Metabolic Disorders across Hepatocellular Carcinoma in Italy

As the main metabolic and detoxification organ, the liver constantly adapts its activity to fulfill the energy requirements of the whole body. Despite the remarkable adaptive capacity of the liver, prolonged exposure to noxious stimuli such as alcohol, viruses and metabolic disorders results in the development of chronic liver disease that can progress to hepatocellular carcinoma (HCC), which is currently the second leading cause of cancer-related death worldwide. Metabolic rewiring is a common feature of cancers, including HCC. Altered mito-nuclear communication is emerging as a driving force in the metabolic reprogramming of cancer cells, affecting all aspects of cancer biology from neoplastic transformation to acquired drug resistance. Here, we explore relevant aspects (and discuss recent findings) of mito-nuclear crosstalk in the metabolic reprogramming of hepatocellular carcinoma.

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Metabolic disorders across hepatocellular carcinoma in Italy

Liver International ◽

10.1111/liv.13877 ◽

2018 ◽

Vol 38 (11) ◽

pp. 2028-2039 ◽

Cited By ~ 2

Author(s):

Filomena Morisco ◽

Maria Guarino ◽

Maria R. Valvano ◽

Francesco Auriemma ◽

Fabio Farinati ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Metabolic Disorders

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NAFLD-Associated Hepatocellular Carcinoma: a Threat to Patients with Metabolic Disorders

Current Hepatology Reports ◽

10.1007/s11901-016-0297-7 ◽

2016 ◽

Vol 15 (2) ◽

pp. 103-112 ◽

Cited By ~ 1

Author(s):

Anna Simona Sasdelli ◽

Lucia Brodosi ◽

Giulio Marchesini

Keyword(s):

Hepatocellular Carcinoma ◽

Metabolic Disorders

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Effects of Positive Hepatitis B Core Antibody and Metabolic Disorders in Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus

Cancer Control ◽

10.1177/10732748211039758 ◽

2021 ◽

Vol 28 ◽

pp. 107327482110397

Author(s):

Hae Lim Lee ◽

Si Hyun Bae ◽

Jaejun Lee ◽

Pil Soo Sung ◽

Sung Won Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B ◽

Liver Function ◽

Clinical Characteristics ◽

Endemic Area ◽

Metabolic Disorders ◽

Advanced Tumor Stage ◽

Advanced Tumor ◽

Significant Difference ◽

The Impact

Background and Aims This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. Methods A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. Results The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002–2011 to 12% in 2012–2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III–V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. Conclusion Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.

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Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002–2033: the ITA.LI.CA database

Gut ◽

10.1136/gutjnl-2021-324915 ◽

2021 ◽

pp. gutjnl-2021-324915

Author(s):

Alessandro Vitale ◽

Gianluca Svegliati-Baroni ◽

Alessio Ortolani ◽

Monica Cucco ◽

Giulio V Dalla Riva ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Metabolic Disorders ◽

Metabolic Dysfunction ◽

Risk Of Death ◽

Cancer Aggressiveness ◽

Nationally Representative ◽

Extrahepatic Metastases ◽

Definition Of ◽

Epidemiological Trends ◽

Representative Cohort

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.MethodsWe analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.ResultsMAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002–2003, to 77.3% and 28.9% in 2018–2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006).ConclusionsThe prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.

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BIOCHEMICAL NUTRITIONAL PROFILE OF LIVER CIRRHOSIS PATIENTS WITH HEPATOCELLULAR CARCINOMA

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032014000100003 ◽

2014 ◽

Vol 51 (1) ◽

pp. 10-15 ◽

Cited By ~ 4

Author(s):

Gabriela Zanatta PORT ◽

Kalinca OLIVEIRA ◽

Jonathan SOLDERA ◽

Cristiane Valle TOVO

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Liver Cancer ◽

Metabolic Disorders ◽

Nutritional Assessment ◽

Cancer Staging ◽

Barcelona Clinic Liver Cancer ◽

Nutritional Profile ◽

Methods Analytical ◽

Transversal Study

Context Liver cirrhosis patients with hepatocellular carcinoma present nutritional alterations and metabolic disorders that negatively impact the prognosis. Objective The objective is to identify alterations in the metabolism of macro and micronutrients among liver cirrhosis patients with and without hepatocellular carcinoma and their relation to the Child-Turcote-Pugh score and Barcelona Clinic Liver Cancer staging. Methods Analytical transversal study, with 31 hepatocellular carcinoma patients and 48 liver cirrhosis patients. Laboratorial exams were carried out. The existence of an association between the biochemical parameters and the disease severity as well as the presence of hepatocellular carcinoma was assessed. Results The metabolic-nutritional profile of liver cirrhosis patients caused by the hepatitis C virus and hepatocellular carcinoma showed alterations, specifically the lipid (total cholesterol, HDL and triglycerides), protein (albumin, creatinine and uric acid), iron (transferrin, iron and ferritin saturation), hematocrit and hemoglobin, zinc and B12 vitamin profiles. There is a relation between nutritional biochemical markers and the Child-Turcote-Pugh, as well as Barcelona Clinic Liver Cancer staging. Conclusions Considering the existence of alterations in the metabolism of nutrients in liver cirrhosis patients with and without hepatocellular carcinoma, and also that conventional nutritional assessment methods present limitations for this population, the biochemical laboratorial exams are valid to complement the diagnosis of the nutritional state in a quick and practical manner.

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METABOLIC DISORDERS ACROSS HEPATOCELLULAR CARCINOMA IN ITALY.

10.26226/morressier.59a6b346d462b80290b54948 ◽

2017 ◽

Author(s):

Valentina Cossiga

Keyword(s):

Hepatocellular Carcinoma ◽

Metabolic Disorders

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Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology

International Journal of Molecular Sciences ◽

10.3390/ijms22157803 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7803

Author(s):

Henriette Huschka ◽

Sabine Mihm

Keyword(s):

Hepatocellular Carcinoma ◽

Metabolic Disorders ◽

Viral Infections ◽

Gene Activation ◽

Hcv Infection ◽

Sequencing Data ◽

Advanced Liver Disease ◽

Specific Host ◽

Infected Liver ◽

Sample Support

Hepatocellular carcinoma (HCC) is a malignancy with a leading lethality. The etiology is quite diverse, ranging from viral infections to metabolic disorders or intoxications, and associates with specific somatic mutational patterns and specific host immunological phenotypes. Particularly, hepatitis C virus (HCV)-infected liver is featured by an activation of interferon (IFN)-stimulated genes (ISGs; IFN signature), which we suppose is driven by type III IFNL4. Taking advantage of the TCGA collection of HCC patients of various different etiologies, this study aimed at validating our previous findings on hepatic IFNL4 gene activation in HCV infection in an independent and larger cohort of patients with advanced liver disease. In a cohort of n = 377 cases, the entirety of the sequencing data was used to assess the IFNL genotypes, and the cases were stratified for etiology. The number of IFNL4 transcripts within nonmalignant and malignant tissues was found to be more abundant in patients with HCV or HCV/HBV infections when compared to other risk factors. Moreover, in patients with HCV infection as a risk factor, a close, positive relationship was found between ISG activation and the number of functional IFNL4 transcripts. Data on this independent TCGA sample support the concept of an IFNL4-dependent HCV-driven activation of hepatic ISGs. In addition to that, they add to the understanding of etiology-related host immunological phenotypes in HCC.

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