NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease (NAFLD) fibrosis score can predict all-cause mortality, cardiac complications, and/or liver complications of patients with NAFLD over long-term follow-up.A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project. The NAFLD fibrosis score (NFS) was used to separate NAFLD patients with and without advanced liver fibrosis. We used the NFS score to classify the probability of fibrosis as -1.5 to 0.67 for high probability. Primary endpoints included all-cause death and cardiovascular- and/or liver-related mortality. From the 479 patients with NAFLD assessed, 302 patients (63%) greater than 18 years old were included. All patients were followed, and medical charts were reviewed until August 31, 2009 or the date when the first primary endpoint occurred. By using a standardized case record form, we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period.A total of 302/479 (63%) NAFLD patients (mean age: 47 ± 13 year) were included with a follow-up period of 12.0 ± 3.9 year. A low probability of advanced fibrosis (NFS -1.5) was found in 121 patients (40%). At the end of the follow-up period, 55 patients (18%) developed primary endpoints. A total of 39 patients (13%) died during the follow-up. The leading causes of death were non-hepatic malignancy (n = 13/39; 33.3%), coronary heart disease (CHD) (n = 8/39; 20.5%), and liver-related mortality (n = 5/39; 12.8%). Thirty patients had new-onset CHD, whereas 8 of 30 patients (27%) died from CHD-related causes during the follow-up. In a multivariate analysis, a higher NFS at baseline and the presence of new-onset CHD were significantly predictive of death (OR = 2.6 and 9.2, respectively; P < 0.0001). Our study showed a significant, graded relationship between the NFS, as classified into 3 subgroups (low, intermediate and high probability of liver fibrosis), and the occurrence of primary endpoints. The use of metformin or simvastatin for at least 3 mo during the follow-up was associated with fewer deaths in patients with NAFLD (OR = 0.2 and 0.03, respectively; P < 0.05). Additionally, the rate of annual NFS change in patients with an intermediate or high probability of advanced liver fibrosis was significantly lower than those patients with a low probability of advanced liver fibrosis (0.06 vs 0.09, P = 0.004). The annual NFS change in patients who died was significantly higher than those in patients who survived (0.14 vs 0.07, P = 0.03). At the end of the follow-up, we classified the patients into 3 subgroups according to the progression pattern of liver fibrosis by comparing the NFS at baseline to the NFS at the end of the follow-up period. Most patients were in the stable-fibrosis (60%) and progressive-fibrosis (37%) groups, whereas only 3% were in the regressive fibrosis.A higher NAFLD fibrosis score at baseline and a new onset of CHD were significantly predictive of death in patients with NAFLD

Outcome of patients with primary sclerosing cholangitis and ulcerative colitis undergoing colectomy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To study the outcomes of primary sclerosing cholangitis (PSC) patients with ulcerative colitis (UC) undergoing colectomy.We identified 193 patients with PSC and UC undergoing colectomy at the Mayo Clinic (Rochester, MN, United States), between January 1, 1995 and December 31, 2008 using a computerized record system. Eighty-nine patients were excluded due to unclear diagnosis, liver transplantation prior to colectomy, age less than 18 years, inadequate follow-up data or known cases of cholangiocarcinoma. We retrospectively reviewed data from patient medical records. Clinical information, date of colectomy, preoperative and follow-up liver tests and pathological findings of the colon were reviewed. The Mayo risk score at baseline was calculated to obtain survival estimates for up to 4 years of follow-up. The primary endpoint was defined by the presence of all-cause mortality and/or liver decompensation requiring liver transplantation. All patients who did not have a clinical note on December 31, 2008 were considered as patients with an incomplete follow-up unless they reached a study endpoint (death or underwent liver transplantation) prior to that date. The study was approved by the Institutional Review Boards of the Mayo Clinic.Of the 2441 patients with PSC observed in this period, 104 patients (4.3%) had UC and underwent colectomy and were included. The median age was 43.2 years, and 67% were male. The leading indications for colectomy were severe colonic inflammation (49%), the presence of colonic dysplasia during routine surveillance (42%) and bowel perforation (3%). Twenty-six patients were lost to follow-up after a median duration of 3.9 years. The remaining 78 patients included 52 patients (66.7%) who were followed for a median duration of 5.5 years and 26 patients (33.3%) who developed primary endpoints including death (n = 13) or underwent liver transplantation (n = 13) with a median follow up of 2.6 years. For the secondary endpoint, the liver complications within 1 mo following the colectomy were found in 9 patients (8.6%) and included worsening liver tests (n = 3), liver failure requiring liver transplantation (n = 2), acute cholangitis (n = 3) and right hepatic vein thrombosis with hepatic infarct (n = 1). A multivariate logistic analysis demonstrated that only lower platelet count and lower albumin level preoperatively were significantly associated with more primary endpoints (OR = 0.99 and 0.05 respectively).One third of patients with PSC and UC undergoing colectomy died or underwent liver transplantation within 2.6 years. PSC patients with lower platelet counts and lower albumin levels were significantly more likely to have a poorer outcome

Cost-utility analysis of non-contrast abbreviated magnetic resonance imaging for hepatocellular carcinoma surveillance in cirrhosis

Background/Aims: Ultrasonography has a low sensitivity for detecting early-stage hepatocellu- lar carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic pa- tients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Methods: Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality- adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of USD 4,665 (160,000 Thai Baht) in Thailand and USD 50,000 in the United States. Results: aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of USD 3,667/QALY in Thailand and USD 37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sen- sitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Conclusions: Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, espe- cially in those with high HCC risks

Non-invasive tests for liver fibrosis assessment in patients with chronic liver diseases: a prospective study

There is an urgent need of non-invasive tests (NITs) for monitoring treatment response and disease progression in chronic liver disease. Liver stiffness (LS) evaluated by transient elastography (TE), shear wave elastography (SWE), and magnetic resonance elastography (MRE) and serum markers e.g. APRI and FIB-4 scores were assessed at baseline and the 1-year follow-up. In all, 89 chronic hepatitis C virus (HCV) patients with sustained virological response and 93 non-alcoholic fatty liver disease (NAFLD) patients were included. There was a significantly strong correlation among imaging techniques. Using MRE as the reference standard, the area under the receiver operating characteristics curves for TE, SWE, APRI, and FIB-4 in detecting stage1–4 fibrosis were 0.88–0.95, 0.87–0.96, 0.83–0.89, and 0.79–0.92, respectively. In chronic HCV patients, the values of TE, SWE, MRE, APRI and FIB-4 significantly decreased from baseline to the 1-year follow-up. Liver steatosis did not significantly change over time. In NAFLD, compared to obese patients, non-obese patients had less LS and steatosis at baseline, and these values did not show significant changes at the 1-year follow-up. Our study suggests that the current NITs have a good correlation and accuracy in monitoring the treatment outcomes in patients with chronic liver diseases

Regional differences in admissions and treatment outcomes for hepatocellular carcinoma patients in Thailand

Background: Hepatocellular carcinoma (HCC) is one of the commonest cancers in Thailand. We report the stage and survival of patients who were admitted under the public universal health fund (NHSO) covering 47 million people to determine if there were regional disparities in the treatment outcomes in the country. Method: We used the 2009-2013 Nationwide Hospital Admission Data, Thailand. Patients with hepatocellular carcinoma (HCC) were identified by the ICD10 code C22.0. Procedures were identified by ICD9-CM codes, and deaths were confirmed from the NHSO database and the national citizen registry. Thailand is divided into 6 regions and Bangkok. Hospitals were identified according to their specific reimbursement codes. Survival time started from the day of first admission and was estimated using the Kaplan-Meier method. The statistical method used to compare regions was Chi-squared tests (Pearson, likelihood ratio, linear-by linear association and Mantel-cox). Results: There were 36,956 HCC patients admitted during the study period. The overall median survival was 36 days. 1.63% of the patients had surgery, 0.96% had radiofrequency ablation (RFA), and 5.24% had trans-arterial chemoembolization (TACE). 90.24% did not have any tumor-specific therapy. The proportion of patients admitted for tumor-specific therapy vs. no tumor-specific therapy was significantly different between regions in all treatment modalities (p<0.01). Each treatment modality showed a wide range of median survival values across the regions (p<0.01). The best survival was seen in Bangkok, the South and the North (for surgery, RFA and TACE) and was often more than twice as long as the regions with the lowest survival, Central, East and West. Conclusions: There was a large previously-unreported disparity in admissions and outcomes in Thailand for different treatment modalities for HCC. Bangkok and the South had the best treatment outcomes and often had median survivals more than twice as long as those in the West and East. Public policy to reduce this disparity will need to be implemented in the future

Changes in hepatic fibrosis and vitamin D levels after viral hepatitis C eradication using direct-acting antiviral therapy

Background: Vitamin D (VD) is important in hepatic fibrogenesis in animal models and human studies. VD deficiency is associated with liver fibrosis progression. Metabolic dysfunction of the liver, as an intermediate organ for VD metabolism, contributes partly to this deficiency. We hypothesized that improving hepatic fibrosis and inflammation in chronic hepatitis C (CHC) patients after eradication with direct-acting antivirals (DAA) would increase 25-hydroxyVD [25(OH)VD] levels. Methods: Eighty CHC patients (17 chronic hepatitis, and 63 cirrhosis) were enrolled. Baseline characteristics, hepatitis C viral load (VL), genotypes, liver enzymes and liver stiffness measurements (LSM) were assessed at baseline. Blood samples for 25(OH)VD and the procollagen type III N-terminal peptide (P3NP) were collected at baseline, 24 and 48 weeks. LSMs were re-evaluated at 48 weeks. Serum 25(OH)VD levels < 30 ng/mL were defined as VD insufficiency/deficiency. Paired t-tests were used for statistical analyses. Results: Among 80 patients, the mean age was 57.7 ± 10.5 years, and 52.5% were men. The mean VL was 6.1 ± 0.7 logIU/mL with genotype 1 predominance (55%). All patients achieved sustained virological response. The alanine aminotransferase levels decreased from 79.9 ± 53.3 U/L at baseline to 25.7 ± 17.2 and 22.3 ± 11.0 U/L at 24 and 48 weeks, respectively (p < 0.001). The mean LSM decreased from 19.2 ± 15.3 to 11.7 ± 8.0 kPa at 48 weeks (p < 0.001). The P3NP levels decreased from 43.6 ± 22.0 ng/mL before treatment to 35.7 ± 21.1 and 29.4 ± 15.0 ng/mL at 24 and 48 weeks, respectively (p < 0.001). The proportions of VD insufficiency/deficiency were 72.5%, 91.3%, and 86.5% at baseline, 24 and 48 weeks, respectively. The 25(OH)VD levels decreased from 26.3 ± 10.7 ng/mL at baseline to 20.8 ± 8.1 and 20.8 ± 8.5 ng/mL at 24 and 48 weeks, respectively (p < 0.001). Conclusions: Curative treatment with DAA attenuated the liver stiffness and inflammation but did not improve VD levels. Over 80% of patients remained VD insufficient/deficient. Whether VD replacement during and after DAA therapy can improve hepatic fibrosis remains unclear. Trial registration The Thai Clinical Trial Registry as TCTR20161025001 (31 October 2016). http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=2136

Effect of vitamin D supplementation in patients with chronic hepatitis C after direct-Acting antiviral treatment a randomized, double-blind, placebo-controlled trial

Background Replacement of vitamin D (VD) among patients with chronic hepatitis C (CHC) before viral eradication has demonstrated a protective effect on serum markers associated with hepatic fibrogenesis. We therefore hypothesized that VD may facilitate further fibrosis amelioration following curative treatment with direct-Acting antivirals (DAA). Methods. This study was a randomized, double-blind, placebo-controlled trial con-ducted between February 2018 and August 2018. Patients with CHC and VD deficiency were randomized in a 1:1 ratio to either receive ergicalciferol or placebo over 6 weeks. Biochemical analysis indicators, including 25-hydroxyvitamin D (25(OH)D), fibrogenic markers [(transforming growth factor beta 1 (TGF-1) and tissue in-hibitors of matrix metalloproteinases 1 (TIMP-1)], and fibrolytic markers [matrix metalloproteinase 9 (MMP-9) and amino terminal type III procollagen peptide (P3NP)], were assessed at baseline and at 6 weeks. Serum 25(OH)D was analyzed by a chemiluminescence immunoassay. Serum hepatic fibrogenesis markers were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Results. Seventy-five patients with CHC and VD deficiency were randomly assigned to VD (nD37) and placebo (nD38) groups. At the end of the study, the mean serum 25(OH)D level had risen to a normal level in the VD group, but was still deficient in the placebo group (41.8 9.1 vs. 18.1 4.6 ng/mL, p 0.001). Upon restoration of the VD level, there were no significant mean differences in the change from baseline for TGF-1 (0.6 ng/mL (95% confidence interval (95% CI) [2.81.7]), pD0:63), TIMP-1 (5.5 ng/mL (95% CI [26.4 15.3]), pD0:60), MMP-9 (122.9 ng/mL (95% CI [69.0 314.8]), pD0:21), and P3NP (0.1 ng/mL (95% CI [2.4 2.2]), pD0:92) between the VD and placebo groups. Conclusion. Short-Term VD supplementation after DAA treatment in patients with CHC does not improve serum fibrogenesis markers and may not expedite the residual liver fibrosis healing process. Future studies are warranted to evaluate the long-Term effect of VD supplementation on hepatic fibrosis regression

The incidence, etiologies, outcomes, and predictors of mortality of acute liver failure in Thailand: a population-base study

Background: Acute liver failure (ALF) is uncommon but progresses rapidly with high mortality. We investigated the incidence, etiologies, outcomes, and predictive factors for 30-day mortality in patients with ALF. Methods: We conducted a population-based study of ALF patients hospitalized between 2009 and 2013 from the Thai Nationwide Hospital Admission database, which comprises 76% of all admissions from 858 hospitals across 77 provinces in Thailand. ALF was diagnosed using ICD-10 codes K72.0 and K71.11. Patients with liver cirrhosis were excluded. Results: There were 20,589 patients diagnosed with ALF during the study period with 12,277 (59.6%) males and mean age of 46.6 ± 20.7 years. The incidence of ALF was 62.9 per million population per year. The most frequent causes of ALF were indeterminate (69.4%), non-acetaminophen drug-induced (26.1%), and viral hepatitis (2.5%). Acetaminophen was the presumptive cause in 1.7% of patients. There were 5502 patients (26.7%) who died within 30 days after admission. One patient (0.005%) underwent liver transplantation. The average hospital stay was 8.7 ± 13.9 days, and the total cost of management was 1075.2 ± 2718.9 USD per admission. The most prevalent complications were acute renal failure (ARF)(24.2%), septicemia (18.2%), and pneumonia (12.3%). The most influential predictive factors for 30-day mortality were ARF (HR = 3.64, 95% CI: 3.43–3.87, p < 0.001), malignant infiltration of the liver (HR = 3.37, 95% CI: 2.94–3.85, p < 0.001), and septicemia (HR = 1.96, 95%CI: 1.84–2.08, p < 0.001). Conclusions: ALF patients have poor outcomes with 30-day mortality of 26.7% and high economic burden. Indeterminate etiology is the most frequent cause. ARF, malignant infiltration of the liver, and septicemia are main predictors of 30-day mortality

Urine Liver-Type Fatty Acid Binding Protein; Biomarker for Diagnosing Acute Kidney Injury and Predicting Mortality in Cirrhotic Patients

Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients. Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality. Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uL-FABP ≥ 4.68 ng/mL (odd ratio 4.15, p=0.02). Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP ≥ 4.68 ng/mL was a significant independent predictor for 28-day mortality

Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications

Severe malaria has a high mortality rate (15–20%) despite treatment with effective antimalarial drugs. Adjunctive therapies for severe malaria that target the underlying disease process are therefore urgently required. Adhesion of erythrocytes infected with Plasmodium falciparum to human cells has a key role in the pathogenesis of life-threatening malaria and could be targeted with antiadhesion therapy. Parasite adhesion interactions include binding to endothelial cells (cytoadherence), rosetting with uninfected erythrocytes and platelet-mediated clumping of infected erythrocytes. Recent research has started to define the molecular mechanisms of parasite adhesion, and antiadhesion therapies are being explored. However, many fundamental questions regarding the role of parasite adhesion in severe malaria remain unanswered. There is strong evidence that rosetting contributes to severe malaria in sub-Saharan Africa; however, the identity of other parasite adhesion phenotypes that are implicated in disease pathogenesis remains unclear. In addition, the possibility of geographic variation in adhesion phenotypes causing severe malaria, linked to differences in malaria transmission levels and host immunity, has been neglected. Further research is needed to realise the untapped potential of antiadhesion adjunctive therapies, which could revolutionise the treatment of severe malaria and reduce the high mortality rate of the disease