2. GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER
Cirrhosis
Irregular surface
Slide 6
GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER
Gross images of two livers. On the left a normal liver with a smooth surface and homogeneous appearance. On the right a cirrhotic liver with an irregular surface and nodules that give it a heterogeneous appearance.
Nodules

3. Causes of Liver Disease: Cirrhosis
Viral Hepatitis: B and C
Genetic Liver Disease: Hemochromatosis, Wilson’s Disease
Alcohol
NASH (non alcoholic steatohepatitis)
Autoimmune Liver Disease
Cryptogenic

4. Synthetic Function:measured by Bilirubin, albumin and INR
Two aspects of Liver Disease
Synthetic Function:measured by Bilirubin, albumin and INR
Portal Hypertension

7. NORMAL VASCULAR ANATOMY OF THE LIVER
Hepatic vein
Coronary vein
Sinusoid
Liver
Slide 43
NORMAL VASCULAR ANATOMY OF THE LIVER
The liver has a dual blood supply: portal vein and hepatic artery. The portal vein is formed by the union of the superior mesenteric vein (that collects blood from the bowel) with the splenic vein (that collects blood from the spleen). Normally, blood from the coronary vein drains into the portal system. After progressive ramifications, blood from the portal vein and hepatic artery join at the hepatic sinusoids, a specialized capillary system that is extensively interconnected. Hepatic sinusoidal blood drains into hepatic venules and then into collecting veins that unite to form the hepatic veins through which blood leaves the liver, draining into the vena cava and the right heart.
Portal vein
Splenic vein
Hepatic artery
Inferior
vena cava
Superior
mesenteric vein
Inferior
mesenteric vein

8. Portal systemic collaterals Cirrhotic Liver
ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCE
Portal systemic collaterals
Cirrhotic Liver
Distorted sinusoidal architecture
leads to increased resistance
Slide 48
ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCE
The deposition of fibrous tissue and the formation of nodules, disrupts the architecture of the liver, leading to an increased resistance to flow and to portal hypertension. Vessels that normally drain into the portal system, such as the coronary vein, reverse their flow and become porto-systemic collaterals. Additionally, with portal hypertension, the spleen increases in size and sequesters platelets and other formed blood cells leading to hypersplenism.
Portal vein
Splenomegaly

9. Complications of Cirrhosis:
Esophageal and gastric Varices
Ascites
Hepatic Encephalopathy
Hepatorenal Syndrome

10. DIAGNOSIS OF CIRRHOSIS – CAT SCAN
CAT Scan in Cirrhosis
Slide 23
DIAGNOSIS OF CIRRHOSIS – CAT SCAN
This slide shows typical computed tomography findings in compensated cirrhosis. The contour of the liver is irregular, there is obvious splenomegaly and the presence of collaterals indicates portal hypertension and secures the diagnosis of cirrhosis.
Liver with an irregular surface
Collaterals
Splenomegaly

11. VARICES INCREASE IN DIAMETER PROGRESSIVELY
Slide 82
VARICES INCREASE IN DIAMETER PROGRESSIVELY
Both development of varices and growth of small varices occurs at a rate of 7-8% per year. Although there are no identified clinical predictors for the development of varices, factors associated with variceal growth are Child B/C cirrhosis, alcoholic etiology and presence of red wale marks on initial endoscopy.
Merli et al., J Hepatol 2003; 38: 266
No varices
Small varices
Large varices
7-8%/year
7-8%/year
Merli et al. J Hepatol 2003;38:266

12. PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE
Slide 97
PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE
In a prospective study, the presence of the following clinical features was associated with a high probability of developing variceal hemorrhage: large variceal size, Child B/C and the presence of red wale markings on varices.
North Italian Endoscopic Club. N Engl J Med 1988; 319: 983
Variceal hemorrhage
Varix with red signs
Predictors of hemorrhage:
Variceal size
Red signs
Child B/C
NIEC. N Engl J Med 1988; 319:983

13. Acute Variceal Bleeding Initial Management
Assessment of severity/resuscitation
airway protection for massive bleed or if agitated
Blood and fluid replacement
Pharmacology therapy
Octreotide
Endoscopy for diagnosis and therapy
Variceal ligation
Sclerotherapy
Balloon tamponade

14. Acute Variceal Bleeding Endoscopic Ligation
Bleeding controlled in 90%
Rebleeding rate reduced to 30%
Band to “obliteration”

15. Acute Variceal Bleeding Sclerotherapy
Bleeding controlled in 80-95%
Rarely used now- massive bleeds?

16. ENDOSCOPIC IMAGES OF GASTRIC VARICES
Slide 189
ENDOSCOPIC IMAGES OF GASTRIC VARICES
The arrow on the panel on the left shows an actively bleeding gastric varix. The panel on the right shows the varix after treatment with cyanoacrylate.
Pretreatment cyanoacrylate
Post-treatment cyanoacrylate

17. Treatment of Varices / Variceal Hemorrhage
MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage
No varices
Small varices
No hemorrhage
1) -blockers (propranolol, nadolol) indefinitely
2) Endoscopic variceal ligation in patients intolerant to -blockers
Medium/ large varices
No hemorrhage
Slide 121
MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR HEMORRHAGE
In patients with medium/large varices who have never bled, non-selective beta-blockers (propranolol, nadolol) should be considered first line therapy in the prevention of first variceal hemorrhage. Endoscopic band ligation can be considered in patients intolerant to beta-blockers or who have contraindications to beta-blockers.
Variceal
hemorrhage
Recurrent
hemorrhage

18. Variceal Bleeding Bleeding Ectopic Varices

19. Tips Transjugular Intrahepatic Portosystemic Shunt

20. ENDOSCOPIC IMAGES OF MILD AND SEVERE PORTAL HYPERTENSIVE GASTROPATHY
Slide 192
ENDOSCOPIC IMAGES OF MILD AND SEVERE PORTAL HYPERTENSIVE GASTROPATHY
Mild portal hypertensive gastropathy (left panel) is characterized by a mosaic pattern. Severe gastropathy consists of a mosaic pattern with superimposed red signs.
Mosaic pattern
Mosaic pattern + red spots
Carpinelli et al. Ital J Gastroenterol Hepatol 1997; 29:533

23. Ascites Malignancy Chronic Liver Disease Heart Failure Turberculosis
Miscellaneous
Nephrogenic
Pancreatic
Fulminant Hepatic Failure
Biliary Leak

24. Ascites

26. Ascites Pathogenesis: Hypotheses
Underfill
Overflow
Vasodilation
Cirrhosis
Portal Hypertension
Primary renal sodium retention (? Stimulus)
Peripheral arterial vasodilation
Ascites
Effective Intravascular volume
Effective Intravascular volume
Blood volume
Renal sodium retention
Renal sodium retention
Ascites

28. Ascites Diagnosis Paracentesis
Indications
New-onset ascites
Admission to hospital
Clinical deterioration
Fever
Contraindications
None

29. Ascites Fluid Analysis
Routine
Cell count
Culture
Albumin
Protein
Optional
Glucose
LDH
Amylase
Gram stain
TB smear and culture
Cytology
Triglyceride

30. Ascites Serum-Ascites Albumin Gradient
[Albumin] – [Albumin]
Serum
Ascites
High (> 11 g/L)
Cirrhosis; alcoholic hepatitis
Cardiac disease
Massive liver metastases
Fulminant hepatic failure
Hepatic outflow block
Portal vein thrombosis
Low (< 11 g/L)
Peritoneal carcinomatosis
Tuberculous peritonitis
Pancreatic duct leak
Biliary leak
Nephrotic syndrome
Serositis

31. Ascites

32. Ascites

33. Ascites Initial Therapy
Sodium restriction
Diuretics
Spironolactone +/- furosemide
Stepwise increase as needed to maximal doses
Large volume paracentesis (for tense ascites)

34. Ascites Therapy of Refractory Ascites

35. Ascites Complications

36. Spontaneous Bacterial Peritonitis (SBP)

37. Spontaneous Bacterial Peritonitis:SBP
Usually caused by gram-negative bacteria and usually only one organism: only 50% of cultures positive
If neutrophil count high in ascites: ie > 250/cc-treat with IV Cefotaxime, even if culture negative
Prophylaxis for SBP or recurrent SBP controversial: high resistance rates develop

38. SURVIVAL AFTER DEVELOPMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)
1.0 .8 .4 .2 .6 3 6 12 24 36
Probability of survival (%)
Slide 297
SURVIVAL AFTER DEVELOPMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)
The development of SBP in a cirrhotic patient with ascites carries a poor prognosis. In a cohort of 75 patients with SBP the one-year survival was 38%, with a median survival of only 9 months.
Tito L, et al., Hepatology 1988; 8(1): 27-31
Months
Tito et al., Hepatology 1988; 8:27

39. Hepatic Encephalopathy
Reversible neuropsychiatric abnormalities
Asterixis and abnormal EEG
Hepatic failure and/or portosystemic shunting

41. Hepatic Encephalopathy

43. BLOOD AMMONIA LEVELS ONLY LEAD TO CONFUSION
“Blood ammonia levels cause as much confusion in those requesting the measurement as in the patients in whom they are being measured”
Slide 356
BLOOD AMMONIA LEVELS ONLY LEAD TO CONFUSION
Adrian Reuben
Hepatology 2002;35:983

44. Hepatic Encephalophathy

45. Hepatic Encephalophathy Precipitants

46. Hepatic Encephalophathy Actions of Lactulose

47. Hepatorenal Syndrome Identify other causes
Establish circulatory volume
Avoid nephrotoxic agents
Consider hemodialysis
Evaluate for liver transplatation

48. Hepatorenal Syndrome Evidence for a Functional Disorder

53. Hematologic Manifestations of Cirrhosis
Mild Anemia and Macrocytosis
Neutropenia secondary to splenic sequestration
Thrombocytopenia secondary to splenic sequestration
Prolonged INR secondary to decreased production of clotting factors by liver

54. Hepatocellular Carcinoma
Other names are Hepatoma, Primary Liver Cell Cancer
Develop in Cirrhotic livers especially Hepatitis B and C
May produce a protein tumour marker: alphafetoprotein
Ultrasound screening every 6 months for early detection

58. Complications of Cirrhosis

59. Child-Pugh Criteria 1 point 2 points 3 points Bilirubin (mg/dL)
Albumin (g/L)
PT (sec prolonged)
Ascites
Encephalopathy
<2
>35
1-3
none
2-3
28-35
4-6
Slight
1-2
>3
<28
>6
Moderate
3-4
Grades: A = 5-6 points; B = 7-9 points; C = 10-15

60. Causes of death in Cirrhosis
Infection
Variceal bleeding
Hepatic encephalopathy
Hepatocellular carcinoma

61. # Hospitalized cirrhotic patients
SPONTANEOUS BACTERIAL PERITONITIS (SBP) IS THE MOST COMMON INFECTION IN CIRRHOTIC PATIENTS
Spontaneous Bacterial Peritonitis (SBP) is the Most Common Infection in Cirrhotic Patients
150
125
100
# Hospitalized cirrhotic patients 75 50
Slide 264
SPONTANEOUS BACTERIAL PERITONITIS (SBP) IS THE MOST COMMON INFECTION IN CIRRHOTIC PATIENTS
In a study of 1,567 admissions for decompensated cirrhosis, bacterial infections developed at admission or during hospitalization in 507 (32%) patients (572 infectious episodes). SBP was the most common type of bacterial infection, present in 138 (24%) of the cases, followed by urinary tract infections (UTI) and pneumonia.
Fernández J, et al., Hepatology 2002; 35: 140 25
SBP
UTI
Pneumonia
Procedure-
related
Spontaneous
Bacteremia
Fernández et al., Hepatology 2002; 35:140

62. SURVIVAL TIMES IN CIRRHOSIS
Decompensation Shortens Survival
100 80
Median survival
~ 9 years
All patients with cirrhosis 60
Probability of survival 40
Slide 16
SURVIVAL TIMES IN CIRRHOSIS
In a prospective cohort study of 257 patients with compensated cirrhosis of different etiologies, median survival for all patients (including those who developed decompensation) was approximately 9 years, while it was significantly lower in patients who developed a decompensating event (ascites, jaundice, encephalopathy or hemorrhage), in whom the median survival was only 1.6 years.
Gines et al. Hepatology 1987; 7:122 20
Decompensated cirrhosis
Median survival
~ 1.6 years 20 40 60 80
100
120
140
160
180
Months
Gines et. al., Hepatology 1987;7:122

63. Liver Transplantation
Only proven treatment for advanced cirrhosis
Long waiting list: insufficient donors
Allocation by MELD score (Bilirubin, creatinine, INR)
Patients with recent alcohol or drug abuse, extrahepatic malignancies or other major co-morbidities excluded

64. Treatment of Fulmimant Liver Failure
Supportive measures
Transfer to transplant centre if encephalopathic
?Mars
Improve with time or need liver transplant
1st on Waiting list for Transplant

65. GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER
Cirrhosis
Irregular surface
Slide 6
GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER
Gross images of two livers. On the left a normal liver with a smooth surface and homogeneous appearance. On the right a cirrhotic liver with an irregular surface and nodules that give it a heterogeneous appearance.
Nodules

66. Causes of Liver Disease: Cirrhosis
Viral Hepatitis: B and C
Genetic Liver Disease: Hemochromatosis, Wilson’s Disease
Alcohol
NASH (non alcoholic steatohepatitis)
Autoimmune Liver Disease
Cryptogenic