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Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

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In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
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Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

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Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
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Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

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Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
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Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

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In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
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Hepatic Drug Excretion: Influencing Factors01:16

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The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
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Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals.

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  • 1Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA.

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Summary
This summary is machine-generated.

Serum alpha-fetoprotein (AFP) significantly decreased in hepatitis C virus (HCV) patients with cirrhosis after successful direct-acting antiviral (DAA) treatment. This finding suggests AFP may be a viable biomarker for hepatocellular carcinoma (HCC) screening post-HCV cure.

Keywords:
Direct-acting antiviralsHepatitis CHepatocellular carcinomaScreening

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Area of Science:

  • Hepatology
  • Oncology
  • Virology

Background:

  • Serum alpha-fetoprotein (AFP) has limited specificity for hepatocellular carcinoma (HCC) screening in hepatitis C virus (HCV)-related cirrhosis.
  • Direct-acting antiviral (DAA) therapy offers a sustained virological response (SVR) for HCV infection.
  • The impact of SVR achieved through DAAs on AFP levels in HCV-cirrhosis patients remains unclear.

Purpose of the Study:

  • To investigate whether serum AFP levels decrease after achieving SVR in patients with HCV-related cirrhosis treated with DAAs.
  • To explore potential correlations between AFP reduction and baseline clinical parameters.

Main Methods:

  • Retrospective study of 56 HCV-cirrhosis patients treated with DAAs at UCLA.
  • Serum AFP levels measured pre-treatment, end-of-treatment, and 12 weeks post-treatment.
  • Analysis of correlations between AFP reduction and baseline MELD, FIB4, APRI, platelet count, AST, and total bilirubin.

Main Results:

  • AFP levels significantly decreased from a median of 7.2 ng/mL pre-DAA to 4.2 ng/mL post-treatment (p < 0.001).
  • Baseline MELD, FIB4, and APRI scores were not significantly associated with AFP reduction.
  • Platelet count, AST, and total bilirubin at baseline were significantly correlated with AFP reduction (p = 0.04, 0.009, 0.04 respectively).

Conclusions:

  • Achieving SVR with DAAs leads to a significant reduction in serum AFP levels in patients with HCV-related cirrhosis.
  • The observed AFP reduction warrants further investigation into its potential role as an HCC screening biomarker post-DAA therapy.
  • Higher baseline AFP levels correlated with greater reduction, suggesting a dynamic response to treatment.