Role of liver biopsy in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the "gold standard" for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

Histological features and severity of oxaliplatin-induced liver injury and clinical associations.

OBJECTIVE: Oxaliplatin, a component of chemotherapy for colorectal carcinoma liver metastases, can result in hepatic sinusoidal injury; rarely, the injury is fatal. The manifestations of injury are variable. There are no known predictors of susceptibility and outcome. A semi-quantitative system for assessing histological features in non-tumor liver was designed to compare with clinical short-term and long-term outcomes. METHODS: A review of 47 patients with metastatic colorectal carcinoma who received liver resection utilizing a system for an aggregate liver injury score (0-4) included hepatocellular and sinusoidal features. Immunohistochemistry (IHC) for aberrant capillarization was included. The proliferation of hepatocytes and sinusoidal lining cells was evaluated with Ki-67 stain. RESULTS: In total, 32 (68.1%) cases showed light microscopic lesions of oxaliplatin-induced liver injury, in which 26 were moderate to severe. Elevated preoperative aspartate aminotransferase (AST) and alkaline phosphatase levels were noted with higher injury scores (P = 0.01). Patients with higher injury scores had no significant increase in short-term postoperative complications, with one notable exception, who died of liver failure 10 months postoperatively. Increased CD34 expression was associated with higher injury scores (P = 0.00004), and abnormal AST levels (P = 0.04). Preoperative use of bevacizumab was not associated with lower injury scores. Steatosis was correlated with body mass index (P = 0.052) but not with exposure to oxaliplatin, bevacizumab or irinotecan. CONCLUSIONS: The proposed liver injury scoring system encompasses the spectrum of sinusoidal and hepatocellular lesions in oxaliplatin-induced liver injury and is correlated with serum liver enzyme levels in this group. Most patients recovered without complications during the 93-month follow-up, indicating that these lesions are reversible.