1. Cirrhosis
Dr. Gerrard Uy

2. Cirrhosis a histopathologically defined condition
pathologic features consist of the development of fibrosis to the point that there is architectural distortion with the formation of regenerative nodules
Decreased mass and function

4. Alcoholic Cirrhosis Excessive alcohol use can lead to development of:
alcoholic fatty liver
alcoholic hepatitis
alcoholic cirrhosis
Chronic alcohol use can produce fibrosis in the absence of accompanying inflammation

5. Alcoholic Cirrhosis Pathogenesis:
Alcohol is the most commonly used drug in US
Ethanol is mainly absorbed by the small intestine
Three enzyme systems account for metabolism of alcohol in the liver
majority of ethanol oxidation occurs via ADH to form acetaldehyde
acetaldehyde-mediated hepatocyte damage
Hepatocyte loss occurs, and with increased collagen production and deposition
liver contracts and shrinks in size

6. Alcoholic Cirrhosis Clinical Features:
requires an accurate history regarding both amount and duration of alcohol consumption
nonspecific symptoms such as vague right upper quadrant pain, fever, nausea and vomiting, diarrhea, anorexia, and malaise
more specific complications of chronic liver disease, including ascites, edema, or upper gastrointestinal (GI) hemorrhage
jaundice or encephalopathy

7. Alcoholic Cirrhosis Physical Exam: Hepatomegaly, splenomegaly
scleral icterus, palmar erythema, spider angiomas, parotid gland enlargement, digital clubbing, muscle wasting, or the development of edema and ascites
Men: decreased body hair and gynecomastia
Women: menstrual irregularities

9. Alcoholic Cirrhosis Lab tests:
may be completely normal – early cirrhosis
advanced liver disease:
Anemia
Serum total bilirubin can be normal or elevated
Prothrombin times are often prolonged
aminotransferases (ALT, AST) are typically elevated

10. Alcoholic Cirrhosis Diagnosis: HISTORY AND PE
Liver biopsy can be helpful to confirm a diagnosis but witheld until abstinence has been maintained for at least 6 months

11. Alcoholic Cirrhosis Treatment: ABSTINENCE - cornerstone of therapy
good nutrition and long-term medical supervision
Glucocorticoids – if no infection
Acetaminophen use is often discouraged

12. Cirrhosis due to Hep B and Hep C
hepatitis C virus (HCV)
approximately 80% develop chronic hepatitis C
and of those, about 20–30% will develop cirrhosis over 20–30 years
liver is small and shrunken with characteristic features of a mixed micro- and macronodular cirrhosis
inflammatory infiltrate is found in portal areas

13. Cirrhosis due to Hep B and Hep C
hepatitis B
about 5% develop chronic hepatitis B
and about 20% of those patients will go on to develop cirrhosis
ENDEMIC in southeast asia
up to 15% of the population may be infected having acquired the infection vertically at the time of birth

14. Cirrhosis due to Hep B and Hep C
CLINICAL FEATURES
can present with the usual symptoms and signs of chronic liver disease
Fatigue, malaise, vague right upper quadrant pain, and laboratory abnormalities
including quantitative HCV RNA testing and analysis for HCV genotype
hepatitis B serologies to include HBsAg, anti-HBs, HBeAg (hepatitis B e antigen), anti-HBe, and quantitative HBV DNA levels

15. Cirrhosis due to Hep B and Hep C
TREATMENT
Management of complications
beneficial effects of antiviral therapy – chr Hep B
Treatment of patients with cirrhosis due to hepatitis C is a little more difficult because the side effects of pegylated interferon and ribavirin
if it is successful, the benefit is great and disease progression is reduced

16. Biliary Cirrhosis Depends on the anatomic site of involvement:
Intrahepatic obstruction
Extrahepatic obstruction
Common causes:
Primary biliary cirrhosis
Autoimmune cholangitis
Primary sclerosing cholangitis
Idiopathic adulthood ductopenia

17. Primary Biliary Cirrhosis
individuals per million
Strong female preponderance
Median age of around 50 years
Cause is unknown
Characterized by portal inflammation and necrosis of cholangiocytes

18. Primary Biliary Cirrhosis
Pathology
4 distinct stages of the disease
Earliest lesion is chronic nonsuppurative destructive cholangitis
Clinical Features
fatigue out of proportion for the severity of the liver disease and age of the patient
Pruritus is seen in 50% of patients

19. Primary Biliary Cirrhosis
Physical Examination
Jaundice
Complications of chronic liver disease
Features that are unique to PBC
Hyperpigmentation
Xanthelasma
Xanthomata

20. Primary Biliary Cirrhosis
Laboratory Findings
Elevated GGT and ALP
Mildy elevated SGPT and SGOT
Hyperbilirubinemia
Thrombocytopenia
Anemia
leukopenia

21. Primary Biliary Cirrhosis
Diagnosis
Considered in middle aged women with chronic cholestatic liver enzyme abnormalities
Liver biopsy is most important

22. Primary Biliary Cirrhosis
Treatment
Ursodeoxycholic acid (UDCA) have been shown to improve both biochemical and histologic features
13-15 mg/kg/day
Frequent naps should be encouraged
Antihistamines for pruritus
Liver transplantation is the treatment of choice

23. Cardiac Cirrhosis Definition
long-standing right-sided congestive heart failure may develop chronic liver injury and cardiac cirrhosis

24. Cardiac Cirrhosis Pathogenesis:
elevated venous pressure transmitted via the inferior vena cava and hepatic veins to the sinusoids of the liver
become dilated and engorged with blood
liver becomes enlarged and swollen, and with long-term passive congestion and relative ischemia due to poor circulation
become necrotic, leading to pericentral fibrosis

25. Cardiac Cirrhosis Diagnosis
diagnosis is usually made in someone with clear-cut cardiac disease who has an elevated ALP and an enlarged liver

26. Other Types of Cirrhosis
Hemochromatosis
Inherited disorder of iron metabolism that results in progressive increase in hepatic iron deposition leading to cirrhosis and hepatocellular carcinoma
Wilson’s Disease
Inherited disorder of copper homeostasis leading to increase deposition of copper in the liver

27. Major Complications

28. Portal Hypertension
Defined as elevation of the hepatic venous pressure gradient to >5 mmhg
Pathogenesis
Increased intrahepatic resistance to the passage of blood flow through the liver
Increased splanchnic blood flow secondary to vasodilation

29. Portal Hypertension Responsible for 2 major complications of cirrhosis
Variceal hemorrhage
ascites
Subcategorized into prehepatic, intrahepatic, and posthepatic
3 primary complications
Gastroesophageal varices
Ascites
hypersplenism

30. Spontaneous Bacterial Peritonitis
SBP is a common and severe complication of ascites
Can occur in up to 30% of individuals with severe cirrhosis and ascites
Bacterial translocation is the presumed mechanism for the development of SBP

31. Spontaneous Bacterial Peritonitis
Most common organisms:
E. coli
Streptococcus viridans
Staphylococcus aureus
Enterococcus sp.
Diagnosis of SBP is made when the fluid sample has an absolute neutrophil count > 250/mm3
Cefotaxime is the most commonly used antibiotic

32. Hepatorenal syndrome
A form of functional renal failure without renal pathology
Occurs in about 10% of patients with advanced cirrhosis
Diagnosis is made in the presence of a large amount of ascites in patients who have a progressive increase in creatinine
Best therapy is liver transplantation

33. Hepatic Encephalopathy
Defined as an alteration in mental status and cognitive function occurring in the presence of liver failure
Results from accumulation of gut derived neurotoxins
Ammonia levels are typically elevated

34. Hepatic Encephalopathy
Clinical Features
Changes in mental status occurs within weeks to months
Brain edema is usually present
Usually precipitated by:
Hypokalemia
Infection
Dehydration
Increase dietary protein load
Electrolyte imbalance

35. Hepatic Encephalopathy
Treatment
Hydration and correction of electrolyte imbalance
Mainstay of treatment is lactulose
Zinc supplementation can sometimes be helpful