Hepatology Communications最新文献

Background: Cirrhosis and other chronic liver diseases are the 12th leading cause of death globally and impose a substantial economic burden. Estimating the macroeconomic burden and distribution can provide a policy rationale for the prevention and treatment of these issues. We aimed to estimate and project the macroeconomic burden of cirrhosis and other chronic liver diseases in 190 countries and territories, as well as their distribution across world regions.

Methods: We calculated the macroeconomic burden of cirrhosis and other chronic liver diseases in 190 countries using a health-augmented macroeconomic model that accounts for the impact of morbidity and mortality on labor supply, age differences in education and experience among those affected by cirrhosis and other chronic liver diseases, and reduced investment due to the shifting of costs of these disease-related treatments from savings.

Results: Our findings suggest that cirrhosis and other chronic liver diseases will cost the world economy INT$ 2.649 trillion (2.502-2.827) in 2021-2050. The United States has the largest economic burden of cirrhosis and other chronic liver diseases, followed by China and India. Although low- and middle-income countries have the highest health burdens (91.4% of the global disability-adjusted life years), their share of the economic burden of cirrhosis is only 57.1% of the global loss.

Conclusions: The macroeconomic burden of cirrhosis and other chronic liver diseases is sizeable and distributed unequally across countries and world regions. Our study emphasizes the need for greater investment globally in controlling cirrhosis and other chronic liver diseases and their associated health and economic burdens.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health problem. Measuring the burden of cirrhosis and its complications in people with MASLD is important to inform health care delivery.

Methods: We aimed to quantify the changes in the burden of MASLD-related cirrhosis and hepatocellular carcinoma (HCC) in a nationwide U.S. healthcare system. We used data from the Veterans Health Administration to examine temporal trends between 2010 and 2021 in the annual incidence and prevalence of cirrhosis and HCC in a large cohort of patients with MASLD, and to compare them to those in patients with hepatitis C virus infection (HCV) and alcohol-associated liver disease (ALD).

Results: The MASLD cohort grew from 78,082 in 2010 to 621,400 patients in 2021. The annual age-standardized incidence rates of MASLD-related cirrhosis rose from 1.39 (95% CI, 1.13, 1.65) to 1.91 (95% CI, 1.80, 2.02) per 1000 patients (37.4% increase). HCC incidence increased from 0.08 (95% CI, 0.02, 0.14) to 0.22 (0.18, 0.26) per 1000 patients (175% increase). Cirrhosis and HCC prevalence also increased, particularly among adults older than age 65, Whites, Hispanics, and individuals with diabetes. Temporal trends in the incidence and prevalence of cirrhosis and HCC among patients with ALD were similar to those in MASLD. In contrast, patients with HCV experienced a sharp decline in the incidence of cirrhosis and HCC in this time frame.

Conclusions: The burden of MASLD-related cirrhosis and HCC is growing. While the burden of liver complications is similar between MASLD and ALD, the substantially larger size of the MASLD population means that the modest increases in incidence of cirrhosis and HCC could translate into a large absolute burden.

Background: Obesity impairs liver regeneration by promoting chronic inflammation and metabolic dysfunction, especially in conditions like non-alcoholic fatty liver disease. Portal vein embolization (PVE), used to stimulate liver growth pre-hepatectomy, is less effective in obese subjects. Nicotinamide riboside (NR), a NAD+ precursor, improves mitochondrial function and lipid metabolism, but its role in liver regeneration under obese conditions remains unclear. Our study tried to investigate the effects and underlying mechanisms of NR on liver regeneration after PVE in high-fat diet (HFD)-induced obese rats.

Methods: HFD-fed rats underwent PVE and were treated with or without NR. Liver regeneration was assessed by histology, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, immunohistochemistry, and liver function tests. NAD+ levels were quantified to confirm NR activity. Proteomics, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Ontology (GO) analysis, quantitative real-time PCR (qPCR), and western blotting were used to explore molecular mechanisms, focusing on the MCART1/ASB3 axis.

Results: Obesity impaired liver regeneration post-PVE, as evidenced by lipid accumulation, inflammation, reduced hepatocyte proliferation, and elevated liver enzymes. NR supplementation restored NAD+ levels, improved liver function, increased proliferative activity, and reduced steatosis. Mechanistically, NR upregulated MCART1 and ASB3 expression, promoting energy and lipid metabolism essential for regeneration.

Conclusions: NR promotes liver regeneration after PVE in obese rats by enhancing NAD+-dependent metabolic pathways through the MCART1/ASB3 axis, offering a potential therapeutic strategy for obesity-associated liver dysfunction.

Background: Intrahepatic cholestasis of pregnancy (ICP) is a multifactorial liver disorder associated with adverse pregnancy outcomes. Chronic hepatitis B (CHB) has been reported with increased risk of ICP, while the clinical characteristics and outcomes of isolated ICP compared with ICP involving CHB remain poorly understood.

Methods: ICP involving CHB was defined as the co-concurrence of ICP with CHB, categorized into immune-tolerant CHB (n=44), inactive CHB (n=86), immune-active CHB (n=127), and grey zone CHB (n=89). Isolated ICP (n=826) was defined as ICP without viral hepatitis, while immune-active CHB with normal elevated total bile acid (TBA) (n=87) serves as controls.

Results: Women with ICP involving immune-active CHB experienced the most severe biochemical abnormalities and adverse outcomes, whereas other CHB subgroups exhibited biochemical profiles and outcomes comparable to isolated ICP cases. Assisted reproductive technology (aOR, 1.24), TBA levels (40-99.9 µmol/L-aOR, 1.27, ≥100 µmol/L-aOR, 1.60), and immune-active CHB (aOR, 1.12) were associated with increased risks of composite adverse outcomes. Stratified analysis revealed that TBA ≥40 µmol/L significantly correlated with increased risks of total and iatrogenic preterm birth and neonatal intensive care unit admission (p<0.05); while TBA ≥100 µmol/L was further associated with elevated risks of meconium-stained amniotic fluid and lower Apgar scores (p<0.05). Immune-active CHB women with normal TBA demonstrated relatively higher levels of transaminase but achieved the most favorable pregnancy outcomes.

Conclusions: ICP involving immune-active CHB demonstrated the most severe biochemical abnormalities and adverse pregnancy outcomes, while ICP involving other CHB immune phases showed transient mild biochemical changes and outcomes comparable to isolated ICP. The findings underscore the need to tailor diagnostic, monitoring, and management strategies based on TBA levels and the immune status of CHB.

Background: There is no consensus scoring system for staging and prognosis in hepatocellular carcinoma (HCC), which is the fourth leading cause of cancer-related mortality worldwide. Commonly used systems include the albumin-bilirubin (ALBI) score, the Barcelona staging classification (Barcelona Clinic Liver Cancer, BCLC), the Model for End-Stage Liver Disease (MELD), and the model to estimate survival in ambulatory HCC patients (MESIAH). Liver secretion of pseudocholinesterase (PCHE) has been linked to liver function but is poorly studied in the natural history of HCC. We evaluated whether serum PCHE level predicts HCC mortality and whether it enhances existing scoring systems.

Methods: We conducted a retrospective cohort study of individuals diagnosed with HCC. We collected variables including PCHE level, clinical data used in scoring systems, and time to mortality or liver transplant. We then analyzed the association between these variables and survival using Kaplan-Meier curves, Cox proportional hazards regression models, receiver operating characteristic (ROC) curves, and area under the curve (AUC) calculations.

Results: We identified 420 individuals with HCC who were tested for PCHE levels, with a follow-up time of more than 20 years. There was a strong inverse relationship between PCHE level and overall survival, with the lowest quartile having high mortality and poor outcomes. Low PCHE level was associated with hepatitis C virus (HCV) infection, vascular invasion, poor liver function, and a high likelihood of liver transplant. In contrast, the highest quartile was associated with metabolic dysfunction-associated steatotic liver disease (MASLD) as the underlying cause. Compared with validated scoring systems, ALBI, BCLC, MELD 3.0, and MESIAH, the PCHE level was an independent predictor of mortality. PCHE levels could predict 3-month survival as well as or better than the other scoring systems, with an AUC of 0.74. PCHE level could also predict mortality related to hepatectomy. The addition of PCHE level to MESIAH and ALBI scoring systems could further improve the ability to predict overall mortality in HCC.

Conclusions: PCHE is a reliable stand-alone biomarker of HCC prognosis. It is an independent predictor of mortality and can improve the accuracy of existing scoring systems. Improved risk stratification could improve outcomes by informing treatment decisions regarding hepatectomy or other interventions.

Background and aims: Immunosuppression can cause hepatitis B virus (HBV) reactivation, leading to severe outcomes in patients with "resolved" HBV infection. This multicenter, randomized, placebo-controlled trial assessed the efficacy of preemptive antiviral therapy in HBsAg-negative, anti-HBc-positive patients receiving rituximab-based chemotherapy for non-Hodgkin lymphoma (NHL).

Methods: Patients were randomized 1:1 to tenofovir alafenamide (TAF)/placebo across 3 phases: chemotherapy plus TAF/placebo (phase 1), TAF/placebo post-chemotherapy (phase 2), and follow-up after therapy cessation (phase 3). The primary endpoint was HBsAg reverse seroconversion. HBsAg and ALT were monitored every 3-12 weeks, depending on treatment phase, and HBV DNA was measured post hoc. ClinicalTrials.gov (NCT02186574).

Results: Among 42 patients (median age 65.2 years, 52.4% male, 52.4% aggressive lymphoma, 73.8% anti-HBs positive), 20 received TAF and 22 received a placebo. Median ALT was 20.0 U/L (IQR: 15.0-28.0) at baseline. Median follow-up was 69.4 weeks (IQR: 63.7-166), with 6.1 weeks (IQR: 4.7-8.3) between visits. During follow-up, 2 patients in the TAF arm, but none receiving placebo, experienced HBsAg reverse seroconversions: occurring in phase 3 at 62.3 weeks from baseline, and in phase 1 at 20.0 weeks from baseline. Neither patient experienced ALT >2× ULN. HBV DNA >1000 IU/mL was observed in 8 instances among 6 patients, 3 in each arm, with no associated hepatitis. Low-level DNA (<1000 IU/mL) was not indicative of reverse seroconversion, DNA increases, or ALT elevations.

Conclusions: The use of preemptive TAF therapy did not reduce the risk of HBsAg reverse seroconversion; however, the findings should be interpreted with caution as the study was underpowered due to slow enrolment leading to early termination. Low-level HBV DNA elevations were not associated with HBV reactivation. Thus, close HBsAg and ALT monitoring are adequate in HBsAg-negative patients undergoing rituximab-based chemotherapy.