Burden Of Nonalcoholic Steatohepatitis Research Articles

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Beyond the boundaries of the liver.

The burden of non-alcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) is drawing attention due to the emerging epidemic of obesity and metabolic syndrome and is expected to increase in the near future. Antidiabetic medications, air pollutants, and newer genetic mutations are latest concerns as risk factors for HCC development in patients with NASH. Although molecular signatures are very accurate, they are not cost-effective and cannot be applied in larger population due to logistic issues. We need multicentric longitudinal studies including diverse geographical areas to evaluate the complex interplay of different risk factors and genetics in these patients.

The burden of non-alcoholic steatohepatitis: A systematic review of health-related quality of life and patient-reported outcomes

Background & AimsNon-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients’ health-related quality of life (HRQoL), but published data on the humanistic burden of disease are limited. This review aimed to summarise and critically evaluate studies reporting HRQoL or patient-reported outcomes (PROs) in populations with NASH and identify key gaps for further research.MethodsMedline, EMBASE, the Cochrane Library and PsycINFO were searched for English-language publications published from 2010 to 2021 that reported HRQoL/PRO outcomes of a population or subpopulation with NASH.ResultsTwenty-five publications covering 23 unique studies were identified. Overall, the data showed a substantial impact of NASH on HRQoL, particularly in terms of physical functioning and fatigue, with deterioration of physical and mental health as NASH progresses. Prevalent symptoms, including fatigue, abdominal pain, anxiety/depression, cognition problems, and poor sleep quality, adversely impact patients’ ability to work and perform activities of daily living and the quality of relationships. However, some patients fail to attribute symptoms to their disease because of a lack of patient awareness and education. NASH is associated with high rates of comorbidities such as obesity and type 2 diabetes, which contribute to reduced HRQoL. Studies were heterogeneous in terms of diagnostic methods, population, outcomes, follow-up time, and measures of HRQoL/utility. Most studies were rated ‘moderate’ at quality assessment, and all evaluable studies had inadequate control of confounders.ConclusionsNASH is associated with a significant HRQoL burden that begins early in the disease course and increases with disease progression. More robust studies are needed to better understand the humanistic burden of NASH, with adequate adjustment for confounders that could influence outcomes.Lay summaryNon-alcoholic steatohepatitis (NASH) has a significant impact on quality of life, with individuals experiencing worse physical and mental health compared with the general population. NASH and its symptoms, which include tiredness, stomach pain, anxiety, depression, poor focus and memory, and impaired sleep, affect individuals’ relationships and ability to work and perform day-to-day tasks. However, not all patients are aware that their symptoms may be related to NASH. Patients would benefit from more education on their disease, and the importance of good social networks for patient health and well-being should be reinforced. More studies are needed to better understand the patient burden of NASH.

The Burden of Nonalcoholic Steatohepatitis: A Systematic Review of Epidemiology Studies.

Nonalcoholic steatohepatitis (NASH) is associated with increased mortality and risk of complications but is often asymptomatic and under-recognized. A systematic review of NASH epidemiology was conducted to provide information on the burden of NASH and highlight important evidence gaps for future research. Medline, EMBASE, and Cochrane Library databases were searched for English-language publications published from 2010 to January 2022 that reported on natural history, risk factors, comorbidities, and complications of a NASH population or subpopulation. Overall, 173 publications were included. NASH was shown to have a variable disease course and high prevalence of comorbid disease. Although many patients progressed to cirrhosis and end-stage liver disease, disease regression or resolution was reported in up to half of patients in some studies. Reported risk factors for disease progression or resolution included levels of (or changes in) serum fibrosis markers, liver enzymes, and platelets. The presence of NASH increased the risk of liver cirrhosis and other serious diseases such as hepatocellular carcinoma, colorectal cancer, chronic kidney disease, and cardiovascular disease. In 2017, NASH was responsible for ∼118,000 cirrhosis deaths globally, and an increasing proportion of patients are receiving liver transplantation for NASH in Europe and the United States. Consolidation of data was hampered by heterogeneity across the studies in terms of patient populations, follow-up time, and outcomes measured. NASH is associated with significant morbidity and mortality, an increased risk of comorbidities, and imposes an increasing burden among liver transplantation recipients. Longer studies with harmonized study criteria are required to better understand the impact of NASH on patient outcomes.

Взаємовплив стану ліпідного спектру крові та вмісту адипокінів на клінічний перебіг неалкогольної жирової хвороби печінки за наявності коморбідної хронічної хвороби нирок

The purpose of the study was to find out the probable mutual influence of the state of the lipid spectrum of blood and content of adipokines in blood: leptin, adiponectin on the clinical course of non-alcoholic fatty liver disease against the background of obesity depending on its form and the presence of comorbid chronic kidney disease. Materials and methods. 444 patients were examined: of which 84 patients with non-alcoholic fatty liver disease with grade I obesity (group 1), which contained 2 subgroups: 32 patients with non-alcoholic hepatic steatosis and 52 patients with non-alcoholic steatohepatitis; 270 patients with non-alcoholic fatty liver disease with comorbid obesity of the I degree and chronic kidney disease of the I-III stage (group 2), including 110 patients with non-alcoholic steatosis of the liver and 160 patients with non-alcoholic steatohepatitis. The control group consisted of 90 patients with chronic kidney disease stage I-III with normal body weight (group 3). The mean age of patients was (45.8±3.81) years. Results and discussion. The study showed that patients with non-alcoholic steatohepatitis and obesity without concomitant chronic kidney disease are characterized by the following changes in the blood lipid spectrum: maximum increase in blood triacylglycerols (by 2.1 times, p <0.05), a probable increase in total cholesterol (by 1.4 times, p <0.05) and proatherogenic low-density lipoproteins (by 1.6 times, p <0.05), a probable decrease in anti-atherogenic high-density lipoproteins (by 1.6 times, p <0.05), which with the addition of comorbid chronic kidney disease are likely to deepen (within 1.5-1.8 times, p <0.05), in addition to hyper triacylglycerol. According to the results of the study, the content of leptin in the blood was significantly increased by 1.4 times (p <0.05) compared with almost healthy individuals, which differed significantly from patients with non-alcoholic steatosis of the liver with chronic kidney disease and non-alcoholic steatohepatitis with chronic kidney disease (p <0.05). The content of adiponectin in the blood was significantly reduced by 1.4 times compared with almost healthy individuals (p <0.05) and also differed significantly from patients with non-alcoholic hepatic steatosis with chronic kidney disease and non-alcoholic steatohepatitis with chronic kidney disease (p <0.05). Conclusion. Based on the results, it was found that significant metabolic prerequisites for the development of non-alcoholic steatohepatitis against the background of obesity and chronic kidney disease are probable postprandial hyperglycemia, hyperinsulinemia, increased glycosylation of hemoglobin. Hyperleptinemia and hypoadiponectinemia are also factors in the burden of non-alcoholic steatohepatitis and obesity due to the progression of mesenchymal inflammation and cytolysis of hepatocytes

Clinical and economic burden of nonalcoholic steatohepatitis in Saudi Arabia, United Arab Emirates and Kuwait

Background and aimsThe Middle East (ME) has a high prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), driven by obesity and type-2 diabetes mellitus (T2DM). Studies in Saudi Arabia (KSA) and United Arab Emirates (UAE) predict an escalating impact of NAFLD/NASH, particularly advanced fibrosis due to NASH (AF-NASH), increasing cases of cirrhosis, liver cancer and death. The scale of this burden in other ME countries is unknown with no reports of NAFLD/NASH healthcare resource utilization (HCRU) or costs. We estimated the clinical and economic burden of NAFLD/NASH in KSA, UAE and Kuwait.MethodsMarkov models populated with country-specific obesity and T2DM prevalence data estimated numbers and progression of NAFLD/NASH patients from 2018 to 2030. Model inputs, assumptions and outputs were collected from literature, national statistics, and expert consensus.ResultsOver 13 years, the KSA model estimated cases increasing as follows: patients with fibrosis F0–3 doubled to 2.5 m, compensated and decompensated cirrhosis and hepatocellular carcinoma trebled to 212,000; liver failure or transplant patients increased four-fold to 4,086 and liver-related death escalated from < 10,000 to > 200,000. Similar trends occurred in UAE and Kuwait. Discounted lifetime costs of NASH standard-care increased totaling USD40.41 bn, 1.59 bn and 6.36 bn in KSA, UAE (Emiratis only) and Kuwait, respectively. NASH-related costs in 2019 comprised, respectively, 5.83%, 5.80% and 7.66% of national healthcare spending.ConclusionsNASH, especially AF-NASH, should be considered a higher priority in ME Public Health policy. Our analyses should inform health policy makers to mitigate the enormity of this escalating regional burden.

Epidemiology and Disease Burden of Non-Alcoholic Steatohepatitis (NASH) in Greater China: A Systematic Review

Background: Non-Alcoholic steatohepatitis (NASH) is a progression of non-alcoholic fatty liver disease, leading to fibrosis, cirrhosis and hepatocellular carcinoma. The increasing burden of NASH has become a major concern of public health in greater China largely contributed by the rapid transition of lifestyle. The study aimed to characterize the epidemiology, disease burden, and treatment of NASH in greater China in order to better inform national disease management and delivery of health services. Methods: We conducted a systematic review searching four English databases (Web of Science, PubMed, Medline, and Cochrane Central) and three Chinese databases (CNKI, Wanfang, and VIP). We identified articles published from database inception to Oct 10, 2020 which reported NASH epidemiology, disease burden, and/or intervention in Chinese adults. The type of studies might include cross-sectional, cohort studies, randomized controlled trials and mathematical models. Exclusion criteria were studies for animal or cellular experiments, about population outside greater China, or with incomplete data. Findings: Of 44,115 articles retrieved, 33 were eligible for inclusion. Overall prevalence of NASH ranged from 2 ·4% to 6·1% in greater China, with a more substantial burden among males, the aged, and those in Hong Kong and Taiwan. Most NASH patients suffered from several comorbidities, including obesity, diabetes, and cardiovascular conditions. For non-obese subjects, PNPLA3 rs738409 G allele and haptoglobin 2-2 genotype drove the fibrosis progression in NASH. Increasingly prevalent cases of cirrhosis and hepatocellular carcinoma caused a higher NASH-related mortality. Compared with normal population, NASH patients experienced markedly poorer quality of life and heavier costs. Clinical trials of medication treatments specific for NASH are still ongoing. Interpretation: This is the first comprehensive overview of NASH among Chinese population that revealed an overwhelming impact of social and healthcare burden associated with the condition. Further high-quality studies are needed to improve the understanding and management of NASH in greater China. Funding: There was no funding source for this study. Declaration of Interests: We declare no competing interests.

CoreNASH: Multi-stakeholder Consensus on Core Outcomes for Decision Making About Nonalcoholic Steatohepatitis Treatment.

The increasing prevalence and burden of nonalcoholic steatohepatitis (NASH) has spurred the development of new treatments and a need to consider outcomes used for NASH treatment decision making. Development of a NASH core outcome set (COS) can help prioritize outcomes of highest importance by incorporating the perspectives from a variety of decision makers. coreNASH was an initiative to develop a COS for NASH using a modified Delphi consensus process with a multi‐stakeholder voting panel. A candidate outcome list was created based on a literature review and key informant interviews. The candidate outcome list was then condensed and prioritized through three rounds of online voting and through discussion at an in‐person meeting. Outcomes were retained or eliminated based on predetermined consensus criteria, which included special weighting of patients’ opinions in the first two voting rounds. The coreNASH Delphi panel included 53 participants (7 patients, 10 clinicians and researchers, 7 health technology assessors, 22 industry representatives, 2 regulators, and 5 payers) who considered outcomes for two NASH‐related COS: one for NASH without cirrhosis (F2‐F3) and one for NASH with cirrhosis (F4). The initial candidate outcome list for both disease stages included 86 outcomes. The panel agreed on including two core outcomes for NASH without cirrhosis and nine core outcomes for NASH with cirrhosis in the COS. Conclusion: A consensus‐based COS has been developed that can be used across the life cycle of NASH treatments. Outcomes included can contribute to decision making for regulatory, market access, and on‐market decision making. Including the coreNASH COS in clinical development programs will facilitate improved comparisons and help decision makers assess the value of new products.

Key molecular pathways in the progression of non-alcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide and also become an emerging risk factor for liver-related complications, such as cirrhosis and hepatocellular carcinoma (HCC). The liver-related burden of NASH is likely to increase and nonalcoholic steatohepatitis (NASH) is probably to be the leading indication for liver transplantation by 2020, as a consequence of increased disease prevalence and of the lack of an effective treatment. The first step in the NAFLD development is represented by fat accumulation in the liver, a condition that is commonly associated with features of the metabolic syndrome. Notably, it has been acknowledged that the step from nonalcoholic fatty liver (NAFL) to NASH is key step in the NASH formation, and the mechanisms behind this transition have been extensively studied. Emerging evidence indicates that innate immunity is a driving force in NAFLD progression because it directly regulates all key pathogenic features of the disease processes, including metabolic dysregulation, inflammation, and fibrosis. In this review, we summarize the currently available signaling pathways of NASH formation, including oxidative stress, NOD-like receptors (NLRs), mitochondria-associated pathways, Toll-like receptors (TLRs), nuclear receptors, and other signal pathways, for the aim of a better understanding of this disease.

THU-347-Economic and clinical burden of non-alcoholic steatohepatitis in patients with type II diabetes in the United States

THU-347-Economic and clinical burden of non-alcoholic steatohepatitis in patients with type II diabetes in the United States

Burden of nonalcoholic fatty liver disease and advanced fibrosis in a Texas Hispanic community cohort.

To investigate the potential burden of nonalcoholic steatohepatitis (NASH) and advanced fibrosis in a hispanic community. Four hundred and forty two participants with available ultrasonography data from the Cameron County Hispanic Cohort were included in this study. Each participant completed a comprehensive questionnaire regarding basic demographic information, medical history, medication use, and social and family history including alcohol use. Values of the nonalcoholic fatty liver disease fibrosis score (NFS), FIB4 index, BARD score, and Aspartate aminotransferase to Platelet Ratio Index (APRI) were computed using the blood samples collected within 6 mo of liver ultrasonography from each participant. Hepatic steatosis was determined by ultrasonography. As part of univariable analysis, for continuous variables, comparisons among groups were performed with student-t test, one way analysis of variance, and Mann-Whitney test. Pearson χ(2) and the Fisher exact test are used to assess differences in categorical variables. For multivariable analyses, logistic regression analyses were performed to identify characteristics associated with hepatic steatosis. All reported P values are based two-sided tests, and a P value of less than 0.05 was considered to indicate statistical significance. The mean age and body mass index (BMI) of the study participants were 49.1 years and 31.3 kg/m(2), respectively. Among them, 65.6% were females, 52% had hepatic steatosis, 49.5% had metabolic syndrome, and 29% had elevated aminotransferases. Based on established cut-offs for diagnostic panels, between 17%-63% of the entire cohort was predicted to have NASH with indeterminate or advanced fibrosis. Participants with hepatic steatosis had significantly higher BMI (32.9 ± 5.6 kg/m(2) vs 29.6 ± 6.1 kg/m(2), P < 0.001) and higher prevalence rates of elevation of ALT (42.2% vs 14.6%, P < 0.001), elevation of aspartate aminotransferase (38.7% vs 18.9%, P < 0.001), and metabolic syndrome (64.8% vs 33%, P < 0.001) than those without hepatic steatosis. The NFS scores (P = 0.002) and the APRI scores (P = 0.002) were significantly higher in those with steatosis but the scores of the FIB4 index and BARD were similar between the two groups. After adjusting for age, gender and BMI, elevated transaminases, metabolic syndrome and its components, intermediate NFS and APRI scores were associated hepatic steatosis in multivariable analysis. The burden of NASH and advanced fibrosis in the Hispanic community in South Texas may be more substantial than predicted from referral clinic studies.

Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial

Introduction. The burden of non-alcoholic steatohepatitis (NASH) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy. Pilot studies suggest that pentoxifylline (PTX) can reduce liver injury in patients with NASH.Objective. We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH.Material and methods. Thirty patients with biopsy proven NASH were randomized in a 2:1 fashion to receive 1,200 mg PTX or placebo for 12 months. Metabolic parameters, aminotransferases, liver histology and hepatic gene expression changes were compared.Results. At baseline the groups were similar. Adverse events were mild, most frequently headache and abdominal cramps, and did not differ between groups (p = NS). After 12 months, ALT and AST decreased from 92 ± 12 IU/L to 67 ± 13 IU/L and 67 ± 6 IU/L to 47 ± 6 IU/L (p < 0.05), respectively in patients treated with PTX. No significant effect was seen with placebo. Steatosis and cellular ballooning improved in the PTX group (p < 0.05), whereas no histological feature of steatohepatitis improved with placebo. However, between groups comparison of both biochemical and histological features were nonsignificant.Conclusion. Pentoxifylline is safe, well tolerated and improves transaminases and histology in patients with NASH when compared to baseline and may be a reasonable therapeutic modality for the treatment of NASH. However PTX failed to reduce transaminases compared to placebo and did not positively affect any of the metabolic markers postulated to contribute to NASH. Although animal data and small pilot studies in humans have suggested that PTX may be effective as a treatment for NASH, translating this therapy to clinical practice may prove challenging.