In hepatocellular carcinoma (HCC), the clinical significance of soluble immune checkpoint protein levels as predictors of patient outcomes or therapeutic responses has yet to be defined. This study profiled the baseline levels of sixteen soluble checkpoint proteins and their changes following sorafenib treatment for HCC. Plasma samples were obtained from 53 patients with advanced HCC at baseline, week 1, 2 and 4 of sorafenib treatment and tested the concentrations of 16 soluble checkpoint proteins using multiplexed fluorescent bead-based immunoassays. Multivariate analysis showed high sBTLA levels at baseline were an independent predictor of poor overall survival (p = 0.038). BTLA was highly expressed in T cells and macrophages in peritumoral areas. At week 2, sCD27 levels were decreased compared to baseline. By contrast, the concentrations of most inhibitory proteins, including sBTLA, sLAG-3, sCTLA-4, sPD-1, sCD80, sCD86 and sPD-L1, had significantly increased. The fold-changes of soluble checkpoint receptors and their ligands, including sCTLA-4 with sCD80/sCD86, sPD-1 with sPD-L1; and the foldchanges of sCTLA-4 with sBTLA or sPD-1 were positively correlated. sBTLA may be a good biomarker for predicting overall survival in HCC patients. Sorafenib treatment in patients with advanced HCC revealed dynamic changes of soluble checkpoint protein levels.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and the second most common cause of cancer deaths worldwide. The top three causes of HCC are hepatitis B virus (HBV), hepatitis C virus (HCV), and alcoholic liver disease. Owing to recent advances in direct-acting antiviral agents, HCV can now be eradicated in almost all patients. HBV infection and alcoholic liver disease are expected, therefore, to become the leading causes of HCC in the future. However, the association between alcohol consumption and chronic hepatitis B in the progression of liver disease is less well understood than with chronic hepatitis C. The mechanisms underlying the complex interaction between HBV and alcohol are not fully understood, and enhanced viral replication, increased oxidative stress and a weakened immune response could each play an important role in the development of HCC. It remains controversial whether HBV and alcohol synergistically increase the incidence of HCC. Herein, we review the currently available literature regarding the interaction of HBV infection and alcohol consumption on disease progression.

No controlled trial in patients with chronic hepatitis B virus (HBV) infection on long-term entecavir (ETV) treatment, comparing switching to tenofovir disoproxil fumarate (TDF) with continuing the therapy, has been reported. Twenty-seven nucleos(t)ide-naïve patients with chronic HBV who underwent ETV therapy for ≥5 years and maintained virological response were included and randomized into two groups: one group continued ETV, and the other switched to TDF, in a 1:2 ratio. The primary endpoint was changed from baseline in serum hepatitis B surface antigen (HBsAg) level at week 48. The baseline characteristics were not different between nineteen patients in the TDF group and eight patients in the ETV group. Mean decreases in HBsAg level at week 48 were 0.023 and 0.042 log 10 IU/mL in the TDF and ETV groups, respectively (P = 0.94).The mean drops in hepatitis B core-related antigens were also not different between the TDF and ETV groups at week 48 (P = 0.80). HBV DNA was sustainedly <2.1 log 10 copies/ mL in all patients throughout the study period. In contrast, the mean aminotransferase levels were significantly higher in the TDF group than in the ETV group at weeks 12, 24, and 36, although being within the reference range. Estimated glomerular filtration rate was lower in the TDF group than in the ETV group at weeks 24 (P = 0.016) and 48 (P = 0.003). In conclusion, we could not find the effect on reducing HBsAg level by switching to TDF in chronic hepatitis B patients with maintained virological response to ETV for ≥5 years. K E Y W O R D S entecavir, hepatitis B virus, nucleos(t)ide analogs, randomized controlled trial (RCT), tenofovir disoproxil fumarate 1 | INTRODUCTION Hepatitis B virus (HBV) infection affects approximately 250 million people worldwide and is the major cause of cirrhosis and liver cancer, accounting for 780 000 deaths annually. 1 The annual incidence rates of hepatocellular carcinoma were reported to be 0.3% to 0.6% in noncirrhotic patients and 2.2% to 3.7% in cirrhotic patients if left untreated. 2 The ultimate goal of antiviral therapy in patients with persistent HBV infection is to improve survival and quality of life, by inhibiting the activity of hepatitis and progression of fibrosis to reduce the risk of liver cancer. Hepatitis B surface antigen (HBsAg) is considered the most effective surrogate marker for achieving this J Med Virol. 2019;91:1295-1300.wileyonlinelibrary.com/journal/jmv

Changes in plasma interleukin-8 and TNF-α levels during the first few days could predict the response to sorafenib therapy in HCC patients.

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