The human patatin-like phospholipase domain containing 3 (PNPLA3) rs738409C>G polymorphism is associated with several types of liver disease. The aim of this meta-analysis was to assess the risk of cirrhosis on the basis of rs738409 allele frequency and genotype. Medline, the Cochrane Library, EMBASE, and Google Scholar were searched for prospective and retrospective studiesassessing the effect of the rs738409 polymorphism on liver cirrhosis.Seven studies, involving 2023 patients with cirrhosis, were included. The G allele was associated with a significantly increased risk of cirrhosis vs the C allele (pooled OR = 1.86, 95% CI = 1.64 to 2.12, Z = 9.55, P<0.001). Both the GC and GG genotypes were associated with a significantly increased risk of cirrhosis vs. the CC genotype (GC vs CC: pooled OR = 1.73, 95% CI = 1.51 to 1.98, Z = 7.86; P < 0.001; GG vs. CC: pooled OR = 3.41, 95% CI = 2.77 to 4.18, Z = 11.65; P < 0.001); OR=3.37, 95% CI=2.73, 4.16,PG polymorphism is identified.

Hepatocellular carcinoma (HCC) is a common cancer in the world, and its incidence is increasing yearly. Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are important causes of HCC. Liver cirrhosis, age, sex, smoking and drinking, and metabolic risk factors will increase the risk of cancer in HBV/HCV patients. And viral load, APRI, FIB-4, and liver stiffness can all predict the risk of HCC in patients with viral infection. In addition, effective prevention strategies are essential in reducing the risk of HCC. The prevention of HCC involves mainly tertiary prevention strategies, while the primary prevention is based on standardized vaccine injections to prevent the occurrence of HBV/HCV. Eliminating the route of transmission and vaccination will lead to a decrease in the incidence of HCC. Secondary prevention involves effective antiviral treatment of HBV/HCV to prevent the disease from progressing to HCC, and tertiary prevention is actively treating HCC to prevent its recurrence.

Non-alcoholic fatty liver disease (NAFLD) has become one of the important causes of cirrhosis and liver cancer, resulting in a huge medical burden worldwide. Currently, effective non-invasive diagnostic indicators and drugs for NAFLD are still lacking. With the development of metabolomics technology, the changes in metabolites during the development of NAFLD have been gradually revealed. Bile acid (BA) is the main endpoint of cholesterol metabolism in the body. In addition, it also acts as a signaling factor to regulate metabolism and inflammation in the body through the farnesyl X receptor and G protein-coupled BA receptor. Studies have shown that BA metabolism is associated with the development of NAFLD, but a large number of animal and clinical studies are still needed. BA homeostasis is maintained through multiple negative feedback loops and the enterohepatic circulation of BA. Recently, treatment of NAFLD by interfering with BA synthesis and metabolism has become a new research direction. Here, we review the changes in BA metabolism and its regulatory mechanisms during the development of NAFLD and describe the potential of studies exploring novel non-invasive diagnostic indicators and therapeutic targets for NAFLD based on BA metabolism.

Background: Transforming growth factor-beta (TGF-β) signaling is essential in initialization and progression of hepatocellular carcinoma (HCC). Therefore, a treatment targeting TGF-β pathway may be a promising option for HCC control. Methods: First, publicly available RNA-seq datasets and clinical characteristics of 374 HCC patients in The Cancer Genome Atlas (TCGA) database were downloaded. Then, Cox regression analysis and LASSO analysis were used to construct a prognostic model for TGF-β family genes. The area under the curve (AUC) of the risk signature was calculated to evaluate the predictive power of the model. Cox regression analysis was applied to predict whether TGF-β1 can be an independent prognosis factor for HCC. Next, hazard ratio and survival analyses were performed to investigate the correlation between TGF-β1 expression and survival time. Furthermore, differential expression level of TGF-β1 in HCC tissues and cells was determined. In addition, Gene Set Enrichment Analysis (GSEA) identified the top significantly activated and inhibited signal pathways related to high expression of TGF-β1. Finally, the CIBERSORT tool was adopted to correlate the tumor-infiltrating immune cells (TICs) with TGF-β1 expression in HCC cohorts. Results: Cox regression analysis and LASSO analysis revealed that seven TGF-β family members (including TGF-β1) could be used as prognostic factors for HCC. Interestingly, TGF-β1 was demonstrated to be an independent prognostic factor of HCC. RT-qPCR and immunofluorescence staining confirmed the high expression of TGF-β1 in HCC cell lines and tissues, which is significantly related to pathological classifications, poor prognosis, and short survival time. Finally, GSEA and CIBERSORT analyses suggested that TGF-β1 may interact with various immune cells and influence the prognosis of HCC patients through Tregs and γδ T cells. Conclusion: We established a novel prognostic prediction method to predict the risk scores of TGF-β genes in HCC prognosis. TGF-β1 is highly expressed in HCC cell lines and tissues, correlates to poor prognosis, and thus can be used as a potential biomarker to predict HCC prognosis. We showed that TGF-β1 may play its roles in HCC prognosis by modulating the immune microenvironment of tumor cells. Our data may shed more light on better understanding the role of TGF-β1 in HCC prognosis.

This study aimed to confirm the association of the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant with non-alcoholic fatty liver disease (NAFLD) and the degree of steatosis, as well as the additive effect of body mass index (BMI) or the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M and TM6SF2 E167K variants in NAFLD. A total of 158 NAFLD patients and 158 matched controls were recruited. Steatosis was classified as mild, moderate and severe by FibroScan. Associations between the TM6SF2 E167K variant and NAFLD as well as clinical parameters were evaluated. Although the frequency of the T allele was low in the Chinese population (MAF=7.4%), there was still a significant association between the E167K variant and NAFLD (odds ratio=3.379, 95% confidence interval: 1.500-7.612, P=0.003). In particular, the TM6SF2 genotype was also associated with the degree of steatosis (P=0.023). The TM6SF2 variant was associated with increased alanine aminotransferase (ALT) but no other clinical parameters, such as aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lipids. Notably, we also found that an additive effect of the TM6SF2 E167K and PNPLA3 I148M variants in NAFLD. Furthermore, we did not identify an association between the TM6SF2 E167K variant and NAFLD in the non-obese population. The TM6SF2 E167K variant was associated with NAFLD in northeast China, and there was an interaction between the PNPLA3 I148M and TMS6F2 E167K variants in NAFLD.

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis–related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis–related complications. Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts’ clinical experiences. Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis–related complications.