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In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA12 IU/mL in Thailand and HCV RNA15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

PURPOSE To determine the incidence, demographic profile, background of reporters, causative agents, severity and clinical outcomes of hepatic adverse drug reaction (ADR) reports in Malaysia using the national ADR reporting database. METHODS The ADR reports recorded between 2000 and 2017 were retrospectively analysed to identify hepatic ADR reports. The trend and characteristics of hepatic ADR cases were described. Multivariate disproportionality analysis of the causative agents was performed to generate signals of hepatic ADRs. RESULTS A total of 2090 hepatic ADRs (1.77% of all ADRs) were reported with mortality rate of 12.7% among cases with known clinical outcomes. The incidence of hepatic ADR reporting in Malaysia increased significantly over 18 years from 0.26 to 9.45 per million population (P

Background and Aim The advent of endoscopic ultrasound‐guided biliary drainage (EUS‐BD) has provided an inimitable alternative for gaining biliary access in patients who fail conventional endoscopic drainage. The antimigratory features of the partially covered metal stent (PCMS), namely, the flange head and uncovered portion of the stent, makes it a valuable option in patients undergoing EUS‐guided hepaticogastrostomy (EUS‐HGS). The aim of the study is to evaluate the clinical outcome of EUS‐BD via the hepaticogastrostomy approach using PCMS in patients with malignant biliary obstruction after failed ERCP. Methods This is a single‐center retrospective observational study of patients with malignant biliary obstruction undergoing EUS‐HGS after failed ERCP between January 2018 and May 2019. The end‐point of the study was to assess the technical and clinical success rate, as well as the stent‐ and procedure‐related complications. Results There were 20 subjects in this study. The average age was 71.8 ± 7.6 years. Most patients were male, 16 (80%). Inaccessible papillae was the most common indication for this procedure, 16 (80%). Technical success was achieved in all patients. The average procedural time was 39.9 ± 1.3 min. Mean preprocedural bilirubin levels were 348.6 ± 28.8 and subsequently decreased to 108.94 ± 37.1 μmol/L at 2 weeks postprocedure. The clinical success rate was 95% (19/20), with one patient requiring percutaneous transhepatic biliary drainage (PTBD). There were no stent‐ or procedure‐related complications reported in this study. Conclusion EUS‐HGS with PCMS is a feasible, effective, and safe alternative for biliary decompression in patients with failed endoscopic retrograde cholangiopancreatography (ERCP)., The partially covered metal stent (PCMS) with the covered distal transgastric portion and the proximal uncovered portion within the intrahepatic ducts.

IntroductionTo achieve the elimination of hepatitis C virus (HCV), substantial scale-up in access to testing and treatment is needed. This will require innovation and simplification of the care pathway, through decentralisation of testing and treatment to primary care settings and task-shifting to non-specialists. The objective of this study was to evaluate the feasibility and effectiveness of decentralisation of HCV testing and treatment using rapid diagnostic tests (RDTs) in primary healthcare clinics (PHCs) among high-risk populations, with referral of seropositive patients for confirmatory viral load testing and treatment.MethodsThis observational study was conducted between December 2018 and October 2019 at 25 PHCs in three regions in Malaysia. Each PHC was linked to one or more hospitals, for referral of seropositive participants for confirmatory testing and pretreatment evaluation. Treatment was provided in PHCs for non-cirrhotic patients and at hospitals for cirrhotic patients.ResultsDuring the study period, a total of 15 366 adults were screened at the 25 PHCs, using RDTs for HCV antibodies. Of the 2020 (13.2%) HCV antibody-positive participants, 1481/2020 (73.3%) had a confirmatory viral load test, 1241/1481 (83.8%) were HCV RNA-positive, 991/1241 (79.9%) completed pretreatment assessment, 632/991 (63.8%) initiated treatment, 518/632 (82.0%) completed treatment, 352/518 (68.0%) were eligible for a sustained virological response (SVR) cure assessment, 209/352 (59.4%) had an SVR cure assessment, and SVR was achieved in 202/209 (96.7%) patients. A significantly higher proportion of patients referred to PHCs initiated treatment compared with those who had treatment initiated at hospitals (71.0% vs 48.8%, pConclusionsThis study demonstrated the effectiveness and feasibility of a simplified decentralised HCV testing and treatment model in primary healthcare settings, targeting high-risk groups in Malaysia. There were good outcomes across most steps of the cascade of care when treatment was provided at PHCs compared with hospitals.

Introduction Malaysia has been actively battling hepatitis C since 2016, primarily through partnerships with access-oriented nonprofit organizations and drug price control by compulsory licensing of sofosbuvir, a patented direct-acting antiviral. This study evaluated the impact of such initiatives on the treatment coverage, health expenditure of the government, and clinical outcomes of patients. Methods The data contributed by 144 public hospitals across the country was used to assess the trend changes in the number of hepatitis C patients treated and the corresponding drug expenditure between 2013 and 2019 (before and after government-driven interventions). The information on the effectiveness of the sofosbuvir-daclatasvir regimen was also gathered from medical records of hepatitis C patients, who sought care from 16 selected hospitals between April 2018 and March 2020. Results While the number of hepatitis C patients receiving treatment increased by >10 times (from 299 in 2013 to 3,116 in 2019; pConclusion The findings demonstrate the sustainability and scalability of the existing hepatitis C care model in Malaysia, along with the great real-world effectiveness of the treatment., Following are the links for the poster on Zenodo Repository: Poster: https://zenodo.org/record/5348564 The presentation slides are also available on Slideshare: Presentation Slides: https://www.slideshare.net/ICRInstituteForClini/midterm-outcome-evaluation-of-governmentled-endeavors-to-eliminate-hepatitis-c-as-a-public-health-threat-by-2030-in-malaysia

Background : Liver Transplantation (LT) is a complicated surgical procedure with high risk for massive intraoperative blood loss due to pre-existing coagulopathy, portosystemic shunts with collateral circulations and splenomegaly. The study purpose was to evaluate single center transfusion strategies and to identify the risk factors associated with the intraoperative blood loss and blood transfusion. Methods : Study includes 18 patients who underwent LT at Hospital Selayang between January 2020 and December 2020. Retrospective analysis of data included preoperative assessment of coagulopathy, intraoperative blood loss, blood component transfusion. Results : Mean age in the study group was 36.4 ± 12.68 years. Mean intraoperative blood loss was 4450 ± 1646 ml requiring 4.17 ± 3.3 Packed Red Blood Cell (PRBC) Units, 7.56 ± 5.5 platelet units, and 9.50 ± 6.0 fresh frozen plasma (FFP) units. Independent risk factor for High Blood Loss (HBL) group was lower pre-operative platelet count and it is statistically significant (p = 0.024). HBL group is associated with higher usage of PRBC (p = 0.024) and Platelet Units (p = 0.031) and it is statistically significant. Length of stay (LOS) in ICU averaging 8.6 ± 4.95 days and there is no significant differences comparing the HBL and LBL group (p = 0.552). Mortality < 90 days for all recipients was 22.2%. Conclusion : The pre-operative platelet count for is the most important factor associated with HBL in LT procedure. Usage of PRBC and Platelet units were statistically higher in HBL. Comparing HBL and LBL patients, there is no difference in terms of the LOS in ICU post-operatively. Disclaimer: Abstract text might vary slightly from what is displayed in the e-poster., This poster was submitted to the 14th National Conference for Clinical Research (NCCR) in August 18-20, 2021. https://nccrconference.com.my/

Background: Malaysia has been fully committed to the global endeavor to eliminate hepatitis C virus (HCV) infection by 2030. In early 2018, the Ministry of Health (MOH) embarked on a “one-size-fits-all strategy” by introducing generic versions of sofosbuvir and daclatasvir as the standard treatment for HCV infection in public hospitals nationwide. Objectives: To evaluate the outcomes of such an initiative in multiple aspects, including the number and characteristics of patients treated, the extent of evidence-based drug use, the treatment completion status, individual responses to treatment, common side effects of treatment, and its economic implications. Methods: The findings were generated from the data compiled by the MOH, capturing the information regarding the treatment provided to adult HCV-infected patients in 16 selected hospitals between April 2018 and March 2020, along with the drug costs incurred. Results: A total of 1,797 patients were treated, nearly four times more than the patients receiving interferon-based treatment across the country in the preceding two years. Approximately one-third of them had liver cirrhosis, and the main HCV genotypes were 3 (46.9%) and 1a (20.0%). Dosing, treatment duration and the addition of ribavirin to the treatment generally agreed with the recommendations of the MOH. More than 90% of the patients completed the treatment course, and a sustained virologic response (SVR) rate of 95.4% (95% CI: 94.2, 96.7%) was recorded in those with a known treatment outcome (n = 1,163). The SVR achievement did not vary across HCV genotypes and cirrhosis status, but those ≥ 50 years of age (adjusted OR: 2.13; 95% CI: 1.16, 3.92) were more likely to fail the treatment. Side effects were rare. Anemia and fatigue caused treatment discontinuation in only 0.3% of the patients. The total drug expenditure reached US$678,258.20, and the mean cost of a 12-week treatment course of sofosbuvir and daclatasvir (US$235.16) was lower than the cost expected by the MOH (US$300). Conclusions: The findings demonstrate a high degree of real-world effectiveness, safety, and affordability of the standard treatment, suggesting that such a government-led initiative was reasonable and timely and could be extended to include more public health institutions.

Background: As Phyllanthus niruri has been shown to have anti-inflammatory, antioxidant and hepatoprotective properties, the current study was designed to examine its efficacy and safety in non-alcoholic steatohepatitis (NASH) treatment. Methods: Fifty-two patients with biopsy-proven possible or definite NASH from eight hospitals across Malaysia were randomized (1:1) to receive two capsules of Phyllanthus niruri (Hepar-P®; n=25) or matched placebo (n=27) three times daily for 48 weeks. The primary endpoint of efficacy was the changes in aspartate transaminase (AST) and alanine transaminase (ALT) levels, while the other biochemical, anthropometric and histological changes were used as the secondary endpoints. Safety of treatment was confirmed through adverse events (AEs) reporting, physical examination and regular monitoring of blood parameters. Results: After 48 weeks of treatment, the changes in the AST (p=0.39) and ALT (p>0.95) levels did not significantly differ between the Phyllanthus and placebo groups. There were also no significant differences in the changes of body mass index, HbA1C and lipid profile between the two groups. Furthermore, six patients in the Phyllanthus group consented to repeat biopsy at week 48, and no histological changes of clinical significance were observed. Mild or moderate AEs occurred throughout the study period in 76.9% of the patients, but were not significantly different between the two groups (p=0.42). Conclusion: Although Phyllanthus niruri was generally well tolerated with no significant safety concerns, the current study was unable to demonstrate its clinical benefits in NASH treatment. Key words: Hepatocellular carcinoma, liver cirrhosis, Malaysia, non-alcoholic fatty liver disease, Phyllanthus.

Background: In low- and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic NS5A inhibitor, and sofosbuvir has shown efficacy and safety in chronically HCV infected patients with genotype (GT) 4. The STORM-C-1 trial aims to assess the efficacy and safety of sofosbuvir plus ravidasvir in a more diverse population of adults chronically infected with HCV. Methods: STORM-C-1 is a two-stage, open-label, multicentre clinical trial in Malaysia and Thailand. HCV infected subjects with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-F3) were eligible to participate, regardless of HCV genotype, HIV infection status, prior interferon-based HCV treatment or source of HCV infection. Stage 1 results are reported here. Once-daily ravidasvir (200mg) and sofosbuvir (400mg) were prescribed for 12 (without cirrhosis) or 24 (with cirrhosis) weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). This trial is registered with ClinicalTrials.gov: NCT02961426 and the National Medical Research Register of Malaysia NMRR-16-747-29183. Findings: Between October 2016 and June 2017, 301 subjects were enrolled and 300 included in the full analysis set: 97 with GT1a, 27 GT1b, 2 GT2, 158 GT3, and 16 GT6; 81 (27%) had compensated cirrhosis; 90 (30%) had HIV co-infection; and 99 (33%) had prior interferon-based treatment. 291/300 subjects (97%, 95% CI 94%-99%) achieved SVR12. Three subjects prematurely discontinued study treatment due to adverse events. There were no deaths or treatment discontinuations due to the study drugs. Interpretation: In this first stage, ravidasvir plus sofosbuvir was found to be highly effective and well tolerated in all subgroups of this diverse adult population chronically infected with HCV. Trial Registration Number: This trial is registered with ClinicalTrials.gov: NCT02961426 and the National Medical Research Register of Malaysia NMRR-16-747-29183. Funding: Drugs for Neglected Diseases initiative; National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia. Conflict of Interest: Dr. Avihingsanon reports grants from National Science and Technology Development Agency (NSTDA) during the conduct of the study, and also from ViiV Healthcare outside of thesubmitted work. Tim Cressey and Nicolas Salvadori report a service agreement with DNDi.Isabelle Andrieux-Meyer, Caroline Menetrey, Francois Simon, Jean-Michel Piedagnel,Sasikala Siva, Alistair Swanson, Francois Bompart, Vishal Goyal, and Bernard Pecoul are employed by the Drugs for Neglected Diseases initiative. All other authors do not report any potential conflicts of interest. Ethical Approval: The initial protocol and all protocol amendments were reviewed and approved before implementation by the applicable individual institutional or national ethics committees. All subjects provided written informed consent.

Background: Hepatitis B virus co-infection with other strains of viral hepatitis is associated with increased risk of liver cirrhosis and hepatic decompensation. Objectives: This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection. Methods: Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test. Results: Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p

Background: Zoonotically acquired HEV has been described as one of the most successful zoonotic viral infections in human history.Aim: In this study we characterized HEV comparative genomic analysis as it relates to swine HEV.Materials and methods: A total of 82 chronic hepatitis B patients were recruited from May 2015 to May 2016 for this study. We conducted a serological and molecular investigation of HEV among these patients. The detected HEV were sequenced and the genomes and deduced amino acids were characterized using molecular evolutionary genetic analysis software version 7.Results: Of the 82 chronic hepatitis B patients that were tested, 9.8% (8/82) were found to be HEV positive. Phylogenetic analysis of the HEV RNA sequences showed they are of genotype 4 and demonstrated high sequence identity with a swine isolate from China, with variation in amino acids at position 22, where leucine was present in the Malaysian human isolate while phenylalanine was present in the China swine isolate.Conclusion: Comparative analysis of the human HEV ORF-2 nucleotide sequence suggest zoonotic origin.Keywords: Co-infection, Chronic hepatitis B, Hepatitis E virus, Zoonotic HEV, Malaysian HEV isolate

BACKGROUND Hepatitis B surface antigen is usually secreted by infected hepatocytes in the form of subviral particles rather than infectious virions, while the hepatitis B e antigen originates from the core gene and is modified and secreted by hepatocytes into the circulation and functions as a marker of active viral replication. This study aimed to study the relationship between HBV DNA and quantitative hepatitis B surface and e antigen in Malaysian patients. METHODS A total of 82 chronic hepatitis B patients were recruited for this study from the Hepatology Department of Selayang Hospital. Quantitative hepatitis surface and e antigen was performed retrospectively on frozen plasma using enzyme linked immunosorbent assay according to the manufacturer's instructions. Hepatitis B viral DNA was extracted from all plasma samples and quantified using real-time PCR. RESULTS Quantitative hepatitis B surface and e antigens were found be high in 54.9% and 52.4% of the patients, respectively, while hepatitis B virus DNA level was high in 70.7%. The median of the viral load of HBV was 8,934.89 IU/mL and both hepatitis B surface and e antigens were also found to be high on average for qHBsAg (M = 5.19 IU/mL, SD ± 4. 33) and qHBeAg (M = 4.74IU/mL, SD ± 4.20), with qHBeAg being more strongly correlated to HBV DNA than qHBsAg (r = 0.893; p < 0.01). CONCLUSIONS This study revealed HBeAg to be the most appropriate marker that correlates well with HBV DNA, thus not completely novel but confirmative, and related to the Malaysian situation.

Purpose Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB. Materials and methods A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differentiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168. Results Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver-operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively. Conclusion The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.

Systemic embolization is a rare but serious complication of variceal injection with cyanoacrylate. We report a case of cerebral embolism a few hours after an injection of Histoacryl into a bleeding esophageal post-banding ulcer. Echocardiogram revealed patent foramen ovale.

Importance There is a need for noninvasive tools to monitor hepatotoxicity in patients with psoriasis who are receiving methotrexate sodium. Objective To evaluate the use of transient elastography (TE) and FibroTest (FibroSURE in the United States), an indirect serum marker of fibrosis, in this population. Design, Setting, and Participants Patients receiving methotrexate therapy for psoriasis between January 2008 and September 2009 were recruited from a dermatology outpatient department. Transient elastography and FibroTest were performed, and patients with abnormal results were considered for liver biopsy. Serial procollagen III peptide (PIIINP) results were recorded. Interventions Transient elastography uses pulse-echo ultrasonography to measure liver stiffness, and this result is an indirect measure of hepatic fibrosis. FibroTest is an indirect serum marker of hepatic fibrosis. Main Outcomes and Measures Procollagen III peptide, TE, and FibroTest results, as well as the need for liver biopsy in this cohort. Results Seventy-seven patients (41 male [53%]) were included. Fifty (65%) patients had a valid TE assessment, and 9 (18%) had an abnormal result (range, 7.1-11.3 kPa). Being overweight or obese increased the possibility of obtaining an invalid TE result significantly ( P = .01). On univariate analysis body mass index ( r = 0.40, P = .005) and age ( r = 0.52, P = .005) were correlated with abnormal TE results. Seventy-one patients received a FibroTest and 11 of 70 analyzed (16%) had an abnormal result (METAVIR score >F1). Age ( r = 0.31, P = .009), cumulative methotrexate dose ( r = 0.31, P = .01), and duration of methotrexate therapy ( r = 0.36, P = .002) were correlated with abnormal FibroTest results. There was no correlation between PIIINP levels and TE results or between PIIINP levels and FibroTest results. Steatosis was demonstrated in all 5 patients who received liver biopsies during the study. Two patients had hepatic fibrosis, with 1 showing a sinusoidal pattern of fibrosis attributed to steatohepatitis. Conclusions and Relevance Transient elastography and FibroTest are effective noninvasive tools for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis. We propose that the need for liver biopsy could be reduced if abnormalities in at least 2 tests (serial PIIINP, TE, or FibroTest) are required before biopsy is considered. This strategy should be evaluated in prospective studies.

4106 Background: Some 20-30% of patients with chronic hepatitis B (CHB) eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis and high mortality unless detected early. Ultrasound and/or alpha-fetoprotein (AFP) are widely used for HCC surveillance. However these technologies are operator-dependent, have low sensitivity and are considered inadequate for screening. This study describes a blood-based gene-expression signature prognostic for HCC in CHB patients. Methods: PaxGene was used to extract RNA from whole blood samples taken from more than 1,000 Malaysian patients (matched HCC, CHB, healthy controls). Complementary DNA was generated from isolated RNA via reverse transcription and analyzed using Affymetrix U133Plus 2.0 with MAS 5.0 normalization. To minimize bias we developed a novel algorithm based on SentinelPair regression analysis to identify biomarker panels. A Monte Carlo search identified pair combinations that could differentiate between cancer and controls. Twelve genes were selected for qRT-PCR Cohort 1 verification (n=139). Six genes were then short-listed for qRT-PCR Cohort 2 verification using independent samples (n=150). Results: Multivariate quantitative microarray analysis of 147 samples (HCC=47; CHB=50; controls=50) identified 12 probe sets differentially expressed between HCC patients and controls and CHB (ROC AUC=0.90). These genes were evaluated using qRT-PCR on the same cohort (ROC AUC=0.86). Six genes were subsequently short listed for qRT-PCR Cohort 2 verification. The AUC of the 6-gene-combination of Cohort 2 (HCC=50; CHB=50; controls=50) was 0.80. Importantly, of the thirteen HCC with low AFP (