Non-invasive Diagnosis Of Cirrhosis Research Articles

Invasive and non-invasive diagnosis of cirrhosis and portal hypertension.

With advances in the management and treatment of advanced liver disease, including the use of antiviral therapy, a simple, one stage description for advanced fibrotic liver disease has become inadequate. Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential, current diagnostic tests have not kept pace with the progression of this new paradigm. Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension (PHT), respectively, and they have diagnostic and prognostic value. However, they are invasive and, as such, cannot be used repeatedly in clinical practice. The ideal noninvasive test should be safe, easy to perform, inexpensive, reproducible as well as to give numerical and accurate results in real time. It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification. Recently, many types of noninvasive alternative tests have been developed and are under investigation. In particular, imaging and ultrasound based tests, such as transient elastography, have shown promising results. Although most of these noninvasive tests effectively identify severe fibrosis and PHT, the methods available for diagnosing moderate disease status are still insufficient, and further investigation is essential to predict outcomes and individualize therapy in this field.

Noninvasive diagnosis of cirrhosis in chronic hepatitis C based on standard laboratory tests

Noninvasive assessment of hepatic fibrosis is gaining popularity.1, 2 Several noninvasive tests have been proposed, including indirect markers of liver fibrosis composed of routine laboratory parameters. We read with great interest the article by Lok et al.3 on the use of the regression formula log odds = −5.56 − 0.0089 × platelet (×109/L) + 1.26 × AST/ALT ratio + 5.27 × INR (“model 3”) for prediction or exclusion of cirrhosis (Ishak fibrosis score F5–F6) in patients with chronic hepatitis C (CHC). Although this model was developed in a cohort of nonresponders to previous antiviral treatment that comprised patients with more advanced stages of fibrosis (Ishak fibrosis score F3–F6), it was also applied to 265 treatment-naïve CHC patients previously studied,4 confirming its diagnostic accuracy across a broad range of fibrosis (Ishak fibrosis score F0–F6). We recently evaluated several noninvasive tests based on standard laboratory parameters, including the aspartate aminotransferase to platelet ratio index (APRI) and platelet count per se, in a cohort of 194 treatment-naïve CHC patients.5 For external validation, we applied model 3 in our CHC study cohort and compared its diagnostic accuracy for prediction/exclusion of cirrhosis (Ishak fibrosis score F5–F6) with that of platelet count and APRI. Ishak fibrosis score correlated moderately with platelet count, APRI, and model 3 (Spearman's R −0.50, 0.62, and 0.53, respectively). Evaluation of the overall diagnostic accuracies for the prediction of cirrhosis by receiver-operating characteristic analysis revealed comparable results: areas under the receiver-operating characteristic curves for platelet count, APRI, and model 3 were 0.89, 0.90, and 0.90, respectively. Our findings on the diagnostic accuracy of model 3 for prediction/exclusion of cirrhosis are very similar to the results reported by Lok et al. (Table 1). Each of the noninvasive tests evaluated was more suited for exclusion of cirrhosis than for its prediction. Using the reported cutoff values of ≥150 × 109/L (platelet count), <1.0 (APRI), and <0.2 (model 3), each of the tests reliably excluded cirrhosis with a negative predictive value of 95% or more in 78%, 59%, and 49% of patients, respectively. Conversely, prediction of cirrhosis using a cutoff value of <150 × 109/L (platelet count), ≥2.0 (APRI), and ≥0.5 (model 3) was much less reliable (positive predictive value 56%, 59%, and 58%, respectively). Our data confirm the excellent diagnostic accuracy of model 3 for the exclusion of cirrhosis; however, we would like to point out that the platelet count per se allows the exclusion of cirrhosis with a fair degree of accuracy without the need for a calculator or computer. Exclusion of cirrhosis in patients with CHC is important, because costly diagnostic workup may be avoided, including (1) endoscopic screening for esophageal varices and (2) surveillance for hepatocellular carcinoma via regular ultrasound and α-fetoprotein examinations. In treatment-naïve patients with CHC typically seen in a referral center, cirrhosis can be reliably excluded in a considerable number of patients using simple noninvasive fibrosis tests based on routine laboratory parameters. Carolin Lackner*, Gerd Struber*, Csilla Bankuti , Bernd Bauer , Rudolf E. Stauber , * Department of Pathology, Medical University Graz, Graz, Austria, Department of Internal Medicine, Medical University Graz, Graz, Austria, Department of Internal Medicine, Landeskrankenhaus Hoergas, Gratwein, Austria.

Earlier hepatic vein transit-time measured by contrast ultrasonography reflects intrahepatic hemodynamic changes accompanying cirrhosis

Background/Aims: Non-invasive diagnosis of cirrhosis by transit-time analysis of an ultrasound contrast agent has been reported, even though the mechanism by which contrast arrives to the hepatic vein earlier in cirrhosis than in normal controls is unknown. The aim of this study is to assess whether the earlier appearance of contrast in the hepatic vein depends on intrahepatic or extrahepatic causes. Methods: There were 15 participants: six volunteers, three patients with hepatitis, and six with cirrhosis. The contrast agent was given intravenously, and transit-time analysis of the hepatic artery, portal vein and hepatic vein was performed. The time-acoustic intensity curves in the three vessels were analyzed by an image and cineloop display and quantification software package. Results: The hepatic artery and portal vein arrival times were not significantly different among the three groups. On the other hand, hepatic vein arrival times were significantly earlier in cirrhosis (median 18 seconds) compared with arrival times in hepatitis patients (median 30 seconds, P<0.001) and in healthy volunters (median 31 seconds, P<0.001). These results give support to a previous pilot study and indicate that most of the time delay in hepatic vein arrival time between cirrhosis and the other groups originated from intrahepatic circulation abnormalities. Conclusions: This study confirms that the earlier appearance of contrast in the hepatic vein observed in cirrhosis is due to intrahepatic, and not extrahepatic, hemodynamic changes.