Coexistence Of Non-alcoholic Fatty Liver Disease Research Articles

The co-existence of NAFLD and CHB is associated with suboptimal viral and biochemical response to CHB antiviral therapy: a systematic review and meta-analysis

Background and aimsChronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are leading causes of liver-related morbidity and mortality. The interaction between these two disease processes is poorly defined and the impact of NAFLD on HBV-related cirrhosis and HCC remains unclear. The aim of this study was to evaluate the impact of NAFLD on response to antiviral CHB therapy to inform the debate on changing CHB treatment thresholds for these comorbid patients.MethodsStudies with a minimum of 50 adult CHB patients on nucleoside analogue therapy with or without concurrent NAFLD were identified from PubMed/Medline and EMBASE to February 21, 2023. Data extraction from each study included HBeAg and treatment status, diagnostic method of NAFLD, frequency of monitoring intervals, patient age, gender, grade of hepatic steatosis, BMI and metabolic comorbidities. The outcomes of interest, complete virological response (CVR), biochemical response (BR) and HBeAg loss/seroconversion, were recorded at each available monitoring interval. Comparing CHB-NAFLD and CHB-only groups, pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using random- or fixed-effects models depending on heterogeneity.ResultsFrom a search of 470 citations, we identified 32 potentially relevant papers. Overall, 11 studies, comprising 2580 unique patients, met the inclusion criteria of the meta-analysis. CHB-NAFLD patients exhibited significantly lower rates of CVR compared to CHB-only patients. This was demonstrated by an OR of 0.59 (0.38-0.93, p=0.001, I2 = 72%) at 12 months, which tapered off to an OR of 0.67 (0.48-0.95, p=0.02) at 60 months. CHB-NAFLD patients also exhibited significantly lower rates of BR compared to CHB-only patients, as demonstrated by ORs of 0.39 (0.24-0.62, p<0.0001, I2 = 53%) at 12 months and 0.33 (0.17-0.63, p=0.0008) at 24 months.ConclusionPatients with concurrent CHB and NAFLD experience delayed CVR to antiviral therapy and more persistent biochemical abnormalities in comparison to patients with CHB only. This supports the argument for earlier antiviral therapy in order to avert CHB complications in these multi-morbid patients, as the global disease burden of NAFLD continues to increase.

Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease

Background: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD. Methods: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3–5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction ≥5.6% according to guidelines. Results: Mean age was 72 ± 4.9 years in patients with CKD and 65.9 ± 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 ± 3.5 kg/m² and 27 ± 4.0 kg/m² in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0–8.5) and 4.1% (2.9–7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI −23; 45, p = 0.7463). Conclusion: These findings do not support any association between NAFLD and CKD (stages 3–5) in patients with type 2 diabetes.

Nonalcoholic Fatty Liver Disease and Its Complex Relation with Type 2 Diabetes Mellitus-From Prevalence to Diagnostic Approach and Treatment Strategies.

Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) are increasing rapidly worldwide, reaching epidemic proportions. Their association, based on common metabolic risk factors (obesity, insulin resistance (IR), unhealthy lifestyle), brings an additional risk of both hepatic and cardiovascular (CV) adverse clinical outcomes. The terminology of “NAFLD” is stigmatizing to some but not all patients, and a more practical one should be announced soon. Medical strategies can address both diseases simultaneously, as they have crossing pathophysiological mechanisms, mainly IR. Strategies vary from lifestyle intervention and pharmacological options, as more molecules designated for T2DM treatment may be helpful in NAFLD, to surgical procedures. This review focuses on the coexistence of NAFLD and T2DM, pointing out the utility of the appropriate terminology, its prevalence, and mortality rates among the diabetic population. Briefly, we have discussed the main pathophysiological mechanisms and the risk stratification algorithm for the development of NAFLD and nonalcoholic steatohepatitis (NASH) as well as the tools for evaluation of fibrosis. Finally, we have focused on the current therapeutic options for the treatment of NAFLD associated with T2DM.

Non-Alcoholic Fatty Liver Disease and other Non-Communicable Diseases: Time for an Integrated Approach

Non-Alcoholic fatty liver disease (NAFLD) is a broad term covering a spectrum of conditions ranging from hepatic steatosis, steatohepatitis and cirrhosis. NAFLD is highly prevalent across all regions of the world with its global prevalence of 25.2%(95%CI:22.1-28.7). It is commonly referred as the ‘hepatic manifestation’ of metabolic syndrome (MetS). Moreover, it is strongly associated with the individual components as well as MetS as a whole. NAFLD has been independently associated with other non-communicable diseases (NCDs) like chronic kidney disease (CKD), Polycystic ovary Syndrome (PCOS), Stroke and Cancers. This strong association of NCDs with NAFLD not only affects the prevalence but also the progression and management of the disease. Thus, this review aims at highlighting the association of NAFLD with other NCDs. A literature search was undertaken in the MEDLINE database using the necessary MeSH terms. The review concludes NAFLD is a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with numerous extra-hepatic manifestations, such as metabolic syndrome, cardiovascular diseases, chronic renal diseases, and malignancy. With co-existence of NAFLD with various NCDs it is expected to become the most overwhelming liver disease in the world in coming years. Hence, to reduce medical and economic impact associated with these comorbidities, it is recommended that all countries should estimate and predict the burden on comorbidities associated with NAFLD and galvanize its health resources in providing integrated therapeutic approaches for management of NAFLD and related comorbidities at an early stage.

The Coexistence of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.

The incidence of nonalcoholic fatty liver disease (NAFLD) is growing worldwide. Epidemiological data suggest a strong relationship between NAFLD and T2DM. This is associated with common risk factors and pathogenesis, where obesity, insulin resistance and dyslipidemia play pivotal roles. Expanding knowledge on the coexistence of NAFLD and T2DM could not only protect against liver damage and glucotoxicity, but may also theoretically prevent the subsequent occurrence of other diseases, such as cancer and cardiovascular disorders, as well as influence morbidity and mortality rates. In everyday clinical practice, underestimation of this problem is still observed. NAFLD is not looked for in T2DM patients; on the contrary, diagnosis for glucose metabolism disturbances is usually not performed in patients with NAFLD. However, simple and cost-effective methods of detection of fatty liver in T2DM patients are still needed, especially in outpatient settings. The treatment of NAFLD, especially where it coexists with T2DM, consists mainly of lifestyle modification. It is also suggested that some drugs, including hypoglycemic agents, may be used to treat NAFLD. Therefore, the aim of this review is to detail current knowledge of NAFLD and T2DM comorbidity, its prevalence, common pathogenesis, diagnostic procedures, complications and treatment, with special attention to outpatient clinics.

Non-alcoholic fatty liver disease and sarcopenia additively increase mortality: a Korean nationwide survey.

BackgroundSarcopenia is an independent risk factor not only for advanced‐stage non‐alcoholic fatty liver disease (NAFLD) but also for mortality. We investigated the association of sarcopenia and/or NAFLD with mortality among the Korean general population.MethodsIndividuals aged 35–75 years without any history of cancer, ischaemic heart disease, ischaemic stroke, or secondary causes of chronic liver disease were selected from the Korean National Health and Nutrition Examination Surveys from 2008 to 2015. Their mortality data until December 2018 were retrieved from the National Death Registry. NAFLD and sarcopenia were defined by hepatic steatosis index and appendicular skeletal muscle mass divided by body mass index (BMI), respectively.ResultsA total of 28 060 subjects were analysed [mean age, 50.6 (standard error, 0.1) years, 48.2 (0.3) % men]; the median follow‐up duration was of 6.8 (interquartile range, 4.8, 8.4) years. NAFLD predicted mortality after adjustment for age, sex, BMI, hypertension, dyslipidaemia, and smoking (HR 1.32, 95% CI 1.03–1.70), but this prediction lost its statistical significance after additional adjustment for diabetes mellitus. In contrast, NAFLD with advanced fibrosis independently increased the risk of mortality after adjustment for all covariates (HR 1.68, 95% CI 1.02–2.79). Stratified analysis revealed that NAFLD and sarcopenia additively increased the risk of mortality as an ordinal scale (HR 1.46, 95% CI 1.18–1.81, P for trend = 0.001). The coexistence of NAFLD and sarcopenia increased the risk of mortality by almost twice as much, even after adjustment for advanced fibrosis (HR 2.18, 95% CI 1.38–3.44).ConclusionsConcurrent NAFLD and sarcopenia conferred a two‐fold higher risk of mortality. The observation that NAFLD and sarcopenia additively increase mortality suggests that risk stratification would be helpful in predicting mortality among those with metabolic derangement.

Role of Agents for the Treatment of Diabetes in the Management of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is an often unrecognized complication of type 2 diabetes (T2DM) associated with significant economic burden and poor long-term hepatic and extrahepatic outcomes. Our goal is to review evidence about the complex association between NAFLD and T2DM and highlight the potential for disease co-management with the available medications used for the treatment of diabetes. A milieu of metabolic factors such as insulin resistance, glucotoxicity, and lipotoxicity, as well as genetics and other factors, contribute to the pathogenesis and co-existence of NAFLD with T2DM. The presence of T2DM in patients with NAFLD increases the risk of disease progression to steatohepatitis (NASH) and advanced fibrosis, cirrhosis, and even hepatocellular carcinoma. In addition to lifestyle modification, pioglitazone and glucagon-like peptide 1 receptor agonists (GLP-1RAs) both reduce the high cardiovascular risk and improve liver histology in patients with NAFLD. Sodium-glucose cotransporter (SGLT-2) inhibitors also appear to reverse metabolic abnormalities as well as liver disease in NAFLD, but their impact on liver histology has not been fully established. Lastly, metformin, dipeptidyl dipetidase-4 (DPP-4) inhibitors, and insulin appear to have modest to no effect on modifying the natural history of NAFLD. Early recognition of NAFLD and monitoring for NASH with advanced liver fibrosis in patients with T2DM are crucial. The presence of NASH in a patient with T2DM should call for taking advantage of antidiabetic medications with proven efficacy to improve cardiometabolic health and prevent liver disease progression.

Concurrence of HBV infection and non-alcoholic fatty liver disease is associated with higher prevalence of chronic kidney disease

Coexistence of non-alcoholic fatty liver disease (NAFLD) and hepatitis B virus (HBV) infection is common in clinical practice. This study was to explore the prevalence of chronic kidney disease (CKD) in patients with NAFLD and/or HBV. Participants who received health examination in a physical examination center were included in this cross-sectional study. Binary logistic regression was used to estimate the odds ratios (ORs) for CKD. A total of 32,578 cases were included in the final analysis, with 52.3% males and an average age of 44.01±13.09 years old. The positive rate of HBV surface antigen was 14.5% and NAFLD was diagnosed in 30.2% cases. The coexistence of NAFLD and HBV-infection was found in 1,275 (3.9%) cases. In overall population, 713 (2.2%) cases were diagnosed with CKD. The CKD prevalence were 1.4%, 2.1%, 3.5% and 5.0% in those without NAFLD or HBV, HBV-infection alone, NAFLD alone and those with concomitant HBV-infection and NAFLD, respectively. After adjustment for age, sex, body mass index, diabetes and hypertension, the correlation between CKD and liver disease was still significant in HBV group (OR=1.388, 95%CI: 1.055-1.809), yet no longer existed in patients with NAFLD (OR=1.183, 95%CI: 0.986-1.420). The concomitant of NAFLD and HBV infection was associated with a higher odds ratio for CKD compared to any other group (OR=1.961, 95%CI=1.454-2.645). The coexistence of NAFLD and HBV increases the risk of CKD by 2-fold. The control of multiple liver diseases will be beneficial not only to liver but also to kidney.

Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

Despite the widespread use of vaccines and antiviral drugs, approximately 350-400million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB is commonly observed, especially in Asian CHB populations; however, little is known regarding the relationship between these two diseases as comorbidities. In this review, we summarize recent advances in clinical and basic researches related to the underlying mutual interactions, as well as potential animal models to facilitate further investigation.

Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus.

Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.

Additive effect of non-alcoholic fatty liver disease on the development of diabetes in individuals with metabolic syndrome.

Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome (MetS), with insulin resistance as the common pathophysiology. In a current longitudinal cohort study, we evaluated the separate and combined effects of MetS and NAFLD on incident diabetes risk. Participants were categorized into four groups on the basis of the presence of NAFLD and MetS at baseline (i.e., with NAFLD, with MetS, with both, or without either). We compared the development of diabetes among these four groups. During the mean follow up of 4years, 435 of the 7849 participants (5.5%) developed diabetes. The age, sex, and smoking-adjusted risk of incident diabetes was higher in the NAFLD only group (HR 1.51, 95% CI 1.14-1.99), MetS only group (HR 2.82, 95% CI 2.01-3.95), and both group (HR 5.45, 95% CI 4.32-6.82) compared with the group of neither. When compared with the NAFLD only group, the adjusted HR for incident diabetes was 1.87 (95% CI 1.29-2.72) in the MetS only group and 3.62 (95% CI 2.74-4.77) in both group. Among individuals with MetS, the presence of NAFLD showed a significant increase in risk of incident diabetes even after further adjustment for MetS components including fasting glucose, TG, BMI, systolic BP, and HDL-C (HR 1.53, 95% CI 1.09-2.16). The presence of NAFLD further increased the risk of incident diabetes in individuals with metabolic syndrome. Our results suggest that the coexistence of NAFLD has an additive effect on the development of diabetes in individuals with MetS.

Can Detection of Non-alcoholic Fatty Liver Disease be Coincidental in Young Patients with Chronic Hepatitis B?

OZ Amac: Bu arastirmanin amaci hepatit B yuzey antijeni (HBsAg) pozitif ve negatif genc hastalarda alkolik olmayan yagli karaciger hastaliginin (AOYKH) sikligini, AOYKH olusumu ile iliskili faktorleri ve hepatit B virusu (HBV) ile AOYKH'nin birlikte saptanmasinin rastlantisal olup olmadigini ortaya koymakti. Gerec ve Yontemler: Bu retrospektif calisma bir askeri hastanede yapildi. Calismaya toplam 384 hasta dahil edildi. Hastalar ultrasonografik (US) olarak saptanan AOYKH'na gore iki gruba ayrildi. Gruplarin sosyodemografik, biyokimyasal, histopatolojik, virolojik ve US bulgulari retrospektif olarak kaydedildi. SPSS 22,0 kullanilarak istatistiksel analizleri yapildi. Bulgular: Tumu erkek olan hastalarin yas ortancasi 26 yil (20-40 yil) saptandi. Hastalarin %16,9'unda AOYKH tanimlandi. AOYKH olan hastalarin %36,9'unda HBsAg pozitifligi saptandi. AOYKH olan ve olmayan hastalar arasinda HBsAg pozitifligi acisindan istatistiksel olarak onemli fark saptanmadi (p=0,661). HBsAg pozitif hastalarin %13,2'sinde, HBsAg negatif hastalarin %20,3'unde AOYKH belirlendi. HBsAg pozitif ve negatif hastalar arasinda AOYKH acisindan onemli fark bulunmadi (p=0,158). HBsAg pozitif hastalarda γ-glutamil transferaz, HBsAg negatif hastalarda yas, alanin transaminaz ve aspartat transaminaz AOYKH varligi ile iliskili en onemli faktorler olarak belirlendi. Sonuc: Bu calismada HBsAg pozitifliginin genc hastalarda AOYKH gelisimi ile iliskili olmadigini, HBV ve AOYKH birlikteliginin rastlantisal olabilecegini saptadik. Anahtar Kelimeler: Alkolik olmayan yagli karaciger hastaligi, kronik hepatit B, ultrasonografi Objective: The objective of this study was to determine the factors associated with the presence of non-alcoholic fatty liver disease (NAFLD) in young persons who are hepatitis B surface antigene (HBsAg)-positive and negative, and to investigate if NAFLD coexisting hepatitis B virus (HBV) is coincidental. Materials and Methods: This retrospective study, conducted in a military hospital in Turkey, included a total of 384 subjects. The subjects were divided into two groups according to the presence of NAFLD detected by ultrasonography (US). Sociodemographic characteristics, biochemical, histopathological, virological and US results were recorded . Statistical analysis was performed using SPSS 22.0. Results: The median age of the patients, all of whom were male, was 26 years (20-40). NAFLD was identified in 16.9% of patients. HBsAg positivity was found in 36.9% of patients with NAFLD. It was remarkable that no statistically significant difference was found in HBsAg positivity between the patients with and without NAFLD (p=0.661). NAFLD was found in 13.2% of HBsAg-positive patients. NAFLD was determined in 20.3% of HBsAg-negative patients. No significant difference was found in NAFLD grades between HBsAg-positive and negative patients (p=0.158). In the present study, only γ-glutamyl transferase in HBsAg positive patients, and age, alanine transaminase and aspartate transaminase in HBsAg negative patients were determined as the most important factors associated with the presence of NAFLD. Conclusion: We found that HBsAg positivity is not correlated with the development of NAFLD in young patients, and coexistence of NAFLD and HBV might

Risk interaction of obesity, insulin resistance and hormone-sensitive lipase promoter polymorphisms (LIPE-60 C &gt; G) in the development of fatty liver

BackgroundHormone sensitive lipase (HSL) promoter (LIPE-60 C > G) polymorphism has been found to be involved in hepatic steatosis, obesity, diabetes and dyslipidemia. The precise interactions between these risk factors and genetic susceptibility that may affect non-alcoholic fatty liver disease (NAFLD) are still not fully determined.MethodsA cross-sectional study was conducted in 1056 men. To avoid the confounding effect of plasma glucose, the study population was classified into normal glucose tolerance (NGT, n = 729) and glucose intolerance (GI, n = 299) groups. NAFLD was diagnosed by abdominal ultrasound after ruling out any history of alcohol abuse. A multivariate regression model was used to estimate the impact of these factors on NAFLD.ResultsIn the NGT group, subjects with NAFLD often have complicated metabolic abnormalities. The coexistence of NAFLD and GI has been demonstrated to have a synergistic effect raising BMI, serum insulin and HOMA-insulin resistance (HOMA-IR). BMI and adipose-insulin resistance (Adipo-IR), but not HOMA-IR, significantly contributed to a greater risk of developing NAFLD. Serum triglyceride was significantly up-regulated in men with the (CG + GG) genotype of HSL promoter polymorphism, NAFLD and Adiopo-IR in sequence.ConclusionAdipo-IR, rather than HOMA-IR, appears to be a consistent insulin resistance index in the study of NAFLD. G allele of the HSL promoter polymorphism may contribute the greatest impact raising serum triglyceride in a state of glucose intolerance.

Coexistence of non-alcoholic fatty liver disease with elevated alanine aminotransferase is associated with insulin resistance in young Han males

Elevated alanine aminotransferase (ALT) and non-alcoholic fatty liver disease (NAFLD) have been associated with insulin resistance (IR). The objective of this study was to determine whether elevated ALT and NAFLD were useful for early and definitive determination of IR and to compare their coexistence with conventional risk factors in young Han males. Anthropometric and metabolic measurements were assessed in 216 young Han males (19.3 ± 0.8 years). NAFLD was diagnosed using ultrasonography, and the homeostasis model assessment of insulin resistance (HOMA-IR) served as an index of IR. Subjects in the fourth HOMA-IR quartile had a significantly higher frequency of abdominal obesity, elevated blood pressure and ALT, and NAFLD compared to subjects in quartiles 1-3 (P < 0.05). Using multivariate logistic regression analysis, risk of IR increased by 2.33-fold (95% CI: 1.00-5.42, P = 0.050) in participants with NAFLD. In addition, the coexistence of NAFLD and elevated ALT were significantly associated with HOMA-IR and participants with both elevated ALT and NAFLD had a 4.65-fold (95% CI: 1.55-13.97, P = 0.006) increased risk of IR. Coexistence of NAFLD and elevated ALT are associated with IR in young Han males and might be useful for early detection of IR as compared to conventional risk factors.