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BACKGROUND AND AIMS: Whether tenofovir or entecavir has different effects on the prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in secondary and tertiary preventive settings is still a matter of debate. This study aimed to compare the long-term prognosis of HCC between tenofovir and entecavir in patients with chronic hepatitis B. METHODS: Chronic hepatitis B patients diagnosed with HCC between November 2008 and December 2018 and treated with either entecavir or tenofovir at a tertiary center in Korea were included. The effect of tenofovir compared with entecavir on the prognosis of HBV-related HCC was assessed using multivariable-adjusted Cox and propensity score (PS)-matched analyses. Various predefined subgroup analyses were conducted. RESULTS: During a median follow-up period of 3.0 years, the mortality rate for entecavir-treated patients (n = 3469) was 41.2%, while tenofovir-treated patients (n = 3056) had a mortality rate of 34.6%. Overall survival (OS) was better in the tenofovir group (adjusted hazard ratio [aHR], 0.79; P < .001), which were consistently observed in the PS-matched analysis. The magnitude of the risk difference in OS was more prominent 2 years after the diagnosis of HCC (aHR, 0.50; P < .001) than 2 years before (aHR, 0.88; P = .005), and it was more pronounced in patients with earlier HCC stages. In all subgroups, except for those with shorter life expectancy, such as those with compromised liver function, tenofovir was associated with better OS compared with entecavir. CONCLUSIONS: Among patients with HBV-related HCC, those treated with tenofovir had a better prognosis than those treated with entecavir, particularly among those with prolonged survival.
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Purpose: To evaluate the effect of diquafosol on corneal epithelium in a dry eye model using Transwell culture and a scopolamine-induced dry eye rat model. Methods: Desiccation stress induced in an in vitro dry eye model using human corneal epithelial cells was used, and the cells were incubated with or without diquafosol media diluted at 1:100. Reactive oxygen species (ROS) generation was measured using 2',7'-dichlorofluorescein diacetate (DCFH-DA). Apoptosis was analyzed, and levels of phosphorylated Erk1/2, phosphorylated p90RSK, phosphorylated Akt, IκB-α, and NF-κB-p65 were determined. Levels of IL-1ß, TNF-α, IL-6, IL-8, and GM-CSF were quantified. To investigate the in vivo effects of diquafosol, we induced dry eye in Wistar rats using scopolamine hydrobromide. The rats were divided into three groups: control, dry eye, and dry eye diquafosol; topical DIQUAS was applied four times daily for 28 days. We used immunohistochemistry to detect the levels of phosphorylated Erk1/2, phosphorylated p90RSK, and IL-1ß, and used the TUNEL assay in corneal tissue. Results: The distribution of highly fluorescent dichlorofluorescein and the proportion of annexin V- and PI-positive cells decreased in the diquafosol medium. Diquafosol increased the levels of phospho-Erk1/2, phospho-90RSK, phospho-Akt, and IκB-α, whereas it significantly decreased the levels of NF-κB-p65, IL-1ß, and TNF-α. In vivo, apoptosis was enhanced in dry eye group. This response was markedly reduced and the level of phosphorylated p90RSK and phosphorylated ERK1/2 were upregulated and IL-1ß was downregulated by DIQUAS. Conclusions: Diquafosol treatment reduced intracellular ROS levels, apoptosis, and inflammation, all of which were increased in the dry eye model through desiccation.