Treatment of chronic liver disease

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Treatment of chronic liver disease
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Treatment

• Cause ( Etiology)
• Complication

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Etiology

• Infection
• Alcohol
• Autoimmune
• Cholestatic
• Infiltrative
• Metabolic
• Vascular
• Drugs

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Complications

• Ascites
• GI bleed
• SBP
• Edema
• Hepatoma
• Encephalopathy
• Hepatorenal syndrome

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Viral hepatitis

• Hepatitis B
• Nucleoside analogues
• Lamivudine
• Adefovir
• Telbivudine
• Entecavir
• Tenofovir
• Interferon

• Hepatitis C
• Alfa interferon
• Pegylated interferon
• Ribavirin

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• Autoimmune hepatitis
• Prednisone
• Azathioprine
• New drugs
• Budesonide
• Cyclosporine
• Tacrolimus
• Rapamycin
• Mycophenolate mofetil

• NAFLD
• Weight loss
• Underlying disease
• Silymarin/metformin
• Bariatric surgery

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• Alcohol
• Abstinence
• Fatty liver
• Liver transplant

• Wilson disease
• Penicillamine
• Trientine
• Zinc acetate
• Tetrathiomolybdate
• Family screening

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• PBC
• Ursodeoxycholic acid
• Symptomatic
• Cholestyramine/Rifampicin
• Calcium/vitamin D
• PSC
• ERCP
• Liver transplant

• Hemochromatosis
• Phlebotomy
• Family screening
• Alpa1 antitrypsin deficiency
• 4-phenylbutyric acid
• Liver transplant
• Genetic counseling

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COMPLICATIONS OF CIRRHOSIS
Complications of Cirrhosis Result from Portal
Hypertension or Liver Insufficiency
Variceal hemorrhage
Portal hypertension
Spontaneous bacterial peritonitis
Ascites
Cirrhosis
Hepatorenal syndrome
Encephalopathy
Liver insufficiency
Jaundice
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MECHANISM OF ACTION OF ENDOSCOPIC THERAPY IN
PORTAL HYPERTENSION
Cirrhosis
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PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE
Varix with red signs
Variceal hemorrhage

• Predictors of hemorrhage
• Variceal size
• Red signs
• Child B/C

NIEC. N Engl J Med 1988 319983
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MANAGEMENT OF PATIENTS WITH VARICES WHO HAVE
NEVER BLED
Treatment of Varices / Variceal Hemorrhage
No varices
Varices No hemorrhage
Variceal hemorrhage
Recurrent hemorrhage
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MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES
WITHOUT PRIOR HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage
No varices
Small varices No hemorrhage
Medium/ large varices No hemorrhage
Variceal hemorrhage
Recurrent hemorrhage
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CONTROL OF ACUTE VARICEAL HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage
No varices
Small varices No hemorrhage
Medium/ large varices No hemorrhage
Variceal hemorrhage
Recurrent hemorrhage
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TREATMENT OF ACUTE VARICEAL HEMORRHAGE
Treatment of Acute Variceal Hemorrhage

• General Management
• IV access and fluid resuscitation
• Do not over transfuse (hemoglobin 8 g/dL)
• Antibiotic prophylaxis
• Specific therapy
• Pharmacological therapy Terlipressin,
  Somatostatin and analogues, Vasopressin
  Nitroglycerin
• Endoscopic therapy Ligation, Sclerotherapy
• Shunt therapy TIPS, surgical shunt

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ENDOSCOPIC VARICEAL BAND LIGATION
Endoscopic Variceal Band Ligation

• Bleeding controlled in 90
• Rebleeding rate 30
• Compared with Sclerotherapy
• Less rebleeding
• Lower mortality
• Fewer complications
• Fewer treatment sessions

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THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT
Transjugular Intrahepatic Porto systemic Shunt
Hepatic vein
TIPS
Splenic vein
Portal vein
Superior mesenteric vein
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ENDOSCOPIC IMAGES OF GASTRIC VARICES
Gastric Varices
Pretreatment cyanoacrylate
Post-treatment cyanoacrylate
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ENDOSCOPIC IMAGES OF MILD AND SEVERE PORTAL
HYPERTENSIVE GASTROPATHY
Mild and Severe Portal Hypertensive Gastropathy
Mild
Severe
Mosaic pattern
Mosaic pattern red spots
Carpinelli et al. Ital J Gastroenterol Hepatol
1997 29533
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ASCITES AND HEPATORENAL SYNDROME
Ascites and Hepatorenal Syndrome
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NATURAL HISTORY OF ASCITES
Natural History of Ascites
HVPG lt10 mmHg Mild Vasodilation
Portal Hypertension No Ascites
Uncomplicated Ascites
HVPG gt10 mmHg Moderate Vasodilation
Refractory Ascites
HVPG gt10 mmHg Severe Vasodilation
HVPG gt10 mmHg Extreme Vasodilation
Hepatorenal Syndrome
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DIAGNOSTIC PARACENTESIS
Diagnostic Paracentesis
Indications

• New-onset ascites
• Admission to hospital
• Symptoms/signs of SBP
• Renal dysfunction
• Unexplained encephalopathy

Contraindications

• None

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MANAGEMENT OF UNCOMPLICATED ASCITES
Management of Uncomplicated Ascites
Definition Ascites responsive to diuretics in
the absence of infection and renal dysfunction

• Sodium restriction
• Effective in 10-20 of cases
• Predictors of response mild or moderate ascites,
  Urine Na excretion gt 50 mEq/day
• Diuretics
• Should be spironolactone-based
• A progressive schedule (spironolactone ?
  furosemide) requires fewer dose adjustments than
  a combined therapy (spironolactone furosemide)

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MANAGEMENT OF UNCOMPLICATED ASCITES SODIUM
RESTRICTION
Management of Uncomplicated Ascites

• Sodium Restriction
• 2 g (or 5.2 g of dietary salt) a day
• Fluid restriction is not necessary unless there
  is hyponatremia (lt125 mmol/L)
• Goal negative sodium balance

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MANAGEMENT OF UNCOMPLICATED ASCITES DIURETIC
THERAPY
Management of Uncomplicated Ascites

• Diuretic Therapy
• Dosage
• Spironolactone 100-400 mg/day
• Furosemide (40-160 mg/d) for inadequate weight
  loss or if hyperkalemia develops
• Increase diuretics if weight loss lt1 kg in the
  first week and lt 2 kg/week thereafter
• Decrease diuretics if weight loss gt0.5 kg/day in
  patients without edema and gt1 kg/day in those
  with edema
• Side effects
• Renal dysfunction, hyponatremia, hyperkalemia,
  encephalopathy, gynecomastia

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DEFINITION AND TYPES OF REFRACTORY ASCITES
Definition and Types of Refractory Ascites
Occurs in 10 of cirrhotic patients

• Diuretic-intractable ascites
• Therapeutic doses of diuretics cannot be
  achieved because of diuretic-induced
  complications
• Diuretic-resistant ascites
• No response to maximal diuretic therapy (400 mg
  spironolactone 160 mg furosemide/day)

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SPONTANEOUS BACTERIAL PERITONITIS (SBP)
COMPLICATES ASCITES AND CAN LEAD TO RENAL
DYSFUNCTION
Spontaneous Bacterial Peritonitis (SBP)
Complicates Ascites and Can Lead to Renal
Dysfunction
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EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL
PERITONITIS (SBP)
Early Diagnosis of SBP

• Diagnostic paracentesis
• If symptoms / signs of SBP occur
• Unexplained encephalopathy and / or renal
  dysfunction
• At any hospital admission
• Diagnosis based on ascitic fluid
• PMN count gt250/mm3

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MICROORGANISMS ISOLATED IN SPONTANEOUS BACTERIAL
PERITONITIS (SBP)
Microorganisms Isolated in Spontaneous Bacterial
Peritonitis
Microorganism of Cases Gram-negative
bacilli 72 Gram-positive cocci 29
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TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS
(SBP)
Treatment of Spontaneous Bacterial Peritonitis

• Recommended antibiotics for initial empiric
  therapy
• i.v. cefotaxime,
• i.v. amoxicillin-clavulanic acid
• avoid aminoglycosides
• Minimum duration 5 days

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INDICATIONS FOR PROPHYLACTIC ANTIBIOTICS TO
PREVENT SPONTANEOUS BACTERIAL PERITONITIS (SBP)
Indications for Prophylactic Antibiotics to
Prevent Spontaneous Bacterial Peritonitis

• Patients who have recovered from SBP (long-term)
• Norfloxacin 400 mg p.o. daily, indefinitely
• Weekly Quinolones

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CHARACTERISTICS OF HEPATORENAL SYNDROME (HRS)
Characteristics of Hepatorenal Syndrome

• Renal failure in patients with cirrhosis,
  advanced liver failure and severe sinusoidal
  portal hypertension
• Absence of significant histological changes in
  the kidney (functional renal failure)
• Marked arteriolar vasodilation in the extra-renal
  circulation
• Marked renal vasoconstriction leading to reduced
  glomerular filtration rate

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TYPES OF HEPATORENAL SYNDROME (HRS)
Two Types of Hepatorenal Syndrome

• Type 1
• Rapidly progressive renal failure (2 weeks)
• Doubling of creatinine to gt2.5
• Type 2
• More slowly progressive
• Creatinine gt1.5 mg/dL or Creatinine Clearance lt
  40 ml/min
• Associated with refractory ascites

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MANAGEMENT OF HEPATORENAL SYNDROME
Management of Hepatorenal Syndrome

• Proven efficacy
• Liver transplantation
• Under investigation
• Vasoconstrictor albumin
• Transjugular intrahepatic portosystemic shunt
  (TIPS)
• Vasoconstrictor TIPS
• Extracorporeal albumin dialysis (ECAD)
• Ineffective
• Renal vasodilators (prostaglandin, dopamine)
• Hemodialysis

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Hepatic Encephalopathy
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PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY
Pathophysiology of Hepatic Encephalopathy
Ammonia Upregulation of astrocytic peripheral
benzodiazepine receptors (PBR) Neurosteroid
production Modulation of GABA receptor
Hepatic encephalopathy
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HEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSIS
Hepatic Encephalopathy is a Clinical Diagnosis

• Clinical findings and history important
• Ammonia levels are unreliable
• Ammonia has poor correlation with diagnosis
• Measurement of ammonia not necessary
• Number connection test
• Slow dominant rhythm on EEG

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STAGES OF HEPATIC ENCEPHALOPATHY
Stages of Hepatic Encephalopathy
Confusion
Drowsiness
Somnolence
Coma
1
2
3
4
Stage
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TREATMENT OF HEPATIC ENCEPHALOPATHY
Treatment of Hepatic Encephalopathy

• Identify and treat precipitating factor
• Infection
• GI hemorrhage
• Prerenal azotemia
• Sedatives
• Constipation
• Lactulose (adjust to 2-3 bowel movements/day)
• Protein restriction, short-term (if at all)

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Liver transplant

• All patients with end stage liver disease should
  be assessed for liver transplant when ever is
  proven to significantly prolong survival and
  improve quality of life in a coast effective
  manner over natural history of the liver disease
  and other medical and non transplant surgical
  intervention.