Histological-hemodynamic correlation in cirrhosis—a histological classification of the severity of cirrhosis
Introduction
Cirrhosis is the end result of chronic liver disease and is defined histologically by the presence of regenerative nodules surrounded by fibrous tissue. This architectural distortion leads to increased intrahepatic resistance that in turn leads to portal hypertension. Complications of cirrhosis, including esophageal varices and ascites, develop once portal pressure reaches a threshold level of 10–12 mmHg, as assessed by the hepatic venous pressure gradient (HVPG) [1], [2], [3]. This threshold level has been found to be of great prognostic value and has been termed ‘clinically significant portal hypertension’ (CSPH) [4], [5].
The extent of fibrosis on liver biopsy is used to evaluate the stage or severity of chronic liver disease, with the most severe stage being the cirrhotic stage. However, the sole histological diagnosis of cirrhosis does not denote the clinical severity of cirrhosis. Determining a relationship between specific histologic parameters on liver biopsies from cirrhotic patients and portal pressure would be valuable in determining whether certain histologic parameters can be used to sub-classify cirrhosis by its ‘severity’. This relationship would be of prognostic value, not only regarding the development of clinical complications, but also regarding the potential for reversibility.
Additionally, this correlation would provide further insight into the pathophysiology of portal hypertension and the relationship that various histologic parameters, such as steatosis and inflammatory activity, have on portal pressure.
Therefore, the aim of this study is to determine the relationship between portal pressure, as determined by the HVPG, and specific histologic parameters on liver biopsies diagnosed as having cirrhosis, and to determine whether any of these parameters correlate with the presence of CSPH and can, therefore, identify different severities of histologic cirrhosis.
Section snippets
Patients
Patients who had a liver biopsy specimen (obtained via a transjugular or percutaneous approach) and hepatic venous pressure measurements (HVPG) performed within six months of each other were included in the study. At our institution, HVPG measurements are performed routinely at the time of transjugular liver biopsy.
Histological assessment
In our institution, all liver biopsies performed for medical disorders are fixed in formalin and routinely stained with the hemotoxylin-eosin (H&E), reticulin, Masson trichrome, DPAS
Results
In the period between 1994 and 2002, 88 patients had a liver biopsy performed within 6 months of HVPG measurements. Nineteen patients were excluded due to (i) fragmented, small specimens (n=2), or (ii) a histological diagnosis unrelated to chronic liver diseases (passive congestion (n=4); graft vs. host disease (n=8), chronic rejection (n=2), sarcoidosis (n=1), drug reaction (n=2)). Of the 69 remaining patients, 19 patients had earlier stages of chronic liver disease (stages 1–3), and seven
Discussion
Liver biopsy remains the gold standard for staging diffuse liver disease. Staging is based on the extent of fibrosis and architectural distortion, and in all classification systems, the most advanced stage is the cirrhotic stage. Although it has been suggested that histological cirrhosis can be further subclassified into different severities [8], this assessment has been based solely on the characteristics of fibrous septae.
Since most complications of cirrhosis are secondary to portal
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