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Fibroblast activation protein (FAP) is expressed on activated fibroblast. Its role in fibrosis and desmoplasia is controversial, and data on pharmacological FAP inhibition are lacking. We aimed to better define the role of FAP in liver fibrosis in vivo and in vitro.FAP expression was analyzed in mice and patients with fibrotic liver diseases of various etiologies. Fibrotic mice received a specific FAP inhibitor (FAPi) at 2 doses orally for 2 weeks during parenchymal fibrosis progression (6 weeks of carbon tetrachloride) and regression (2 weeks off carbon tetrachloride), and with biliary fibrosis (Mdr2-/-). Recombinant FAP was added to (co-)cultures of hepatic stellate cells (HSC), fibroblasts, and macrophages. Fibrosis- and inflammation-related parameters were determined biochemically, by quantitative immunohistochemistry, polymerase chain reaction, and transcriptomics.FAP+ fibroblasts/HSCs were α-smooth muscle actin (α-SMA)-negative and located at interfaces of fibrotic septa next to macrophages in murine and human livers. In parenchymal fibrosis, FAPi reduced collagen area, liver collagen content, α-SMA+ myofibroblasts, M2-type macrophages, serum alanine transaminase and aspartate aminotransferase, key fibrogenesis-related transcripts, and increased hepatocyte proliferation 10-fold. During regression, FAP was suppressed, and FAPi was ineffective. FAPi less potently inhibited biliary fibrosis. In vitro, FAP small interfering RNA reduced HSC α-SMA expression and collagen production, and FAPi suppressed their activation and proliferation. Compared with untreated macrophages, FAPi regulated macrophage profibrogenic activation and transcriptome, and their conditioned medium attenuated HSC activation, which was increased with addition of recombinant FAP.Pharmacological FAP inhibition attenuates inflammation-predominant liver fibrosis. FAP is expressed on subsets of activated fibroblasts/HSC and promotes both macrophage and HSC profibrogenic activity in liver fibrosis.

Aims: Asian Pacific Association for the Study of Liver (APASL) acute-on-chronic liver failure (ACLF) Research Consortium (AARC) proposed new prognostic scoring system of ACLF in cluding lactate. However, lactate is not routinely checked in clinical practice of patient with ACLF in Korea. Therefore, we aimed to investigate the predictive accuracy of lactate-free AARC-ACLF score for predicting short-term mortality in patients with alcoholic liver disease. Methods: A total of 749 ALD patients who had liver failure (bilirubin≥5mg/dL and INR≥1.5) in AARC database were in vestigated. Diagnostic performances for short-term mortality were compared according to the area under receiver operating characteristic (AUROC) curve. Predictive accuracy of lactate-free AARC-ACLF score were compared with other prognostic scores in 143 ALD patients with liver failure and 60 ALD patients with ACLF according to AARC definition in Korean ACLF cohort. Results: Among 749 patients, 30-day and 90-day mortality were 40.3% and 51.5%. There were no significant differences in AUROC for predicting 30-day and 90-day mortality between AARC-ACLF score and lactate-free AARC-ACLF score (30-day mortality: 0.752 vs. 0.751, P=0.918, 90-day mortality: 0.728 vs. 0.736, P=0.346). In Korean ACLF cohort, the AUROCs of lactate-free AARC-ACLF score for predicting 28-day and 90- day mortality were 0.861 and 0.846 in ALD with liver failure, and 0.884 and 0.874 in ALD patients with ACLF according to AARC definition, respectively. In Korean ALD patients with liver failure and ACLF according to AARC definition, diagnostic per formance of lactate-free AARC-ACLF score for predicting 28- day and 90-day mortality was comparable to those of Model for End-stage Liver Disease (MELD), MELD-Na, Chronic Liver Failure-Sequential Organ Failure Assessment score. Conclusions: Lactate-free AARC-ACLF score is as excellent as AARC-ACLF score in predicting short-term mortality in ALD patients with liver failure of AARC database and Korean ACLF cohort.

Chronic hepatitis B infection is a very important health problem in China, which is carrying an enormous economic and social burdens. The major routs of chronic hepatitis B infection in China are mother-infant vertical transmission and early childhood horizontal transmission. After more than 10 years implementation of universal vaccination against hepatitis B in newborns and safety injection in health care settings, the prevalence of HBsAg in general population has decreased from 9.75% to around 7%. In China, patients with hepatitis are cared by either hepatologists or physicians of infectious diseases. The Chinese Society of Hepatology, and Chinese Society of Infectious Diseases jointly issued an evidence-based guideline on the prevention and treatment of chronic hepatitis B in 2005. This guideline concisely describes the virology, epidemiology, natural history and prevention, as well as diagnosis and management of chronic hepatitis B. It also highlights the importance of active viral replication in disease progression in chronic HBV infection and explicitly states the necessity of antiviral therapy in patient care. The cornerstone of anti-hepatitis B therapy is optimal use of interferons or nucleos(t)ide analogs in those patients with active viral replication and elevated serum transaminase levels. Through an independent continue medical educational agency, a panel of selected speakers were trained to give well-formatted talks on the key points of the guideline in over 60 major cities across China. This educational campaign among health care providers has greatly improved the awareness and the stand of care for antiviral therapy.