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  1. Wong SW, Chan WK, Mohamed R
    J Viral Hepat, 2020 12;27(12):1297-1305.
    PMID: 32668489 DOI: 10.1111/jvh.13361
    Hepatic steatosis is increasingly common and has been implicated in progression of liver fibrosis in chronic hepatitis B (CHB) patients. We aimed to investigate the impact of hepatic steatosis on liver fibrosis and clinical outcomes in CHB patients. Consecutive CHB patients who underwent transient elastography between 2013 and 2017 at a tertiary hospital were included in this longitudinal cohort study. Presence of hepatic steatosis was defined as controlled attenuation parameter, CAP ≥ 248 dB/m, while advanced liver fibrosis was defined as liver stiffness measurement, LSM ≥ 9.4 kPa. Cardiovascular events, liver-related complications, malignancy and mortality and a composite of these outcomes were evaluated with Kaplan-Meier analysis and Cox proportional hazards regression. Our study cohort included 614 patients with median follow-up of 45 (32-63) months. Hepatic steatosis was present in 294 patients (47.9%), and advanced liver fibrosis was present in 127 patients (21.0%). Presence of hepatic steatosis (OR: 1.956, 95% CI: 1.250-3.060) and diabetes mellitus (OR: 3.507, 95% CI: 2.069-5.944) was independently associated with advanced fibrosis. Advanced fibrosis was independently associated with composite outcome (HR: 2.496, 95% CI: 1.352-4.606), liver-related complications (HR: 3.765, 95% CI: 1.380-10.271) and mortality (HR: 3.632, 95% CI: 1.342-9.826), but not cardiovascular events and malignancy. Hepatic steatosis was not associated with any adverse outcomes. We conclude that hepatic steatosis is common and associated with advanced fibrosis in CHB patients. Unlike advanced fibrosis, hepatic steatosis does not predict adverse outcomes in CHB patients.
    Matched MeSH terms: Liver Cirrhosis/epidemiology
  2. Sumithran E, Prathap K
    Cancer, 1976 May;37(5):2263-6.
    PMID: 177187
    Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people.
    Matched MeSH terms: Liver Cirrhosis/epidemiology
  3. Mohamed R, Yip C, Singh S
    Eur J Gastroenterol Hepatol, 2023 Jul 01;35(7):742-752.
    PMID: 37161976 DOI: 10.1097/MEG.0000000000002548
    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.

    Matched MeSH terms: Liver Cirrhosis/epidemiology
  4. Wong SW, Chan WK
    Indian J Gastroenterol, 2020 02;39(1):1-8.
    PMID: 32152903 DOI: 10.1007/s12664-020-01018-x
    The growing burden of non-alcoholic fatty liver disease (NAFLD) parallels the increasing prevalence of obesity in Asia. The overall prevalence of NAFLD in Asia is now estimated to be 29.6% and may have surpassed that in Western populations. NAFLD increases with increasing age and is closely associated with metabolic syndrome. Ethnic differences exist in the prevalence of NAFLD, but the underlying factors are unclear. There were initial concerns about lean NAFLD being associated with more severe liver disease and increased mortality, but subsequent studies suggested otherwise. Only some NAFLD patients progress to develop advanced liver fibrosis and cirrhosis, while the liver status remains unchanged in the majority; fibrosis stage is the most important predictor of disease-specific mortality in NAFLD. Surveillance for hepatocellular carcinoma (HCC) remains a challenge due to undiagnosed cirrhosis and the development of HCC in non-cirrhotic NAFLD patients. Diabetes mellitus shares a bidirectional relationship with NAFLD; NAFLD is highly prevalent among patients with diabetes mellitus, and diabetes mellitus is associated with more severe NAFLD. Chronic hepatitis B (CHB) is a major cause of chronic liver disease in Asia; NAFLD and CHB are increasingly observed together because of the increasing prevalence of NAFLD. Despite studies reporting favorable virologic outcome in CHB patients with NAFLD, NAFLD has been found to be independently associated with fibrosis progression and poorer prognosis in CHB patients. Therefore, NAFLD in CHB patients should be given more attention.
    Matched MeSH terms: Liver Cirrhosis/epidemiology
  5. Kudva MV, Zawawi MM
    Singapore Med J, 1990 Aug;31(4):368-73.
    PMID: 2255936
    This study was undertaken to analyse the clinical spectrum of chronic liver disease (cirrhosis, and others with portal hypertension) in Kuala Lumpur. Eighty patients were diagnosed over a 6-year period. Twenty-two had biopsy proven cirrhosis while 58 others had portal hypertension with clinical and biochemical evidence of chronic liver disease. The commonest aetiology was alcohol (36%), followed by the idiopathic variety and hepatitis B. The male to female ratio was 4.4:1. Indians had a high prevalence of alcohol-associated chronic liver disease. Overall, ascites was the commonest presentation. Eight patients presented with hepatocellular carcinoma. Spontaneous bacterial peritonitis was diagnosed in 13% of patients undergoing abdominal paracentesis. Gallstones were detected in 37% of patients who underwent ultrasonography. Diabetes mellitus and peptic ulcer disease were noted in 22% and 31% of patients respectively.
    Matched MeSH terms: Liver Cirrhosis/epidemiology
  6. Mohammed OK, Mahadeva S
    J Gastroenterol Hepatol, 2015 Sep;30(9):1423-8.
    PMID: 25867030 DOI: 10.1111/jgh.12978
    BACKGROUND AND AIM: The consequences of the association between the metabolic syndrome and cryptogenic cirrhosis are uncertain. We aimed to compare the differences in clinical outcomes between cryptogenic and non-cryptogenic cirrhosis.
    METHODS: A retrospective cohort study was conducted in a large, single academic center, over a 5-year duration.
    RESULTS: Complete data were available in 301 patients with cirrhosis (cryptogenic n = 94, non-cryptogenic n = 207). Compared with non-cryptogenic cirrhosis, patients with cryptogenic cirrhosis were older (mean age 66.4 ± 12.5 vs 60.7 ± 11.3 years, P liver-related morbidity (median 14.0 days vs 8.0 days, P = 0.04), rather than liver-related morbidity (median 10.5 days vs 8.0 days, P = 0.34), in patients with cryptogenic compared with non-cryptogenic cirrhosis. Kaplan-Meier survival analysis showed no significant differences in survival between both types of cirrhosis for all grades of severity.
    CONCLUSIONS: Cryptogenic cirrhosis is associated with a longer duration of hospitalization compared with non-cryptogenic cirrhosis at an early stage of the disease. This difference is due to a greater burden of non-liver-related complications in the former.
    KEYWORDS: clinical burden; cryptogenic cirrhosis; metabolic syndrome; non-alcoholic fatty liver disease
    Matched MeSH terms: Liver Cirrhosis/epidemiology*
  7. Lai LL, Wan Yusoff WNI, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    J Gastroenterol Hepatol, 2019 Aug;34(8):1396-1403.
    PMID: 30551263 DOI: 10.1111/jgh.14577
    BACKGROUND AND AIM: The recommendation in regard to screening for non-alcoholic fatty liver disease (NAFLD) among type 2 diabetes mellitus (T2DM) patients differs in major guidelines. The aim of this paper was to study the prevalence of NALFD and advanced fibrosis among T2DM patients.

    METHODS: This is a cross-sectional study of consecutive adult T2DM patients attending the Diabetes Clinic of a university hospital. Significant hepatic steatosis and advanced fibrosis was diagnosed based on transient elastography if the controlled attenuation parameter was ≥ 263 dB/m, and the liver stiffness measurement was ≥ 9.6 kPa using the M probe or ≥ 9.3 kPa using the XL probe, respectively. Patients with liver stiffness measurement ≥ 8 kPa were referred to the Gastroenterology and Hepatology Clinic for further assessment, including liver biopsy.

    RESULTS: The data of 557 patients were analyzed (mean age 61.4 ± 10.8 years, male 40.6%). The prevalence of NAFLD and advanced fibrosis based on transient elastography was 72.4% and 21.0%, respectively. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR 4.856, 95% confidence interval [CI] 2.749-8.577, P = 0.006), serum triglyceride (OR 1.585, 95% CI 1.056-2.381, P = 0.026), and alanine aminotransferase levels (OR 1.047, 95% CI 1.025-1.070, P liver biopsy. The majority had non-alcoholic steatohepatitis (83.1%) and ≥ F1 fibrosis (87.3%) while advanced fibrosis was seen in 36.6%.

    CONCLUSION: The prevalence of NAFLD and advanced fibrosis based on transient elastography is high among T2DM patients.

    Matched MeSH terms: Liver Cirrhosis/epidemiology*
  8. Tan EZ, Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    J Gastroenterol Hepatol, 2021 Mar;36(3):751-757.
    PMID: 32583444 DOI: 10.1111/jgh.15160
    BACKGROUND: The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear.

    METHODS: This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy.

    RESULTS: Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease.

    CONCLUSION: Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.

    Matched MeSH terms: Liver Cirrhosis/epidemiology
  9. Hudu SA, Niazlin MT, Nordin SA, Tan SS, Omar H, Shahar H, et al.
    Afr Health Sci, 2018 Dec;18(4):1117-1133.
    PMID: 30766578 DOI: 10.4314/ahs.v18i4.33
    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<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).

    Conclusion: This study revealed that genetic diversity was found to have a significant impact on the severity of infection.

    Matched MeSH terms: Liver Cirrhosis/epidemiology
  10. Newsome PN, Sasso M, Deeks JJ, Paredes A, Boursier J, Chan WK, et al.
    Lancet Gastroenterol Hepatol, 2020 04;5(4):362-373.
    PMID: 32027858 DOI: 10.1016/S2468-1253(19)30383-8
    BACKGROUND: The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]).

    METHODS: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009.

    FINDINGS: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0.

    INTERPRETATION: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease.

    FUNDING: Echosens and UK National Institute for Health Research.

    Matched MeSH terms: Liver Cirrhosis/epidemiology
  11. Chan TT, Chan WK, Wong GL, Chan AW, Nik Mustapha NR, Chan SL, et al.
    Am J Gastroenterol, 2020 06;115(6):867-875.
    PMID: 32149781 DOI: 10.14309/ajg.0000000000000588
    OBJECTIVES: Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD).

    METHODS: This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection.

    RESULTS: In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity.

    DISCUSSION: Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.

    Matched MeSH terms: Liver Cirrhosis/epidemiology*
  12. Andrieux-Meyer I, Tan SS, Thanprasertsuk S, Salvadori N, Menétrey C, Simon F, et al.
    Lancet Gastroenterol Hepatol, 2021 Jun;6(6):448-458.
    PMID: 33865507 DOI: 10.1016/S2468-1253(21)00031-5
    BACKGROUND: 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.

    METHODS: 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 RNA <12 IU/mL in Thailand and HCV RNA <15 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.

    FINDINGS: 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.

    INTERPRETATION: 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.

    FUNDING: 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.

    Matched MeSH terms: Liver Cirrhosis/epidemiology
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