The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis

Background & Aims

The aim of this study was to systematically assess the diagnostic and prognostic value of early liver biopsy in patients who require hospital admission with acute deterioration of alcoholic cirrhosis.

Methods

Sixty-eight patients with acute deterioration of alcoholic cirrhosis underwent a liver biopsy within 7 days and the biopsies were processed using routine stains and K8/18 immunohistochemistry to characterize balloon degeneration. The biopsies were scored by two independent histopathologists using pre-defined criteria. The patients were managed according to institutional protocols and followed until the time of hospital discharge or death.

Results

With use of K8/18 immunohistochemistry, very high concordance rate for the diagnosis of balloon degeneration was reached (r = 0.7; p = 0.0001). The presence of a systemic inflammatory response (SIRS) suggestive of acute alcoholic steatohepatitis (ASH), predicts severe ASH histologically in only 50% patients. Moreover, in 41% of SIRS negative patients who were thought not to have ASH, a diagnosis of ASH was subsequently confirmed on histological grading. Patients that have SIRS criteria but no evidence of histological ASH are more likely to develop infection which may be indicated by the severity of canalicular cholestasis. Nineteen patients died during follow up. Patients manifesting ASH on biopsy who were also SIRS positive, had a significantly greater risk of mortality compared to those that were SIRS positive but ASH negative (p <0.01) and those that were SIRS negative (p <0.0001).

Conclusions

The use of K8/18 immunostaining allows grading of the severity of alcoholic steatohepatitis. Early liver biopsy in these patients presenting with acute deterioration of cirrhosis is safe and provides important diagnostic and prognostic information.

Introduction

Alcoholic steatohepatitis (ASH) is a severe end of the spectrum of alcoholic liver disease and often occurs on the background of cirrhosis in patients with a high alcohol intake (alcohol consumption of >80 g alcohol/day for men and >60 g/day for women). Inflammation is believed to play a central role in the development of further liver injury and progression to organ failure [1], [2], [3] and despite some advances in therapeutic interventions, this condition still carries a mortality of over 40% in several series [4]. From the clinical perspective, the diagnosis is made by an appropriate history of alcohol abuse that results in progressive jaundice, requires admission to the hospital, and is associated with evidence of a systemic inflammatory response (SIRS) with no other identifiable cause of liver disease. To date, published data, in which patients have been described as having ASH distinct from decompensated alcoholic cirrhosis, have been obtained in studies assessing interventions targeting inflammation [5], [6], [7], [8], [9]. In these studies, clinical, and inflammatory parameters have been used to define ASH patients, with some studies using liver biopsy to further substantiate the diagnosis. However, at present, it is not clear whether a liver biopsy is useful for diagnosing ASH in patients who are admitted to the hospital with acute deterioration of alcoholic cirrhosis, and there is no agreed systematic grading of liver biopsies to estimate the degree of disease activity on which to classify patients to rationalize intervention. There is also a lack of data defining the relationship between such a histological grade and outcome in ASH. This indeed may be one explanation for the significant differences reported between response to corticosteroid treatment in earlier clinical trials and also for the variation in the responses to anti-tumour necrosis factor alpha (TNFα) strategies reported in the ASH literature [7], [9], [10], [11].

The most important, previously specified manifestations of ASH on biopsy include centrilobular accentuated steatosis, hepatocellular ballooning eventually associated with Mallory-Denk bodies (MDBs) [12], a mixed inflammatory reaction consisting of neutrophilic granulocytes and mononuclear cells, and perivenular and pericellular fibrosis. However, these histological features are not specific for ASH but are also found in liver biopsies of patients with non-alcoholic steatohepatitis (NASH) [12]. Several formal systems used to grade disease activity and stage fibrosis have been proposed for NASH [13] but data on such systems are limited for ASH [14]. Due to the broad overlap of histological features between ASH and NASH, it has been proposed that grading and staging systems of NASH may be adopted for ASH as well [12]. The aim of this study was, therefore, to systematically assess the value of early liver biopsy in patients who require hospital admission with acute deterioration of alcoholic cirrhosis in order to: (i) diagnose ASH, (ii) grade the severity of ASH based on the histological parameters of hepatocellular ballooning and lobular inflammation, and (iii) determine its prognostic value. We also evaluated the prognostic role of measurement of the hepatic venous pressure gradient.