CIRRHOSIS AND ITS COMPLICATIONS
the pathologic features consist :
o development of fibrosis to the point that there is
architectural distortion
o formation of regenerative nodules.
o This results in a decrease in hepatocellular mass,
and thus function, and an alteration of blood
flow.
Advanced fibrosis usually includes
o bridging fibrosis with nodularity designated as
stage 3 and
o cirrhosis designated as stage 4.
Patients who have developed complications of their liver
disease and have become decompensated should be
considered for liver transplantation
o Portal hypertension is a significant complicating
feature of decompensated cirrhosis
o responsible for the development of ascites
o bleeding from esophagogastric varices,
Loss of hepatocellular function results in jaundice,
coagulation disorders, and hypoalbuminemia and
contributes to the causes of portosystemic
encephalopathy
ALCOHOLIC CIRRHOSIS
Excessive chronic alcohol use can cause several different
types of chronic liver disease, including
o alcoholic fatty liver
o alcoholic hepatitis
o alcoholic cirrhosis.
Chronic alcohol use can produce fibrosis in the absence of
accompanying inflammation and/or necrosis.
o Fibrosis can be centrilobular, pericellular, or
periportal.
o When fibrosis reaches a certain degree, there is
disruption of the normal liver architecture and
replacement of liver cells by regenerative
nodules.
o Micronodular-- In alcoholic cirrhosis, the nodules
are usually <3 mm in diameter. With cessation of
alcohol use, larger nodules may form, resulting in
a mixed micronodular and macronodular
cirrhosis
Ethanol is mainly absorbed by the small intestine and, to a
lesser degree, through the stomach.
o Gastric alcohol dehydrogenase (ADH) initiates alcohol
metabolism.
o Three enzyme systems account for metabolism of
alcohol in the liver. These include
 cytosolic ADH,
 the microsomal ethanol oxidizing system
(MEOS), and
 Peroxisomal catalase.
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CLINICAL FEATURES:
 vague right upper quadrant pain,
 fever,
 Nausea
 vomiting,
 diarrhea,
 anorexia
 malaise.
 Ascites
 edema,
 upper gastrointestinal (GI) hemorrhage.
 jaundice
 encephalopathy.
 liver and spleen may be enlarged,
 liver edge being firm and nodular.
 scleral icterus,
 Palmar
 Erythema
 Spider angiomas
 parotid gland enlargement,
 digital clubbing,
 muscle wasting,
 Men may have decreased body hair and
gynecomastia as well as testicular atrophy,
 women with menstrual irregularities usually occur,
may be amenorrheic
 Patients may be anemic either from chronic GI blood
loss, nutritional deficiencies, or hypersplenism related
to portal hypertension, or as a direct suppressive
effect of alcohol on the bone marrow
 Zieve’s syndrome can occur in patients with severe
alcoholic hepatitis
 Platelet counts are often reduced
 Serum total bilirubin can be normal or elevated with
advanced disease.
 Direct bilirubin is frequently mildly elevated in
patients with a normal total bilirubin but the
abnormality typically progresses as the disease
worsens.
 Prothrombin times are often prolonged and usually
do not respond to administration of parenteral
vitamin K.
 Serum sodium levels are usually normal unless
patients have ascites and then can be depressed,
largely due to ingestion of excess free water.
 Serum alanine and aspartate aminotransferases (ALT,
AST) are typically elevated, particularly in patients
who continue to drink, with AST levels being higher
than ALT levels, usually by a 2:1 ratio.
DIAGNOSIS:
 liver biopsy is withheld until abstinence has been
maintained for at least 6 months to determine
residual, nonreversible disease those individuals who
are able to remain abstinent,
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 CIRRHOSIS AND ITS COMPLICATIONS
 liver transplantation for pts who are able to remain
abstinent.
TREATMENT:
 Glucocorticoids
o Treatment isrestricted to patients with a
discriminant function (DF) value of >32. The DF is
calculated as the serum total bilirubin plus
o Glucocorticoids are occasionally used in patients
with severe alcoholic hepatitis in the absence of
infection.
o complications can occur,
 oral pentoxifylline,
o which decreases the production of tumor
necrosis factor other proinflammatory cytokines.
In contrast
o easy to administer and has few side effects.
 the cornerstone to treatment is cessation of alcohol
use.
 Acetaminophen use is often discouraged in patients
with liver disease;
o however, if no more than 2 g of acetaminophen per
day are consumed, there generally are noproblems.
CIRRHOSIS DUE TO HEPATITIS B AND C
Progression of liver disease due to chronic
hepatitis C is characterized by
o portal-based fibrosis with bridging fibrosis
o nodularity developing,
o liver is small and shrunken with characteristic
features of a mixed micro- and macronodular
cirrhosis
o an inflammatory infiltrate is found in portal areas
with interface hepatitis and occasionally some
lobular hepatocellular injury and inflammation.
o In patients with HCV genotype 3, steatosis is
oftenpresent.
Special stains for hepatitis B core (HBc) and hepatitis B
surface (HBs) antigen will be positive, and ground-glass
hepatocytes signifying hepatitis B surface antigen (HBsAg)
may be present
Clinical features and diagnosis
 Fatigue,
 malaise,
 vague right upper quadrant pain,
 Diagnosis
o quantitative HCV RNA testing and
o analysis for HCV genotype,
o or hepatitis B serologies to include HBsAg, anti-
HBs, HBeAg (hepatitis B e antigen), anti-HBe,
and quantitative HBV DNA levels.
TREATMENT:
 For HEp B- antiviral therapy, which is effective at viral
suppression, reducing aminotransferase levels and
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HBV DNA levels, and improving histology by reducing
inflammationand fibrosis
 EXAMPLES:lamivudine, adefovir, telbivudine,
entecavir, and tenofovir.
 Interferon for treating hepatitis B,
o but it should not be used in cirrhotics.
CIRRHOSIS FROM AUTOIMMUNE HEPATITIS AND NON
ALCOHOLIC FATTY LIVER DISEASE
autoimmune hepatitis (AIH) present with cirrhosis
o these patients will not benefitfrom
immunosuppressive therapy with glucocorticoids
or azathioprine
o liver biopsy does not show a significant
inflammatory infiltrate.
o Diagnosis
 positive autoimmune markers such as
antinuclear antibody (ANA) or anti-smooth-
muscle antibody (ASMA).
o When patients with AIH present with cirrhosis and
active inflammation,there can be considerable
benefit from the use of immunosuppressive
therapy.
Management
o similar to that for other forms of cirrhosis
BILIARY CIRRHOSIS
Biliary cirrhosis has pathologic features that are different
from either alcoholic cirrhosis or posthepatitic cirrhosis,
yet the manifestations of end-stage liver disease are the
same.
categories reflect the anatomic sites of abnormal bile
retention:
o Intrahepatic
 Will not improve from urgical or endoscopic
biliary tract decompression
o Extrahepatic .
 May benefit from surgical or endoscopic
biliary tract decompression
PRIMARY BILIARY CIRRHOSIS
female preponderance
a median age of around 50
characterized by portal inflammation and necrosis of
cholangiocytes in small- and medium-sized bile ducts.
Cholestatic features prevail, and biliary cirrhosis is
characterized by an elevated bilirubin level and
progressive liver failure.
Liver transplantation is the treatment of choice
(decompensated) cirrhosis due to PBC. 2014 -2015
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 CIRRHOSIS AND ITS COMPLICATIONS GASTRO
ursodeoxycholic acid (UDCA)is the only approved o Plasmapheresis for severe intractable
treatment pruritus.
o slowing the rate of progression of the disease.  osteopenia
o bone density testing
Antimitochondrial antibodies (AMA) are present in about o bisphosphonate shouldbe instituted when
90% bone disease is identified
o are not pathogenic but rather are useful markers
for making a diagnosis of PBC. PRIMARY SCLEROSING CHOLANGITIS
characterized by diffuse inflammation and fibrosis
Clinical features involving the entire biliary tree, resulting in chronic
 most prominently- fatigue cholestasis.
 Pruritus 50% ,bothersome in the evening. In some This pathologic process ultimately results in obliteration
patients, of both the intra- and extrahepatic biliary tree, leading to
o can develop toward the end of pregnancy, biliarycirrhosis, portal hypertension, and liver failure
o patients having been diagnosed with cholestasis of Periductal fibrosis-biopsy
pregnancy rather thanPBC.
o Pruritus that presents prior to the development of Clinical features
jaundiceindicates severe disease and a poor  fatigue,
prognosis.  pruritus,
 hepatomegaly,  Steatorrhea
 splenomegaly  , deficiencies of fat-solublevitamins,
 osteopenia  fatigue is nonspecific.
 edema.  Pruritus -debilitating and is related to the cholestasis.
 unique toPBC include  Metabolic bone disease
o hyperpigmentation
o , xanthelasma, and Laboratory findings
o xanthomata,  least a twofold increase in ALP
o related to the altered cholesterol  may have elevated aminotransferases
metabolism  . Albumin levels may be decreased,
 prothrombin times are prolonged
Laboratory findings o may occur with parenteral vitamin K
 Elevation in γ-glutamyl transpeptidase and alkaline  aminotransferase elevations greater than five times
phosphatase (ALP) the upper limit of normal
 mild elevations in aminotransferases (ALT and AST).  may have features of AIH on biopsy.
 IgM, are typically increased. o These individuals are thought to have an overlap
 Hyperbilirubinemia usually is seen once cirrhosis has syndrome between PSC and AIH.
developed. o Autoantibodies are frequently positive in patients
 Thrombocytopenia, leukopenia, and anemia may be with the overlap syndrome but are typically
seen in patients with portal hypertension and negative in patients who only have PSC
hypersplenism. o antineutrophil cytoplasmic antibody (p-ANCA), is
Diagnosis positive in about 65% of patients with PSC.
 .AMA testing may be negative o Over 50% of patients with PSC also have
o Liver biopsy is most important in this setting ulcerative colitis (UC);
of AMA-negative PBC.
o Inpatients who are AMA-negative with Diagnosis
cholestatic liver enzymes, PSC should be
ruled out by way of cholangiography. o MRI with magnetic resonance
TREATMENT: cholangiopancreatography (MRCP) has been used as
 UDCA, the imaging technique of choice for initial evaluation.
o diarrhea or headache as a side effect o endoscopic retrograde cholangiopancreatography
o slow the rate of progression of PBC (ERCP)
o it does not reverse or cure the disease  whether or not a dominant stricture is
 Fatigue present.
o frequent naps should be encouraged.
 Typical cholangiographic findings in PSC are
 Pruritusis
multifocal stricturing and beading involving
o antihistamines, narcotic receptor antagonists 2014 -2015
(naltrexone), and rifampin. Cholestyramine,
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 CIRRHOSIS AND ITS COMPLICATIONS
both the intrahepatic and extrahepatic biliary
tree.
TREATMENT:
 high-dose (20 mg/kg per day) of UDCA
 Endoscopic dilatation of dominant strictures
can be helpful,
 ultimate treatment is liver transplantation.
CARDIAC CIRRHOSIS
Patients with long-standing right-sided congestive
heart failure may develop chronic liver injury and
cardiac cirrhosis
Etiology and pathology
 In the case of long-term right-sided heart failure,
there
o elevated venous pressure transmitted via the
inferior vena cava and hepatic veins to the
sinusoids of the liver,
o which become dilatedand engorged with
blood.
o The liver becomes enlarged and swollen, and
with long-term passive congestion and
relative ischemia dueto poor circulation,
centrilobular hepatocytes can become
necrotic,leading to pericentral fibrosis.
Clinical features
 enlarged firm liver
 .ALP levels areelevated
 aminotransferases may be normal or slightly
increased
o AST usually higher than ALT.
 unlikely that patients will develop variceal
hemorrhage or encephalopathy.
Diagnosis
 The diagnosis is usually made in someone with clear-
cut cardiacdisease who has an elevated ALP and an
enlarged liver
OTHER TYPES
Hemochromatosis
 is an inherited disorder of iron metabolism that
results in a progressive increase in hepatic iron
 can lead to a portal-based fibrosis progressing to
cirrhosis, liver failure, and hepatocellular cancer.
 Diagnosis-elevated transferrin saturation and an
elevated ferritinlevel,
 Treatment is regular therapeutic phlebotomy.
Wilson’s disease
 is an inherited disorder of copper homeostasis
with failure to excrete excess amounts of copper,
leading to anaccumulation in the liver.
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GASTRO
 Diagnosis requires determination of
ceruloplasminlevels, which are low; 24-hour
urine copper levels, which are elevated
 Kayser- Fleischer corneal rings, and
characteristic liver biopsy findings.
 Treatment consists of copper-chelating
medications
α 1 AT deficiency results
 from an inherited disorder that causesabnormal
folding of the α 1 AT protein, resulting in failure
of secretionof that protein from the liver
 greatest risk for developing chronic liver disease
have the ZZ phenotype
 periodic acid–Schiff (PAS)-positive,
 diastase-resistant globules are seen on liver
biopsy.
 treatment is liver transplantation,
Cystic fibrosis
 is an uncommon inherited disorder affecting
Caucasians of Northern European descent.
 benefit from the chronic useof UDCA.
MAJOR COMPLICATIONS OF CIRRHOSIS
PORTAL HYPERTENSION
 is defined as the elevation of the hepatic venous
pressure gradient (HVPG) to >5 mmHg.
 2 hemodynamic processes:
(1) increased intrahepatic resistance to the passage
of blood flow through the liver due to cirrhosis and
regenerative nodules, and
(2) increased splanchnic blood flow secondary to
vasodilation within the splanchnic vascular bed
Variceal hemorrhage
 is an immediate life-threatening problem with a
20–30% mortality rate associated with each
episode of bleeding.
The causes of portal hypertension are usually
subcategorized as
 prehepatic,
o causes of portal hypertension are those
affecting the portal venous system before it
enters the liver
o they include portal vein thrombosis
o and splenic vein thrombosis
 intrahepatic,
 Presinusoidal
 congenital hepatic fibrosis and
schistosomiasis.
 Sinusoidal
 related to cirrhosis from
variouscauses.
 postsinusoidal
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 CIRRHOSIS AND ITS COMPLICATIONS
 posthepatic.
o causes encompass thoseaffecting the
hepatic veins and venous drainage to
the heart;
o they include BCS, venoocclusive disease,
and chronic right-sided
Clinical features
three primary complications of portal hypertension are
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o gastroesophageal varices with hemorrhage,
o ascites,
o and hypersplenism.
Esophageal varices
 should be identified by endoscopy.
 CT or MRI, a nodular liver and in finding changes
of portal hypertension with intraabdominal
collateral circulation
 The average normal wedged-to-free gradient is 5
mmHg,
 patients with a gradient>12 mmHg are at risk for
variceal hemorrhage.
TREATMENT
1) primary prophylaxis
 endoscopy of all patients with cirrhosis
 nonselective beta blockade by variceal band
ligation.

2) prevention of re-bleeding
 accomplished with repeated variceal band ligation
until varices are obliterated.
 Treatment of acute bleeding requires both fluid
and blood-product replacement as well as
prevention of subsequent bleeding with EVL.
 vasoconstricting agents, usually somatostatin or
Octreotide.
 Balloon tamponade (Sengstaken-Blakemoretube
or Minnesota tube) can be used in patients who
cannot get endoscopic therapy immediately or
who need stabilization prior to endoscopic
therapy.
 Endoscopic intervention is employed as first-line
treatment tocontrol bleeding acutely.
 when bleeding continues from gastric varices,
consideration for transjugular
intrahepaticportosystemic shunt (TIPS) should be
made.
o This technique creates a portosystemic
shunt by a percutaneous approach using
an expandable metal stent, which is
advanced under angiographic guidance to
the hepatic veins and then through the
substance of the liver to create a direct
portocaval shunt.
o This offers an alternative to surgery for
acute decompression of portal
hypertension.
o Encephalopathy-20% of patients
o problematic in elderly patients and
o in those patients with preexisting
encephalopathy.
o Should be reserved for those individuals
who fail endoscopic or medical
management or who are poor surgical
risks.
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 CIRRHOSIS AND ITS COMPLICATIONS
 PREVENTION OF RECURRENT bleeding
o This usually requires repeated variceal band
ligation untilvarices are obliterated.
o Beta blockade may be of adjunctive benefit
in patients who are having recurrent variceal
band ligation;owever, once varices have
been obliterated, the need for beta blockade
is lessened.
o Nonselective beta blockade maybe helpful to
prevent further bleeding from portal
hypertensive gastropathy once varices have
been obliterated.
SPLENOMEGALY AND HYPERSPLENISM
splenomegaly is common in patients with portal
hypertension.
Clinical features: i
o enlarged spleen
o thrombocytopenia nd leukopenia
o left-sided and left upper quadrant abdominal
pain
no specific treatment, although splenectomy can be
successfully performed under very special circumstances.
GASTRO
 When the gradient between the serum albumin level
and the ascitic fluid albumin level is >1.1 g/dL, the
cause of the ascites is most likely due to portal
hypertension; this is usually in the setting of cirrhosis
 When thegradient is <1.1 g/dL, infectious or
malignant causes of ascites should be considered
 When levels of ascitic fluid proteins are very low,
patients are at increased risk for developing SBP.
 A high levelof red blood cells in the ascitic fluid
signifies a traumatic tap orperhaps a hepatocellular
cancer or a ruptured omental varix.
 When the absolute level of polymorphonuclear
leukocytes is >250/μL, the question of ascitic fluid
infection should be strongly considered.
TREATMENT:
 moderate amount of ascites
o diuretic therapy
 spironolactone at 100–200 mg/d as a single
dose is started, and
 furosemide may be added at 40–80 m

ASCITES

Ascites is the accumulation of fluid within the peritoneal

cavity.
the most common cause of ascites is portal hypertension
Clinical features
 an increase in abdominal girth
 peripheral edema.
 usually have at least 1–2 L of fluid in the abdomen
 . If asciticfluid is massive, respiratory function can be
compromised, and patients will complain of shortness
of breath.
 Hepatic hydrothorax
 malnourished
 muscle wasting and excessive fatigue and weakness

Diagnosis
 bulging flanks,
 may havea fluid wave,
 or may have the presence of shifting dullness.
 Hepatic hydrothorax is more common on the right
side
 diagnostic paracentesis be performed to characterize
the fluid.
o This should include the determination of total
protein and albumin content, blood cell counts
with differential, and cultures.
 amylase may be measured and cytology
 patients with cirrhosis, the protein concentration
ofthe ascitic fluid is quite low, with the majority of
patients having an ascitic fluid protein concentration
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<1 g/dL
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SPONTANEOUS BACTERIAL PERITONITIS

SBP is a common and severe complication of ascites
characterized by spontaneous infection of the ascitic fluid
without an intraabdominal source
Bacterial translocation is thepresumed mechanism
for development of SBP, with gut flora traversing he
intestine into mesenteric lymph nodes, leading to
bacteremia and seeding of the ascitic fluid.
The most common organismsare Escherichia coli and
other gut bacteria;
If more than two organisms arere identified, secondary
bacterial peritonitis due to a perforated viscus should be
considered.
Diagnosis:fluid sample has an absolute neutrophil count
>250/μL.
Treatment -second-generation cephalosporin, with
cefotaxime
.

HEPATORENAL SYNDROME

The hepatorenal syndrome (HRS) is a form of functional

renal failure without renal pathology
There are marked disturbances in the arterial renal
circulation in patients with HRS;
o these include an increase in vascular resistance
accompanied by a reduction in systemic vascular
resistance.
Diagnosis -presence of a large amount of ascites in
patients who have a stepwise progressive increase in
creat inine.

2014 -2015

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 CIRRHOSIS AND ITS COMPLICATIONS
TYPES
 Type 1 HRS
o is characterized by a progressive impairment in
renal function
o a significant reduction in creatinine clearance
within 1–2 weeks of presentation.
 Type 2 HRS
o is characterized by a reduction in glomerular
filtration rate with an elevation of serum
creatinine level
o fairly stable,with a better outcome than that of
Type 1 HRS.
.Treatment –difficult
o past(dopamine or prostaglandin analogues
were used as renal vasodilating medications).
o Currently, patients are treated with midodrine,
an α-agonist, along with octreotide and
intrave- nous albumin.
o The best therapy for HRS is liver
transplantation
HEPATIC ENCEPHALOPATHY
defined as an alteration in mental status and cognitive
function occurring in the presence of liver failure.
In acute liver injury with fulminant hepatic failure, the
development of encephalopathy is a requirement for a
diagnosis of fulminant failure. E
ncephalopathy is much more commonly seen in
patients with chronic liver disease.
Ammonia levels are typically elevated in patients with
hepatic encephalopathy
Clinical features
 In acute liver failure, changes in mental status can
occur within weeks to months.
 Brain edema can be seen in these patients, with
severe encephalopathy associated with swelling of
the gray matter.
 Cerebral herniation is a feared complication of brain
edema in acute liver failure
o treatment is meant to decrease edema with
mannitol and judicious use of intravenous
fluids.
 often found as a result of certain precipitating events
such as
o hypokalemia,
o infection,
o an increased dietary protein load
o , or electrolyte disturbances.
 confused or exhibit a change in personality.
 quite violent and difficult to manage; alternatively,
patients
 may be very sleepy and difficult to rouse.
 Asterixis is often present-
o extend their arms and bend their wrists back
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GASTRO
o “liver flap”—a sudden forward movement of
the wrist.
 diagnosis :clinical and requires an experienced
clinician.
TREATMENT
 hydration and correction of electrolyte imbalance
 restriction of dietary protein was considered for
patients with encephalopathy;
o discouraged. There may be some benefit to
replacing animal-based protein with
vegetable-based protein in some patients
with enceph alopathy that is difficult to
manage.
 The mainstay of treatment :
o lactulose, a nonabsorbable disaccharide,
which results in colonic acidification.
 Catharsis ensues, contributing to the elimination
of nitrogenous products in the gut that are
responsible for the development of
encephalopathy.
 The goal of lactulose therapy is to promote 2–3
soft stools per day.
 Poorly absorbed antibiotics are often used as
adjunctive therapies(neomycin and metronidazole)
 neomycin for renal insufficiency and
ototoxicity
 metronidazole for peripheral neuropathy.
 rifaximin at 550 mg twice daily has been very
effective in treating encephalopathy without
the known side
 Zinc supplementation
 .Intravenous or intramuscular vitamin K
OTHERS:
BONE DISEASE
 Dual x-ray absorptiometry (DEXA) is a useful method
for deter mining osteoporosis or osteopenia in
patients with chronic liver disease.
 treatment bisphosphonates that are effective at
inhibiting resorption of bone and efficacious in the
treatment of osteoporosis.
HEMATOLOGIC ABNORMALITIES IN CIRRHOSIS
Macrocytosis is a common abnormality in red blood cell
morphology seen in patients with chronic liver disease,
and neutropenia may be seen as a result of
hypersplenism.
MALNUTRITION IN CIRRHOSIS
 . Dietary supplementation for patients with
cirrhosis is helpful in preventing patients from
becoming catabolic.
ABNORMALITIES IN COAGULATION
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