1. Internal medicine L-4 Liver cirrhosis & portal hypertension
Prepared by:
Kholod Hamad
MSc clinical pharmacy, BCPS

2. Cirrhosis
Cirrhosis is defined as fibrosis of the hepatic parenchyma resulting in nodule formation, altered hepatic function, restricted venous outflow, and portal hypertension.
It results from a sustained wound-healing response to chronic or acute liver injury from a variety of causes, the most common being chronic viral hepatitis chronic alcohol consumption.

3. The illustration below shows the nodular changes that occur in cirrhosis

4. Cirrhosis Hepatocytes fibrous tissue Complications Portal hypertension
Varices and ascites
Hepatic encephalopathy (HE)
Coagulopathy

6. Child-Pugh Classification of the Severity of Cirrhosis
Class A = total score of 5 or 6
Class B = total score of 7–9
Class C = total score of 10 or more

7. Model for End-Stage Liver Disease (MELD)

8. Gastroesophageal Varices
Background
a. Resistance to blood flow within the liver secondary to cirrhosis results in the development of portal hypertension. Collateral blood vessels (e.g., esophageal varices) are formed because of this increased resistance to blood flow.
b. Variceal hemorrhage may occur in around 25%–35% of patients with cirrhosis and varices; mortality rates are as high as 30%–50% per bleed; recurrence rates are as high as 70% within the first 6 months after an initial bleed.

9. Gastroesophageal Varices

10. Management of acute variceal bleeding
Fluid resuscitation and hemodynamic stabilization
Endoscopy to assess the extent of disease with potential intervention
Medical management of acute variceal bleeding to reduce splanchnic blood flow and portal pressure (Vasopressin, Octreotide)
Antibiotic therapy

11. Ascites
Definition: Free fluid in the abdominal cavity secondary to increased resistance within the liver (forces lymphatic drainage into the abdominal cavity) and reduced osmotic pressure within the bloodstream (hypoalbuminemia); develops at a 5-year cumulative rate of 30% in compensated liver disease

12. Ascites

13. Clinical features: Protuberant abdomen, shifting dullness, fluid wave, bulging flanks, abdominal pain
Diagnosis
a. Clinical features
b. Abdominal ultrasonography
c. Paracentesis. Can use serum-ascites albumin gradient, calculated by subtracting the ascites albumin concentration from the serum albumin concentration; a value greater than 1.1 indicates ascites secondary to portal hypertension

14. Treatment of Ascites Alcohol cessation if alcohol induced
Dietary sodium restriction and water restriction
Diuretics: combination of furosemide and spironolactone (ratio 40:100)
If tense ascites is present, may use large-volume paracentesis. Administer albumin at a dose of 6–8 g/L of ascitic fluid removed over 5 L
If refractory ascites is present, may consider midodrine add-on therapy

15. Spontaneous Bacterial Peritonitis
Background
Infection of previously sterile ascitic fluid without an apparent intra-abdominal source. SBP is considered a primary, as opposed to secondary, peritonitis.
May be present in 10%–30% of hospitalized patients with cirrhosis and ascites c. A ssociated with 20%–40% of in-hospital mortality; poor prognosis after recovery, with 2-year survival after initial episode reported as about 30%

16. Pathophysiology
Principal theory is seeding of the ascitic fluid from an episode of bacteremia.
The bacteria present are usually enteric pathogens; thus, they may enter the blood because of increases in gut permeability secondary to portal hypertension, suppression of hepatic reticuloendothelial cells, or translocation of the gut wall and dissemination through the mesenteric lymph system.

17. Reduced opsonic activity of the ascitic fluid and alterations in neutrophil function may also be contributing factors.
Enteric gram-negative pathogens are most commonly involved, and more than 90% of cases involve a single bacterial species.

18. Management
Broad-spectrum antibiotic therapy to cover Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae.
IV Cefotaxime or Oral ofloxacin
Antibiotic prophylaxis with daily norfloxacin 400 mg or double-strength trimethoprim-sulfamethoxazole.

19. References
Clinical pharmacy & therapeutics, Edi 5, chapter 16 Liver disease. Page 238