CIRRHOSIS AND ITS
COMPLICATIONS
Dr. P. Dienhart, M.D
[Gastroenterology]
Dr.Padma Poddutoori
[PGY3,I.M]
Definition
Cirrhosis is a late stage of
progressive hepatic fibrosis
characterized by distortion of
the hepatic architecture and the
formation of regenerative
nodules. It is considered to be
irreversible in its advanced
stages.
Etiology of cirrhosis
Alcoholic liver disease
Chronic Hep B,C
PBC
PSC
NASH
Autoimmune hepatitis
Hereditary Hemochromatosis
Alfa1 AT deficiency
Wilsons disease
Cardiac cirrhosis
Clinical manifestations
and presentation
Stigmata of chronic liver disease discovered on
routine PE [spider angioma, palmar erythema,
terrys nails, Muehrcke's nails, clubbing and HOCM,
dupuytrens contracture, ascites, splenomegaly,
hepatomegaly, caput medusae, testicular atrophy,
Cruveilhier-Baumgarten murmur, fetor hepaticus,
jaundice and asterexis
Laboratory/ radiologic tests or an unrelated
surgical procedure that incidentally uncovered
cirrhosis.
Decompensated cirrhosis, which is characterized
by the presence of life-threatening complications,
such as variceal hemorrhage, ascites, SBP, or
hepatic encephalopathy.
Some never come to clinical attention. Cirrhosis is
diagnosed at autopsy in ~30- 40% of patients
Complications of
Cirrhosis
Portal hypertension
Variceal bleeding
Ascites
Splenomegaly leading to
thrombocytopenia
SBP
Hepato-renal syndrome
Hepatic encephalopathy
Hepatopulmonary syndrome
Hepatocellular carcinoma
Portal Hypertension
Portal venous pressure > 10 mm of Hg
3 types: presinusoidal[eg:portal vein thrombosis,
Schistosomiasis], sinusoidal and postsinusoidal
[Budd-Chiari syndrome]
Cirrhosis- most common, 2nd most common- portal
vein obstruction
Usually revealed by the appearance of
splenomegaly, ascites, encephalopathy, esophageal
varices
Treatment- B-blockade with non selective agents
like propranolol or nadolol, TIPS
Therapeutic goals-HVPG<12 mm of Hg or by 20%
from baseline or reduction of resting pulse by 25%
Variceal bleeding
Most common from varices in the GE
junction
Factors for bleeding are degree of portal
hypertension[>12mm of Hg] and variceal
size
Bleeding is painless, massive hematemesis
with/without malena can occur
Symptoms/signs could range from mild
postural tachycardia to profound shock
Management of variceal
bleed
Prompt estimation and vigorous
replacement of blood loss
Avoid excessive fluid administration-
could be deleterious
Close monitoring of central venous
pr or pulmonary capillary wedge pr,
urine output and mental status is
needed
Vasopressors like Somatostatin-250
mcg bolus followed by 250 mcg/hr
infusion or octreotide 50-100mcg/hr
or vasopressin 0.1-0.4U/min.
Management of variceal
bleed contd
Balloon tamonade with senstaken blackmore or
Minesota tube if endoscopy not available-
complications aspiration, esophageal rupture.
EVL controls acute bleed in 90%
Portal systemic shunts-non selective end to side,
side to side PC shunts and proximal SR shunts.
Selective-distal SR shunt
TIPS-expandable metal shunt to the hepatic veins
to create direct PC shunt
Prevention prophylactic non-selective B-blockers-
propranolol and nadolol-goal to reduce resting HR
by 25% or HVPG to 12mm of Hg or 20% below
baseline
Ascites
Three theories-underfilling, overflow, peripheral
arterial vasodilation-splanchnic arteriolar dilation
Portal hypertension plays important role in ascites
formation, hypoalbuminemia,reduced plasma
oncotic pr also favor. Renal factors also contribute
>500 ml of fluid is needed for ascites to be
demonstrated on PE
Salt restriction-800 mg Na or 2 gm NaCl
Fluid restriction of 1 L/day may be necessary to
correct hyponatremia.
Spironolactone 100400 and furosemide 40160
Large volume paracentesis with albumin
replacement.
Side-side PC shunt and TIPS
SBP-definition and
etiology
SBP or primary peritonitis-without an
apparent source of contamination
Most commonly in pts with
cirrhosis[alcoholic], but also with
metastatic malignant disease,
postnecrotic cirrhosis, chr.active
hepatitis, acute viral
hepatitis,CHF,SLE, lymphedema
Hematogenous spread of organisms
in pts with diseased liver and altered
portal circulation resulting in defect
in usual filtration function
Presentation and
diagnosis
Most common manifestation-fever-80%
Abdominal pain, acute onset of symptoms
and peritoneal irritation
Vital to sample peritoneal fluid of any
cirrhotic pt with ascites and fever
Diagnosis of SBP-
temperature > 37.8[100F]
Abd pain and/or tenderness
change in MS
ascitic fluid PMN >250
Gm negative org like E.coli, Gm +ve org
strep, enterococci and pneumococci
Treatment of SBP
Empiric therapy shd cover Gm ve aerobic bacilli
and Gm +ve cocci
Third gen cephalosporins like cefotaxime 2 gm q8,
zosyn 3.375 gm q6, ceftriaxone 2gm q24. Pts
usually respond in 72 hrs- total 5 days Rx-if rapid
improvement and blood cultures are negative, 2
wks Rx if slow improvement or bacteremia
Prevention-70% recurrence. Antibiotics reduce to
20%.ciprofloxacin 750 wkly or noflox 400qd bactrim
1DS qd .
Prolonged prophylaxis (ie, indefinite duration) of
patients with cirrhosis and ascitic fluid total protein
<1.5 g/dL with a) Child-Pugh >9 points and serum
bilirubin >3 mg/dL or b) serum creatinine >1.2 mg/dL
or blood urea nitrogen >20 mg/dL or serum sodium
<130 mEq/L is recommended.
Hepatorenal syndrome
Definition: charecterized by worsening azotemia with
avid sodium retention and oliguria in the absence of
identifiable causes of renal dysfunction
There is evidence for inappropriate intense renal
vasoconstriction, in response to the splanchnic
vasodilation
Worsening azotemia, hyponatremia,progressive oliguria
and hypotension are the hallmarks
Precipitating factors: severe GI bleed, sepsis or overly
vigorous attempts at diuresis or paracentesis
Diagnosis: elevated creatinine >1.5g/dl that fails to
improve with volume expansion or withdrawal of
diuretics, with a normal urine sediment
Urine sodium is typically <5mmol/l
Some may respond to salt free albumin
Terlipressin, norepinephrine with albumin and octreotide
with midodrine have recently emerged
TIPS
Liver transplantation
In SBP, early I.V albumin infusion can prevent HRS in
some
Hepatic Encephalopathy
Definition: Is a complex neuropsychiatric syndrome ch.
by disturbances in consciousness and behaviour,
personality changes, fluctuating neurologic signs,
asterexis or flapping tremor and distinctive EEG changes.
It could be acute and reversible or chronic and
progressive
Pathogenesis:
Severe hepatocellular dysfunction and/or intrahepatic and
extrahepatic shunting of portal venous blood into
systemic circulation, hence bypassing liver
Ammonia is the most common one. Others include
mercaptans,short chain fatty acids and phenol.
Increased concentrations of GABA and direct
enhancement of GABA receptor activation by ammonia.
Hyperintensity in the basal ganglia by MRI in cirrhotic
pts suggests that excessive manganese deposition may
contribute
Common precipitants of
HE
Increased nitrogen load:
GI bleeding
Excess dietary protein
Azotemia
Constipation
Electrolyte and metabolic imbalance:
Hypokalemia
Hypoxia
Hyponatremia
Hypovolemia
Alkalosis
Drugs:
Narcotics, tranquilizers, sedatives
Diuretics
Others:
Infection
Surgery
Superimposed acute liver disease
Progressive liver disease
Portal systemic shunts
Diagnosis of HE
HE should be considered when 4 major factors are
present
1.Acute or chr. hepatocellular disease and/or
extensive portal systemic collateral shunts-
spontaneous or sec to TIPS
2.Disturbance of awareness and mentation
3.Shifting combinations of neurologic signs inc.
asterexis, rigidity, hyperreflexia, extensor plantar
signs, seizures
4.Charecteristic symmetric high voltage triphasic
slow wave[2-5/sec] pattern on EEG
Asterexis: a non rhythmic asymmetric lapse in
voluntary sustained position of the extremities,
head and trunk.
Disturbances of sleep with reversal of sleep/wake
cycles are the earliest signs.
Fetor hepaticus is the musty odour of the breath
and urine due to mercaptans
Clinical stages of HE
STAGE
MENTAL ASTEREXIS EEG
STATUS
1 EUPHORIA OR
DEPRESSION, MILD +/- TRIPHASIC
CONFUSION, SLURRED WAVES
SPEECH, DISORDERED
SLEEP
2 LETHARGY, MODERATE
CONFUSION + TRIPHASIC
WAVES
3 MARKED CONFUSION,
INCOHERENT SPEECH, + TRIPHASIC
INCOHERENT WAVES
SPEECH,SLEEPING BUT
AROUSABLE
4 COMA; INITIALLY
RESPONSIVE TO - DELTA
NOXIOUS STIMULI, ACTIVITY
LATER UNRESPONSIVE
Treatment of HE
Lactulose- a non absorbable disaccharide, acts as
an osmotic laxative. Turns Ph acidic and hence
converts ammonia to ammonium, may also diminish
ammonia production thru direct effects on bacterial
metabolism.
Initially 30-60 ml/hr until diarrhea occurs and then
15-30 ml tid-2-4 soft BM
Neomycin 0.5 TO 1gm q 6 hrs
Metronidazole
Hemoperfusion, extracorporeal liver assist
devices may bridge pts to recovery or
transplantation- yet unproven.
Chronic encephalopathy dietary protein
restriction[60 g/d], vegetable protein preferable to
animal protein
Hepatopulmonary
syndrome
Manifest by hypoxemia, platypnea and
orthodeoxia
Hypoxia: usually due to R-L intrapulmonary
shunts thru dilatations in intrapulmonary
vessels detected by contrast enhanced
echo or a macro aggregated albumin lung
perfusion scan. Endothelin-1 and
pulmonary NO correlate with degree of
shunting.
Large A-V shunts may be embolized
Liver transplantation
THANK YOU!
