An observational study describing the number and type of chronic conditions and medications taken by diabetic patients with NAFLD and identifying characteristics that may impact liver disease severity or clinical management.Adults with type 2 diabetes have a high prevalence of nonalcoholic fatty liver disease (NAFLD) and increased risk of developing advanced liver disease. Appropriate management should consider the characteristics of the diabetic NAFLD population, as comorbid conditions and medications may increase the complexity of treatment strategies.Diabetic patients with NAFLD at risk of clinically significant liver disease (as assessed by the FIB-4 or NAFLD fibrosis scores) were recruited consecutively from the Endocrine clinic or primary care. Medical conditions, medication history, anthropometric measurements, and laboratory tests were obtained during assessment. NAFLD severity was classified by transient elastography and liver ultrasound into "no advanced disease" (LSM < 8.2 kPa) or "clinically significant liver disease" (LSM ≥ 8.2 kPa).The most common coexistent chronic conditions were metabolic syndrome (94%), self-reported "depression" (44%), ischaemic heart disease (32%), and obstructive sleep apnoea (32%). Polypharmacy or hyperpolypharmacy was present in 59% and 31% of patients respectively. Elevated LSM (≥ 8.2 kPa) suggesting significant liver disease was present in 37% of this at-risk cohort. Increasing obesity and abdominal girth were both independently associated with likelihood of having significant liver disease.There is a high burden of multimorbidity and polypharmacy in diabetic NAFLD patients, highlighting the importance of multidisciplinary management to address their complex health care needs and ensure optimal medical treatment.
Endocrine Disorders (2), Neuroscience (1), Cardiovascular Diseases (1) Liver Diseases (6), Diabetes Mellitus, Type 2 (2), Fibrosis (1), more mentions
AbstractText: To evaluate the association of lifestyle with the development of alcoholicliverdisease (ALD) or alcoholic pancreatitis (AlcP) AbstractText: A case-control study was conducted on 80 patients attending a tertiary university hospital, subdivided into three groups: ALD (n = 34), AlcP (n = 21) and a ... Keyword: alcoholicliverdisease.
Reply to the Letter to the Editor (HEP-17-1029) in regards to the paper on "An Endoplasmic Reticulum Protein, Nogo-B, Facilitates AlcoholicLiverDisease Through Regulation of Kupffer Cell Polarization"..
BACKGROUND & AIMS: Chronic hepatitis affects phenotypes of innate and adaptive immune cells. Mucosal associated invariant T (MAIT) cells are enriched in the liver as compared to the blood, respond to intra-hepatic cytokines, and (via the semi-invariant T-cell receptor) to bacteria translocated from the gut. Little is known about the role of MAIT cells in livers of patients with chronic hepatitis C virus (HCV) infection and their fate after antiviral therapy.
METHODS: We collected blood samples from 42 patients with chronic HCV infection who achieved a sustained virologic response after 12 weeks of treatment with sofosbuvir and velpatasvir. Mononuclear cells were isolated from blood before treatment, at weeks 4 and 12 during treatment, and 24 weeks after the end of treatment. Liver biopsies were collected from 37 of the patients prior to and at week 4 of treatment. Mononuclear cells from 56 blood donors and 10 livers that were not suitable for transplantation were used as controls. Liver samples were assessed histologically for inflammation and fibrosis. Mononuclear cells from liver and blood were studied by flow cytometry and analyzed for responses to cytokine and bacterial stimulation.
RESULTS: The frequency of MAIT cells among T cells was significantly lower in blood and liver samples of patients with HCV infection than of controls (median 1.31% vs 2.32% for blood samples, P=.0048 and median 4.34% vs 13.40% for liver samples, P=.001). There was an inverse correlation between the frequency of MAIT cells in the liver and histologically determined levels of liver inflammation (r=-.5437, P=.0006) and fibrosis (r=-.5829, P=.0002). MAIT cells from the liver had higher levels of activation and cytotoxicity than MAIT cells from blood (P<.0001). Production of interferon gamma (IFNG) by MAIT cells was dependent on monocyte-derived interleukin 18 (IL18), and was reduced in patients with HCV infection in response to T-cell receptor-mediated but not cytokine-mediated stimulation, as compared to controls. Anti-viral therapy rapidly decreased liver inflammation and MAIT cell activation and cytotoxicity, and increased the MAIT cell frequency among intra-hepatic but not blood T cells. The MAIT cell response to T-cell receptor-mediated stimulation did not change during the 12 weeks of antiviral therapy.
CONCLUSIONS: In analyses of paired blood and liver samples from patients with chronic HCV infection before, during and after antiviral therapy with sofosbuvir and velpatasvir, we found that intrahepatic MAIT cells are activated by monocyte-derived cytokines and depleted in HCV-induced liver inflammation.
Infectious Diseases (3), Immune System Diseases (3) Infections (5), Fibrosis (2), Cirrhosis (1), more mentions
BACKGROUND & AIMS: Little is known about the absolute risk of hepatocellular carcinoma (HCC) and liver-disease related death, in association with metabolic risk factors, for patients with hepatitis B virus (HBV) infection.
METHODS: We collected data from 5373 male Taiwanese civil servants who visited Taiwan's Government Employees' Central Clinics and received routine free physical examinations from 1989 through 1992. We obtained information on liver-related morbidity and mortality in HBV carriers, 40-65 years of age (n=1690), with different metabolic risk factors. We compared their medical histories with those of study participants without HBV or HCV infection in the same age range (n=1289). We used patients' baseline data on obesity, diabetes, hypertriglyceridemia, and high blood pressure to assign them to metabolic risk categories. We then performed a case-cohort analysis of the effects of hepatitis B viral factors on risk for HCC, based on metabolic factors and insulin resistance.
RESULTS: Over a median follow-up period of 19 years, 158 of the 1690 HBV carriers developed HCC and 126 died from liver-related diseases. Among participants without HBV or HCV infection, only 6 developed HCC or died from liver-related disease. HBV carriers with different metabolic risk factors had significant differences in cumulative incidence of HCC and liver-related death. Patients with 3 or more metabolic risk factors had a substantially higher risk for HCC (10-year cumulative incidence, 13.60%) than patients with a low metabolic risk profile (10-year cumulative incidence, 4.83%; adjusted-hazard ratio, 2.32; 95% CI, 1.18-4.54). Smoking had a significant effect on this association (Pinteraction = .0044). Having 3 or more metabolic risk factors, compared with no factors, significantly increased the risk of HCC (adjusted-hazard ratio, 5.06; 95% CI, 2.23-11.47) and 10-year cumulative incidence of HCC (25.0% in smokers with 3 or more metabolic risk factors vs 3.87% in smokers with none; P < .0001) in smokers, but did not increase risk of HCC in nonsmokers. Metabolic risk factors and insulin resistance had the largest effect on HCC risk in patients with levels of HBV-DNA <10,000 copies/mL.
CONCLUSIONS: In a study of men with chronic HBV infection ages 40-65 years in Taiwan, we associated a high burden of metabolic risk factors with increased risk of HCC; smoking has a significant effect on this association.
Endocrine Disorders (3), Infectious Diseases (3), Cardiovascular Diseases (1) Infections (4), Hepatocellular Carcinoma (2), Hepatitis B (2), more mentions
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Women with polycystic ovary syndrome (PCOS) were treated with the GLP-1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT) and the prevalence of nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled, randomized clinical trial 72 women with PCOS, with a BMI > 25 kg/m(2) and/or insulin resistance, were treated with liraglutide or received placebo 1.8 mg/d (2:1) for 26 weeks. Liver fat content was assessed by (1) HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test. Compared with placebo, liraglutide treatment reduced body weight by 5.2 kg (5.6%), liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two-thirds (all P < .01). Sex-hormone-binding-globulin (SHBG) levels increased by 19% (P = .03), and free testosterone decreased by 19% (P = .054). HbA1c, fasting glucose and leptin were reduced (all: P < .05), whereas measures of insulin resistance, adiponectin and glucagon did not change. In conclusion, 26 weeks of liraglutide treatment in PCOS resulted in significant reductions in liver fat content, VAT and the prevalence of NAFLD.
PURPOSE: To explore the role of glucose as a stimulation agent in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) for liver cirrhosis and hepatocellular carcinoma (HCC).
MATERIALS AND METHODS: Twenty HCC patients with cirrhosis and 10 healthy volunteers were recruited. BOLD fMRI was performed for all participants prior to and 30 min after oral administration of glucose to measure the T2* values of normal liver parenchyma, HCC liver parenchyma, HCC center, and HCC edge. Variations of the T2*(△T2*) before and after administration were calculated.
RESULTS: Data from 16 patients and 10 healthy volunteers were reported. Before and after oral administration of glucose, T2* values of the normal liver parenchyma, HCC liver parenchyma, and HCC center were statistically different (p < 0.01), while no statistical difference was found in T2* value of the HCC edge (p = 0.35). △T2* values of the normal liver parenchyma, HCC liver parenchyma, HCC center, and HCC edge were 2.8 ± 1.1 ms, -1.3 ± 1.2 ms, -2.1 ± 1.8 ms, and 0.8 ± 3.2 ms before and after administration, respectively. △T2* value was statistically different in the liver parenchyma between healthy volunteers and HCC patients and between HCC center and HCC edge (both p < 0.01).
CONCLUSION: Use of glucose as the stimulation agent in BOLD fMRI may facilitate the assessment of liver function for patients with liver cirrhosis. The potential of △T2* to correlate with severity of liver cirrhosis, as well as to evaluate hepatic artery perfusion and bioactivity of HCC center should be further investigated.
Liver Cirrhosis (4), Hepatocellular Carcinoma (2), Cirrhosis (1), more mentions
After an initial exposure, subjects can develop test-taking/learning strategies called the "test sophistication effect. Cirrhotics wth prior overt hepatic encephalopathy (OHE) could have persistent learning impairments.
AIM: To define learning/test-sophistication on EncephalApp (downloadable Application) in OHE patients compared to no-OHE patients and controls cross-sectionally and longitudinally.
METHODS: The EncephalApp Stroop App consists of 2 sections; the easier "Off" run assesses psychomotor speed while the difficult "On" run assesses cognitive flexibility. Cross-sectional Analysis: Cirrhotic outpatients with/without controlled OHE and healthy controls underwent EncephalApp testing, which requires 5 "off" and 5 "on" runs. We studied the difference in time required between completing trial 1 compared with trial 5 (delta 1-5) in the both the "On" and "Off" runs in controls, all cirrhotics; and between prior OHE/no-OHE cirrhotics. Longitudinal Analyses: Two groups of cirrhotics were studied; one was administered EncephalApp, ≥ 2 weeks apart and the second before, and 6 months post-liver transplantation.
RESULTS: 89 controls and 230 cirrhotics (85 prior OHE, MELD 11) with similar age (64 vs 61, p=0.9) were included. Cirrhotic patients had impaired EncephalApp total times and impaired learning on the On runs compared to controls. OHE patients had worse EncephalApp times and learning with the On runs compared to no-OHE patients, which persisted in the longitudinal cohort. No differences in learning were seen in the Off runs. After transplant there was restoration of learning capability with the On runs in the OHE patients.
CONCLUSION: Cognitive flexibility tested by the EncephalApp On runs improves over time in healthy controls and no-OHE but not prior OHE. Psychomotor speed remains similar over time. The learning Impairment manifested by cirrhotics with OHE is restored post-transplant. This article is protected by copyright. All rights reserved.
BACKGROUND AND OBJECTIVES: Hepatitis C virus infection is common in patients with CKD and leads to accelerated progression to ESRD. Sofosbuvir is a potent direct-acting antiviral therapy against hepatitis C virus; however, there are concerns about its safety in patients with CKD. The objective of our study was to determine the safety and efficacy of sofosbuvir in patients with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a retrospective observational cohort of patients with CKD defined by eGFR<60 ml/min per 1.73 m(2), ≥30 mg albuminuria per 1 g creatinine, or ≥200 mg proteinuria per 1 g creatinine who received sofosbuvir-based therapy in a large health care system. Regression models were constructed to predict likelihood of sustained virologic response, detect adverse events, and examine changes in eGFR from baseline to follow-up.
RESULTS: Ninety-eight patients with CKD (42% stage 1 or 2 CKD and 58% stage 3 CKD) were included. Mean age was 62 years old, 78% were men, and 65% were white. Additionally, 49% of patients had diabetes, 38% of patients had cirrhosis, and 33% of patients had prior solid organ transplant. Overall sustained virologic response was 81% and varied by regimen used and viral genotype. Average baseline eGFR was equivalent to average on-treatment eGFR, but seven patients experienced a rise in creatinine ≥1.5 times baseline while taking sofosbuvir; all but one recovered. In patients with eGFR<60 ml/min per 1.73 m(2) at baseline (stage 3 CKD), regression models showed that hepatitis C cure was associated with a 9.3 (95% confidence interval, 0.44 to 18) ml/min per 1.73 m(2) improvement in eGFR during the 6-month post-treatment follow-up period. Adverse events were common (81%), but serious adverse events (17%) and treatment discontinuations (8%) were uncommon.
CONCLUSIONS: Sofosbuvir-based direct-acting antiviral therapy is safe and effective in a cohort of patients with CKD infected with hepatitis C.
Infectious Diseases (6), Endocrine Disorders (3), Immune System Diseases (3) Hepatitis C (6), Diabetes Mellitus (3), Cirrhosis (2), more mentions
INTRODUCTION: Patients with cirrhosis have a high risk of sepsis, which confers a poor prognosis. The systemic inflammatory response syndrome (SIRS) criteria have several limitations in cirrhosis. Recently, new criteria for sepsis (Sepsis-3) have been suggested in the general population (increase of Sequential Organ Failure Assessment (SOFA) ≥2 points from baseline). Outside the intensive care unit (ICU), the quick SOFA (qSOFA (at least two among alteration in mental status, systolic blood pressure ≤100 mm Hg or respiratory rate ≥22/min)) was suggested to screen for sepsis. These criteria have never been evaluated in patients with cirrhosis. The aim of the study was to assess the ability of Sepsis-3 criteria in predicting in-hospital mortality in patients with cirrhosis and bacterial/fungal infections.
METHODS: 259 consecutive patients with cirrhosis and bacterial/fungal infections were prospectively included. Demographic, laboratory and microbiological data were collected at diagnosis of infection. Baseline SOFA was assessed using preadmission data. Patients were followed up until death, liver transplantation or discharge. Findings were externally validated (197 patients).
RESULTS: Sepsis-3 and qSOFA had significantly greater discrimination for in-hospital mortality (area under the receiver operating characteristic (AUROC)=0.784 and 0.732, respectively) than SIRS (AUROC=0.606) (p<0.01 for both). Similar results were observed in the validation cohort. Sepsis-3 (subdistribution HR (sHR)=5.47; p=0.006), qSOFA (sHR=1.99; p=0.020), Chronic Liver Failure Consortium Acute Decompensation score (sHR=1.05; p=0.001) and C reactive protein (sHR=1.01;p=0.034) were found to be independent predictors of in-hospital mortality. Patients with Sepsis-3 had higher incidence of acute-on-chronic liver failure, septic shock and transfer to ICU than those without Sepsis-3.
CONCLUSIONS: Sepsis-3 criteria are more accurate than SIRS criteria in predicting the severity of infections in patients with cirrhosis. qSOFA is a useful bedside tool to assess risk for worse outcomes in these patients. Patients with Sepsis-3 and positive qSOFA deserve more intensive management and strict surveillance.
INTRODUCTION: Natural language processing is a powerful technique of machine learning capable of maximizing data extraction from complex electronic medical records.
METHODS: We utilized this technique to develop algorithms capable of "reading" full-text radiology reports to accurately identify the presence of fatty liver disease. Abdominal ultrasound, computerized tomography, and magnetic resonance imaging reports were retrieved from the Veterans Affairs Corporate Data Warehouse from a random national sample of 652 patients. Radiographic fatty liver disease was determined by manual review by two physicians and verified with an expert radiologist. A split validation method was utilized for algorithm development.
RESULTS: For all three imaging modalities, the algorithms could identify fatty liver disease with >90% recall and precision, with F-measures >90%.
DISCUSSION: These algorithms could be used to rapidly screen patient records to establish a large cohort to facilitate epidemiological and clinical studies and examine the clinic course and outcomes of patients with radiographic hepatic steatosis.
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) worldwide. NAFLD-HCC often occurs in noncirrhotic liver raising important surveillance issues.
AIM: To determine the temporal trends for prevalence, clinical characteristics and outcomes of NAFLD-HCC in patients undergoing liver resection.
METHODS: Consecutive patients with histologically confirmed HCC who underwent liver resection over a 20-year period (1995-2014). NAFLD was diagnosed based on past or present exposure to obesity or diabetes without other causes of chronic liver disease.
RESULTS: A total of 323 HCC patients were included, 12% with NAFLD. From 1995-1999 to 2010-2014, the prevalence of NAFLD-HCC increased from 2.6% to 19.5%, respectively, P = .003, and followed the temporal trends in the prevalence of metabolic risk factors (28% vs 52%, P = .017), while hepatitis C-HCC decreased (from 43.6% to 19.5%, P = .003). NAFLD-HCC occurred more frequently in the absence of bridging fibrosis/cirrhosis (63% of cases, P < .001 compared to other aetiologies). Within the NAFLD group, tumour characteristics were similar between F0-F2 and F3-F4 patients, except for a higher proportion of single nodules (95% vs 54%, P < .01). A total of 53% patients had tumour recurrence and 40% died. NAFLD-HCC had similar time to recurrence and survival as HCCs of other aetiologies. Satellite nodules, tumour size, microvascular invasion and male sex but not the aetiology were independently associated with recurrence.
CONCLUSION: Non-alcoholic fatty liver disease increased substantially over the past 20 years among resectable HCCs. It is now the leading cause of HCC occuring without/or with only minimal fibrosis. NAFLD patients are older, with larger tumours while survival and recurrence rates are as severe as in other aetiologies.
Endocrine Disorders (1), Infectious Diseases (1), Anti-Obesity and Weight Loss (1) Alcoholic Fatty Liver (3), Hepatocellular Carcinoma (2), Fibrosis (2), more mentions