Displaying publications 81 - 100 of 165 in total

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  1. Seng LK, Mahadaven M, Musa A
    Br J Surg, 1993 Sep;80(9):1149.
    PMID: 8402117
    Matched MeSH terms: Liver Cirrhosis/complications
  2. Abdul Aziz KA, Draman N, Wan Isa WYH, Mustaffa N
    Med J Malaysia, 2020 07;75(4):396-399.
    PMID: 32724001
    Cirrhotic cardiomyopathy is a recognised complication of liver cirrhosis and predicts poor outcomes. Detection of diastolic dysfunction, an early indicator of left ventricular dysfunction can help identify those patients at risk of disease progression. In our study we showed that there was a high prevalence of diastolic dysfunction amongst patients with liver cirrhosis at our outpatient clinic, with the majority being Child-Pugh A/low MELD score. Multiple regression analysis indicated that age and sodium levels were significantly associated with the presence of diastolic dysfunction. This further reinforces the importance of dietary sodium restriction amongst patients with liver cirrhosis.
    Matched MeSH terms: Liver Cirrhosis/complications*
  3. Sumithran E, Prathap K
    Cancer, 1977 Oct;40(4):1618-20.
    PMID: 198100
    Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.
    Matched MeSH terms: Liver Cirrhosis/complications*
  4. Korenek J
    Vnitr Lek, 1970 Apr;16(4):371-8.
    PMID: 4910163
    Matched MeSH terms: Liver Cirrhosis/diagnosis
  5. Rajaram R, Subramani B, Abdullah BJJ, Mahadeva S
    JGH Open, 2017 Dec;1(4):153-155.
    PMID: 30483553 DOI: 10.1002/jgh3.12027
    Mesenchymal stem cell (MSC) transplant may offer an alternative to liver transplantation in patients with end-stage liver disease. However, its efficacy remains uncertain. MSC was performed on a 50-year-old male with decompensated (Child-Turcotte-Pugh grade C) alcoholic liver cirrhosis due to an absence of donors for adult-deceased and living-related liver transplantation. Autologous bone marrow-derived MSCs were harvested from the patient and cultured using standard protocols. The MSCs were subsequently re-administrated into the liver via hepatic intra-arterial infusion on two separate occasions. After infusion, there was an improvement in biochemical parameters (serum total bilirubin, serum albumin), and a reduction of diuretic use for ascites for up to 8 weeks. However, all biochemical and clinical parameters deteriorated on long-term follow-up without any further infusions. The patient eventually succumbed to his disease. MSC transplantation may have a clinical benefit on adult patients with end-stage liver cirrhosis, but this appears to be transitory.
    Matched MeSH terms: Liver Cirrhosis; Liver Cirrhosis, Alcoholic
  6. Chan WK, Treeprasertsuk S, Goh GB, Fan JG, Song MJ, Charatcharoenwitthaya P, et al.
    Clin Gastroenterol Hepatol, 2019 11;17(12):2570-2580.e37.
    PMID: 30876959 DOI: 10.1016/j.cgh.2019.03.006
    BACKGROUND & AIMS: Measuring liver stiffness only in patients with indeterminate or high nonalcoholic fatty liver disease (NAFLD) fibrosis scores (called a 2-step approach) was reported to reduce indeterminate or discordant results while maintaining the accuracy to identify patients with advanced fibrosis. We aimed to validate this approach using data collected from the Gut and Obesity in Asia Workgroup.

    METHODS: We performed a retrospective analysis of data from 759 patients with biopsy-proven NAFLD (24% with advanced fibrosis), seen at 10 centers in 9 countries in Asia, from 2006 through 2018. By using liver biopsies as the reference standard, we calculated percentages of misclassifications and indeterminate or discordant results from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score) and liver stiffness measurements (LSMs), alone or in combination. The analysis was repeated using randomly selected subgroups with a different prevalence of advanced fibrosis (histologic fibrosis stage ≥F3).

    RESULTS: In groups in which 3.7% and 10% of patients had advanced fibrosis, a 2-step approach (using the NFS followed by LSM only for patients with indeterminate or high NFS) and using a gray zone of 10 to 15 kPa for LSM, produced indeterminate or discordant results for 6.9% of patients and misclassified 2.7% of patients; only 25.6% of patients required LSM. In the group in which 10% of patients had advanced fibrosis, the same approach produced indeterminate or discordant results for 7.9% of patients and misclassified 6.6% of patients; only 27.4% of patients required LSM. In groups in which 24% and 50% of patients had advanced fibrosis, using LSM ≥10 kPa alone for the diagnosis of advanced fibrosis had the highest accuracy and misclassified 18.1% and 18.3% of patients, respectively. These results were similar when the Fibrosis-4 score was used in place of NFS.

    CONCLUSIONS: In a retrospective analysis, we found that a 2-step approach using fibrosis scores followed by LSM most accurately detects advanced fibrosis in populations with a low prevalence of advanced fibrosis. However, LSM ≥10 kPa identifies patients with advanced fibrosis with the highest level of accuracy in populations with a high prevalence of advanced fibrosis.

    Matched MeSH terms: Liver Cirrhosis/diagnosis*
  7. Vasudevan AE, Goh KL, Bulgiba AM
    Am J Gastroenterol, 2002 Jul;97(7):1717-21.
    PMID: 12135024
    The aim of this study was to determine whether the number connection test (NCT) times of a group of cirrhotic patients without clinically overt hepatic encephalopathy and a group of healthy patients without liver disease who were undergoing endoscopy were prolonged after sedation with short acting i.v. benzodiazepines.
    Matched MeSH terms: Liver Cirrhosis/surgery*
  8. Tan EX, Lee JW, Jumat NH, Chan WK, Treeprasertsuk S, Goh GB, et al.
    Metabolism, 2022 01;126:154911.
    PMID: 34648769 DOI: 10.1016/j.metabol.2021.154911
    BACKGROUND: A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients.

    METHODS: 1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients.

    FINDINGS: One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p liver disease.

    CONCLUSION: A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

    Matched MeSH terms: Liver Cirrhosis/pathology*
  9. Kothare SN
    Singapore Med J, 1978 Dec;19(4):220-4.
    PMID: 87015
    This is a preliminary report of 46 sera tested for alpha-fetoprotein (AFP) by the Counter immuno-electrophoresis technique in which biopsies for histopathology were also submitted. In 42 cases the needle biopsy of the liver was available. The material was divided into two groups on the basis of AFP positive and AFP negative sera and their histological diagnosis. The overall positivity rate in proven Primary liver cell carcinoma was 64.2 per cent.
    Matched MeSH terms: Liver Cirrhosis/blood
  10. Younossi ZM, Yu ML, Yilmaz Y, Alswat KA, Buti M, Fernandez MIC, et al.
    J Viral Hepat, 2023 Apr;30(4):335-344.
    PMID: 36601668 DOI: 10.1111/jvh.13800
    Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.
    Matched MeSH terms: Liver Cirrhosis/drug therapy
  11. Chan WK, Petta S, Noureddin M, Goh GBB, Wong VW
    Aliment Pharmacol Ther, 2024 Jun;59 Suppl 1:S23-S40.
    PMID: 38813831 DOI: 10.1111/apt.17866
    BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease and an important cause of cirrhosis and hepatocellular carcinoma. It is strongly associated with type 2 diabetes and obesity. Because of the huge number of patients at risk of MASLD, it is imperative to use non-invasive tests appropriately.

    AIMS: To provide a narrative review on the performance and limitations of non-invasive tests, with a special emphasis on the impact of diabetes and obesity.

    METHODS: We searched PubMed and Cochrane databases for articles published from 1990 to August 2023.

    RESULTS: Abdominal ultrasonography remains the primary method to diagnose hepatic steatosis, while magnetic resonance imaging proton density fat fraction is currently the gold standard to quantify steatosis. Simple fibrosis scores such as the Fibrosis-4 index are well suited as initial assessment in primary care and non-hepatology settings to rule out advanced fibrosis and future risk of liver-related complications. However, because of its low positive predictive value, an abnormal test should be followed by specific blood (e.g. Enhanced Liver Fibrosis score) or imaging biomarkers (e.g. vibration-controlled transient elastography and magnetic resonance elastography) of fibrosis. Some non-invasive tests of fibrosis appear to be less accurate in patients with diabetes. Obesity also affects the performance of abdominal ultrasonography and transient elastography, whereas magnetic resonance imaging may not be feasible in some patients with severe obesity.

    CONCLUSIONS: This article highlights issues surrounding the clinical application of non-invasive tests for MASLD in patients with type 2 diabetes and obesity.

    Matched MeSH terms: Liver Cirrhosis/diagnosis
  12. Panjasawatwong N, Avihingsanon A, Menétrey C, Ribeiro I, Salvadori N, Swanson A, et al.
    Antimicrob Agents Chemother, 2024 Jul 09;68(7):e0000824.
    PMID: 38767383 DOI: 10.1128/aac.00008-24
    Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.
    Matched MeSH terms: Liver Cirrhosis/drug therapy
  13. Chua HS, Soh YH, Ibrahim S, Abdullah NH, Che Mat Seri NAA, AbuBakar S, et al.
    Trop Biomed, 2024 Jun 01;41(2):220-223.
    PMID: 39154277 DOI: 10.47665/tb.41.2.014
    Vibrio vulnificus infection is associated with high morbidity and mortality in high-risk patients. Poor prognoses could lead to >50% mortality rate. The present report describes a case of V. vulnificus bacteremia in a cirrhotic patient with underlying hepatitis C. He presented with generalised abdominal pain associated with distention and could not ambulate for one week. He also complained of fever for six days and pruritus for 10 days. Tea-coloured urine was noted in continuous bag drainage. The abdomen was distended but soft, with mild tenderness palpated over the left lumbar and iliac region. Blood investigation indicated ongoing infection and inflammation. The aerobic blood culture was identified using the matrix-assisted laser desorption/ionisation-time of flight mass spectrometry and confirmed via 16S rDNA sequencing as V. vulnificus. Multilocus sequence typing of the isolated V. vulnificus revealed a novel sequence type, ST540. The patient responded well to the intravenous cefoperazone and was then discharged with a four day-course of oral ciprofloxacin, 500 mg twice daily after completing the intravenous cefoperazone for 10 days. Clinical history and physical examination are important for early antibiotic therapy initiation and appropriate surgical intervention. Furthermore, bacterial strain typing is also essential for epidemiological surveillance and potentially anticipating the pathogen's virulence traits, which are vital in controlling and preventing the spread of infection.
    Matched MeSH terms: Liver Cirrhosis/complications
  14. Wu X, Zhang S, Lai J, Lu H, Sun Y, Guan W
    Exp Clin Transplant, 2020 12;18(7):823-831.
    PMID: 33349209 DOI: 10.6002/ect.2020.0108
    OBJECTIVES: Liver fibrosis is inevitable in the healing process of liver injury. Liver fibrosis will develop into liver cirrhosis unless the damaging factors are removed. This study investigated the potential therapy of Bama pig adipose-derived mesenchymal stem cells in a carbon tetrachloride-induced liver fibrosis Institute of Cancer Research strain mice model.

    MATERIALS AND METHODS: Adipose-derived mesenchymal stem cells were injected intravenously into the tails of mice of the Institute of Cancer Research strain that had been treated with carbon tetrachloride for 4 weeks. Survival rate, migration, and proliferation of adipose-derived mesenchymal stem cells in the liver were observed by histochemistry, fluorescent labeling, and serological detection.

    RESULTS: At 1, 2, and 3 weeks after adipose-derived mesenchymal stem cell injection, liver fibrosis was significantly ameliorated. The injected adipose-derived mesenchymal stem cells had hepatic differentiation potential in vivo, and the survival rate of adipose-derived mesenchymal stem cells declined over time.

    CONCLUSIONS: The findings in this study confirmed that adipose-derived mesenchymal stem cells derived from the Bama pig can be used in the treatment of liver fibrosis, and the grafted adipose-derived mesenchy-mal stem cells can migrate, survive, and differentiate into hepatic cells in vivo.

    Matched MeSH terms: Liver Cirrhosis/chemically induced; Liver Cirrhosis/metabolism; Liver Cirrhosis/pathology; Liver Cirrhosis/surgery*
  15. Pitisuttithum P, Chan WK, Goh GB, Fan JG, Song MJ, Charatcharoenwitthaya P, et al.
    World J Gastroenterol, 2020 May 21;26(19):2416-2426.
    PMID: 32476802 DOI: 10.3748/wjg.v26.i19.2416
    BACKGROUND: Gamma-glutamyl transferase (GGT) is associated with the risk of cardiovascular disease (CVD) in the general population.

    AIM: To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).

    METHODS: This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis.

    RESULTS: A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02).

    CONCLUSION: The CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk.

    Matched MeSH terms: Liver Cirrhosis/blood; Liver Cirrhosis/complications; Liver Cirrhosis/diagnosis*; Liver Cirrhosis/pathology
  16. Lai LL, Chan WK, Sthaneshwar P, Nik Mustapha NR, Goh KL, Mahadeva S
    PLoS One, 2017;12(4):e0174982.
    PMID: 28369100 DOI: 10.1371/journal.pone.0174982
    Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) has been suggested to be useful for the assessment of disease severity in non-alcoholic fatty liver disease (NAFLD). Consecutive adult NAFLD patients who had a liver biopsy were included. Serum WFA+-M2BP level was measured using a lectin-antibody sandwich immunoassay using a chemiluminescence enzyme immunoassay machine (HISCL-5000, Sysmex, Kobe, Japan). The measured levels were indexed using the following equation: Cut-off index (COI) = ([WFA+-M2BP]sample-[WFA+-M2BP]NC) / ([WFA+-M2BP]PC-[WFA+-M2BP]NC), where PC = positive control and NC = negative control. Histopathological examination of liver biopsy specimen was reported according to Non-Alcoholic Steatohepatitis (NASH) Clinical Research Network Scoring System. Data for 220 cases were analyzed. The AUROC of the COI for the diagnosis of NASH was 0.65. The AUROC of the COI for the diagnosis of steatosis grade ≥2 and 3 was 0.64 and 0.53, respectively. The AUROC of the COI for the diagnosis of lobular inflammation grade ≥1, ≥2 and 3 was 0.57, 0.68 and 0.59, respectively. The AUROC of the COI for the diagnosis of hepatocyte ballooning grade ≥1 and 2 was 0.64 and 0.65, respectively. The AUROC of the COI for the diagnosis of fibrosis stage ≥1, ≥2, ≥3 and 4 was 0.61, 0.71, 0.74 and 0.84, respectively. Out of the 220 cases, 152 cases were the same 76 patients who had a repeat liver biopsy after 48 weeks of intervention. The AUROC of the change in the COI to detect improvement in steatosis, lobular inflammation, hepatocyte ballooning and fibrosis was 0.57, 0.54, 0.59 and 0.52, respectively. In conclusion, serum WFA+-M2BP was most useful for the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in NAFLD patients. However, it was less useful for differentiating NASH from non-NASH, and for diagnosis and follow-up of the individual histopathological components of NASH.
    Matched MeSH terms: Liver Cirrhosis/blood; Liver Cirrhosis/pathology*
  17. Riazalhosseini B, Mohamed R, Apalasamy YD, Langmia IM, Mohamed Z
    Rev Soc Bras Med Trop, 2017 Mar-Apr;50(2):161-166.
    PMID: 28562750 DOI: 10.1590/0037-8682-0416-2016
    INTRODUCTION: Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC.

    METHODS:: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB.

    RESULTS:: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression.

    CONCLUSIONS:: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.
    Matched MeSH terms: Liver Cirrhosis/genetics; Liver Cirrhosis/metabolism*
  18. Lim SG, Phyo WW, Shah SR, Win KM, Hamid S, Piratvisuth T, et al.
    J Viral Hepat, 2018 12;25(12):1533-1542.
    PMID: 30141214 DOI: 10.1111/jvh.12989
    There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4-3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3-3.1, P = 0.002). In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype.
    Matched MeSH terms: Liver Cirrhosis/pathology; Liver Cirrhosis/virology
  19. Haskins IN, Chang J, Nor Hanipah Z, Singh T, Mehta N, McCullough AJ, et al.
    Surg Obes Relat Dis, 2018 03;14(3):342-346.
    PMID: 29519663 DOI: 10.1016/j.soard.2017.11.032
    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized.

    OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity.

    SETTING: A tertiary, academic, referral hospital.

    METHODS: All patients who underwent bariatric surgery with intraoperative liver biopsy from 2008 to 2015 were identified. Patients with preoperative hypertension, dyslipidemia, or prediabetes/diabetes were excluded to identify a cohort of metabolically healthy obesity patients. Liver biopsy reports were reviewed to determine the prevalence of NAFLD.

    RESULTS: A total of 270 patients (7.0% of the total bariatric surgery patients) met the strict inclusion criteria for metabolically healthy obesity. The average age was 38 ± 10 years and the average body mass index was 47 ± 7 kg/m2. Abnormal alanine aminotransferase (>45 U/L) and asparate aminotransferase levels (>40 U/L) were observed in 28 (10.4%) and 18 (6.7%) patients, respectively. A total of 96 (35.5%) patients had NAFLD with NALFD Activity Scores 0 to 2 (n = 61), 3 to 4 (n = 25), and 5 to 8 (n = 10). A total of 62 (23%) patients had lobular inflammation, 23 (8.5%) had hepatocyte ballooning, 22 (8.2%) had steatohepatitis, and 12 (4.4%) had liver fibrosis.

    CONCLUSION: Even with the use of strict criteria to eliminate all patients with any metabolic problems, a significant proportion of metabolically healthy patients had unsuspected NAFLD. The need and clinical utility of routine screening of obese patients for fatty liver disease and the role of bariatric surgery in the management of NAFLD warrants further investigation.

    Matched MeSH terms: Liver Cirrhosis/complications; Liver Cirrhosis/surgery
  20. Abdulaziz Bardi D, Halabi MF, Hassandarvish P, Rouhollahi E, Paydar M, Moghadamtousi SZ, et al.
    PLoS One, 2014;9(10):e109424.
    PMID: 25280007 DOI: 10.1371/journal.pone.0109424
    This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells.
    Matched MeSH terms: Liver Cirrhosis/chemically induced; Liver Cirrhosis/pathology; Liver Cirrhosis/prevention & control*
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