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News Review

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HEPATITIS JOURNAL REVIEW:
A Bi-Monthly Publication of the Hepatitis Support Project

October 12 , 2005 Volume 2, Issue 15


Liz Highleyman

To download pdf version click here


In This Issue: Hepatitis C

Liver Biopsy in Patients with Normal ALT

Fine-Needle Aspiration Biopsy

Reconsidering the Role of Liver Biopsy

Family and Household HCV Transmission


Liver Biopsy in Patients with Normal ALT

Several recent journal articles have looked at the role of liver biopsy in the management of hepatitis C. In the October 2005 Journal of Hepatology, T. Okanoue and colleagues from Japan conducted a long-term follow-up study of 129 HCV positive individuals with persistently normal aminotransferase (ALT) levels. At baseline, 17 had normal liver histology, 102 had mild hepatitis, and 10 had moderate hepatitis. A subset of 69 patients was followed for a mean 8.5 years; 35 of these had serial liver biopsies. During this time, 10 maintained persistently normal ALT levels, 39 had transient ALT elevations, and 20 developed symptomatic hepatitis; the rate of fibrosis progression in these three groups was 0.05, 0.04, and 0.08, respectively. The authors concluded that 30% of chronic HCV carriers became candidates for hepatitis C treatment within five years. This study suggests the need for regular liver biopsies (most experts recommend every 3-5 years) even in hepatitis C patients with normal ALT levels, since liver damage can occur in the absence of liver enzyme elevation.

Nevertheless, researchers continue to search for less invasive alternatives to biopsy. Also looking at patients with persistently normal ALT (never exceeding 1.2 times the upper limit of normal), C. Colletta and colleagues from Italy studied 40 HCV positive participants who underwent two liver biopsies (median interval 78.5 months apart), as well as the shear elasticity test (Fibroscan, a method of elastography) and evaluation using the FibroTest algorithm – two experimental noninvasive means of determining fibrosis progression. The researchers found that Fibroscan yielded results that corresponded closely with those obtained from biopsy, but that FibroTest performed poorly; these findings were published in the October issue of Hepatology.

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Fine-Needle Aspiration Biopsy

In the September Journal of Viral Hepatitis, D. Sprengers and colleagues from the Netherlands reported on another use for biopsy: monitoring the response of immune cells – such as T-cells and natural killer cells - within the liver. Such monitoring is currently not of much clinical use in predicting disease progression or response to therapy, so it typically would not justify a standard tissue-needle biopsy. The researchers instead used a fine-needle aspiration biopsy (FNAB) technique. They found that flow cytometry results from FNAB samples were similar to those from tissue biopsy samples, but differed from peripheral blood cell samples. They concluded that fine-needle aspiration biopsy allows “easy, atraumatic and reliable” analysis of immune cells within the liver, and thus is “a valuable tool in the study of the immunopathology of viral hepatitis.”

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Reconsidering the Role of Liver Biopsy

While tissue biopsy remains the “gold standard” for monitoring liver disease progression, not all experts agree on when the procedure is appropriate, considering the expense, discomfort, and small risk of complications. As reported in the September Journal of Hepatology, N. Alamasio and colleagues surveyed 61 Italian experts on hepatitis C (gastroenterologists, hepatologists, and infectious disease and internal medicine specialists), asking them whether they would recommend liver biopsy in 12 clinical scenarios. In four cases, a majority of experts (61-86%) agreed not to perform liver biopsy; in two cases, opinions were about evenly split; and in six cases, a majority recommended biopsy. In a second round of questioning in an attempt to determine a consensus, 54 out of 431 (13%) of the original judgments were changed. The researchers concluded that the survey “showed a great divergence of management of similar patients and should provide a stimulus for an evidence-based evaluation of liver histology in chronic HCV infection.”

In an editorial in the same issue, Steven Herrine and Lawrence Friedman discuss the role of liver biopsy in hepatitis C management. They note that both the European Association for the Study of the Liver and the National Institutes of Health recommend liver biopsy to aid clinical decision-making in hepatitis C patients, thus establishing it as the standard of care. To date, they conclude, noninvasive techniques (blood tests, biochemical panels, imaging techniques, elastography) “have not inspired sufficient confidence to displace reliance on hepatic histology.” Nevertheless, “[o]pinion regarding the use of liver biopsy in the management of chronic hepatitis C is likely to remain a moving target,” as new noninvasive methods emerge. In addition, the future role of liver biopsy will be influenced by the availability of new biomarkers of matrix metabolism that indicate fibrosis progression. Herrine and Friedman conclude that it is premature to scale back the use of liver biopsy at this time. “As long as histologic evaluation of the liver provides information that contributes to treatment decisions, the data remain potentially useful,” they state. “[Alamasio and colleagues] are correct to call for evidence-based use of liver biopsy and studies of cost-effectiveness, but such goals should not blind us to the potential value of the procedure in any patient with hepatitis C.”

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Family and Household HCV Transmission

Although direct blood exposure is known to be the most common risk factor for HCV transmission, experts continue to study other potential exposure routes – such as sexual and perinatal transmission – since the route of infection remains unknown in a substantial number (about 10%) of cases. In the September issue of Hepatology, M.K. Mohamed and colleagues reported on a study on intrafamilial transmission of hepatitis C in Egypt. The researchers prospectively assessed HCV incidence and associated risk factors in a cohort of 6,734 Egyptians from two rural villages, one in the Nile Delta and one in Upper Egypt. During an average of 1.6 years of follow-up, 33 individuals seroconverted to HCV positive (3.1/1,000 person-years [PY]). But incidence varied dramatically between the two villages: in the Nile Delta village (where baseline HCV prevalence was 24%), the incidence rate was 6.8/1,000 PY; in the Upper Egypt village (where baseline prevalence was 9%), the incidence rate was 0.8/1,000 PY. The strongest predictor for contracting HCV was having an HCV-positive family member; in fact, 27 of the 33 newly infected individuals (82%) had an HCV positive family member. As expected, parenteral (direct blood) exposure increased HCV risk, but was not statistically significant. The highest incidence rate (14.1/1,000 PY) was seen in Nile Delta village children younger than age 10 who were living in households with an HCV positive parent; overall, 67% of seroconverters were younger than age 20. The authors concluded that, “young children would especially benefit from measures reducing exposures or preventing infection with HCV.”


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