Terminal Stage Hepatocellular Carcinoma Research Articles

Clinicopathological Features and Survival of Patients with Hepatocellular Carcinoma in Ethiopia: A Multicenter Study.

(1) Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers globally, killing over 700,000 people each year. Despite the rising incidence and mortality rates of HCC in Ethiopia, only few single-centered studies have been conducted; therefore, we aimed to explore the clinicopathological characteristics and survival of patients with HCC in multicenter settings. (2) Methods: We conducted a retrospective analysis of 369 patients with confirmed HCC diagnosed between 2016 and 2021. The survival of patients weas determined using the Kaplan−Meier method, and hazard ratios of the prognostic factors were estimated in Cox proportional hazard models. (3) Results: Majority patients were male (67%) and had a mean age of 52.0 ± 15.6 years. The majority of patients (87%) had a large tumor size (>5 cm) at diagnosis and presented with an advanced-stage condition. Cirrhosis (58%) and viral hepatitis (46.5%) were the main risk factors associated with HCC. The median overall survival was 141 days (95% CI: 117−165). Patients who took antivirals for HBV had a higher survival benefit compared to the untreated group (469 vs. 104 days; p < 0.001). The risk of death was 12 times higher in patients with Barcelona Clinic Liver Cancer-D (BCLC-D) terminal stage HCC compared to patients with an early stage (BCLC-A) HCC. The stage of HCC and treatment against HBV are the most significant survival predictors. (4) Conclusions: The overall survival of HCC patients in Ethiopia is poor. Cirrhosis and viral hepatitis are the primary risk factors linked with HCC. Patients who received antiviral therapy for HBV had a better survival outcome.

Poly(ADP-Ribose) Polymerase Inhibition as a Promising Approach for Hepatocellular Carcinoma Therapy.

Simple SummaryLiver cancer has very high incidence and mortality rates, making it a major public health problem. Indeed, the available treatments are not numerous, and few strategies exist for patients with advanced cancers. Thus, there is an urgent need to search for new treatment targets. This review provides an overview of one potential target, poly(ADP)ribose polymerase 1, a protein involved in DNA repair pathways and its expression profiles in liver cancer. Inhibition of this protein could potentiate the effects of current treatments and improve therapeutic outcomes for patients.Primary liver cancer is the sixth most common cancer in men and seventh in women, with hepatocellular carcinoma (HCC) being the most common form (75–85% of primary liver cancer cases) and the most frequent etiology being viral infections (HBV and HCV). In 2020, mortality represented 92% of the incidence—830,180 deaths for 905,677 new cases. Few treatment options exist for advanced or terminal-stage HCC, which will receive systemic therapy or palliative care. Although radiotherapy is used in the treatment of many cancers, it is currently not the treatment of choice for HCC, except in the palliative setting. However, as radiosensitizing drugs, such as inhibitors of DNA repair enzymes, could potentiate the effects of RT in HCC by exploiting the modulation of DNA repair processes found in this tumour type, RT and such drugs could provide a treatment option for HCC. In this review, we provide an overview of PARP1 involvement in DNA damage repair pathway and discuss its potential implication in HCC. In addition, the use of PARP inhibitors and PARP decoys is described for the treatment of HCC and, in particular, in HBV-related HCC.

Selecting the first line treatment in non-metastatic hepatocellular carcinoma - comparing clinical practice guidelines.

Primary malignancy of the liver or hepatocellular carcinoma (HCC) is unique in its presentation, disease process, and management. Unlike breast or colon cancer, the staging of HCC depends on performance status and baseline liver function along with pathological characteristics. Apart from traditional options like surgery and systemic therapy, effective management can be achieved in selected cases with liver transplant and locoregional therapy (LRT) like transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and ablation. Liver study societies and cancer groups across the globe proposed guidelines to aid the treating physicians in choosing first-line treatment for liver cancer. It is tough to compare these guidelines as they differ not only in treatment recommendations but also in risk assessment (and staging). The approach to the same patient may be different in the country he or she is managed. In clinical practice, decisions are usually taken on the consensus of multidisciplinary tumor boards and do not necessarily adhere to any guidelines. In the early (and very early) stage HCC, curative options like surgery, transplant, and ablation are recommended. In intermediate stage HCC, LRT (TACE and TARE) is preferred in the first line and systemic therapy for treatment failure or residual disease. Systemic therapy, including the atezolizumab/bevacizumab combination and tyrosine kinase inhibitors (TKI) like sorafenib and lenvatinib, is used for advanced stages. Supportive care is advised for terminal stage HCC.

Identification of a role for serum aldo-keto reductase family 1 member B10 in early detection of hepatocellular carcinoma.

Despite improved screening programs, the vast majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. A lack of effective diagnosis methods for preclinical HCC has resulted in a low rate of early detection. Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with several cancer types. However, to the best of our knowledge, the diagnostic value of AKR1B10 in early stage HCC is poorly understood. In the current study, the diagnostic performance of serum AKR1B10 in hepatitis B virus/hepatitis C virus (HBV/HCV)-related liver disorders was evaluated and the unique role of AKR1B10 in diagnosing HCC was assessed. Serum AKR1B10 was detected by sandwich ELISA in 84 patients with HBV/HCV-related HCC, 74 patients with liver cirrhosis, 29 patients with chronic hepatitis and 30 healthy controls. Serum AKR1B10 and α-fetoprotein (AFP) levels were analyzed and compared. Elevated levels of serum AKR1B10 were identified in patients with HCC compared with patients with other liver disorders (P<0.05). Compared with advanced and terminal stage HCC, a significant increase in AKR1B10 levels was primarily detected in early and intermediate stage HCC. The sensitivity (81.0%) and specificity (60.9%) for HCC diagnosis with AKR1B10 were high at a cutoff value of 1.51 ng/ml. Conversely, a prominent increase in AFP was observed in advanced and terminal stage HCC. Furthermore, concurrent measurement of serum AKR1B10 and AFP significantly increased sensitivity and negative predictive value for HCC diagnosis. The results presented in the current study strongly indicate AKR1B10 has a unique role as a biomarker for early stage HBV/HCV-related HCC. Compared with AFP alone, a combination of serum AKR1B10 and AFP increased the diagnostic performance in patients with HCC. In summary, the current results identify a unique role of AKR1B10 in HCC diagnosis.

The Relationship between Psychological Distress and Coping Strategies in Patients with Advanced or Terminal Stage Hepatocellular Carcinoma: A Cross-Sectional Descriptive Study

Objectives: This study was aim to describe the relationship between psychological distress and coping strategies among patients with advanced or terminal stage hepatocellular carcinoma.Material and Method: This is a cross-sectional descriptive study. Data were collect from hospitalized sample at medical units in a tertiary care hospital in southern Thailand during April 2015 - December 2016. Ninety-six sample of advanced or terminal stage hepatocellular carcinoma. Research instruments consisted of 4 parts: (1) a demographic data form, (2) The Karnofsky Performance Status Scale, (3) psychological distress questionnaires using Hospital Anxiety and Depression Scale, and (4) coping strategies questionnaire developed by researchers based on Lazarus and Folkman’s stress and coping theory and literature reviews. Cronbach’s alphas for Hospital Anxiety and Depression Scale and coping strategies questionnaire were 0.89 and 0.84. Data were analyzed using descriptive statistics and Pearson’s product moment correlation coefficient was used.Results: A relationship analysis found that there was a moderate, negative correlation between psychological distress and coping strategies (r=-0.66, p-value&lt;0.001)Conclusion: The results of this study reveal that increases in psychological distress were correlated with decreases in coping strategies among patients with advanced or terminal stage hepatocellular carcinoma. A screening assessment for psychological distress is needed. The results of this study can be used for developing nursing program to promote effective coping strategies among patients with advanced or terminal stage hepatocellular carcinoma to help them live well at the end of life.

Impact of tumor burden on prognostic prediction for patients with terminal stage hepatocellular carcinoma: A nomogram study.

BackgroundThe recently proposed nomogram of Barcelona Clinic Liver Cancer (BCLC) lacks predictive accuracy for patients with stage D hepatocellular carcinoma (HCC). Tumor burden is crucial in prognostic prediction but is not included in the criteria of stage D HCC. This study aims to develop a nomogram with tumor burden as the core element for BCLC stage D patients.MethodsA total of 386 patients were randomly grouped into derivation and validation sets (1:1 ratio). The multivariate Cox proportional hazards model was used to select factors with significant prognostic effect and generate the nomogram. Concordance indices and calibration plots were used to evaluate the performance of nomogram.ResultsOverall survival of study patients was significantly associated with tumor burden as well as hepatitis B, serum α-fetoprotein level, cirrhosis and performance status in multivariate Cox regression (all p<0.05). Beta-coefficients of these variables in derivation set were used to generate the nomogram. Each patient was assigned with a total nomogram point that predicted individualized 6-month and 1-year survival. The derivation and validation sets had a c-index of 0.759 (95% confidence interval [CI]: 0.552–0.923) and 0.741 (95% CI: 0.529–0.913), respectively. The calibration plots were close to the 45-degree line for 6-month and 1-year survival prediction for all quarters of patients in both derivation and validation sets.ConclusionTumor burden is significantly associated with the outcome for patients with stage D HCC. The tumor burden-incorporated nomogram may serve as a feasible and easy-to-use tool in predicting survival on an individual level.

Management of hepatocellular in the United States.

Hepatocellular carcinoma (HCC) is a major cause of cancer burden globally. In the United States, the incidence of HCC is forecast to continue to rise for the next 15 years. Patients with HCC vary markedly owing to heterogeneous tumor characteristics and concomitant liver dysfunction. In the United States and Europe, HCC is staged and managed according to the Barcelona Clinic Liver Cancer (BCLC) system. For very early and early stage HCC, or BCLC 0/A, liver transplant is the optimal treatment option. Liver resection and radiofrequency or microwave ablation are alternative treatment options. For intermediate stage HCC, or BCLC B, transarterial chemoembolization (TACE) is the standard of care. An alternative locoregional therapy, transarterial radioembolization using yttrium-90, has shown comparable outcomes with TACE and may be used in patients for whom TACE is contraindicated. For advanced stage HCC, or BCLC C, systemic chemotherapy with sorafenib, a multikinase inhibitor, is the only evidence-based treatment option available. Another multikinase inhibitor, regorafenib, was recently approved as a second-line therapy for this patient group. Randomized clinical trials investigating other agents in enriched patient groups and novel therapeutics including checkpoint inhibitors are underway. Patient with prohibitive performance status and/or end stage liver dysfunction are classified terminal stage HCC, or BCLC D, and are managed with best supportive care. The future direction for the management of HCC will rely on continuing efforts to uncover molecular pathways and actionable genetic aberrations in HCC.

Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma.

To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher's exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral bleeding and another patient had an esophageal ulcer after treatment. The Cyberknife can be safely administered to patients with advanced or terminal stage HCC. High AFP levels were associated with worse survival, but a higher radiation dose improved the survival.

Experiences of Family of Patient with Newly Diagnosed Advanced Terminal Stage Hepatocellular Cancer

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide due to its generally poor prognosis. Caregiver burden for liver cancer cases is higher than with other cancer and needs especial attention. To explore the experiences of families of patients with newly diagnosed advanced terminal stage hepatocellular cancer by interview. Nine participants were recruited in this study. Content analysis of the interviews revealed four themes: blaming oneself, disrupting the pace of life, searching all possible regimens, and not letting go. This study provides new insight into the needs and support of family members especially when they are facing loved ones with newly diagnosed advanced terminal stage HCC. These results will inform future supportive care service development and intervention research aimed at providing assistance in reducing unmet supportive care needs and psychological distress of these family members.

Rather than interleukin‐27, interleukin‐6 expresses positive correlation with liver severity in naïve hepatitis B infection patients

Effective cytokines can drive the commitment of naive T cells to regulate immune response after antigen-mediated activation. Aims are to elucidate the clinical role of serum IL-27 and IL-6 in the different stages of naïve hepatitis B virus (HBV)-infected patients. Samples with well-characterized clinical profiles were assessed from 395 HBV-infected patients including chronic hepatitis B (CHB) group in 291 patients, liver cirrhosis (LC) group in 57 patients, hepatocellular carcinoma (HCC) group in 47 patients. Another 139 non-HBV infected individuals were enrolled as control group (CG) including 104 with normal liver function (NF) and 35 with liver dysfunction (LD). The HBV-infected group and separated groups presented significantly higher IL-27 and IL-6 expression than the CG or subgroups of CG. In contrast to IL-27, IL-6 showed significant differences with deteriorating liver condition compared with LC or HCC with CHB groups. Furthermore, IL-6, rather than IL-27, showed significant statistical differences in patients with advanced liver disease compared with those of mild or moderate to severe liver disease and in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. The data associated with liver function, including Albumin, Bilirubin, INR, Platelet and AFP levels, were significantly correlated to IL-6 expression, but had weak correlation to IL-27 expression in HBV patients. Serum IL-27 can trigger immune response to prevent hepatic injury in different clinical-pathologic stages of HBV-infected patients earlier, but IL-6 may play an extremely important role to determine the liver progression.