The Assessment of the Quality of Life in Children with Chronic Liver Disease

Background: Improvement in the quality of life (QoL) of patients with chronic diseases is as important as medical care. This study aimed to evaluate the QoL of children with chronic liver diseases and to determine related factors.Methods: For this study, 101 children with chronic liver disease, 100 healthy controls, and their parents were included. The Pediatric Quality of Life Scale (PedsQL) was used to evaluate health-related QoL; higher scores indicate better QoL. Patients were evaluated before and after initiation of treatment and being educated about their illness.Results: The mean patient age was 12.9 ± 3.9 years. Total PedsQL scores of the patients and the healthy control group were 38.6 ± 18.9 and 55.4 ± 14.3, respectively (P = .01). The scores of the parents of the patient and control groups were 35.4 ± 14.2 and 54.0 ± 16.9, respectively (P = .02). Patient and parent scores were positively correlated. Significantly higher scores were found in the 5-10 age group compared to the 10-15 and 15-18 age groups in the psychosocial score category. An increase in the QoL scores of patients who were started on medication other than steroid treatment was observed in the sixth month of treatment (35.8 ± 13.4 vs. 33.6 ± 8.9, P = .01, respectively).Conclusion: Both children with chronic liver diseases and their parents have a perceived lower QoL than healthy peers. The effect of chronic liver disease on psychosocial health is more pronounced in children older than 10 years. The quality of life is inversely proportional to the severity of the disease. It was observed that primary or symptomatic treatments have a positive impact on the perception of QoL, with the exception of steroid treatment.     

Alterations in Serum Leptin in Chronic Liver Disease

The role of leptin in anorexia associated with liver cirrhosis remains controversial. The aim of this study was to quantify the serum leptin level in patients with hepatocellular or cholestatic liver disease and to assess its relationship with serum insulin, body mass index, and serum lipoproteins. The study population included 30 women, 15 with chronic hepatocellular liver disease and 15 with primary biliary cirrhosis; severity of disease was determined by Child-Pugh and histological criteria, respectively. Ten healthy, age-matched women served as controls. Levels of serum leptin and insulin were determined by radioimmunoassay. Mean serum leptin level was significantly lower in the primary biliary cirrhosis group compared to both the control (P 0.05) and the hepatocellular groups (P 0.05). Serum leptin level strongly correlated with body mass index in the hepatocellular group (P < 0.0001) and the controls (P < 0.001), but not in the primary biliary cirrhosis group; it showed no correlation with severity of liver disease. A positive correlation was found between serum leptin and serum cholesterol (P = 0.02), low density lipoprotein (P = 0.01), and triglycerides (P = 0.04) in the hepatocellular group and in the controls between serum leptin and serum high density lipoproteins (P = 0.01). Serum leptin is low in patients with primary biliary cirrhosis. The combined findings of normal insulin response less insulin resistance, and lower serum leptin level in primary biliary cirrhosis compared to hepatocellular liver disease may indicate that serum leptin is merely a passive marker and not a cause of anorexia in liver disease.     

类风湿关节炎患者血清铁调素与贫血及疾病活动性的关系

目的 探讨血清铁调素（hepcidin,Hepc）在类风湿关节炎（rheumatoid arthritis,RA）患者中的作用及其与贫血及病情活动度的关系.方法 用酶联免疫吸附法测定80例RA患者（RA组）、20例其他结缔组织病（connective tissue disease,CTD）患者（其他CTD组）、20例健康志愿者（健康对照组）血清Hepc水平及RA患者白介素（interleukin,IL）-6、IL-1β、肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）水平,比较3组间Hepc的差异,分析RA患者中贫血与非贫血、不同病情活动度间Hepc及其他细胞因子水平差异,以及RA患者血清Hepc水平与其他因素间的相关性.结果 血清Hepc水平在RA组中明显升高,与其他CTD组及健康对照组相比,差异有统计学意义（均P〈0.01）.血清Hepc升高的RA患者病情活动度评分和IL-6浓度均高于Hepc正常组（均P〈0.05）.RA贫血者血清IL-6水平明显高于非贫血者（P〈0.05）,TNF-α、IL-1β及Hepc在RA贫血者与非贫血者间差异无统计学意义（均P〉0.05）.RA高度活动者的血红蛋白浓度明显低于非高度活动者（P〈0.05）,而Hepc水平则较非高度活动者升高,但差异无统计学意义（P=0.063）.RA患者血清Hepc水平与IL-6（r=0.298）和RF（r=0.264）均存在正相关（均P〈0.05）;与DAS28存在明显正相关（r=0.359,P〈0.01）.结论 Hepc可能作为一个炎性因子参与了RA的发展,检测Hepc可能作为RA病情活动度和预后的评价指标之一.     

HFE Gene Mutation, Chronic Liver Disease, and Iron Overload In Turkey

We aimed to determine the relationships between iron overload and HFE gene mutation in chronic liver disease in Turkey. One hundred thirteen chronic liver disease patients and 138 healthy controls were evaluated regarding their clinical, biochemical, and genetic parameters. Each group was divided into two subgroups according to transferrin saturation (TS) (45% and >45%). HFE gene mutation was analyzed by the PCR-RFLP method. C282Y homozygote, heterozygote, and wild-type mutation rates were 1.7%, 0%, and 98.3% in patients and 0%, 1.4%, and 98.6% in controls, respectively. H63D homozygote, heterozygote, and wild-type mutation rates were 1.8%, 24.7%, and 73.5% in patients and 1.4%, 24%, and 74.6% in controls, respectively. Mutation rates were not statistically different in patients with high and normal TS. Iron overload was positively correlated with biochemical activity and Child-Pugh score (P < 0.05). In multivariate analysis, H63D homozygotic mutation was an independent factor for the development of hepatocellular carcinoma (P = 0.004). We conclude that C282Y mutation is very rare in Turkey. Iron overload is not related to H63D mutation but is positively correlated with biochemical activity and Child-Pugh score in chronic liver diseases.     

Chronic Liver Disease and Silymarin: A Biochemical and Clinical Review

Chronic liver disease (CLD) is an under-recognized epidemic that continues to increase in prevalence and is a major health concern. Silymarin, the active compound of Silybum marianum (Milk thistle), has historically been used in CLD. A significant barrier to silymarin use is its poor bioavailability. Attempts at improving the bioavailability of silymarin have led to a better understanding of formulation methods, pharmacokinetics, dosing, and associated drug interactions. Clinically, silymarin exerts its hepatoprotective effects through antioxidative, antifibrotic, anti-inflammatory, antitoxin, and anticancerous mechanisms of actions. Despite the use of silymarin being extensively studied in alcoholic liver disease, metabolic-associated fatty liver disease, viral hepatitis, and drug-induced liver injury, the overall efficacy of silymarin remains unclear and more research is warranted to better elucidate the role of silymarin in CLD, specifically regarding its anti-inflammatory effects. Here, we review the current biochemical and clinical evidence regarding silymarin in CLD.     

终末期肝病模型在评估慢性重型肝炎预后中的应用

目的 探讨终末期肝病模型(MLED)评分系统对慢性重型肝炎患者短期(3个月)预后的预测能力及其临床应用价值.方法 应用MELD模型公式对125例慢性重型肝炎患者进行评分,观察其3月内的死亡率,以受试者工作特征(ROC)曲线和曲线下面积评价该系统预测患者短期(3个月)预后的准确性,并求出作为判断患者3个月内死亡与否的ME...     

Hepcidin/Ferritin Ratios Differ Among Non‐Dialyzed Chronic Kidney Disease Patients,and Patients on Hemodialysis and Peritoneal Dialysis

The serum levels of hepcidin generally increase in patients with chronic kidney disease (CKD) due to inflammation or a decline in the glomerular filtration rate. However, the differences in the ferrokinetics among dialysis modalities are unclear. We investigated the relationship between serum levels of hepcidin and ferritin among non‐dialyzed CKD (ND), hemodialysis (HD), and peritoneal dialysis (PD) patients. We recruited 285 CKD patients (117 ND, 80 HD, and 88 PD patients) and measured the serum levels of hepcidin‐25, ferritin, hemoglobin, iron, transferrin saturation (TSAT), albumin, and high sensitivity C‐reactive protein (hs‐CRP). Hepcidin‐25 levels were elevated in all CKD patients and were significantly higher in PD than in ND and HD patients. The hepcidin/ferritin ratio was significantly higher in PD patients independent of TSAT, hemoglobin, hs‐CRP, and serum albumin. Hepcidin/ferritin ratio, associated with both dialysis modality and inflammation, is expected to be a useful indicator of anemia in CKD.     

Cytokine Storm of COVID-19 and Its Impact on Patients with and without Chronic Liver Disease

The coronavirus pandemic has resulted in increased rates of hepatic decompensation, morbidity and mortality in patients suffering from existing liver disease, and deranged liver biochemistries in those without liver disease. In patients with cirrhosis with coronavirus disease 2019 (COVID-19), new onset organ failures manifesting as acute-on-chronic liver failure have also been reported. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) also directly binds to enterocytes and cholangiocytes via the angiotensin converting enzyme receptor 2, although the lung remains the portal of entry. Superadded with the COVID-19 related bystander hepatitis, a systemic inflammatory response is noted due to unregulated macrophage activation syndrome and cytokine storm. However, the exact definition and diagnostic criteria of the ‘cytokine storm’ in COVID-19 are yet unclear. In addition, inflammatory markers like C-reactive protein, ferritin, D-dimer and procalcitonin are frequently elevated. This in turn leads to disease progression, activation of the coagulation cascade, vascular microthrombi and immune-mediated injury in different organ systems. Deranged liver chemistries are also noted due to the cytokine storm, and synergistic hypoxic or ischemic liver injury, drug-induced liver injury, and use of hepatotoxic antiviral agents all contribute to deranged liver chemistry. Control of an unregulated cytokine storm at an early stage may avert disease morbidity and mortality. Several immunomodulator drugs and repurposed immunosuppressive agents have been used in COVID-19 with varying degrees of success.     

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease: Results from the Thai Association for the Study of the Liver (THASL) DILI Registry

Background and AimsThe impact of drug-induced liver injury (DILI) on patients with chronic liver disease (CLD) is unclear. There are few reports comparing DILI in CLD and non-CLD patients. In this study, we aimed to determine the incidence and outcomes of DILI in patients with and without CLD.MethodsWe collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies, causes, and the severity of DILI. We compared the causative agents, clinical features, and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry. Subjects with definite, or highly likely DILI were included in the analysis.ResultsA total of 200 subjects diagnosed with DILI were found in the registry. Of those, 41 had CLD and 159 had no evidence of CLD in their background. Complementary and alternative medicine (CAM) products were identified as the most common class of DILI agents. Approximately 59% of DILI in the CLD and 40% in non-CLD group were associated with CAM use. Individuals with pre-existing CLD had similar severity including mortality. Twelve patients (6%) developed adverse outcomes related to DILI including seven (3.5%) deaths and five (2.5%) with liver failure. Mortality was 4.88% in CLD and 3.14% in non-CLD subjects over median periods of 58 (8–106) days and 22 (1–65) days, respectively.ConclusionsIn this liver disease registry, the causes, clinical presentation, and outcomes of DILI in subjects with CLD and without CLD patients were not different. Further study is required to confirm our findings.     

Chronic Hepatitis B Infection with Low Level Viremia Correlates with the Progression of the Liver Disease

Background and AimsCurrently, insufficient clinical data are available to address whether low-level viremia (LLV) observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs. This study compared the clinical outcomes of patients with a maintained virological response (MVR) and patients who experienced LLV and their treatment strategies.MethodsA retrospective cohort of 674 patients with chronic hepatitis B virus (HBV) infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period. End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma (HCC).ResultsDuring a median 42-month follow-up, end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR (7.73% and 15.85% vs. 0.77% and 5.52% at 5 and 10 years, respectively; p=0.000). The trend was consistent after propensity score matching. In the high-risk group of four HCC risk models, LLV patients had a higher risk of HCC development (p<0.05). By Cox proportional hazard model analysis, LLV was an independent risk factor for end-stage liver disease and HCC (hazard ratio [HR]=6.280, confidence interval [CI]=2.081–18.951, p=0.001; HR=5.108, CI=1.392–18.737, respectively; p=0.014). Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred (p<0.05).ConclusionsLLV is an independent risk factor for end-stage liver disease and HCC, and treatment adjustments can be considered.     

Hepcidin is a Potential Regulator of Iron Status in Chronic Kidney Disease

Hepcidin is a small defensin‐like peptide produced primarily by hepatocytes, but also by other cells, including macrophages. In addition to hepcidin's antimicrobial properties, it is the main regulator of iron metabolism and controls both the amount of dietary iron absorbed in the duodenum and the iron release by reticuloendothelial cells. Hepcidin expression is upregulated by a variety of stimuli, including inflammation and iron overload, and downregulated by anemia, hypoxia, and iron deficiency. Chronic kidney disease (CKD) is associated with increased serum hepcidin levels, and the increased levels may contribute to the development and severity of anemia and to resistance to erythropoiesis‐stimulating agents (ESAs). Elevated serum hepcidin levels contribute to the dysregulation of iron homeostasis in CKD patients. Although parenteral iron supplementation can bypass some of the iron‐blocking effects of hepcidin in CKD patients with anemia, and free iron and iron stores increase as a result, the anemia is only partially corrected, and the ESA dose requirements remain significantly higher than needed for physiological replacement. Treatment with agents that lower serum hepcidin levels or inhibit its actions may be an effective strategy for restoring normal iron homeostasis and improving anemia in CKD patients. The aim of this article was to review the regulation of hepcidin levels and the role of hepcidin in CKD‐related anemia, and to discuss hepcidin's potential as a clinical biomarker and several investigational treatments designed to lower serum hepcidin levels.     

COVID-19 Vaccination in Patients with Chronic Liver Disease

Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions.