Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been... Show moreBackground & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection.Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves.Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10-17 in 57.7%, and >-18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03-3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61-1.25), and the pooled c-index was 0.77 (range 0.73-0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of >-10 would spare unnecessary HCC screening in 27% of individuals.Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Simple Summary The incidence of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has increased in recent years. Compared to HCC caused by other chronic... Show moreSimple Summary The incidence of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has increased in recent years. Compared to HCC caused by other chronic liver diseases, NAFLD-related HCC is often detected later, because it more commonly arises before cirrhosis has occurred. Because of this late diagnosis, NAFLD-related HCC is often more advanced at time of diagnosis, resulting in fewer curative treatment options. Most research in the pathogenesis of HCC has focused on the disease processes in hepatocytes, the most abundant type of liver cells. However, other cell types, such as cells of the immune system and cells that regulate connective tissue formation, also play an important role in the development of NAFLD-related HCC, both by contributing to the development of HCC itself and by interfering with the immune system's ability to attack cancer cells. In this paper, we review the role of different cell types in the development of NAFLD-related HCC. Hepatocellular carcinoma (HCC) in the setting of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis and even in the pre-cirrhotic state is increasing in incidence. NAFLD-related HCC has a poor clinical outcome as it is often advanced at diagnosis due to late diagnosis and systemic treatment response is poor due to reduced immune surveillance. Much of the focus of molecular research has been on the pathological changes in hepatocytes; however, immune cells, hepatic stellate cells, liver sinusoidal endothelial cells and the extracellular matrix may play important roles in the pathogenesis of NAFLD-related HCC as well. Here, we review the role of non-parenchymal cells in the liver in the pathogenesis of HCC in the context of NAFLD-NASH, with a particular focus on the innate and the adaptive immune system, fibrogenesis and angiogenesis. We review the key roles of macrophages, hepatic stellate cells (HSCs), T cells, natural killer (NK) cells, NKT cells and liver sinusoidal endothelial cells (LSECs) and the role of the extracellular matrix in hepatocarcinogenesis within the steatotic milieu. Show less
Simple Summary: Hepatocellular carcinoma (HCC) is one of the deadliest forms of cancer. Selective internal radiation therapy (SIRT) is one of the therapeutic options for treatment of advanced HCC.... Show moreSimple Summary: Hepatocellular carcinoma (HCC) is one of the deadliest forms of cancer. Selective internal radiation therapy (SIRT) is one of the therapeutic options for treatment of advanced HCC. Studies show that SIRT has a high objective response rate, but lack of survival benefit when compared to different treatment modalities. We hypothesized that this is due to potential damage in healthy liver parenchyma as a side-effect of SIRT, resulting in functional changes to the liver. This can ultimately result in liver decompensation and potentially death. The aim of this retrospective study was to assess long-term liver-related complications after SIRT in patients with HCC. We analyzed patients who underwent SIRT and found that liver decompensation occurred more often after SIRT when compared to sorafenib. However, careful patient selection may result in a survival benefit after SIRT when compared to other treatments. The ABLI score may be a valuable prognostic score for selecting patients.Selective internal radiation therapy (SIRT) is used as a treatment for hepatocellular carcinoma (HCC). The aim of this study was to assess long-term liver-related complications of SIRT in patients who had not developed radioembolization-induced liver disease (REILD). The primary outcome was the percentage of patients without REILD that developed Child-Pugh (CP) & GE; B7 liver decompensation after SIRT. The secondary outcomes were overall survival (OS) and tumor response. These data were compared with a matched cohort of patients treated with sorafenib. Eighty-five patients were included, of whom 16 developed REILD. Of the remaining 69 patients, 38 developed liver decompensation CP & GE; B7. The median OS was 18 months. In patients without REILD, the median OS in patients with CP & GE; B7 was significantly shorter compared to those without CP & GE; B7; 16 vs. 31 months. In the case-matched analysis, the median OS was significantly longer in SIRT-treated patients; 16 vs. 8 months in sorafenib. Liver decompensation CP & GE; B7 occurred significantly more in SIRT when compared to sorafenib; 62% vs. 27%. The ALBI score was an independent predictor of liver decompensation (OR 0.07) and OS (HR 2.83). After SIRT, liver decompensation CP & GE; B7 often developed as a late complication in HCC patients and was associated with a shorter OS. The ALBI score was predictive of CP & GE; B7 liver decompensation and the OS, and this may be a valuable marker for patient selection for SIRT. Show less
