ALBI grade: Evidence for an improved model for liver functional estimation in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) usually arises in the context of a chronically damaged liver. Liver functional estimation is of paramount importance in clinical decision making. The Child-Pugh score (CPS) can be used to categorise patients into 3 classes (A to C) based on the severity of liver functional impairment according to 5 parameters (albumin, bilirubin, prothrombin time, presence of ascites and hepatic encephalopathy). The albumin-bilirubin (ALBI) grade has emerged as an alternative, reproducible and objective measure of liver functional reserve in patients with HCC, defining worsening liver impairment across 3 grades (I to III). The ALBI score can identify different subgroups of patients with different prognoses across the diverse Barcelona Clinic Liver Cancer stages and CP classes, making it an appealing clinical predictor. In patients treated with potentially curative approaches (resection, transplantation, radiofrequency ablation, microwave ablation), ALBI grade has been shown to correlate with survival, tumour relapse, and post-hepatectomy liver failure. ALBI grade also predicts survival, toxicity and post-procedural liver failure in patients treated with transarterial chemoembolisation, radioembolisation, external beam radiotherapy as well as multi-kinase inhibitors (sorafenib, lenvatinib, cabozantinib, regorafenib) and immune checkpoint inhibitor therapy. In this review, we summarise the body of evidence surrounding the role of ALBI grade as a biomarker capable of optimising patient selection and therapeutic sequencing in HCC. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL)

Surveillance for hepatocellular carcinoma in chronic viral hepatitis: Is it time to personalize it?

Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma (HCC), including those with cirrhosis, advanced fibrosis and special subgroups of chronic hepatitis B (CHB). Application of the standard surveillance strategy to all patients with chronic liver disease (CLD) with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems. Thus, a number of HCC risk scores were constructed, mainly from Asian cohorts, to stratify the HCC prediction in patients with CHB. Similarly, even if less than for CHB, a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies. Recently, a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters. Overall, the HCC risk stratification appears at hand by several validated multiple score systems, but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic, epidemiologic, etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice. A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics, epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future, with the possibility to achieve a real and cost/effective personalization of surveillance

Modeling Hepatocellular Carcinoma Cells Dynamics by Serological and Imaging Biomarkers to Explain the Different Responses to Sorafenib and Regorafenib

Simple Summary Systemic therapy in advanced hepatocellular-carcinomas (HCC) has limited benefits, but some patients show partial responses (PR) and a few even a complete response (CR). Understanding the biological mechanisms could help clinicians in decision-making. Aim of this study was to develop a physic-mathematical model to investigate tumor dynamics using alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) measures combined with digital imaging. The model was set-up in three prototype patients with CR/PR to sorafenib and PR to regorafenib, and then applied in seven patients with different types of response. Overall, the rate constant of cancer cells production ranged between 0.250-0.372 C x day(-1). During therapy, neo-angiogenesis reduction was higher in four CR than in four PR or stable disease (SD) and in two non-responders (median: 83.2% vs. 29.4% vs. 2.0%). Tumor vasculature decay appeared accelerated in CR. We conclude that modeling serological and imaging biomarkers could help personalization of systemic therapy. In advanced HCC, tyrosine-kinase inhibitors obtain partial responses (PR) in some patients and complete responses (CR) in a few. Better understanding of the mechanism of response could be achieved by the radiomic approach combining digital imaging and serological biomarkers (alpha-fetoprotein, AFP and protein induced by vitamin K absence-II, PIVKA-II) kinetics. A physic-mathematical model was developed to investigate cancer cells and vasculature dynamics in three prototype patients receiving sorafenib and/or regorafenib and applied in seven others for validation. Overall four patients showed CR, two PR, two stable-disease (SD) and two progressive-disease (PD). The rate constant of cancer cells production was higher in PD than in PR-SD and CR (median: 0.398 vs. 0.325 vs. 0.316 C x day(-1)). Therapy induced reduction of neo-angiogenesis was greater in CR than in PR-SD and PD (median: 83.2% vs. 29.4% and 2.0%), as the reduction of cell-proliferation (55.2% vs. 7.6% and 0.7%). An additional dose-dependent acceleration of tumor vasculature decay was also observed in CR. AFP and cancer cells followed the same kinetics, whereas PIVKA-II time/dose dependent fluctuations were influenced also by tissue ischemia. In conclusion, pending confirmation in a larger HCC cohort, modeling serological and imaging biomarkers could be a new tool for systemic therapy personalization

Retrospective evaluation of cirrhosis development in chronic hepatitis C patients

Kronik hepatit C (HCV) hastalarında karaciğer siroz gelişimini etkileyen faktörler arasında kalıcı viral yanıt (KVY) ile birlikte bazı laboratuar değerleri ve basit skorlama modellerinin bulunduğu eski çalışmalarda gösterilmiştir. Biz bu çalışmamızda interferon (IFN) bazlı tedaviler ile kalıcı viral yanıt oranlarının, basit laboratuar değerleri ve skorlamaların karaciğer siroz gelişimi üzerine etkilerini değerlendirmeyi amaçladık. Ocak 2000-Mart 2015 tarihleri arasında Uludağ Üniversitesi Tıp Fakültesi Gastroenteroloji polikliniğine başvuran, en az 1 yıl takip edilen 100 kronik HCV hastasının verileri çalışmaya dahil edildi. Hastalar tedavi almayan ve alan olarak 2 gruba ayrıldı. Tedavi alan 82 hasta, tedavi protokollerine göre 4 gruba ayrıldı. Tüm hastalarda bazal laboratuvar parametreler, AST/ALT skoru, AST/platelet (APRİ) skoru, fibrozis-4 (FİB-4) skoru, kalıcı viral yanıt oranları hesaplandı ve siroz gelişimi incelendi. Tedavi alan hastalarda, almayanlara göre daha az oranda siroz geliştiği saptandı (%19,5 - %44,4, p=0,025). Tedavi alan hastalardan KVY sağlananların hiçbirinde rekürrens ve siroz gelişmezken, KVY sağlanamayan hastaların %33,3'de siroz gelişti (p 150.000 (p 150.000 (p<0.001), low AST/ALT score (p=0.003), low FIB-4 score (p<0.001), low APRI score (p<0.001), sustained viral response achievement (p<0.001) resulted in statistically significant less cirrhosis. In cox regression analysis; SVR was found to be the only independent factor affecting development of cirrhosis (Hazard ratio, HR=0.279; Confidence Interval, CI=0.082-0.943; p=0.04) In conclusion; although impact of many factors on the development of cirrhosis in chronic hepatitis C patients are known, achieving SVR is the single independent factor in preventing the development of cirrhosis

Impact of COVID-19 Pandemic on Gastroenterology Fellowship Training in Turkey: A Prospective Nationwide Survey Study

Background: The Coronavirus-2019 disease (COVID-19) pandemic has markedly restricted endoscopic and clinical activities in gastroenterology (GI), with a negative impact on trainee education. We aimed to investigate how and to what extent has GI trainees in Turkey are affected by the current pandemic in terms of general, psychological, and educational status. Methods: We conducted a web-based survey sent electronically to 103 official GI trainees in Turkey from 37 centers. The 32-item survey included questions to capture demographic (5-questions), endoscopic (7-questions), personal protective equipment (PPE) (3-questions), psychological and general well-being (11-questions), and educational (6-questions) data. Results: Ninety-six (93.2%) trainees completed the survey, of which 56.3% (n = 54) reported a decrease in independently performed endoscopic procedures. Due to pandemic, 91.7% of standard diagnostic endoscopic procedures, 57.2% of standard therapeutic procedures, and 67.7% of advanced endoscopic procedures were decreased. Out of 96 respondents, we detected signs of anxiety in 88.5%, exposure concern in 92.7%, concerns for prolongation of training period in 49%, loss of concentration and interest in 47.9%, and burnout syndrome in 63.5%. Female gender (odds-ratio: 3.856, 95% confidence interval: 1.221-12.174, P =.021) was the only independently associated factor with pandemic-related anxiety. Conclusions: COVID-19 pandemic has led to high amounts of anxiety and non-negligible rates of burnout syndrome among GI trainees, with a significant reduction in endoscopic activities. More effort and novel strategies are required to deliver sufficient competence and general-psychological well-being to GI trainees

Programmed Cell Death 1 and Hepatocellular Carcinoma: An Epochal Story

In recent years, immune-based therapies have emerged as novel pillars for hepatocellular carcinoma (HCC). The rationale of immune-checkpoint inhibitors (ICIs) trial in HCC originated from the fact that the tumor cells and the infiltrating stromal and immune cells promote an immunosuppressive tumor microenvironment, including the up-regulation of immune checkpoint molecules on their surface. Antibody-based blockage targeting inhibitory checkpoint molecules on cytotoxic T cells, including programmed cell death-1 (PD-1) or its counterpart on antigen-presenting cells has shown strong anti-tumor activity in a subset of HCC patients. Single nucleotide polymorphisms (SNP) of PD-1 gene may affect the PD-1 expression or function, which eventually can cause dysfunctionality of immune balance. Based on the inhibitory role of PD-1 in anti-tumor responses, it has been investigated in several studies as a candidate to test for genetic susceptibility of individuals to HCC. The present paper highlights the knowledge on cross-talks for liver immunology and HCC course, recent studies investigating the role of functional SNPs of PD-1 gene in Turkish HCC population, and the data on already investigated PD-1 inhibitor molecules in clinical trials

Surveillance of hepatocellular carcinoma in cirrhotic patients: Current knowledge and future directions

Patients with cirrhosis are at the highest risk to develop hepatocellular carcinoma (HCC), with a variable annual risk of 1-8%. Currently, biannual abdominal ultrasound (USG) with or without alpha fetoprotein (AFP) is the recommended HCC surveillance strategy of major professional liver societies for all cirrhotic patients. However, the effectiveness of USG and AFP has been a sprawling subject of debate due to conflicting results and the low quality of the evidence. The role of cross-sectional imaging is controversial due to potential harm and cost-effectiveness concerns. Several novel serum biomarkers have been introduced for HCC screening, but have yet to be validated for various geographic regions. A risk-stratified algorithm is needed to increase the yield of HCC surveillance by distinguishing a high-risk group that requires more intense screening with cross-sectional imaging and serum biomarkers, and a low-risk group, where the standard surveillance strategy is continued. In this review, the strengths and concerns related to standard USG-based surveillance strategy are discussed, as well as efforts to increase the effectiveness of surveillance

Surveillance Strategies for Hepatocellular Carcinoma: Recent Advances and the Shifting Paradigm

Currently, international liver societies recommend screening at-risk individuals for HCC (patients with cirrhosis regardless of etiology, and/or chronic hepatitis B virus, and/or advanced liver fibrosis) with biannual abdominal ultrasound (USG) with or without alpha-fetoprotein (AFP). The global acceptance of USG in surveillance relies on the absence of risks, non-invasiveness, and lower costs. However, the suboptimal performance of USG +/- AFP in reaching direct and indirect goals of HCC surveillance highlights the need for alternative surveillance strategies. Several studies targeted contrast-enhanced magnetic resonance imaging techniques, but the main barriers for their entrance to surveillance programs have been concerns about cost-effectivity and long scan times. Overall, the HCC risk stratification appears at hand by several validated multiple score systems, but their optimal performance is obtained only in populations who show highly homogenous clinical, pathological, epidemiologic, etiologic, and therapeutic characteristics, and this limitation poses a major drawback to their sustainable use in clinical practice. We need globally validated and molecular integrated risk stratification tools to shape the future tailored HCC surveillance decision algorithms. A dynamic process for HCC surveillance algorithms awaits us owing to the expected further prospective studies focusing on risk-stratified screening strategy

Myeloperoxidase and calprotectin; Any role as non-invasive markers for the prediction of inflammation and fibrosis in non-alcoholic steatohepatitis?

Background/Aims: Specific serum markers reflecting hepatic inflammation and fibrosis are required to tailor the treatment strategies in non-alcoholic steatohepatitis (NASH). We aimed to investigate the roles of myeloperoxidase (MPO) and calprotectin in predicting the hepatic inflammation status and disease severity in NASH. Materials and Methods: A total of 48 patients with biopsy-proven NASH and 25 healthy volunteers with normal weight were prospectively enroiled Serum MPO and calprotectin levels were compared between the NASH and control groups. Hepatic MPO and calprotectin expressions were compared in terms of histologic non-alcoholic fatty liver disease activity scores (NAS) (low NAS [5]) and fibrosis stage (insignificant [F0-1]/significant [F2-4]). Results: Serum MPO and calprotectin levels were not significantly different between the NASH and control groups. In the subgroup analysis, hepatic MPG expression was significantly increased in patients with NASH with significant fibrosis than in those with insignificant fibrosis (F2-4: 7.04 +/- 3.61 vs. F0-1: 4.83 +/- 2.42, p=0.01). We found no difference between the groups with low and high NAS with regard to serum MPG and calprotectin levels and hepatic MPG and calprotectin expressions. Conclusion: This study demonstrated that hepatic MPG expression can reflect advanced fibrosis in NASH. However, when serum MPO and calprotectin levels were evaluated as potential serum markers, both did not associate with hepatic inflammation status and fibrosis stage in NASH. Therefore, our study results preclude their use as serum markers for hepatic inflammation in NASH