Associations between metabolic dysfunction-associated fatty liver disease and extrahepatic cancers: a cohort in China.

Background: To evaluate the associations between a new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) and extrahepatic cancers and compare with nonalcoholic fatty liver disease (NAFLD). Methods: We enrolled 151,391 Chinese participants in the Kailuan cohort. Hepatic steatosis was detected by abdominal ultrasound. Fine and Gray competing risk regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI) between MAFLD and extrahepatic cancers. Results: MAFLD was associated with increased risk of prostate (HR =1.49, 95% CI: 1.07-2.08) and obesity-related cancers, including thyroid (HR =1.47, 95% CI: 1.01-2.12), kidney (HR =1.54, 95% CI: 1.18-2.00), colorectal (HR =1.15, 95% CI: 0.98-1.34) and breast cancer (HR =1.31, 95% CI: 1.04-1.66). The results were consistent in NAFLD vs. non-NAFLD and MAFLD-NAFLD vs. neither FLD. Compared with the neither FLD group, the NAFLD-only group had a higher risk of extrahepatic cancers (HR =1.57, 95% CI: 1.18-2.09), esophageal (HR =5.11, 95% CI: 2.25-11.62), and bladder cancer (HR =3.36, 95% CI: 1.23-9.17). The additional risk of extrahepatic cancers (HR =1.42, 95% CI: 1.17-1.73), esophageal (HR =4.37, 95% CI: 2.55-7.49), and breast cancer (HR =1.99, 95% CI: 1.01-3.92) was observed in MAFLD with metabolic dysregulation, and kidney (HR =1.83, 95% CI: 1.38-2.43), prostate (HR =1.46, 95% CI: 1.00-2.14) and breast cancer (HR =1.33, 95% CI: 1.02-1.74) was observed in MAFLD with overweight and metabolic dysregulation, as well as colorectal (HR =1.45, 95% CI: 1.07-1.96) and prostate cancer (HR =2.44, 95% CI: 1.42-4.21) in MAFLD with three risk factors. Additionally, MAFLD with excessive alcohol consumption would increase extrahepatic cancers (HR =1.14, 95% CI: 1.01-1.29) and breast cancer (HR =7.27, 95% CI: 2.33-22.69) risk. Conclusions: MAFLD and NAFLD shared similar excessive risks of obesity-related cancers, suggesting a driving role of FLD in these cancers. Metabolic dysregulation beyond obesity may play additional kidney, colorectal, and prostate cancer risks in MAFLD patients. It may be helpful in the clinic to relieve symptoms by treating metabolic disorders and preventing adverse outcomes of extrahepatic cancers.

Effect of cumulative body mass index exposure and long-term related change on incident non-alcoholic fatty liver disease.

BACKGROUND: To evaluate the association between cumulative body mass index (BMI) and long-term BMI change with non-alcoholic fatty liver disease (NAFLD). METHODS: We included 19 477 adult participants (12 556 men and 6921 women) from the Kailuan study from January 2006 to December 2013. Cumulative BMI was assessed using a quadratic mixed-effects method by sex before the index year; then, the NAFLD outcome was followed till December 2019. The long-term BMI change was calculated as the percentage change in average cumulative BMI from the baseline BMI. RESULTS: During a median follow-up of 5.63 years, 6229 individuals developed incident NAFLD. Independent of baseline BMI, the NAFLD risk escalated with the cumulative BMI with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 1.60 (1.48-1.73) and 2.28 (2.06-2.53) for the intermediate tertile and the highest tertile (Ptrend <0.001). The association is amplified in women and the young. Compared to a stable weight (BMI change: -3% to 3%), NAFLD risk increased in the baseline BMI < 24 kg/m2 group with weight gain (BMI change: >3%) and decreased in BMI ≥24 kg/m2 group with weight loss (BMI change: <-3%) for men and women. However, we only observed a decreased NAFLD risk in men (HR: 0.82, 95% CI: 0.69-0.97) with BMI < 24 kg/m2 and weight loss. CONCLUSIONS: Monitoring cumulative BMI may help to identify high-risk NAFLD populations. The association between weight gain or loss varies by sex and baseline BMI, suggesting the importance of individualized weight management for NAFLD prevention.

Outcomes of subjects who are lean, overweight or obese with nonalcoholic fatty liver disease: A cohort study in China.

The ability to determine the prognosis of lean nonalcoholic fatty liver disease (NAFLD) is essential for decision making in clinical settings. Using a large community-based Chinese cohort, we aimed to investigate NAFLD outcomes by body mass index (BMI). We used the restricted cubic splines method to investigate the dose-response relationship between BMI and outcomes in subjects with NAFLD and those without NAFLD. We included 73,907 subjects from the Kailuan cohort and grouped all subjects into four phenotypes by using NAFLD and BMI (<23 kg/m2 ). The probability of developing outcomes for individuals with lean NAFLD (LN), overweight/obese NAFLD (ON), overweight/obese non-NAFLD (ONN), and lean non-NAFLD (LNN) was estimated. We found a U-shaped association between BMI and death but a linear positive association concerning cardiovascular disease (CVD) after adjusting for age and other covariates. Compared with the LNN group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the LN, ON, and ONN groups were 1.30 (1.14-1.49), 0.86 (0.80-0.91), 0.84 (0.80-0.89) for all-cause death, 2.61 (1.13-6.03), 0.74 (0.44-1.26), 1.10 (0.70-1.74) for liver-related death, 2.12 (1.46-3.08), 1.23 (0.99-1.54), 1.19 (0.98-1.43) for digestive system cancers, and 2.04 (1.40-2.96), 1.30 (1.05-1.61), 1.21 (1.01-1.46) for obesity-related cancers. Subjects with LN had a significantly higher risk of colorectal cancer and esophagus cancer. However, the ON group had the highest CVD risk (HR, 1.39; 95% CI, 1.27-1.52). The LN group with hypertension had a higher risk of adverse outcomes, and those without hypertension had a similar risk compared to LNN. Conclusion: Subjects with LN may experience a higher risk of all-cause death, digestive system cancers, and obesity-related cancers than the other three groups but a lower risk of CVD than ON subjects. LN with hypertension may be a high-risk phenotype.

Short-term weight loss decreased the risk of chronic kidney disease in men with incident nonalcoholic fatty liver disease.

OBJECTIVE: The study aimed to examine the association of obesity and chronic kidney disease (CKD) after nonalcoholic fatty liver disease (NAFLD) occurrence. METHODS: The study enrolled 10,311 adult men with newly diagnosed NAFLD and without CKD in the Kailuan cohort (2006-2013). The Fine-Gray model was used to compare advanced CKD risk in NAFLD with different baseline or trajectories in obesity measures. RESULTS: During a median follow-up of 10 years, maintaining normal waist circumference or waist-hip ratio, or transition from obesity to nonobesity determined by BMI, decreased 31% (hazard ratio [HR] = 0.69; 95% CI: 0.51-0.93), 34% (HR = 0.66; 95% CI: 0.45-0.95), and 38% (HR = 0.62; 95% CI: 0.40-0.96) of the CKD hazard compared with the "constantly without obesity" subgroup, respectively. NAFLD patients with at least 10% weight loss (HR = 0.58; 95% CI: 0.34-0.97) and with 7.0% to 9.9% weight loss (HR = 0.53; 95% CI: 0.28-0.99) had a lower risk for CKD than those with weight change ±4.9%. Compared with the stable weight population, the lower risk of ≥7% weight loss was observed only in patients with elevated blood pressure (adjusted HR = 0.48; 95% CI: 0.28-0.81). CONCLUSIONS: Short-term weight loss of at least 7% could decrease CKD risk, especially among patients with obesity and elevated blood pressure. It is important to monitor waist circumference, waist-hip ratio, and weight for NAFLD management.

Entecavir combined with interferon-α Is superior to entecavir monotherapy in reducing hepatic and extrahepatic cancer in patients with chronic hepatitis B.

BACKGROUND: The objective of this study was to assess whether entecavir (ETV) in combination with interferon-α (IFN-α) could reduce hepatocellular cancer (HCC) and extrahepatic cancers (EHCs) in patients with chronic hepatitis B (CHB). METHODS: The cohort consisted of 4194 patients with CHB treated with ETV combined with IFN-α or ETV monotherapy at a tertiary hospital in Beijing, China, from January 2009 to December 2017. The risks, hazard ratios (HRs), and 95% confidence intervals (CIs) of HCC and EHCs were compared in the 2 groups. RESULTS: In a multivariate Cox regression analysis, a significantly lower risk of HCC (HR, 0.6; 95% CI, 0.3-0.9; P = .0310) and a marginally significantly lower risk of EHCs (HR, 0.2; 95% CI, 0.02-1.3; P = .0854) were observed in the group receiving ETV combined with IFN-α in comparison with the ETV monotherapy group. The annual virological response rates were significantly higher in the combination therapy group versus the monotherapy group (33.8% vs 21.2%; P < .0001), but the hepatitis B surface antigen (HBsAg) seroclearance rates were not (1.2% vs 0.9%; P = .8537). The HRs were consistent with propensity score-based matching, inverse probability weighting adjustments, and adjustments for virological response and HBsAg seroclearance. CONCLUSIONS: ETV combined with IFN-α therapy is superior to ETV monotherapy in reducing the risk of HCC and EHCs for patients with CHB. People who can tolerate and benefit from IFN-α therapy could consider combination therapy.

Metabolic Dysfunction-associated Fatty Liver Disease and Mortality Among Chinese Adults: a Prospective Cohort Study.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction associated with fatty liver disease (MAFLD) recently. OBJECTIVE: We aimed to explore the risk of all-cause deaths in MAFLD participants and compare it with NAFLD in Chinese adults. METHODS: We enrolled 152 139 participants with abdominal ultrasonography in the Kailuan Cohort from 2006 to 2012. We categorized the participants into MAFLD and non-MAFLD, NAFLD and non-NAFLD, and 4 groups of Neither FLD, MAFLD only, NAFLD only, and MAFLD-NAFLD, respectively. We used Cox regression models to estimate the hazard ratios (HRs) and 95% CI of death. RESULTS: The prevalence of MAFLD and NAFLD was 31.5% and 27.3%, respectively. After a median follow-up of 12.7 years, MAFLD and NAFLD both were associated with increased mortality, especially in men younger than 40 years, with HR (95% CI) of 1.51 (1.19-1.93) and 1.37 (1.06-1.78), respectively. The MAFLD-only group had higher mortality than the NAFLD-only in males 60 years or older (adjusted HR = 1.43; 95% CI, 1.00-2.03) and lower risk in males aged 40 to 59 years (adjusted HR = 0.65; 95% CI, 0.48-0.90). MAFLD with overweight/obesity-only decreased, but those with diabetes and/or metabolic dysregulation increased the risk of death. MAFLD with positive hepatitis B surface antigen and/or excessive alcohol consumption further increased the risk of death, especially in men younger than 40 years (HR = 9.86; 95% CI, 2.44-39.98). CONCLUSION: MAFLD was associated with increased all-cause mortality among the Chinese population, which was different according to the status of overweight/obesity, diabetes, other metabolic indicators, and second causes. MAFLD patients should be managed by metabolic indicators and second causes to fulfill precise treatment and management.

Cost-effectiveness of combination antiviral treatment with extended duration for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B in China.

BACKGROUND: Hepatitis B surface antigen clearance or seroconversion is rarely achieved for patients using nucleoside analogs or pegylated interferon alpha monotherapy approaches. Several recent studies have confirmed the benefit of a combination of these two approaches for selected chronic hepatitis B patients. However, few reports have investigated long-term outcomes or health economic evaluation for hepatitis B surface antigen clearance. The aim of this study was to perform a cost-effectiveness analysis of the long-term use of this combination strategy among selected hepatitis B e antigen-negative patients. METHODS: Drawing on experience in China, we used a Markov model to simulate disease progression among a population of hepatitis B e antigen-negative chronic hepatitis B patients with surface antigen levels of ≤1,000 IU/mL through a discrete series of health states. We compared nucleoside analog monotherapy to the combination strategy over a prolonged period. We measured lifetime costs, quality-adjusted life-years and incremental cost-effectiveness ratios. RESULTS: The combination therapy produced 15.8 quality-adjusted life-years, and cost US dollars (USD) 45,032 per patient. The monotherapy gave 13.9 quality-adjusted life-years, and had a cost of USD 52,064. The incremental cost-effectiveness ratio of the monotherapy (USD -3,755 per quality-adjusted life-year) did not obtain extended dominance over combination therapy. The most cost-effective option was combination therapy among patients with hepatitis B surface antigen levels of ≤10 IU/mL, which had the lowest calculated cost of USD 35,318 and most quality-adjusted life-years (16.7). CONCLUSIONS: A long-term combination treatment strategy for selected hepatitis B e antigen-negative chronic hepatitis B patients may prolong quality-adjusted life-years compared with nucleoside analog monotherapy. Chronic hepatitis B patients with a hepatitis B surface antigen level of ≤10 IU/mL were the most cost-effective population under this strategy.

Virologic response maintenance and hepatocellular carcinoma in chronic hepatitis B patients treated with entecavir.

INTRODUCTION: The treatment evidence for entecavir-treated chronic hepatitis B (CHB) patients without maintaining of virologic response (MVR, defined as persistent HBV DNA <20 IU/mL during therapy) remains uncertain. We aimed to determine the relationship between non-MVR and hepatocellular carcinoma (HCC) risk in entecavir-treated CHB patients. METHODS: A cohort of 1447 entecavir-treated CHB patients were enrolled. Multivariate and propensity score-based inverse probability weighting (IPW) model was performed to estimate the effect of MVR on HCC. RESULTS: During a median follow-up of 5 years, 214 (14.8%) patients occurred with non-MVR. Non-MVR patients had a higher risk of HCC [the IPW model: hazard ratio (HR) = 3.59, 95% confidence interval (CI): 2.23-5.75] than MVR patients, especially in those with cirrhosis (HR = 4.60, 95% CI: 2.81-7.56) and the high HCC score by the Chinese University of Hong Kong (HR = 4.35, 95% CI: 2.58-7.32). MVR patients with transient (HR = 4.72, 95% CI: 1.98-11.24) or persistent (HR = 12.16, 95% CI: 3.58-41.31) abnormal ALT after virologic response had higher HCC hazard. CONCLUSIONS: Our study indicated an elevated HCC probability for entecavir-treated CHB patients with Non-MVR, especially for those with cirrhosis or a high predicted score at baseline. For MVR patients, the trajectories of ALT after virologic response suggested different HCC risks.

Associations Between Nonalcoholic Fatty Liver Disease and Cancers in a Large Cohort in China.

BACKGROUND & AIMS: The relationship between nonalcoholic fatty liver disease (NAFLD) and cancer, especially extrahepatic cancers, has not been fully clarified. We analyzed data from a large prospective cohort study to determine the relationship between NAFLD and development of cancers in men. METHODS: We collected data from the Kailuan cohort, a community-based cohort of 54,187 adult men in China, from June 2006 through October 2007. NAFLD was diagnosed by ultrasonography after excluding other causes related to chronic liver disease. Fine and Gray competing risk regression model was used to evaluate associations between NAFLD (without cirrhosis) and cancers. RESULTS: The prevalence of NAFLD was 32.3%. NAFLD was associated with increased risk of all cancers (hazard ratio [HR], 1.22; 95% CI, 1.10-1.36; P = .0001), thyroid cancer (HR, 2.79; 95% CI, 1.25-6.21; P = .01), and lung cancer (HR, 1.23; 95% CI, 1.02-1.49; P = .03). The association between NAFLD and risk of thyroid cancer increased with level of alanine aminotransferase (ALT). In men with NAFLD, level of ALT 80 U/L or more was associated with hepatocellular carcinoma (HR, 8.08; 95% CI, 2.46-26.56; P = .0006). NAFLD increased risk of colorectal cancer (HR, 1.96; 95% CI, 1.17-3.27) and lung cancer (HR, 1.38; 95% CI, 1.03-1.84) only in smokers. An association between NAFLD and kidney cancer (HR, 1.57; 95% CI, 1.03-2.40) was only observed in men without diabetes. CONCLUSIONS: A cohort study from China found that men with NAFLD have a higher risk of extrahepatic cancers, including thyroid and lung cancer. In men with NAFLD, higher levels of ALT were associated with higher risk of thyroid and hepatocellular cancer. NAFLD increased risk of colorectal and lung cancer only in smokers, and increased risk of kidney cancer in men without diabetes.

Hospitalizations for peptic ulcer disease in China: Current features and outcomes.

BACKGROUND AND AIM: Rates and outcomes of hospitalizations for peptic ulcer disease (PUD) are unknown in mainland China. We aimed to describe characteristics and treatments of PUD inpatients in secondary and tertiary care hospitals registered in the national Health Statistics and Information Reporting System in 2015 and to explore factors related to inpatient outcomes. METHODS: We retrieved and validated PUD hospitalization data from 4441 hospitals reporting to Health Statistics and Information Reporting System in 2015. Sensitivity analyses were performed to examine the robustness of findings considering different reporting rates across provinces. Current analyses focused on ulcer sites, complications, therapies, and rates of in-hospital death or unauthorized discharge. RESULTS: Total admissions for PUD were 443 433 (mean age 55.14 years), constituting 0.59% of all-cause hospitalizations of 2015 in 4441 hospitals. Duodenal ulcers were more common than gastric ulcers (44.69% vs 37.42%). About 61% of inpatients had complications (46.45% for bleeding and 14.66% for perforation). Over 96% of uncomplicated or bleeding inpatients were managed medically. Surgery was provided to 64.22% of perforated cases. Endoscopic hemostasis and transcatheter embolization were performed for 1.59% of the bleeding and 0.59% of the perforation cases. For all PUD cases, the average in-hospital mortality was 0.35%. Six percent of inpatients left hospitals without authorization. Multinomial logistic regressions showed that inpatient death and unauthorized discharge were associated with older age, gastric ulcer, bleeding, perforation, and comorbidity after controlling for gender, insurance status, hospital type, area, and region. CONCLUSIONS: Currently, pharmacologic management is dominant, and endoscopic hemostasis is notably underutilized for PUD hospitalizations in mainland China.

Out-of-pocket payments and economic consequences from tuberculosis care in eastern China: income inequality.

BACKGROUND: Despite the availability of free tuberculosis (TB) diagnosis and treatment, TB care still generates substantial costs that push people into poverty. We investigated out-of-pocket (OOP) payments for TB care and assessed the resulting economic burden and economic consequences for those with varying levels of household income in eastern China. METHODS: A cross-sectional study was conducted among TB patients in the national TB programme networks in eastern China. TB-related direct OOP costs, time loss, and coping strategies were investigated across households in different economic strata. Analysis of Variance was used to examine the differences in various costs, and Kruskal-Wallis tests were used to compare the difference in total costs as a percentage of annual household income. RESULTS: Among 435 patients, the mean OOP total costs of TB care were USD 2389.5. In the lower-income quartile, OOP payments were lower, but costs as a percentage of reported annual household income were higher. Medical costs and costs prior to treatment accounted for 66.4 and 48.9% of the total costs, respectively. The lower the household income was, the higher the proportion of medical costs to total costs before TB treatment, but the lower the proportion of medical costs patients spent in the intensive phase. TB care caused 25.8% of TB-affected households to fall below the poverty line and caused the poverty gap (PG) to increase by United States Dollar (USD) 145.6. Patients in the poorest households had the highest poverty headcount ratio (70.2%) and PG (USD 236.1), but those in moderately poor households had the largest increase in the poverty headcount ratio (36.2%) and PG (USD 177.8) due to TB care. Patients from poor households were more likely to borrow money to cope with the costs of TB care; however, there were fewer social consequences, except for food insecurity, in poor households. CONCLUSIONS: Medical and pretreatment costs lead to high costs of TB care, especially among patients from the poorest households. It is necessary to train health system staff in general hospitals to promptly identify and refer TB patients. Pro-poor programmes are also needed to protect TB patients from the medical poverty trap.