Invasive and non-invasive diagnosis of cirrhosis and portal hypertension

Abstract

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.

Keywords: Hepatic fibrosis; Hepatic venous pressure gradient; Liver biopsy; Non-invasive test; Portal hypertension; Transient elastography.

Figure 1

Heterogeneity of cirrhosis in histology. All pictures are histological finding of cirrhosis however, they show different feature in thickness of sepata and the size of nodules. A: Shows mild cirrhosis with thin septa (MTC stain, × 100); B: Shows moderate cirrhosis with at least two broad septa; C: Shows severe cirrhosis with at least one very broad septa (MTC stain, respectively, × 200). A, B, C are correspond to subclass of Laennec fibrosis scoring system F4A, F4B and F4C respectively, The widths between two arrows show the significant difference among subclass of cirrhosis. n: Regenerating nodule; MTC: Masson trichrome stain[8].

Figure 2

Doppler ultrasonography showing change in the hepatic vein waveform and damping index (A) before and (B) 3 mo after propranolol treatment in a patient with liver cirrhosis. Hepatic vein waveform changed from biphasic to near triphasic, quantitative measurement of damping index (DI) decreased from 0.61 to 0.33 in association with a hepatic venous pressure gradient (HVPG) decrease from 18 to 11 mmHg[92]. HVPG: Hepatic venous pressure gradient.

Figure 3

Hepatic vein enhancement with microbubble contrast-enhanced ultrasound and measurement of Hepatic vein arrival time and the correlation between Hepatic Venous Pressure Gradient and Hepatic vein arrival time. A: Ultrasound images showing the HV (white arrows) before the contrast injection; B: Arrival of microbubble contrast agent in the HV after contrast enhancement; HVAT was calculated as the time (in seconds) from injection to a sustained increase in signal in the TIC to more than 10% above baseline; C: Recorded TIC profile shows early HVAT (11.0 s; the 10-s lead time was subtracted from 21.0 s) in a patient with cirrhosis with HVPG of 20 mmHg; D: Recorded TIC profile shows an HVAT of 27.0 s (37.0 min 10 s) in a healthy control; E: HVAT was significantly linearly correlated with HVPG in the patients with compensated cirrhosis (r² = 0.545; P < 0.001). HV: Hepatic vein; CEUS: Contrast-enhanced ultrasonography; HVAT: Hepatic vein arrival time; HVPG: Hepatic venous pressure gradient; TIC: Time intensity curve[102].