Diagnostic Methods For Cirrhosis And Portal Hyp...
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.
Diagnostic Methods for Cirrhosis and Portal Hyp...
Regarding the diagnostic performance of both approaches, although previously transjugular liver biopsy was considered inferior because of the use of thinner needles (18G), there is strong evidence suggesting that the two techniques are similar in terms of sample length and the number of complete portal spaces . The greatest advantage of the transjugular route is that it allows concomitant HVPG measurement and multiple passes without increasing the risk of complications.
Liver fibrosis and its patterns remain of paramount importance in risk stratification of patients, even in those who have fully established liver cirrhosis. Four main patterns of fibrosis development according to different aetiologies are described: (i) portal-to-central fibrosis distribution (characteristic to viral and autoimmune hepatitis); (ii) portal-to-portal distribution (specific for biliary diseases); (iii) perisinusoidal and pericellular distribution (metabolic diseases, alcoholic and non-alcoholic liver diseases) and (iv) central-to-central fibrosis distribution (for venous outflow obstruction such as Budd-Chiari syndrome) . According to the different types of fibrosis distribution, the portal hypertension occurs earlier, as in the case of viral, autoimmune or Budd-Chiari syndrome, or later in the course of the disease, as in the case of metabolic diseases. Interestingly, even if sinusoidal portal hypertension develops later in the case of biliary diseases, due to the portal-to-portal distribution of fibrosis and development of porto-portal septa, there is an increased presinusoidal resistance that will increase portal pressure, so that the HVPG underestimates the value of the portal pressure gradient in patients with cholestatic liver disease.
Magnetic resonance elastography (MRE) has been proposed as a method to evaluate both liver and spleen stiffness, overcoming some of the limitations of ultrasound-elastography methods (no need for an acoustical window, freely oriented field of view, lack of sensitivity to body habitus) [86,87]. MRE has proved to be accurate in stage of liver fibrosis (being marginally better than TE and pSWE in two studies [88,89]) and is a highly promising method for diagnosing cirrhosis in patients unsuitable to ultrasound elastography. It holds high reproducibility and, interestingly, changes in MRE correlate with changes in fibrosis.
Recently, Ronot et al used multiparametric MRE in a small series of 36 patients on the waiting list for orthotopic liver transplantation undergoing HVPG measurement and endoscopy . Three different liver and spleen parameters were assessed, namely storage, loss and shear moduli. The spleen loss modulus was the best parameter for identifying patients with severe portal hypertension (AUC = 0.81, p = 0.019) or high-risk varices (AUC = 0.93, p = 0.042), confirming previous data regarding the potential of spleen stiffness on the evaluation of portal hypertension in cirrhosis.
Ultrasound signs of cirrhosis on grey-scale (B mode) include changes in liver morphology and signs of portal hypertension (Table 4). Most signs have a high specificity and can be considered sufficient to confirm the diagnosis of cirrhosis. On the other hand, the sensitivity of most individual signs is low, indicating that a negative result cannot fully rule out cirrhosis in patients with compensated chronic liver disease.
Similarly to what has previously been discussed regarding cirrhosis, most ultrasound signs of portal hypertensions are specific, but their sensitivity is moderate, especially in compensated cirrhosis; therefore, while the presence of a sign or a combination of signs permits confirming portal hypertension, the absence of ultrasound signs cannot exclude this diagnosis [95,96]. Only two signs are 100% specific (pathognomonic) signs of portal hypertension, namely porto-systemic collaterals (e.g. paraumbilical vein, spleno-renal collaterals, etc.) and reversal of flow in the portal vein system.
Splenomegaly is commonly associated with portal hypertension; this sign is more sensitive than other signs, but less specific. However, increasing spleen size is an independent predictor of gastroesophageal varices in compensated cirrhosis .
Taken together, gray scale and Doppler US are safe, inexpensive and simple to use at the bedside or for outpatients, and combining multiple US indices can improve the diagnostic accuracy of cirrhosis under some conditions.
Esophageal and paraesophageal varices are common complications of cirrhosis, and arise from the impaired venous drainage of the esophageal vein due to increased portal venous pressure. A gastric varix is less common than an esophageal varix and occurs in approximately 20% of patients with PHT. In general, the estimation of the risk of variceal bleeding is made by using endoscopic findings such as the size, color, and location of varices. However, in the era of multidetector CT, which enables CT scanning at a submillimeter thickness, CT can be used to obtain information not only about the cirrhotic liver itself but also about the PHT caused by cirrhosis. Various portosystemic collateral veins can also be depicted in the CT scan, and physicians can plan a strategy for the treatment of varices, including the insertion of a transjugular intrahepatic portosystemic shunt and balloon-occluded retrograde transvenous obliteration. Moreover, as with endoscopy, demonstrating the presence of esophageal and gastric varices is now possible using CT. The sensitivity and specificity of CT were found to be 96% and 55%, respectively, to detect esophageal varices and 93% and 80%, respectively to detect high-risk esophageal varices. Using the 1- to 3-mm multiplanar reformat or surface-shaded display can also increase the specificity of CT for the risk stratification of esophageal varices101. With regard to gastric varices, the sensitivity and specificity were 83%-89% and 75%-79%, respectively[153,154]. Although these results are not bad, the accuracy for small varices remains low.
The complications of portal hypertension can be life-threatening, especially internal bleeding. Not everyone will have these complications, but the risk increases as portal hypertension increases. The greater the pressure, the more enlarged your veins become and the more likely they are to rupture. Portal hypertension is the most common cause of hospitalization and death in people with cirrhosis.
You may not have any symptoms until complications develop. Up to 90% of people with cirrhosis already have portal hypertension before they have symptoms. Up to 40% already have large varices (enlarged veins). The first noticeable symptoms of portal hypertension are usually related to new, enlarged, leaky and bleeding veins, such as:
Liver cirrhosis is the fourth cause of death in adults in Western countries, with complications of portal hypertension being responsible for most casualties. In order to reduce mortality, development of accurate diagnostic methods for early diagnosis, effective etiologic treatment, improved pharmacological therapy for portal hypertension, and effective therapies for end-stage liver failure are required.
Early detection of cirrhosis and portal hypertension is now possible using simple non-invasive methods, leading to the advancement of individualized risk stratification in clinical practice. Despite previous assumptions, cirrhosis can regress if its etiologic cause is effectively removed. Nevertheless, while this is now possible for cirrhosis caused by chronic hepatitis C, the incidence of cirrhosis due to non-alcoholic steatohepatitis has increased dramatically and effective therapies are not yet available. New drugs acting on the dynamic component of hepatic vascular resistance are being studied and will likely improve the future management of portal hypertension.
Over the last decades, new knowledge on the pathophysiology, diagnostic methods, and therapy of cirrhosis and portal hypertension have significantly improved the management of this disease, with a marked reduction in mortality related to some of its complications, particularly variceal bleeding . However, in a recent analysis based on over 100,000 cases, 30-day mortality following discharge for any decompensation of cirrhosis was equal to or even higher than that observed 10 years prior, suggesting that the burden of mortality was merely shifted to the immediate postdischarge period . Among the major determinants of mortality are inflammation in acute-on-chronic liver failure (associated with different complications of end-stage liver disease) and HCC  (not discussed in the present paper), both of which have been the subject of extensive research but remain unsatisfactorily resolved. 041b061a72