Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Understanding the knowledge, awareness, and attitudes of the public towards liver diseases in Malaysia.

BACKGROUND: Viral hepatitis B and C (HBV, HCV) and non-alcoholic fatty liver disease (NAFLD) are the commonest etiologies of liver-related deaths in Malaysia. Herein, this study aims to explore and understand the knowledge and attitudes of the public toward liver-related health and diseases in Malaysia. METHODS: A cross-sectional, self-reported, web-based questionnaire was conducted among 500 adults between February and March 2020. Questionnaire items pertained to the knowledge and attitudes toward liver-related health and diseases. RESULTS: Half of the respondents were aged ≥35 years and 52.0% were males. Gaps in knowledge included the lack of awareness of different types of hepatitis, including the potential transmission risks and complications of HBV and HCV. About half acknowledged liver fibrosis and cirrhosis as key determinants of liver-related disease progression. A higher proportion rightly recognized the diagnostic test for HCV (40.8%) than HBV (30.0%) despite more being aware of HBV than HCV. Less than one-third were aware of the risk factors, screening tests, and complications of NAFLD. Despite the majority (92.8%) agreeing that regular screening was important for liver health, only 67.0% attended recent health screening and one-fifth were unlikely to seek medical consultation upon exposure to viral hepatitis risk factors. Reasons for this low urgency included the perception of being healthy, cost-related concerns, and societal discrimination. CONCLUSION: Robust education efforts are needed to raise awareness and empower the community with knowledge of liver-related diseases, particularly viral hepatitis and NAFLD in Malaysia.

Pathway to global elimination of hepatitis B: HBV cure is just the first step.

Hepatitis B (HBV) is a major cause of global morbidity and mortality, and the leading cause of liver cancer worldwide. Significant advances have recently been made toward the development of a finite HBV treatment that achieves permanent loss of HBsAg and HBV DNA (so-called "HBV cure"), which could provide the means to eliminate HBV as a public health threat. However, the HBV cure is just one step toward achieving WHO HBV elimination targets by 2030, and much work must be done now to prepare for the successful implementation of the HBV cure. In this review, we describe the required steps to rapidly scale-up future HBV cure equitably. We present key actions required for successful HBV cure implementation, integrated within the World Health Organization (WHO) Global Health Sector Strategy (GHSS) 2022-2030 framework. Finally, we highlight what can be done now to progress toward the 2030 HBV elimination targets using available tools to ensure that we are preparing, but not waiting, for the cure.

Budget impact analysis of two treatment approaches for hepatitis C in Malaysia through the use of voluntary and compulsory licensing options.

Introduction: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to sofosbuvir/daclatasvir (SOF/DAC) is available through compulsory licensing, with access to sofosbuvir/velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes but has higher drug acquisition costs compared to SOF/DAC. A stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. Methods: This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications. Results: The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years. Discussion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region.

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Hepatitis B virus DNA methylation and its potential role in chronic hepatitis B.

Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.

Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.

Triglyceride to high-density lipoprotein cholesterol ratio is an independent predictor of liver fibrosis among pediatrics non-alcoholic fatty liver disease.

Background: Insulin resistance (IR), one of the key components of the metabolic syndrome, is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the relationship between surrogate markers of IR and the severity of NAFLD among overweight or obese children. Methodology: A total of 56 consecutive children aged 6 to 18 years old were recruited from the pediatric obesity and type 2 diabetes mellitus (T2DM) clinic in University Malaya Medical Centre (UMMC) from 2016 to 2019. Data on anthropometric measurements, clinical components of metabolic syndrome and fasting serum insulin were collected. Triglyceride to high-density lipoprotein cholesterol ratio (TG: HDL-C), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Single Point Insulin Sensitivity Estimator (SPISE) were calculated. Transient elastography was performed with hepatic steatosis and liver fibrosis assessed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Results: A total of 44 children (78.6%) had liver steatosis and 35.7% had presence of significant liver fibrosis (stage F≥2). Majority (89.3%) are obese and 24 children (42.9%) were diagnosed with metabolic syndrome. Higher number of children with T2DM and significant liver fibrosis were associated with higher tertiles of TG: HDL-C ratio (p<0.05). Top tertile of TG: HDL-C ratio was an independent predictor of liver fibrosis (OR=8.14, 95%CI: 1.24-53.36, p=0.029). ROC analysis showed that the area under the curve (AUC) of HOMA-IR (0.77) and TG: HDL-C ratio (0.71) were greater than that of metabolic syndrome (0.70), T2DM (0.62) and SPISE (0.22). The optimal cut-off values of HOMA-IR and TG: HDL-C ratio for detecting liver fibrosis among children with NAFLD are 5.20 and 1.58, respectively. Conclusion: Children with NAFLD and higher TG: HDL-C ratio are more likely to have liver fibrosis. TG: HDL-C ratio is a promising tool to risk stratify those with NAFLD who are at risk of developing advanced liver disease.

Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study.

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual-level and macro-level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0-100-point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20-2.79) or higher HCV death rate (80% IOR: 1.35-3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p-values<0.001). The overall liver index was positively associated with the two macro-level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases.

Risk factors of nonalcoholic fatty liver disease in lean body mass population: A systematic review and meta-analysis.

The pathophysiology and risk factors of nonalcoholic fatty liver disease (NAFLD) among lean patients is poorly understood and therefore investigated. We performed a meta-analysis of observational studies. Of 1175 articles found through searching from Medline/PubMed, Banglajol, and Google Scholar by two independent investigators, 22 were selected. Data from lean (n = 6768) and obese (n = 9253) patients with NAFLD were analyzed; lean (n = 43 398) and obese (n = 9619) subjects without NAFLD served as controls. Age, body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure (DBP) had significantly higher estimates in lean NAFLD patients than in lean non-NAFLD controls. Fasting blood sugar [MD(mean difference) 5.17 mg/dl, 95% CI(confidence interval) 4.14-6.16], HbA1c [MD 0.29%, 95% CI 0.11-0.48], and insulin resistance [HOMA-IR] [MD 0.49 U, 95% CI 0.29-0.68]) were higher in lean NAFLD patients than in lean non-NAFLD controls. All components of the lipid profile were raised significantly in the former group except high-density lipoprotein. An increased uric acid (UA) level was found to be associated with the presence of NAFLD among lean. Cardio-metabolic profiles of nonlean NAFLD patients significantly differs from the counter group. However, the magnitude of the difference of lipid and glycemic profile barely reached statistical significance when subjects were grouped according to lean and nonlean NAFLD. But DBP (slope: 0.19, P < 0.037), HOMA-IR (slope: 0.58, P < 0.001), and UA (slope: 0.36, P = 0.022) were significantly higher if NAFLD was present compared to that of non-NAFLD group. Lean and nonlean NAFLD patients are metabolically similar and share common risk factors.

Comparative expression of pro-inflammatory and apoptotic biosignatures in chronic HBV-infected patients with and without liver cirrhosis.

The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.

Association of deleted in liver cancer-1 gene polymorphism with increased risk of chronicity of disease among Malaysian patients with hepatitis B infection.

OBJECTIVE: The aim of this study is to examine the association between genetic variations in deleted in liver cancer 1 (DLC1) gene with progression of the hepatitis B virus (HBV) infection. METHODS: A total of 623 subjects were included in this study, of whom, 423 were chronic hepatitis B (CHB) patients without liver cirrhosis or hepatocellular carcinoma (HCC), 103 CHB with either liver cirrhosis ± HCC and 97 individuals who had resolved HBV. Two single-nucleotide polymorphisms rs3739298 and rs532841 of DLC1 gene were genotyped using the Sequenom MassARRAY platform. RESULTS: Our results indicated significant differences between the chronic HBV and resolved HBV groups in genotype and allele frequencies of DLC1-rs3739298 [odds ratio (OR) = 2.23; 95% confidence interval (CI): 1.24-3.99; P = 0.007] and (OR = 1.54; 95% CI: 1.07-2.22; P = 0.021), respectively. Moreover, haplotype analysis revealed significant associations between chronicity of HBV with TG and GA haplotypes (P = 0.041 and P = 0.042), respectively. CONCLUSION: A significant association exists between the rs3739298 variant and susceptibility to CHB infection.

Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort.

BACKGROUND/AIMS: 17ß-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients. METHODS: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded. RESULTS: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00-0.64; P=0.033 and HR, 0.01; 95% CI, 0.00-0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese. CONCLUSION: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.

Chronic inflammation involves CCL11 and IL-13 to facilitate the development of liver cirrhosis and fibrosis in chronic hepatitis B virus infection.

The pathogenesis involving non-alcoholic fatty liver disease (NAFLD) in the context of chronic HBV (CHB) virus infection requires to be understood for developing improved modalities of diagnosis and treatment. We retrospectively investigated the association between NAFLD and CHB virus infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between years 2013 and 2016, we studied 455 subjects in the current investigation. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the hepatitis B virus (HBV) viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. We found that there was a high concurrence of NAFLD among patients with CHB virus infection. The presence of metabolic syndrome and chronic inflammation in CHB virus-infected patients were two independent factors that led to the progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components.

Hepatitis C virus core antigen as alternative diagnostic algorithm for active hepatitis C virus infection among haemodialysis population: Cost implications.

AIMS: In Malaysia, majority anti-HCV positive haemodialysis patients do not undergo hepatitis C confirmation due to the high cost of HCV RNA. HCV Core Antigen might be a cost-effective diagnostic test to identify HD patients who have active HCV infection eligible for Direct Acting Anti-viral therapy. METHODS: A cross-sectional study was conducted to assess the correlation between HCV Ag and HCV RNA and the cost implications of different diagnostic algorithms to diagnose active HCV infection using Anti-HCV, HCV Ag, and HCV RNA. Pre-dialysis blood was tested for both HCV Ag and HCV RNA. HCV Ag was tested with Abbott ARCHITECT HCV Ag test. RESULTS: Two-hundred twenty-seven haemodialysis patients were recruited from 20 centres with mean age of 57.68 ± 12.48 years, and male constitutes 56.8% (129) of the study population. HCV Ag correlated well with HCV RNA (Spearman test coefficient 0.943, p < .001) with sensitivity of 93.9%, specificity 99.3%, and the accuracy was 97.36%. Cost analysis indicated that a sequential test involving Anti-HCV antibody as initial screening, followed by HCV Ag on Anti-HCV positive and HCV RNA on HCV Ag negative cases translated to a modest cost-saving algorithm compared to standard diagnostic algorithm. CONCLUSION: HCV Ag correlated well with HCV RNA and can potentially be fused in an alternative diagnostic algorithm to generate cost savings methods to diagnose active HCV infection among haemodialysis patients. This alternative algorithm is especially relevant in low to middle-income countries such as Malaysia to optimize the use of the healthcare resource and gains in clinical outcomes.

Mucosal-Associated Invariant T Cells: Diplomatic Front-Runners in the Fight against Hepatitis B Virus Infection.

Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T cells that bridge between innate and adaptive immunity. MAIT cells act like a 'biliary firewall' protecting the epithelial lining of the liver against pathogenic intruders. MAIT1 and MAIT17 subsets respond rapidly to pathogenic presence both in the liver as well as in the peripheral circulation. In addition to chronic hepatitis B virus (HBV) infection, MAIT cells also appear to serve as potential therapeutic targets in several other chronic ailments. Evidence indicates that MAIT cells have tissue repair functions also paving way for fibrotic changes during chronic HBV infection. Observations also suggest that HBV-hepatitis delta virus (HDV) co-infection disease progression is closely associated with loss of MAIT cells. Furthermore, reduction in the number of hepatic MAIT cells in patients with cirrhotic non-alcoholic fatty liver disease and HBV-associated primary liver cancer has also been reported. Given their concrete role against HBV disease progression, and has also become evident that the tumor microenvironment can cause functional impairment of MAIT cells. Here, we reviewed the protective and the pathological role of MAIT cells in chronic HBV infection and certain other related medical conditions based on the understanding that an optimal functioning of the MAIT cell arsenal is key to a "host-friendly" immune defense against HBV disease progression.

Use of simple scoring systems for a public health approach in the management of non-alcoholic fatty liver disease patients.

BACKGROUND AND AIM: Advanced fibrosis is the most important predictor of liver-related mortality in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting. METHODS: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score. RESULTS: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score < 1.3 ruled out advanced fibrosis in 72% of the patients, with 6% being understaged. Further stratification of the indeterminate group patients by other non-alcoholic steatohepatitis (NASH) clinical predictors, such as abnormal gamma-glutamyl transpeptidase (GGT) level and presence diabetes mellitus (DM), could further reduce the number of patients who are unlikely to have advanced fibrosis by 52% and 35%, respectively. CONCLUSION: We found that FIB-4 score outperforms other scoring systems based on AUROC and NPV. The use of a simple scoring system such as FIB-4 as first-line triage to risk-stratify NAFLD patients in the primary care setting, with further stratification of those in the indeterminate group using clinical predictors of NASH, can help in the development of a simplified strategy for a public health approach in the management of NAFLD.

Hepatitis C core antigen testing to diagnose active hepatitis C infection among haemodialysis patients.

BACKGROUND: Hepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost. METHODS: We conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test. RESULTS: We recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients. CONCLUSIONS: Although HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.

2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report.

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.