Imaging of chemotherapy-induced liver toxicity: an illustrated overview

Chemotherapy is a potential cause of focal and diffuse hepatobiliary lesions. Many of these lesions may be demonstrated on imaging, especially computed tomography and MRI. Some of these lesions, especially those of steatosis and sinusoidal obstruction syndrome, are associated with a worse prognosis and risk of hepatic failure in the context of surgical management. Notably, some chemotherapy-induced hepatic alterations, such as sinusoidal obstruction syndrome, pseudocirrhosis and focal hepatopathies, may be mistakenly interpreted as signs of cancer progression, misguiding the therapeutic planning for patients receiving chemotherapy.

Portal vein embolization: rationale, techniques, outcomes and novel strategies

The incidence of liver cancer has grown in the past decade, with 905,677 new cases and 830,180 deaths in 2020. According to the highest annual fatality ratio, liver cancer is the third-leading cause of cancer-related deaths worldwide. Surgical resection is the mainstay treatment for long-term survival. However, only 25% of patients are surgical candidates. Recent surgical concepts, techniques and multidisciplinary management were developed, including interventional radiology procedures that improve the management algorithm, expand the indications and limit dropouts from curative treatment. This review summarizes up-to-date information on interventional radiology in the management of liver tumors.

Systematic literature review of trials assessing recommended systemic treatments in hepatocellular carcinoma

Aim: To identify and evaluate the similarity of all trials assessing recommended treatments for advanced hepatocellular carcinoma. Materials & methods: Single arm and randomized trials from any phase and published any time up to February 2021 were systematically searched. Results: From 5677 records reviewed, 50 trials were included in the review, and 24 for assessed for similarity. In the first-line (1L) setting, several trials assessing sorafenib were noted for enrolling patients with more severe disease and/or performance status than other 1L trials; trials within the second-line (2L) setting were generally similar. Median survival was <2 years in all trial arms. Conclusions: Trials assessing recommended treatments are largely similar and appropriate for quantitative comparisons of several efficacy and safety outcomes.

Evaluation of tumor mutational burden in small early hepatocellular carcinoma and progressed hepatocellular carcinoma

While researchers know that tumor mutational burden (TMB) is low in hepatocellular carcinoma (HCC), prior studies have not investigated TMB in cirrhosis, small early HCC and progressed HCC. HCC (n = 18) and cirrhosis (n = 6) cases were identified. TMB was determined by a 1.7 megabase, 409-gene next-generation sequencing panel. TMB values were defined as the number of nonsynonymous variants per megabase of sequence. There was no significant difference between cirrhosis versus small early HCC or between cohorts when stratified by size, early versus progressed, differentiation or morphology. There was a significant difference between cirrhosis and small early HCC versus progressed HCC (p = 0.045), suggesting TMB may be related to HCC progression. TMB similarities in small early HCC and background cirrhosis suggest TMB is not a useful tool for diagnosing small early HCC. Additional study is needed to address TMB in histological and molecular subsets of HCC.

Transarterial chemoembolization alone or followed by bevacizumab for treatment of colorectal liver metastases

Aims: Bevacizumab (B) in association with systemic chemotherapy is commonly used for the treatment of colorectal cancer liver metastases. The aim of this study was to monitor tumor response, overall survival (OS) and progression-free survival (PFS) of patients with colorectal cancer liver metastases treated with transarterial chemoembolization (TACE) + B compared with TACE alone and to correlate the results with KRAS mutational status. Patients & methods: This was an observational multicentric case–control study (NCT03732235) on the efficacy and safety of B administered after TACE. Results: The disease control rate was significantly higher for the TACE + B than the TACE alone group (p < 0.001). KRAS wild-type patients had a significantly better disease control rate than those with KRAS mutations in the TACE + B group. Median OS and PFS were similar for the TACE + B and TACE groups, whereas median time to progression was significantly higher for the TACE + B group (p < 0.01). Conclusion: The combination of TACE with B may improve tumor response and delay disease progression.

Unresectable hepatocellular carcinoma treatment with doxorubicin-eluting polyethylene glycol microspheres: a single-center experience

Background: Transarterial chemoembolization (TACE) is indicated for unresectable hepatocellular carcinoma. Methods: This was a retrospective study of 50 hepatocellular carcinoma patients treated with TACE using doxorubicin-loaded LifePearl™ to investigate the safety and efficacy of TACE. Results: There was no 30-day mortality, and limited adverse events were reported. At best tumor response, complete response and disease control were 58% and 94%, respectively, with a median of 4.5 months of follow-up. Median overall survival was 33.8 months. Patients with Barcelona Clinic Liver Cancer stage 0 and stage A at best tumor response showed a higher complete response rate (83%) than patients with Barcelona Clinic Liver Cancer stage B (complete response: 50%; p = 0.0414). Conclusion: Doxorubicin-loaded LifePearl™ TACE might be an effective treatment, with a good safety profile, for patients with early/intermediate-stage hepatocellular carcinoma. Further prospective data, especially with a small cohort of selected patients, are required to confirm these results.

Locoregional therapy patterns and healthcare economic burden of patients with hepatocellular carcinoma in the USA

Aim: To examine the locoregional therapy (LRT) patterns and the healthcare economic burden of patients with hepatocellular carcinoma (HCC) in the USA. Patients & methods: Patients with newly diagnosed HCC were identified from the MarketScan® databases (1 July 2015–31 May 2018). The LRTs received and all-cause and HCC-related healthcare costs were measured. Results: Among 2101 patients with HCC, most received embolization therapy as their first LRT treatment (57.8%, n = 1215); 17.1% (n = 360) received ablative therapy and 8.7% (n = 182) radiation therapy; 16.4% (n = 344) received multiple LRTs. After patients received their first LRT treatment, total all-cause healthcare costs averaged $20,316 per patient per month; 70.7% ($14,359) were HCC related. Conclusion: Among newly diagnosed HCC patients treated with LRT in the USA, the economic burden is high.

Endotrophin, a pro-peptide of Type VI collagen, is a biomarker of survival in cirrhotic patients with hepatocellular carcinoma

Aim: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer types with a high amount of fibrosis activity, namely for outcome in hepatocellular carcinoma (HCC) cirrhotic patients. Patients & methods: Plasma C6M, PRO-C6 and alphafeto-protein (AFP) were assessed in 309 patients with mixed etiologies (hepatitis C, hepatitis B, alcohol and nonalcoholic fatty liver) diagnosed as cirrhotics, cirrhotics with HCC, noncirrhotics and healthy controls. Progression-free survival and overall survival (OS) data were collected up to 6120 days after diagnosis. The ability of each marker to predict survival was investigated. Results & conclusion: The level of endotrophin assessed by PRO-C6 was able to separate healthy controls, noncirrhotics and cirrhotics from HCC (p < 0.05–0.0001). Both endotrophin and C6M provided value in the prediction of OS in cirrhotic patients with HCC. In the multivariate analysis for identifying HCC, in patients with high endotrophin (highest quartile) and that were positive for AFP (≥20 IU/ml), the hazard ratio for predicting OS was increased from 3.7 (p = 0.0006) to 14.4 (p = 0.0001) when comparing with AFP positive as a stand-alone marker. In conclusion, plasma levels for markers of Type VI collagen remodeling were associated with survival in cirrhotic patients with HCC. A combination of AFP with endotrophin improved the prognostic value compared with AFP alone for predicting OS in cirrhotic patients with HCC.

Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma

Hepatocellular carcinoma (HCC) developed in non-alcoholic fatty liver disease (NAFLD) individuals presents substantial clinical and biological characteristics, which remain to be elucidated. Its occurrence in noncirrhotic patients raises issues regarding surveillance strategies, which cannot be considered as cost-effective given the high prevalence of obesity and metabolic syndrome, and furthermore delineates specific oncogenic process that could be targeted in the setting of primary or secondary prevention. In this context, the identification of a genetic heterogeneity modulating HCC risk as well as specific biological pathways have been made possible through genome-wide association studies, development of animal models and in-depth analyses of human samples at the pathological and genomic levels. These advances must be confirmed and pursued to pave the way for personalized management of NAFLD-related HCC.

Hepatitis B-related hepatocellular carcinoma and stress: untangling the host immune response from clinical outcomes

Chronic hepatitis B virus (HBV) infection is a major public health challenge on the global scale. Affecting hundreds of millions worldwide, HBV is a leading risk factor for hepatocellular carcinoma (HCC). Clinical outcomes from chronic HBV infection are varied and appear to be influenced by a complex and dysregulated host immune response. In turn, much attention has been given to the immunologic response to HBV in an effort to identify host factors that lead to the development of HCC. However, the role of nonimmunologic host factors, such as chronic stress, in HBV-related HCC is poorly defined. Indeed, a growing appreciation for the effects of stress on chronic liver diseases raises the question of its role in chronic HBV infection. In this light, the present review will untangle the roles of key host factors in HBV-related HCC with an emphasis on chronic stress as a viable contributor. First discussed is the interplay of stress, inflammation and chronic liver disease. The host immune response’s role as a driver of HBV-related HCC is then reviewed, allowing for a close exploration of the effects of stress on immune function in chronic hepatitis B and as a potential risk factor for HBV-related HCC.