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

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

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat

The predictors of complications in patients with drug-induced liver injury caused by antimicrobial agents

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Antimicrobials are the leading cause of idiosyncratic drug-induced liver injury in most series. AIM: To determine the incidence and the predictors of complications in patients with drug-induced liver injury caused by antimicrobial agents requiring hospitalization. METHODS: Medical records of patients with drug-induced liver injury caused by antimicrobial agents were identified by ICD-10, for the period between 2002 and 2006. Clinical information and blood tests during hospitalization were recorded. The causality assessment of drug-induced liver injury was determined by the Roussel UCLAF causality assessment method (RUCAM) scale. RESULTS: Of 47 594 in-patient admissions per year, the annual incidence of drug-induced liver injury was 0.03%. Male: female ratio was 7:3 with a median age of 47 years. Eighty reactions of drug-induced liver injury were caused by anti-tuberculosis drugs (85%) and by antibiotics (15%). The median (IQR) of RUCAM scale was 6 (5-8). A total of 36% had HIV infection and 9% of patients had diabetes mellitus. Median (IQR) duration of hospitalization was 9 (5-15) days. Serious complications and death were found in 27.5% and 26%, respectively. By a multivariable logistic analysis, the presence of jaundice was found to be significantly associated with an unfavourable outcome. CONCLUSION: Although rare, antimicrobial agents-related drug-induced liver injury requiring hospitalization has a high mortality rate. The presence of jaundice predicts poor outcome

Health care burden and mortality of acute on chronic liver failure in Thailand: a nationwide population-based cohort study

Background Accurate population-based data are required concerning the rate, economic impact, and long-term outcome from acute on chronic liver failures (ACLF) in hospitalized patients with cirrhosis. We aimed to discover time trends for the epidemiology, economic burden, and mortality of ACLF in Thailand. Methods We conducted a nationwide, population-based, cohort study which involved all hospitalized patients with cirrhosis in Thailand during the period between 2009 and 2013, with data from the National Health Security Office. ACLF was defined by two or more extrahepatic organ failures in patients with cirrhosis. Primary outcomes were trends in hospitalizations, hospital costs, together with inpatient mortality. Results The number of ACLF hospitalizations in Thailand doubled between 3185 in 2009 and 7666 in 2013. The average cost of each ACLF hospitalization was 3.5-fold higher than for cirrhosis (USD 1893 versus USD 519). The hospital is paid using a diagnosis-related group (DRG) payment system that is only 15% of the average treatment costs (USD 286 from USD 1893). The in-hospital fatality rate was 51% for ACLF while the additional fatality rate was 85% up to 1 year. The ACLF organ failure trends indicated sepsis with septic shock and renal failure as the majority proportion. Age, the number and types of organ failure and male sex were predictors of ACLF death. Conclusions and relevance Cirrhosis and ACLF both represent substantial and increasing health and economic burdens for Thailand. These data can assist national health care policy stakeholders to target high-risk patients with cirrhosis for care