IM II: ACUTE HEPATITIS, CHRONIC HEPATITIS, ALCOHOLIC LIVER DISEASE AND CIRRHOSIS

INTERNAL MEDICINE II
ACUTE HEPATITIS, CHRONIC HEPATITIS,
ALCOHOLIC LIVER DISEASE, & CIRRHOSIS
Gerard Perlas, MD, FPCP, FPSG, FPSDE

ACUTE HEPATITIS Admit the patient if with nausea/vomiting or is anorexic but if

not, can treat the patient as outpatient
The hepatotrophic virus that may cause acute viral hepatitis
Admit patients with prolonged prothrombin time
would include the following:
Prothrombin time: marker o hepatic synthetic activity, there is
o A, B common in the Phlippines
marked derangement of liver function
o C more in Europe, US
o D
o E sometimes
o G
PATHOLOGY OF ACUTE VIRAL HEPATITIS
Panlobular infiltration with mononuclear cells
Hepatocytes necrosis, bridging hepatic necrosis, also termed
subacute or confluent necrosis
Hyperplasia of the Kupffer cells and variable degrees of cholestasis
Hepatic cells regeneration
A B C D E G
Fever Often Rare Rare Rare Often Rare
Carrier None Yes Yes Yes None Yes
state
potential
Transmission Fecal- ParenteralParenteral Parenteral Fecal-oralParentera
oral l
Prevention Ig vaccine Ig vaccine None HepB None None
vaccine
*Fever flu-like symptoms in a weekm lysis of fever followed by jaundice the next
day (usually A & E).
CASE 1
The patient had a history of low grade fever with anorexia and
nausea 3 days prior to the onset of jaundice. Defervescence of the
fever noted 1 day prior to the observation of tea-colored urine
which was followed by yellowing of the eyes. Physical examination
revealed icteric sclerae and an enlarged tender liver edge felt 2 cm
below the right subcostal margin.
Laboratory result: AST = 2000 IU/L, ALT = 3000 IU/L, PT = normal,
total bilirubin = 129 umol/L, B2 70 umol/L
What is your interpretation of the work-up?
o ALT: Specific to the liver
o AST: Muscles, heart, liver, kidneys
Diagnosis of acute hepatitis becomes likely when the COMPLICATIONS OF ACUTE VIRAL HEPATITIS
transaminases (AST, ALT) are more than 400 IU/L for more than RELAPSING HEPATITIS
10x the upper limit of normal) o Characterized by recurrence of symptoms,
Would you admit this patient to the hospital? aminotransferase elevations, jaundice and fecal excretion of
What are the clinical and chemical parameters for hospital hepatitis A virus weeks to months after apparent recovery
admission of patient with acute viral hepatitis? from acute hep. A
What are the initial laboratory examinations would you order to CHOLESTATIC HEPATITIS
determine the etiology of acute viral hepatitis? How should it be o Occasionally In patients with hepatitis A characterized by
interpreted? protracted jaundice and pruritus
o Cholestatic swelling of the bile canaliculi
o Alkaline phosphatase: elevated (cholestasis)
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 IM II: ACUTE HEPATITIS, CHRONIC HEPATITIS, ALCOHOLIC LIVER DISEASE AND CIRRHOSIS
FULMINANT HEPATITIS presentation to document virology clearance: disappearance of
o Occurs with B, D, and E and rarely with A and C anti-HBs would document complete virologic recovery
o Signs and symptoms of hepatic encephalopathy, may Hepatitis A immunity
deteriorate to deep coma o Anti-HAV IgG: Recovered hepatitis A, with immunity
o Liver is small
o Prothrombin time is excessively prolonged CHRONIC VIRAL HEPATITIS
o Cerebral edema is common and BS compression
o GI bleeding, sepsis, respiratory failure, CV collapse, renal CLASSIFICATION OF CHRONIC HEPATITIS
failure are terminal events. It is based upon:
cause
FEATURES THAT SUGGEST PROGRESSION FROM ACUTE histologic activity, or grade
TO CHRONIC HEPATITIS degree of progression, or stage
Lack of complete resolution of clinical symptoms of anorexia,
weight loss and fatigue and the persistence of hepatomegaly 1. Classification by CAUSE
Presence of bridging or multilobar hepatic necrosis on liver biopsy o Chronic Hepatitis B, C and D. G?
during protracted, severe acute viral hepatitis o Autoimmune hepatitis
Failure of serum aminotransferase, bilirubin and globulin levels to o Drug-associated
return to normal within 6 to 12 months after the acute illness o Cryptogenic (unknown)
HBsAg beyond 6 months after acute hepatitis 2. Classification by GRADE
o Histologic activity index (knodell-ishak score) in chronic
DIFFERENTIAL DIAGNOSIS
hepatitis
Systemic viral infection EBV, CMV, leptospirosis,
mycobacteria, pneumocystitis 3. Classification by STAGE
Drug-induced hepatitis o based on the degree of fibrosis as follows:
High doses of acetaminophen 0 = No fibrosis
Anti-TB drugs 1 = Mild fibrosis
CPC of the liver due to RV failure 2 = Moderate fibrosis
Alcoholic hepatitis 3 = Severe fibrosis, including bridging fibrosis
4 = Cirrhosis
Obstructive jaundice - *herbal induced hepatitis

TREATMENT
Supportive management

PREVENTION A
Hepatitis A Ig passive immunization with immunoglobulin
Hepatitis A vaccine passive immunization
o If reactive from anti-HAV IgG: protected from hep A virus

PREVENTION B
Hepatitis B Ig for rapid achievement of high titers of circulating
antibodies
Hepatitis B vaccine for achievement of long lasting immunity as
well as its efficacy in attenuating clinical illness after exposure CHRONIC HEPATITIS B
Presence of anti-HBs reactivity protection
o For rapid achievement of high titers of circulating antibodies WHERE IS THE HBV INFECTION IN ASIA PACIFIC?
Hepatitis B vaccine active immunization COUNTRY LONG TERM CARRIERS
o 3 doses (MILLIONS)
o Achievement of long-lasting immunity as well as its efficacy in
attenuating clinical illness after exposure China 120
o *Anti-HBs negative: No infection but needs to have India 48
immunization Indonesia 11.6
No vaccine for Hepatitis C, D, E
PHILIPPINES 2.6
Acute Hepatitis B
Korea 2.5
o Test for HBsAg (-), anti-HBs (+) about 6 months, appearance
Japan 1.3
of anti-HBs means virologic recovery
Hong Kong 0.7
Acute Hepatitis C
Singapore 0.03
o Incidence of developing to chronic hepatitis C is very high
Australia 0.2
All patients diagnosed to have acute hepatitis should undergo
testing for HBsAg and anti-HBs about 6 months after the initial Taiwan 3.0

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 IM II: ACUTE HEPATITIS, CHRONIC HEPATITIS, ALCOHOLIC LIVER DISEASE AND CIRRHOSIS
NATURAL HISTORY OF CHRONIC HBV (CHB) INFECTION

SPECTRUM OF THE DISEASE

PHASES OF CHB INFECTION

MODE OF TRANSMISSION
Mother to child
o During pregnancy and childbirth
Sexual contact
Exposure to contaminated blood or body fluids
o Semen
o Vaginal secretions
o Synovial fluids
Examples:
Cuts or grazes on the skin and mucosa
Needle stick and sharp injuries
Sharing personal items (toothbrush, razors)
Manicure, pedicure, ear piercing, tattooing
HBV has not been documented to be transmitted by the PHYSICAL EXAMINATION
following: Mental status
o Coughing and sneezing o Asterixis
o Sharing utensils, plates, glasses, cutlery o Spider angiomas: violaceous discoloration on the chest
o Sharing lavatory seats o Palmar erythema
o Handshaking, hugging, kissing o Ascites
o Swimming pools o Dilated superficial abdominal veins
o Public dinning places o Liver mass
o Crowded places o Splenomegaly: sign of portal HPN
o Drinking fountains

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 IM II: ACUTE HEPATITIS, CHRONIC HEPATITIS, ALCOHOLIC LIVER DISEASE AND CIRRHOSIS
WHEN TO TREAT? Pale icteric sclera, presence of spider angioma noted. Asterixis
Elevated ALT (twice the level of normal or higher) is present. Shifting dullness and fluid wave appreciated
A high viral load (HBV DNA 10 5th copies/ml or higher) CAUSES OF CIRRHOSIS
o HBV DNA: quantitative marker of viral replication
Alcoholism
Available treatment options
Cardiac cirrhosis
Immunomodulators
Chronic viral hepatitis B and C
Interferon alpha (IFN)
Non- alcoholic steatohepatitis
Thymosin
Biliary cirrhosis
Oral antivirals
Inherited
Lamivudine (LAM)
o Hemochromatosis
Adefovir dipivoxil (ADV) o Wilsons disease
Entecavir Miscellaneous
Telbivudine o Schistosomiasis
Tenofovir Cryptogenic (unknown cirrhosis)
HOLISTIC APPROACH TO CHRONIC HEPATITIS B
CHB is a life-long infection PATHOLOGY
o Identification of those at risk of liver disease Alcoholic fatty liver liver is enlarged, yellow greasy and firm
o Education (life-long monitoring, reactivation) Alcoholic Hepatitis hepatocyte degeneration and necrosis
o Vaccination (all sexual/household contacts) with PMN leukocytes and lymphocyte infiltration
o Judicious use of antiviral therapy Alcoholic cirrhosis liver shrinks in size, becomes hard. End
o Appropriate screening for HCC Stage cirrhosis
Transaminase findings:
CHRONIC HEPATITIS C o AST/ALT ratio >2 due to the greater inhibition of ALT
TESTS FOR CHRONIC HEPATITIS C synthesis by alcohol
o Anti HCV: Qualitative test for Hepatitis C o Transaminase levels not >300 units
o HCV-RNA: Quantitative marker for Hepatitis C PROGNOSIS
o ALT: If there is need to treat
The presence of ascites, variceal hemorrhage, deep
encephalopathy or hepatorenal syndrome predicts a dismal
ACCEPTED INDICATIONS FOR INTERFERON THERAPY IN
prognosis
CHRONIC HEPATITIS C
o Elevated ALT more than 1.5 times the upper limit of normal
o Chronic hepatitis of moderate severity on liver biopsy POST-HEPATIC OR CRYPTOGEN IC CIRRHOSIS
o Detectable HCV-RNA (UNKNOWN ETIOLOGY)
Represents the final common pathway of many types of
ABSENCE OF BENEFIT FOR INTERFERON USE chronic liver disease
o Decompensated liver disease Cryptogenic cirrhosis has been used interchangeable with
o Normal ALT posthepatitic cirrhosis, but this designation should be reserved
o Failure to respond to a previous course of Interferon for those cases in which the etiology of cirrhosis is unknown
(10%)
TREATMENT FOR CHRONIC HEPATITIS C
o PEGylated Interferon - Ribavirin combination DIAGNOSIS OF CRYPTOGENIC CIRRHOSIS
given for 6 months Reserved for those patients in whom no known etiology can
be demonstrated
ALCOHOL LIVER DISEASE/CIRRHOSIS OF THE LIV ER CARDIAC CIRRHOSIS
Most common Prolonged, severe right-sided congestive heart failure may
Diffuse fine scarring referred to as micronodular cirrhosis lead to chronic liver injury and cardiac cirrhosis
Threshold for developing severe alcoholic liver disease
o Male 60-80g/d for 10 years ETIOLOGY AND PATHOLOGY
o Female 20-40g/d for 10 years In right-sided heart failure, retrograde transmission of
o 12g alcohol = 1 beer = 4 ounces of wine = 1 ounce of 80% elevated venous pressure via the inferior vena cava and
spirits hepatic veins leads to congestion of the liver
CASE 1 Hepatic sinusoids become dilated and engorged with blood,
and the liver becomes tensely swollen
Pedro, a 50 year male, chronic alcohol drinker presented with
vomiting of 500mL of fresh blood and passage of black, tarry stools DIAGNOSIS
a few hours prior to admission. Patient is drowsy and responds The presence of a firm, enlarged liver with signs of chronic liver
slowly to verbal commands disease in a patient with valvular heart disease, constrictive
BP 60/50 mmHg pericarditis or cor pulmonale of long duration (>10 years)
CAR 110/min should suggest cardiac cirrhosis

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 IM II: ACUTE HEPATITIS, CHRONIC HEPATITIS, ALCOHOLIC LIVER DISEASE AND CIRRHOSIS
CLINICAL MANIFESTATIONS
Palmar erythema
Spider angiomas
Telangiectasias
Icteresia

COMPLICATIONS OF CIRRHOSIS
Portal hypertension and its consequences (e.g.,
gastroesophageal varices and splenomegaly)
Ascites
Hepatic encephalopathy
Spontaneous bacterial peritonitis
Hepatorenal syndrome
Hepatocellular carcinoma
Coagulopathy: factor deficiency, low platelets, fibrinolysis
Bone disease: osteopenia, osteoporosis
Hematologic abnormalities: anemia, hemolysis, low platelets,
neutropenia

MAJOR SITES OF COLLATERAL CIRCULATION

Cardioesophageal junction (esophagogastric varices)
Rectum varices
Retroperitoneal space
Falciform ligament of the liver (periumbilical or abdominal wall
collaterals
Abdominal wall collaterals (caput medusae)

PORTAL HYPERTENSION
Normal pressure in the portal vein is low
(5-10mmHg) because vascular resistance in the hepatic
sinusoids is minimal
Portal hypertension (>10mmHg) results from increased
resistance to portal blood flow

DIAGNOSIS
Ascites
Splenomegaly
Encephalopathy
Esophageal varices

VARICEAL BLEEDING
Bleeding is most common from varices in the region of the
gastroesophageal junction
The factors contributing to bleeding from gastroesophageal
varices are not entirely understood but include the degree
of portal hypertension (>12mmHg) and the size of the
varices

CLINICAL FEATURES AND DIAGNOSIS

Painless but massive hematemesis with or without melena
Signs range from mild postural tachycardia to profound
shock, depending on the extent of blood loss and degree of
hypovolemia
Endoscopy is the best approach to evaluate upper
gastrointestinal hemorrhage in patients with known or
suspected portal hypertension

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 IM II: ACUTE HEPATITIS, CHRONIC HEPATITIS, ALCOHOLIC LIVER DISEASE AND CIRRHOSIS
TREATMENT ASCITES
Variceal bleeding is a life-threatening emergency Ascites is the accumulation of excess fluid within the
Replacement of blood loss peritoneal cavity. It is most frequently encountered in patients
Replacement of clotting factors by giving fresh frozen plasma with cirrhosis
Somatostatin or octreotide IV
Endoscopic treatment
Variceal band ligation
SURGERY:
Porto-systemic shunts
Esophageal devascularisation
TIPS (transcutaenous intrahepatic porto-systemic shunt)

PREVENTION
Pharmacological Therapy
Propranolol, isosorbide mononitrates THEORIES OF ASCITES FORMATION
Endoscopic Therapy
Underfilling theory an apparent decrease in intravascular
Serial variceal band ligations
(underfilling) is sensed by the kidney, which responds by
retaining salt and water
Overflow Theory suggests that the primary abnormality is
inappropriate renal retension of salt and water in the absence
of volume depletion
Peripheral arterial vasodilation hypothesis may unify the
earlier theories and accounts for the constellation of arterial
hypotension and increased cardiac output in association with
high levels of vasoconstrictor substances

SPLENOMEGALY
CLINICAL FEATURES
Although usually asymptomatic
Splenomegaly contribute to the thrombocytopenia or
pancytopenia

TREATMENT
No specific treatment
Massive splenomegaly
o Splenectomy at the time of shunt surgery

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 IM II: ACUTE HEPATITIS, CHRONIC HEPATITIS, ALCOHOLIC LIVER DISEASE AND CIRRHOSIS
CLINICAL FEATURES & DIAGNOSIS OF ASCITES
Increasing abdominal girth
Shortness of breath because of elevation of the diaphragm
Physical examination by the presence of shifting dullness, a fluid
wave or bulging flanks
Ultrasound examination
PRECIPITATING FACTORS FOR PROGRESSION OF ASCITES
FORMATION
Excessive salt intake
Medication non- compliance
Superimposed infection
Worsening liver disease
Portal vein thrombosis
Development of hepatocellular carcinoma
TREATMENT
Paracentesis
Salt restriction. A diet containing 800 mg sodium (2g NaCl)
Spironolactone or other distal tubule- acting diuretics
(triamterene, amiloride) are the drugs of choice
Furosemide, thiazide or ethcrynic acid
Aggressive therapy must be used wit great caution to avoid
plasma volume, depletion, azotemia, and hypokalemia, which
may lead to encephalophathy
ASCITIC FLUID EXAM COMPATIBLE WITH SBP
Leukocyte count of >500 cells/L ( with a proportion of
polymorphonuclear leukocytes of 50%)
Polymorphonuclear leukocytes of > 250 cell/L
+ bacterial cultures
SPONTANEOUS BACTERIA L PERITONITIS
Treatment
Cefotaxime or ampicillin and an aminoglycoside
HEPATORENAL SYNDROME
The kidneys are structurally intact; urinalysis and pyelography
are usually normal
Characterized by worsening azotemia with avid sodium
retention and oliguria in the absence of identifiable specific
causes of renal dysfunction
CLINICAL FEATURES
Worsening azotemia, hyponatremia
Progressive oliguria
Hypotension are the hallmarks of the hepatorenal syndrome
PRECIPITATING CONDITIONS
Severe gastrointestinal bleeding
Sepsis
Overly vigorous attempts at diuresis o paracentesis
It may also occur without an obvious cause
Iit is essential to exclude other causes of renal impairment often
seen in these patients
DIAGNOSIS
An elevated serum creatinine level (>133 umol/L (>1.5 g/dl)) that
fails to improve with volume expansion or withdrawal of
diuretics, togeteher with an unremarkable urine sediment
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TREATMENT
Treatment is usually unsuccessful
Infusions of salt poor albumin
HEPATIC ENCEPHALOPAT HY
Hepatic (portal-systemic) encephalopathy is a complex
neuropsychiatric syndrome
Characterized by disturbances in consciousness and behaviour
Personality changes
Fluctuating neurologic signs, asterixis or flapping tremor
Distinctive electroencephalographic changes
Asterixis (liver flap, flapping tremor) is a non -rhythmic
asymmetric lapse in voluntary sustained position of the
extremities, head, and trunk. It is best demonstrated by having
the patient extend the arms and dorsiflex the hands.
PRECIPITATING FACTORS
GI bleeding
Increased dietary protein
Electrolyte disturbances particularly hypokalemic alkalosis
secondary to overzealous use of diuretics, vigorous paracentesis
or vomiting
Use of CNS-depressants (e.g., barbiturates, benzodiazepines)
Acute infection
Acute viral hepatitis, alcoholic hepatitis, extrahepatic bile duct
obstruction, constipation surgery
TREATMENT
Elimination or treatment of the precipitating factors
Lowering of blood ammonia (and other toxin) levels by
decreasing the absorption of protein and nitrogenous products
from the intestine.
In the setting of acute gastrointestinal bleeding, blood in the
bowel shoud be promptly evacuated with laxatives ( and enemas
if necessary) in order to reduce thr nitrogen load
Protein should be excluded from the diet, and constipation
should be avoided
Lactulose, a nonabsorbable dissacharide that acts an osmotic
laxative
Antibiotics- rifaximin, metronidazole
COAGULOPATHY
Abnormalities in both cellular and humoral clotting function.
Thrombocytopenia may result from hypersplenism
Of these factors VII appears to be pivotal. In cirrhosis, it is the
first of the factors become depleted and because of its short half
life, replacement with plasma often fails to correct an elevated
prothrombin time.
HYPOXEMIA AND HEPATOPULMONARY SYNDROME
Mild hypoxemia occurs in the approximately one-third of
patients with chronic liver disease.
No specific treatment is consistently effective
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