Incidence Rate Of Hepatocellular Carcinoma Research Articles

Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) is responsible for more than 50% of hepatocellular carcinoma (HCC) in HBV hyperendemic areas, such as the Asia-Pacific region. Several hepatitis B viral factors are involved in HBV-related hepatocarcinogenesis. Hepatitis B viral load is the most important risk factor of HCC development. In addition, HBV integration, HBV genotype C, and core-promoter mutations are also associated with a risk of HCC development. For untreated chronic hepatitis B (CHB) patients, the estimated HCC incidence rates per 100 patient-years were 0.03-0.17 in inactive carriers, 0.07-0.42 in asymptomatic carriers, 0.12-0.49 in chronic hepatitis, and 2.03-3.37 in cirrhosis. Complementary to HBV DNA, serum levels of the hepatitis B surface antigen and hepatitis B core-related antigen (HBcrAg) can predict the occurrence of HCC for untreated patients with low and intermediate viral loads, respectively. For patients receiving antiviral therapy, the risks of HCC occurrence 40-60% lower than those for untreated patients. Patients treated with residual detectable HBV DNA or intrahepatic cccDNA still have a risk of HCC. Serum levels of HBcrAg, M2BPGi and fibrosis-4 are predictive of the risk of HCC development in treated patients. Several well-developed HCC risk scores can help clinicians identify high-risk CHB patients for HCC surveillance, regardless of treatment status. These strategies can help minimize the threat of HCC and prolong survival in CHB patients.

Therapeutic options in hepatocellular carcinoma: a comprehensive review.

Hepatocellular carcinoma (HCC) is a chronic liver disease that is highly fatal if not detected and treated early. The incidence and death rate of HCC have been increasing in recent decades despite the measures taken for preventive screening and effective diagnostic and treatment strategies. The pathophysiology of HCC is multifactorial and highly complex owing to its molecular and immune heterogeneity, and thus the gap in knowledge still precludes making choices between viable therapeutic options and also the development of effective regimens. The treatment of HCC demands multidisciplinary approaches and primarily depends on tumor stage, hepatic functional reserve, and response to treatment by patients. Although curative treatments are limited but critical in the early stages of cancer, there are numerous palliative treatments available for patients with intermediate and advanced-stage HCC. In recent times, the use of combination therapy has succeeded over the use of monotherapy in the treatment of HCC by achieving effective tumor suppression, increasing survival rate, decreasing toxicity, and also aiding in overcoming drug resistance. This work focuses on reviewing the current and emerging treatment strategies for HCC.

Etiologies of cirrhosis by ethnicities of patients with hepatocellular carcinoma.

515 Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. While there are several factors that can impact patient outcomes, ethnicity remains a major contributor towards disease incidence and the expected clinical course. There are various etiologies that can lead to the development of HCC among different ethnic groups, though further studies are required to identify the most pertinent risk factors in recent years. Methods: This was a single center, retrospective study in HCC patients to identify differences in cirrhosis etiologies based on ethnicity. All patients were diagnosed with HCC between March 2014 and April 2022. Possible causes of cirrhosis included alcohol, hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and other chronic liver disease. Results: A total of 276 patients were included in this study. For ethnic background, there were 97 Latino, 97 White, 50 Asian, 16 Black, and 16 patients of other ethnicities. With regards to significant differences in the etiologies of cirrhosis, 58 patients (59.8%) of White ethnicity were found to have cirrhosis related to HCV compared to 71 patients (39.7%) of all other ethnic groups (p = 0.002). In addition, when comparing Latino to non-Latino patients, there was a greater proportion of patients with cirrhosis due to NAFLD (24.7% vs 10.1%, p = 0.002) and cirrhosis from alcohol consumption (24.7% vs 10.1%, p = 0.002). HBV also varied significantly by ethnicity with 16 Asian patients (32%) found to have HBV cirrhosis compared to 5 patients (2.2%) of other ethnic groups (p <0.001). See table for additional details. Conclusions: Our study demonstrates significant differences in the cirrhosis etiologies of HCC patients depending on ethnicity. With the incidence and mortality rates of HCC continuing to rise worldwide, it is important for clinicians to be aware of these differences so that the appropriate preventative measures can be pursued.[Table: see text]

Time-trends in liver cancer incidence and mortality rates in the U.S. from 1975 to 2017: a study based on the Surveillance, Epidemiology, and End Results database.

A previous study has examined the overall cancer statistics. However, more detailed statistics regarding liver cancer have not been provided. We evaluated the incidence and mortality trends of liver and intrahepatic bile duct cancer in the United States from 1975 to 2017 based on the data in the Surveillance, Epidemiology, and End Results (SEER) database. Age, gender, race, metastasis, tumor site, and tumor grade of patients were extracted from the SEER database. Codes C22.0 and C22.1 of the International Classification of Disease for Oncology were applied to identify patients with hepatocellular carcinoma (HCC) and/or intrahepatic cholangiocarcinoma (ICC). Age-specified incidence, age-standardized incidence and mortality, 5-year relative survival, race-specific accumulative incidence and mortality, and geographic-specific accumulative mortality were calculated in different groups. Changes in trends of liver cancer incidence and mortality were assessed using Joinpoint regression. The overall incidence increased significantly from 2.641/100,000 person-years in 1975 to 8.657/100,000 person-years in 2017 [average annual percent change (AAPC) =3.42, 95% confidence interval (CI): 3.28-3.62, P<0.001]. The steepest incidence rate increase was observed in the 60-69-year-old age group (AAPC =4.40, 95% CI: 4.10-4.70, P<0.001). Males exhibited a more rapid increase in cancer incidence, from 3.928/100,000 to 13.128/100,000 person-years (AAPC =3.41, 95% CI: 3.21-3.61, P<0.001), than females [from 1.642/100,000 to 4.783/100,000 person-years (AAPC =3.03, 95% CI: 2.91-3.21, P=0.001)]. The overall mortality rate increased from 2.808/100,000 person-years in 1975 to 6.648/100,000 person-years in 2017 (AAPC =2.41, 95% CI: 2.29-2.51, P<0.001). The highest mortality rate was observed in Hawaii (6.996/100,000 person-years). The incidence and mortality rates of HCC and ICC increased from 1975 to 2017, especially in males, non-Hispanic Blacks and older individuals. Comprehensive policy and control measures should be implemented to reduce the burden of disease, particularly through health monitoring and intervention for high-risk groups.

A glimpse into the future of hepatocellular carcinoma (HCC): Predicting the future incidence based on the current epidemiological data.

615 Background: Accounting for 90% of primary liver cancers, HCC is the fourth-most common cause of cancer-related deaths in the United States. While the vaccination against hepatitis B and awareness on hepatitis C transmission possibly decreased the incidence of HCC in Eastern World, there was an uptrend in the HCC incidence the Western World over the past few years possibly related to metabolic causes. With this changing paradigm of hepatocellular carcinoma, it is important to estimate its future burden stratified based on the age, sex, and race, that could possibly help plan prevention, control, and treatment strategies for this cancer. Methods: We obtained histologically confirmed cases of HCC (ICD-0-3 Site: C220 and 228; codes: 8170-8175) from National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) 18 registries between 2000 to 2017 and predicted the incidence between the years 2018-2029. We applied age-period-cohort models to estimate future HCC incidence rates (per 100, 000) and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: A total of 76029 patients with HCC were included in the final analysis. The median age was 62 (range: 20-79) years with male predominance (70%). The overall observed age-adjusted incidence of HCC between 2000-2017 was 6.22, which is predicted to increase to 9.03 by 2029 with a predominant increase in incidence rate observed in the age groups 70-79 and White males. Interestingly, we noticed a progressive decrease in incidence rate in Asian cohort (both males and females) and Black males. Incidence rates by sub-groups based on the age, sex, and race are summarized in the Table. Conclusions: We predict an overall increased incidence of hepatocellular carcinoma over the next decade in the United States, predominantly in 70-79 years age group irrespective sex and race, with an exception to Asian cohort probably representing differential risk factors. Further epidemiological studies are needed to determine the etiological factors contributing to predicted increase in incidence rate.[Table: see text]

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C

Background & aimsLife-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical–biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. ResultsDuring a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01–1.05), age (HR, 1.04; 95% CI, 1.01–1.08) and albumin levels (HR, 0.90; 95% CI, 0.84–0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08–1.37) and albumin (HR, 0.90; 95% CI, 0.84–0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. ConclusionSimple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.

Ethnic disparities in the epidemiology, treatment, and outcome of patients with hepatocellular carcinoma in the United States

There are significant ethnic disparities in incidence, tumor stage, curative therapy receipt, and survival among patients with hepatocellular carcinoma (HCC) in the US. While previous models had predicted an increasing trend in the incidence rate of HCC until 2030 in the US, recent studies have shown that HCC incidence plateaued in 2013 and then started to decline in 2015. The decreasing trend has been observed in all ethnicities except for American Indians/Alaska Natives, whose incidence rates of HCC continue to rise. Current evidence shows that African-Americans and Hispanics are two groups that are more likely to be diagnosed with late-stage HCC, and this finding has been consistent in different socioeconomic statuses of the patients. These two ethnic minority groups are also among those who are less likely to have curative therapy for early-stage HCC. Finally, advances in early diagnosis and treatment approaches have led to an improvement in HCC survival for all ethnicities; however, African-Americans continue to have the worst survival. More studies to find the causes of these disparities and interventions to eliminate them are urgently needed.

Abstract C110: The role of generation on hepatocellular carcinoma risk among US Mexicans in Los Angeles

Abstract Background. Incidence of hepatocellular carcinoma (HCC) is nearly twice as likely to occur among Hispanics/Latinos compared to their Non-Hispanic White counterparts. Studies show that birthplace may play a role specifically where US-born Hispanic/Latinos are at a greater risk of developing HCC compared to foreign-born Hispanic/Latinos, which may be due to acculturation. Given this information, we looked at how generations in the US impact HCC risk among US Mexicans. Methods. The Multiethnic Cohort (MEC), a prospective study with over 215,000 participants in Los Angeles, CA and Hawaii. The MEC regularly performs linkages with the Surveillance, Epidemiology, End Results (SEER) Program. International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes C.22 and histology codes 8170-8175 to identify HCC cases up until December 31st, 2017. We subset our sample to self-identified Mexicans with information on parental birthplace (n=32,239). Generation status was categorized by 1st generation as born in the Mexico with both parents born in Mexico; 2nd generation as US-born with at least one parent born in Mexico; and 3rd generation as US-born with both parents also born in the US. To assess HCC risk, we performed multivariable Cox models adjusting for age, sex, body mass index (BMI), smoking status, alcohol intake, history of diabetes, and daily coffee consumption. Results. After an average follow-up time of 23.4 years there were a total of 220 HCC incident cases. With successive generation, US-Mexicans were more likely to be current smokers, have a greater intake of alcohol, consume more coffee, and have an elevated BMI. In addition, there was an increase in age-adjusted HCC incidence rates (per 100,000) with each increasing generation (1st generation: 20.9, 2nd generation: 27.5, 3rd generation: 34.7). In the multivariable model, 2nd and 3rd generation US Mexicans had a 35% (95% CI: 1.00-1.84) and 61% (95% CI: 1.10-2.36) increased risk of HCC compared to 1st generation US Mexicans, respectively (Ptrend=0.009). While we did not observe significant heterogeneity by diabetes status (Pheterogeneity=0.41); those who did not have diabetes and were 3rd generation had an 82% (95% CI: 1.17-2.84) increased risk of HCC compared to a 1st generation US Mexicans who also did not have diabetes. There was also no heterogeneity by BMI status (Pheterogeneity=0.92) and alcohol intake (Pheterogeneity=0.46) for the association between generation status and HCC risk. Among HCC cases, similar distributions of tumor grade or stage at diagnosis were observed across generations. Conclusions. 2nd and 3rd generation US Mexicans have a significantly higher risk of HCC compared to 1st generation US Mexicans. Targeted interventions focusing on healthier lifestyle behaviors are much needed for US-born Mexicans reduce HCC risk. Citation Format: Nicholas Acuna, Kali Zhou, Paulo Pinheiro, Tiffany Lim, Lynne Wilkens, Loic Le Marchand, Veronica Wendy Setiawan. The role of generation on hepatocellular carcinoma risk among US Mexicans in Los Angeles [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C110.

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.

Effect of sofosbuvir and velpatasvir therapy on clinical outcome in hepatitisC virus patients with decompensated cirrhosis.

To determine the impact of direct-acting antiviral therapy on the long-term prognosis of decompensated cirrhotic patients. A total of 37 patients with hepatitisC virus-induced decompensated cirrhosis treated with sofosbuvir and velpatasvir (SOF/VEL group) were prospectively enrolled. For historical control, 65 hepatitisC virus-positive decompensated cirrhotic patients who did not receive direct-acting antiviral therapy were included (control group). The incidence rates of hepatocellular carcinoma (HCC), decompensated events with hospitalization, and overall survival were compared between both groups. A total of 41 patients experienced decompensated events during 15.0months in the control group, and six patients during 21.6months in the SOF/VEL group. The cumulative incidence rates of decompensated events after 2years were significantly higher in the control group (53.1%) than in the SOF/VEL group (14.5%; p<0.001). A total of 27 patients died within 22.0months in the control group, and three patients died within 25.6months in the SOF/VEL group. The overall survival rates after 2years were significantly lower in the control group (67.6%) than in the SOF/VEL group (91.3%; p=0.010). A total of 13 patients in the control group developed HCC during 15.8months, and 10 patients during 17.3months in the SOF/VEL group. The HCC incidence rates after 2years were 20.3% and 29.6% in the control and SOF/VEL groups, respectively, with no significant difference (p=0.327). SOF/VEL therapy may suppress the development of decompensated events and improve the prognosis in decompensated cirrhotic patients; however, the incidence of HCC remains prevalent in these patients irrespective of SOF/VEL therapy.

Imaging features of hepatobiliary MRI and the risk of hepatocellular carcinoma development

Objective This study aimed to determine whether hepatocellular carcinoma (HCC) risk and time to HCC development differ according to hepatobiliary magnetic resonance imaging (MRI) findings among people at risk for developing HCC. Materials and methods A total of 199 patients aged 40 years or older with liver cirrhosis or chronic liver disease who underwent gadoxetic acid-enhanced hepatobiliary MRI between 2011 and 2015 were analyzed. An independent radiologist retrospectively reviewed MRI findings, blinded to clinical information, and categorized them into low-risk features, high-risk features and high-risk nodules. High-risk features were defined as liver cirrhosis diagnosed by imaging. High-risk nodules were defined as LR-3 or LR-4 nodules based on LI-RADS version 2018. The primary outcome was development of HCC within 5-year of MRI evaluation. Results HCC was diagnosed in 28 patients (14.1%). HCC development was null for those with low-risk features (n = 84). The cumulative incidence rates of HCC were 0%, 2.3%, 13.4% and 22.1% at 1-, 2-, 3- and 5-year for those with high-risk features (n= 64), and were 19.1%, 31.8%, 37.3% and 46.7% at 1-, 2-, 3- and 5-year for those with high-risk nodules (n= 51). Among 28 patients developed HCC, the median time from baseline MRI to HCC diagnosis was 33.1 months (interquartile range: 25.9–46.7 months) for high-risk feature group, and 17.3 months (interquartile range: 6.2–26.5 months) for high-risk nodule group. Conclusions HCC risk and time to HCC development differ according to baseline hepatobiliary MRI findings, indicating that hepatobiliary MRI findings can be used as biomarkers to differentiate HCC risk.

Trends in hepatocellular carcinoma in Louisiana, 2005-2015.

Louisiana has one of the highest incidence and mortality rates of hepatocellular carcinoma (HCC) in the nation. The aim of this study was to analyze the trends in HCC incidence and relative survival rates in Louisiana and compare them with corresponding national rates, which can be used to formulate strategies to improve Louisiana HCC outcomes. Data on primary invasive HCC diagnosed in patients 20 years or older between 2005 and 2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) program and Louisiana Tumor Registry. Time trends in HCC incidence and 12-month relative survival were analyzed using Joinpoint regression. Case characteristics were compared on 2 time periods (2005-2009 and 2010-2015) using Chi-squared tests. Cause-specific survival was analyzed via log-rank and multivariable Cox proportional hazard model. Over the study period, the average annual percent change (AAPC) in age-adjusted HCC incidence in Louisiana was nearly double that of the national estimate, 6% (95% CI: 4.7, 7.3) compared to 3.1% (95% CI: 2.4, 3.7). 12-month relative survival among HCC patients in Louisiana was 40.7% (95% CI: 38.9, 42.4) which was significantly less than the US rate of 48.2% (95% CI: 47.8, 48.6). Relative survival did improve in Louisiana from 2000 to 2015 at a rate similar to that of the US (AAPC (95% CI): 2.9 (0.7, 5.2) vs. 2.7 (2.3, 3.1), p = 0.8). In multivariable survival analysis, factors amongst Louisianans associated with worse survival were older age at diagnosis, advanced stage of disease, and lack of surgical therapy. The incidence of HCC continues to rise more dramatically in Louisiana than in the US. While some modest improvements in HCC survival have been realized, outcomes remain dismal. Future work identifying the most at-risk populations are needed to inform statewide public health initiatives.

Repeated Measurement of FIB-4 to Predict Long-Term Risk of HCC Development Up to 10 Years After SVR.

It is unclear whether and how the long-term risk of hepatocellular carcinoma (HCC) will change in hepatitis C virus (HCV) infected patients who have reached sustained virologic response (SVR) with direct-acting antivirals (DAA). In this study, we assessed the long-term risk of HCC up to 10 years after SVR using fibrosis 4 score (FIB-4) and its dynamic changes. A total of 701 DAA-treated patients who achieved SVR between January 2012 to October 2020 were enrolled in the study. The FIB-4 score of each patient was measured at the date of SVR and each follow-up visit annually. Patients were followed until December 31, 2021, with the longest follow-up time being 9.82 years. Following SVR, 27 cases of HCC were observed. The annual incidence rate of HCC remained stable with no obvious downward trend. Patients with a FIB-4 >3.25 at baseline or anytime during follow-up were at a higher risk of developing HCC than those whose FIB-4 remained below 3.25. Patients with cirrhosis and patients with no cirrhosis but a FIB-4 >3.25 were at higher risk of developing HCC than patients with no cirrhosis and a FIB-4 ≦3.25. FIB-4 >3.25 measured at SVR or any time post-SVR was associated with HCC risks. The repeated measurement of FIB-4 revealed a better predictive ability of HCC risks than the simple measurement of FIB-4 at baseline. The additional stratification of patients by combining FIB-4 and cirrhosis leads to more accurately identifying high-risk patients. Surveillance of HCC is recommended for virologically cured patients with a FIB-4 >3.25 at SVR or anytime afterward and patients diagnosed with cirrhosis.

A framework for identification and classification of liver diseases based on machine learning algorithms.

Hepatocellular carcinoma (HCC) is one of the most commonly seen liver disease. Most of HCC patients are diagnosed as Hepatitis B related cirrhosis simultaneously, especially in Asian countries. HCC is the fifth most common cancer and the second most common cause of cancer-related death in the World. HCC incidence rates have been rising in the past 3 decades, and it is expected to be doubled by 2030, if there is no effective means for its early diagnosis and management. The improvement of patient’s care, research, and policy is significantly based on accurate medical diagnosis, especially for malignant tumor patients. However, sometimes it is really difficult to get access to advanced and expensive diagnostic tools such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET-CT)., especially for people who resides in poverty-stricken area. Therefore, experts are searching for a framework for predicting of early liver diseases based on basic and simple examinations such as biochemical and routine blood tests, which are easily accessible all around the World. Disease identification and classification has been significantly enhanced by using artificial intelligence (AI) and machine learning (ML) in conjunction with clinical data. The goal of this research is to extract the most significant risk factors or clinical parameters for liver diseases in 525 patients based on clinical experience using machine learning algorithms, such as regularized regression (RR), logistic regression (LR), random forest (RF), decision tree (DT), and extreme gradient boosting (XGBoost). The results showed that RF classier had the best performance (accuracy = 0.762, recall = 0.843, F1-score = 0.775, and AUC = 0.999) among the five ML algorithms. And the important orders of 14 significant risk factors are as follows: Total bilirubin, gamma-glutamyl transferase (GGT), direct bilirubin, hemoglobin, age, platelet, alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, alanine aminotransferase (ALT), cholesterol, albumin, urea nitrogen, and white blood cells. ML classifiers might aid medical organizations in the early detection and classification of liver disease, which would be beneficial in low-income regions, and the relevance of risk factors would be helpful in the prevention and treatment of liver disease patients.

Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis.

DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83–88%), the development of HCC 7% (95% CI 5–9%), and mortality 6% (95% CI 4–8%). Improvement in liver function was observed in 51% (95% CI 44–58%) of patients, and 16% (95% CI 5–40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.

Hepatocellular carcinoma (HCC) is changing its face: analysis of the temporal trends in aetiology and clinical patterns of HCC in South Australia.

The epidemiology of chronic liver disease is changing with the introduction of potent antiviral therapies for chronic hepatitis C virus (HCV) and the increasing prevalence of non-alcoholic steatohepatitis (NASH). To establish the impact of this change on the rates and clinical patterns of hepatocellular carcinoma (HCC) in South Australia (SA). Newly diagnosed HCC patients from January 2014 until December 2019 from four tertiary centres in SA were included. The overall age-standardised incidence rates (ASIR) of HCC were calculated using 2016 SA population as the standard. To assess the trends, Join-Point regression models were used to calculate the average annual percentage change (AAPC). Forecasting of overall and aetiology-specific HCC from 2020 to 2024 was performed using linear regression. There were 626 new cases of HCC in SA (males 80%; median age 64 years) during the study period. There was a significant increase in NASH-related HCC (AAPC: +7.0%; P < 0.05) from 2014 to 2019. However, there were no significant differences in the ASIR for overall HCC (AAPC: -4.1%), HCV-related HCC (AAPC: -8.0%) and stage of HCC diagnosis (AAPC: +3.0%; P > 0.05). Forecasting analysis projected the decline and increase in the incidence of HCV and NASH-related HCC, respectively, over the next few years. Overall ASIR of HCC has plateaued in SA. However, NASH-related HCC has increased significantly and is expected to continue to increase in the near future. Further research and intervention is required to reduce NASH-related HCC, a major contributor to the current and future burden of HCC.

Older Age and High α-Fetoprotein Predict Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis-B-Related Cirrhotic Patients Receiving Long-Term Nucleos(t)ide Analogue Therapy.

Background: Nucleos(t)ide analogues (NUCs) were proved to reduce hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients, but data were limited on their efficacy in cirrhotic CHB patients. Methods: A total of 447 cirrhotic CHB patients treated with tenofovir/entecavir were retrospectively analyzed and divided into HCC (n = 48) and non-HCC (n = 399) groups. The median follow-up period was 62.1 months. Results: A total of 48 patients (10.7%) developed HCC during surveillance. The annual incidence rate of HCC was 2.04 per 100 person-years. The cumulative incidence of HCC was 0.9%, 9.8%, and 22.1% at 1, 5, and 10 years, respectively. Significant predictors for HCC identified using a multiple Cox regression analysis were age ≥50 years (hazard ratio (HR): 2.34) and α-fetoprotein (AFP) ≥8 ng/mL (HR: 2.05). The incidence rate of HCC was 8.67-fold higher in patients with age ≥50 years and AFP ≥8 ng/mL (3.14 per 100 person-years) than those with age <50 years and AFP <8 ng/mL (0.36 per 100 person-years). Conclusions: Cirrhotic CHB patients with age <50 years and AFP <8 ng/mL had the lowest annual incidence of HCC. However, those with age ≥50 years or/and AFP ≥8 ng/mL had a significantly higher risk for HCC development and warrant a careful surveillance schedule.

The Texas collaborative center for hepatocellular cancer: Reducing liver cancer mortality in Texas through coordination, collaboration and advocacy.

Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. To address cancer prevention and early detection through research, Cancer Prevention and Research Institute of Texas (CPRIT) has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate liver cancer research, education and advocacy activities. This paper describes the organizational structure, program measures, the actions completed and future plans of TeCH. This center is comprised of several cores and committees including the Administrative Core, Steering Committee, Data and Biospecimen Core, Scientific Committee, Clinical Network Committee, and the Community Outreach Committee. Each core and committee provide its own level of connectivity and necessary research support. We have developed and published a TeCH Framework, a conceptual model designed for improving primary and secondary prevention of HCC. TeCH and its committees facilitate connections and collaborations among HCC researchers and clinicians, healthcare leaders, biotechnology companies and the public to reduce liver cancer mortality in Texas by 2030.

Comparison of Cholangiocarcinoma and Hepatocellular Carcinoma Incidence Trends from 1993 to 2012 in Lampang, Thailand.

Liver cancer is the most common cancer in Northern Thailand, mainly due to the dietary preference for raw fish, which can lead to infection by the parasite, O. viverrini, a causal agent of cholangiocarcinoma. We conducted a temporal trend analysis of cross-sectional incidence rates of liver cancer in Lampang, Northern Thailand. Liver cancer data from 1993–2012 were extracted from Lampang Cancer Registry. The multiple imputation by chained equations method was used to impute missing histology data. Imputed data were analyzed using Joinpoint and age-period-cohort (APC) models to characterize the incidence rates by gender, region, and histology, considering hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). We observed a significant annual increase in CCA incidence and a considerable decrease in HCC incidence for both genders in Lampang. The APC analysis suggested that CCA incidence rates were higher in older ages, younger cohorts, and later years of diagnosis. In contrast, HCC incidence rates were higher in older generations and earlier years of diagnosis. Further studies of potential risk factors of CCA are needed to better understand and address the increasing burden of CCA in Lampang. Our findings may help to draw public attention to cholangiocarcinoma prevention and control in Northern Thailand.

Risk of hepatocellular carcinoma after sustained virologic response in hepatitis C virus patients without advanced liver fibrosis.

Hepatocellular carcinoma (HCC) after sustained virologic response (SVR) has been observed even in hepatitis C virus (HCV) patients without advanced liver fibrosis. Identifying predictors for HCC incidence in patients without advanced liver fibrosis will enable efficient post-SVR HCC surveillance. This study aimed to develop a scoring system to predict the incidence of HCC after SVR in HCV patients without advanced liver fibrosis. A total of 1682 HCV patients without advanced liver fibrosis (defined as Fibrosis-4 index <3.25) with no history of HCC who initiated direct-acting antiviral treatment between September 2014 and October 2020 at 26 institutions, and achieved SVR24, were included. We divided 1682 patients into training (1122) and validation (560) cohorts. In the multivariate analysis, baseline age ≥65years (p=0.030), alanine aminotransferase (ALT) levels at SVR24≥30 U/l (p=0.001), and α-fetoprotein (AFP) levels at SVR24≥5.0ng/ml (p=0.001) were independent predictors for HCC incidence in the training cohort. We developed a scoring system to predict HCC incidence after SVR24 using these three factors (1 point was added for each factor). The cumulative HCC incidence rates at 5years were 7.1% in patients who scored 2 or 3, and no patients developed HCC in those who scored 0 in the validation cohort. Our scoring system using the three factors of baseline age, ALT levels at SVR, and AFP levels at SVR is useful for post-SVR HCC surveillance of patients without advanced liver fibrosis.