Confirmation Of Hepatocellular Carcinoma Research Articles

Raised Alpha-Fetoprotein Level and its Association with Hepatocellular Carcinoma

Objective: To evaluate raised alpha feto-protein levels for socio-demographic and clinicopathological features in hepatocellular carcinoma. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medical Oncology, Jinnah Postgraduate Medical Center, Karachi Pakistan, from Jan 2019 to Jan 2020. Methodology: Two hundred and thirty-six patients of age more than 20 years, of either gender diagnosed with hepatocellular carcinoma were included. Detailed demographic data, information regarding addiction and medical history were collected. According to The National Comprehensive Cancer Network, Hepatocellular carcinoma was diagnosed using a multiphasic liver protocol CT scan with intravenous contrast. The alpha-fetoprotein levels were checked after confirmation of hepatocellular carcinoma on a multiphasic CT scan. The cut-off value for elevated alpha feto-protein was ≥20 ng/mL. Results: The median alpha protein levels were reported as 411 ng/mL. About 183(78%) patients had elevated alpha protein levels. In univariate analysis, age, gender, diabetes mellitus, hepatitis B, hepatitis C, portal vein thrombosis, number of lesions, cirrhotic liver, features of portal hypertension, anti-viral treatment status, cigarette smoking, and segment of the liver showed a statistically significant relationship with elevated alpha protein levels (p<0.05). On the multivariate model, age, hepatitis C, number of lesions, portal vein thrombosis, and Child Pugh score showed statistically significant association with elevated alpha protein (p<0.05). Conclusions: The elevated alpha protein levels level was found to be higher among hepatocellular carcinoma and associated with age, hepatitis C, number of lesions, portal vein thrombosis and Child Pugh score.

Debelalactone Prevents Hepatic Cancer via Diminishing the Inflammatory Response and Oxidative Stress on Male Wistar Rats.

The current study was conducted to exemplify the effect of debelalactone on tissue protection, chronic hepatic inflammation, hepatic protection and oxidative stress induced by diethyl nitrosamine in Wistar rats. Therefore, DEN (200 mg/kg) was used for the induction the hepatocellular carcinoma (HCC) and the level of serum alpha fetoprotein was used for the estimation and confirmation of HCC. The study illustrated that debelalactone (DL) significantly downregulated the hepatic, non-hepatic parameters such as aspartate aminotransferase, alanine aminotransferase, alpha fetoprotein, NO levels, total protein, albumin, blood urea nitrogen, total bilirubin, and direct bilirubin in dose dependent manner, as well as noticeably improving the body weight, of treated animals. The macroscopically observation of DEN-induced rat liver showed the formation of informalities in liver tissue, which was reduced with treatment of DL at dose dependent manner. However, antioxidant markers and inflammatory mediators such as lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and transferase, TNF-α, IL-1β, IL-6, and NF-kB restored up to the normal level by DL. The histopathology studies showed that the treated group of animals returned to a normal status. Collectively, it can be concluded that debelalactone mediated chemoprevention in the DEN-induced rats via an increase in the activities of endogenous enzymes and/or inhibition the precancerous cells.

Profile of patients with hepatocellular carcinoma: An experience from a tertiary care center in India

BackgroundThe prevalence of hepatocellular carcinoma (HCC) is increasing worldwide and it is now the third most common cause of cancer-related death. HCC is becoming a major health burden with steadily increasing incidence globally.MethodsThis is an observational study over a 3-year period in a tertiary care center in India. Three hundred and thirty-nine patients diagnosed to have HCC were included in this study. Patients’ clinical, etiological, radiological and cytohistological data and therapy offered were recorded and analyzed.ResultsCirrhosis of the liver was seen in 73.2% of the patients. 16.8% of patients were asymptomatic at the time of presentation. Ascites (57.2%) and jaundice (22.4%) were the most common signs of hepatic decompensation. The most common etiology of HCC was cryptogenic/non-alcoholic fatty liver disease (NAFLD) in 51% of the patients, while hepatitis B and C were seen in 17.4% and 5.8% of the patients, respectively. Advanced and end-stage disease with Barcelona Clinic Liver Cancer (BCLC) stages C and D were seen in 62.4% of patients. 56.6% had Albumin-bilirubin (ALBI) score of 2, while 62.8% had Okuda stage II disease. High alpha-fetoprotein (AFP) levels (>400 ng/mL) were seen in 48.9% of patients. Macrovascular invasion and metastases were seen in 45.9% and 22.2% of the patients, respectively. 17.6% of patients had evidence of tumor thrombus. 14.5% of biopsy specimens showed associated steatosis/steatohepatitis along with confirmation of HCC. Only 26.6% of the cirrhotic HCC patients were diagnosed during surveillance.ConclusionsHCC due to unknown cause/NAFLD appears to be overtaking hepatitis B as the commonest cause for HCC. Despite the advances in diagnostic methods and surveillance, most cases of HCC tend to be diagnosed at advanced stages.

Spectrum of histological diagnoses among clinically suspected PLCC patients in a Nigerian teaching hospital

Background and Objective: Hepatocellular carcinoma (HCC) is a common rapidly growing tumor with poor outcomes and hence requires precise, accurate, and timely diagnosis for early intervention. Although it may be suspected clinically and by imaging investigation such as ultrasound scan (USS) of the liver, there are insufficient data correlating these two modalities with histological diagnosis. This study aims at determining the relevance of liver biopsy in the diagnostic confirmation of HCC in clinically suspected Nigerian patients. Materials and Methods: This is a retrospective cross-sectional study of 105 clinically diagnosed Nigerian patients with HCC who had liver biopsy between January 1, 2001 and December 31, 2017 at the GIT/liver Unit of UCH, Ibadan. After securing the appropriate ethical clearance from the UI/UCH Ibadan ERC, relevant data were collected from patients' Pathology Departmental records and analyzed using appropriate statistical instruments. Results: There were 105 cases of clinically diagnosed HCC patients, 45 of which had imaging (USS/or computerized tomography scan) diagnosis. The mean age of the patients was 44 ± 14.8 years, ranging from 0.25 to 85 years. They consisted of 69 males and 36 females with M:F ratio of 1.9:1. Histological diagnosis was not ascertained in 8 cases (7.6%), while 97 cases (92.4%) had varied diagnoses. Malignant neoplasms, benign neoplasms, liver dysplasia, and nonneoplastic liver diseases were established in 74.1%, 2%, 9.6%, and 14.5% of cases, respectively. Primary liver cancers accounted for 62.8% of cases and included HCC (59.8%), cholangiocarcinoma (1%), hepatoblastoma (1%), and NHL (1%). The sensitivities of clinical and USS diagnoses were 100% and 93%, respectively. The positive and negative predictive values for USS were 65.1% and 0%, respectively. The overall clinical and USS diagnostic accuracies for HCC were 59.8% and 62.2%, respectively. Conclusion: The clinical accuracy for the diagnosis of HCC among clinically suspected and USS diagnosed HCC is limited in comparison to histological diagnosis by liver biopsy. Hence there should be the utilization of liver biopsies for confirmation of HCC in such suspected Nigerian patients.

Predictors and Cumulative Frequency of Hepatocellular Carcinoma in High and Intermediate LI-RADS Lesions: A Cohort Study from a Canadian Academic Institution.

The frequency and predictors of hepatocellular carcinoma (HCC) within each liver imaging reporting and data system (LI-RADS) category remains unclear. We sought to estimate the cumulative frequency of HCC in LI-RADS observations of high/intermediate category and identify clinical/radiographic features associated with HCC. Our diagnostic imaging database was searched for computed tomography/magnetic resonance imaging reports of patients with evidence of cirrhosis and liver observations. LI-RADS categories were determined by imaging review, while demographic and clinical outcomes were assigned by chart review. A composite outcome of clinical/radiographic confirmation of HCC was used. We used multivariable analysis to identify features associated with HCC, and competing risks regression to estimate the cumulative frequency of HCC in each category. Our search returned 95 patients with 137 observations (LR2 = 4, LR3 = 53, LR4 = 37, and LR5 = 43). On multivariable analysis, increasing age (hazard ratio [HR] 1.76 per 10years, p = 0.049), washout (HR 5.34, p < 0.002), and increasing size (size < 10mm reference, 10-20mm, HR 3.93, p = 0.014; size > 20mm, HR 21.69, p < 0.001) were associated with HCC. Median time to diagnosis was 6.13months (interquartile range [IQR] 4.6-13.1), 4.7months (IQR 2.5-14.5), and 3.6months (IQR 1.9-6.6) for LR3, 4, and 5 category observations, respectively. The cumulative frequency of HCC was 59.8% in LR3, 84.62% in LR4, and 99.84% in LR5, at last follow-up. The frequency of HCC within each LI-RADS category reflects the intended purpose, intermediate probability for LR3, probable HCC for LR4, and definite HCC for LR5.

B-Mode Ultrasonography versus Contrast-Enhanced Ultrasonography for Surveillance of Hepatocellular Carcinoma: A Prospective Multicenter Randomized Controlled Trial

Background: Current practice guidelines recommend the use of ultrasound (US) as an initial surveillance tool for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. Patients with liver cirrhosis, however, frequently have coarse liver parenchyma, masking the presence of tiny nodules during B-mode US. Contrast-enhanced US (CEUS) with Sonazoid has a long-lasting, stable Kupffer phase, which makes it possible to scan the entire liver to depict small lesions. In addition, defect reperfusion imaging (reinjection imaging) enables to determine whether the detected nodule is HCC or not. This prospective, multicenter, randomized, controlled trial was conducted to demonstrate the usefulness of Kupffer phase surveillance in the detection of small HCC compared to B-mode US. Methods: A total of 23 institutions joined this study. In total, 656 patients with hepatitis B- or C-related liver cirrhosis were randomized either to the B-mode US surveillance group (n = 313) or the Kupffer phase CEUS with Sonazoid surveillance group (n = 309). The primary endpoint was the maximum size of HCC at the time of the first detection. Secondary endpoints included time to HCC detection, number of tumors, and Barcelona Clinic Liver Cancer stage at the first detection, and sensitivity, specificity, and accuracy of each method in the diagnosis, and the cumulative detection rate of HCC. Results: The mean HCC size at the first detection was significantly smaller in the CEUS (13.0 ± 4.1 mm; n = 28) than in the B-mode US group (16.7 ± 4.1 mm; n = 26) (p = 0.011). Of the 38 patients with HCV cirrhosis diagnosed with HCC by US alone, mean tumor size at the first detection was significantly smaller in the 20 patients diagnosed by CEUS alone than in the 18 diagnosed by B-mode US alone (12.7 ± 3.1 vs. 17.6 ± 7.0 mm, p = 0.012). In contrast, among the 16 patients with HBV cirrhosis diagnosed by US alone, mean tumor size at the first detection was similar in the 8 patients diagnosed by CEUS alone and the 8 diagnosed by B-mode US (13.6 ± 6.0 vs. 14.5 ± 2.7 mm, p = 0.715). Conclusion: Kupffer phase CEUS surveillance with Sonazoid is extremely useful for the early detection and confirmation of HCC using a reinjection technique. Kupffer phase CEUS with Sonazoid contrast combined with the reinjection technique is, therefore, recommended as first-line screening tool for HCC in patients with liver cirrhosis, especially those with very coarse liver parenchyma.

MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma

Current recommendations for patients with cirrhosis are to undergo surveillance for hepatocellular carcinoma (HCC) with ultrasonography (US) every 6 months. However, the sensitivity of US screening to detect early-stage HCC is suboptimal. Magnetic resonance imaging (MRI) with liver-specific contrast may detect additional HCCs missed by US in high-risk patients with cirrhosis. To compare the HCC detection rate of US and MRI in patients with cirrhosis who are at high risk for HCC. A prospective surveillance study of 407 patients with cirrhosis and an estimated annual risk of HCC greater than 5% who underwent 1 to 3 biannual screening examinations with paired US and liver-specific contrast-enhanced MRI at a tertiary care hospital between November 2011 and August 2014. All patients were followed-up with dynamic computed tomography (CT) at 6 months after the study. The confirmation of HCC was based on the results of histologic examination and/or typical CT images of HCC. HCC detection rates and false-positive findings of US vs MRI. A total of 407 eligible patients received 1100 screenings with paired US and MRI. Hepatocellular carcinomas were diagnosed in 43 patients: 1 detected by US only, 26 by MRI only, 11 by both, and 5 were missed by both. The HCC detection rate of MRI was 86.0% (37/43), significantly higher than the 27.9% (12/43) of US (P < .001). Magnetic resonance imaging showed a significantly lower rate of false-positive findings than US (3.0% vs 5.6%; P = .004). Of the 43 patients with HCC, 32 (74.4%) had very early-stage HCC (a single nodule <2 cm), and 29 (67.4%) received curative treatments. The 3-year survival rate of the patients with HCC (86.0%) was not inferior to those without HCC (94.2%; hazard ratio, 2.26; 95% CI, 0.92-5.56; P = .08). In patients with cirrhosis at high-risk of HCC, screening that used MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. With MRI screening, most of the cancers detected were at very early stage, which was associated with a high chance of curative treatments and favorable survival of patients. Whether surveillance with MRI would reduce mortality from HCC in high-risk patients requires further investigation. clinicaltrials.gov Identifier: NCT01446666.

Contrast Enhanced MRI in the Diagnosis of HCC.

Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide. Imaging plays a critical role in HCC screening and diagnosis. Initial screening of patients at risk for HCC is performed with ultrasound. Confirmation of HCC can then be obtained by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), due to the relatively high specificity of both techniques. This article will focus on reviewing MRI techniques for imaging HCC, felt by many to be the exam of choice for HCC diagnosis. MRI relies heavily upon the use of gadolinium-based contrast agents and while primarily extracellular gadolinium-based contrast agents are used, there is an emerging role of hepatobiliary contrast agents in HCC imaging. The use of other non-contrast enhanced MRI techniques for assessing HCC will also be discussed and these MRI strategies will be reviewed in the context of the pathophysiology of HCC to help understand the MR imaging appearance of HCC.

A phase I study of GC33 in Japanese patients with advanced hepatocellular carcinoma (HCC).

235 Background: Glypican-3 (GPC3) belongs to a family of cell-surface heparan sulfate proteoglycans and is specifically expressed in HCC. In this phase I study, we examined the safety, tolerability, and pharmacokinetics of GC33, a recombinant, humanized monoclonal antibody against GPC3, in Japanese patients (pts) with advanced HCC. Methods: This study was a 3+3 design for dose escalation to determine the maximum tolerated dose (MTD) of GC33 given intravenously at 5, 10, and 20 mg/kg weekly. Key eligibility criteria included histological or cytological confirmation of HCC, ECOG PS ≤ 1, Child-Pugh A or B, adequate organ function, and tumor tissues available for GPC3 immunohistochemistry. Results: Thirteen pts were enrolled at 3 dose levels: median age=65 years (range 48-78), M/F=12/1, ECOG PS 0/1=9/4, HBV/HCV=4/8, liver cirrhosis +/-=8/5, Child-Pugh A (5-6)/B (7) =10/3. All pts received prior systemic therapy including sorafenib. Treatment was well tolerated at all dose levels without DLT, and MTD was not reached. The most common AEs were lymphocyte count decrease (77%), Natural Killer cell count decrease (77%), C-reactive protein increase (69%) and pyrexia (62%). Grade 3 AEs (≥ 2 pts) were lymphocyte count decrease (23%), blood pressure increase (23%) and platelet count decrease (15%). Infusion reactions were seen in 62% of pts and medically manageable. Anti-GC33 antibody was not detected in any of the patients. PK analysis of GC33 showed a half-life of 4 to 7 days and dose proportional for AUC after the first dose. Trough concentrations reached a steady state after 4 to 6 doses. Twelve out of 13 biopsied tumor specimens showed immunoreactivity with mouse GC33 antibody. There was no CR or PR, but 7 SD and 3 of them had SD for more than 5 months before progression (all with GPC3 expression). Conclusions: GC33 was well-tolerated up to 20 mg/kg weekly in Japanese HCC pts with Child-Pugh A or B liver cirrhosis and potentially beneficial to GPC3+ HCC. A randomized phase II study of GC33 monotherapy as 2nd line therapy in advanced HCC pts is currently ongoing. Clinical trial information: JapicCTI-101255.

Distribution of microsomal epoxide hydrolase in humans: an immunohistochemical study in normal tissues, and benign and malignant tumours.

Microsomal epoxide hydrolase is a biotransformation enzyme which is involved in the hydrolysis of various epoxides and epoxide intermediates. In the present study, its distribution was investigated in both normal human tissues and human tumours of different histogenetic origin using immunohistochemical techniques. In normal tissue, epithelial cells were more often and more intensely immunostained than mesenchymal cells. The main epithelial cell types expressing microsomal epoxide hydrolase were hepatocytes, acinus cells of the pancreas, and cells of salivary and adrenal glands. Immunostained cells of mesenchymal origin included monocytes, fibrocytes, fibroblasts, vessel endothelium, muscle cells, and cells of the reproductive system. Three patterns of expression were observed in tumour tissues: (1) moderate or strong in hepatocellular carcinomas, tumours of the adrenal gland, and theca-fibromas of the ovary; (2) inhomogeneous staining pattern of variable intensity in breast cancer, lung cancer, colorectal carcinomas, carcinoid tumours, and some tumours of mesenchymal origin; and (3) no expression in malignant melanomas, malignant lymphomas, and renal carcinomas. These data indicate that microsomal epoxide hydrolase expression is not restricted to tissue of any particular histogenetic origin. Nonetheless, immunohistochemical identification of microsomal epoxide hydrolase may be helpful in some well-defined histological settings, for example, confirmation of hepatocellular carcinoma.