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SOURCE

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Source: Sease JM, Clements JN. Portal hypertension and cirrhosis. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146059650. Accessed January 23, 2017.

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DEFINITION

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  • Chronic liver injury causes damage to normal liver tissue resulting in the development of regenerative nodules surrounded by fibrous bands.

  • Cirrhosis is an advanced stage of liver fibrosis that leads to shunting of the portal and arterial blood supply directly into hepatic outflow through the central veins with compromised exchange between hepatic sinusoids and hepatocytes.

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EPIDEMIOLOGY

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  • Exact prevalence is unknown, but estimated 1% of the population has histologically diagnosable cirrhosis.

  • Chronic liver disease and cirrhosis responsible for nearly 35,000 deaths in the United States in 2012.

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ETIOLOGY

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  • Most common causes are excessive alcohol intake and chronic viral hepatitis (types B and C, Table 1).

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Table Graphic Jump Location
TABLE 1.Etiology of Cirrhosis
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PATHOPHYSIOLOGY

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  • Elevation of portal blood pressure because of fibrotic changes within hepatic sinusoids, changes in levels of vasodilatory and vasoconstrictor mediators, and increase in blood flow to splanchnic vasculature.

  • Resistance to blood flow contributes to portal hypertension and the development of varices, ascites, hepatic encephalopathy (HE), and coagulopathy.

  • Portal hypertension is characterized by:

    • Hypervolemia.

    • Increased cardiac index.

    • Hypotension.

    • Decreased systemic vascular resistance.

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CLINICAL PRESENTATION

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  • Ranges from asymptomatic, with abnormal laboratory or radiographic tests, to decompensated with ascites, spontaneous bacterial peritonitis, HE, or variceal bleeding.

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SIGNS AND SYMPTOMS
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  • Anorexia.

  • Malaise.

  • Weight loss.

  • Pruritus.

  • Jaundice.

  • Palmar erythema.

  • Spider angiomata.

  • Hyperpigmentation.

  • Hepatomegaly.

  • Splenomegaly.

  • Gynecomastia and reduced libido.

  • Ascites.

  • Edema.

  • Pleural effusion.

  • Respiratory difficulties.

  • Coagulopathy.

  • Mental status changes.

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DIAGNOSIS

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MEANS OF CONFIRMATION AND DIAGNOSIS
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  • Child–Pugh classification system to assess and define severity of cirrhosis and predict patient survival, surgical outcome, and risk of variceal bleeding.

  • MELD scoring system takes into account a patient’s serum creatinine, bilirubin, INR, and etiology of liver disease.

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LABORATORY TESTS
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  • No laboratory or radiographic tests of hepatic function can accurately diagnose cirrhosis.

  • Elevated alkaline phosphatase.

  • Elevated aspartate transaminase (AST), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT)

    • Markers of hepatocyte integrity.

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