The Role of Liver Biopsy in Chronic Hepatitis C
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This study looks at using several blood work tests to see if they are useful for people with HCV so as to avoid biopsies. The authors conclude that biopsy is required to assess the stage of liver disease, disease activity, to address prognosis, and to manage disease including treatment.

In this study, the authors evaluated the utility of liver biopsy in patients with chronic hepatitis C and its role in excluding other forms of liver pathology and in establishing the stage of liver disease. Furthermore, they calculated a cirrhosis discriminant score16 to predict cirrhosis in patients with chronic hepatitis C infection. The cirrhosis determinant score predicted the presence of cirrhosis found by biopsy 32% of the time (12/37). In 82 of 85 cases the cirrhosis discriminant score predicted a finding of no cirrhosis from biopsy. The study data showed that no alternative diagnoses (0 of 126) and few additional diagnoses (3 of 126), all of which consisted of variants of NASH, were provided by liver biopsy. None of these would preclude interferon-based antiviral therapy for hepatitis C.

The authors conclude, the role of sequential liver biopsy in clinical research in assessing the natural history of HCV infection or the impact of therapy on the rate of progression of fibrosis remains important. In the future, development of accurate indirect markers of fibrosis (procollagen peptide III, hyaluronidase, etc.) may further refine our ability to detect fibrosis or cirrhosis without a liver biopsy. Until these markers are developed and validated, liver biopsy remains important in the majority of patients with HCV.

Possible additional diagnoses were suspected prebiopsy in 47 patients. These included alcohol-induced liver disease, hepatitis B, hemochromatosis, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, medication-induced disease, and other miscellaneous causes including graft-versus-host disease, malignancy, granulomatous disease, and cytomegalovirus hepatitis. Additional suspected diagnoses were confirmed in 3 of 47 patients (6.4%): these included hereditary hemochromatosis (n = 1), steatohepatitis (n = 1), and hepatitis B (n = 1). Unsuspected additional diagnoses were discovered by the liver biopsy in only 3 patients: NASH (n = 2) and steatosis alone (n = 1). Two of these patients were obese and 1 was also diabetic. Only 1 had no obvious risk factors for NASH. All cases of hepatitis C seen at the Cleveland Clinic Department of Gastroenterology between January 31, 1990 and February 1, 1997 were identified. Records of patients infected with HCV who met the following inclusion criteria were reviewed: (1) an abnormal alanine transaminase (ALT) level, defined as a value greater than 40 IU/L on at least 2 separate occasions (values of ALT were not adjusted for sex and body mass index)17; (2) positive enzyme-linked immunosorbent assay antibody for HCV confirmed by supplemental testing either by recombinant immunoblot assay (RIBA) or HCV RNA (polymerase chain reaction or branched DNA); and (3) a liver biopsy after serologic testing was performed. Clinical and demographic data, laboratory data, and the clinicians' prebiopsy diagnosis (primary diagnosis and additional diagnoses) as well as clinical suspicion for cirrhosis were recorded. Prebiopsy suspicion of cirrhosis required one or more of the following: reduced platelet or white blood cell counts, prothrombin time elevation, prominent abdominal venous collaterals, and history of ascites, esophageal varices, or hepatic encephalopathy. Suspected additional diagnoses included alcohol-induced liver disease, hepatitis B, iron-induced liver disease, autoimmune disease, and nonalcoholic fatty liver disease. Information regarding former or current use of alcohol at the time of biopsy was abstracted. Up to 3 months before the liver biopsy, laboratory data were collected, which included measurements of white blood cell count, platelet count, prothrombin time, and international normalized ratio of the prothrombin time (INR), ALT/aspartate transaminase (AST) ratio, hepatitis A and B serologies, smooth muscle antibody titer, anti-nuclear antibody titer, anti-mitochondrial antibody titer, serum iron, ferritin, total iron binding capacity, 1 antitrypsin, ceruloplasmin, bilirubin, lactate dehydrogenase, and alkaline phosphatase levels. Physical findings and signs of cirrhosis (ascites, hepatosplenomegaly, spider angiomata) were also recorded, using a standardized liver-specific physical examination form.

A cirrhosis discriminant score based on the platelet count, ALT/AST ratio, and INR was calculated using Bonacini's method. The presence or absence of fibrosis and or cirrhosis in the liver biopsy specimens was recorded. All liver biopsy specimens were reviewed by experienced hepatopathologists and were scored using the histologic activity index, developed by Knodell et al.18 This included the presence of portal and/or parenchymal inflammation, bile duct damage, steatosis, fibrosis, and cirrhosis.

Liver Biopsy Required to Identify the Stage of Liver disease and to Establish the Presence of Cirrhosis

A cirrhosis discriminant score can predict cirrhosis without a liver biopsy in a minority of HCV-infected patients.16,25 A discriminant score of greater than 7 predicts cirrhosis and less than 3 predicts no cirrhosis. By using this score in our patients, liver biopsy could have been avoided in approximately 23% of patients (26 of 111). However, for the larger group (>75% [85 of 111]) with a discriminant score of 3 to 7, a liver biopsy was required to define the stage of their liver disease and to establish the presence or absence of cirrhosis. This finding has an important prognostic implication and can influence further management options of patients with chronic hepatitis C. In a recent study reported by Poynard et al.,12 the lack of fibrosis or fibrosis limited to the portal tract was associated with favorable outcome and sustained virologic response to antiviral therapy. In this regard, discriminant score analysis is inferior to liver biopsy in establishing the presence or absence of fibrosis and/or cirrhosis, and its role in the clinical management of these patients remains limited.

Authors Conclude Biopsy is Safe

No major biopsy complications were reported from the 126 liver biopsies performed. Minor complications included pain not requiring medication in 12 (9.5%), pain requiring medication in 19 (15.1%), hypotension/vasovagal reaction in 2 (1.6%), and admission to an emergency room or hospital in 4 (3.2%). There was no difference related to the method used for liver biopsy.