Evaluating liver fibrosis by using serum direct biomarkers

Abstract

Introduction: The liver fibrosis is a wound healing response in which damaged regions are encapsulated by an extracellular matrix or scar. Previously liver fibrosis thought to be irreversible process, but nowadays it is recognized as dynamic process with the potential for resolution1,2. The exact point when fibrosis becomes irreversible is incompletely understood. However, even in early stages of cirrhosis may have potential to regression.3 Prevalence of hepatitis C (HCV) infection in Mongolia is approximately 11-16% [4, 5] and hepatitis B (HBV) prevalence is approximately 10.9-11.1%6, which make us the one of the highly infected countries in the world. Mongolia has the highest liver cancer incidence in the world, ranking in number one and which is eight times higher than the world average7. Hepatic stellate cell activation is the common pathway leading to hepatic fibrosis. In healthy liver homeostasis of ECM is precisely regulated by group of endopeptidases called MMPs and their specific inhibitors, TIMPs. Once hepatic stellate cell is activated, they release chemokines and other leukocyte chemo-attractants while simulating the liver fibrogenesis by upregulating matrix production and scar formation. During inflammation, activated stellate cells secrete EMMPD-1, thereby inhibiting MMPs and promoting fibrogenesis by causing protein accumulation8,9. Thus, the balance between fibrogenesis and fbirolysis is disrupted. The golden standard for diagnosing liver fibrosis is liver biopsy which has its limitation, due to being invasive, it may be associated with complication and patient may refuse the offer. Therefore, it has been recommended by scientists and professionals to have more simplified methods to diagnose it. There are two main types of serum biomarkers for detection liver fibrosis. Indirect markers of hepatic fibrosis include serologic biochemical tests that reflect alterations in hepatic function but do not directly reflect extracellular matrix metabolism. Direct markers of fibrosis can be divided into markers associated with matrix deposition, markers associated with matrix degradation and markers associated with matrix degradation. Patel et al. published that hyaluronic acid, EMMPD-1 and α2-macroglobulin can distinguish the patients with moderate-to-severe fibrosis from those with mild fibrosis, both caused by hepatitis C virus. Direct markers of fibrosis have been combined into panels to predict hepatic fibrosis. The panels may also include indirect markers of fibrosis. These panels have comparable sensitivity and specificity in terms of detection liver fibrosis and inflammation activity levels. Thus, serum direct fibrosis markers may play crucial role in detection liver fibrosis in early stages and monitoring its activity, especially MMPs. Conclusion: 1. Liver fibrosis serum direct biomarker tests have been relatively fully studied and have not been introduced into daily clinical use, but in the future, they can be widely used for early detection of liver fibrosis and to monitor the dynamic process. 2. Investigate the cellular and molecular mechanisms of MMPs during hepatitis C virus inflammation, and their fibrolytic activity may lead to liver fibrosis. Therefore, there is a need for research to determine the mechanism of MMP inactivation during hepatitis C virus inflammation. 3. The limited number of studies on the regulation of hepatic MMPs in the progression of liver fibrosis in humans opens the door for further investigation.