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  1. Wong MM, Chan HY, Aziz NA, Ramasamy TS, Bong JJ, Ch'ng ES, et al.
    Mol Biol Rep, 2021 Apr;48(4):3695-3717.
    PMID: 33893928 DOI: 10.1007/s11033-021-06334-9
    Liver cancer is the sixth most common cancer and the fourth leading cause of cancer deaths in the world. The most common type of liver cancers is hepatocellular carcinoma (HCC). Autophagy is the cellular digestion of harmful components by sequestering the waste products into autophagosomes followed by lysosomal degradation for the maintenance of cellular homeostasis. The impairment of autophagy is highly associated with the development and progression of HCC although autophagy may be involved in tumour-suppressing cellular events. In regards to its protecting role, autophagy also shelters the cells from anoikis- a programmed cell death in anchorage-dependent cells detached from the surrounding extracellular matrix which facilitates metastasis in HCC. Liver cancer stem cells (LCSCs) have the ability for self-renewal and differentiation and are associated with the development and progression of HCC by regulating stemness, resistance and angiogenesis. Interestingly, autophagy is also known to regulate normal stem cells by promoting cellular survival and differentiation and maintaining cellular homeostasis. In this review, we discuss the basal autophagic mechanisms and double-faceted roles of autophagy as both tumour suppressor and tumour promoter in HCC, as well as its association with and contribution to self-renewal and differentiation of LCSCs.
    Matched MeSH terms: Liver Neoplasms/metabolism*
  2. Pham TS, Reda A, Ngan Nguyen TT, Ng SJ, Huan VT, Viet DC, et al.
    Transfus Apher Sci, 2020 Dec;59(6):102907.
    PMID: 32883595 DOI: 10.1016/j.transci.2020.102907
    We report a case of blood exchange transfusion to treat acute liver failure following hepatitis B infection at the Infectious Disease Department of Children's Hospital No.2 in Ho Chi Minh City, Vietnam. A 3.5-month old baby boy was admitted to the hospital with a presentation of progressively worsening jaundice for the past one month. The patient was diagnosed with hepatitis B infection with a positive HBV DNA quantitative assay. Plasma exchange was indicated in view of progressive liver failure and gradually increasing hepatic coma. However, it was impossible to perform plasmapheresis in this case because the patient was small (in terms of age and weight) and there was no suitable plasma exchange filter. Accordingly, the patient was treated with 3 times of blood exchange transfusion in combination with an antiviral drug, lamivudine. After each blood exchange transfusion, the biochemical values (bilirubin, liver enzymes, and coagulation profile) gradually improved and he was discharged after 1 month of treatment. Blood exchange transfusion is an effective procedure for managing acute liver failure, where plasma exchange is not possible while waiting for the recovery of liver functions or liver transplantation.
    Matched MeSH terms: Liver Failure, Acute/therapy*
  3. Ting YW, Kong AS, Zain SM, Chan WK, Tan HL, Mohamed Z, et al.
    Clin Mol Hepatol, 2021 Jul;27(3):486-498.
    PMID: 33618508 DOI: 10.3350/cmh.2020.0162
    BACKGROUND/AIMS: 17β-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.

    Matched MeSH terms: Liver; Liver Neoplasms
  4. Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen V, et al.
    J Hepatol, 2017 05;66(5):1022-1030.
    PMID: 28039099 DOI: 10.1016/j.jhep.2016.12.022
    BACKGROUND & AIMS: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis.

    METHODS: A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades.

    RESULTS: Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively.

    CONCLUSIONS: CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes.

    LAY SUMMARY: There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.

    Matched MeSH terms: Fatty Liver/pathology
  5. Murugasu R, Dissanaike AS
    Trans R Soc Trop Med Hyg, 1973;67(6):880.
    PMID: 4788765
    Matched MeSH terms: Liver/pathology
  6. Al-Faqeh, H.H., Muhammad, B.Y., Nafie, E.M., Khorshid, A.
    MyJurnal
    We attempted to investigate possible hepatoprotective effect of Eurycoma longifolia jack (ELJ) using carbon tetrachloride-induced (CC14) acute hepatotoxicity model in rats. Hepatotoxicity was induced by oral administration of 4.0mg/kg of CCI4 in corn oil (1:1) once to one experimental group of 5 rats and, in three other similar groups, challenged doses (300, 750 and 1500 mg/kg respectively) of ELJ were given one day before and one hour after 4.0 mg/kg CC14 and then once daily for three consecutive days. Three other groups of 5 rats each serving as controls were administered with distilled water, corn oil and ELJ (750mg/kg) only respectively. Rats were sacrificed on day three (corn oil & CC14 treated groups) and on day 4 (Distilled water, ELJ alone and CC14 with graded doses of ELJ treated groups) and samples of blood and liver tissue were taken for biochemical (serum) and histopathological examinations to assess hepatoprotection of ELJ against CC14-induced hepatotoxicity. In the low (300mg/kg) and medium (750 mg/kg) dose ELJ treated groups, CCI4 induced moderate inflammation, fatty acid change and necrosis of hepatocytes while in the high (1500mg/kg) dose ELJ, CC14 induced severe inflammation, fatty acid change and necrosis of hepatocytes. Biochemical measurements of ALT and ALP shows a moderate and insignificant reduction of serum levels in the low dose ELJ group but a more significant reduction in the medium and high dose ELJ groups when compared with the CC14 only group. The increase in serum total bilirubin caused by CC14 was non-significantly reduced by all the doses of ELJ. Animals treated with CC14 alone and in groups treated with both CC14 and graded doses of ELJ had a reduction in body weight, food and water intake but in ELJ (750mg/kg) only treated group, no such reduction in body weight, food and water intake was observed. This observation suggest that ELJ administered alone did not cause any toxic effect to the liver but in combination with CCI4, appeared to synergize the CC14-induced hepatotoxicity which increases as the dose of ELJ is increased. The anorexic, hypodypsic and reduced body weight evident in the CC14 alone and in ELJ plus CC14 treated groups but not in animals treated with ELJ alone, suggests that ELJ alone does not induce anorexia, hypodypsia or loss of weight. In conclusion, the results of our study suggest that ELJ is not hepatotoxic when given alone and appeared to have some degree of protective effects in rats against CC14-induced hepatotoxicity.
    Matched MeSH terms: Liver; Liver Function Tests
  7. Murugasu R, Wang F, Dissanaike AS
    Trans R Soc Trop Med Hyg, 1978;72(4):389-91.
    PMID: 705845
    The first living patient with a Schistosoma japonicum-type infection who presented with the nephrotic syndrome is reported in detail. It is not clear whether the nephrotic syndrome was due to the schistosome infection or to the deposition of hepatitis B antigen and antibody complexes. This is the tenth case of schistosomiasis reported from aborigines in Malaysia and a sylvatic source of infection is suggested.
    Matched MeSH terms: Liver/parasitology
  8. Cheek, Ken Lim, So, Har Ton
    Medicine & Health, 2007;2(1):1-25.
    MyJurnal
    Infection by hepatitis B virus (HBV) is a major global health-care problem. HBV is an accepted factor in the elevated risks for liver disease such as cirrhosis and development of hepatocellular carcinoma. This problem is particularly prevalent in the Asia-Pacific region which includes Malaysia. During infection, the hepatitis B e antigen (HBeAg) is produced in the hosts. This antigen is an important serological marker for diagnosing chronic hepatitis B. Seroconversion to anti-body (anti-HBe) corresponds to the improvement of disease prognosis. However, certain mutations such as the core promoter dual mutations (A1762G1764→T1762A1764), the codon 15 variants (C1858/ T1858) and the precore stop codon mutations (TGG→TAG) can affect the HBeAg expression. This has diagnostic and clinical implications. Besides that, the HBV can be grouped into eight genotypes (A to H). Moreover, genotypic subtypes and recombinants have been observed as well. Studies have observed that these can differ in their affiliations with the mutations above as well as with disease prognosis.
    Matched MeSH terms: Liver Cirrhosis; Liver Neoplasms
  9. Ellyda, M.N., Mohd Shafie, A.
    MyJurnal
    Metastatic spread of tumors to the skull is quite unusual and often represents diagnostic and therapeutic issues. Skull involvement can be observed in various neoplasms of epithelial origin and are most often due to lung, breast, thyroid, kidney and prostate cancers. However, skull metastases from hepatocellular carcinoma (HCC) have been rarely reported. The prognosis for patients with hepatocellular carcinoma is so poor that treatment of such distant metastatic lesion cannot be achieved before death occurs due to the primary malignancy. Therefore, the clinical manifestations of cranial metastasis prior to that of primary hepatocellular carcinoma have rarely been reported. This case illustrates a rare case of skull metastasis as an initial manifestation of hepatocellular carcinoma. Although a solitary skull metastasis prior to the diagnosis of HCC demonstrates rare metastatic behavior for HCC, especially in Asia, skull metastases from HCC should be included in the differential diagnosis of skull tumors, even if the patient is asymptomatic of liver cirrhosis.
    Matched MeSH terms: Liver Cirrhosis; Liver Neoplasms
  10. Kutty MK, Balasegaram M
    J R Coll Surg Edinb, 1972 Mar;17(2):102-7.
    PMID: 5021743
    Matched MeSH terms: Liver Neoplasms/epidemiology
  11. Ibrahim M, Mikail MA, Ahmed IA, Hazali N, Abdul Rasad MSB, Abdul Ghani R, et al.
    Eur J Nutr, 2018 Aug;57(5):1817-1828.
    PMID: 28516253 DOI: 10.1007/s00394-017-1466-3
    PURPOSE: Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice showed that it possesses antioxidant properties. Therefore, further work is needed to confirm the efficacy and proper dosage of B. angulata as a potential natural antioxidant. The present study was thus carried out to compare the effects of three different B. angulata whole fruit (WF) juice doses administered at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) as well as total antioxidant capacity in rabbits fed high-cholesterol diet.

    METHODS: Thirty-five male rabbits of New Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50 ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00 ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50 ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1 was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was fed standard pellet and 1.00 ml/kg/day B. angulata WF juice.

    RESULTS: The three doses reduced the formation of MDA and enhanced the expression of endogenous antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as the most potent.

    CONCLUSION: Higher doses of B. angulata juice exerted better antioxidant activity.

    Matched MeSH terms: Liver/metabolism*
  12. Nazratun Nafizah AH, Budin SB, Zaryantey AH, Mariati AR, Santhana RL, Osman M, et al.
    Arab J Gastroenterol, 2017 Mar;18(1):13-20.
    PMID: 28336227 DOI: 10.1016/j.ajg.2017.02.001
    BACKGROUND AND STUDY AIMS: The complex series of deleterious events among diabetes patients leads to multiple organ failure. Therefore, a holistic approach of treatment is urgently required to prevent worsening of complications. The present investigation was carried out to study the possible protective effects of Roselle or Hibiscus sabdariffa Linn (HSL) calyxes aqueous extract, as an antidiabetic and antioxidant agent against oxidative liver injury in streptozotocin-induced diabetic rats.

    MATERIAL AND METHODS: A single dose of streptozotocin (45mg/kg body weight, iv) was used to induced diabetes in male Sprague Dawley rats which were then divided into two groups: Diabetic control (DC) and HSL-treated diabetic (DR) group. Normal rats were divided into normal control (NC), HSL-treated control (NR). Aqueous calyxes extract of HSL (100mg/kg/day, orally) was given for 28 consecutive days in the treated group. Weight, biochemical and histopathological (light and electron microscopic) parameters were compared in all groups.

    RESULTS: Supplementation of HSL significantly lowered the level of fasting blood glucose and increased plasma insulin level in DR group compared to DC group (p<0.05). Alanine aminotransaminases and aspartate aminotransferase enzymes level were found to be significantly reduced in DR compared to DC. Microscopic examination demonstrated destruction of the liver architecture, cytoplasmic vacuolation of the hepatocytes and signs of necrosis in diabetic rats. Moreover, dilatation and congestion of blood vessels with leucocytes adherence were detected. Ultrastructural study using electron microscope showed homogeneous substance accumulation in nuclear chromatin, a decrease of organelles and mitochondrial degeneration in the diabetic rats.

    CONCLUSION: Administration of HSL in diabetic rats causes significant decrease in hepatocyte destruction and prevented the changes associated with the diabetic condition. Thus, our findings provide a scientific rationale for the use of HSL as promising agent in preventing liver injury in diabetes.

    Matched MeSH terms: Liver/drug effects; Liver/metabolism; Liver/ultrastructure*; Liver Failure/diagnosis; Liver Failure/etiology; Liver Failure/prevention & control*
  13. Garner CW, Behal FJ
    Biochemistry, 1975 Nov 18;14(23):5084-8.
    PMID: 38
    The presence of at least two ionizable active center groups has been detected by a study of the effect of pH upon catalysis of hydrolysis of L-alanyl-beta-naphthylamide by human liver alanine aminopeptidase and upon the inhibition of hydrolysis by inhibitors and substrate analogs. Octanoic acid, octylamine, and peptide inhibitors have been found to be competitive inhibitors and are therefore thought to bind the active center. L-Phe was previously shown to bind the active center since it was found to be a competitive inhibitor of the hydrolysis of tripeptide substrates (Garner, C. W., and Behal, F. J. (1975), Biochemistry 14, 3208). A plot of pKm vs. pH for the substrate L-Ala-beta-naphthylamide showed that binding decreased below pH 5.9 and above 7.5, the points at which the theoretical curve undergoes an integral change in slope. These points are interpreted as the pKa either of substrate ionizable groups or binding-dependent enzyme active center groups. Similar plots of pKm vs. pH for L-alanyl-p-nitroanilide (as substrate) and pKi vs. pH for L-Leu-L-Leu-L-Leu and D-Leu-L-Tyr (as inhibitors) gave pairs fo pKa values of 5.8 and 7.4, 6.0 and 7.5, and 5.7 and 7.5, respectively. All the above substrates (and D-Leu-L-Tyr) have pKa values near 7.5; therefore, the binding-dependent group with a pKa value near 7.5 is possibly this substrate group. Similar plots of pKi vs. pH for the inhibitors L-Phe, L-Met, L-Leu, octylamine, and octanoic acid had only one bending point at 7.7, 7.6, 7.4, 6.3, and 5.9, respectively. Amino acid inhibitors, octylamine, and octanoic acid have no groups with pKa values between 5 and 9. These data indicate that there are two active center ionizable groups with pKa values of approximately 6.0 and 7.5 which are involved in substrate binding or inhibitory amino acid binding but not in catalysis since Vmax was constant at all pH values tested.
    Matched MeSH terms: Liver/enzymology*
  14. Alirr OI, Abd Rahni AA
    Int J Comput Assist Radiol Surg, 2020 Feb;15(2):239-248.
    PMID: 31617057 DOI: 10.1007/s11548-019-02078-x
    PURPOSE: For the liver to remain viable, the resection during hepatectomy procedure should proceed along the major vessels; hence, the resection planes of the anatomic segments are defined, which mark the peripheries of the self-contained segments inside the liver. Liver anatomic segments identification represents an essential step in the preoperative planning for liver surgical resection treatment.

    METHOD: The method based on constructing atlases for the portal and the hepatic veins bifurcations, the atlas is used to localize the corresponding vein in each segmented vasculature using atlas matching. Point-based registration is used to deform the mesh of atlas to the vein branch. Three-dimensional distance map of the hepatic veins is constructed; the fast marching scheme is applied to extract the centerlines. The centerlines of the labeled major veins are extracted by defining the starting and the ending points of each labeled vein. Centerline is extracted by finding the shortest path between the two points. The extracted centerline is used to define the trajectories to plot the required planes between the anatomical segments.

    RESULTS: The proposed approach is validated on the IRCAD database. Using visual inspection, the method succeeded to extract the major veins centerlines. Based on that, the anatomic segments are defined according to Couinaud segmental anatomy.

    CONCLUSION: Automatic liver segmental anatomy identification assists the surgeons for liver analysis in a robust and reproducible way. The anatomic segments with other liver structures construct a 3D visualization tool that is used by the surgeons to study clearly the liver anatomy and the extension of the cancer inside the liver.

    Matched MeSH terms: Liver/surgery*
  15. Tengku Ibrahim TZ, Thambiah SC, Samsudin IN, Nasuruddin AN, Zakaria MH
    Malays J Pathol, 2019 Dec;41(3):355-358.
    PMID: 31901922
    INTRODUCTION: Thyroid storm (TS) is an endocrine emergency. Early diagnosis for prompt treatment is essential as it has a high mortality rate.

    CASE REPORT: A 31-year-old lady with underlying hyperthyroidism, dilated cardiomyopathy with severe mitral regurgitation presented with shortness of breath. She was intubated and admitted due to decreasing Glasgow Coma Score. Her blood investigations revealed increased white cell count, raised free thyroxine with suppressed thyroid stimulating hormone, deranged liver, renal and coagulation profiles. As her condition did not improve with initial treatment, plasmapheresis was commenced on day 4. Biochemically, her thyroid function test (TFT) showed improvement; however, she succumbed due to multi-organ failure.

    DISCUSSION: Plasmapheresis is considered in TS if there is no clinical improvement within 24-48 hours of initial treatment. The improvement in patient's TFT post plasmapheresis signifies its role in treating TS. Unfortunately, there was a delay in commencing plasmapheresis due to haemodynamic instability in this patient.

    Matched MeSH terms: Liver/pathology
  16. Wahab NWA, Guad RM, Subramaniyan V, Fareez IM, Choy KW, Bonam SR, et al.
    Curr Stem Cell Res Ther, 2021;16(5):563-576.
    PMID: 32957893 DOI: 10.2174/1574888X15999200918105623
    Stem cells can multiply into more cells with similar types in an undifferentiated form and differentiate into other types of cells. The great success and key essence of stem cell technology is the isolation of high-quality Mesenchymal Stem Cells (MSCs) with high potency, either with multipotent or pluripotent property. In this line, Stem cells from Human Exfoliated Deciduous teeth (SHEDs) are highly proliferative stem cells from dental pulp and have multipoint differentiation capacity. These cells play a pivotal role in regenerative medicine, such as cell repair associated with neurodegenerative, hepatobiliary, and pancreatic diseases. In addition, stem cell therapy has been widely used to regulate immune response and repair of tissue lesions. This overview captured the differential biological characteristics, and the potential role of stem cell technology and paid special attention to human welfare SHEDs in eliminating the above-mentioned diseases. This review provides further insights into stem cell technology by expanding the therapeutic potential of SHEDs in tissue engineering and cell organ repairs.
    Matched MeSH terms: Liver Diseases/therapy
  17. Lee, W.S.
    JUMMEC, 2010;13(2):72-79.
    MyJurnal
    The liver is an important organ of the human body, playing a major role in the metabolism and storage of nutrients, synthesis of protein and other nutrients, as well as detoxifying many metabolic by-products. The response of the foetal and newborn liver to external insult and injury is limited. This is because the ability of the closely interdependent structures of a developing liver of expressing in the face of a variety of insults is limited as well. Thus most infants with insults to the liver present as cholestatic jaundice with variable degree of pale stools, enlarged liver and conjugated hyperbilirubinaemia. Biliary atresia, an idiopathic condition characterized by progressive fibrosing obliteration of both intra- and extrahepatic bile ducts, is the most important cause of neonatal cholestasis worldwide, including Malaysia. It is also the most important indication for childhood liver transplantation the world over. Challenges facing infants with biliary atresia include a delay in the diagnosis and late surgery, leading to a poor outcome. This often results from a failure to recognise the potential serious nature of an infant with prolonged cholestatic jaundice and pale stools among health care professionals.
    Matched MeSH terms: Liver Diseases; Liver Transplantation
  18. Thangavelu L, Geetha RV, Devaraj E, Dua K, Chellappan DK, Balusamy SR
    Environ Toxicol, 2022 Mar;37(3):446-456.
    PMID: 34800081 DOI: 10.1002/tox.23411
    Acacia catechu Willd (Fabaceae) is a thorny tree widely distributed in India and commonly used as traditional Ayurvedic medicine for various ailments. The current study evaluates the cytotoxic potentials of A. catechu ethanolic seed extract (ACSE) in HepG2 cells, a human hepatocellular carcinoma cell line. The HepG2 cells were treated with 0.1, 0.3, 1, 3, 10, 30, 100, 300 and 1000 μg/ml of ACSE and the cytotoxic effect was evaluated by MTT and lactate dehydrogenase (LDH) leakage assays. The IC50 of ACSE was found at 77.04 μg/ml and therefore, further studies were carried out with the concentrations of 35 and 70 μg/ml. The intracellular reactive oxygen species (ROS) generation and apoptosis-related morphological changes were evaluated. Gene expressions of Bax, Bcl-2, cytochrome C (Cyt-c), caspases-9 and 3 were analyzed by qPCR. The ACSE treatments caused LDH leakage was associated with an increased ROS generation. The increased ROS generation was associated with the downregulation of intracellular antioxidant enzyme superoxide dismutase and reduced glutathione content. AO/EB and PI staining also confirmed chromatin condensation and apoptosis. The flow cytometric analysis showed an accumulation of HepG2 cells at sub G0/G1 (apoptotic) phase upon ACSE treatments. The ACSE induced cytotoxicity and oxidative stress were related to increased apoptotic marker gene expressions such as Bax, Cyt-c, caspase-9 and 3, and decreased anti-apoptotic marker Bcl-2. The current finding suggests that ACSE has apoptosis-inducing potential via the mitochondrial pathway in HepG2 cells.
    Matched MeSH terms: Liver Neoplasms*
  19. Choudhury A, Jindal A, Maiwall R, Sharma MK, Sharma BC, Pamecha V, et al.
    Hepatol Int, 2017 Sep;11(5):461-471.
    PMID: 28856540 DOI: 10.1007/s12072-017-9816-z
    BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models.

    METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922).

    RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001).

    CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

    Matched MeSH terms: Acute-On-Chronic Liver Failure/mortality*
  20. Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen V, et al.
    Aliment Pharmacol Ther, 2018 Apr;47(7):989-1000.
    PMID: 29446106 DOI: 10.1111/apt.14529
    BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis.

    AIM: To determine how to use CAP in interpreting liver stiffness measurements.

    METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP.

    RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis.

    CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

    Matched MeSH terms: Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
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