1. CIRRHOSIS

2. • Cirrhosis is a condition that is defined
histopathologically.
characterised by:
 Development of fibrosis
 Architectural distortion
 Formation of regenerative nodules
• This results :
 Decrease in hepatocellular mass, and thus
function,
 Alteration of blood flow.

4. • Patients who have cirrhosis have varying
degrees liver function
Stable, Compensated cirrhosis
Decompensated cirrhosis.
• Patients who have developed complications of
their liver disease and have become
decompensated should be considered for liver
transplantation

5. Causes
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Alcoholic Cirrhosis(50%)
Chronic viral Hepatitis
Autoimmune hepatitis
Nonalcoholic steatohepatitis
Biliary cirrhosis
Cardiac cirrhosis
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Hemochromatosis
Wilson's disease
Alpha 1 Antitrypsin deficiency
Cystic fibrosis
Cryptogenic cirrhosis

6. Symptoms
• Patient may present with complications of
chronic liver disease:
o Ascites
o Edema,
o Upper gastrointestinal hemorrhage
o Jaundice
o Encephalopathy.

7. Signs
• The liver and spleen may be enlarged, with the liver edge being firm
and nodular.
• Scleral icterus,
• Palmar erythema
• Spider angiomas
• Parotid gland enlargement,
• Fetor Hepaticus.
• Digital clubbing, white nails.
• muscle wasting,
• Edema and ascites.
• Dupuytrens Contracture, Flapping tremors.
• Men may have decreased body hair and gynecomastia as well as
testicular atrophy,
• In women with advanced alcoholic cirrhosis, menstrual
irregularities usually occur.
• Kayser Fleischer rings should be looked for in all young cirrhotics.

8. Investigations
• Laboratory tests may be completely normal in patients
with early compensated cirrhosis.
• Decreased Serum Albumin Levels may be the only
abnormality.
• Bilirubin (may remain normal),aminotransferases and
prothrombin time may rise with progressing disease.
• ALP is elevated in patients with biliary cirrhosis.
• Platelet counts are often reduced early in the disease.
• Ultrasonography is the most informative and least
costly imaging technique.

9. Model for End stage Liver Disease.
MELD Score =
3.78[serum bilirubin (mg/dL)] + 11.2[Ln INR] +
9.57[serum creatinine (mg/dL)] + 6.43.
3 month Mortality
•
•
•
•
•
40 or more — 71.3% mortality
30–39 — 52.6% mortality
20–29 — 19.6% mortality
10–19 — 6.0% mortality
<9 — 1.9% mortality

10. Child Pugh Score
Measure
Total bilirubin,
(mg/dl)
1 point
2 points
3 points
(<2)
(2-3)
(>3)
Serum albumin, g/dl >3.5
2.8-3.5
<2.8
PT INR
<1.7
1.71-2.30
> 2.30
Ascites
None
Mild
Moderate to Severe
Hepatic
encephalopathy
None
Grade I-II (or
suppressed with
medication)
Grade III-IV (or
refractory)
Points
5-6
7-9
10-15
Class
A
B
C
One year survival
100%
81%
45%
Two year survival
85%
57%
35%

11. Alcoholic Liver Disease.
• Cause several different types of chronic liver disease:
1. alcoholic fatty liver,
2. alcoholic hepatitis, alcoholic
3. cirrhosis.
Chronic alcohol use can produce fibrosis in the absence of
accompanying inflammation and/or necrosis(80 g/day for 10 to 20
years).
• A unique form of hemolytic anemia (with spur cells and
acanthocytes) with hyperlipoproteinaemia called Zieve's syndrome
can occur in patients with severe alcoholic hepatitis.
• The underlying cause is liver delipidization, that can occur during
withdrawal from prolonged alcohol abuse.
• AST levels are higher than ALT levels, usually by a 2:1 ratio.

12. Treatment
• Abstinence of alcohol is the cornerstone of therapy
• In patients for Discrimination Fraction. >32, there is improved
survival at 28 days with the use of glucocorticoids.
The DF is calculated as the serum total bilirubin plus the difference in
the patient's prothrombin time compared to control (in seconds)
multiplied by 4
• Oral Pentoxifylline, which decreases the production of tumor
necrosis factor (TNF-) and other proinflammatory cytokines.
• Inhibitors of TNF- such as infliximab or etanercept.; however, there
was no clear-cut improvement in survival.
• Anabolic steroids,
• Propylthiouracil,
• Aantioxidants,
• Colchicine,
• penicillamine have all been used but do not show clear-cut benefits
and are not recommended.

13. Cirrhosis Due to Chronic
Viral Hepatitis B or C
• Several clinical trials demonstrated that patients with
decompensated liver disease can become
compensated with the use of antiviral therapy directed
against hepatitis B
• Interferon should not be used in cirrhotics.
• Treatment of patients with cirrhosis due to hepatitis C
is a little more difficult because the side effects of
pegylated interferon and ribavirin therapy are
oftentimes difficult to manage.
• If patients can tolerate treatment, and if it is successful,
the benefit is great and disease progression is reduced.

14. Autoimmine hepatitis
• Many patients with autoimmune hepatitis (AIH)
present with cirrhosis that is already established.
• Patients will not benefit from immunosuppressive
therapy with because the AIH is "burned out.“
• Diagnosis is supported by (ANA) or anti-smooth-muscle
antibody (ASMA).
• When patients with AIH present with cirrhosis and
active inflammation accompanied by elevated liver
enzymes, there can be benefit from the use of
immunosuppressive therapy.[ Glucocorticoids and
Azathioprine]

15. Biliary Cirrhosis.
• Biliary cirrhosis has pathologic features that
are different from other forms of cirrhosis.
o
o
o
o
Cholate stasis;
Copper deposition;
Xanthomatous transformation of hepatocytes;
Irregular, so-called biliary fibrosis
• Due to Abnormal bile retention: intrahepatic
and extrahepatic.

16. The major causes of chronic cholestatic
syndromes are
• Primary biliary cirrhosis (PBC),
• Autoimmune cholangitis (AIC),
• Primary sclerosing cholangitis (PSC),
• Idiopathic adulthood ductopenia

17. Primary Biliary Cirrhosis
• Strong female preponderance
• The cause is unknown
• A median age of around 50 years at the time
of diagnosis.
• Portal inflammation and necrosis of
cholangiocytes in small- and medium-sized
bile ducts.
• Antimitochondrial antibodies (AMA) are
present in about 90% of patients with PBC

18. • Most patients are actually asymptomatic
• Fatigue out of proportion to the severity of the
liver disease
• Pruritus is seen 50% of patients and it can be
debilitating…usually is most bothersome in the
evening.
• Hyperpigmentation, xanthelasma, and
xanthomata, which are related to the altered
cholesterol metabolism seen in this disease.
• There is an increased incidence of osteopenia and
osteoporosis in patients with cholestatic liver
disease, and bone density testing should be
performed

19. • UDCA (15 mg/kg/day)has been shown to slow
the rate of progression of PBC, but it does not
reverse or cure the disease.
• Pruritus is treated with antihistamines,
naltrexone, and rifampin.
• Plasmapheresis has been used rarely in
patients with severe intractable pruritus.
• Bisphosphonate should be instituted when
bone disease is identified.

20. Primary Sclerosing Cholangitis




Characterized by diffuse inflammation and fibrosis involving the entire biliary tree.
Fatigue, pruritus, steatorrhea, deficiencies of fat-soluble vitamins.
As in PBC, the fatigue is profound and nonspecific.
Metabolic bone disease is also seen.
•
•
•
(p-ANCA), is positive in about 65% of patients with PSC
Over 50% of patients with PSC also have ulcerative colitis
The definitive diagnosis of PSC requires cholangiographic imaging.
is the first choice]
[MRCP
 There is no specific proven treatment for PSC, although studies are currently
ongoing using high-dose (20 mg/kg per day) UDCA to determine its benefit.
 Endoscopic dilatation of dominant strictures can be helpful.
 Cholangiocarcinoma can develop, which is a contraindication to Liver
transplantation.

21. Complications of Cirrhosis

22. • Portal hypertension
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Gastroesophageal varices
Portal hypertensive gastropathy
Splenomegaly, hypersplenism
Ascites
Spontaneous bacterial peritonitis
• Hepatorenal syndrome
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Type 1
Type 2
Hepatic encephalopathy
Hepatopulmonary syndrome
Portopulmonary hypertension
Malnutrition

23. • Coagulopathy
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•
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Factor deficiency
Fibrinolysis
Thrombocytopenia
• Bone disease
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Osteopenia
Osteoporosis
Osteomalacia
• Hematologic abnormalities
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Anemia
Hemolysis
Thrombocytopenia
Neutropenia

24. Portal Hypertension
• Portal hypertension is defined as the elevation of the hepatic
venous pressure gradient (HVPG) to >5 mmHg. It is a result of:
• (1) increased intrahepatic resistance to the passage of blood flow
through the liver due to cirrhosis and regenerative nodules
• (2) increased splanchnic blood flow secondary to vasodilation
within the splanchnic vascular bed
• The three primary complications of portal hypertension are
1. Gastroesophageal varices with hemorrhage,
2. Ascites, and
3. Hypersplenism

25. Esophageal varices
• Approximately one-third of patients with histologically
confirmed cirrhosis have varices.
• The majority of patients with cirrhosis will develop
varices over their lifetimes.
• One-third of patients with varices will develop
bleeding.
• TREATMENT:
• (1) Primary prophylaxis
• (2) Prevention of re-bleeding once there has been an
initial variceal hemorrhage.

26. • Primary prophylaxis requires routine screening
by endoscopy of all patients with cirrhosis.
• Once varices that are at increased risk for
bleeding are identified, primary prophylaxis
can be achieved
1. Through nonselective beta blockade or
2. variceal band ligation

27. Variceal haemorrage.
• Treatment of Acute bleeding requires both fluid and blood-product
replacement as well as prevention of subsequent bleeding with
EVL.
• The use of vasoconstricting agents, usually somatostatin or
Octreotide.
• Balloon tamponade 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 to
control bleeding acutely.
• When bleeding continues from gastric varices, consideration for
transjugular intrahepatic portosystemic shunt (TIPS) should be
made.
• Encephalopathy can occur in as many as 20% of patients after TIPS

28. Prevention of rebleed
• This usually requires repeated variceal band
ligation until varices are obliterated.
• Despite successful variceal obliteration, many
patients will still have portal hypertensive
gastropathy from which bleeding can occur.
• Nonselective beta blockade may be helpful to
prevent further bleeding from portal
hypertensive gastropathy once varices have
been obliterated.

29. Splenomegaly and Hypersplenism.
• Congestive splenomegaly is common in patients
with portal hypertension.
• Splenomegaly itself usually requires no specific
treatment.
• Hypersplenism with the development of
thrombocytopenia is a common feature of
patients with cirrhosis .
• It is usually the first indication of portal
hypertension.

30. Ascites
.

31. • Patients usually have at least 1–2 L of fluid in the abdomen
before they are aware that there is an increase.
• When patients present with ascites for the first time, it is
recommended that a diagnostic paracentesis be performed
to characterize the fluid.
• In patients with cirrhosis, the protein concentration of the
ascitic fluid is quite low, with the majority of patients
having an ascitic fluid protein concentration <1 g/dL
• 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

32. Treatment.
• Sodium Restriction : ingest <2 g of sodium per day,
which is the recommended amount.
• Traditionally, spironolactone at 100–200 mg/d as a
single dose is started, and furosemide may be added at
40–80 mg/d.
• spironolactone can be increased to 400–600 mg/d and
furosemide increased to 120–160 mg/d.
• If ascites is still present with these dosages of diuretics
in patients who are compliant with a low-sodium diet,
then they are defined as having refractory ascites.

33. Managing refractory ascitis.
o Repeated large-volume paracentesis,+ Albumin
Infusion.
o TIPS procedure should be done . It does not improve
survival in these patientsbe considered . Unfortunately,
TIPS is often associated with an increased frequency of
hepatic encephalopathy.
• The prognosis for patients with cirrhosis with ascites is
poor, and some studies have shown that <50% of
patients survive 2 years after the onset of ascites.

34. Spontaneous Bacterial Peritonitis
• Spontaneous infection of the ascitic fluid without
an intraabdominal source.
• Bacterial translocation is the presumed
mechanism.
• SBP can occur in up to 30% of individuals and can
have a 25% in-hospital mortality rate.
• The most common organisms are Escherichia coli
and other gut bacteria; however, gram-positive
bacteria, including Streptococcus viridans,
Staphylococcus aureus, and Enterococcus sp., can
also be found.

35. • The diagnosis of SBP is made when the fluid sample has an absolute
neutrophil count >250/μL.
• If more than two organisms are identified, secondary bacterial
peritonitis due to a perforated viscus should be considered.
• Treatment is with a second-generation cephalosporin, with
cefotaxime being the most commonly used antibiotic
• In patients with variceal hemorrhage, the frequency of SBP is
significantly increased, and prophylaxis against SBP is
recommended.
• Furthermore, in patients who have had an episode(s) of SBP and
recovered, once-weekly administration of antibiotics is used as
prophylaxis for recurrent SBP.

36. Hepatoernal Syndrome.
• Form of functional renal failure without renal
pathology that occurs in about 10% of patients with
advanced cirrhosis or acute liver failure.
• There is marked disturbance in the arterial renal
circulation in patients with HRS.
• There is reduction in systemic vascular resistance
• The reason for renal vasoconstriction is most likely
multifactorial
• HRS is often seen in patients with refractory ascites and
requires exclusion of other causes of acute renal failure

37. • Type 1 HRS is characterized by a progressive impairment in
renal function and a significant reduction in creatinine
clearance within 1–2 weeks of presentation.
• Type 2 HRS is characterized by a reduction in glomerular
filtration rate with an elevation of serum creatinine level,
but it is fairly stable and is associated with a better
outcome than that of Type 1 HRS.
• Patients are treated with midodrine, an -agonist, along with
octreotide and intravenous albumin.
• The prognosis is poor unless transplant can be achieved
within a short period of time.

38. Hepatic Encephalopathy.
• Broadly defined as an alteration in mental status and
cognitive function occurring in the presence of liver
failure.
• Gut-derived neurotoxins that are not removed by the
liver because of vascular shunting and decreased
hepatic mass get to the brain and cause the symptoms
.
• The correlation between severity of liver disease and
height of ammonia levels is often poor.
• Other compounds that may contribute to the
development of encephalopathy include certain false
neurotransmitters and mercaptans.

39. Precipitating events :
• Hypokalemia,
• Infection, an
• Increased dietary protein load,
• Electrolyte disturbances.
• If patients have ascites, this should be tapped to rule
out infection.
• In patients presenting with encephalopathy, asterixis is
often present

40. • Hydration and correction of electrolyte imbalance.
• Restrtiction of dietary protien is discouraged.
• There may be some benefit to replacing animal-based protein with
vegetable-based protein.
• The mainstay of treatment, is to use lactulose, a nonabsorbable
disaccharide, which results in colonic acidification, 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 .
• Rifaximin at 550 mg twice daily has been very effective without the known
side effects of neomycin (oto, nephrotoxicity) or metronidazole(peripheral
neuropathy).
• Zinc supplementation is sometimes helpful

41. Malnutrition in Cirrhosis
• Poor dietary intake,
• Alterations in gut nutrient absorption,
• Alterations in protein metabolism.
• Dietary supplementation for patients with
cirrhosis is helpful in preventing patients from
becoming catabolic.

42. Abnormalities in coagulation.
• There is decreased synthesis of clotting factors
and impaired clearance of anticoagulants.
• Patients may have thrombocytopenia from
hypersplenism due to portal hypertension.
• Platelet function is often abnormal in patients
with chronic liver disease, in addition to
decreases in platelet levels due to
hypersplenism.

43. Bone disease in Cirrhosis
• Osteoporosis is common in patients with chronic
cholestatic liver disease because of
malabsorption of vitamin D and decreased
calcium ingestion.
• Dual x-ray absorptiometry (DEXA) is a useful
method for determining osteoporosis or
osteopenia.
• Treatment should be administered with
bisphosphonates that are effective at inhibiting
resorption of bone

44. Hematological Abnormalities.
ANEMIA from a variety of causes including
o hypersplenism,
o hemolysis,
o iron deficiency
o folate deficiency from malnutrition.
• Macrocytosis is a common abnormality.
• Neutropenia may result as a result of
hypersplenism.

45. Hepatopulmonary syndrome
• Hepatopulmonary syndrome is a syndrome
of shortness of breath and hypoxemia) caused
by vasodilation in the lungs of patients with liver
disease.
• Platypnoea is a peculiar feature.
• Results from the formation of microscopic
intrapulmonary arteriovenous dilatations in patients
with both chronic and acute liver failure.
• Increased hepatic production or decreased hepatic
clearance of vasodilators, possibly involving nitric
oxide.

46. Thank You.