肝脏与痛风和肝性骨营养不良的中文综述

Nonalcoholic fatty liver disease (NAFLD) is characterized by over 5% hepatic fat accumulation without secondary causes. The prevalence of NAFLD has escalated in recent years due to shifts in dietary patterns and socioeconomic status, making it the most prevalent chronic liver disease and a significant public health concern globally. Serum uric acid (SUA) serves as the end product of purine metabolism in the body and is intricately linked to metabolic syndrome. Elevated SUA levels have been identified as an independent risk factor for the incidence and progression of NAFLD. This paper reviews the relationship between SUA and NAFLD, the underlying mechanisms of SUA involved in NAFLD, and the potential benefits of SUA-lowering therapy in treating NAFLD. The aim is to raise awareness of SUA management in patients with NAFLD, and to encourage further investigation into pharmacological interventions in this area.

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes patients with hepatic steatosis and at least one of five cardiometabolic risk factors. Xanthine oxidase (XO) represents a treatment target for MASLD. We aimed to evaluate the effect of two xanthine oxidase inhibitors, allopurinol and febuxostat, plus lifestyle modifications compared to lifestyle modifications alone on improving steatosis. Ninety MASLD patients were assigned to one of three groups for three months. Patients with hyperuricemia were given either allopurinol 100 mg or febuxostat 40 mg daily, along with lifestyle modifications. The third control group was only given lifestyle modifications, excluding all patients with hyperuricemia due to ethical concerns. The primary outcome was to measure the change in the controlled attenuation parameter (CAP) score as an indicator of steatosis from baseline after three months. The secondary outcome was to measure the change in serum uric acid (SUA) three months from baseline. The study found that the CAP score decreased significantly in the allopurinol group (p = 0.009), but the decline in the febuxostat or lifestyle groups was non-significant (p = 0.189 and 0.054, respectively). The SUA levels were significantly reduced in both the allopurinol and febuxostat groups (p < 0.001), with no statistical difference between the two groups (p = 0.496).

INTRODUCTION This study aimed to evaluate the effects of denosumab and alendronate on bone mineral density (BMD) and liver fibrosis markers in patients with both primary osteoporosis (OP) and metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS This was a single-center, retrospective observational study. A total of 60 patients diagnosed with both OP and MASLD were identified from Zhejiang Hospital and categorized into two groups based on their actual treatment received: denosumab (n=30) or alendronate (n=30). Baseline data, including demographic information, clinical characteristics, BMD, and liver fibrosis markers, were obtained from medical records. These measures were again obtained from records after approximately one year of treatment to evaluate changes in BMD and liver fibrosis markers. RESULTS In the denosumab group, marked improvements in BMD were observed at the lumbar spine (L1-4), femoral neck, and total hip (all P < 0.01). Additionally, there were notable reductions in liver fibrosis markers, such as FIB-4 and NFS (P < 0.01 and P < 0.05, respectively). In the alendronate group, only an increase in lumbar spine (L1-4) BMD was noted (P < 0.05), with no statistically significant changes observed in femoral neck or total hip BMD (P > 0.05), nor in liver fibrosis markers. CONCLUSION Denosumab use was associated with improvements in BMD and reductions in liver fibrosis in patients with OP and MASLD, suggesting it may be a promising therapeutic option.

CONTEXT Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown. OBJECTIVE This study aims to investigate the relationship between BMD and the risk of incident cirrhosis in the Hong Kong Osteoporosis Study (HKOS). METHODS BMD was measured at the lumbar spine, femoral neck, total hip, and trochanter of 7,752 participants by the dual-energy X-ray absorptiometer (DXA), and the incidence of cirrhosis and mortality were followed by linking to the territory-wide electronic health records database. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI. RESULTS With a median follow-up of 18.43 years, 42 incident cirrhosis were identified. Higher BMD T-scores at the femoral neck, total hip and trochanter were significantly associated with a reduced risk of cirrhosis (femoral neck: HR 0.56, 95% CI 0.39 to 0.82; total hip: HR 0.60, 95% CI 0.44 to 0.82; trochanter: HR 0.63, 95% CI 0.46 to 0.88). Similar associations were observed in participants without risk factors of cirrhosis at the baseline and further adjusting for the baseline level of alkaline phosphatase, albumin, and alanine transaminase. Consistent relationships in multiple sensitivity analyses suggest the robustness of the results. CONCLUSION Low BMD could be a novel risk factor and early predictor for cirrhosis, with consistent associations observed in multiple sensitivity analyses.

Background and aims Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly emerged term that is suggested to better reflect the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, the association between hyperuricemia and MAFLD has not been explored in the Chinese population. Meantime, this study also examined the temporal relationship between the two entities in a longitudinal cohort. Methods We conducted a retrospective cross-sectional study including 1,587,962 individuals from 19 health check-up centers in China from 2009-2017 and a longitudinal study with 16,112 individuals. A logistic regression model was applied to determine the association between hyperuricemia and MAFLD in a cross-sectional study. The Cox regression model was used to explore the association between hyperuricemia at baseline and subsequent onset of MAFLD or the association between the presence of MAFLD at baseline and the subsequent incidence of hyperuricemia. The cross-lagged analysis was applied to exam the temporal relationship between hyperuricemia and MAFLD. Results In the cross-sectional study, hyperuricemia showed a strong positive association with MAFLD after controlled potential confounders. In the longitudinal cohorts, hyperuricemia at baseline was associated with the new-onset of MAFLD, with a hazard ratio (HR) of 1.765 (95% CI: 1.512, 2.060). Interestingly, baseline MAFLD was also associated with the subsequent incidence of hyperuricemia, with an HR of 1.245 (95% CI: 1.106, 1.400). The cross-lagged path analysis revealed a bidirectional relationship between hyperuricemia and MAFLD. Conclusions The results suggested that hyperuricemia and MAFLD form a vicious cycle, resulting in more deterioration of metabolic status.

Abstract Hyperuricemia and metabolic dysfunction–associated steatotic liver disease share overlapping risk factors, yet the mechanistic contribution of uric acid remains unclear. Generation of uric acid occurs exclusively by xanthine oxidoreductase, a process intrinsically linked to electron transfer and oxidant generation, a relationship that can be viewed through electron accounting. This biochemical coupling makes it difficult to determine whether elevated uric acid drives pathology or reflects broader changes in increased redox/oxidative stress. This review highlights mechanisms of uric acid production, its dual antioxidant and pro-oxidant effects, and regulation of urate transporters. We then discuss how western dietary patterns, adiposity, and insulin resistance reshape uric acid homeostasis and intersect with pathways that promote steatosis, inflammation, and fibrogenesis. In conclusion, by framing uric acid within a liver-centered redox perspective, we consider whether elevated uric acid functions as a biomarker of metabolic stress, a contributor to disease progression, and a potential therapeutic target in metabolic dysfunction–associated steatotic liver disease.

Hyperuricemia has moved from a niche biochemical finding to a clinically relevant cardio-renal-metabolic risk state. This review synthesises contemporary evidence on uric acid biology, epidemiology, and management. We outline sources and biochemistry of urate, the hepatic xanthine oxidoreductase pathway, and the coordinated roles of renal and intestinal transporters that set steady-state serum levels, emphasising URAT1, GLUT9, NPT1, NPT4, and ABCG2, as well as the organic anion transporters OAT1 and OAT3, which import uric acid from the blood into proximal tubule cells. We summarise definitions, diagnostic thresholds, and global prevalence with sex-specific ranges, then differentiate asymptomatic hyperuricemia from crystal disease. Clinical sections integrate mechanistic links between soluble and crystalline urate and organ injury: inflammasome-mediated gout; tubulointerstitial injury, arteriolopathy, and obstructive pathways in kidney disease; oxidative stress, endothelial dysfunction, and vascular remodelling in hypertension, atherosclerosis, and coronary events; and metabolic pathways involving fructose metabolism, insulin resistance, and hepatic lipogenesis that connect hyperuricemia to metabolic syndrome and MAFLD. We appraise clinical evidence across cohorts, imaging, genetics, and randomised trials, distinguishing strong causal domains such as gout and uric acid nephrolithiasis from associative domains where treatment decisions should be individualised. A practical, phenotype-driven treat-to-target framework is presented that prioritises xanthine oxidase inhibition, adds uricosuric therapy for underexcretion, embeds lifestyle therapy, and applies safety strategies including HLA-B*58:01 screening in high-risk ancestries. We conclude with research gaps and priorities, including transporter-targeted strategies, intestinal urate quantification, pragmatic trials in enriched phenotypes, and clarity on long-term cardiovascular and renal outcomes.

Patients with cirrhosis are at increased risk for osteoporosis, and those who suffer a fracture are at high risk for mortality. Despite this, osteoporosis is often overlooked and undertreated. This study aimed to evaluate osteoporosis screening, management, and adverse osteoporosis medication events in patients with cirrhosis.

Purpose: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. Methods: This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). Results: Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child–Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. Conclusions: The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.