MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options.

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC.

Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis.

BACKGROUND: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET. METHODS: Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs). RESULTS: A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities. CONCLUSIONS: In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).

Electrocardiographic abnormalities in patients with sickle cell disease: A systematic review and meta-analysis.

BACKGROUND: Previous studies have documented that electrocardiography (ECG) can reveal a range of abnormalities, offering valuable insights into the cardiac evaluation of patients with sickle cell disease (SCD). The objective of this study is to assess the patterns of ECG abnormalities observed in these patients with SCD, and to determine their prevalence. METHOD: We systematically reviewed the literature using online databases of PubMed, Scopus, Web of Science, Embase, and Google Scholar to identify original studies that reported findings of standard ECG assessments in patients with SCD. Statistical analyses were performed using the random effects model. Additional analyses including sensitivity analysis and subgroup analysis were also conducted. RESULTS: Analysis of data from 59 studies involving 897,920 individuals with SCD revealed that 75% of these patients had abnormal ECG findings (67%-81%), which were predominantly nonspecific ST-T changes, left ventricular hypertrophy, T-wave changes, prolonged corrected QT (QTc) interval, and ischemic changes. Besides, it was shown that these patients had significantly higher odds of having any ECG abnormalities (OR of 17.50, 4.68-65.49), right atrial enlargement (6.09, 1.48-25.09), left ventricular hypertrophy (3.45, 1.73-6.89), right ventricular hypertrophy (7.18, 2.28-22.57), biventricular hypertrophy (10.11, 1.99-51.38), prolonged QTc interval (5.54, 2.44-12.59), ST depression (3.34, 1.87-5.97), and T-wave changes (5.41, 1.43-20.56). Moreover, the mean of QTc interval was significantly higher among those with SCD (23.51 milliseconds, 16.08-30.94). CONCLUSION: Our meta-analysis showed a higher prevalence of abnormal ECG findings among individuals with SCD. A significant proportion of these patients had various ECG abnormalities, suggesting a potential need for regular ECG assessments for patients with SCD.

Epidemiological and clinical characteristics of long COVID-19 among Iranians: A community-based study in southern Iran.

BACKGROUND: The study aimed to evaluate the prevalence and pattern of long COVID-19 (LC) symptoms among individuals who had contracted COVID-19, to calculate the incidence of LC, and to provide insights into risk factors associated with developing LC in this population. METHODS: This population-based cross-sectional survey was conducted in Fars province in 2023. Adult participants with a history of COVID-19 were recruited using a cluster random sampling method, alongside a control group with similar characteristics through the same methodology. Data were collected through in-person interviews using two researcher-developed data collection forms focused on demographic and clinical information. RESULTS: A total of 2010 participants, comprising 1561 (77.7%) and 449 (22.3%) individuals with and without a previous history of COVID-19 were included. Among those with COVID-19 history, the prevalence of experiencing any symptoms was 93.7% (95% CI of 92.3%-94.8%) during the disease acute phase and 36.4% (95% CI of 34.0%-38.8%) after recovery. The incidence of symptoms specifically related to COVID-19, calculated by comparing the symptom rates between participants with and without a history of COVID-19, was found to be 13%. Factors such as older age, previous hospitalization for COVID-19, presence of cardiovascular disease, and use of steroids/chemotherapy were associated with LC symptoms. CONCLUSIONS: Our investigation sheds light on long-term aspects of COVID-19, demonstrating a significant prevalence of LC with diverse manifestations. It also underscores the importance of establishing standardized criteria and control groups in research on LC to address challenges related to heterogeneity and potential overestimation of symptoms.

The effect of mass media campaigns on oral health knowledge: A systematic review and meta-analysis.

OBJECTIVES: Knowledge and awareness gained from mass media can prepare people for lifestyle changes and impact their health and well-being. Considering the differences in the results of primary studies, we decided to conduct this study to evaluate the effect of mass media campaigns on oral health knowledge as a systematic meta-analysis and review. METHOD: The databases such as the Web of Sciences (ISI), Scopus, PubMed/Medline, and the Cochrane Library were searched systematically until February 2022. Data pooling was performed using a random effects model. The effect sizes were estimated as odds ratios (ORs) with their 95% confidence intervals (CIs). Additional analyses, including sensitivity, subgroup, and publication bias analyses, were also conducted. RESULTS: Our meta-analysis comprised a total number of seven articles. The pooled results indicated significant increases in oral health knowledge among included studies (OR = 1.64, 95% CI: 1.20-2.24, p < 0.001). In subgroup analyses, the effects of mass media campaigns on oral health knowledge remained significant for the studies with follow-up of less than 150 weeks (OR = 1.69, 95% CI: 1.49-1.91) and working-age populations (OR = 1.80, 95% CI: 1.40-2.32) compared to other categories. CONCLUSION: In general, this study showed that mass media campaigns may have positive effects on oral health knowledge, especially in the working-age population; it seems that for improving health knowledge among children, more initiatives are needed. Besides, the effects of these campaigns seem to be time-dependent and higher in shorter follow-up periods.

The COVID-19 Pandemic, Socioeconomic Effects, and Intimate Partner Violence Against Women: A Population-Based Cohort Study in 2020, Iran.

Objectives. To investigate the prevalence, pattern, and socioeconomic risk factors of intimate partner violence (IPV) before and 6 months after the pandemic onset among a cohort of Iranian women. Methods. We conducted a population-based IPV survey among 2502 partnered Iranian women aged 18 to 60 years before (n = 2502) and 6 months after (n=2116) the pandemic's onset. We estimated prevalence and incidence of psychological, physical, and sexual IPV, and the odds of different forms of IPV associated with main exposure variables, adjusted for participant relationship factors. Results. Pandemic prevalence of IPV (65.4%; 95% confidence interval [CI] = 63.4%, 67.4%) was higher than prepandemic prevalence (54.2%; 95% CI = 52.2%, 56.3%). At follow-up, the incidence of IPV was 25.5% (95% CI = 22.9%, 28.4%). The highest incidence was in cases of physical and sexual IPV. Women whose partners lost their employment were at significant risk of new exposure to IPV. Highest socioeconomic status (SES) was associated with less physical IPV (odds ratio = 0.03; 95% CI = 0.01, 0.14). Conclusions. IPV prevalence has risen since the COVID-19 epidemic began with many women who had never experienced IPV now facing it. Unemployment of women or their partners and prepandemic lower socioeconomic status are risk factors of IPV. Monitoring programs should target these populations. (Am J Public Health. 2023;113(2):228-237. https://doi.org/10.2105/AJPH.2022.306839).

The effect of green cardamom on blood pressure and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized clinical trials.

Research shows that herbal spices, including seeds of Elettaria cardamomum, may exert beneficial effects on unhealthy metabolic status. This study is a systematic review of the effect of green cardamom in patients with metabolic syndrome and its related disorders. PubMed/Medline, Scopus, EMBASE, Web of Science, and Cochrane Library were searched to identify the relevant randomized clinical trials. The data were pooled using the random-effects model, and weighted mean difference (WMD) was considered as summary effect size. Of 625 clinical trials, eight reports with 595 patients (299 in intervention group and 296 in control group) were included. The findings indicated that green cardamom significantly decreased diastolic blood pressure (WMD: -0.91 mmHg, 95%CI; -1.19, -0.62), high-sensitivity C-reactive protein (WMD: -1.21 mg/L, 95%CI; -2.18, -0.24), interleukin 6 levels (WMD: -2.41 ng/L, 95%CI; -4.35, -0.47). However, cardamom supplementation did not significantly affect systolic blood pressure. This meta-analysis demonstrated that green cardamom could improve blood pressure control and exert antiinflammatory effects which could help patients with unhealthy metabolic profile better manage their health. Importantly, there were few eligible randomized trials with quite a low number of participants. Further prospective studies on larger sample sizes and longer duration of supplementation are warranted for its widespread use.

Validity and reliability of the Persian version of modified motivated strategies for learning questionnaire: a methodological study among medical students.

BACKGROUND: Medical undergraduates need to improve their techniques for learning in the different settings of learning in clinical rotations. Reflective learning, in which a person can learn from their experiences, is among the most well-known learning skills. In this study, we aim to translate the newly developed modified form of the motivated strategies for learning questionnaire (MSLQ) to Persian and evaluate its reliability and validity among medical students. METHODS: This study was performed on medical students in clinical stages at the Shiraz University of Medical Science in 2022. The modified MSLQ questionnaire was used in this study which is a 32-item tool measuring different aspects of self-reflecting, including self-orientation, feedback-seeking, critical thinking, and self-regulation. This questionnaire was translated into Persian properly. Cronbach's alpha and confirmatory factor analysis were used to ascertain the reliability and validity of the tool. RESULTS: A total of 325 medical students consisting of 174 men and 151 women with an average age of 23.79 (± 2.21) were enrolled. Path diagrams of confirmatory factor analysis for both standardized regression coefficients and t-values and all the fitness indicators were in favor of the proper validation of the translated version. The overall Cronbach's alpha for the questionnaire was 0.9, and the value for each of four subscales was above 0.7. CONCLUSIONS: Our study showed that the Persian-translated version of the modified MSLQ is valid and reliable without taking too much time and effort to implement. We recommend that the developed tool be distributed to medical students from other Iran universities.

Effect of deep brain stimulation on freezing of gait in patients with Parkinson's disease: a systematic review.

BACKGROUND AND OBJECTIVES: Freezing of gait (FOG) is a disabling gait disorder in patients with Parkinson's disease (PD), characterized by recurrent episodes of halting steps. Dopaminergic drugs are common treatments for PD and FOG; however, these drugs may worsen FOG. Deep brain stimulation (DBS) is another option used to treat selected patients. The device needs to be programmed at a specific frequency, amplitude, and pulse width to achieve optimum effects for each patient. This systematic review aimed to evaluate the efficacy of DBS for FOG and its correlation with programmed parameters and the location of the electrodes in the brain. MATERIALS AND METHODS: Data for this systematic review were gathered from five online databases: Medline (via PubMed), Scopus, Embase, Web of Science, and Cochrane Library (including both Cochrane Reviews and Cochrane Trials) with a broad search strategy. We included those articles that reported clinical trials and a specific measurement for FOG. RESULTS: This review included 13 studies of DBS that targeted the subthalamic nucleus (STN), substantia nigra (SNr), or pedunculopontine nucleus (PPN). Our analysis showed that low-frequency stimulation (LFS) was superior to high-frequency stimulation (HFS) for improving FOG. In the long term, the efficacy of both LFS and HFS decreased. The effect of amplitude was variable, and this parameter needed to be adjusted for each patient. Bilateral stimulation was better than unilateral stimulation. CONCLUSION: DBS is a promising choice for the treatment of severe FOG in patients with PD. Bilateral, low-frequency stimulation combined with medical therapy is associated with better responses, especially in the first 2 years of treatment. However, individualizing the DBS parameters should be considered to optimize treatment response.

The Prevalence of Obstructive Sleep Apnea and Associated Symptoms among Patients with Sickle Cell Disease: A Systematic Review and Meta-analysis.

Previous studies have shown that patients with sickle cell disease (SCD) are at high risk for obstructive sleep apnea (OSA). In the current study, we aimed to systematically review the literature to address the prevalence of OSA and associated symptoms among patients with SCD. Electronic databases, including Web of Science, Scopus, PubMed, Google Scholar, and Embase were systematically searched to identify the relevant original articles on patients with SCD. Newcastle Ottawa scale was used for quality assessment. Data were pooled by using random effects models. Subgroup analyses were performed by age groups. Thirty-nine studies containing details of 299,358 patients with SCD were included. The pooled results showed that more than half of these patients had OSA with different severities. The prevalence rates of OSA among children with apnea hypopnea index (AHI) cutoffs of above 1, 1.5, and 5 were 51% (95% confidence interval (CI) 36-67%), 29% (95% CI 19-40%), and 18% (95% CI 14-23%), respectively. The prevalence of OSA among adults with AHI cutoff of 5 was 43% (95% CI 21-64%). The pooled rates of snoring, nocturnal enuresis, nocturnal desaturation, and daytime sleepiness were 55% (95% CI 42-69%), 37% (95% CI 33-41%), 49% (95% CI 26-72%), and 21% (95% CI 12-30%), respectively. Given the high prevalence of OSA in patients with SCD, probable greater burden of SCD complications, and irreversible consequences of OSA, screening for OSA symptoms and signs seems useful in these patients. By screening and identifying this heterogeneous disorder earlier, available treatment modalities can be individualized for each patient.

Endovascular therapy for acute stroke with a large infarct core: A systematic review and meta-analysis.

OBJECTIVE: In this meta-analysis, we aimed to investigate the efficacy and safety of endovascular treatment (EVT) for acute ischemic stroke (AIS) patients with large core infarct. METHODS: Three online databases of Web of Science, PubMed and Scopus were systematically searched. Original studies which evaluated AIS participants with large core infarction who underwent EVT were included. R statistical software was used for statistical analyses. Effect sizes were presented with odds ratios (ORs) with their 95% confidence intervals (CIs). The effect sizes were pooled using random effects modeling. RESULTS: Including 47 studies and 15,173 patients, this meta-analysis showed that compared with medical management (MM), EVT was significantly associated with decreased odds of mortality (0.67, 95% CI: 0.51-0.87) and increased odds of favorable outcomes, including a modified Rankin Scale of 0-3 (2.36, 95% CI: 1.69-3.291) and of 0-2 (3.54, 95% CI: 1.96-6.4) in 90 days and remarkable improvement in National Institutes of Health Stroke Scale within 48 h after the procedure (3.6, 95% CI:1.32-9.79). Besides, there was a higher chance of intracranial hemorrhage (ICH) development (1.88, 95% CI: 1.32-2.68) but not symptomatic ICH (1.34, 95% CI: 0.78-2.31) in those who underwent EVT. CONCLUSION: Our study suggests that EVT might be an effective and relatively safe treatment option for the treatment of AIS patients with large vessel occlusion who have large core infarcts, although more large-scale trials are needed to consolidate the results and to make inclusion criteria and the patient selection process clearer.

Population-based pattern of medication use and prevalence of polypharmacy among patients with cardiovascular diseases: results of the Pars cohort study from Iran.

BACKGROUND: Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. METHOD: We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. RESULTS: Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57-4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07-2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00-1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30-1.53), high physical activity (PR: 0.66; 95% CI 0.45-0.95), use of opiate ever (PR: 0.46; 95% CI 0.26-0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12-0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. CONCLUSION: Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.

Population-based prevalence of polypharmacy and patterns of medication use in southwestern Iran: A cross-sectional study.

BACKGROUND: Pharmaceutical medications are considered an important component of healthcare delivery and there is a need for its rational use; although there have been major improvements in the pharmaceutical sector in the recent past, inappropriate medication use is considered a major threat to patients' health. Therefore, the pattern of medication use should be monitored routinely. The aim of this study was to investigate the population-based prevalence of polypharmacy and the patterns of medication use in southwestern Iran. We also investigated correlates between polypharmacy and patterns of medication use. METHODS: Data from the Khuzestan Comprehensive Health Study (KCHS) which consists information of 30 506 with age range to 20 to 65 years were used. Crude and age-standardized prevalence of polypharmacy and their 95% confidence intervals were estimated for different subpopulations. Multivariable Poisson regression modeling was applied, and adjusted prevalence ratios and their 95% confidence intervals were estimated. The Anatomical Therapeutic Chemical classification system (first and second levels) was used for drug classification in different groups based on age, gender, and socioeconomic status. RESULTS: Out of 30 506 adults, 93.3% were not on any medications, and age- and gender-standardized prevalence of polypharmacy was 0.24%. The lowest estimated prevalence was among Arab participants (0.13%). The prevalence of polypharmacy was 1.57% among elderly people, and 4.78% among patients with heart diseases. Socioeconomic status was not associated with polypharmacy (prevalence ratio: 0.95; p = 0.573) but was significantly associated with patterns of medications use for alimentary tract and metabolism and nervous system diseases. The most common drug classes were cardiovascular system (3.93%), alimentary tract and metabolism (2.79%), nervous system (1.01%), systemic hormonal preparations (0.69%), and blood and blood-forming organs (0.38%). CONCLUSIONS: The prevalence of polypharmacy is very low in Khuzestan province, especially in the Arab population. Future research is needed to investigate the causes of medication underuse in this population.

The prevalence of risk factors associated with non-communicable diseases in Afghan refugees in southern Iran: a cross-sectional study.

BACKGROUND: Refugees are highly vulnerable to many health-related risks. Monitoring non-communicable diseases (NCDs) is of overriding importance in these populations. This study aimed to investigate the prevalence of risk factors for NCDs amongst Afghan refugees in a refugee camp located in southern Iran. METHODS: This cross-sectional sturdy was conducted in 2018. Risk factors such as inadequate nutrition, physical inactivity, tobacco smoking, obesity and overweight, hypertension (HTN), elevated fasting plasma glucose (FPG), and dyslipidaemia were assessed. Data were gathered with a modified WHO STEPS procedure. Prevalence and age-standardized prevalence and their 95% confidence intervals (CI) were estimated. RESULTS: The estimated prevalence were 94% for inadequate fruit/vegetable consumption, 18% for physical inactivity, 9% for tobacco smoking, 3% for FPG, 20% for HTN, 51% for central obesity, 24% for overweight, 19% for obesity, and 69% for dyslipidaemia. CONCLUSIONS: Except for inadequate fruit and vegetable intake and dyslipidaemia, the prevalence of other NCD risk factors was low among Afghan refugees in Iran. Raising awareness about healthy diet and its importance and the provision of more affordable fruit and vegetables are two effective measures toward improving the health of refugees in Iran.

An Infant with Acute Bloody Diarrhea and Gastrointestinal Basidiobolomycosis: An Unusual Presentation of a Rare Disease.

Basidiobolomycosis is a fungal infection caused mainly by Basidiobolus ranarum, a filamentous fungus of the order Entomophthorales and the family Basidiobolaceae. This infection typically involves the skin and soft tissue; however, visceral organ involvement has also been reported. Here, we report a case of gastrointestinal basidiobolomycosis in a young child who presented with acute bloody diarrhea which was initially misdiagnosed as intussusception.

Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities.

In response to Dr. Yue et al's study on prognostic factors for post-hemihepatectomy outcomes in hepatocellular carcinoma (HCC) patients, this critical review identifies methodological limitations and proposes enhancements for future research. While the study identifies liver stiffness measure and standard residual liver volume as potential predictors, concerns regarding small sample size, reliance on biochemical markers for safety assessment, and inadequate adjustment for confounding variables are raised. Recommendations for rigorous methodology, including robust statistical analysis, consideration of confounding factors, and selection of outcome measures with clinical components, are proposed to strengthen prognostic assessments. Furthermore, validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hemihepatectomy.

The effect of the four pharmacological pillars of heart failure on haemoglobin level.

Anaemia, a condition characterized by low levels of haemoglobin, is frequently observed in patients with heart failure (HF). Guideline-directed medical therapy improves HF outcomes by using medications like beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, along with mineralocorticoid receptor antagonists and sodium-glucose cotransporter 2 inhibitors. In this study, we aimed to review the pathophysiology of anaemia in patients with HF and present the current evidence regarding the relationship between the main recommended medications for these patients and haemoglobin levels. The authors conducted a comprehensive search in the medical literature for relevant original clinical articles in which the four pharmacological pillars of HF were given to the patients; we, then, assessed whether the association of use of these medications and haemoglobin level or development of anaemia was provided. These common medications have been shown in the literature that may exacerbate or ameliorate anaemia. Besides, it has been shown that even in the case that they result in the development of anaemia, their use is associated with positive effects that outweigh this potential harm. The literature also suggests that among patients receiving medications with negative effects on the level of haemoglobin, there was no difference in the rate of mortality between anaemic and non-anaemic patients when both were on treatment for anaemia; this point highlights the importance of the detection and treatment of anaemia in these patients. Further research is needed to explore these relationships and identify additional strategies to mitigate the risk of anaemia in this population.

Biomarkers for Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma: A Comprehensive Review.

Hepatocellular carcinoma (HCC), the most common primary liver malignancy and the sixth most common cancer globally, remains fatal for many patients with inappropriate responses to treatment. Recent advancements in immunotherapy have transformed the treatment landscape for advanced HCC. However, variability in patient responses to immunotherapy highlights the need for biomarkers that can predict treatment outcomes. This manuscript comprehensively reviews the evolving role of biomarkers in immunotherapy efficacy, spanning from blood-derived indicators-alpha-fetoprotein, inflammatory markers, cytokines, circulating tumor cells, and their DNA-to tissue-derived indicators-programmed cell death ligand 1 expression, tumor mutational burden, microsatellite instability, and tumor-infiltrating lymphocytes. The current body of evidence suggests that these biomarkers hold promise for improving patient selection and predicting immunotherapy outcomes. Each biomarker offers unique insights into disease biology and the immune landscape of HCC, potentially enhancing the precision of treatment strategies. However, challenges such as methodological variability, high costs, inconsistent findings, and the need for large-scale validation in well-powered two-arm trial studies persist, making them currently unsuitable for integration into standard care. Addressing these challenges through standardized techniques and implementation of further studies will be critical for the future incorporation of these biomarkers into clinical practice for advanced HCC.