Risk Of Liver Disease Progression Research Articles

Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma. On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030, there is an increasing call to expand the indications for treatment of chronic hepatitis B. Currently, the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus. There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration. This editorial addresses key questions about the topic and whether indications for treatment should be expanded.

High prevalence of diabetes among young First Nations Peoples with metabolic dysfunction-associated steatotic liver disease: a population-based study in Australia

BackgroundLiver disease is an important contributor to the mortality gap between First Nations Peoples and non-Indigenous Australian adults. Despite a high burden of metabolic comorbidities among First Nations Peoples, data about the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population is scarce.MethodsA retrospective analysis of all adults hospitalized with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) with/without cirrhosis during 2007–2019 in the state of Queensland was performed. Patients were followed from the first admission with MASLD/MASH (identified based on validated algorithms) to decompensated cirrhosis and overall mortality. We explored differences according to Indigenous status using Multivariable Cox regression.Findings439 First Nations Peoples and 7,547 non-Indigenous Australians were followed for a median of 4.6 years (interquartile range 2.7–7.2). Overall, women were overrepresented, but more so in the First Nations cohort (72.7% vs. 57.0%, p < 0.001). First Nations patients were younger, a higher proportion lived in remote and socioeconomic disadvantaged areas, and had higher comorbidity compared to non-Indigenous Australians (all p < 0.001). Diabetes, the most common comorbidity affecting both groups, was overrepresented in First Nations Peoples versus non-Indigenous Australians (43.5% vs. 30.8%, p < 0.001, respectively). Nineteen (4.3%) First Nations Peoples and 332 (4.4%) of non-Indigenous patients progressed to cirrhosis decompensation (9.0% [95%CI 4.5–17.7] vs. 7.7% [95%CI 6.6–8.9; p = 0.956] respectively within 10 years). In multivariable analysis, there was no association between Indigenous status and progression to decompensated cirrhosis (p = 0.759) and survival (p = 0.437).ConclusionsThis study provides the first population-based epidemiological data on MASLD in First Nations Australians. The high prevalence of diabetes (that is associated with advanced fibrosis and liver disease mortality) among young First Nations Peoples with MASLD raises concern about future risk of progressive liver disease in this patient population. These data highlight the importance of early identification of MASLD, and providing culturally appropriate intervention to reduce disease progression in parallel with the management of cardiometabolic comorbidities.

Impact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among US Veterans With Steatotic Liver Disease

Background & AimsConflicting data exists on impact of alcohol use on risk of liver disease progression in patients with steatotic liver disease. We aim to evaluate the effect of longitudinal alcohol use on risk of cirrhosis among Veterans with steatotic liver disease. MethodsU.S. Veterans with steatotic liver disease were identified from January 2010 to December 2022. Alcohol use was assessed using documented AUDIT-C scores and categorized as no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1-3 for men), high-risk alcohol (AUDIT-C > 3 for women and > 4 for men). Incidence of cirrhosis was evaluated with competing risks Nelson-Aalen methods. Adjusted multivariable regression models evaluated risks of cirrhosis associated with baseline alcohol use and changes in alcohol use during follow up. Results1,156,189 Veterans with steatotic liver disease were identified (54.2% no alcohol, 34.6% low-risk alcohol, 11.2% high-risk alcohol). Veterans with steatotic liver disease and high-risk alcohol have 43% higher incidence of cirrhosis compared to patients reporting no alcohol use. Compared to patients with baseline high-risk alcohol who reported no change in alcohol use, those who decreased their alcohol use during follow up experienced a 39% reduction in long-term risk of cirrhosis (HR 0.61, 95% CI 0.45-0.83, p< 0.01). ConclusionsOne in nine Veterans with steatotic liver disease report concurrent high-risk alcohol use, which is associated with 43% greater risk of cirrhosis compared to no alcohol use. However, reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease.

Serum hepatitis B virus spliced RNA proportion increases with liver disease progression in patients with chronic hepatitis B.

Serum hepatitis B virus (HBV) spliced RNAs (spRNAs) are ubiquitous in HBV-infected patients; however, their clinical significance remains unknown. Therefore, we aimed to explore the relationship between HBV spRNAs and liver disease progression in chronic hepatitis B (CHB) patients; in vitro cell line assessment was also performed. The serum HBV wild-type RNA (wtRNA) and spRNA levels were individually quantified in a cohort of 279 treatment-naïve, hepatitis B e antigenpositive CHB patients with or without cirrhosis. The spRNA proportion was determined as (spRNA × 100%)/(spRNAs + wtRNA). 20 patients'serum samples underwent spRNA species profiling using next-generation sequencing. Serum spRNA species 1, 2, 3, 4, and 5 were the most common variants. The spRNA proportion varied from 0.00% to 19.02%, with higher levels in HBV genotype C patients than in those with genotype B (1.76% vs. 0.84%, p < 0.001). The spRNA proportion was positively associated with the alanine aminotransferase levels (r = 0.144, p = 0.053) and significantly higher in cirrhotic than in non-cirrhotic patients (1.69% vs. 1.04%, p = 0.001). Multivariate analysis revealed a 2.566-fold higher risk of cirrhosis in patients with elevated spRNA proportion (p = 0.024). In vitro experiments confirmed that spRNAs contributed to hepatic stellate cell activation, which is critical in liver fibrosis development. Therefore, increased HBV spRNA expression poses a risk for liver disease progression. Quantifying serum HBV spRNAs can aid in monitoring liver disease progression. Furthermore, the therapeutic targeting of spRNAs may improve the prognosis of patients with CHB.

A novel gene signature to diagnose MASLD in metabolically unhealthy obese individuals

Visceral adipose tissue (VAT) contributes to metabolic dysfunction-associated steatotic liver disease (MASLD), releasing lipogenic substrates and cytokines which promote inflammation. Metabolic healthy obese individuals (MHO) may shift towardsunhealthy ones (MUHO) who develop MASLD, although the mechanisms are still unexplained. Therefore, we aimed to identify dysfunctional pathways and transcriptomic signatures shared by liver and VAT and to outline novel obesity-related biomarkers which feature MASLD in MUHO subjects, at higher risk of progressive liver disease and extrahepatic comorbidities.We performed RNA-sequencing in 167 hepatic samples and in a subset of 79 matched VAT, stratified in MHO and MUHO. A validation analysis was performed in hepatic samples and primary adipocytes from 12 bariatric patients, by qRT-PCR and western blot.We identified a transcriptomic signature that discriminate MUHO vs MHO, including 498 deregulated genes in liver and 189 in VAT. According to pathway and network analyses, oxidative phosphorylation resulted the only significantly downregulated pathway in both tissues in MUHO subjects. Next, we highlighted 5 genes commonly deregulated in liver and VAT, encompassing C6, IGF1, OXA1L, NDUFB11 and KLHL5 and we built a tissue-related score by integrating their expressions. Accordingly to RNAseq data, serum levels of C6 and IGF1, which are the only secreted proteins among those included in the gene signature were downregulated in MUHO vs MHO. Finally, the expression pattern of this 5-genes was confirmed in hepatic and VAT samples.We firstly identified the liver and VAT transcriptional phenotype of MUHO and a gene signature associated with the presence of MASLD in these at risk individuals.

Non-alcoholic hepatic steatosis and its relation with metabolic syndrome

Objective: The aim of this study is to investigate the relationship between Non-Alcoholic Hepatic Steatosis (NASH) and Metabolic Syndrome (MS). Bibliographic review: NASH is a common liver condition in western industrialized countries, affecting individuals who do not consume alcohol. The pathogenesis of NASH involves environmental, genetic, and gut microbiota factors, and there is a strong association between NASH and MS, a condition that increases the risk of cardiovascular disease and type 2 diabetes. The relationship between NASH and MS is complex, with both sharing features such as obesity, insulin resistance and inflammation. The study analyzed 13 articles and found a strong association between NASH and MS. Patients with NASH often have features of MS, including type 2 diabetes, obesity, and hypertension. Furthermore, the presence of MS is related to a higher risk of liver disease progression. The relationship between these conditions appears to be driven by factors such as elevated glucose, insulin resistance and increased visceral fat. Final considerations: NASH and MS are conditions that pose significant public health challenges, especially in developed countries. The prevention and control of these conditions are closely linked to the promotion of lifestyle changes, including a healthy diet and physical exercise. These changes can have a positive impact on the incidence and progression of both NASH and MS, improving quality of life and reducing the risks associated with these pathological conditions. In addition, the importance of considering genetics and other individual factors in the evaluation and management of these multifactorial conditions is highlighted.

FIB-4 Reliability in Patients With Severe Obesity: Lower Cutoffs Needed?

Liver biopsy is the gold standard to evaluate hepatic fibrosis; however, it has many drawbacks, especially in patients with severe obesity. Noninvasive testing such as the FIB-4 score is increasingly being used as the initial screening tool to identify patients at risk for advanced fibrosis. The broader applicability of FIB-4 and the precision of its cutoff values remain uncertain in metabolic dysfunction-associated steatotic liver disease and patients with severe obesity. Our study explored the correlation between FIB-4 scores and intraoperative liver biopsy in patients with severe obesity undergoing bariatric surgery. A total of 632 patients with severe obesity underwent preoperative vibration-controlled transient elastography and intraoperative liver biopsy during bariatric surgery from January 2020 to August 2021. Variables collected included patient demographics, laboratory values, abdominal ultrasound, vibration-controlled transient elastography, and liver biopsy results. ANOVA 1-way test, χ2 tests, and Fisher exact tests were used for quantitative and qualitative variables, respectively. The 95% CIs for the mean FIB-4 scores were used to generate surrogate cutoff values. The proposed FIB-4 cutoffs for F0-1, F2, F3, and F4 were 0.62 (CI: 0.59, 0.64), 0.88 (0.74, 1.01), 1.24 (0.94, 1.54), and 1.53 (0.82, 2.24), respectively. Area under the curve (AUC) methods were used to compare traditional to proposed cutoff values. Applying the traditional FIB-4 cutoffs to approximate advanced fibrosis yielded an AUC of 0.5748. Use of the proposed FIB-4 cutoffs increased the AUC to 0.6899. The proposed FIB-4 cutoffs correctly identified 40 patients with biopsy-proven advanced fibrosis (F3-F4), all of which would have been missed using traditional cutoffs. Our study revealed that the use of the currently accepted FIB-4 cutoffs as the screening modality for identifying patients with advanced fibrosis due to metabolic dysfunction-associated steatotic liver disease is insufficient and will result in missing patients with histologically confirmed advanced fibrosis. Use of the revised FIB-4 scores should be considered to diagnose patients with severe obesity at high risk of liver disease progression.

Perlemakan Hati Non-Alkoholik dan Risiko Fibrosis Hati pada Pasien Hepatitis B Kronik

Introduction. Prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing throughout the world due to sedentary lifestyle and dietary habit, including in patients with chronic hepatitis B (CHB). In several studies, advanced of liver disease were more likely observed among those CHB patients with NAFLD. NAFLD might increase the risk of liver disease progression in CHB patients, but prior investigations were still limited. This study aimed to determine the association between NAFLD and risk of liver fibrosis in CHB patients. Methods. All patients with positive serum hepatitis B surface antigen in the Hepatobilier Data Registry, Cipto Mangunkusumo Hospital, were included in this study. Based on abdominal ultrasonography, patients were divided into two group (group I: non-NAFLD – hepatitis B patients vs. group II: NAFLD – hepatitis B patients). Data demographic and clinical examination were collected. Significant liver fibrosis was defined as stage liver fibrosis above 7 kPa (≥ F2). Logistic regression was used to identify NAFLD as risk factor for significant fibrosis. Variables were expressed as prevalence odd ratio (POR) with 95% CI. P values &lt;0.05 were considered statistically significant. Results. Among 130 hepatitis B patients, 45 patients (34.6%) were diagnosed with NAFLD. Of 45 patients in group II, 36 patients (80%) had significant liver fibrosis. It was observed that a higher percentage of patients in group II were HBeAg negative compared to those in group I (66.7% vs. 35.9%; p=0.038). Furthermore, group II also displayed higher levels of liver stiffness compared to group I (12.22 (8.6 kPa) vs. 8.57 (7.8 kPa); p 0.016). In multivariate analysis, NAFLD was significantly associated with significant liver fibrosis (POR: 5.87; CI95%: 2.48 – 13.86; p &lt; 0.001) after adjusted with HBeAg status. Conclusion. NAFLD associated with the higher risk of liver fibrosis in patients with hepatitis B. Modification of lifestyle and potential therapeutic intervention may help in reducing the progression of liver fibrosis.

Fibro-scan Based Score and Novel Noninvasive Serum Marker, FGF-21, to Assess Liver Fibrosis in Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in the Western world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation status. Aim of the Work This prospective cohort study aims to develop and validate noninvasive scoring system for assessment liver fibrosis in morbidly obese patients with NAFLD. Subjects and Methods This is a Prospective cohort study, was carried out on 50 morbidly obese patients selected from endocrinology department, AIN SHAMS UNIVERSITY, through a period of six months. Results The main results of the study revealed that: There were 32(64.0%) male and 18(36.0%) female with mean age 40.48 (± 12.16) SD. There were 14(28.0%) between (20 -30), 11(22.0%) between (30-40), 9(18.0%) between (40-50) and 16(32.0%) ≥50. Mean Weight (Kg) was 106.6 (± 13.31) SD with range (82.50 – 145.5), mean Height (Cm) was 171.7 (± 6.25) SD with range (158.0 – 185.0), mean BMI (Kg/m2) was 36.17 (± 4.15) SD with range (29.30 – 43.40), mean Waist circumference 113.1 (± 8.64) SD with range (92.0 – 129.0). There were 37(74.0%) with Comorbidity. 10(20.0%) have DM, 11(22.0%) have HTN, 11(22.0%) have CDK and 5(10.0%) have COPD. mean Hb was 12.24 with range (11.0 – 13.50), mean Plts was 193.2 with range (151.0 – 250.0), mean WBCs with range (4.70 – 8.20), mean AST was 85.20 with range (21.0 – 210.0), mean ALT was 86.64 with range (15.0 – 212.0), mean Cholesterol was 181.4 with range (122.0 – 248.0), mean Triglycerides was 156.3 with range (12.0 – 294.0), mean LDL was 119.1 with range (61.0 – 193.0), mean HDL was 61.32 with range (23.0 – 96.0), mean GGT (U/l) was 18.22 with range (7.0 – 33.0), mean HBA1C was 5.72 with range (4.70 – 9.30), mean Fasting blood sugar was 101.8 with range (81.0 – 155.0) and mean Uric acid was 6.23 with range (4.0 – 10.10). Regarding ultrasound outcome there were 33(66.0%) have Gallbladder wall blurring, 34(68.0%) have Portal vein wall blurring, 42(84.0%) have Hepatic vein blurring and 50 (100.0%) have fatty liver. Regarding fibrosis grade there were 12(24.0%) F1, 17(34.0%) F2, 18(36.0%) F3 and 3(6.0%) F4. Conclusion That the combination of Fibroscan and, APRI, FGF-21 and FIB-4 methods provides a valuable approach for assessing liver fibrosis in NAFLD patients. This can eliminate the need for liver biopsy in patients without clear indication. In addition, several recent studies have also validated the used of non-invasive markers in the diagnosis of NAFLD. The establishment of a national program for the recognition of NAFLD is therefore essential to reduce the risk of liver disease progression.

Mild Crigler-Najjar Syndrome with Progressive Liver Disease-A Multicenter Retrospective Cohort Study.

Crigler-Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler-Najjar Syndrome. Most of these patients need medical treatment for enzyme induction (phenobarbital) to lower blood levels of unconjugated bilirubin (UCB). Apart from this, no long-term problems have been described so far. The phenotype of patients with the homozygous pathogenic variant c.115C>G p.(His39Asp) in UGT1A1 is described as variable. Clinical observations of our patients led to the assumption that patients with variant c.115C>G have a mild CNS phenotype while having a high risk of developing progressive liver disease. For mild CNS disease, progressive liver disease has not been described so far. Therefore, we conducted a retrospective multicenter analysis of 14 patients with this particular variant, aiming for better characterization of this variant. We could confirm that patients with variant c.115C>G have a high risk of progressive liver disease (seven of fourteen), which increases with age despite having a very mild CNS phenotype. Earlier predictors and causes for an unfavorable disease course are not detectable, but close follow-up could identify patients with progressive liver disease at the beginning. In conclusion, these patients need close and specialized follow-up. Our study questions whether fibrosis in the CNS is really driven by high amounts of UCB or phototherapy.

Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder.

Fungal plasma biomarkers have not been studied in patients with unhealthy alcohol use and no apparent end-stage liver disease. We examined the prevalence of fungal plasma biomarkers, assessed by the presence of anti-Saccharomyces cerevisiae antibodies (ASCA; IgA and IgM), and its disease correlates in patients with alcohol use disorder (AUD). We performed logistic regression analyses to detect the association between clinical and laboratory characteristics and the presence of fungal plasma biomarkers. We included 395 patients (75.9% male, median age of 49 years, and median body mass index of 25.6) who drank a median of 150 g of alcohol daily and had a median duration of AUD of 20 years. ASCA IgA and IgG were present in 34.4% and 14.9%, respectively, and 9.9% had both ASCA IgA and ASCA IgG. The presence of ASCA IgA was associated with male sex (p < 0.01); values of serum aspartate transferase (AST) (p = 0.02), gamma-glutamyl transferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01), and bilirubin in the highest quartile (p < 0.01); Fibrosis-4 Index (FIB-4) values suggestive of advanced liver fibrosis (p < 0.01); and values of the macrophage activation factors sCD163 (p < 0.01) and sCD14 (p < 0.01), the cytokine IL-6 (p = 0.01), and lipopolysaccharide-binding protein in the highest quartile (p < 0.01). The presence of ASCA IgG was associated with omeprazole use (p = 0.04); values of AST (p = 0.04) and GGT (p = 0.04) in the highest quartile; FIB-4 values suggestive of advanced liver fibrosis (p < 0.01); and values of sCD163 (p < 0.01) in the highest quartile. The variables associated with the presence of both ASCA IgA and IgG were male sex (p = 0.04) and values of GGT (p = 0.04) and sCD163 in the highest quartile (p < 0.01). In AUD patients, the presence of fungal biomarkers in plasma was common and associated with FIB-4 values suggestive of advanced liver fibrosis and with markers of liver damage, monocyte activation, and microbial translocation, male gender, and omeprazole use. These findings suggest that the presence of plasma anti-Saccharomyces cerevisiae antibodies could be used as a biomarker for an elevated risk of progressive liver disease in patients with AUD.

Current Therapy of Chronic Viral Hepatitis B, C and D.

The majority of chronic viral hepatitis cases are induced via infection with the hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). These patients are at increased risk for progressive liver disease leading to cirrhosis as well as hepatocellular carcinoma (HCC). HBV infection is well controlled by the currently available nucleosides as well as nucleotides, and the development of cirrhosis can be prevented. Additionally, it has been shown that HBV-induced liver fibrosis can regress during successful antiviral treatment; however, a "functional cure", i.e., loss of HBsAg, is a rare event when these drugs are used. Therefore, novel therapeutic strategies are aiming at the selective suppression of HBsAg levels in combination with immunostimulation. The development of directly acting antivirals (DAAs) has revolutionized HCV therapy, as almost all patients can be cured via this treatment. Additionally, DAA therapy has few, if any, side effects, and is generally well tolerated by patients. HDV remains the most challenging type of chronic viral hepatitis. Although novel therapeutic options have recently been approved, response rates are still less favorable compared to HBV and HCV. This review discusses current and future options for the treatment of chronic HBV, HCV, and HDV infection.

Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers

The study enrolled 284 patients with chronic hepatitis B virus infection. Participants included people with mild fibrotic lesions (32.5%), moderate to severe fibrotic lesions (27.5%), cirrhotic lesions (22%), hepatocellular carcinoma (HCC) in 5%, and people with no fibrotic lesions in 13%. Eleven SNPs within DIO2, PPARG, ATF3, AKT, GADD45A, and TBX21 were genotyped by mass spectrometry. The rs225014 TT (DIO2) and rs10865710 CC (PPARG) genotypes were independently associated with susceptibility to advanced liver fibrosis. However, cirrhosis was more prevalent in individuals with the GADD45A rs532446 TT and ATF3 rs11119982 TT genotypes. In addition, the rs225014 CC variant of DIO2 was more frequently found in patients with a diagnosis of HCC. These findings suggest that the above SNPs may play a role in HBV-induced liver damage in a Caucasian population.

Outcomes and Follow-Up after Hepatitis C Eradication with Direct-Acting Antivirals.

Treatment of hepatitis C (HCV) has been revolutionized with the introduction of direct-acting antivirals (DAAs). Patients can be treated at more advanced stages of liver disease, with a growing number of cirrhotic patients achieving sustained virological response (SVR). Long-term outcomes for cured patients and the optimal follow-up care of patients after SVR are yet to be defined, because most studies on cirrhotic patients cured with DAAs have a short follow-up period. There are many open questions related to patient management after viral eradication with DAAs, such as which could be the most reliable non-invasive tool to predict liver-related complications, or to what extent viral eradication reduces the risk of liver disease progression in the long term. Growing evidence supports the personalization of follow-up care based on individual risk. The aim of this narrative review is to analyze the impact of viral eradication with DAAs on clinically significant portal hypertension, hepatocellular carcinoma, and extrahepatic manifestations, as well as to summarize indications for optimal follow-up care of HCV patients treated with DAAs.

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controlswere recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p=.01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Diabetes and Risk of Hepatocellular Carcinoma in Cirrhosis Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. NAFLD is a hepatic manifestation of insulin resistance, the core pathophysiology of diabetes. Multiple clinical studies show that diabetes increases the risk of liver disease progression and cirrhosis development in patients with NAFLD. Diabetes has causal associations with many different cancers, including hepatocellular carcinoma (HCC). More recent studies demonstrate that diabetes increases the risk of HCC in patients with underlying NAFLD cirrhosis, confirming the direct hepatocarcinogenic effect of diabetes among cirrhosis patients. Diabetes promotes hepatocarcinogenesis via the activation of inflammatory cascades producing reactive oxygen species and proinflammatory cytokines, leading to genomic instability, cellular proliferation, and inhibition of apoptosis. Given the global increase in the burden of NAFLD and HCC, high-risk patients such as older diabetic individuals should be carefully monitored for HCC development. Future larger studies should explore whether the effect of diabetes on HCC risk in NAFLD cirrhosis is modifiable by the type of antidiabetic medication and the effectiveness of diabetes control.

A practical use of noninvasive tests in clinical practice to identify high-risk patients with nonalcoholic steatohepatitis.

Patients with nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) or other components of metabolic syndrome are at high risk for disease progression. We proposed an algorithm to identify high-risk NAFLD patients in clinical practice using noninvasive tests (NITs). Evidence about risk stratification of NAFLD using validated NITs was reviewed by a panel of NASH Experts. Using the most recent evidence regarding the performance of NITs and their application in clinical practice were used to develop an easy-to-use algorithm for risk stratification of NAFLD patients seen in primary care, endocrinology and gastroenterology practices. The proposed algorithm uses a three-step process to identify NAFLD patients who are potentially at high risk for adverse outcomes. The first step is to use clinical data to identify most patients who are at risk for having potentially progressive NAFLD (e.g. having T2D or multiple components of metabolic syndrome). The second step is to calculate the FIB-4 score as a NIT that can further risk stratifying individuals who are at low risk for progressive liver disease and can be managed by their primary healthcare providers to manage their cardiometabolic comorbidities. The third step is to use second-line NITs (transient elastography or enhanced liver fibrosis tests) to identify those who at high risk for progressive liver disease and should be considered for specially care by providers with NASH expertise. The use of this simple clinical algorithm can identify and assist in managing patients with NAFLD at high risk for adverse outcomes.

Impact of treatment compliance in chronic hepatitis B

The incidence rate of chronic hepatitis B remains high in China. Antiviral therapy can significantly reduce the risk of progressive liver disease and hepatocellular carcinoma in patients with chronic hepatitis B. However, all current antiviral treatments can only inhibit HBV replication and not completely eliminate the hepatitis B virus, so antiviral therapy for chronic hepatitis B is probably a long-term or even lifelong treatment. Antiviral therapy compliance is essential for achieving long-term clinical benefits and preventing nucleot(s)ide drugs resistance. Herein, we analyzed the relevant factors of antiviral therapy compliance and their impact on CHB treatment and explored feasible programs that can improve compliance with nucleot(s)ide drug treatment by conducting a literature search using PubMed and Scopus with search terms including hepatitis B, compliance, nucleot(s)ide drugs, antiviral therapy, viral suppression, and drug resistance.

Polycystic ovary syndrome is associated with nonalcoholic steatohepatitis in women of reproductive age

Polycystic ovary syndrome (PCOS) occurs in approximately 10% of all reproductive‐age women, with over 50% of these patients having imaging‐confirmed nonalcoholic fatty liver disease (NAFLD). Whether PCOS increases the risk for more clinically relevant disease, such as nonalcoholic steatohepatitis (NASH), is unclear. Such findings are relevant to prognosticating risk of progressive liver disease in the growing population of young adults with NAFLD. Using weighted discharge data from the United States National Inpatient Sample from 2016 to 2018, we evaluated the association of PCOS with the presence of NASH among reproductive‐age women with NAFLD. The association of PCOS with NASH was assessed by logistic regression, adjusting for demographic and comprehensive metabolic comorbidities. Other causes of hepatic steatosis and chronic liver diseases were excluded. Our analysis included 189,440 reproductive‐age women with NAFLD, 9415 of whom had PCOS. Of those with PCOS, 1390 (15%) had a distinct code for NASH. Women with PCOS were younger (median age, 33 vs. 40 years; p < 0.001) and more likely to have diabetes (37.0% vs. 34.0%), obesity (83.0% vs. 58.0%), dyslipidemia (26.0% vs. 21.0%), and hypertension (38.0% vs. 35.0%) (all p ≤ 0.01). On adjusted analysis accounting for these metabolic comorbidities, PCOS remained independently associated with an increased prevalence of NASH (adjusted odds ratio, 1.22; 95% confidence interval, 1.05–1.42; p = 0.008). Conclusions: Among reproductive‐age women with NAFLD, metabolic risk factors were more common in those with PCOS. Despite adjustment for these metabolic comorbidities, PCOS remained associated with a 22% higher odds of having NASH. These findings support efforts to increase NAFLD screening in young women with PCOS and highlight the potential “head start” in progressive liver disease among young women with PCOS.

THU386 - Hepatitis Delta virus infection in patients with chronic hepatitis B is associated with greater risk of liver disease progression and liver-related mortality: a systematic review and meta-analysis

THU386 - Hepatitis Delta virus infection in patients with chronic hepatitis B is associated with greater risk of liver disease progression and liver-related mortality: a systematic review and meta-analysis