The Spectrum of Hepatic Functional Impairment in Compensated Chronic Hepatitis C: Results From the H

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From Alimentary Pharmacology & Therapeutics

The Spectrum of Hepatic Functional Impairment in Compensated Chronic Hepatitis

C: Results From the Hepatitis C Anti-Viral Long-term Treatment Against Cirrhosis

Trial

Posted 05/22/2008

G. T. Everson; M. L. Shiffman; T. R. ; J. C. Hoefs; R. K. Sterling; D. A.

Wagner; C. C. Kulig; T. M. Curto; E. C. ; The HALT-C Trial Group

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Summary

Background: The spectrum of functional impairment in patients with compensated

chronic hepatitis C is incompletely defined.

Aim: To define hepatic impairment by quantitative tests (quantitative liver

function tests) and correlate results with disease severity in patients with

chronic hepatitis C.

Methods: We studied 285 adult patients with chronic hepatitis C prior to

treatment in the Hepatitis C Anti-viral Long-term Treatment against Cirrhosis

Trial; 171 had Ishak fibrosis stages 2–4 (fibrosis) and 114 had stage 5 or 6

(cirrhosis). None had had clinical decompensation. A battery of 12 quantitative

liver function test assessed the spectrum of hepatic microsomal, mitochondrial

and cytosolic functions, and hepatic and portal blood flow.

Results: Twenty-six to 63% of patients with fibrosis and 45–89% with cirrhosis

had hepatic impairment by quantitative liver function test; patients with

cirrhosis had the greatest impairment (P-value ranging from 0.15 to < 95 and

cholate shunt>35% identified 91% of patients with medium- or large-sized

varices.

Conclusions: Hepatic impairment is common in compensated patients with fibrosis

or cirrhosis because of chronic hepatitis C. Cholate shunt, and cholate Cloral

and perfused hepatic mass, identify patients at risk for cirrhosis or varices.

Introduction

In routine clinical practice, chronic hepatitis C (CHC) is monitored by history

and physical examination, standard blood testing, ultrasonography and liver

biopsy. Goals of monitoring include definition of disease severity, assessment

for progression and evaluation of the impact of treatments or interventions.

Patients with late stages of disease are identified by deterioration in

laboratory tests and development of clinical complications, but patients with

earlier stages of disease have stable laboratory tests and no clinical findings

despite hepatic functional impairment and portal hypertension.[1] Prior to

laboratory or clinical deterioration, the progression of CHC from fibrosis to

cirrhosis disrupts hepatocyte function, distorts the hepatic architecture, and

alters hepatic and portal blood flow. Therefore, tests measuring hepatic

function, blood flow or mass might better define the spectrum of hepatic

impairment in fibrotic stages of CHC prior to obvious laboratory or clinical

deterioration.

Hepatic metabolism, blood flow, portal-systemic shunt and perfused mass can be

defined by administration of test compounds and measuring clearance or

quantifying metabolites.[2-5] These tests are collectively categorized as

quantitative liver function tests (QLFTs). Clearances of certain compounds, such

as aminopyrine, antipyrine, caffeine, erythromycin and formation of

monoethylglycine xylidide (MEGX) from lidocaine, assess hepatic metabolism. In

contrast, clearances of others, such as bile acids, lidocaine, propranolol,

nitroglycerin and indocyaninine green, assess hepatic or portal blood flow.

Simultaneous measurement of clearances of orally and intravenously administered

cholate assesses portal-systemic shunting (cholate shunt).[6] Hepatic uptake of

intravenously administered 99m-technetium (99Tcm) sulphur colloid, measured by

Single Photon Emission liver-spleen scan (SPECT-LSS), defines perfused hepatic

mass (PHM).[7,8]

The primary goal of our study was to define the severity of hepatic impairment

in a cohort of patients with CHC who had fibrosis, including cirrhosis, but who

lacked biochemical or clinical decompensation. In this study, we defined hepatic

impairment from a battery of QLFTs. This battery assessed hepatic metabolic

capacity, hepatic blood flow, portal blood flow, portal-systemic shunt and PHM.

Our study subjects were patients with CHC who were participants in the Hepatitis

C Anti-viral Long-term Treatment against Cirrhosis (HALT-C) Trial.[9] They had

Ishak fibrosis scores from 2 to 6, and, most notably, none had prior clinical

decompensation. Finally, because HALT-C patients were comprehensively evaluated,

we were able to examine relationships of QLFTs to standard laboratory tests,

liver histology, and ultrasonographic and endoscopic findings.

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