High Prevalence of Hepatitis B and C Virus Infections Among Rohingya Refugees in Bangladesh: A Growing Concern for the Refugees and the Host Communities.

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Intestinal alkaline phosphatase deficiency increases the risk of diabetes.

INTRODUCTION: Our previous case-control study demonstrated that a high level of intestinal alkaline phosphatase (IAP), an endotoxin-detoxifying anti-inflammatory enzyme secreted by villus-associated enterocytes and excreted with stool, plays a protective role against type 2 diabetes mellitus (T2DM) irrespective of obesity. In the current study, we investigated the long-term effect of IAP deficiency (IAPD) on the pathogenesis of T2DM. RESEARCH DESIGN AND METHODS: A healthy cohort of participants without diabetes (30-60 years old), comprising 188 without IAPD (IAP level: ≥65 U/g stool) and 386 with IAPD (IAP level: <65 U/g stool), were followed up for 5 years. We measured stool IAP (STAP) and fasting plasma glucose, and calculated the risk ratio (RR) using log-binomial regression model. RESULTS: T2DM incidence rates were 8.0%, 11.7%, 25.6%, and 33.3% in participants with 'persistent no IAPD' (IAP level: always ≥65 U/g stool), 'remittent IAPD' (IAP level: increased from <65 U/g stool to ≥65 U/g stool), 'persistent IAPD' (IAP level: always <65 U/g stool), and 'incident IAPD' (IAP level: decreased from ≥65 U/g stool to <65 U/g stool), respectively. Compared with 'persistent no IAPD' the risk of developing T2DM with 'incident IAPD' was 270% higher (RR: 3.69 (95% CI 1.76 to 7.71), χ2 p<0.001). With 'persistent IAPD' the risk was 230% higher (RR: 3.27 (95% CI 1.64 to 6.50), p<0.001). 'Remittent IAPD' showed insignificant risk (RR: 2.24 (95% CI 0.99 to 5.11), p=0.0541). Sensitivity analyses of persistent IAP levels revealed that, compared with participants of the highest persistent IAP pentile (always >115 U/g stool), the rate of increase of fasting glycemia was double and the risk of developing T2DM was 1280% higher (RR: 13.80 (95% CI 1.87 to 101.3), p=0.0099) in participants of the lowest persistent IAP pentile (always <15 U/g stool). A diabetes pathogenesis model is presented. CONCLUSIONS: IAPD increases the risk of developing T2DM, and regular STAP tests would predict individual vulnerability to T2DM. Oral IAP supplementation might prevent T2DM.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. METHODS: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. RESULTS: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. CONCLUSIONS: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

Comparative role of tenofovir versus entecavir for treating patients with hepatitis B virus-related acute on chronic liver failure.

INTRODUCTION: The aim of the study was to compare the safety and efficacy of tenofovir versus entecavir for treatment of naive acute on chronic liver failure (ACLF) due to hepatitis B virus (HBV) (ACLF-B). METHODS: Thirty-two patients aged 14-65 years were enrolled in the study. Diagnosis of ACLF was confirmed by clinical condition, biochemical analysis, and virological data. The causes of both chronic liver damages and acute insult in all patients were HBV. They were expressing HBV DNA in the sera, positive for IgM anti-HBc, had increased levels of serum bilirubin, compromised prothrombin time; and more than 50% patients had encephalopathy. The standard dose of tenofovir and entecavir was given. RESULTS: The antiviral effects of tenofovir and entecavir were evident as most patients became negative for HBV DNA in the sera after 90 days of therapy. Also, the levels of serum bilirubin, CTP (Child-Turcotte-Pugh) and MELD (model for end-stage liver disease) score exhibited significant improvement due to antiviral therapy. Although the improvement of liver functions, and liver damages were detected in patients receiving both tenofovir and entecavir, the survival of the patients was significantly higher in those receiving tenofovir compared to entecavir-treated patients. CONCLUSION: This prospective study with limited number patients provides a challenge to assess the real potential of tenofovir over entecavir as therapeutic option for ACLF-B by conducting a multicenter clinical trial enrolling patient of different races and background.

Observational study on the response of tenofovir monotherapy versus tenofovir plus telbivudine dual therapy in patients with hepatitis B virus related acute on chronic liver failure.

INTRODUCTION: HBV is major health problem globally due to complications, including ACLF, cirrhosis and hepa¬tocellular carcinoma. ACLF due to exacerbation of CHB is associate with 30%-70% mortality. Reduction of HBV-DNA is therefore a target of therapy in ACLF-B. METHODS: Patients with spontaneous reactivation of HBV [(ALT >5×ULN or >2× baseline) and HBV-DNA >20,000 IU/ml] were randomized to Tenofovir mono therapy (300 mg/day) or Tenofovir plus Telbivudine (600 mg/day) dual therapy with standard care. Clinical and biochemical parameters were evaluated at baseline, 1 week, 4 weeks and at 3 months. Virological evaluation was done at baseline and at 3 months. Primary end points were reduction of HBV-DNA and resolution of ascites, as applied. Secondary end point was reduction of liver related complications, therapy related adverse effects and survival at 3 months. RESULTS: 27 patients were enrolled. 15 received mono therapy with Tenofovir and 12 received dual therapy (Tenofovir plus Telbivudine). Baseline parameters in 2 groups had no significant difference. In both groups there was significant improvement of S. bilirubin, ALT, INR, CTP score and MELD score. Only MELD score showed significant improvement in patient with dual therapy at 3 months in comparison to mono therapy. 11 patients on Tenofovir mono therapy (n=15) showed undetected HBV-DNA (91.7%) at 3 months and one patient had detectable HBV-DNA (<2,000 IU/ml). 10 patients on dual therapy (n=12) had undetectable HBV-DNA (100%). Ascites resolved in 3 patients in both groups. Patients receiving dual therapy showed significant improvement in AKI on follow up compared to those on Tenofovir mono therapy. Among 5 deaths, 3 received mono therapy with Tenofovir and 2 dual therapy. Predictors of mortality had high S. bilirubin, HBV-DNA, MELD score and CTP score. CONCLUSION: In spontaneous reactivation of HBV presenting as ACLF, combination of Telbivudine plus Tenofovir is safer with less nephrotoxicity and better outcomes.

Role of tenofovir and telbivudine in treatment of hepatitis B related acute on chronic liver failure.

INTRODUCTION: ACLF is characterized by acute deterioration of liver function in patients with chronic liver disease. HBV is one of the most important causes of both acute insult and underlying chronic liver disease in ACLF. Reactivation of HBV is one of the common causes of ACLF in our region. ACLF requires multiple organ support and is associated with high short and medium term mortality. This is the reason why early, rapid reduction of HBV DNA is essential in treating ACLF-B. METHODS: Consecutive patients of ACLF-B due to spontaneous reactivation of HBV (ALT> 5xULN or >2 x baseline and HBV DNA >20,000 IU/ml) were randomized into tenofovir group (300mg/day) and telbivudine group (600mg/day) along with standard medical treatment. Clinical and laboratory parameters were evaluated at baseline, day-7, day-14, day-30 and day-90. HBV DNA was evaluated at baseline and after three months of therapy. Primary end point was survival or death at three months. Secondary end point was improvement of liver function assessed by Child-Turcotte Pugh score and MELD score at three months. RESULTS: 30 patients were enrolled in the study and 15 of them received tenofovir and 15 patients received telbivudine. Most of the baseline parameters showed no difference except serum AST and serum creatinine level that showed statistically significant difference between two groups. After antiviral therapy both groups showed significant clinical improvement along with CTP and MELD scores. However statistically significant improvement between tenofovir and telbivudine groups was only seen with MELD score. Survival rate was 80% in tenofovir group and 60% in telbivudine group, but this was not statistically significant. Low serum albumin at baseline was predictor of mortality. CONCLUSION: In patients of ACLF-B, antiviral therapy with both tenofovir and telbivudine improve liver function, but there is no statistically significant difference in survival between tenofovir and telbivudine.

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

Effect of Granulocyte Colony-stimulating Factor and Erythropoietin on Patients with Acute-on-chronic Liver Failure.

INTRODUCTION: Patients with acute-on-chronic liver failure (ACLF) have low survival without liver transplantation. Granulocyte colony-stimulating factor (G-CSF) improves survival in ACLF and erythropoietin (EPO) promotes hepatic regeneration in animal studies. The aim of this study is to determine whether coadministration of G-CSF and EPO improves the outcome in ACLF. METHODS: The study was conducted in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka. Consecutive patients with ACLF were randomly assigned into group A and group B. Group A patients received subcutaneous G-CSF (5 mcg/kg/d) for 6 days and subcutaneous EPO (40 mcg/wk) for 4 weeks and group B patients received only standard medical care (control group). All patients were followed up for 3 months. The primary end point was to see survival at 3 months. RESULTS: Patients had comparable baseline characteristics; hepatitis B virus infection was the commonest etiology of ACLF as both acute and chronic events. A higher proportion of patients were male in both groups. The survival was higher in group A than in group B at the end of 3 months (36.4% vs 29.4%; p = 0.457), but this was not statistically significant. Regarding complications, hepatorenal syndrome was higher in group B than in group A (36.7% vs 41.7%). In both the groups, Child-Turcotte-Pugh score and model for end-stage liver disease scores were similar before treatment and improved during follow-up. CONCLUSION: This is one of the early human studies that demonstrate potential hepatic regeneration using EPO in ACLF patients. Further study with a larger cohort will be needed to reproduce the results of the present work. HOW TO CITE THIS ARTICLE: Haque Md N, Al-Mahtab M, Das DC, et al. Effect of Granulocyte Colony-stimulating Factor and Erythropoietin on Patients with Acute-on-chronic Liver Failure. Euroasian J Hepato-Gastroenterol 2020;10(2):64-67.

Correction to: Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update.

The article Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update, written by [Shiv Sarin], was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 06, 2019 without open access.

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients.

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and Hepatocellular Carcinoma.

INTRODUCTION: Hepatitis B virus (HBV) infection is an established cause of hepatocellular carcinoma (HCC) and is associated with poor prognosis. High HBV deoxyribonucleic acid (DNA) load has been identified in HCC and hepatitis B surface antigen-positive patients. MATERIALS AND METHODS: This study was done in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from January 2006 to December 2007. Thirty patients with HBV infection-related HCC were enrolled. Another 30 patients with HBV-related liver diseases without HCC were analyzed as controls. RESULTS: The HCC patients had a high viral load (>105 copies/mL), while all of the controls had low (<105 copies/mL) viral load. CONCLUSION: It seems that patients with HCC bear high HBV DNA loads in Bangladesh, but the causes underlying this remain to be resolved.How to cite this article: Hussain MM, Al Mahtab M, Islam S, Ahmed N, Rahman S, Khan M. Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and Hepatocellular Carcinoma. Euroasian J Hepato-Gastroenterol 2017;7(1):111-112.

Therapeutic implications of granulocyte colony stimulating factor in patients with acute-on-chronic liver failure: increased survival and containment of liver damage.

BACKGROUND AND PURPOSE: Mobilization of bone marrow-derived stem cells by granulocyte colony stimulating factor (G-CSF) supports hepatic regeneration and may augment clinical improvement in patients with acute-on-chronic liver failure (ACLF). The aim of this study is to assess the impact of G-CSF on complications and transplant-free survival in patients with ACLF. METHODS: Thirty-two patients with ACLF defined by Asian Pacific Association for the Study of the Liver (APASL) criteria were openly randomized to control (group A) or intervention (group B) receiving G-CSF (5 µg/kg/day, for 6 consecutive days) in addition to standard medical therapy with antiviral drugs. The patients were followed for 90 days. RESULTS: Simultaneous use of G-CSF and antiviral drugs in hepatitis B virus (HBV) ACLF significantly improved survival over antiviral drugs alone. Incidence of hepatorenal syndrome and hyponatremia were reduced due to use of G-CSF. Baseline parameters of the two groups of patients were comparable. Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD), disease severity scores improved in patients treated with G-CSF, with significant difference only for the CTP score at 90 days follow-up. In addition, mean white blood cell (WBC) count at day 15 was significantly higher in G-CSF group in absence of infection compared with control group. CONCLUSIONS: G-CSF therapy improved survival and clinical recovery in HBV-ACLF. G-CSF therapy also prevented renal failure and hyponatremia. We strongly recommend use of G-CSF therapy in addition to standard medical therapy.

Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of 'golden window': A prospective study.

BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis. METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death. RESULTS: Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P < 0.001). CONCLUSION: Liver failure predicts the development of SIRS. New onset SIRS in the first week is an important determinant of early sepsis, organ failure, and survival. Prompt interventions in this 'golden window' before development of sepsis may improve the outcome of ACLF.

Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure.

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. CONCLUSIONS: The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure.

Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study.

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLS-DA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance (ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the Mann-Whitney U test was used to compare metabolite levels depending on hepatitis B e-antigen (HBeAg) status and treatment with anti-viral therapy. A Benjamini-Hochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05. RESULTS: There were significant differences in age (P < 0.001), weight (P < 0.001), and body mass index (P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase (ALT) was significantly higher in the HCC group compared to controls (P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group (P = 0.004). A three-factor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine (DMA), formate, glycine, hippurate, and trimethylamine-N-oxide (TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBeAg negative patients showed a significant increase in creatinine (P = 0.001) compared to HBeAg positive patients in the chronic hepatitis B subgroup, whilst HBeAg negative patients showed a significant decrease in DMA (P = 0.004) in the cirrhosis subgroup compared to HBeAg positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.

The Evaluation of Serum Ascites Albumin Gradient and Portal Hypertensive changes in Cirrhotic Patients with Ascites.

INTRODUCTION: Ascites is a common complication of chronic liver diseases and is related to the extent of portal hypertension. This study evaluated whether the serum ascites albumin gradient (SAAG) (the difference between the albumin level of serum and of ascitic fluid) is endowed with clinical implications. MATERIALS AND METHODS: This is a prospective study involving 50 patients with cirrhosis of liver with ascites. The SAAG was measured in all patients and its relation with portal hypertensive changes was analyzed. RESULTS: Based on SAAG values, the patients were divided into three groups: Group 1 - SAAG value 1.1 to 1.49 gm/dL (n = 15); group 2 - SAAG value 1.5 to 1.99 gm/dL (n = 9); and group 3 - SAAG value 2.0 gm/dL (n = 26). In group 1, 14 patients had esophageal varices (93.3%) and 13 had gastropathy (86.6%). In group 2, all 9 patients had esophageal varices (100%), 7 (77.7%) had gastropathy, and 1 (11.1%) had gastric varices. In group 3, all 26 patients had esophageal varices (100%), 24 patients (92.3%) had gastropathy, and 1 patients (3.8%) had gastric varices. CONCLUSION: Serum ascites albumin gradient value is weakly related to the extent of portal hypertension in patients with liver cirrhosis and its implication seems to be limited in clinics. HOW TO CITE THIS ARTICLE: Shahed FHM, Al-Mahtab M, Rahman S. The Evaluation of Serum Ascites Albumin Gradient and Portal Hypertensive changes in Cirrhotic Patients with Ascites. Euroasian J Hepato-Gastroenterol 2016;6(1):8-9.

Biochemical Scoring System for diagnosing Nonalcoholic Steatohepatitis.

Noor-E-Alam M, Alam S, Alam AKMK, Al Mahtab M, Rahman S. Biochemical Scoring System for diagnosing Nonalcoholic Steatohepatitis. Euroasian J Hepato-Gastroenterol 2016;6(2):202-204.

Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder to cause Chronic Liver Disease.

The Budd-Chiari syndrome (BCS) is a rare disorder due to chronic liver disease (CLD), which is caused by the obstruction of hepatic venous outflow that can be located at any place from the small hepatic venules up to the entrance of the inferior vena cava (IVC) into the right atrium. Among the causes of BCS, the rarer one is coagulation factor deficiencies. Here, we report a case of BCS associated with deficiency of protein C resulting in thrombus in IVC. The patient was a 50-year-old male, who had been suffering from recurrent abdominal and leg swelling for a long period of 7 years. He was evaluated thoroughly, and other causes of liver cirrhosis were excluded. HOW TO CITE THIS ARTICLE: Begum R, Al Mahtab M, Al Mamun A, Moben AL, Hossain SMS, Das DC, Malakar D, Rashid HO, Roy PP, Rahman S. Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder to cause Chronic Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):194-197.

Abdominal cystic echinococcosis in Bangladesh: a hospital-based study.

INTRODUCTION: Cystic echinococcosis (CE) is reported from nearly all geographic areas of Bangladesh, but little information is available on its epidemiologic and clinical features. The aim of this study was to describe the clinical manifestations of hepatic and abdominal CE cases presenting to tertiary referral hospitals in Dhaka, Bangladesh. METHODOLOGY: A retrospective study was conducted via chart reviews of hepatic and abdominal CE patients under care at tertiary referral hospitals in Dhaka, Bangladesh, between 2002 and 2011. Age, sex, education level, occupation, urban versus rural residence, drinking water source, history of dog ownership, cyst type and location, and clinical manifestations were recorded for all patients. RESULTS: Of the 130 patients enrolled, 92 (70.8%) were female and 38 (29.2%) were male. The majority of patients were from rural (76.2%) rather than urban (23.8%) areas. All cases were from the northern part of the country, with no cases reported from the south or southeast. Most patients were between 21 and 40 years of age. A total of 119 patients (91.5%) had cysts only in the liver, with the remaining 8.5% having cysts in both the liver and lungs or in the abdominal cavity. Seventy-six (58.5%) of the hepatic cysts were stage CE1, indicating recent infection. CONCLUSIONS: Active transmission of Echinococcus granulosus appears to be occurring in Bangladesh, as indicated by the high number of CE1 hepatic cysts seen at tertiary care hospitals. Community ultrasound screening studies are warranted to better define the distribution of cases and risk factors for parasite transmission.