cirrhosis?

Laboratory Liver insufficiency

Low albumin (< 3.8 g/dL) Prolonged prothrombin time (INR > 1.3) High bilirubin (> 1.5 mg/dL)

Portal hypertension Low platelet count (< 175 x1000/l)

AST / ALT ratio > 1


Imaging studies Liver-spleen scan

Small liver, irregular uptake Splenomegaly Colloid shift to bone marrow

CAT scan / Ultrasound Nodular liver Splenomegaly Venous collaterals


Small liver,irregular uptakeSmall liver,irregular uptake

SplenomegalySplenomegaly

Colloid shift to bone marrow and ribsColloid shift to bone marrow and ribs

Normal Cirrhosis

Liver-Spleen ScanLiver-Spleen Scan

DIAGNOSIS OF CIRRHOSIS – LIVER-SPLEEN SCAN

CAT Scan in CirrhosisCAT Scan in Cirrhosis

Liver with an irregular surfaceLiver with an irregular surface SplenomegalySplenomegalyCollateralsCollaterals

DIAGNOSIS OF CIRRHOSIS – CAT SCAN

Liver biopsy is not necessary in the presence of any of the following:◦Decompensated cirrhosis (variceal

hemorrhage, ascites, encephalopathy)

◦Liver-spleen and/or CAT scan diagnostic of cirrhosis

◦Liver biopsy is not necessary for pre-transplant evaluation

Confirmatory Liver Biopsy Is Not Confirmatory Liver Biopsy Is Not Always Necessary in CirrhosisAlways Necessary in Cirrhosis

• A 55-year-old asymptomatic Caucasian

man is referred to hepatology clinic for

evaluation of chronic elevation of

aminotransferases.

• He has no significant medical problems,

takes no medications and denies a family

history of liver disease.

• A 55-year-old asymptomatic Caucasian

man is referred to hepatology clinic for

evaluation of chronic elevation of

aminotransferases.

• He has no significant medical problems,

takes no medications and denies a family

history of liver disease.

Case KL

Case PresentationCase Presentation

Case KL – CASE PRESENTATION

Physical ExamPhysical Exam

• He is generally healthy appearing.

• There are no stigmata of chronic liver

disease including:

• No jaundice

• No vascular spiders or palmar

erythema

• A non-palpable liver and spleen.

• He is generally healthy appearing.

• There are no stigmata of chronic liver

disease including:

• No jaundice

• No vascular spiders or palmar

erythema

• A non-palpable liver and spleen.

Case KL

Case KL – PHYSICAL EXAM

Case KL

Laboratory ResultsLaboratory Results

Bilirubin 1.2 mg/dL

AST 80 U/L

ALT 94 U/L

Albumin 4.0 g/dL

PT 12 sec

Bilirubin 1.2 mg/dL

AST 80 U/L

ALT 94 U/L

Albumin 4.0 g/dL

PT 12 sec

WBC

4.0 x1000/uL

Hgb

17 g/dL

Platelets

175 x1000/uL

Anti-HCV

positive

HBsAg

negative

WBC

4.0 x1000/uL

Hgb

17 g/dL

Platelets

175 x1000/uL

Anti-HCV

positive

HBsAg

negative

Case KL – LAB RESULTS

Diagnostic StudiesDiagnostic Studies

Abdominal ultrasound:

mildly increased hepatic echogenicity

mild splenomegaly

Liver-spleen scan increased uptake in spleen no colloid shift to bone marrow

Abdominal ultrasound:

mildly increased hepatic echogenicity

mild splenomegaly

Liver-spleen scan increased uptake in spleen no colloid shift to bone marrow

Case KL

Case KL – DIAGNOSTIC STUDIES

Does this patient have cirrhosis?

Maybe

Does this patient need a liver biopsy?

Liver biopsy is necessary to confirm/rule out cirrhosis


Maybe


Liver biopsy is necessary to confirm/rule out cirrhosis

Case KL

Case KL – QUESTIONCase KL – QUESTION

Case DW

A 55 year-old, previously healthy man, complains of fatigue for several months.

He denies excessive alcohol use, but admits to using IV drugs when he was a teenager.

A 55 year-old, previously healthy man, complains of fatigue for several months.

He denies excessive alcohol use, but admits to using IV drugs when he was a teenager.

Case DW – CASE PRESENTATIONCase DW – CASE PRESENTATION

Physical ExamPhysical Exam

Exam shows vascular spiders on his back.

Abdominal exam reveals a firm liver edge, and an easily palpated left lobe, 2 cm below the xyphoid.

The spleen tip is palpable.

There is no shifting dullness on abdominal percussion.

Exam shows vascular spiders on his back.

Abdominal exam reveals a firm liver edge, and an easily palpated left lobe, 2 cm below the xyphoid.

The spleen tip is palpable.

There is no shifting dullness on abdominal percussion.

Case DW

Case DW – PHYSICAL EXAMCase DW – PHYSICAL EXAM

Case DW

Laboratory ResultsLaboratory Results

Bilirubin 1.1 mg/dL

AST 110 U/L

ALT 92 U/L

Albumin 3.5 g/dL

PT 12.5 sec

Bilirubin 1.1 mg/dL

AST 110 U/L

ALT 92 U/L

Albumin 3.5 g/dL

PT 12.5 sec

WBC 4.0 x1000/uL

Hgb 12 g/dL

Platelets 95 x1000/uL

Anti-HCV positive

HBsAg negative

WBC 4.0 x1000/uL

Hgb 12 g/dL

Platelets 95 x1000/uL

Anti-HCV positive

HBsAg negative

Case DW – LAB RESULTSCase DW – LAB RESULTS

Diagnostic StudiesDiagnostic Studies

Abdominal ultrasound: Echogenic, heterogeneous liver

parenchyma Enlarged caudate lobe Enlarged spleen (15.5 cm)

Liver-spleen scan: Colloid shift to bone marrow Increased uptake by spleen

Abdominal ultrasound: Echogenic, heterogeneous liver

parenchyma Enlarged caudate lobe Enlarged spleen (15.5 cm)

Liver-spleen scan: Colloid shift to bone marrow Increased uptake by spleen

Case DW

Case DW – DIAGNOSTIC STUDIESCase DW – DIAGNOSTIC STUDIES


Yes


Liver biopsy is NOT necessary to establish the diagnosis of cirrhosis


Yes


Liver biopsy is NOT necessary to establish the diagnosis of cirrhosis

Case DW

Case DW – QUESTIONS

Portal HypertensionPortal Hypertension

Hepatic Blood FlowHepatic Blood Flow

Portal Hypertension

Cirrhotic Liver

Portal Blood Flow

Systemic Blood Flow

Portal HypertensionPortal HypertensionDefined by pathological increase in portal venous pressure

Complications arise when portal pressure gradient exceed 10-12 mm Hg (normal <6 mm Hg)

Cirrhosis is the most common cause of portal hypertension

The site of increased resistance in cirrhosis is sinusoidal

Cirrhosis is the most common cause of portal hypertension

Portal HypertensionPortal Hypertension

Architectural disturbances(fibrosis, scarring, vascular thrombosis, etc.)

Functional alterations(contraction of vascular smooth muscle and stellate cells)

Cirrhotic liver

Increased hepatic resistance

Portal hypertension

Splanchnic vasodilatation

Collaterals and PSS

Increased portalblood inflow

Effective hypovolemia

Activation of endogenousvasoactive systems

Na retentionHypervolemia

Increased cardiac index

Increased Intrahepatic Increased Intrahepatic ResistanceResistance1. Architectural distortion of the

liver◦ Fibrous tissue and regenerative nodules◦ Thrombosis of portal and hepatic veins

2. Dynamic reversible contractile elements

Normal Liver

Hepatic vein

Hepatic vein

SinusoidSinusoid

Portal vein

Portal vein

LiverLiver

Splenic veinSplenic vein

Coronary veinCoronary vein

Portal systemic collaterals

Portal systemic collaterals

Distorted sinusoidal

architectureleads to

increased resistance

Distorted sinusoidal

architectureleads to

increased resistance

Portal vein

Portal vein

Cirrhotic Liver

SplenomegalySplenomegaly

Increased Intrahepatic Increased Intrahepatic ResistanceResistance1. Architectural distortion of the liver

2. Dynamic reversible contractile elements◦ 40% of increased intrahepatic vascular

resistance◦ Involves:

Vascular smooth muscle cells Activated hepatic stellate cells that contract around

sinusoids reducing caliber Hepatic myofibroblasts that compress cirrhotic nodules Vasoactive mediators that modulate intrahepatic

resistance

Increased Intrahepatic Increased Intrahepatic ResistanceResistance

◦ Increased production of vasoconstrictors with exaggerated response by hepatic vascular bed

◦ Insufficient release of vasodilators and insufficient response by hepatic vascular bed

Vasoconstrictors

EndothelinAngiotensin

NorepinephrineVasopressinLeukotrienesThromboxaneOthers?

Vasodilators

Nitric OxideCarbon Monoxide

Others?

Variceal HemorrhageVariceal Hemorrhage

Prevalence of Esophageal Varices in Cirrhosis

Prevalence of Esophageal Varices in Cirrhosis

%%

100100

6060

4040

2020

00OverallOverall Child AChild A Child BChild B

8080

Child CChild C

Pagliaro et al., In: Portal Hypertension: Pathophysiology and Management, 1994: 72Pagliaro et al., In: Portal Hypertension: Pathophysiology and Management, 1994: 72

PREVALENCE OF ESOPHAGEAL VARICES IN CIRRHOSIS

Lowest Rebleeding Rates are Obtained in HVPG Responders and With Ligation + -

Blockers

Lowest Rebleeding Rates are Obtained in HVPG Responders and With Ligation + -

Blockers

(19 trials)(19 trials)(26 trials)(26 trials) (54 trials)(54 trials)

%%RebleedingRebleeding

8080

6060

4040

2020

00UntreatedUntreated -

blockers-

blockersSclero-therapySclero-therapy

(18 trials)(18 trials)

LigationLigation


HVPG-Responders

*

HVPG-Responders

*(6 trials)(6 trials)

-blockers+ ISMN

-blockers+ ISMN


Ligation +

-blockers

Ligation +

-blockers

Bosch and García-Pagán, Lancet 2003; 361:952Bosch and García-Pagán, Lancet 2003; 361:952 * HVPG <12 mmHg

or >20% from baseline

* HVPG <12 mmHg or >20% from

baseline

LOWEST REBLEEDING RATES ARE OBTAINED IN HVPG RESPONDERS AND IN PATIENTS TREATED WITH VARICEAL BAND LIGATION + BETA-BLOCKERS

AscitesAscites

AscitesAscitesMost common cause of decompensation in patients with cirrhosis

Occurs at rate of 7-10% per year

5% of patients with ascites can develop right sided pleural effusions—hepatic hydrothorax◦Develops through diaphragmatic defects

AscitesAscitesDiagnosis◦Physical Exam◦Ultrasonography◦Diagnostic Paracentesis

Peritoneal pathology- Malignancy- Tuberculosis

Peritoneal pathology- Malignancy- Tuberculosis

Sinusoidal hypertension-Cirrhosis-Late Budd-Chiari

Sinusoidal hypertension-Cirrhosis-Late Budd-Chiari

Source of ascites

Source of ascites

Hepatic sinusoidsSAAG > 1.1

Hepatic sinusoidsSAAG > 1.1

PeritoneumSAAG < 1.1 PeritoneumSAAG < 1.1

“Capillarized” sinusoidAscites protein < 2.5

“Capillarized” sinusoidAscites protein < 2.5

Peritoneal lymphAscites protein > 2.5

Peritoneal lymphAscites protein > 2.5

Post-sinusoidal hypertension

- Cardiac ascites- Early Budd-Chiari - Veno-occlusive disease

Post-sinusoidal hypertension

- Cardiac ascites- Early Budd-Chiari - Veno-occlusive disease

Normal “leaky” sinusoidAscites protein > 2.5

Normal “leaky” sinusoidAscites protein > 2.5

Ascites Can Be Characterized by Serum-Ascites Albumin Gradient (SAAG) and Ascites Protein

ASCITES CAN BE CHARACTERIZED BY SERUM-ASCITES ALBUMIN GRADIENT (SAAG) AND ASCITES PROTEIN

Ascites: ManagementAscites: ManagementSodium restriction—2 grams dailyOral diuretics◦Spironolactone (more effective than loop diuretics) Started at dose of 50-100 mg/daily Adjust 13-4 days to maximal effective dose of 400 mg/day

◦Furosemide can be added as well 5:2 ratio

Fluid restriction not required unless there is hyponatremia—Na<130

Ascites: ManagementAscites: ManagementWeight loss goal◦1 kg in first week◦2 kg/wk subsequently

Excessive loss of weight (>1 lb./day)◦Can lead to intravascular depletion◦Can lead to Pre-Renal Kidney Injury

Avoid ASA and NSAIDs◦Can reduce diuretic induced natriuresis

◦May precipitate Renal Failure

Ascites: ManagementAscites: ManagementLarge Volume Paracentesis (LVP)◦For patients with tense ascites◦Albumin is to be given at rate of 6-8 gram/liter, particularly with removal of >5 liters

10% of patients with cirrhosis and ascites may become diuretic resistant◦Recurrent LVP plus albumin ◦TIPS

Encephalopathy

Spontaneous Bacterial Spontaneous Bacterial PeritonitisPeritonitis

Spontaneous Bacterial Spontaneous Bacterial PeritonitisPeritonitisThe most life-threatening complication of ascites

~1/3 of hospitalized patients with cirrhosis are diagnosed as having a bacterial infection—most common is SBP

All Patients with cirrhosis and ascites who are hospitalized emergently should undergo a diagnostic paracentesis

Diagnosis is established with ascitic fluid neutrophil count greater than 250/mm3

Bacteria are isolated in only 40-50% of casees

Spontaneous Bacterial Spontaneous Bacterial PeritonitisPeritonitisOnce diagnosis established◦Empiric antibiotic therapy with IV 3rd generation cephalosporin

◦Success rates for 3rd generation cephalosporins have been as low as 40% in nosocomial SBP

◦In this case use Pip/Tazo or a Carbapenem

Avoid Aminoglycosides—High Incidence of Renal Toxicity in Patients with Cirrhosis

For prevention of progressive renal dysfunction administer albumin◦1.5 g/kg day 1 and 1g/kg on day 3

Spontaneous Bacterial Spontaneous Bacterial PeritonitisPeritonitis~70% Risk of RecurrenceProphylactic Antibiotic◦Recommended Antibiotic is Norfloxacin 400 mg daily

Per UpToDate:◦In settings where norfloxacin is unavailable Ciprofloxacin 500 mg daily Trimethoprim-Sulfamethoxazole one double strength tablet daily

All SBPsAll SBPs SBP caused by gram-negative bacteria

SBP caused by gram-negative bacteria

Probability of SBP

recurrence

Probability of SBP

recurrence

MonthsMonths

p=0.0063p=0.0063

PlaceboPlacebo

NorfloxacinNorfloxacin

PlaceboPlacebo

p=0.0013p=0.0013

NorfloxacinNorfloxacin

00

1.01.0

.8.8

.4.4

.2.2

.6.6

44 88 1212 2020

00

1616 00 44 88 1212 20201616

MonthsMonths

Norfloxacin Reduces Recurrence of Spontaneous Bacterial Peritonitis

Norfloxacin Reduces Recurrence of Spontaneous Bacterial Peritonitis

Gines et al., Hepatology 1990; 12:716Gines et al., Hepatology 1990; 12:716

NORFLOXACIN REDUCES RECURRENCE OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Hepatic Hepatic EncephalopathyEncephalopathy

Hepatic EncephalopathyHepatic EncephalopathyReversible syndrome caused by astrocyte swelling

Ammonia and other toxins play key role in pathogenesis

Ammonia accumulates due to shunting of blood through portosystemic collaterals and decreased liver metabolism

Hepatic EncephalopathyHepatic Encephalopathy HE associated with cirrhosis is of gradual onset and rarely fatal

Distinguished from encephalopathy from acute liver failure and portosystemic bypass in absence of cirrhosis

Stage 1: Forgetfulness and Inversion of Sleep/Wake Pattern

Stage 2: Confusion, Bizarre behavior and Disorientation

Stage 3: Lethargy and Profound Disorientation

Stage 4: Coma

Hepatic EncephalopathyHepatic EncephalopathyOn Exam◦Asterixis◦Fetor Hepaticus (sweet smelling odor to breath)

Diagnosis◦Made Clinically◦Serum Ammonia levels are unreliable/correlate poorly with stage

◦Number connection test and EEG are used in research but not routinely in clinical setting

Ong et al., Am J Med 2003; 114:188Ong et al., Am J Med 2003; 114:188

Poor Correlation of Ammonia Levels With Presence or Severity of

Encephalopathy

Venous total

ammoniamol/L

Venous total

ammoniamol/L

00

400400

350350

300300

250250

200200

150150

100100

5050

Grade 0Grade 0 Grade 1Grade 1 Grade 2Grade 2 Grade 3Grade 3 Grade 4Grade 4

Severity of Hepatic EncephalopathySeverity of Hepatic Encephalopathy

POOR CORRELATION OF AMMONIA LEVELS WITH PRESENCE OR SEVERITY OF HEPATIC ENCEPHALOPATHY

Hepatic EncephalopathyHepatic EncephalopathyMainstay of therapy is identification and treatment of precipitating factors◦Dehydration◦Infections◦Overdiuresis◦GI bleeding◦High Oral Protein Load◦Constipation◦Use of Narcotics◦TIPS

Hepatic EncephalopathyHepatic EncephalopathyTreatment:◦Lactulose and Rifaxamin◦Consider change in dietary protein from animal to vegetable source

◦Strict protein restriction is not necessary and is discouraged long-term

Hepatocellular Hepatocellular CarcinomaCarcinoma

Hepatocellular Hepatocellular CarcinomaCarcinomaHCC can occur in both compensated and decompensated cirrhotics and can be the event that leads to decompensation

5th most common cause of cancer worldwide

3rd most common cause of cancer related mortality worldwide

In the United States there ahs been a twofold increase in assess of HCC over the past two decades◦ Relates to the increase in prevalence of chronic hepatitis C

Hepatocellular Hepatocellular CarcinomaCarcinomaEntertains in patients with compensated cirrhosis who:◦Suddenly decompensate◦Develop Portal Vein Thrombosis

Diagnosis◦Dynamic Radiologic Imaging (CT or MRI with contrast)

◦Elevated AFP may support diagnosis◦In some instances liver biopsy may be needed to conform

Cabibbo G et al. (2009) Multimodal approaches to the treatment of hepatocellular carcinomaNat Clin Pract Gastroenterol Hepatol doi:10.1038/ncpgasthep1357

Figure 1 Algorithm for staging and treating patients diagnosed as having hepatocellular carcinoma

ConclusionConclusion Cirrhosis is the result of a common pathway from numerous causes of liver inflammation

Decompensated cirrhosis carries a significant mortality and complications should be closely monitored in the inpatient and outpatient setting

Ascites should always be sampled with emergent hospitalization

Hepatic Encephalopathy severity does not directly correlate with ammonia level and should prompt evaluation of inciting cause

Patients with HCC should undergo timely evaluation and triage into the appropriate management arm so as to maximize survival potential

ReferencesReferences Bosch J, D’Amico G, Garcia-Pagan JC. Portal Hypertension and

Nonsurgical Management. In: Schiff ER, Sorrell MF, Maddrey WC, editors. Tenth edition. Schiff’s Diseases of the Liver, Vol. 1. Philadelphia: Lippincott Williams & Wilkins; p. 419-483

Friedman SL. Hepatic fibrosis. In: Schiff ER, Sorrell MF, Maddrey WC, editors. Tenth edition. Schiff’s Diseases of the Liver, Vol. 1. Philadelphia: Lippincott Williams & Wilkins; p. 395-418

Friedman SL. Pathogenesis of hepatic fibrosis. Up-to-Date. May 2010.

Rockey DC, Friedman SL(2006). Hepatic fibrosis and cirrhosis. In: Boyer TD, Wright TL, Manns MP, editors. 5th edition. Zakim and Boyer’s hepatology, vol.1. New York: Elsevier;. p. 87–109.

Rodriguez-Vilarrupla et al (2007). Current concepts on the pathophysiology of portal hypertension. Annals of Hepatology; 6(1): Jan-March: 28-36.

Vorobioff J; Bredfeldt JE; Groszmann RJ. Increased blood flow through the portal system in cirrhotic rats. Gastroenterology 1984 Nov;87(5):1120-6.

Documents

Cirrhosis and Associated Complications Luke Gessel October 2 nd, 2014