2021 消化系聯合學術演講年會
外賓演講（四） ANTIVIRAL THERAPY AND FIBROSIS REGRESSION IN CHRONIC HEPATITIS C Massimo Pinzani University College London, Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
The established success of anti-HCV treatment with DAA has consolidated the possibility of their efficacy in blocking or reversing the fibrogenic progression of HCV-induced chronic liver disease (CLD) and, more in general, has unearthed vital information about the natural history of fibrosis regression. Although more and more data on post-SVR are becoming available, there are, however, two main limitations: 1. the large majority of the current knowledge is based on the treatment of patients with cirrhosis and 2. post-SVR liver biopsy are rare since this is not the standard of care. Therefore, any definitive conclusion about the regression/stabilization of liver fibrosis following DAA-induced SVR will need to wait for further confirmations. Regardless, while it is evident that in patients with HCV-related CLD, SVR reduces the risk of liverrelated complications such as hepatic decompensation, hepatocellular carcinoma (HCC) as well as all-cause mortality, it is also increasingly apparent that in patients with clinically significant and severe portal hypertension (PH), HCV clearance does not induce a significant reduction of PH and that cirrhosis, once advanced may progress to decompensation even in absence on HCV replication. In biological terms, this can be explained by the relative autonomy acquired by the fibrogenic process
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beyond a certain level of development over decades characterised by chronic fibro-inflammation and neoangiogenesis. In particular, it is conceivable that, at this stage of the disease, two major determinants may condition further clinical progression independently of the reduction of hepatocellular necrosis and inflammation induced by SVR. The first is represented by the remarkable hyperplasia of different types of activated fibrogenic myofibroblasts which is associated by a strong activation of anti-apoptotic pathways in these cells. The second is due to the extensive changes in hepatic angio-architecture consequent to neo-angiogenesis and to the contraction of scar tissue leading to elevated tissue tension which are only minimally affected by the reduction of necroinflammation following SVR. Currently, there is much debate on the possible use of non-invasive tests, such as serum markers and liver elastography, for monitoring post-SVR fibrosis regression. However, this contention occurs in the absence of clear-cut criteria for the histopathological assessment of fibrosis regression. Therefore, serum markers and elastography are not accurate in detecting fibrosis regression after SVR in HCV patients with CLD and their routine use is presently not recommended. However, yearly determinations by liver elastography could be helpful to refine the stratification of residual liver-related risk.
