Hepatocellular carcinoma screening and surveillance in 2293 chronic hepatitis B patients in an endemic area

AIM To determine the role of screening and surveillance of hepatocellular carcinoma(HCC) in treatment-na?ve chronic hepatitis B(CHB) patients. METHODS We recruited 2293 CHB patients(both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography(AUS) and serum alpha-fetoprotein(AFP) assay every 6 mo. The diagnosis,staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis.RESULTS Among 2293 treatment-na?ve CHB patients,seven cases had HCC at initial screening,giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis,all of which were Child-Pugh class A. With a median follow-up time of 42(range,3-48) mo,10 additional cases were diagnosed with HCC,resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged ≥ 40 years. Most were at an early stage(Stage 0,A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation,with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis,increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels ≥ 20 mg/L at diagnosis were observed in only 7/17 patients,most with a tumor size 5 cm. For HCC screening and surveillance,AUS had a sensitivity and specificity of 94% and 82%,respectively,whereas the sensitivity and specificity of AFP at a cut-off value of ≥ 20 mg/L were 41% and 98%,respectively. Combined use of AUS and AFP assay did not improve effectiveness. CONCLUSION Implementation of active screening and surveillance using AUS to detect early-stage HCC in na?ve CHB patients aged ≥ 40 years in an endemic area is of benefit.     

Highly sensitive and selective antibody microarrays based on a Cy5-antibody complexes coupling ES-biochip for E. coli and Salmonella detection

Foodborne pathogens are threats in food and a cause of major health issues globally. Microbial safety has become a key concern to eliminate disease-causing pathogens from the food supply. For this purpose, the Cy5 dye conjugated with a double-biotin DNA linkage and a detection antibody (Cy5-Ab complexes) was developed to amplify a foodborne detection signal on a microarray. Additionally, the ES-biochip was designed to attain a visual screening of an antibody microarray for the simultaneous threat detection of Salmonella and Escherichia coli (E. coli). Quantification was also performed by fluorescence. After optimizing the Cy5-Ab complex appendage and enhancing the detection signal from a sandwich immunoassay, high sensitivity and selectivity were observed. The limits of detection for both pathogens in buffer and food samples were 10³ CFU mL⁻¹ and less than 9 CFU mL⁻¹ by visual screening and fluorescent intensity quantification, respectively. Mono and duplex responses were not significantly different which means that no cross-reactivity occurred. Uniquely, the assays hold great potential to be used in several fields, such as clinical diagnosis of foodborne microbes, food hygiene screening, and pathogen detection.

A visual ES-biochip was highly sensitive and selective as well as enabled simultaneous detection. An optimized amount of Cy5 dye was attached to a Cy5-Ab complex label using a double-biotin DNA linkage.     

Video-assisted liver ultrasound training for non-radiologists: protocol and preliminary results

BackgroundUltrasound (US) is increasingly used as a bedside diagnostic tool, with training courses for non-radiologists being developed. However, the training time constraint is an important barrier for non-radiologists. We therefore created a short self-learning course for liver-US for non-radiologists.AimAssess the participants’ ability in identifying the organ structures during a liver-US.MethodA short video-lecture on liver-US training and a portable guidebook for image acquisition were developed. Eighteen non-radiologist physicians studied the course and attended hands-on liver-US examinations to capture the assigned images and label the acquired organ/structures, which were evaluated by an expert radiologist.Result130 liver-US examinations were performed, 44 (33.8%) was cirrhosis. The overall of mean image acquisition score was 84.5 ± 9.7%. The mean score of the 1st examination was 75.2 ± 16.4. The mean score was >80% since the 2nd examination. The score was significant lower in cirrhotic cases as compared to non-cirrhotic cases (78.8 ± 17.3 vs. 88.3 ± 14.4, p = 0.001). The participants’ year of study and experience in previous US training did not affect the image acquisition score.ConclusionThe liver-US training course in a short video format with a portable guidebook is effective and relatively low time-consuming for teaching non-radiologists to perform bedside liver-US.     

Characterization of a novel deletion causing (deltabeta)0-thalassemia in a Thai family

A novel deletion of the human beta-globin gene cluster associated with the increased level of fetal hemoglobin (Hb F) in adult life has been demonstrated in a Thai family. A Thai girl who was mistakenly diagnosed as beta-thalassemia/HbE is found to be the compound heterozygote of this mutation and Hb E. The heterozygous father had mild hypochromic and microcytic red blood cells and a high level of Hb F (23.2%). Polymorphic restriction sites in the beta-globin gene cluster identified the homozygous alleles, which localized the deletion region between the psibeta-globin and the 3' beta-globin genes. DNA polymerase that can amplify a long DNA template was employed to examine DNA fragment encompassing this deletion. A 11.3 kilobases (kb) of DNA deletion, beginning approximately 3.1 kb 5' to the delta-globin gene and end in the intron 2 of the beta-globin gene was detected. DNA analysis revealed that this is a case of (deltabeta)(0)-thalassemia with a novel mutation, which can lead to a mild form of beta-thalassemia upon interaction with Hb E.     

Does hepatobiliary phase sequence qualitatively outperform unenhanced T1-weighted imaging in assessment of the ablation margin 24 hours after thermal ablation of hepatocellular carcinomas?

Purpose

To retrospectively determine whether hepatobiliary phase (HBP) sequence outperforms unenhanced T1-weighted imaging (uT1wI) in distinguishing the ablation margin (AM) from hepatocellular carcinoma (HCC) 24 h after thermoablation.

Material and methods

Ninety-one patients [mean age, 65.7 years; 68 M/23F] with 138 HCCs (>6 months follow-up) underwent pre- and postablation gadoxetate disodium-enhanced MRI. AM showed a hyperintense middle zone (MZ) surrounding central hypo- or hyperintense HCCs on uT1wI, and an intermediate-intense MZ encompassing central hypo- or hyperintense HCCs during HBP. The visible AM was defined as persistent MZ around HCCs, which were demarcated from MZ, or peripherally band encompassing MZ, which were not demarcated from HCC. The indefinite AM was defined as no demarcating HCCs from MZ. The ability to distinguish AM from HCC was classified as visible or indefinite on axial (ax)-uT1wI, ax-HBP, coronal (cor)-HBP, and combined all images. To investigate the AM visibility during HBP, significance of differences upon comparison of ax-uT1wI with combined images was analyzed. Preablation liver-tumor contrast ratio (LTCR) on ax-uT1wI and ax-HBP sequence is compared between the visible and indefinite AM.

Results

The McNemar test demonstrated a significant increase (p < 0.05) in visible AM from ax-uT1wI (60), to ax-HBP (70), cor-HBP (79), and combined images (83). TLCR with visible AM was significantly higher than that with indefinite AM on ax-uT1wI (0.4 vs. 0.2, p = 0.001) and ax-HBP sequence (0.9 vs. 0.6, p = 0.004).

Conclusions

HBP sequence might have higher feasibility to distinguish AM from tumor than ax-uT1wI. The TLCR value in visible AM was higher than that in indefinite AM on both ax-uT1wI and ax-HBP sequences.

     

Microwave ablation of liver tumors: degree of tissue contraction as compared to RF ablation

Purpose

To compare the amount of tissue contraction after microwave (MW) versus radiofrequency (RF) ablation of liver tumors.

Materials and methods

Seventy-five hepatic tumors in 65 patients who underwent percutaneous MW or RF ablations were included in this retrospective study. All patients underwent MRI within 6 months before the ablation and 24 h after the procedure. Two blinded radiologists, by consensus, performed measurements on the corresponding series of pre and post-ablation MRI. Absolute and relative contraction of liver, tumor, and control were calculated and compared.

Results

Thirty-one patients underwent MW ablations, and 44 patients underwent RF ablations. The absolute and relative contraction of the ablation zone were significantly greater with MW than RF ablation (p = 0.003 to <0.001). Thirty-two lesions were visible on both pre- and post-ablation MRI. MW ablation had significantly more tumor contraction as compared to RF ablation (p = 0.003 to 0.009). The control measurements demonstrated no significant difference in normal tissue variation between MW and RF groups.

Conclusions

MW ablation of hepatic tumors produced significantly more contraction of tumor and ablated hepatic tissue compared to RF ablation. Tissue contraction should be taken into account during pre-procedural planning and assessing treatment response by comparing pre- and post-ablation images.

     

Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the United States

Purpose

The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated.

Methods

Four hundred thirteen HBsAg-positive patients, 173 with HCC and 240 without HCC, were subgrouped into those with or without a family history of HCC and analyzed for risk factors associated with HCC development. In families with HCC clustering, the ages of HCC onset in parents and siblings were compared.

Results

Forty-four of 173 (25.4 %) HCC patients, all of Asian descent, had 82 other blood relatives with HCC. Of these, 69 (84.1 %) were first-degree relatives. Compared to HCC patients without HCC family history, male HCC patients with family history developed HCC at a younger age than either their mothers or fathers with HCC (45.2 ± 10.3 years vs. 63.0 ± 6.8 years, p < 0.001 and 41.2 ± 14.8 years vs. 60.5 ± 5.5 years, p = 0.001, respectively); however, this was not observed in female HCC patients. In mothers of index HCC cases, 22/26 (84.6 %) tested were HBsAg positive and 14 (63.6 %) had HCC; in fathers, 11/21 (52.4 %) tested were HBsAg positive and 10 (90.9 %) had HCC. By multivariate analysis, independent risk factors for HCC development included family history (OR = 2.58, p = 0.05), male gender (OR = 3.23, p = 0.03), cirrhosis (OR = 2.4, p = 0.04), Child-Pugh classification (OR = 7.62, p = 0.004), AFP per log₁₀ increase (OR = 1.68, p = 0.01), precore mutation (OR = 3.77, p = 0.003), and basal core promoter mutation (OR = 8.33, p < 0.001).

Conclusions

HBsAg-positive male HCC patients presented at a younger age than their parents with HCC. In adult patients with an HCC family history, HCC surveillance should begin at the time of the initial clinic encounter.