scholarly journals Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

2020 ◽  
Vol 9 (3) ◽  
pp. 765
Author(s):  
Chung-Man Moon ◽  
Sang Soo Shin ◽  
Suk Hee Heo ◽  
Yong Yeon Jeong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Lactate Dehydrogenase ◽  
Enzymatic Activity ◽  
Viral Hepatitis ◽  
Potential Risk ◽  
Early Stage ◽  
Liver Parenchyma ◽  
Cirrhotic Liver ◽  
1H Mrs

Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60–80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60–80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity.

scholarly journals The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Cirrhosis ◽  
Early Stage ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Serum Samples ◽  
Disease Etiology ◽  
Risk Patients ◽  
Scoring Tool

(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.

scholarly journals The expression of microRNA-331-3p and microRNA-23b3 in Egyptian patients with early-stage hepatocellular carcinoma in hepatitis C-related liver cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Reham A. Aboelwafa ◽  
Walid Ismail Ellakany ◽  
Marwa A. Gamaleldin ◽  
Marwa A. Saad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis C ◽  
Early Stage ◽  
Group Iii ◽  
Real Time Quantitative Pcr ◽  
Early Stages ◽  
Group I ◽  
Egyptian Patients ◽  
Cirrhotic Patients

Abstract Background Hepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR. Results Levels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls. Conclusion Serum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.

Hepatocellular carcinoma in the non-cirrhotic liver

2021 ◽  
pp. 1-14
Author(s):  
Dong Yi ◽  
Wang Wen-Ping ◽  
Won Jae Lee ◽  
Maria Franca Meloni ◽  
Dirk-Andre Clevert ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Risk Factor ◽  
High Risk ◽  
Current Knowledge ◽  
Cirrhotic Liver ◽  
Imaging Features ◽  
Advanced Stage ◽  
High Risk Factor ◽  
Cirrhotic Patients

Liver cirrhosis is an established high-risk factor for HCC and the majority of patients diagnosed with HCC have cirrhosis. However, HCC also arises in non-cirrhotic livers in approximately 20 %of all cases. HCC in non-cirrhotic patients is often clinically silent and surveillance is usually not recommended. HCC is often diagnosed at an advanced stage in these patients. Current information about HCC in patients with non-cirrhotic liver is limited. Here we review the current knowledge on epidemiology, clinical features and imaging features of those patiens.

scholarly journals Magnetic resonance imaging of the cirrhotic liver: diagnosis of hepatocellular carcinoma and evaluation of response to treatment - Part 1

2017 ◽  
Vol 50 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Miguel Ramalho ◽  
António P. Matos ◽  
Mamdoh AlObaidy ◽  
Fernanda Velloni ◽  
Ersan Altun ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Magnetic Resonance ◽  
Cirrhotic Liver ◽  
Response To Treatment ◽  
Arterial Phase ◽  
Resonance Imaging ◽  
Regenerative Nodules ◽  
Magnetic Resonance Imaging Mri

Abstract Magnetic resonance imaging (MRI) is the modern gold standard for the noninvasive evaluation of the cirrhotic liver. The combination of arterial phase hyperenhancement and delayed wash-out allows a definitive diagnosis of hepatocellular carcinoma (HCC) in patients with liver cirrhosis or chronic liver disease, without the requirement for confirmatory biopsy. That pattern is highly specific and has been endorsed in Western and Asian diagnostic guidelines. However, the sensitivity of the combination is relatively low for small HCCs. In this two-part review paper, we will address MRI of the cirrhotic liver. In this first part, we provide a brief background on liver cirrhosis and HCC, followed by descriptions of imaging surveillance of liver cirrhosis and the diagnostic performance of the different imaging modalities used in clinical settings. We then describe some of the requirements for the basic MRI technique, as well as the standard MRI protocol, and provide a detailed description of the appearance of various types of hepatocellular nodules encountered in the setting of the carcinogenic pathway in the cirrhotic liver, ranging from regenerative nodules to HCC.

scholarly journals Sub-Classification of Cirrhosis Affects Surgical Outcomes for Early Hepatocellular Carcinoma Independent of Portal Hypertension

2021 ◽  
Vol 11 ◽  
Author(s):  
Er-lei Zhang ◽  
Jiang Li ◽  
Jian Li ◽  
Wen-qiang Wang ◽  
Jin Gu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Surgical Outcomes ◽  
Early Stage ◽  
Surgical Mortality ◽  
Tumor Capsule ◽  
B Virus ◽  
Independent Risk Factors

Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, p &lt;0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, p = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.

scholarly journals The transition in the etiologies of hepatocellular carcinoma-complicated liver cirrhosis in a nationwide survey of Japan

2020 ◽  
Author(s):  
Hirayuki Enomoto ◽  
◽  
Yoshiyuki Ueno ◽  
Yoichi Hiasa ◽  
Hiroki Nishikawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Viral Hepatitis ◽  
Real Number ◽  
Nationwide Survey ◽  
Hcv Infection ◽  
Annual Number ◽  
The Real ◽  
Number Of Patients ◽  
Viral Etiologies

Abstract Background We recently reported the real-world changes in the etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed the etiologies of LC with hepatocellular carcinoma (HCC). Methods Fifty-five participants from 68 institutions provided data on 23,637 patients with HCC-complicated LC. The changing trends in etiologies were assessed. We further analyzed the data from 29 hospitals that provided the annual number of newly identified HCC-complicated LC patients from 2008 to 2016 (N = 9362) without any missing years and assessed the transition in the real number of newly identified HCC-complicated LC cases. Results In the overall cohort, hepatitis C virus (HCV) infection (60.3%) and hepatitis B virus (HBV) infection (12.9%) were the leading and third-most common causes of HCC-complicated LC in Japan, respectively. HCV infection was found to be the leading cause throughout Japan. The rate of viral hepatitis-related HCC decreased from 85.3 to 64.4%. Among non-viral etiologies, notable increases were observed in nonalcoholic steatohepatitis (NASH)-related HCC (from 1.5 to 7.2%) and alcoholic liver disease (ALD)-related HCC (from 8.5 to 18.6%). Regarding the real number of newly diagnosed patients, the number of patients with viral hepatitis-related HCC decreased, while the number of patients with non-viral HCC, particularly NASH-related HCC, increased. Conclusions Viral hepatitis has remained the main cause of HCC in Japan. However, the decrease in viral hepatitis-related HCC, particularly HCV-related HCC highly contributed to the etiological changes. In addition, the increased incidence of non-viral HCC, particularly NASH-related HCC, was involved in the changing etiologies of HCC-complicated LC in Japan.

Spine stereotactic radiosurgery as a promising modality in patients with metastatic hepatocellular and cholangiocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13551-e13551
Author(s):  
Olsi Gjyshi ◽  
Ahmed Omar Kaseb ◽  
Amol J. Ghia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Therapy ◽  
Viral Hepatitis ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Cox Regression ◽  
Early Stage ◽  
Spinal Metastases ◽  
High Dose ◽  
Cox Regression Analysis

e13551 Background: While stereotactic body radiation therapy (SBRT), a form of high-dose rate radiation therapy, is often used in the local management of early-stage hepatocellular carcinoma (HCC), its role in managing metastatic hepatobiliary malignancies is currently unclear. Here, we investigate the role of spine stereotactic radiosurgery (SSRS), a form of SBRT that targets spinal metastases, in the management of late-stage HCC or cholangiocarcinoma. Methods: We retrospectively reviewed a total of 28 patients with 43 HCC or cholangiocarcinoma metastases treated with SSRS between 2004 and 2017 at our institution. We used Kaplan-Meier curves to estimate overall survival (OS) and local control (LC), and Cox regression analysis to identify potential predictive factors of the two. Results: The median patient age was 63 (range 28 to 78) years old. Four patients had a histology-proven diagnosis of metastatic cholangiocarcinoma, while 39 had hepatocellular carcinoma. Of the patients with HCC, 47% had predisposing viral hepatitis, while 53% had either non-alcoholic steatohepatitis (NASH) or no known predisposing factors. Twenty-nine cases were treated with 24Gy in 1 fraction, 11 with 27Gy in 3 fractions, 2 with 18Gy in 2 fractions, and 1 with 30Gy in 5 fractions. The 1-year actuarial OS and LC rates were 23% and 75%, respectively. The median OS was 6.3 months, while the median time to local failure was not reached. On univariate modeling, negative predictors of LC included history of prior RT to the site of metastasis (p < 0.005) and tumor volume > 60cc (p = 0.03), while biologic equivalent dose (BED) > 52Gy was the only positive predictive factor (p < 0.05). Presence of epidural disease, Bilsky grade, presence of viral hepatitis, or type histology were not predictors of LC (all p > 0.05). In patients who had pain or neurologic findings at presentation, 56% reported improvement in their symptoms on follow up. Three patients (11%) developed compression deformity and one patient (4%) developed radiation-induced neuritis. Conclusions: SSRS provides promising and durable local control in patients with metastatic hepatobiliary disease, and early intervention with high BED are necessary to ensure high level of local control, improvement in symptoms, and a low rate of long-term toxicity.

Serum Dickkopf-1 as a diagnostic & prognostic marker for Hepatocellular Carcinoma

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Enas Mahmoud Foda ◽  
Khaled Amr Mansour ◽  
Walaa Mohamed Hashem ◽  
Nancy Zakaria Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Prognostic Marker ◽  
Early Stage ◽  
Serum Levels ◽  
University Hospitals ◽  
Post Intervention ◽  
Curative Therapy ◽  
Diagnostic Role ◽  
Dickkopf 1

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading reason of cancer-associated deaths around the world.The poor outcome of patients with HCC is attributed to late detection, with more than two-thirds of patients diagnosed at advanced stages of the disease. However, a considerable improvement in survival has been observed (5-year survival up from 40% to 70%) when patients are diagnosed at an early stage and receive potentially curative therapy in the form of liver transplantation, surgical resection, or tumor ablation. Objective Evaluate levels of serum Dickkopf-1, & its significance as a diagnostic & prognostic marker for Hepatocellular Carcinoma. Aim of the work assess the possible diagnostic role of serum DKK1 compared to alpha- fetoprotein which is the slandered marker used for diagnosis of HCC.also DKK1 act as prognostic marker for Hepatocellular Carcinoma. Pateints and Methodes This study had been carried out on 45 subjects diveded into 2 groups,first group include 30 pateints with liver cirrhosis,and second group 15 pateints with HCC.In this group of patients DKK1 was withdrawn before TACE & 3 months post intervention, age range 25-73 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals from March 2019 till January 2020.They were distributed as 25 males and 20 females. There were 13 pateints with child A,17 pateints with child B, & 15 pateints (20%) with child C. Results In this study, the serum levels of serum DKK1 were highest in patients with HCC compared to those with liver cirrhosis. Also DKK1 values significally decreased after intervention(TACE). Conclusion Serum DKK1 act as a diagnostic marker for HCC and its level significally decrease after TACE

scholarly journals Diagnostic and therapeutic potential of the gut microbiota in patients with early hepatocellular carcinoma

2019 ◽  
Vol 11 ◽  
pp. 175883591984818 ◽  
Author(s):  
Francesca Romana Ponziani ◽  
Alberto Nicoletti ◽  
Antonio Gasbarrini ◽  
Maurizio Pompili
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Gut Microbiota ◽  
Therapeutic Potential ◽  
Early Stage ◽  
Intestinal Flora ◽  
Early Hepatocellular Carcinoma ◽  
Pathological Conditions ◽  
Immunological Alterations

The gut microbiota is involved in the maintenance of the homeostasis of the human body and its alterations are associated with the development of different pathological conditions. The liver is the organ most exposed to the influence of the gut microbiota, and recently important connections between the intestinal flora and hepatocellular carcinoma (HCC) have been described. In fact, HCC is commonly associated with liver cirrhosis and develops in a microenvironment where inflammation, immunological alterations, and cellular aberrations are dramatically evident. Prevention and diagnosis in the earliest stages are still the most effective weapons in fighting this tumor. Animal models show that the gut microbiota can be involved in the promotion and progression of HCC directly or through different pathogenic mechanisms. Recent data in humans have confirmed these preclinical findings, shedding new light on HCC pathogenesis. Limitations due to the different experimental design, the ethnic and hepatological setting make it difficult to compare the results and draw definitive conclusions, but these studies lay the foundations for a pathogenetic redefinition of HCC. Therefore, it is evident that the characterization of the gut microbiota and its modulation can have an enormous diagnostic, preventive, and therapeutic potential, especially in patients with early stage HCC.

scholarly journals Abundance of Immunologically Active Alanine Aminotransferase in Sera of Liver Cirrhosis and Hepatocellular Carcinoma Patients

2009 ◽  
Vol 55 (5) ◽  
pp. 1022-1025 ◽  
Author(s):  
Hyun Jeong Kim ◽  
Sang Wook Oh ◽  
Dong Joon Kim ◽  
Eui Yul Choi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Enzymatic Activity ◽  
Enzyme Immunoassay ◽  
Roc Curve ◽  
Alanine Aminotransferase ◽  
Liver Diseases ◽  
Serum Samples ◽  
Sandwich Enzyme Immunoassay

Abstract Background: Although alanine aminotransferase (ALT) is a widely used indicator of liver function, ALT enzymatic activity may not always reflect the degree of liver damage. Improved methods or approaches would be useful. Methods: Monoclonal antibodies (mAbs) to ALT were generated to develop a sandwich enzyme immunoassay system. We used an immunoassay to measure ALT mass concentration and a common biochemical analyzer to assay ALT enzymatic activity in serum samples from patients with liver diseases and healthy individuals. The results from the 2 methods were compared and analyzed by ROC curve analysis. Results: The ALT sandwich enzyme immunoassay system demonstrated reliable performance in linearity, recovery, and imprecision studies. The ALT activity assay exhibited a higher diagnostic accuracy in acute hepatitis (AH) patients, but the ALT immunoassay exhibited higher sensitivity and specificity in patients with chronic liver diseases. The areas under the ROC curve for ALT mass and enzymatic activity were 0.82 and 0.98, respectively, in AH, 0.99 and 0.52 in hepatocellular carcinoma (HCC), and 0.94 and 0.45 in liver cirrhosis (LC). Serum samples from HCC and LC patients had higher amounts of ALT–immunoglobulin complexes [median A450, 1.7 (interquartile range, 1.4–1.9)] than the other groups [1.3 (interquartile range, 0.9–1.6)]. Conclusions: Our analysis of sera from the HCC and LC patient groups revealed considerable amounts of immunologically active but catalytically inactive ALT. The amount of the ALT–immunoglobulin complex increased with the severity of the liver disease. The 2-site immunoassay method may be useful in the differential diagnosis of some causes of liver disease.

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