Publications by authors named "Apinya Leerapun"

16 Publications

  • Page 1 of 1

The effects of dapagliflozin on hepatic and visceral fat in type 2 diabetes patients with non-alcoholic fatty liver disease.

J Gastroenterol Hepatol 2021 Jun 15. Epub 2021 Jun 15.

Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Background And Aim: Sodium-glucose cotransporter 2 inhibitors have shown excellent results in glucose control in type 2 diabetes mellitus (T2DM) patients, while also promoting weight loss. These mechanisms may be beneficial in the treatment of non-alcoholic fatty liver disease (NAFLD). Our study aims to investigate the effect of dapagliflozin on hepatic and visceral fat contents and related biochemical markers in T2DM with NAFLD patients.

Methods: This is a double-blinded placebo-controlled randomized, single-center study. Non-insulin-dependent T2DM patients with NAFLD were prospectively enrolled and randomly assigned to receive either dapagliflozin (10 mg/day) or placebo for 12 weeks. The primary end-point was the changes in intrahepatic lipid contents, evaluated by the liver attenuation index.

Results: Of 40 patients enrolled, 38 patients completed the study (dapagliflozin group, n = 18; placebo group, n = 20). Baseline demographic and laboratory findings were similar in both groups. After 12 weeks of treatment, dapagliflozin significantly decreased intrahepatic lipid contents demonstrated by an increase in liver attenuation index in comparison with the placebo treatment (5.8 ± 5.1 vs 0.5 ± 6.1 Hounsfield units, P = 0.006). Significant reduction in bodyweight, bodyfat, visceral fat/subcutaneous fat ratio, hemoglobin A1c, and alanine aminotransferase were also observed in the dapagliflozin-treated group as compared with the placebo group (all P < 0.05). There was no significant difference in adipokines including adiponectin, leptin, and tumor necrosis factor-α changes between the dapagliflozin-treated group and the placebo group (all P = nonsignificant).

Conclusion: Dapagliflozin treatment for 12 weeks is associated with improvement in hepatic fat content, a decrease in visceral fat and bodyweight, enhanced glycemic control, and improved liver biochemistry among T2DM patients with NAFLD.
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http://dx.doi.org/10.1111/jgh.15580DOI Listing
June 2021

Clinical Study of Single Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients with Chronic Hepatitis B.

Hepatology 2021 May 26. Epub 2021 May 26.

Roche Innovation Centre, Welwyn Garden City, United Kingdom.

RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded locked nucleic acid oligonucleotide complementary to HBV RNA. GalNAc conjugation targets the liver via the asialoglycoprotein receptor (ASGPR). This two-part phase 1 study evaluated the safety, pharmacokinetics and pharmacodynamics of RO7062931 in healthy volunteers and virologically suppressed patients with chronic hepatitis B (CHB). Part 1 was a single ascending dose study in healthy volunteers randomized to receive a single RO7062931 dose (0.1-4.0 mg/kg), or placebo. Part 2 was a multiple ascending dose study in patients with CHB randomized to receive RO7062931 at 0.5, 1.5, or 3.0 mg/kg, or placebo every month (QM) for a total of 2 doses (Part 2a), or RO7062931 at 3.0 mg/kg every 2 weeks (Q2W), 3.0 mg/kg every week (QW), or 4.0 mg/kg QW, or placebo for a total 3-5 doses (Part 2b). Sixty healthy volunteers and 59 patients received RO7062931 or placebo. The majority of adverse events (AEs) reported were mild in intensity. Common AEs included self-limiting injection site reactions and influenza-like illness. Supra-dose proportional increases in RO7062931 plasma exposure and urinary excretion occurred at doses ≥3.0 mg/kg. In CHB patients, RO7062931 resulted in dose- and time-dependent reduction in HBsAg versus placebo. The greatest HBsAg declines from baseline were achieved with the 3.0 mg/kg QW dose regimen (mean nadir ~0.5 log  IU/mL) independent of HBeAg status. RO7062931 is safe and well tolerated at doses up to 4.0 mg/kg QW. Supra-dose proportional exposure at doses of 3.0-4.0 mg/kg was indicative of partial saturation of the ASGPR-mediated liver uptake system. Dose-dependent declines in HBsAg demonstrated target engagement with RO7062931. Clinical trial number: NCT03038113.
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http://dx.doi.org/10.1002/hep.31920DOI Listing
May 2021

Human fascioliasis presenting as liver abscess: clinical characteristics and management.

Hepatol Int 2021 Jun 17;15(3):804-811. Epub 2021 Apr 17.

Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

Background: Human fascioliasis, caused by the liver flukes F. hepatica, and F. gigantica, is a neglected tropical disease that causes health problems in many regions of the world. This disease can be classified as either acute or chronic based depending on the clinical manifestations and laboratory findings.

Methods: We retrospectively reviewed the demographic data, clinical features, radiologic manifestations, and the response to specific treatment of patients diagnosed with hepatic fascioliasis as well as fasciola liver abscess in Thailand.

Results: A total of 175 patients were included in the study, 126 patients were females (72%), while the mean age was 47.8 years (16-84 years). The most common symptoms were abdominal pain (74.9%), weight loss (29.1%) and fever (28%). Peripheral eosinophilia was observed in 92% of patients. The typical radiologic findings discovered conglomerated hypodensity which are rim-enhancing lesions located in the subcapsular and peripheral region of the liver. Most of patients were improved after a single dose of triclabendazole treatment. Adding antibiotic had no statistical impact on treatment outcome (p = 0.78).

Conclusions: Human fascioliasis presents with a wide clinical spectrum; therefore, a high index of suspicion is required to establish a correct diagnosis. Clinicians need to be aware of hepatic fascioliasis when patients in such endemic areas present as hypereosinophilia and typical liver imaging. Prompt specific treatments will contribute towards a satisfactory outcome in patients.
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http://dx.doi.org/10.1007/s12072-021-10180-zDOI Listing
June 2021

Effects of Metformin on Hepatic Steatosis in Adults with Nonalcoholic Fatty Liver Disease and Diabetes: Insights from the Cellular to Patient Levels.

Gut Liver 2021 Apr 7. Epub 2021 Apr 7.

Cardiac Electrophysiology Research and Training Center, Chiang Mai, Thailand.

Nonalcoholic fatty liver disease (NAFLD) patients with diabetes constitute a subgroup of patients with a high rate of liver-related complications. Currently, there are no specific drug recommendations for these patients. Metformin, a conventional insulin sensitizer agent, has been widely prescribed in patients with diabetes. Metformin treatment has been shown to be effective at alleviating hepatic lipogenesis in animal models of NAFLD, with a variety of mechanisms being deemed responsible. To date, most studies have enrolled diabetic patients who are treated with metformin, with the drug being taken continuously throughout the study. Although evidence exists regarding the benefits of metformin for NAFLD in preclinical studies, reports on the efficacy of metformin in adult NAFLD patients have had some discrepancies regarding changes in liver biochemistry and hepatic fat content. Evidence has also suggested possible effects of metformin as regards the prevention of hepatocellular carcinoma tumorigenesis. This review was performed to comprehensively summarize the available and clinical studies regarding the effects of metformin on liver steatosis for the treatment of adult NAFLD patients with diabetes. Consistent reports as well as controversial findings are included in this review, and the mechanistic insights are also provided. In addition, this review focuses on the efficacy of metformin as a monotherapy and as a combined therapy with other antidiabetic medications.
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http://dx.doi.org/10.5009/gnl20367DOI Listing
April 2021

Efficacy and Safety of Clidinium/Chlordiazepoxide as an Add-on Therapy in Functional Dyspepsia: A Randomized, Controlled, Trial.

J Neurogastroenterol Motil 2020 Apr;26(2):259-266

Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Background/aims: The treatment of refractory functional dyspepsia (FD) is a challenge. Clidinium/chlordiazepoxide is a combination of antispasmodic and anxiolytic drugs that has been used as an adjunct treatment for FD in clinical practice with limited supporting evidence of efficacy. The aim of the study is to assess the efficacy and safety of clidinium/chlordiazepoxide as an adjunct treatment to a proton pump inhibitor (PPI) in refractory dyspepsia.

Methods: We performed a study of patients who met the Rome IV criteria for FD who failed to respond to PPIs. Patients were randomly assigned to groups that received clidinium/chlordiazepoxide or placebo as an add-on treatment to PPI for 4 weeks. The primary outcome was the rate of responders, which was defined as a > 50% reduction in dyspepsia symptom score after 4 weeks of treatment. The secondary outcomes were an improvement in the quality of life and the safety profile.

Results: Between March 2017 and February 2018, 78 patients were enrolled. The rates of responders in the clidinium/chlordiazepoxide group and placebo groups were 41.03 % and 5.13% at week 4 ( < 0.001). The clidinium/chlordiazepoxide group also showed significant improvement in overall quality of life over placebo. However, the clidinium/chlordiazepoxide group had more frequent drowsiness than the placebo group (30.27% vs 6.52%, = 0.034). There were no major adverse events in either group.

Conclusions: Clidinium/chlordiazepoxide significantly improved dyspeptic symptoms and quality of life. This combination may be used as an add-on therapy in FD patients without major adverse events.
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http://dx.doi.org/10.5056/jnm19186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176503PMC
April 2020

Evaluation of aspartate aminotransferase to platelet ratio index and fibrosis 4 scores for hepatic fibrosis assessment compared with transient elastography in chronic hepatitis C patients.

JGH Open 2020 Feb 26;4(1):69-74. Epub 2019 Jun 26.

Department of Medicine Khon Kaen University Khon Kaen Thailand.

Background And Aim: Fibrotic stage (FS) assessment is essential in chronic hepatitis C treatment cascade. Liver stiffness measurement (LSM) using transient elastography (TE) is reliable and correlated with liver biopsy. However, TE may not be widely available. This study aimed to evaluate the diagnostic performances of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB-4) scores compared with TE.

Methods: We conducted a multicenter, cross-sectional study, including all chronic hepatitis C virus (HCV) monoinfection patients with successful and reliable LSM, at 10 centers in Thailand from 2012 to 2017. Characteristics and laboratory data within 3 months of TE were retrospectively reviewed. Using TE as a reference standard, the diagnostic performances of APRI and FIB-4 were evaluated. TE cut-off levels of 7.1 and 12.5 kPa represented significant fibrosis (SF) and cirrhosis, respectively.

Results: The distribution of FS by TE in 2000 eligible patients was as follows: no SF 28.3%, SF 31.4%, and cirrhosis 40.3%. APRI ≥ 1 provided 70.1% sensitivity and 80.6% specificity, with an area under the receiver operator characteristics curve (AUROC) of 0.834 for cirrhosis. The specificity increased to 96.3% when using a cut-off level of APRI ≥ 2. FIB-4 ≥ 1.45 provided a sensitivity, specificity, and AUROC of 52.4%, 91.0%, and 0.829 for cirrhosis, respectively. For SF, APRI performed better than FIB-4, with an AUROC of 0.84 0.80 ( < 0.001). APRI score < 0.5 and FIB-4 score > 1.45 yielded sensitivities of 82.3% and 74.4% and specificities of 65.4% and 69.8%, respectively.

Conclusions: APRI and FIB-4 scores had good diagnostic performances for FS assessment compared with TE, especially for cirrhosis. APRI may be used as the noninvasive assessment in resource-limited settings for HCV patients' management.
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http://dx.doi.org/10.1002/jgh3.12219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008156PMC
February 2020

Vitamin D-Binding protein Gene Polymorphism Predicts Pegylated Interferon-Related HBsAg Seroclearance in HBeAg-Negative Thai Chronic Hepatitis B Patients: A Multicentre Study

Asian Pac J Cancer Prev 2019 Apr 29;20(4):1257-1264. Epub 2019 Apr 29.

Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Email:

Background: Vitamin D deficiency is related to poor clinical outcomes in patients with chronic hepatitis B virus (HBV) infection. Methods: We aimed to investigate the association between the genetic variants in the vitamin D metabolic pathway and the response to pegylated interferon (Peg-IFN) therapy in patients with HBeAg-negative chronic HBV infection. One hundred seven patients treated with Peg-IFN for 48 weeks were selected from 13 specialty hospitals. Eight genotypes of vitamin D cascade genes, including CYP27B1 (rs10877012), DHCR7 (rs12785878), CYP2R1 (rs2060793, rs12794714) and GC (rs4588, rs7041, rs222020, rs2282679), were found. Results: Eighty-two patients (83.7%) were infected with HBV genotype C. Eight patients had compensated liver cirrhosis (8.7%). At 24 weeks after treatment discontinuation, 41 patients (42.3%) achieved sustained treatment response, 53 (55.2%) obtained HBV DNA<2,000 IU/ml, 6 (5.6%) gained HBsAg seroclearance, 2 (1.9%) had HBsAg seroconversion and 69 (64.5%) exhibited alanine aminotransferase (ALT) normalization. Multivariate analysis revealed that baseline HBsAg level (OR =0.06, 95% CI: 0.08-0.49, p=0.008) and the GC rs222020 TT genotype (OR=17.72, 95% CI: 1.07-294.38, p=0.04) independently predicted sustained HBsAg seroclearance. In addition, this genotype was a predictor for normalization of ALT (OR=4.61, 95%CI: 1.59-13.40, p=0.005) after therapy. The HBsAg levels at baseline and during and post-treatment tended to be reduced with the GC rs222020 TT compared with the non-TT genotypes. The other studied polymorphisms were not associated with treatment response. Conclusions: The GC rs222020 TT genotype, which is a variant in the vitamin D-binding protein gene, could identify HBeAg-negative patients who have a high probability to achieve HBsAg clearance and ALT normalization after treatment with Peg-IFN.
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http://dx.doi.org/10.31557/APJCP.2019.20.4.1257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948901PMC
April 2019

Risk of Liver Fibrosis in Hepatitis B Virus and HIV Coinfected Youths Receiving Tenofovir-Containing Antiretroviral Regimen.

J Int Assoc Provid AIDS Care 2019 Jan-Dec;18:2325958218823259

4 The HIV Netherlands, Australia, Thailand Research Collaboration (HIVNAT), Bangkok, Thailand.

Background: Hepatitis B virus (HBV) and HIV coinfection is associated with risk of progression to chronic liver disease. We assessed liver stiffness in HBV-HIV coinfected youths.

Methods: A cross-sectional study in HBV-HIV coinfected youths aged 18 to 25 years who received a tenofovir (TDF)-containing antiretroviral therapy regimen for >96 weeks. Measurements included HBV DNA level, HBV serology profiles, and transient elastography (TE). The cutoff for TE results included ≥5.9 kPa for F2-moderate fibrosis, ≥7.4 kPa for F3-severe fibrosis, and ≥9.6 kPa for F4-cirrhosis.

Results: From March to December 2016, 15 HBV-HIV coinfected youths with a median duration on TDF-containing regimens of 3.3 years were enrolled. Five (33%) youths had significant liver fibrosis, 3 with F2-moderate, 1 with F3-advanced fibrosis, and 1 with F4-cirrhosis. Other 5 without liver fibrosis had hepatitis B surface e antigen (HBsAg) and hepatitis B surface e antigen (HBeAg) loss. Higher mean alanine transaminase (ALT) was observed among the group with F2-F4 when compared to those with F0.

Conclusion: Liver fibrosis was evidenced in HBV-HIV coinfected youths in Thailand. Transient elastography might be considered for those who do not achieve HBsAg loss or have persistent ALT elevation while on treatment.
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http://dx.doi.org/10.1177/2325958218823259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748531PMC
April 2020

Association of the S267F variant on NTCP gene and treatment response to pegylated interferon in patients with chronic hepatitis B: a multicentre study.

Antivir Ther 2018 ;23(1):67-75

Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Background: Sodium taurocholate co-transporting polypeptide (NTCP) is a cell receptor for HBV. The S267F variant on the NTCP gene is inversely associated with the chronicity of HBV infection, progression to cirrhosis and hepatocellular carcinoma in East Asian populations. The aim of this study was to determine whether the S267F variant was associated with response to pegylated interferon (PEG-IFN) in patients with chronic HBV infection.

Methods: A total of 257 patients with chronic HBV, treated with PEG-IFN for 48 weeks, were identified from 13 tertiary hospitals included in the hepatitis B database of the Thai Association for the Study of the Liver (THASL).

Results: Of these, 202 patients were infected with HBV genotype C (84.9%); 146 patients were hepatitis B e antigen (HBeAg)-positive (56.8%). Genotypic frequencies of the S267F polymorphism were 85.2%, 14.8% and 0% for the GG, GA and AA genotypes, respectively. S267F GA was associated with sustained alanine aminotransferase (ALT) normalization (OR = 3.25, 95% CI 1.23, 8.61; P=0.02) in HBeAg-positive patients. Patients with S267F variant tended to have more virological response, sustained response with hepatitis B surface antigen (HBsAg) loss at 24 weeks following PEG-IFN treatment. There was no association between the S267F variant and improved patient outcomes in HBeAg-negative patients.

Conclusions: The S267F variant on the NTCP gene is independently associated with sustained normalization of ALT following treatment with PEG-IFN in patients with HBV infection who are HBeAg-positive. The findings of this study provide additional support for the clinical significance of the S267F variant of NTCP beyond HBV entry.
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http://dx.doi.org/10.3851/IMP3179DOI Listing
September 2019

Genetic variation in the vitamin D pathway CYP2R1 gene predicts sustained HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon: A multicenter study.

PLoS One 2017 15;12(3):e0173263. Epub 2017 Mar 15.

Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Evidence of a role of vitamin D in the immune system is increasing. Low serum vitamin D is associated with increased hepatitis B virus replication. Genome-wide association study (GWAS) data has revealed a number of the single nucleotide polymorphisms (SNPs) within the vitamin D synthetic pathway that affect vitamin D functions. We aimed to determine the association between SNPs in the vitamin D gene cascade and response to pegylated interferon (PegIFN) therapy in hepatitis B e-antigen (HBeAg)-positive patients. One hundred and eleven patients treated for 48 weeks with PegIFN-alfa 2a at 13 hospitals were retrospectively evaluated. Thirteen SNPs derived from vitamin D cascade-related genes, including DHCR7 (rs12785878), CYP27B1 (rs10877012), CYP2R1 (rs2060793, rs12794714), GC (rs4588, rs7041, rs222020, rs2282679), and VDR (FokI, BsmI, Tru9I, ApaI, TaqI), were genotyped. Thirty-one patients (27.9%) seroconverted to HBeAg after 24 weeks of treatment. Multivariate analysis found pretreatment qHBsAg <10,000 IU/mL (OR = 7.73, 95% CI: 2.36-25.31, P = 0.001), CYP2R1 rs12794714 TT genotype (OR = 4.16, 95% CI: 1.07-16.25, P = 0.04), and baseline ALT >2 times the upper limit of normal (OR = 3.83, 95% CI: 1.31-11.22, P = 0.014) predicted sustained HBeAg seroconversion after completion of PegIFN treatment. HBV DNA during study period tended to be lower with the rs12794714 CYP2R1 TT than the non-TT genotype. The rs12794714 CYP2R1 polymorphism may be a useful pretreatment factor predictive of sustained HBeAg seroconversion after PegIFN therapy. This study provides evidence that not only vitamin D level but also genetic variation of CYP2R1 in the vitamin D cascade influences host immune response in chronic HBV infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173263PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351865PMC
September 2017

Fluorescence in situ hybridization compared with conventional cytology for the diagnosis of malignant biliary tract strictures in Asian patients.

Gastrointest Endosc 2016 Jun 10;83(6):1228-35. Epub 2015 Dec 10.

Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota, USA.

Background And Aims: Fluorescence in situ hybridization (FISH) has improved the diagnostic performance of cytology for the evaluation of malignant biliary strictures in the United States and Europe. The utility of FISH for the diagnosis of biliary strictures in Asia is currently unknown. We aimed to compare the sensitivity of FISH and conventional cytology for the diagnosis of malignant biliary strictures in Thai patients.

Methods: A prospective study was performed at 2 university hospitals between 2010 and 2013. Patients being evaluated for malignant-appearing biliary strictures were included (N = 99). Bile duct brushings were collected and assessed by cytology and FISH. Sensitivities with 95% confidence intervals of cytology and FISH were the main outcome measures.

Results: The overall sensitivities of cytology and FISH were 38% and 55%, respectively (P = .001). For those with a diagnosis of cancer based on clinical evidence without biopsy confirmation (n = 44), the sensitivities of cytology and FISH were 43% and 57%, respectively (P = .06). For the 49 patients for whom a cancer diagnosis was confirmed by pathology, FISH had a significantly higher sensitivity than cytology, with a sensitivity of 53% versus 33%, respectively (P = .008).

Conclusions: FISH improves the diagnostic performance of cytology and can be used as a complementary tool to bile duct brushing and biopsy for the evaluation of malignancy in biliary strictures in Asian populations.
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http://dx.doi.org/10.1016/j.gie.2015.11.037DOI Listing
June 2016

Three-day versus five-day somatostatin infusion combination with endoscopic variceal ligation in the prevention of early rebleeding following acute variceal hemorrhage: A randomized controlled trial.

Hepatol Res 2015 Dec 6;45(13):1276-82. Epub 2015 Apr 6.

Gastrohepatology Unit, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Aim: Combined pharmacological and endoscopic therapy is recommended for initial treatment of acute variceal bleeding (AVB). The optimal duration of therapy with a vasoactive agent is not well established. The aim of this study was to compare the efficacy and safety of 3-day and 5-day somatostatin treatment in the prevention of early rebleeding after endoscopic variceal ligation (EVL).

Methods: In a double-blind, prospective trial, cirrhotic patients with AVB who underwent EVL were randomly assigned to receive a continuous infusion of somatostatin for either 3 days or 5 days.

Results: A total of 95 patients were enrolled; 50 patients in the 3-day group and 45 patients in the 5-day group after initial hemostasis by combination therapy with somatostatin and EVL. Both groups were comparable in terms of baseline data. Very early and early rebleeding within 5 days and 42 days occurred in one and three patient (2%, 6%) in the 3-day group and three and two patients (6.67%, 4.45%) in the 5-day group (P = 0.342, 0.735), respectively. Overall, eight patients died (three from variceal rebleeding and five from causes other than variceal bleed); four (8%) in the 3-day group and four (8.89%) in the 5-day group (P = 0.876). Multivariate analysis revealed that none of the factors was a predictor of rebleeding. No serious side-effects and complications were observed.

Conclusion: A 3-day course of somatostatin is as effective as a 5-day course for the control of variceal bleeding and prevention of early rebleeding when used as combination therapy with EVL.
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http://dx.doi.org/10.1111/hepr.12503DOI Listing
December 2015

Clinical features and prognostic factors for liver cancer from a referral center in northern Thailand.

J Med Assoc Thai 2013 May;96(5):531-7

Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Background: Primary liver cancer included hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is the leading cancer with high mortality in Thailand. We aim to evaluate the overall survival and predictor of mortality in patients with HCC and CCA.

Material And Method: We reviewed medical records of 786 patients with liver mass between July 2007 and June 2010, 287 patients were HCC and 449 patients were CCA. The overall survival and prognostic variables for survival were analyzed.

Results: The mean age of HCC patients and CCA patient were 53.8 years and 59.2 years. Male was predominant, 85% and 74% in HCC and CCA. By BCLC staging for HCC, patients at early stage (A), intermediate stage (B), advanced stage (C), and terminal stage (D) were 40 (13.9%), 105 (36.6%), 95 (33.1%), and 43 (15.0%). Among 449 CCA patients, 143 (31.8%) were intrahepatic type and 306 (68.2%) were ductal type. The mean follow-up time for HCC and CCA patients were 20.1 and 16.7 months. The 1-year, 2-year, and 3-year survival of HCC and CCA were 55%, 34%, 31.3% and 54%, 21.2%, 19.1%, respectively. Predictor of death in HCC patients included portal vein thrombosis and did not receive any treatment (p < 0.05). Meanwhile, the predictor of death in CCA patient included intrahepatic type, total bilirubin > 2 mg/dl, CA 19-9 > 100, and unresectable tumor (p< 0.05).

Conclusion: The survival of patients who received any type of treatment was much better than in the past. Still, in patients with advanced disease whom only supportive treatments were provided, the prognosis is grave.
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May 2013

The utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: evaluation in a United States referral population.

Clin Gastroenterol Hepatol 2007 Mar;5(3):394-402; quiz 267

Miles and Shirley Fiterman Center for Digestive Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Background & Aims: The percentage of Lens culinaris agglutinin-reactive (alpha)-fetoprotein (AFP-L3%) is proposed as a diagnostic and prognostic marker for hepatocellular carcinoma (HCC). We evaluated the utility of AFP-L3% for diagnosis of HCC in a US referral population.

Methods: This retrospective study included 272 patients: 166 with HCC and 106 with benign liver disease (chronic liver disease, 77; benign liver mass, 29). The AFP-L3% was measured using a clinical auto-analyzer.

Results: The AFP-L3% is not reported for a total alpha-fetoprotein (AFP) less than 10 ng/mL, and all patients with an AFP greater than 200 ng/mL had HCC; thus the AFP-L3% was noninformative for these patients. In patients with a total AFP of 10-200 ng/mL, an AFP-L3% greater than 10% had a sensitivity of 71% and a specificity of 63% for diagnosis of HCC. An AFP-L3% greater than 35% had a reduced sensitivity of 33%, but an increased specificity of 100%. The high specificity of the AFP-L3% cut-off of 35% allowed the confident diagnosis of an additional 10% of HCCs not diagnosed using an AFP cut-off of 200 ng/mL. After adjustment for AFP level, no association was observed between AFP-L3% and tumor size, stage, vascular invasion, grade, or survival.

Conclusions: Patients with indeterminate total AFP values of 10-200 ng/mL present a diagnostic dilemma. We found that an AFP-L3% greater than 35% has 100% specificity for HCC in these patients. AFP-L3%, used in combination with AFP, may be a clinically useful adjunct marker for the diagnosis of HCC.
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http://dx.doi.org/10.1016/j.cgh.2006.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1931510PMC
March 2007

Per rectal portal scintigraphy as a useful tool for predicting esophageal variceal bleeding in cirrhotic patients.

World J Gastroenterol 2007 Feb;13(5):791-5

Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Aim: To investigate potential roles of per rectal portal scintigraphy in diagnosis of esophageal varices and predicting the risk of bleeding.

Methods: Fifteen normal subjects and fifty cirrhotic patients with endoscopically confirmed esophageal varices were included. Patients were categorized into bleeder and non-bleeder groups according to history of variceal bleeding. All had completed per rectal portal scintigraphy using (99m)Technetium pertechnetate. The shunt index was calculated from the ratio of (99m)Technetium pertechnetate in the heart and the liver. Data were analyzed using Student's t-test and receiver operating characteristics.

Results: Cirrhotic patients showed a higher shunt index than normal subjects (63.80 +/- 25.21 vs 13.54 +/- 6.46, P < 0.01). Patients with variceal bleeding showed a higher shunt index than those without bleeding (78.45 +/- 9.40 vs 49.35 +/- 27.72, P < 0.01). A shunt index of over 20% indicated the presence of varices and that of over 60% indicated the risk of variceal bleeding.

Conclusion: In cirrhotic patients, per rectal portal scintigraphy is a clinically useful test for identifying esophageal varices and risk of variceal bleeding.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066015PMC
http://dx.doi.org/10.3748/wjg.v13.i5.791DOI Listing
February 2007

Hypothyroidism: a possible risk factor for liver cancer in patients with no known underlying cause of liver disease.

Clin Gastroenterol Hepatol 2007 Jan 26;5(1):118-23. Epub 2006 Sep 26.

Miles and Shirley Fiterman Center for Digestive Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Background & Aims: Up to 25% of hepatocellular carcinomas (HCCs) seen in U.S. centers are of unknown etiology. Animal studies suggest that hypothyroidism can directly cause liver cell damage and might be a risk factor for HCC. We conducted a case-control study to evaluate the relationship between hypothyroidism and HCC.

Methods: Cases (n = 54) were HCC patients seen at Mayo Clinic Rochester in whom no underlying etiology for chronic liver disease could be determined. Two groups of controls were selected, HCC patients with HCV (n = 57) and HCC patients with alcoholic liver disease (n = 49). Hypothyroidism was defined as thyroid-stimulating hormone level >5.0, history of hypothyroidism before HCC diagnosis, or a history of being on thyroid replacement at the time of HCC diagnosis. We used multivariate logistic regression to model the relationship between hypothyroidism and HCC etiology.

Results: Of the 160 patients, 18 (11%) had a history of hypothyroidism. Twelve (22%) of those with no known etiology for HCC, 2 (4%) of those with HCV, and 4 (8%) of those with alcoholic liver disease had hypothyroidism. Patients with HCC of unknown etiology were significantly more likely to have a history of hypothyroidism as compared with HCC patients with HCV (adjusted odds ratio, 12.7; 95% confidence interval, 1.4-117.1) and as compared with all controls (adjusted odds ratio, 6.8; 95% confidence interval, 1.1-42.1).

Conclusions: Hypothyroidism is more prevalent in HCC patients with an unknown etiology. It should be further investigated as a potential risk factor in liver carcinogenesis.
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http://dx.doi.org/10.1016/j.cgh.2006.07.011DOI Listing
January 2007