Diagnostic value of betatrophin for hepatocellular carcinoma in patients with liver cirrhosis

Background Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third cause of cancer-related mortality world- wide. The incidence of HCC is on the increase, and it is a major threat to our modern life. Epidemiological studies have indicated that HCC are related to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Aim of the Work To evaluate the role of AFU as a diagnostic marker versus AFP in HCC post viral cirrhotic Egyptian patients. Patients and Methods This study had been carried out on 90 subjects, age range 21-75 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals from January 2022 to June 2022. Results We found that serum levels of AFU were highest in patients of group A with HCC (129.867 ± 32.997 μl U/ml) compared to those with liver cirrhosis (33.433± 14.818 μl U/ml) with P value < 0.001 and the control groups (3.177 ± 1.199 μl U/ml) with P value < 0.001. Similarly alpha fetoprotein its serum levels were much higher in the HCC group (4688.223±11490.009 ng/ml) compared to the cirrhotic patients (4.407±3.107 ng/ml) with P value 0.02 Also, compared to healthy individuals (2.623±1.566 ng/ml) with p value 1.00. We found that there is No significant statistical correlation between serum AFP and AFU in our studied HCC and cirrhotic patients (R 0.332, P 0.073 for HCC and R 0.222, P 0.238 for cirrhotic). Regarding the negative correlation between serum AFU level and AFP level in order to predict the diagnostic value, sensitivity and specificity of both of them in term of tumor size, our study show that for AFU when the best cut off value was >52μl U/ml the sensitivity was 100% and specificity was 90% while for AFP when the best cut off value was > 10.5 ng/ml the sensitivity was 96.67% and specificity 96.67%. AFU is a promising serum tumor marker for HCC diagnosis and can be combined with AFP. Conclusion We concluded from this study that: Serum AFP was highly significant increase in HCC patients compared to cirrhotic and healthy controls, this is in agreement with many several reports that consider AFP in high serum levels as diagnostic for HCC combined with triphasic CT abdomen or dynamic MRI. Serum AFU levels were significantly higher in patients with HCC and mildly elevated in patients with liver cirrhosis compared to the control group. So it can be used as a tumor marker for HCC diagnosis. No correlation between AFU and laboratory data and child score. AFU was not influenced by clinical condition of the liver itself but with HCC. Around 40% of HCC patients have normal or low AFP level so AFU may be useful as a diagnostic marker in those patients. Serum AFP is the standard tumor marker used in clinical practice for diagnosis and surveillance of HCC in cirrhotic patients in spite of normal and low AFP HCC patients that may reach 40%. Sensitivity and specificity of AFU was nearly similar to sensitivity and specificity of AFP. Combined use of AFU with AFP or possibly other markers will improve the diagnostic field and can help in early detection of HCC in surveillance programms.

Objectives: This study was conducted to investigate whether leptin is involved in the etiogenesis of hepatocellular carcinoma (HCC) in cirrhotic patients. Methods: Thirty-one male cirrhotic patients with HCC, 26 male cirrhotic patients without HCC, and 25 control subjects were included in this study. Body fat mass (FM) was determined by bioelectrical impedance analysis, and serum leptin and hormone concentrations were measured by immunoassay. Results: A significant correlation of serum leptin levels to FM was observed in both patient groups and control subjects (r = 0.760, p < 0.001; r = 0.520, p < 0.01; r = 0.460, p < 0.05, respectively). The serum leptin levels in cirrhotic patients with or without HCC were significantly higher than those in control subjects (6.0 ± 1.1 vs. 6.1 ± 0.6 vs. 3.8 ± 0.3 ng/ml, p < 0.05), though their body FM was lower. Using a multiple logistic regression analysis, it was found that the odds ratio of serum leptin for HCC was 1.04 (95% CI 0.79–1.33) after adjustment of several known risk factors. Conclusions: Our study demonstrated that cirrhotic patients with or without HCC had increased serum leptin concentrations. However, leptin did not appear to be associated with the development of HCC in cirrhotic patients.

The significance of serum levels of glycosaminoglycans (GAGs) and insulin like growth factor-1 (IGF-1) in early screening of hepatocellular carcinoma in cirrhotic patients was evaluated. The effect of diabetes on GAGs and IGF-1 levels was also estimated. Fifty cirrhotic patients with early stage Hepatocellular carcinoma (HCC) (22 were diabetic), thirty control cirrhotic patients without HCC (11 were diabetic) and twenty normal control subjects, were enrolled to the study. Serum α-fetoprotein (AFP), the commonly used marker for HCC, was measured in all HCC patients. Serum GAGs increased significantly, while IGF-1 was reduced in patients with cirrhosis and early stage HCC compared to normal control (P < 0.001). There was a significant reduction in GAGs and IGF-1 levels in control cirrhotic group compared to HCC group (P < 0.05). HCC patients who had normal AFP showed significantly increased GAGs and reduced IGF-1 levels compared to normal control. In comparison with corresponding non-diabetic patients, diabetic patients showed a significant increase in serum GAGs in both cirrhotic control and HCC (P < 0.01), while a significant decrease was observed in serum IGF-1 only in HCC (P < 0.05). Concomitant determination and monitoring of serum GAGs and IGF-1 could be used as a simple, low cost and non-invasive marker for HCC in cirrhotic patients. Key words: Hepatocelluar carcinoma, liver cirrhosis, alpha fetoprotein, glycosaminoglycans, insulin like growth factor-1.

Background: Hepatocellular carcinoma (HCC) is the leading cause of death in HCV-related liver diseases and the third most common cause of cancer-related mortality worldwide. A reliable serum marker for early diagnosis of HCC is currently lacking. Objectives: The aim of this study was to identify the serum levels of soluble Human leukocyte antigen-G (sHLAG) in HCC and liver cirrhosis (LC) patients. As well, we aimed to estimate the diagnostic performance of sHLA-G for HCC by comparing its levels with the levels of Alpha fetoprotein (AFP). Subjects and methods: The study included 100 subjects divided into: 25 apparently healthy volunteers who served as healthy control subjects (group I), and 50 patients with untreated HCC on top of liver cirrhosis (group II) in addition to 25 cirrhotic patients (group III). HCC group was divided into two subgroups, 25 patients with AFP levels ≤ 200 ng/ml and 25 patients with AFP levels >200 ng/ml. All subjects were subjected to routine laboratory investigations plus detection of serum levels of both AFP and sHLA-G by Enzyme Immune Assay (EIA). Results: Blind parallel detection was conducted for sHLA-G and AFP. AFP was highly significantly increased in HCC and LC patients when compared to healthy controls (p=0.001). Also, there was a highly significant increase in AFP level in HCC patients when compared to cirrhotic ones (p=0.001). sHLA-G was highly significantly increased in HCC patients when compared to both healthy controls and cirrhotic patients (p=0.001). sHLA-G was not significantly increased in cirrhotic patients when compared to healthy controls (p=0.001). There was a significant strong positive correlations between sHLA-G and AFP in HCC patients (p<0.001) while weak negative correlation between sHLA-G and AFP was detected in cirrhotic group. The area under the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacies of both markers. The superiority of sHLA-G over AFP was more profound in the diagnosis of HCC [AUC: 0.993], in discriminating HCC from LC patients [AUC: 0.992] as well as in the diagnosis of HCC patients with AFP levels ≤ 200 ng/ml or in discriminating this HCC subgroup from LC patients [AUC: 0.986 and 0.984 respectively]. Conclusion: sHLA-G was found to be superior over AFP because of its higher AUC than that of AFP. As well, sHLA-G has better diagnostic performance with higher sensitivity and specificity than AFP. According to our data, sHLA-G could serve as a new efficient marker for early diagnosis of HCV-related HCC patients and to discriminate HCC from LC patients. Thus, measuring sHLA-G levels can help to reduce both false negative and false positive rates of AFP. Moreover, sHLA-G could have predictive value for tumorogenesis in HCV-related LC patients and could be used along with other tumor markers for early detection of malignant transformation.

Impact of Surveillance on Survival of Patients With Initial Hepatocellular Carcinoma: A Study From Japan

To evaluate the perioperative outcomes and long-term survival of extended hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis. Hepatic resection is a well-established treatment for HCC in cirrhotic patients with preserved liver function and limited disease. However, the role of extended hepatic resection (more than four segments) for HCC in cirrhotic patients has not been elucidated. Between 1993 and 2000, 45 consecutive patients with histologically confirmed cirrhosis underwent right or left extended hepatectomy for HCC (group A). Perioperative outcomes and long-term survival of these patients were compared with 161 patients with HCC and cirrhosis who underwent hepatic resection of a lesser extent in the same period (group B). All clinicopathologic and follow-up data were collected prospectively. Group A patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than group B. However, the two groups were similar in overall morbidity and hospital mortality. There were no significant differences in the incidence of liver failure or other complications. The resection margin width was similar between the two groups. Despite significantly larger tumor size in group A compared with group B, long-term survival was comparable between the two groups. Extended hepatic resection for HCC can be performed in selected cirrhotic patients with acceptable morbidity, mortality, and long-term survival that are comparable to those of lesser hepatic resection. Extended hepatectomy for large HCC extending from one lobe to the other or central HCC critically related to the hepatic veins is justifiable in cirrhotic patients with preserved liver function and adequate liver remnant.

Is there sufficient evidence to recommend antiviral therapy in hepatitis C?

Chapter 2: Diagnosis and surveillance

Background:As most cases of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have concurrent cirrhosis, viral factors identified to be associated with HCC might be related to cirrhosis rather than HCC.Methods:Hepatitis B virus DNA levels, genotypes and precore/basal core promoter (BCP) mutants were compared between cirrhotic HCC and non-cirrhotic HCC patients. Age- and sex-matched case–control studies were performed to identify the risk factors.Results:Hepatitis B virus DNA levels showed no significant difference betwen non-cirrhotic HCC patients (n=20) and cirrhotic HCC patients (n=140) or 1 : 3 age- and sex-matched cirrhotic HCC patients (n=60), but genotype C and BCP mutant were significantly more prevalent in the latter than in the former. In multiple logistic regression, BCP mutant but not genoype C correlated significantly with the presence of cirrhosis in HCC patients. Compared with inactive carriers (n=60), non-cirrhotic HCC patients (n=20) had significantly higher HBV DNA levels but no difference in HBV genotypes and precore/BCP mutants. Furthermore, HBV DNA levels, the distribution of HBV genotypes and the prevalence of precore/BCP mutants all failed to show any significant difference between cirrhotic HCC patients (n=60) and cirrhotic patients without HCC (n=60).Conclusion:Basal core promoter mutant is associated with progression to cirrhosis rather than HCC in chronic HBV infection.

A comparison of surgical outcomes for noncirrhotic and cirrhotic hepatocellular carcinoma patients in a Western institution

Can We Move on From the Discussion of Direct Antiviral Agents and Risk of Hepatocellular Carcinoma Recurrence?

Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality globally, with a strong association with chronic liver disease, particularly cirrhosis. In cirrhotic patients, the overlapping clinical manifestations of HCC and underlying liver dysfunction complicate timely diagnosis and management. Understanding the clinical characteristics of HCC in this population is essential for improving outcomes. Objective: To evaluate the clinical characteristics of HCC in cirrhotic patients, focusing on differences in liver function, demographic profiles, and etiological factors. Methodology: A cross-sectional observational study was conducted at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, between December 2019 and August 2020. The study included 66 participants divided into two groups: cirrhotic patients with HCC (n=33) and cirrhotic patients without HCC (n=33). Data were collected through clinical, biochemical, and radiological assessments, with HCC diagnosis confirmed via fine-needle aspiration. Statistical analysis included t-tests, Chi-square tests, and ROC analysis. Results: The mean age of HCC patients was 49.85 ± 14.40 years, with 87.9% male predominance, similar to the cirrhosis group (mean age: 46.15 ± 11.06 years, 72.7% male). Significant differences were observed in prothrombin time (p=0.002), INR (p&lt;0.001), and serum albumin (p=0.009), indicating relatively preserved liver function in HCC patients. HCC patients predominantly fell into Child-Pugh class B (54.5%), whereas cirrhotic patients were more commonly class C (39.4%, p=0.037). Hepatitis B virus (HBV) was the leading etiological factor in both groups, with HBsAg detected in 84.8% of HCC and 93.9% of cirrhotic patients. Conclusion: HCC in cirrhotic patients presents with distinct clinical and biochemical profiles, including better-preserved liver function and higher serum albumin levels compared to cirrhotic patients without HCC. The high prevalence of HBV in the region underscores the need for targeted surveillance and early intervention strategies. Further multicenter studies are recommended to validate these findings and enhance diagnostic and therapeutic approaches.

Background: Hepatocellular carcinoma (HCC) is the fifth most common malignancy. Midkine (MK) is a cytokine or a growth factor belongs to the carbohydrate-binding proteins. MK is over expressed in hepatocellular carcinoma. Furthermore, patients with high MK expression in the tumor frequently have a worse prognosis than those with low MK expression. Objectives: The aim of the work was to evaluate serum midkine as a marker for Hepatocellular carcinoma in cirrhotic patients. Patients and Methods: This study was conducted on 90 subjects who were divided into three groups: group I included 40 patients with liver cirrhosis and hepatocellular carcinoma, group II included 40 patients with HCV related liver cirrhosis without HCC and group III with 10 healthy subjects as controls. Plasma level of midkine was measured for all subjects. Results: Serum levels of midkine were highest in patients of group I with HCC compared to those with liver cirrhosis and the control groups (p value< 0.001). Also midkine values increased with tumor number and overall size. According to the ROC curve, the best cutoff value for midkine differentiating HCC from liver cirrhosis cases was 8500pg/mL, above which the sensitivity to discriminate HCC = 100% and below which the specificity to discriminate liver cirrhosis = 87.5% with 94.5% accuracy. Conclusion: Serum midkine level was significantly elevated in HCC patients, so it can be used as a diagnostic marker for HCC. Also, it was directly correlated to the tumor number and overall size so it has a good prognostic value.

Background: Hepatocellular carcinoma (HCC) is the fifth most common malignancy. Midkine (MK) is a cytokine or a growth factor belongs to the carbohydrate-binding proteins. MK is over expressed in hepatocellular carcinoma. Furthermore, patients with high MK expression in the tumor frequently have a worse prognosis than those with low MK expression. Objectives: The aim of the work was to evaluate serum midkine as a marker for Hepatocellular carcinoma in cirrhotic patients. Patients and Methods: This study was conducted on 90 subjects who were divided into three groups: group I included 40 patients with liver cirrhosis and hepatocellular carcinoma, group II included 40 patients with HCV related liver cirrhosis without HCC and group III with 10 healthy subjects as controls. Plasma level of midkine was measured for all subjects. Results: Serum levels of midkine were highest in patients of group I with HCC compared to those with liver cirrhosis and the control groups (p value< 0.001). Also midkine values increased with tumor number and overall size. According to the ROC curve, the best cutoff value for midkine differentiating HCC from liver cirrhosis cases was 8500pg/mL, above which the sensitivity to discriminate HCC = 100% and below which the specificity to discriminate liver cirrhosis = 87.5% with 94.5% accuracy. Conclusion: Serum midkine level was significantly elevated in HCC patients, so it can be used as a diagnostic marker for HCC. Also, it was directly correlated to the tumor number and overall size so it has a good prognostic value.

Recognizing the significant prevalence of hepatocellular carcinoma (HCC) in Saudi Arabia, and the difficulties often faced in early and accurate diagnoses, evidence-based management, and the need for appropriate referral of HCC patients, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) formed a multi-disciplinary task force to evaluate and update the previously published guidelines by the Saudi Gastroenterology Association. These guidelines were later reviewed, adopted and endorsed by the Saudi Oncology Society (SOS) as its official HCC guidelines as well. The committee assigned to revise the Saudi HCC guidelines was composed of hepatologists, oncologists, liver surgeons, transplant surgeons, and interventional radiologists. Two members of the task force served as guidelines editors. A wide based search on all published reports on all aspects of the epidemiology, natural history, risk factors, diagnosis, and management of HCC was performed. All available literature was critically examined and available evidence was then classified according to its strength. The whole document and the recommendations were then discussed in details by members and consensus was obtained. All recommendations in these guidelines were based on the best available evidence, but were tailored to the patients treated in Saudi Arabia. We hope that these guidelines will improve HCC patient care and enhance the multidisciplinary care needed for these patients.