Risk Of Hepatocellular Carcinoma In Patients Research Articles

Aspirin in Patients with Viral Hepatitis: Systematic Review and Meta-Analysis of Observational Studies.

Hepatocellular carcinoma (HCC) is a disease demonstrating increasing morbidity and mortality, especially in patients with chronic viral hepatitis. Studies have shown that aspirin can reduce the incidence of liver cancer; however, the degree of benefit in patients with viral hepatitis is unclear. This study focused on the association between aspirin use and HCC risk in patients with chronic viral hepatitis. A systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from the earliest available date to December 16, 2023. The primary outcome was HCC incidence, and the secondary outcome was gastrointestinal bleeding. The results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analyses were performed by using random or fixed-effects models based on the heterogeneity assessed via the I2 statistic. A total of 13 articles (303,414 participants and 14,423 HCC patients) were included in the analysis. The incidence of HCC in aspirin users was lower than that in non-aspirin users (HR 0.75; 95% CI, 0.68-0.83; P < 0.001; I2 = 90.0%). Subgroup analysis further showed that this effect may be more obvious in HCV patients, non-cirrhotic patients, patients with statins, and long-term aspirin users, but it may have the risk of gastrointestinal bleeding (HR 1.13; 95% CI, 1.07-1.20; P = 0.906; I2 = 0.0%). Our meta-analysis shows that in patients with chronic viral hepatitis, aspirin use is associated with a significantly reduced risk of liver cancer, but attention should be paid to the possible risk of gastrointestinal bleeding, and this conclusion needs further validation in the future.

Magnetic resonance elastography for the prediction of hepatocellular carcinoma in chronic hepatitis B.

Magnetic resonance elastography (MRE) is used for the evaluation of liver fibrosis; however, it remains unclear whether MRE-based liver stiffness is associated with hepatocellular carcinoma (HCC) development, particularly in patients with chronic hepatitis B. A total of 504 patients with chronic hepatitis B receiving MRE were enrolled. The primary endpoint was the association between MRE-based liver stiffness and HCC. In a cross-sectional analysis at the time of MRE measurement, the median (interquartile range) liver stiffness values in patients with presence or history of HCC and those without HCC were 3.68 (2.89-4.96) and 2.60 (2.22-3.45) kPa, respectively, and liver stiffness was significantly higher in patients with presence or history of HCC than in those without HCC (P < 0.001). In a longitudinal analysis of patients without HCC, the 1-, 3-, and 5-year cumulative incidence of HCC in patients with liver stiffness ≥3.6 kPa and those with liver stiffness <3.6 kPa were 3.8%, 7.0%, and 22.9%, and 0%, 0.9%, and 1.5%, respectively (P < 0.001). In the multivariable analysis, MRE-based liver stiffness (per 1 kPa) or liver stiffness ≥3.6 kPa was an independent factor for HCC development with an adjusted hazard ratio (aHR) of 1.61 (95% confidence interval [CI], 1.3-2.0) or aHR of 8.22 (95% CI, 2.1-31). MRE-based liver stiffness is associated with HCC risk in patients with chronic hepatitis B and may be used for the early prediction of HCC development and determination of indications for treatment.

CAMP-B score predicts the risk of hepatocellular carcinoma in patients with chronic hepatitis B after HBsAg seroclearance.

Risk of hepatocellular carcinoma (HCC) persists after hepatitis B surface antigen (HBsAg) seroclearance in patients with chronic hepatitis B (CHB). To identify risk factors and construct a predictive model for HCC development. We retrospectively analysed patients with CHB with HBsAg seroclearance. Primary outcome was HCC development. Factors identified from a multivariate Cox model in the training cohort, consisting of 3476 patients from two Korean hospitals, were used to construct the prediction model. External validation was performed using data from 5255 patients in Hong Kong. In the training cohort, HCC occurred in 102 patients during 24,019 person-years of observation (0.43%/year). Risk scores were assigned to cirrhosis (C:3), age ≥50 years (A:2), male sex (M:3) and platelet count <150,000/mm3 (P:1); all were independently associated with an increased risk of HCC in multivariate analysis The time-dependent area under receiver operating characteristic curves for 5, 10 and 15 years in the training and validation cohorts were 0.782, 0.817 and 0.825 and 0.785, 0.771 and 0.796, respectively. In the validation cohort, 85 patients developed HCC (0.24%/year). The corresponding incidence of HCC in the low-, intermediate- and high-risk groups were 0.07%, 0.37% and 0.90%, respectively. The CAMP-B score (cirrhosis, age ≥50 years, male sex and platelet count <150,000/mm3/L) was significantly associated with HCC development after HBsAg seroclearance. CAMP-B score can be easily implemented in real-world clinical practice and helps stratify HCC risk in patients with CHB following HBsAg seroclearance.

Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy.

No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806.

Metabolic dysfunction-associated steatotic liver disease increases hepatocellular carcinoma risk in chronic hepatitis B patients: a retrospective cohort study.

Background: The combined effect of hepatitis B virus infection and metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) risk remains unclear. The current study sought to elucidate the impact of MASLD on HCC progression in chronic hepatitis B (CHB) patients. Method: This retrospective cohort study included CHB patients who had undergone liver biopsy and abdominal imaging at the Guangdong Provincial Hospital of Chinese Medicine between 2013 and 2019. We investigated the correlation between MASLD and HCC risk, and inverse probability treatment weighting (IPTW) was used to adjust for patient characteristics. Results: A total of 1,613 patients were included, and 483 (29.9%) were diagnosed with MASLD. Over a median follow-up period of 5.02 years, 36 (2.2%) developed HCC, comprising 4.8% (23/483) of those with MASLD and 1.2% (13/1,130) of those without. Those with MASLD had a significantly higher cumulative incidence of HCC than those without (p < 0.001). The presence of MASLD was associated with a higher risk of HCC (adjusted hazard ratio [HR], 3.996; 95% confidence interval [CI], 2.007-7.959; p < 0.001). After adjustment using IPTW, the patients with MASLD retained a higher cumulative incidence of HCC (p < 0.001). Moreover, MASLD was found to be an independent risk factor for the development of HCC (adjusted HR, 10.191; 95% CI, 4.327-24.002; p < 0.001). However, among patients with MASLD, there were no significant differences in the cumulative risk of HCC between patients with and without overweight, between those with <2 and ≥2 cardiometabolic risk factors (CMRFs), between those with <3 and ≥3 CMRFs, or between those with <4 and ≥4 CMRFs (p = 0.110, p = 0.087, p = 0.066, and p = 0.490, respectively). Conclusion: The presence of MASLD is associated with a higher risk of HCC in patients with CHB. Notably, this higher risk is present in patients with MASLD, irrespective of the presence or absence of overweight or the number of CMRFs they have.

Leveraging metformin to combat hepatocellular carcinoma: its therapeutic promise against hepatitis viral infections

Hepatocellular carcinoma (HCC) is categorized among the most common primary malignant liver cancer and a primary global cause of death from cancer. HCC tends to affect males 2-4 times more than females in many nations. The main factors that raise the incidence of HCC are chronic liver diseases, hepatotropic viruses like hepatitis B (HBV) and C (HCV), non-alcoholic fatty liver disease, exposure to toxins like aflatoxin, and non-alcoholic steatohepatitis (NASH). Among these, hepatitis B and C are the most prevalent causes of chronic hepatitis globally. Metformin, which is made from a naturally occurring compound called galegine, derived from the plant Galega officinalis (G. officinalis ), has been found to exhibit antitumor effects in a wide range of malignancies, including HCC. In fact, compared to patients on sulphonylureas or insulin, studies have demonstrated that metformin treatment significantly lowers the risk of HCC in patients with chronic liver disease. This article will first describe the molecular mechanism of hepatitis B and C viruses in the development of HCC. Then, we will provide detailed explanations about metformin, followed by a discussion of the association between metformin and hepatocellular carcinoma caused by the viruses mentioned above.

Air pollution as a potential risk factor for hepatocellular carcinoma in Taiwanese patients after adjusting for chronic viral hepatitis.

Air pollution is a risk factor for hepatocellular carcinoma (HCC). However, the effect of air pollution on HCC risk in patients with hepatitis remains unclear. This cross-sectional study recruited 348 patients with chronic hepatitis who were tested for serum hepatitis B surface antigen (HBsAg) and for antibodies against hepatitis B core antigen (HBcIgG) and hepatitis C virus (anti-HCV) in 2022. The diagnosis of HCC was based on the International Classification of Diseases, 10th revision (ICD-10). Daily estimates of air pollutants were aggregated into mean estimates for the previous year based on the date of recruitment or HCC diagnosis. Out of 348 patients, 12 had HCC (3.4%). Patients with HCC were older (71.7 vs 50.9 years; p = 0.004), had higher proportion of HBsAg seropositivity (41.7% vs 5.1%; p < 0.001), and substantially higher levels of particulate matter 2.5 (PM 2.5 ) (21.5 vs 18.2 μg/m 3 ; p = 0.05). Logistic regression analysis revealed that the factors associated with HCC were age (odds ratio [OR]: 1.10; CI, 1.03-1.17; p = 0.01), PM 2.5 level (OR: 1.51; CI, 1.02-2.23; p = 0.04), and HBsAg seropositivity (OR: 6.60; CI, 1.51-28.85; p = 0.01) ( Table 3 ). There was a combined effect of PM 2.5 and HBsAg seropositivity on the risk of HCC development (OR: 22.17; CI, 3.33-147.45; p = 0.001). In this study, we demonstrated that PM 2.5 and HBsAg seropositivity were associated with HCC occurrence and had synergistic effects after adjusting for confounding factors.

Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases

Background and aimsTo explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated...

Dynamic evaluation of liver fibrosis to assess hepatocellular carcinoma risk in patients with chronic hepatitis B receiving nucleoside analogs treatment.

Despite good hepatitis B virus (HBV) inhibition by nucleoside analogs (NAs), cases of hepatocellular carcinoma (HCC) still occur. This study proposed a non-invasive predictive model to assess HCC risk in patients with chronic hepatitis B (CHB) receiving NAs treatment. Data were obtained from a hospital-based retrospective cohort registered on the Platform of Medical Data Science Academy of Chongqing Medical University, from 2013 to 2019. A total of 501 patients under NAs treatment had their FIB-4 index updated semiannually by recalculation based on laboratory values. Patients were divided into three groups based on FIB-4 index values: < 1.45, 1.45-3.25, and ≥ 3.25. Subsequently, HCC incidence was reassessed every six months using Kaplan-Meier curves based on the updated FIB-4 index. The median follow-up time of CHB patients after receiving NAs treatment was 2.5 years. HCC incidences with FIB-4 index < 1.45, 1.45-3.25, and ≥ 3.25 were 1.18%, 1.32%, and 9.09%, respectively. Dynamic assessment showed that the percentage of patients with FIB-4 index < 1.45 significantly increased semiannually (P < 0.001), and of patients with FIB-4 index ≥ 3.25 significantly decreased (P < 0.001). HCC incidence was the highest among patients with FIB-4 index ≥ 3.25. The FIB-4 index effectively predicted HCC incidence, and its dynamic assessment could be used for regular surveillance to implement early intervention and reduce HCC risk.

Metformin and Hepatocellular Carcinoma Risk Reduction in Diabetic Patients with Chronic Hepatitis C: Fact or Fiction?

Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC. the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy. A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome. Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET. according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.

Accurate prediction of HCC risk after SVR in patients with hepatitis C cirrhosis based on longitudinal data

BackgroundMost existing predictive models of hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) are built on data collected at baseline and therefore have limited accuracy. The current study aimed to construct an accurate predictive model incorporating longitudinal data using a novel modeling strategy. The predictive performance of the longitudinal model was also compared with a baseline model.MethodsA total of 400 patients with HCV-related cirrhosis who achieved SVR with direct-acting antivirals (DAA) were enrolled in the study. Patients were randomly divided into a training set (70%) and a validation set (30%). Informative features were extracted from the longitudinal variables and then put into the random survival forest (RSF) to develop the longitudinal model. A baseline model including the same variables was built for comparison.ResultsDuring a median follow-up time of approximately 5 years, 25 patients (8.9%) in the training set and 11 patients (9.2%) in the validation set developed HCC. The areas under the receiver-operating characteristics curves (AUROC) for the longitudinal model were 0.9507 (0.8838–0.9997), 0.8767 (0.6972,0.9918), and 0.8307 (0.6941,0.9993) for 1-, 2- and 3-year risk prediction, respectively. The brier scores of the longitudinal model were also relatively low for the 1-, 2- and 3-year risk prediction (0.0283, 0.0561, and 0.0501, respectively). In contrast, the baseline model only achieved mediocre AUROCs of around 0.6 (0.6113, 0.6213, and 0.6480, respectively).ConclusionsOur longitudinal model yielded accurate predictions of HCC risk in patients with HCV-relate cirrhosis, outperforming the baseline model. Our model can provide patients with valuable prognosis information and guide the intensity of surveillance in clinical practice.

A Liver Stiffness–Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma

Background & AimsThe existing hepatocellular carcinoma (HCC) risk scores have modest accuracy and most are specific to chronic hepatitis B infection. In this study, we developed and validated a liver stiffness-based machine learning algorithm (ML) for prediction and risk stratification of HCC in various chronic liver diseases (CLDs). MethodsMLs were trained for prediction of HCC in 5155 adult patients with various CLDs in Korea and further tested in two prospective cohorts from Hong Kong (HK, N=2732) and Europe (N=2384). Model performance was assessed according to Harrell’s C-index and time-dependent receiver operating characteristic (ROC) curve. ResultsWe developed the SMART-HCC score, a liver stiffness-based ML HCC risk score, with liver stiffness measurement ranked as the most important among 9 clinical features. The Harrell’s C-index of the SMART-HCC score in HK and Europe validation cohorts were 0.89 (95% confidence interval [CI] 0.85-0.92) and 0.91 (95%CI 0.87-0.95), respectively. The area under ROC curves of the SMART-HCC score for HCC in 5 years were ≥0.89 in both validation cohorts. The performance of SMART-HCC score was significantly better than existing HCC risk scores including aMAP score, Toronto HCC risk index, and seven hepatitis B related risk scores. Using dual cut-offs of 0.043 and 0.080, the annual HCC incidence was 0.09%-0.11% for low-risk group, and 2.54%-4.64% for high-risk group in the HK and Europe validation cohorts. ConclusionThe SMART-HCC score is a useful machine learning-based tool for clinicians to stratify HCC risk in patients with CLDs.

Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitisB patients.

Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitisB virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development. Among a total of 882 chronically hepatitisB virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1year of treatment was obtained were evaluated for the incidence of HCC. The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1year (P<0.001), but the reduction was small at 2years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5years, the area under the curve of FIB-4 at 1year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10years, P<0.001). Additionally, an abnormal alanine aminotransferase (≥31U/L) at 1year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1)score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10years, P<0.001). FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles.

To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles. PDFFES was 70% higher in patients with HCC when compared to those without HCC (9.6 ± 5.5% versus 5.7 ± 3.0%, respectively, p < 0.001). In multivariate logistic regression, PDFFES was a significant predictor of the presence of HCC (AUC = 0.72, 95% CI 0.57-0.86, p = 0.002) independently from age, sex, visceral fat area, and liver fibrosis stage (all p < 0.05). The relationship between PDFFES and HCC was exacerbated in patients with NASH (AUC = 0.79, 95% CI 0.63-0.86, p = 0.006). In patients with NASH, radiomics features of heterogeneity such as energy and entropy in any of the paraspinal muscles (i.e., ES, QL, or psoas) were independent predictors of HCC. EnergyES identified patients with HCC (n = 13) in the NASH population with AUC = 0.92 (95% CI 0.82-1.00, p < 0.001). In patients with NAFLD, and more specifically in those with NASH, the degree and heterogeneity of myosteatosis is independently associated with HCC irrespective of liver fibrosis stage. Our data suggest that myosteatosis could be used as a biomarker of HCC in the ever-expanding NAFLD population and pave the way for further investigation in longitudinal studies. • HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles. • Association between myosteatosis and HCC is independent from liver fibrosis stage. • Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

Fibrosis-4 index is associated with the risk of hepatocellular carcinoma in patients with cirrhosis and nonalcoholic steatohepatitis.

Identification of high-risk patients for hepatocellular carcinoma (HCC) is essential for long term monitoring of nonalcoholic steatohepatitis (NASH) cirrhosis progression. We sought to evaluate the association between Fibrosis-4 (FIB-4) index and incidence of HCC risk among patients with NASH cirrhosis. We conducted a retrospective cohort study of adult patients with NASH cirrhosis (n= 1,338) who were evaluated in a single medical center between 2005 and 2015. Those who developed HCC were identified through electronic medical records using International Classification of Diseases (ICD) 9 and 10 codes until the end of September 2021. During a median follow-up time of 3.7 years, 157 (11.7%) patients with NASH cirrhosis developed HCC. At index visit, the study population had a median age 57 years, 43% males, 78.8% White, and mean FIB-4 index 4.2. The final multivariable Cox regression model revealed that male sex, BMI 25-29.9 kg/m2, and hypertension were independent factors associated with development of HCC in patients with NASH cirrhosis. Compared to patients with FIB-4 ¾ 1.45, patients with FIB-4 between 1.45-3.25 had a similar hazard of HCC (Hazard Ratio [HR] 1.12, 95% CI: 0.67-1.86, p=0.670), whereas patients with FIB-4 >3.25 had a 1.93 (95% CI: 1.22-3.05, p=0.005) increased hazard of HCC. FIB-4 > 3.25 was an independent factor associated with increased HCC risk among NASH cirrhosis patients. FIB-4 index is a promising tool for determining high-risk patients and may be used in routine clinical practice to monitor risk of HCC in patients with NASH cirrhosis.

Presence of diabetes further heightens hepatocellular carcinoma risk in patients with hepatitis B or hepatitis C virus-related cirrhosis: A meta-analysis

ObjectiveImpact of diabetes mellitus on the development of hepatocellular carcinoma (HCC) remained controversial in cirrhotic patients. This meta-analysis aimed to investigate the association of diabetes and the occurrence of HCC in patients with hepatitis B or hepatitis C virus-related cirrhosis. MethodsTwo authors comprehensively searched PubMed and Embase databases until June 22, 2023, to identify studies that evaluated the association of diabetes with the occurrence of HCC in patients with hepatitis B or hepatitis C virus-related cirrhosis. ResultsSixteen retrospective/prospective cohort studies reporting on 15 articles (5357 cirrhotic patients) were included. The prevalence of diabetes in hepatitis B and hepatitis C virus-related cirrhosis patients ranged from 4 to 46%. Diabetes was associated with higher risk of HCC (risk ratio [RR] 1.74; 95% confidence intervals [CI] 1.24–2.45) in patients with hepatitis C virus-related cirrhosis. However, no significant relationship of diabetes with the occurrence of HCC was present in studies with less than 48-month follow-up among patients with hepatitis C virus-related cirrhosis (RR 1.28; 95% CI 0.68–2.43). Moreover, diabetes also conferred an increased risk of HCC (RR 2.67; 95% CI 2.03–3.51) in patients with hepatitis B virus-related cirrhosis. ConclusionPresence of diabetes significantly predicted the occurrence of HCC in patients with hepatitis B or hepatitis C virus-related cirrhosis.

A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B.

Machine learning (ML) algorithms can be used to overcome the prognostic performance limitations of conventional hepatocellular carcinoma (HCC) risk models. We established and validated an ML-based HCC predictive model optimized for patients with chronic hepatitis B (CHB) infections receiving antiviral therapy (AVT). Treatment-naïve CHB patients who were started entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were enrolled. We used a training cohort (n = 960) to develop a novel ML model that predicted HCC development within 5 years and validated the model using an independent external cohort (n = 1937). ML algorithms consider all potential interactions and do not use predefined hypotheses. The mean age of the patients in the training cohort was 48 years, and most patients (68.9%) were men. During the median 59.3 (interquartile range 45.8-72.3) months of follow-up, 69 (7.2%) patients developed HCC. Our ML-based HCC risk prediction model had an area under the receiver-operating characteristic curve (AUC) of 0.900, which was better than the AUCs of CAMD (0.778) and REAL B (0.772) (both p < .05). The better performance of our model was maintained (AUC = 0.872 vs. 0.788 for CAMD and 0.801 for REAL B) in the validation cohort. Using cut-off probabilities of 0.3 and 0.5, the cumulative incidence of HCC development differed significantly among the three risk groups (p < .001). Our new ML model performed better than models in terms of predicting the risk of HCC development in CHB patients receiving AVT.

Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B

Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB. The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated. Of the 1,632 patients (TAF, n= 1,093; TDF, n= 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p= 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p= 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively). This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis. Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB. NCT01940341; NCT02836249; NCT01940471; NCT02836236.

Association between TLR2, TLR4, and TLR5 genetic variants and the risk of hepatocellular carcinoma in Moroccan population

Hepatocellular carcinoma (HCC) is the fifth most common human malignancy and the fourth most frequent cause of cancer-related deaths worldwide. Toll-like receptors (TLRs), are known to play a key role in hepatocarcinogenesis through induction of inflammation. We aimed to investigate the association between TLR2 rs3804099, TLR4 rs4986790, rs4986791, and rs11536889 and TLR5 rs5744174 and HCC risk in a total of 306 Moroccan subjects, including 152 HCC patient and 154 controls using a TaqMan allelic discrimination assay. Our result showed that the frequency of TLR4 rs11536889 C allele was higher in control group than in HCC patients (OR = 0.52, 95% CI = 0.30-0.88, p = 0.01). Moreover, under the dominant model, we observed that CG/CC genotypes were protective factors against HCC risk (OR = 0.51, 95% CI = 0.28-0.91, p = 0.02). However, no significant differences were found in the allele and genotype frequencies of TLR4 rs4986790 and rs4986791, between HCC patients and controls. Similarly, genotypic frequencies of TLR2 and TLR5 polymorphisms did not differ significantly between HCC patients and controls. However, TLR4 haplotype analysis revealed that ACC haplotype may be protective of HCC risk in patients with HCC (OR = 0.53, 95% CI = 0.31-0.92, p = 0.02). In conclusion, our result suggest that TLR4 rs11536889 polymorphism and ACC haplotype may decrease risk of hepatocellular carcinoma in Moroccan population

Alcohol use and hepatocellular carcinoma risk in patients with alcohol-related cirrhosis

Objectives Insights into risk factors for hepatocellular carcinoma (HCC) among patients with alcohol-related cirrhosis (ALD cirrhosis) are important for decisions about HCC surveillance. We studied the effects of continued hazardous alcohol use in ALD cirrhosis on HCC risk. Methods Within a nationwide registry-based cohort of patients with ALD cirrhosis, we compared HCC risk between patients with a continued hazardous alcohol use and matched comparators. We used Fine-Gray regression to compare the risk of HCC and Cox regression to compare all-cause mortality. We also included patients with ALD cirrhosis in a clinical case-control study. Cases had HCC, and controls did not. Alcohol use was quantified using the AUDIT-C-questionnaire. Logistic regression was used to analyze the association between hazardous alcohol use and HCC risk. Results In the registry-based study, we included 8,616 patients with continued hazardous alcohol use and 8,616 matched comparators. Patients with a continued hazardous alcohol use had a lower HCC risk (subdistribution hazard ratio: 0.64, 95% confidence interval [CI]: 0.57 − 0.72) and higher mortality (hazard ratio: 1.62, 95% CI: 1.56 − 1.67). In the clinical study, we included 146 patients with ALD cirrhosis of whom 53 had newly diagnosed HCC. Hazardous alcohol use was insignificantly associated with a lower HCC risk (odds ratio: 0.61, 95% CI: 0.25 − 1.46). Conclusions Hazardous alcohol use in patients with ALD cirrhosis is associated with higher mortality and, consequently, a lower HCC risk. Even if alcohol is carcinogenic, HCC surveillance will therefore likely be more effective in patients with ALD cirrhosis without a hazardous alcohol use.