No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS: No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

Implementing Promising Strategies to Reduce the Risk for Viral Hepatitis and Liver Cancer Among People Who Inject Drugs.

PURPOSE: To describe a 3-year demonstration project with selected Centers for Disease Control and Prevention National Comprehensive Cancer Control Program (NCCCP) award recipients to build partnerships with local organizations to improve knowledge and awareness of the association between injecting drugs and the risk for viral hepatitis and liver cancer, improve delivery of viral hepatitis services, and implement comprehensive syringe services programs. DESIGN: A mixed-methods descriptive evaluation of selected evidence-based interventions or promising strategies that each award recipient implemented based on the needs of their population. SETTING: Selected provider and patient populations served by NCCCP award recipients in Iowa, Minnesota (American Indian Cancer Foundation), Mississippi, and West Virginia. SUBJECTS: Four award recipients that implemented individually-tailored strategies and activities. MEASURES: Processes were assessed through monitoring and tracking tools. Challenges, lessons learned, and recommendations were collected via qualitative interviews. ANALYSIS: We used descriptive statistics to analyze quantitative data. We analyzed award recipient interviews using thematic analysis. RESULTS: Activities were implemented across four strategies. Strong public-private partnerships, ongoing technical assistance, a deep understanding of individual populations, and a shared commitment to remaining flexible were main factors. CONCLUSION: While challenges existed, award recipients implemented key strategies and activities in their populations. Findings contribute to the scaling of best practices to the larger cancer control community especially those whose populations are at higher risk for viral hepatitis.

Coffee, Green Tea Intake, and the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies.

Several studies suggest an inverse relationship between coffee intake and risk of hepatocellular carcinoma (HCC), but the association between green tea intake and the risk of HCC is still inconclusive. We performed a meta-analysis of observational studies to clarify the association. We identified eligible studies published from January 1, 1992, to February 28, 2022, by searching PubMed, Web of Science, and EMBASE. A total of 32 studies were included in the meta-analysis. Among them, 21 studies involving 2,492,625 participants and 5980 cases of HCC reported coffee intake, 18 studies involving 1,481,647 participants and 6985 cases of HCC reported green tea intake, and seven studies reported both coffee intake and green tea intake. The results showed that a higher coffee (RR = 0.53; 95% CI: 0.47-0.59; I2 = 0.0%; Pheterogeneity = 0.634) or green tea (RR = 0.80; 95% CI: 0.67-0.95; I2 = 72.30%; Pheterogeneity < 0.001) intake may be associated with a lower risk of HCC. The same results were observed in both cohort and case-control subgroups. Our findings suggest that drinking coffee or green tea may be a potentially effective approach for the prevention or mitigation of HCC, but this still needs to be confirmed by further well-designed observational studies and clinical experimental research.

Population-attributable risk of modifiable lifestyle factors to hepatocellular carcinoma: The multi-ethnic cohort.

BACKGROUND AND AIMS: Lifestyle factors are well associated with risk of hepatocellular carcinoma (HCC). However, the impact of reducing adverse lifestyle behaviours on population-level burden of HCC is uncertain. METHODS: We conducted prospective analysis of the population-based multi-ethnic cohort (MEC) with linkage to cancer registries. The association of lifestyle factors (smoking, alcohol, diet quality assessed by alternate Mediterranean diet score, coffee drinking, physical activity and body mass index) with HCC incidence was examined using Cox regression. Population-attributable risk (PAR, %) for the overall, lean and overweight/obese populations was determined. RESULTS: A total of 753 incident cases of HCC were identified in 181,346 participants over median follow-up of 23.1 years. Lifestyle factors associated with elevated HCC risk included former/current smoking, heavy alcohol use, poor diet quality, lower coffee intake and obesity, but not physical activity. The lifestyle factor with highest PAR was lower coffee intake (21.3%; 95% CI: 8.9%-33.0%), followed by current smoking (15.1%; 11.1%-19.0%), obesity (14.5%; 9.2%-19.8%), heavy alcohol use (7.1%; 3.5%-10.6%) and lower diet quality (4.1%; 0.1%-8.1%). The combined PAR of all high-risk lifestyle factors was 51.9% (95% CI: 30.1%-68.6%). A higher combined PAR was observed among lean (65.2%, 26.8%-85.7%) compared to overweight/obese (37.4%, 11.7%-58.3%) participants. Adjusting for viral hepatitis status in a linked MEC-Medicare dataset resulted in similar PAR results. CONCLUSIONS: Modifying lifestyle factors, particularly coffee intake, may have a substantial impact on HCC burden in diverse populations, with greater impact among lean adults. Diet and lifestyle counselling should be incorporated into HCC prevention strategies.

Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased among the general population and chronic hepatitis B (CHB) patients worldwide. Although fatty liver disease is a well-known risk factor for adverse liver outcomes like cirrhosis and hepatocellular carcinoma, its interactions with the hepatitis B virus (HBV) and clinical impacts seem complex. The presence of hepatic steatosis may suppress HBV viral activity, potentially leading to attenuated liver injury. In contrast, the associated co-morbidities like diabetes mellitus or obesity may increase the risk of developing adverse liver outcomes. These findings implicate that components of MAFLD may have diverse effects on the clinical manifestations of CHB. To this end, a clinical strategy is proposed for managing patients with concurrent CHB and MAFLD. This review article discusses the updated evidence regarding disease prevalence, interactions between steatosis and HBV, clinical impacts, and management strategies, aiming at optimizing holistic health care in the CHB population.

Opium Use and the Risk of Liver Cancer: A Case-Control Study.

Limited evidence is available to acknowledge the association between opium use and liver cancer. In a case-control study, we recruited 117 cases of primary liver cancer (PLC) and 234 age and sex-matched neighborhood controls from 2016 to 2018. We calculated odds ratios (OR) for opium use and 95% confidence intervals (95% CI), using conditional logistic regressions. Compared with non-users the adjusted OR (AOR, 95% CI) for opium use was 6.5 (95% CI, 2.87-13.44). Compared with people who had no history of use, a strong dose-response effect of opium use was observed by amount of use (AOR, 10.70; 95% CI, 3.92-28.70). Cumulative use of opium also indicated that using over 30 gr-year could increase the PLC risk dramatically (AOR, 11.0; 95% CI, 3.83-31.58). Those who used opium for more than 21 years were highly at risk of PLC (AOR, 11.66; 95% CI, 4.43-30.67). The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). PREVENTION RELEVANCE: The results of this study indicate that opium use dramatically increased the risk of liver cancer. Because opioids are increasing for medical and non-medical use globally; accordingly, severe health consequences such as liver cancer have to be investigated widely.

Cumulative consumption of tea is associated with lower risk of liver cancer: Updated results from the Shanghai Women's Health Study.

Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range = 1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer.

The survival outcomes and prognostic factors of hepatocellular carcinoma among type 2 diabetes patients: a two-centre retrospective cohort study.

BACKGROUND: To determine the survival outcomes and prognostic factors associated with hepatocellular carcinoma (HCC) survival in type 2 diabetes (T2D) patients. METHODS: This was a retrospective cohort study involving two hepatobiliary centres from January 1, 2012, to June 30, 2018. Medical records were analysed for sociodemographic, clinical characteristics, laboratory testing, and HCC treatment information. Survival outcomes were examined using the Kaplan-Meier and log-rank test. Prognostic factors were determined using multivariate Cox regression. RESULTS: A total of 212 patients were included in the study. The median survival time was 22 months. The 1-, 3-, and 5-year survival rates were 64.2%, 34.2%, and 18.0%, respectively. Palliative treatment (adjusted hazard ratio [AHR] = 2.82, 95% confidence interval [CI] 1.75-4.52), tumour size ≥ 5 cm (AHR = 2.02, 95%CI: 1.45-2.82), traditional medication (AHR = 1.94, 95%CI: 1.27-2.98), raised alkaline phosphatase (AHR = 1.74, 95%CI: 1.25-2.42), and metformin (AHR = 1.44, 95%CI: 1.03-2.00) were significantly associated with poor prognosis for HCC survival. Antiviral hepatitis treatment (AHR = 0.54, 95% CI: 0.34-0.87), nonalcoholic fatty liver disease (NAFLD) (AHR = 0.50, 95% CI: 0.30-0.84), and family history of malignancies (AHR = 0.50, 95%CI: 0.26-0.96) were identified as good prognostic factors for HCC survival. DISCUSSION: Traditional medication, metformin treatment, advanced stage and raised alkaline phosphatase were the poor prognostic factors, while antiviral hepatitis treatment, NAFLD, and family history of malignancies were the good prognostic factors for our HCC cases comorbid with T2D.

The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs.

For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.

The role of dietary factors in nonalcoholic fatty liver disease to hepatocellular carcinoma progression: A systematic review.

BACKGROUND AND AIMS: Dietary factors play an important role in promoting nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) development through regulation of metabolism and inflammation. However, so far there was no evidence regarding how dietary factors may influence different disease outcomes in the NAFLD to HCC progression. Our study aimed to comprehensively evaluate the role of dietary factors on the risk of progression from NAFLD to HCC. METHODS: A comprehensive literature research was conducted in PubMed, Web of Science and Embase databases to identify case-control and cohort studies published up to March 15, 2022 in English. We included studies investigating associations of food and beverage items (excluding alcohol), food groups, dietary patterns, and dietary habits with incidence risk of four main chronic liver diseases involved in the NAFLD-to-HCC progression (i.e., NAFLD, liver fibrosis, liver cirrhosis, and HCC). Three researchers independently performed the literature search, selected eligible articles, performed data abstraction and evaluated study quality. After evaluating adequacy and credibility of the associations reported for each dietary factor and each liver disease outcome, we summarized and evaluated the consistency of associations based on a priori determined criteria considering study design and the proportion of significant associations. RESULTS: There were 109 studies included in this review (47 on NAFLD, 1 on liver fibrosis, 6 on liver cirrhosis, and 55 on HCC). Consistent evidence suggested that higher dietary inflammatory potential was associated with increased risk of both NAFLD and HCC whereas Mediterranean diet was associated with lower risk of both diseases. Additionally, greater conformity to the Healthy Eating Index, Dietary Approaches to Stop Hypertension score, and Mediterranean Diet Score, and dietary patterns with high dietary antioxidant capacity reduced NAFLD risk. Some specific foods including soft drinks and red and/or processed meat were associated with increased NAFLD risk while total vegetables and spinach were associated with reduced NAFLD risk. Coffee and white meat consumption were inversely related to HCC risk. CONCLUSIONS: Dietary patterns or individual foods representing a more anti-inflammatory potential were associated with reduced risk of both NAFLD and HCC, which implied diet-induced inflammation may impact NAFLD progression towards HCC.

Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B.

BACKGROUND & AIMS: Chronic hepatitis B (CHB) and liver fibrosis are associated with a high risk of hepatocellular carcinoma (HCC) development. We assessed whether entecavir (ETV) plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese patients with CHB and an Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial. METHODS: After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis. RESULTS: A total of 1,000 patients were recruited; the median age was 42.0 years; 69.9% were male and 58.3% were HBeAg positive. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV monotherapy (p = 0.008 [p = 0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than ETV monotherapy (p = 0.018). There were no differences in the other 2 secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis, including the treatment allocation as a parameter, also demonstrated that ETV+BRC treatment was associated with a reduced incidence of HCC. The ITT and PP analyses showed consistent results. CONCLUSIONS: ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in patients with CHB and advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention. LAY SUMMARY: Patients with chronic hepatitis B virus infection are at an increased risk of developing liver cancer (specifically hepatocellular carcinoma [HCC]). While there are effective antiviral treatments that can suppress the virus in chronically infected patients, the risk of HCC remains. Herein, we show that adding a traditional Chinese medicine called Biejia-Ruangan compound to an antiviral reduced the risk of HCC in patients with chronic hepatitis B.

Associations between six dietary habits and risk of hepatocellular carcinoma: A Mendelian randomization study.

Diet is reported to be associated with hepatocellular carcinoma (HCC), but whether there is a causal relationship remains unclear. This study aimed to explore the potential causal associations between dietary habits and HCC risk using Mendelian randomization in an East Asian population. From the BioBank Japan, we obtained summary-level genome-wide association studies data for the following six dietary habits: ever/never drinker (n = 165,084), alcohol consumption (n = 58,610), coffee consumption (n = 152,634), tea consumption (n = 152,653), milk consumption (n = 152,965), and yoghurt consumption (n = 152,097). We also obtained data on HCC (1866 cases and 195,745 controls). Single-nucleotide polymorphisms (SNPs) that were associated with exposures (p < 5 × 10-8 ) were selected as instrumental variables (IVs). Five, two, and six SNPs were identified for ever/never drinkers, alcohol consumption, and coffee consumption. One SNP was used for consumption of tea, milk, and yoghurt. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by inverse variance weighted (for an IV with more than one SNP) or Wald ratio (for an IV with one SNP). Ever/never drinkers (OR, 1.11; 95% CI, 1.05-1.18; p < 0.001) and alcohol consumption (OR, 1.57; 95% CI, 1.32-1.86; p < 0.001) were positively associated with HCC risk. Conversely, coffee consumption was inversely related to HCC risk (OR, 0.69; 95% CI, 0.53-0.90; p = 0.007). Similar inverse associations were observed for consumption of tea, milk, and yoghurt, with ORs (95% CIs) of 0.11 (0.05-0.26), 0.18 (0.09-0.34), and 0.18 (0.09-0.34), respectively (all p < 0.001). Conclusion: There are potential causal associations between six dietary habits and HCC risk. Our findings inform clinical practice by providing evidence on the impact of dietary habits on HCC.

Association between Coffee Consumption/Physical Exercise and Gastric, Hepatic, Colon, Breast, Uterine Cervix, Lung, Thyroid, Prostate, and Bladder Cancer.

Although the effects of coffee consumption and physical exercise on the risk of cancer have been suggested, their interactions have not been investigated. The present cross-sectional study aimed to investigate the correlation of coffee consumption and physical exercise with cancer. Participants ≥40 years old in the Korean Genome and Epidemiology Study 2004-2016 were included (n = 162,220). Histories of gastric cancer, hepatic cancer, colon cancer, breast cancer, uterine cervix cancer, lung cancer, thyroid cancer, prostate cancer, and bladder cancer were analyzed according to the coffee consumption groups using logistic regression models. The odds among individuals in the >60 cups/month coffee group were lower for gastric cancer (adjusted odds ratio (aOR) = 0.80 (95% confidence intervals = 0.65-0.98)), hepatic cancer (0.32 (0.18-0.58)), colon cancer (0.53 (0.39-0.72)), breast cancer (0.56 (0.45-0.70)), and thyroid cancer (0.71 (0.59-0.85)) than for individuals in the no coffee group. Physical exercise of ≥150 min/week was correlated with higher odds for gastric cancer (1.18 (1.03-1.36)), colon cancer (1.52 (1.26-1.83)), breast cancer (1.53 (1.35-1.74)), thyroid cancer (1.42 (1.27-1.59)), and prostate cancer (1.61 (1.13-2.28)) compared to no exercise. Coffee consumption and physical exercise showed an interaction in thyroid cancer (p = 0.002). Coffee consumption was related to a decreased risk of gastric cancer, hepatic cancer, colon cancer, breast cancer, and thyroid cancer in the adult population. Physical exercise was positively correlated with gastric cancer, colon cancer, breast cancer, thyroid cancer, and prostate cancer.

Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma.

BACKGROUND & AIMS: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function. METHODS: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up. RESULTS: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08). CONCLUSION: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy. CLINICAL TRIAL NUMBER: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.

All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study.

BACKGROUND: Chronic liver disease (CLD) is a growing cause of morbidity and mortality worldwide, particularly in low to middle-income countries with high disease burden and limited treatment availability. Coffee consumption has been linked with lower rates of CLD, but little is known about the effects of different coffee types, which vary in chemical composition. This study aimed to investigate associations of coffee consumption, including decaffeinated, instant and ground coffee, with chronic liver disease outcomes. METHODS: A total of 494,585 UK Biobank participants with known coffee consumption and electronic linkage to hospital, death and cancer records were included in this study. Cox regression was used to estimate hazard ratios (HR) of incident CLD, incident CLD or steatosis, incident hepatocellular carcinoma (HCC) and death from CLD according to coffee consumption of any type as well as for decaffeinated, instant and ground coffee individually. RESULTS: Among 384,818 coffee drinkers and 109,767 non-coffee drinkers, there were 3600 cases of CLD, 5439 cases of CLD or steatosis, 184 cases of HCC and 301 deaths from CLD during a median follow-up of 10.7 years. Compared to non-coffee drinkers, coffee drinkers had lower adjusted HRs of CLD (HR 0.79, 95% CI 0.72-0.86), CLD or steatosis (HR 0.80, 95% CI 0.75-0.86), death from CLD (HR 0.51, 95% CI 0.39-0.67) and HCC (HR 0.80, 95% CI 0.54-1.19). The associations for decaffeinated, instant and ground coffee individually were similar to all types combined. CONCLUSION: The finding that all types of coffee are protective against CLD is significant given the increasing incidence of CLD worldwide and the potential of coffee as an intervention to prevent CLD onset or progression.

Twelve-month post-treatment parameters are superior in predicting hepatocellular carcinoma in patients with chronic hepatitis B.

BACKGROUND & AIMS: There are currently several prediction models for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) receiving oral antiviral therapy. However, most models are based on pre-treatment clinical parameters. The current study aimed to develop a novel and practical prediction model for HCC by using both pre- and post-treatment parameters in this population. METHODS: We included two treatment-naïve CHB cohorts who were initiated on oral antiviral therapies: the derivation cohort (n = 1480, Korea prospective SAINT cohort) and the validation cohort (n = 426, the US retrospective Stanford Bay cohort). We employed logistic regression, decision tree, lasso regression, support vector machine and random forest algorithms to develop the HCC prediction model and selected the most optimal method. RESULTS: We evaluated both pre-treatment and the 12-month clinical parameters on-treatment and found the 12-month on-treatment values to have superior HCC prediction performance. The lasso logistic regression algorithm using the presence of cirrhosis at baseline and alpha-foetoprotein and platelet at 12 months showed the best performance (AUROC = 0.843 in the derivation cohort. The model performed well in the external validation cohort (AUROC = 0.844) and better than other existing prediction models including the APA, PAGE-B and GAG models (AUROC = 0.769 to 0.818). CONCLUSIONS: We provided a simple-to-use HCC prediction model based on presence of cirrhosis at baseline and two objective laboratory markers (AFP and platelets) measured 12 months after antiviral initiation. The model is highly accurate with excellent validation in an external cohort from a different country (AUROC 0.844) (Clinical trial number: KCT0003487).

Caffeinated Coffee Consumption and Health Outcomes in the US Population: A Dose-Response Meta-Analysis and Estimation of Disease Cases and Deaths Avoided.

To explore the role of coffee on health outcomes in the United States, where coffee consumption is common, we conducted a meta-analysis of prospective studies investigating the magnitude (any compared with no consumption) and the dose-response shape (cups per day) of the associations between caffeinated coffee consumption and incidence/mortality of cardiovascular disease (CVD), as well as incidence of type 2 diabetes (T2D), hepatocellular carcinoma (HCC), endometrial cancer, melanoma, and nonmelanoma skin cancer. We selected the desirable health outcomes that have been shown to be positively associated with coffee consumption. Studies were identified by searching PubMed/Embase databases up to September 2019. Inclusion criteria included prospective studies that investigated the relation of ≥3 categories of caffeinated coffee consumption and the outcomes of interest. Twenty-six studies (42 distinct cohorts), with 93,706 cases/deaths and 3,713,932 participants, met the inclusion criteria. In any coffee consumers, there was a significant inverse association with the risk of CVD (RR = 0.90; 95% CI: 0.84, 0.96), T2D (RR = 0.90; 95% CI: 0.85, 0.96), endometrial cancer (RR = 0.85; 95% CI: 0.78, 0.92), melanoma (RR = 0.89; 95% CI: 0.80, 0.99), and nonmelanoma skin cancer (RR = 0.92; 95% CI: 0.89, 0.95). Coffee consumption was also inversely associated with HCC (RR = 0.93; 95% CI: 0.80, 1.08), without reaching statistical significance. The dose-response relation was nonlinear uniquely for CVD (P-nonlinearity = 0.01). In particular, the largest risk reduction was observed for 3-4 cups/d (∼120 mL/cup) and no reduction thereafter. For other outcomes, the risk decreased linearly over the whole coffee consumption range. Current patterns of consumption in the United States would account for a fraction of avoided cases/deaths ranging from 6% to 12% according to the outcome considered. This study confirms the beneficial health effects of caffeinated coffee consumption in the US population on the health outcomes considered, and quantifies their possible magnitude.