scholarly journals Paradigm shift in the treatment options of hepatocellular carcinoma

2021 ◽  
Author(s):  
Tung‐Hung Su ◽  
Shih‐Jer Hsu ◽  
Jia‐Horng Kao
2020 ◽  
Vol 20 (5) ◽  
pp. 382-389 ◽  
Author(s):  
Shimaa EL-Sharawy ◽  
Osama El- Sayed Negm ◽  
Sherief Abd-Elsalam ◽  
Hesham Ahmed EL-Sorogy ◽  
Mona Ahmed Helmy Shehata

Background & Aims: Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate the association between TLR3 gene polymorphism and HCV-related hepatocellular carcinoma in Egypt. Methods: This work was conducted on 70 individuals; fifty HCV cirrhotic patients were included in two groups; with HCC (30 patients) and without HCC (20 patients) compared with a group of 20 apparently healthy controls. All of the studied individuals underwent clinical-laboratory evaluation. TLR3 gene single-nucleotide polymorphism (SNP) (+1234C/T) was tested by polymerase chain reaction- restriction fragment length polymorphism. Results: This study reported that the prevalence of TLR3 +1234TT genotype was significantly increased in cirrhotic patients with HCC than without HCC, while it was not detected at all among the controls. When analyzing the TLR3 SNP +1234C/T with different clinical parameters in HCC patients, there was a significant association between+1234C/T SNP; namely TT genotype and each of the hepatic focal lesions᾽ number, size and the patients᾽ higher Okuda and BCLC stages. No association could be detected between TLR3 SNP and the age, sex, Child-Pugh grades, MELD score or AFP of the studied HCC cases. Conclusion: TLR3 gene SN P +1234C/T could be a novel risk factor for the HCV-related HCC among the Egyptian population.


2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1681
Author(s):  
José Debes ◽  
Pablo Romagnoli ◽  
Jhon Prieto ◽  
Marco Arrese ◽  
Angelo Mattos ◽  
...  

Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Major etiologies of HCC relate to chronic viral infections as well as metabolic conditions. The survival rate of people with HCC is very low and has been attributed to late diagnosis with limited treatment options. Combining ultrasound and the biomarker alpha-fetoprotein (AFP) is currently one of the most widely used screening combinations for HCC. However, the clinical utility of AFP is controversial, and the frequency and operator-dependence of ultrasound lead to a variable degree of sensitivity and specificity across the globe. In this review, we summarize recent developments in the search for non-invasive serum biomarkers for early detection of HCC to improve prognosis and outcome for patients. We focus on tumor-associated protein markers, immune mediators (cytokines and chemokines), and micro-RNAs in serum or circulating extracellular vesicles and examine their potential for clinical application.


2021 ◽  
Vol 13 ◽  
pp. 175883592110311
Author(s):  
Chiun Hsu ◽  
Lorenza Rimassa ◽  
Hui-Chuan Sun ◽  
Arndt Vogel ◽  
Ahmed O. Kaseb

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3740
Author(s):  
Chunye Zhang ◽  
Ming Yang

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.


2017 ◽  
Author(s):  
◽  
Andrew Douglas Huber

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Chronic hepatitis B virus (HBV) infection leads to liver disease, cirrhosis, and hepatocellular carcinoma. Globally, an estimated 50% of all hepatocellular carcinoma cases are linked to chronic HBV infection. More than 240 million people are chronically infected, and there are 0.5-1 million deaths per year due to HBVrelated liver conditions. HBV treatment options rarely cure infections and are associated with adverse side effects that often outweigh the potential benefits of treatment. New treatments, therefore, are highly desired for HBV therapy. Towards this goal, we have developed novel compounds targeting two viral targets and assessed the mechanisms of action by which these compounds act. We have developed systems for the discovery and evaluation of compounds that inhibit 2 distinct steps in the HBV life cycle. Using these systems, we have developed potent inhibitors of HBV replication that have potential to become clinically used HBV drugs. Furthermore, we have used our methods to evaluate which properties of these compounds are likely to result in better viral inhibition. The work described in this thesis has led to at least 2 new compound groups for potential use as HBV antivirals and provides insight into mechanisms by which potent antivirals can be achieved.


Author(s):  
Andrew S. Niekamp ◽  
Govindarajan Narayanan ◽  
Brian J. Schiro ◽  
Constantino Pena ◽  
Alex Powell ◽  
...  

AbstractRadioembolization has become a widespread treatment modality for both primary and metastatic hepatic malignancies. Although the majority of data and indication for yttrium-90 radioembolization have been for hepatocellular carcinoma and metastatic colorectal cancer, radioembolization with yttrium-90 has rapidly expanded into the treatment options for multiple tumor types with metastases to the liver. This article reviews the clinical data and expanding utilization of radioembolization for rare metastatic diseases with an emphasis on efficacy and safety.


2020 ◽  
Author(s):  
yongchol cha ◽  
Hyok Choe ◽  
Songjin Oh ◽  
ZinHwa Cha

Abstract Background; Hepatocellular carcinoma (HCC) represents a major and steadily increasing global health challenge as the most common primary liver malignancy and leading cause of death in cirrhotic patients. The only hope for curative treatment or significant increase in life expectancy is early detection. Once patients have progressed towards end-stage HCC, effective treatment options are extremely limited on the background of a very high degree of heterogeneity in clinical presentation and outcome. Objectives; The purpose of this study is to perform clinical trial on an end-stage HCC patient by mineral pulse light stimulus on LV acupoints without any drugs use. Methods; End-stage HCC patient was stimulated by mineral pulse light stimulator (MPLS). Stimulus acupoints; LV3, LV14, SP6. The selected acupoints were stimulated by MPLS for 50~60 minutes once a day. The same method was performed on the patient for 25days and rested for 5days, and again repeated every month without any drugs use. Results; After treatment, the general patient conditions and alfa-fetoprotein level were improved and hepatoma size was decreased to 9.1×8.5cm from 11.0×9.7cm before treatment (a), and the decay areas was disappeared.Conclusions; End-stage HCC patient was improved by mineral pulse light stimulus on LV acupoints without any drugs use.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1272 ◽  
Author(s):  
Laura Marconato ◽  
Silvia Sabattini ◽  
Giorgia Marisi ◽  
Federica Rossi ◽  
Vito Ferdinando Leone ◽  
...  

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.


1994 ◽  
Vol 80 (5) ◽  
pp. 315-326 ◽  
Author(s):  
Marco Colleoni ◽  
Fernando Gaion ◽  
Guido Liessi ◽  
Giorgio Mastropasqua ◽  
Patrizia Nelli ◽  
...  

Background Hepatocellular carcinoma (HCC) remains one of the most common neoplasms worldwide. Curative treatment options include liver transplantation or resection. Unfortunately, most patients still have unresectable or untransplantable HCC due to disease extension or comorbid factors and are therefore candidate only for palliative treatments. Methods In this review we have analyzed the different medical approaches employed in the treatment of HCC in an attempt to better define their roles. Results Palliative medical treatments including systemic chemotherapy, immunotherapy or hormonal manipulation rarely influence survival of the patients. Although a high response rate is often reported with new local therapies such as transcatheter arterial embolization, intraarterial chemotherapy or percutaneous ethanol injection, the real impact of these treatment modalities on patient survival remains to be determined. Conclusion One way to improve the diagnosis of HCC patients would be an appropriate approach to evaluate new drugs or treatment modalities. To answer all the open questions, further trials, possibly randomized, should be conducted on a substantial number of patients with homogeneous prognostic factors.


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