Alcoholic liver disease

doi:10.1053/j.semdp.2006.11.002

Seminars in Diagnostic Pathology

Volume 23, Issues 3–4, August–November 2006, Pages 149-160

https://doi.org/10.1053/j.semdp.2006.11.002 Get rights and content

Alcohol excess is associated with a spectrum of disease ranging from simple steatosis through steatohepatitis to cirrhosis and, in some, hepatocellular carcinoma. Alcoholic steatohepatitis itself has a variable histological picture, but a constant feature is the presence of ballooning degeneration of hepatocytes. Recent studies have emphasized the importance of apoptosis as a mechanism of cell death in this condition. It is accompanied by varying degrees of perivenular, centrilobular, and pericellular fibrosis. When severe and associated with perivenular liver cell necrosis (central sclerosing hyaline necrosis), there may be precirrhotic portal hypertension. The pattern of fibrosis may initially be diffuse with little nodule formation, but in time there is frequently the development of a micronodular cirrhosis. In approximately 15% of patients with established cirrhosis, hepatocellular carcinoma develops; several precursor lesions are now recognized which can be detected histologically. Several authors have drawn attention to additional components of the spectrum of alcoholic liver disease, including vascular changes, portal tract inflammation and fibrosis, ductular reaction, and iron overload. The morphology of alcoholic liver disease can be significantly affected by abstinence; furthermore, the clinical and morphological phenotype can be significantly influenced by the presence of comorbid conditions such as nonalcoholic fatty liver disease or viral hepatitis. Biopsy appearances can provide important prognostic information in alcoholic liver disease, and this review incorporates a proposed grading and staging schema for assessment of histological severity.

Section snippets

Steatosis

Steatosis—the accumulation of lipids within hepatocytes—is the earliest histological abnormality with alcohol-induced injury.10, 12 It is observed in the vast majority of individuals with a history of chronic alcohol abuse and is largely explicable on biochemical grounds as a consequence of the interactions between alcohol and lipid metabolism13, 14; as noted below, fat may disappear at the stage of cirrhosis in some who continue to imbibe. There are three histological patterns of steatosis

“Noninflammatory” perivenular fibrosis

As noted above, perivenular fibrosis is a common accompanying feature of alcoholic steatohepatitis. In some cases, however, such thickening of the terminal hepatic venules may be present in the absence of necroinflammation and accompanied by pericellular fibrosis in acinar zone 3. This may represent an intermediate stage between steatosis and cirrhosis, representing a distinct pathway from that which involves steatohepatitis. This concept is supported by observations in experimental ALD in

Effects of abstinence

Progressive ALD carries a poor prognosis; this is particularly the case for those developing the clinical syndrome of acute alcoholic hepatitis. Treatment is generally aimed at providing nutritional support and encouraging abstinence from alcohol, although there is increasing interest in other therapeutic interventions.⁷⁰ Abstinence in most centers is a prerequisite for those being considered for transplantation for end-stage cirrhosis.⁷¹ Cessation of alcohol can lead to changes in the

Other fatty liver diseases

Although we generally consider ALD and NAFLD as separate entities, there may, in some patients, be a contribution from both. Thus, obesity and other features of metabolic syndrome are now known to be risk factors for more advanced ALD.66, 73, 74, 78 Interestingly, steatosis has also been identified as a cofactor in the development of more advanced disease in genetic hemochromatosis and in hepatitis C infection.⁷⁵ It remains possible that alcohol plays a role in some patients labeled as having

Distinction between alcoholic and non-alcoholic fatty liver disease

The histological changes seen in ALD are not pathognomonic, and there is considerable overlap with other conditions. There are numerous causes of simple steatosis, and Mallory bodies are also noted in a wide range of conditions.¹⁰ Steatohepatitis is frequently seen in patients with metabolic syndrome but is also encountered following some forms of bowel surgery, notably jejunoileal bypass and intestinal resections.¹⁰ Several therapeutic agents may also give rise to nonalcoholic steatohepatitis,

Prognostication in ALD: grading and staging

Although there is a relationship between cumulative alcohol intake and severity of disease, alcohol is seen to be permissive and the clinical phenotype is influenced by other genetic and environmental factors. It is therefore difficult to predict the prognosis in individual patients. Clinically scoring systems, notably MELD⁸³ and the Glasgow scale,⁸⁴ have been developed to predict outcome as have surrogate markers.⁸⁵ Important information can also, however, be gleaned from histological

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