scholarly journals Alcohol and hepatocellular carcinoma

2019 ◽  
Vol 6 (1) ◽  
pp. e000260 ◽  
Author(s):  
Hiroshi Matsushita ◽  
Akinobu Takaki

BackgroundAlcohol is classified as a Group 1 carcinogen by the International Agency for Research on Cancer because it induces hepatocellular carcinoma (among other cancers) in humans. An excessive alcohol intake may result in fatty liver, acute/chronic hepatitis, and cirrhosis and eventually lead to hepatocellular carcinoma. It has been reported that alcohol abuse increases the relative risk of hepatocellular carcinoma by 3- to 10-fold.Aim and MethodsTo clarify the known mechanisms of alcohol-related carcinogenesis, we searched Pubmed using the terms alcohol and immune mechanism, alcohol and cancer, and immune mechanism and cancer and summarized the articles as a qualitative review.ResultsFrom a clinical perspective, it is well known that alcohol interacts with other factors, such as smoking, viral hepatitis, and diabetes, leading to an increased risk of hepatocellular carcinoma. There are several possible mechanisms through which alcohol may induce liver carcinogenicity, including the mutagenic effects of acetaldehyde and the production of ROS due to the excessive hepatic deposition of iron. Furthermore, it has been reported that alcohol accelerates hepatitis C virus-induced liver tumorigenesis through TLR4 signaling. Despite intense investigations to elucidate the mechanisms, they remain poorly understood.ConclusionThis review summarizes the recent findings of clinical and pathological studies that have investigated the carcinogenic effects of alcohol in the liver.

2020 ◽  
Vol 26 (4) ◽  
pp. 736-741
Author(s):  
Makiko Taniai

An excessive alcohol intake may result in fatty liver, acute/chronic hepatitis, cirrhosis, and lead to hepatocellular carcinoma (HCC). The aim of this review is to clarify the present condition and the mechanisms of alcohol-related hepatocarcinogenesis and clinical risk factors for alcohol-related HCC. There are several possible mechanisms through which alcohol may induce hepatocarcinogenesis, including the mutagenic effects of acetaldehyde toxicity through the formation of protein and DNA adducts and the production of reactive oxygen species due to the excessive hepatic deposition of iron, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. Furthermore, it has been reported that alcohol accelerates liver carcinogenesis through several signaling pathways including gut-liver axis. From a clinical perspective, it is well known that alcohol interacts with other factors, such as age, gender, viral hepatitis, obesity, and diabetes leading to an increased risk of HCC.


2015 ◽  
Vol 42 (5) ◽  
pp. 835-840 ◽  
Author(s):  
Shaowei Wu ◽  
Eunyoung Cho ◽  
Wen-Qing Li ◽  
Jiali Han ◽  
Abrar A. Qureshi

Objective.Alcohol intake has been associated with an increased risk of psoriasis. However, the association between alcohol intake and risk of psoriatic arthritis (PsA) has been unclear. We evaluated the association between alcohol intake and risk of incident PsA in a large cohort of US women.Methods.Our present study included a total of 82,672 US women who provided repeated data on alcohol intake over the followup period (1991–2005). Self-reported PsA was validated using the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire. Cox proportional hazards models were used to estimate the age-adjusted and multivariate-adjusted HR and 95% CI for the PsA in association with alcohol intake.Results.We documented 141 incident PsA cases during 14 years (1,137,763 person-yrs) of followup. Compared to non-drinkers, the multivariate HR for PsA were 0.70 (95% CI 0.48–1.01) for 0.1–14.9 g/day, 1.43 (95% CI 0.67–3.08) for 15.0–29.9 g/day, and 4.45 (95% CI 2.07–9.59) for ≥ 30.0 g/day of cumulative average alcohol intake. Risk estimates were generally consistent when using updated alcohol intake and baseline alcohol intake in 1991 as the exposures, and when the analysis was restricted to those who developed psoriasis during the followup.Conclusion.Excessive alcohol intake was associated with an increased risk of incident PsA in a cohort of US women.


2004 ◽  
Vol 112 (11) ◽  
pp. 1188-1192 ◽  
Author(s):  
Giuseppe Mastrangelo ◽  
Ugo Fedeli ◽  
Emanuela Fadda ◽  
Flavio Valentini ◽  
Roberto Agnesi ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2499
Author(s):  
Lisanne Noordam ◽  
Zhouhong Ge ◽  
Hadiye Özturk ◽  
Michail Doukas ◽  
Shanta Mancham ◽  
...  

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nghiem Xuan Hoan ◽  
Pham Thi Minh Huyen ◽  
Mai Thanh Binh ◽  
Ngo Tat Trung ◽  
Dao Phuong Giang ◽  
...  

AbstractThe inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojing Chen ◽  
Per-Olof Hansson ◽  
Erik Thunström ◽  
Zacharias Mandalenakis ◽  
Kenneth Caidahl ◽  
...  

AbstractThe QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50–60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07–2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1023
Author(s):  
Eirini I. Rigopoulou ◽  
George N. Dalekos

Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.


Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 210
Author(s):  
Martynas Ridziauskas ◽  
Birutė Zablockienė ◽  
Ligita Jančorienė ◽  
Artūras Samuilis ◽  
Rolandas Zablockis ◽  
...  

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1098.2-1098
Author(s):  
S. Barsotti ◽  
C. Roncella ◽  
A. Valentini ◽  
L. Cavagna ◽  
R. Castellana ◽  
...  

Background:Interstitial lung disease (ILD), is common in patients with idiopathic inflammatory myopathies (IIM) and strongly impact on patients’ morbidity and mortality. Patients with anti-aminoacyl-transfer RNA-synthetases (anti-ARS) antibodies are associated with an increased risk of ILD.Objectives:Defining the radiological characteristics of IIM patients, with special focus on serological groups, through qualitative, semiquantitative and quantitative analysis of lung CT.Methods:This was a prospective study conducted from 2016 to 2019. Ninety-eight IIM patients (35 men, 63 women) were included. Myositis specific autoantibodies (MSA) were assessed with Myositis Prophyle III (Euroimmune, Lubeck).Each patient had a baseline CT; the total score of Warrick (WS) was obtained at semiquantitative analysis. The radiological scores ILD% (interstitial lung disease %) and PVRS% (pulmonary vascular related structure) were the result of quantitative analysis in 61 patients (CALIPER). Pulmonary function tests (PFTs) included TLC%, FVC% and DLCO% (65 patients). The analysis was conducted in the whole group and divided in subgroups based on their MSA pattern: in particular anti-ARS (Group 1) and patients negative to MSA (Group 2) were analysed.Results:Positive correlations between ILD% and PVRS% (Rho=0.916; ρ=0.000), WS and ILD% (Rho=0.663; ρ=0.000) and WS and PVRS% (Rho=0.637; ρ<0.001) were found.The most relevant inverse correlations were found between ILD% and DLCO% (Rho=-0.590; ρ=0.001), PVRS% and DLCO% (Rho=-0.549; ρ<0.001) and WS and DLCO% (Rho=-0.471; ρ<0.001).Statistically significant higher values of WS, ILD% and PVRS% were found in Group 1 (WS=15, ILD%=11 and PVRS%=3.5), compared to Group 2 (WS=2.5, ILD%=0.84 and PVRS%=2.2). NSIP pattern resulted dominant represented in the two groups (80% Group 1, 75% Group 2). No statistically significant differences of DLCO%, FVC% and TLCO% were found.Conclusion:The inverse correlations between the radiological scores and the functional data TLC% and DLCO% (ρ<0.001) confirm the role of lung CT in the clinical management of ILD in IIM patients, and may represent a promising tool for clinical trials. For the first time anti-ARS and serological negative patients were defined through qualitative, semiquantitative and quantitative analysis of lung CT. Further study should be conducted in order to define the prognostic value of the quantitative analysis of lung CT in the follow up of IIM patients.Disclosure of Interests:None declared


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