Presence Of Advanced Fibrosis Research Articles

221-LB: Association between Muscle Strength and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: Korean Nationwide Survey

Background: We investigated the association between muscle strength and the prevalence of advanced fibrosis among individuals with nonalcoholic fatty liver disease (NAFLD) using a nationwide cross-sectional survey. Methods: Individuals, 20 to 79 years of age, from the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2016 were selected (n = 14,861), with sample weights applied. Muscle strength was quantified as the hand grip strength (HGS) divided by the body mass index (BMI); low muscle strength (LMS) was defined as the lowest quartile (Q1) of the HGS/BMI scores for our sample population. NAFLD was defined by hepatic steatosis index (HSI) >36 (NAFLDHSI). The highest quartile of NAFLD fibrosis score (NFS) (FibrosisNFS) was used to define advanced fibrosis. Results: In a crude analysis, LMS was associated with the increased prevalence of NAFLDHSI (OR 3.62, 95% CI 3.25-4.03), which remained significant even after adjustment for age, sex, obesity, and insulin resistance (OR 1.69, 95% CI 1.30-2.18). Even in those without obesity, individuals with LMS had a higher prevalence of NAFLDHSI compared to those without LMS (OR 1.93, 95% CI, 1.42-2.63). Among individuals with NAFLDHSI (n = 3,320), LMS was also associated with the presence of advanced fibrosis (FibrosisNFS) even after adjustment for age, sex, obesity, and insulin resistance (OR 1.68, 95% CI 1.09-2.58). Conclusion: Muscle strength is independently associated with NAFLD and advanced fibrosis. Disclosure S. Kang: None. M. Moon: None. B. Koo: None.

A Microbial Signature Identifies Advanced Fibrosis in Patients with Chronic Liver Disease Mainly Due to NAFLD

The presence of advanced fibrosis is an important measure of the severity of chronic liver disease. Prior works that have examined the gut microbiome as a novel biomarker for advanced fibrosis have only examined patients with nonalcoholic fatty liver disease. Therefore, our goal was to examine the gut microbiome across varying etiologies of liver disease to create a predictive model for liver fibrosis based upon a microbial signature. Stool samples were obtained from patients with chronic liver disease (n = 50) undergoing FibroScan (ultrasound elastography) at the VA Greater Los Angeles Healthcare System. Healthy control patients (n = 25) were also recruited as a reference population. Fecal samples underwent 16S ribosomal RNA sequencing. Using differentially abundant microbes, a random forest classifier model was created to distinguish advanced fibrosis from mild/moderate fibrosis. The findings were then validated in a separate cohort of chronic liver disease patients (n = 37). Etiologies for liver disease included non-alcoholic liver disease (58.0%), hepatitis C (26.0%), hepatitis B (10.0%), and alcohol (6.0%). Microbiome composition was distinct in liver patients with advanced fibrosis compared to those with minimal fibrosis and healthy controls (p = 0.003). In multivariate negative binomial modeling, 26 bacterial taxa were differentially abundant in patients with advanced fibrosis as compared to those with minimal/moderate fibrosis (q-value < 0.05). A random forests classifier based on these taxa had an AUROC of 0.90 to predict advanced fibrosis. Prevotella copri, which was enriched in patients with advanced fibrosis, was the most strongly predictive microbe in the classifier. The classifier had an AUROC of 0.82 for advanced fibrosis in the validation cohort and Prevotella copri remained the strongest predictive microbe for advanced fibrosis. There is a distinct microbial signature for patients with advanced fibrosis independent of liver disease etiology and other comorbidities. These results suggest that microbial profiles can be used as a non-invasive marker for advanced fibrosis and support the hypothesis that microbes and their metabolites contribute to hepatic fibrosis.

Arterial stiffness is associated independently with liver stiffness in biopsy-proven nonalcoholic fatty liver disease: a transient elastography study

Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased arterial stiffness. However, the question as to whether an association exists between the extent of vascular and liver stiffness in patients with biopsy-proven NAFLD remains open. In this study, we sought to investigate whether pulse wave velocity (PWV) and augmentation index (AIx) - two common indices of arterial stiffness - are associated with (a) liver stiffness measurement (LSM) on transient elastography (TE) and (b) histological liver fibrosis. We examined 125 patients with biopsy-proven NAFLD and 55 age-matched and sex-matched controls. Arterial stiffness of the brachial artery was measured using a Mobil-O-Graph arteriography system. LSM was assessed using TE, whereas the presence of advanced fibrosis (F ≥ 3) was determined on histology. Patients with NAFLD had higher PWV [median: 7.2 (6.3-8.2) and 6.2 (5.5-6.7) m/s, respectively, P < 0.001] and AIx (mean: 21.3 ± 13.5 and 17.2 ± 11.9%, respectively, P=0.01) compared with the controls. LSM showed positive correlations with both PWV (ρ = 0.300; P<0.01) and AIx (ρ = 0.223, P = 0.02). Both indices of arterial stiffness were higher in patients with advanced fibrosis than in those with nonadvanced fibrosis (F ≤ 2). The severity of arterial and liver stiffness increases in parallel in patients with biopsy-proven NAFLD. Systematic risk assessment for reducing arterial stiffness is recommended in the presence of TE-determined advanced fibrosis.

The natural course of non-alcoholic fatty liver disease.

Background and AimThe present study aims to describe the characteristics and long-term clinical outcomes of patients with non-alcoholic fatty liver disease (NAFLD).Material and MethodsA total of 1308 individuals with NAFLD were seen in the Liver Diseases Outpatient Clinic. Diagnosis of NAFLD in each case was based on biochemical, radiological and histological criteria, when available. After diagnosis, all NAFLD patients were administered a conventional diet and exercise program. The median follow-up period was 55.3 months.ResultsAt the time of the diagnosis, the mean age was 50.8±11.3 years, and female gender was slightly predominant (51.4%). The median body mass index was 29.2±4.7 kg/m2: 39% were obese. Seventeen percent of the patients had diabetes mellitus, 53% insulin resistance, 60% hyperlipidemia, and 32% hypertension. Median serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels were 31 U/L (range: 10–248 U/L), 45 U/L (range: 10–285 U/L) and 41 (range: 8–1200 U/L), respectively. Liver biopsy was performed in 293 individuals. The median NAFLD activity score was 5.0, median hepatic steatosis 2, ballooning 1, lobular inflammation 1, portal inflammation 0, and fibrosis 0. Of note, 41.3% of the samples (121/293) revealed the presence of fibrosis and 31% of the samples (37/121) showed significant fibrosis. With multivariate analysis, diabetes and obesity were associated with the presence of significant fibrosis. Among them, 765 patients (M/F: 353/412, mean age: 51.0±10.9) had at least six months of follow-up. In this group, from baseline to the end of the follow-up period, a significant improvement in the serum AST and ALT levels was observed.ConclusionNAFLD is a potentially progressive disease. Diabetes and obesity were associated with the presence of advanced fibrosis.

Quantification of hepatic steatosis with ultrasound: promising role of attenuation imaging coefficient in a biopsy-proven cohort.

To prospectively assess the role of the US attenuation imaging coefficient (AC) for the diagnosis and quantification of hepatic steatosis. One hundred and one patients underwent liver biopsy and US-AC measurement on the same day. Liver steatosis was graded according to biopsy as absent (S0 < 5%), mild (S1 5-33%), moderate (S2 33-66%), or severe (S3 > 66%); liver fibrosis was graded from F0 to F4. The correlation between AC and steatosis on pathology (%) was calculated using the Pearson correlation coefficient. The Student t or Mann-Whitney U test was used to compare continuous variables and ROC curve analysis was used to assess diagnostic performance of AC in diagnosing steatosis. Overall, 43 (42%), 35 (35%), 12 (12%), and 11 (11%) patients were classified as S0, S1, S2, and S3, respectively. The AC was positively correlated with steatosis as a continuous variable (%) on pathology (r = 0.58, p < 0.01). Patients with steatosis of any grade had a higher AC than those without steatosis (mean 0.77 ± 0.13 vs. 0.63 ± 0.09 dB/cm/MHz, respectively; p < 0.01, AUROC = 0.805). Patients with S2-S3 had a higher AC than patients with S0-1 (0.85 ± 0.11 vs. 0.67 ± 0.11 dB/cm/MHz, respectively; p < 0.01, AUROC = 0.892). AC > 0.69 dB/cm/MHz had a sensitivity and specificity of 76% and 86%, respectively, for diagnosing any grade of steatosis (S1-S3), and AC > 0.72 dB/cm/MHz had a sensitivity and specificity of 96% and 74%, respectively, for diagnosing S2-S3. The presence of advanced fibrosis (F3-F4) did not affect the calculated AC. The attenuation imaging coefficient is a promising quantitative technique for the non-invasive diagnosis and quantification of hepatic steatosis. • Measurement of the attenuation coefficient is achieved with a very high rate of technical success. • We found a significant positive correlation between the attenuation coefficient and the grade of steatosis on pathology. • The attenuation imaging coefficient is a promising quantitative technique for the noninvasive diagnosis and quantification of hepatic steatosis.

The Role of Noninvasive Tests for Differentiating NASH From NAFL and Diagnosing Advanced Fibrosis Among Patients With NAFLD.

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need. The search for noninvasive tests has been more successful for advanced fibrosis than for NASH. Clinical prediction models and elastography have acceptable accuracy for ruling out advanced fibrosis; when used together, as in a fibrosis prediction algorithm presented in this review, it can avoid the need for liver biopsy among many patients with NAFLD. Several biomarkers for identifying the presence of NASH have been studied but none are sufficiently accurate or validated. Of those studied, the most promising include CK-18 fragments, lipodomic and metabolomics candidates, and magnetic resonance elastography with proton density fat fraction. However, none are ready for clinical use and ultimately large multicenter prospective cohort studies are needed to validate select novel biomarkers.

Should We Screen High-Risk Populations for NAFLD?

Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and yet remains largely underdiagnosed. However, whether a systematic screening in high-risk population for NAFLD should be performed remains debated. Over the past decade, a better knowledge of the natural history and epidemiology of NAFLD has identified high-risk population for NAFLD including obese and type 2 diabetes patients. Moreover, the presence of advanced fibrosis has been identified as the major determinant of overall and liver-related mortality. Moreover, several non-invasive biomarkers have been developed for the screening of advanced fibrosis while therapeutic clinical trials are intensive field of research. Screening for advanced fibrosis in high-risk population for NAFLD should be performed as it would benefit to the patients. However further studies are needed to determine the optimal strategy and cost-effectiveness of such screening.

Prevalence of Advanced Liver Fibrosis in Patients With Severe Psoriasis

Advanced liver fibrosis is a precursor to cirrhosis, a leading cause of mortality. People with severe psoriasis are at risk for liver disease, but our understanding of advanced fibrosis in individuals with psoriasis is limited. To describe the prevalence of and evaluate the clinical factors associated with advanced liver fibrosis in people with severe psoriasis. The Co-morbidities in Severe Psoriasis study, a prospective observational cohort study in a large center serving London and Southeast England, was conducted from October 18, 2012, to April 2, 2015; 400 adults with severe psoriasis (Psoriasis Area Severity Index score, ≥10) were recruited from outpatient clinics. Statistical analysis was conducted from October 2, 2016, to March 3, 2017. The primary outcome was a diagnosis of advanced liver fibrosis determined by transient elastography, a noninvasive criterion standard test. Clinical factors evaluated included psoriasis-specific and metabolic indices, alcohol use, and methotrexate exposure. Of 400 patients recruited (108 women and 289 men; mean [SD] age, 49.5 [13] years), 333 had a successful transient elastography scan and were included in final analysis. Forty-seven patients (14.1%; 95% CI, 10.4%-17.9%) had advanced liver fibrosis as diagnosed by transient elastography. The clinical factors that produced the best-fit model for advanced fibrosis were central obesity (waist circumference), insulin resistance, aspartate aminotransferase level, platelet count, psoriasis disease severity, and reduced alcohol use (R2 = 0.54). Findings from this study suggest that advanced fibrosis is common in severe psoriasis. Abdominal obesity (by waist circumference) and insulin resistance were associated with the presence of advanced fibrosis. Longitudinal work to characterize the hepatic sequelae of central obesity, insulin resistance, and inflammation as well as the influence of systemic drugs (methotrexate and biologics) will inform future personalized therapeutic decision-making. ClinicalTrials.gov identifier: NCT02174367.

SUN-142 High Prevalence of NAFLD and Advanced Fibrosis in Patients with Obesity and Diabetes

Non-alcoholic fatty liver disease (NAFLD) is the most common, chronic liver disorder in the United States (US). Non-alcoholic steatohepatitis (NASH), the more severe form of NAFLD with hepatocyte necroinflammation that may lead to cirrhosis and hepatocellular carcinoma (HCC), is believed to be common, but its true prevalence is unclear. To bridge this knowledge gap, we aimed to estimate the prevalence of NAFLD and NASH in the US obesity and diabetes populations using the National Health and Nutrition Examination Survey (NHANES) 2015-2016 data. NAFLD was defined as a US fatty liver index (USFLI) of ≥30 (1) and NASH as a NAFLD fibrosis score (NFS) of >0.676 (2). Data were collected from 5,662 individuals, aged ≥18 years. Of these, 2,246 (39.7%) patients had obesity (body mass index [BMI] ≥30 kg/m2) and 869 (15.3%) had diabetes (self-reported based on physician diagnosis and/or taking diabetes medications). We observed a significant overlap between diabetes, obesity, and NAFLD. In the obese population, 62.7% of patients had NAFLD and 14.2% had NAFLD and diabetes. In the diabetes cohort, 61.2% of patients had obesity, 61.7% had NAFLD alone and 47% had obesity and NAFLD. The presence of advanced fibrosis (NFS) was high in patients with obesity (16.7%), higher in patients with diabetes (32.4%) and the highest in patients with both obesity and diabetes (37.5%). The prevalence of NAFLD was higher in patients with diabetes and worse glycemic control (i.e., 70% in patients with glycated hemoglobin [HbA1c] > 8% vs. 55% in patients with HbA1c ≤ 8%). In conclusion, patients with obesity and/or diabetes have a very high risk of NAFLD and fibrosis. Advanced fibrosis was two-fold higher in patients with diabetes vs. obese patients, making these patients a high-risk population to consider for screening. The USFLI and NFS could be useful tools to screen populations at risk for NAFLD and NASH.

Looking Into the Crystal Ball: Predicting the Future Challenges of Fibrotic NASH Treatment.

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide, and its aggressive form of nonalcoholic steatohepatitis (NASH) is becoming a leading cause for end‐stage liver disease and liver transplantation in the United States. In patients with NASH, the presence of advanced fibrosis is considered the most important prognostic factor in predicting liver‐related morbidity and mortality. Unfortunately, there are no US Food and Drug Administration (FDA)–approved medications to treat patients with NASH‐induced advanced fibrosis. However, the field of drug development to treat NASH and fibrosis has witnessed major advances over the past 5 years with several medications in phase III trials. Results from some of these trials are expected in 2019 with potential FDA approval in 2020. Clinicians who treat patients with NAFLD are likely to face several challenges over the next few years related to identifying patients with advanced fibrosis who may derive most benefit from pharmacologic treatment, the requirement for liver biopsy to assess histologic severity and response to treatment, and the urgent need to validate noninvasive tests to replace liver biopsy—to determine treatment initiation, response, futility, and the need for combination therapy with multiple drugs. Conclusion: In this review, we aim to dissect each of these challenges and attempt to provide suggested solutions while fully realizing that knowledge gaps still exist where future research is likely to provide urgently needed answers.

Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease.

Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis. To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD. We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients. Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis. CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.

Ultrasonographic Nonalcoholic Fatty Pancreas Is Associated with Advanced Fibrosis in NAFLD: A Retrospective Analysis.

Nonalcoholic fatty pancreas disease (NAF-P) is strongly linked with nonalcoholic fatty liver disease (NAFLD), but its relationship with advanced liver disease is unknown. This study investigated the association between NAF-P and both advanced fibrosis and nonalcoholic steatohepatitis (NASH). This retrospective study evaluated adults with biopsy-proven NAFLD with a sonogram within 1year of liver biopsy. NAF-P was diagnosed by comparing the echogenicity of the pancreas to the kidney and was graded by severity. The primary outcome was the effect of NAF-P on the presence of advanced fibrosis and NASH, while secondary outcomes included the association of extensive NAF-P (grade II/III). Propensity score matching for independent risk factors of advanced fibrosis (age, gender, body mass index, and diabetes) was performed. One hundred and four patients were included in the study and 91 (87.5%) had NAF-P. After propensity score matching, NAF-P was significantly associated with advanced fibrosis (OR 10.52, p < 0.001) but not NASH (p = 0.27). Extensive NAF-P was predictive of advanced fibrosis (OR 3.35, p = 0.006) and NASH (OR 5.37, p < 0.001). NAF-P had a negative predictive value (NPV) of 93% for advanced fibrosis. When matching for the NAFLD fibrosis score in addition to the variables above, both NAF-P (OR 5.36, p = 0.001) and extensive NAF-P (OR 5.38, p = 0.002) still significantly predicted advanced fibrosis. NAF-P is predictive of advanced fibrosis, even when controlling for independent predictors of advanced fibrosis and the NAFLD fibrosis score. NAF-P has an excellent NPV and is a safe, inexpensive finding that can rule out advanced fibrosis.

Elast PQ Ultrasound - a Noninvasive, Reproducible, Easily Performed Method and a New Era in Liver Fibrosis Assessment

Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infection has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive technique and has been the standard of care of fibrosis assessment for years; however, it has several limitations and procedure related complications. Recently, several methods of noninvasive assessment of liver fibrosis have been developed which require either serologic testing or imaging of liver. Imaging based noninvasive techniques are reviewed here and their clinical use is described. Some of the imaging based tests are becoming widely available, and collectively they are shown to be superior to liver biopsy in important aspects. Clinical utilization of these methods requires understanding of performance and quality related parameters which can affect the results and provide wrong assessment of the extent of liver fibrosis. Familiarity with the strengths and weakness of each modality is needed to correctly interpret the results in appropriate clinical content. A new technique called Elast PQ uses ultrasound shear wave elastography to provide a noninvasive, reproducible, easily performed method of assessing liver fibrosis. It can easily combine a routine ultrasound imaging exam of the liver anatomy with targeted tissue stiffness values, assess liver fibrosis in patient with clinically suspected disease even before abnormalities are detected with ultrasound imaging, evaluate and obtain a baseline stiffness value in patients with chronic liver disease, follow up patients under treatment to monitor progression, stabilization or regression of liver disease and help avoid the need for liver biopsies when elastography results are consistent with other clinical findings. Both the prognosis and potential treatment of chronic liver diseases greatly depend on the progression of liver fibrosis, which is the ultimate outcome of chronic liver damage. Historically, liver biopsy has been instrumental in adequately assessing patients allows clinicians both to obtain diagnosis information and initiate adequate therapy. However, the technique is not exempt of deleterious effects. Multiple diagnostic tests have been developed for the staging of fibrosis using noninvasive methods, most of them in the setting of chronic hepatitis C. The goal of this paper is to review available data on the staging and assessment of liver fibrosis with two methods: serum markers &amp; transient elastography (FibroScan).Faridpur Med. Coll. J. Jan 2018;13(1): 44-46

A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary Care.

Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB‐4], or enhanced liver fibrosis [ELF] test) are recommended as first‐line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed. Clinically significant fibrosis was defined as LSM ≥8.2 kPa or ELF ≥9.8. A subgroup of patients underwent liver biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were 57.3 ± 12.3 years old with a high prevalence of metabolic syndrome (84.5%), type 2 diabetes (82.5%), and body mass index (BMI) ≥40 kg/m2 (21.8%). LSM met quality criteria in 230 (91.3%) patients. NFS and FIB‐4 combined had a high negative predictive value (90.0%) for excluding LSM ≥8.2 kPa. However, 84.1% of patients had indeterminate or high NFS or FIB‐4 scores requiring further assessment. LSM ≥8.2 kPa and ELF ≥9.8 were present in 31.3% and 28.6% of patients, respectively. Following adjustment for age, BMI, sex, and presence of advanced fibrosis, older age was independently associated with ELF ≥9.8 (adjusted odds ratio, 1.14; 95% confidence interval, 1.06‐1.24), whereas increasing BMI was independently associated with LSM ≥8.2 kPa (adjusted odds ratio, 1.15; 95% confidence interval, 1.01‐1.30). Concordant LSM <8.2 kPa and ELF <9.8 and concordant LSM ≥8.2 kPa and ELF ≥9.8 had a high negative predictive value (91.7%) and positive predictive value (95.8%) for excluding and identifying clinically significant fibrosis, respectively. Conclusion: Simple scoring tools alone lack accuracy. LSM accuracy is influenced by severe obesity, whereas age impacts the ELF test. Further studies are required to confirm whether combining LSM and ELF may enhance accuracy and confidence in identifying clinically significant fibrosis. (Hepatology Communications 2018; 00:000‐000)

Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis.

Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood. Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30IU/L for men and >19IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB-4 score. Of the 6738 participants (mean age 46.3years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20-39years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high-density lipoprotein cholesterol (P for trend <.05 respectively). In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors.

Bile duct paucity in childhood-spectrum, profile, and outcome.

PILBD was present in 11% of pediatric liver biopsies and has a varied etiological spectrum. Destructive PILBD has poor outcome. Need for LT is guided by the presence of advanced fibrosis. What is Known: • Natural history of syndromic ductal paucity (Alagille syndrome) is complex. • Duct loss is commonly seen with late presentation of biliary atresia. What is New: • The study classifies the etiological spectrum of ductal paucity histologically into destructive and non-destructive. • Destructive duct loss carries poor prognosis regardless of the etiology of liver disease with subsequent need for liver transplantation.

Renal Dysfunction in Patients With Nonalcoholic Fatty Liver Disease is Related to the Presence of Diabetes Mellitus and Severity of Liver Disease

There is sparse data on the prevalence of renal dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the presence of renal dysfunction in patients with NAFLD and correlate it with the severity of liver disease. One hundred nonalcoholic patients with ultrasound showing hepatic steatosis were enrolled into the study after exclusion of other causes. Presence of renal dysfunction was estimated by glomerular filtration rate and by evaluating 24h urinary protein and microalbumin. Various risk factors including components of metabolic syndrome, severity of hepatic steatosis (as assessed on ultrasound), hepatic necro-inflammation (as assessed by hepatic transaminases) and hepatic fibrosis (as assessed by transient elastography) were correlated with the presence of renal dysfunction. Twenty eight (28%) patients with NAFLD had evidence of impaired renal function with 5 (5%) having abnormal glomerular filtration rate, 18 (18%) having significant proteinuria and 5 (5%) having both. Presence of type 2 diabetes mellitus, raised hepatic transaminases and advanced fibrosis on transient elastography were found as independent predictors of impaired renal function with raised hepatic transaminases having the best sensitivity (89%) and presence of advanced fibrosis the best specificity (90%). A model comprising of these three parameters had good accuracy (AUROC=0.763) in predicting impaired renal function in patients with NAFLD. Around one-third of patients with NAFLD have impaired renal functions. Prevalence of impaired renal function in patients with NAFLD is dependent on the severity of liver disease and presence of diabetes mellitus.

IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD – a pilot study

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3–4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD.Methods: Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3–4).Results: Patients with advanced fibrosis (stage 3–4 vs. 0–2) had lower IGF-SD (−1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0–1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44–0.92, p = .02).Conclusions: This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

Barriers to Hepatitis C Virus (HCV) Treatment Initiation in Patients With Human Immunodeficiency Virus/HCV Coinfection: Lessons From the Interferon Era.

Hepatitis C is a major cause of mortality among human immunodeficiency virus (HIV)-infected patients, yet hepatitis C virus (HCV) treatment uptake has historically been low. Although the removal of interferon removes a major barrier to HCV treatment uptake, oral therapies alone may not fully eliminate barriers in this population. Within the Johns Hopkins Hospital HIV cohort, a nested case-control study was conducted to identify cases, defined as patients initiating HCV treatment between January 1996 and 2013, and controls, which were selected using incidence density sampling (3:1 ratio). Controls were matched to cases on date of enrollment. Conditional logistic regression was used to evaluate factors associated with HCV treatment initiation. Among 208 treated cases and 624 untreated controls, the presence of advanced fibrosis (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.26-3.95), recent active drug use (OR, 0.36; 95% CI, 0.19-0.69), and non-black race (OR, 2.01; 95% CI, 1.26-3.20) were independently associated with initiation of HCV therapy. An increasing proportion of missed visits was also independently associated with lower odds of HCV treatment (25%-49% missed visits [OR, 0.49; 95% CI, 0.27-0.91] and ≥50% missed visits [OR, 0.24; 95% CI, 0.12-0.48]). Interferon-free treatments may not be sufficient to fully overcome barriers to HCV care in HIV-infected patients. Interventions to increase engagement in care for HIV and substance use are needed to expand HCV treatment uptake.

Post-Liver Transplant Management of Hepatitis C

Recurrent hepatitis C virus (HCV) infection confers higher complication and mortality rates in liver transplant (LT) recipients. Prior treatment with interferon (IFN)-based regimens yielded poor response and many adverse reactions. Recently, direct-acting antiviral agents have replaced IFN-based therapy; these are highly effective in LT patients, regardless of previous treatment experience or presence of advanced fibrosis or cirrhosis, and even with hepatic decompensation. However, specific clinical conditions frequently encountered in this population may still impact the safety and tolerability of HCV treatment, and should be carefully considered prior to initiation of therapy. Once a difficult-to-treat disease and a threat to graft and patient survival, recurrent HCV has now become highly curable and will cease to be a major cause of graft loss or patient mortality in LT recipients.