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Protocol liver biopsies in long-term management of patients transplanted for hepatitis B-related liver disease

World Journal of Gastroenterology 2006年第11期12卷 1706-1712页

作者： Stefano Targhetta Federico Villamil Paolo Inturri Patrizia Pontisso Stefano Fagiuoli Umberto Cillo Attilio Cecchetto Simona Gianni Remo Naccarato Patrizia Burra Gastroenterology Section Department of Surgical and Gastroenterological Sciences University of PadovaItaly Liver Unit Fundacion Favaloro Buenos AiresArgentina Gastroenterology Unit San Bonifacio Hospital VeronaItaly Clinica Medica 5 Department of Clinical and Experimental Medicine University of PadovaItaly Surgery Section Department of Surgical and Gastroenterological Sciences University of PadovaItaly Department of Pathology University of Padova Italy

AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis （CH） B after LT was classified as minimal, mild, moderate or severe. RESULTS： HBV recurred in 7/42 （16.6%） patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg＋/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients （7.1%）, minimal/non-specific changes were observed in 18 （64.2%）, and at least 1 biopsy showed CH in the remaining 8 （28.5%）. Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg＋ or HBsAg- liver ***： Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.

关键词： Liver transplantation Hepatitis B virus liverbiopsy Anti-HBs Immunoglobulins

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Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy

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World Journal of Gastroenterology 2006年第23期12卷 3682-3694页

作者： Giada Sebastiani Alfredo Alberti Department of Clinical and Experimental Medicine University of PadovaPadovaItaly

Chronic liver diseases are very common worldwide, particularly those linked to viral hepatitis and to alcoholic and non-alcoholic fatty liver. Their natural history is variable and long-term evolution differs in individual patients. Optimised clinical management of compensated chronic liver diseases requires precise definition of the stage of liver fibrosis, the main determinant of prognosis and of most therapeutic decisions. Liver biopsy is the gold standard for assessment of hepatic fibrosis. However, it is invasive with possible complications, costly and prone to sampling errors. Many non-invasive markers of liver fibrosis have been recently proposed and assessed in the clinical setting as surrogates of liver biopsy. Direct markers are based on biochemical parameters directly linked to fibrogenesis while indirect markers use simple or more sophisticated parameters that correlate with liver fibrosis stages. Non-invasive markers of liver fibrosis have been tested in different forms of chronic liver disease and showed variable diagnostic performance, but accuracy rarely was above 75%-80%. Better results were obtained when markers were combined. On this line, we have recently proposed a set of algorithms that combine sequentially indirect non-invasive markers of liver fibrosis, reaching 90%-95% diagnostic accuracy with significant reduction in the need for liver biopsy. Based on available evidence, it can be anticipated that non-invasive markers of liver fibrosis and their combined use will soon become a most useful tool in the clinical management of many forms of chronic liver disease. However, their implementation is expected to reduce, but not to completely eliminate, the need for liver biopsy.

关键词： Chronic liver diseases Hepatic fibrosis liverbiopsy Non invasive fibrosis markers

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Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B

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World Journal of Gastroenterology 2007年第4期13卷 525-531页

作者： Giada Sebastiani Alessandro Vario Maria Guido Alfredo Alberti Depart-ment of Clinical and Experimental Medicine University of Pado-va Padova Italy Department of Oncological and Surgical Sciences University of Padova Padova Italy

AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.METHODS： One hundred and ten consecutive patients （80 males, 30 females, mean age： 42.6 ± 11.3） with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio （APRI）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, Hui＇s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive （PPV） and negative （NPV） predictive values, accuracy and area under the curve （AUC）. RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest had the best PPV and NPV for cirrhosis （87% and 90%, respectively）. Fibrotest showed the best AUC for both significant fibrosis and cirrhosis （0.85 and 0.76, respectively）. Stepwise combination algorithms of APR1, Fibrotest and biopsy showed excellent performance （0.96 AUC, 100% NPV） for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION： In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.

关键词： Chronic hepatitis B Hepatic fibrosis liverbiopsy Non-invasive markers Stepwise combinationalgorithms

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