Predictors Of Advanced Fibrosis Research Articles

Predictors of advanced liver fibrosis and the performance of fibrosis scores: lean compared to non-lean metabolic dysfunction-associated steatotic liver disease (MASLD) patients.

Non-alcoholic fatty liver disease (NAFLD) in lean patients differs from that of NAFLD in non-lean patients. However, current data regarding predictors of advanced fibrosis and the performance of fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) in lean compared to non-lean metabolic dysfunction-associated steatotic liver disease (MASLD) patients is insufficient. This was a cross-sectional study. Lean was defined as Body Mass Index <25 kg/m2. Advanced fibrosis (F3-F4) was detected by liver biopsy or two-dimension shear wave elastography (2D-SWE). Predictors of advanced fibrosis were identified using logistic regression and area under ROC curves (AUROC) were derived for FIB-4 and NFS. Lean patients (N.=153) comprised 19.2% of the MASLD cohort. Advanced fibrosis was associated with the number of cardiometabolic risk factors (CMRF) in lean (OR=2.06, P=0.011) and non-lean (OR=1.58, P<0.001) patients, however, hypertension and diabetes or impaired fasting glucose were significant only among non-lean. Age was associated with advanced fibrosis in both subgroups with age ≥65 showing higher odds in lean compared to non-lean patients (P=0.016). Non-lean patients had higher odds for advanced fibrosis relative to lean patients (OR=4.8, P=0.048). FIB-4 and NFS predicted advanced fibrosis among lean (AUROC=0.79 and AUROC=0.85, respectively) and non-lean (AUROC=0.79 and AUROC=0.76, respectively) patients. NFS ≥-1.445 showed higher specificity among lean compared to non-lean (P<0.001) and compared to that of FIB-4 ≥1.3 in lean patients (P<0.001). The number of CMRF was predictive of advanced fibrosis in both subgroups while age ≥65 showed higher odds among lean patients. NFS ≥-1.445 is more specific than FIB-4 ≥1.3 for advanced fibrosis prediction in lean patients. These findings may help identify high-risk lean MASLD patients for further liver fibrosis stage assessment.

MAFLD fibrosis score: Using routine measures to identify advanced fibrosis in metabolic-associated fatty liver disease.

Early screening may prevent fibrosis progression in metabolic-associated fatty liver disease (MAFLD). We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients. This cross-sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]). Patients completed liver biopsy, vibration-controlled transient elastography (VCTE), and clinical and laboratory assessment within 1 week. We used machine learning to select 'highly important' predictors of advanced fibrosis, followed by backward stepwise regression to construct MFS formula. MFS was composed of seven variables: age, body mass index, international normalised ratio, aspartate aminotransferase, gamma-glutamyl transpeptidase, platelet count, and history of type 2 diabetes. MFS demonstrated an area under the receiver-operating characteristic curve of 0.848 [95% CI 0.800-898] and 0.823 [0.760-0.886] in training and validation cohorts, significantly higher than aminotransferase-to-platelet ratio index (0.684 [0.603-0.765], 0.663 [0.588-0.738]), Fibrosis-4 index (0.793 [0.735-0.854], 0.737 [0.660-0.814]), and non-alcoholic fatty liver disease fibrosis score (0.785 [0.731-0.844], 0.750 [0.674-0.827]) (DeLong's test p < 0.05). MFS could include 92.3% of patients using dual cut-offs of 14 and 15, with a correct prediction rate of 90.4%, resulting in a larger number of patients with correct diagnosis compared to other scores. A two-step MFS-VCTE screening algorithm demonstrated positive and negative predictive values and overall diagnostic accuracy of 93.4%, 89.5%, and 93.2%, respectively, with only 4.0% of patients classified into grey zone. MFS outperforms conventional non-invasive scores in predicting advanced fibrosis, contributing to screening in MAFLD patients.

Development and Validation of the Nonalcoholic Fatty Liver Disease Familial Risk Score to Detect Advanced Fibrosis: A Prospective, Multicenter Study

Nonalcoholic fatty liver disease (NAFLD)-related fibrosis is heritable, but it is unclear how family history may be used to identify first-degree relatives with advanced fibrosis. We aimed to develop and validate a simple risk score to identify first-degree relatives of probands who have undergone assessment of liver fibrosis who are at higher risk of NAFLD with advanced fibrosis. This prospective, cross-sectional, familial study consisted of a derivation cohort from San Diego, California, and a validation cohort from Helsinki, Finland. This study included consecutive adult probands (n= 242) with NAFLD and advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 of their first-degree relatives. All included probands and first-degree relatives underwent evaluation of liver fibrosis, the majority by magnetic resonance elastography. A total of 396 first-degree relatives (64% male) were included. The median age and body mass index were 47 years (interquartile range, 32-62 y) and 27.6 kg/m2 (interquartile range, 24.1-32.5 kg/m2), respectively. Age (1 point), type 2 diabetes (1 point), obesity (2 points), and proband with NAFLD and advanced fibrosis (2 points) were predictors of advanced fibrosis among first-degree relatives in the derivation cohort (n= 220) and formed the NAFLD Familial Risk Score. The area under the receiver operator characteristic curve of the NAFLD Familial Risk Score for detecting advanced fibrosis was 0.94 in the validation cohort (n= 176). The NAFLD Familial Risk Score outperformed the Fibrosis-4 index in the validation cohort (area under the receiver operator characteristic curve, 0.94 vs 0.70; P= .02). The NAFLD Familial Risk Score is a simple and accurate clinical tool to identify advanced fibrosis in first-degree relatives. These data may have implications for surveillance in NAFLD.

Baseline Hepatitis B Virus Surface Antigen Titers in Childhood Predict the Risk of Advanced Liver Fibrosis in Adulthood

Hepatitis B virus (HBV) surface antigen (HBsAg) is a marker of both HBV covalently closed circular DNA and integrated HBV genome, whereas the HBV core-related antigen (HBcrAg) indicates the transcriptional activity of covalently closed circular DNA. This study examined the relationship between HBsAg and HBcrAg titers in childhood and advanced fibrosis in adulthood. We recruited 214 initially hepatitis B e antigen-positive chronic HBV-infected patients who were followed for a total of 6371 person-years. None of the patients were co-infected with hepatitis C or D virus. Serum HBsAg and HBcrAg titers were assessed at 10 and 15 years of age. Transient elastography was performed at a mean final age of 38.21 years to identify advanced fibrosis. Patients with advanced fibrosis in adulthood had a higher rate of genotype C HBV infection and a higher HBsAg titer at 10 and 15 years of age (P= .003, P = .03, and P = .005, respectively). The HBcrAg titer was not correlated with advanced fibrosis (P > .05). Receiver operating characteristic curve analysis showed that HBsAg cutoffs of >4.23 and >4.44 log10 IU/mL at 10 and 15 years of age, respectively, best predicted advanced fibrosis in the fourth decade of life (P= .001 and P < .001, respectively). In a multivariate analysis, both an HBsAg titer >4.44 log10 IU/mL at 15 years of age and HBV genotype C were predictors of advanced fibrosis (odds ratios, 15.43 and 4.77; P= .01 and P= .02, respectively). HBsAg titers in childhood predict the progression to liver fibrosis in adulthood.

Clinical profile of NAFLD patients and predictors of advanced fibrosis

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is a frequently encountered condition in clinical practice, particularly in obese and diabetic patients. Spectrum of liver disorders in non alcoholic patients comprises of fatty liver, steatohepatitis, fibrosis and cirrhosis. The present study is designed to study the clinical and biochemical profile of patients with NAFLD with varying degrees of severity as diagnosed by Ultrasonography and evaluate the relationship between fibrosis as accessed by fibroscan with various parameters.

Comparison of ADAPT, FIB-4 and APRI as non-invasive predictors of liver fibrosis and NASH within the CENTAUR screening population

The development of accurate non-invasive tests to detect and measure the extent of fibrosis and disease activity in patients with non-alcoholic steatohepatitis (NASH) - the progressive phenotype of non-alcoholic fatty liver disease (NAFLD) - is of great clinical importance. Herein, we aimed to validate the performance of PRO-C3 and ADAPT for the detection of moderate/severe fibrosis within the CENTAUR screening population. PRO-C3 was assessed in plasma from the screening population of the phase IIb CENTAUR study (NCT02217475) in adults with NASH and liver fibrosis. The relation between PRO-C3 and histologic features of NASH was evaluated, as well as the demographics of patients with high and low levels of PRO-C3. The diagnostic ability of PRO-C3, as a standalone marker or incorporated into ADAPT, to identify patients with F≥2 and NASH was estimated using receiver-operating characteristic analysis and logistic regression models. A total of 517 individuals with matched biopsy and PRO-C3 measurements were included. Patients with PRO-C3 levels ≥20.2 ng/ml showed increased levels of insulin, HOMA-IR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and platelet count compared to patients with low PRO-C3 (p <0.05). PRO-C3 increased stepwise with increasing liver fibrosis, lobular inflammation, hepatocyte ballooning, steatosis, and NAFLD activity score (p <0.05), and could distinguish between NAFL and NASH (p <0.0001). PRO-C3 was independently associated with fibrosis and NASH when adjusted for clinical confounders. ADAPT outperformed Fibrosis-4, AST-to-platelet ratio index, and AST/ALT ratio as a predictor of advanced fibrosis and NASH (p <0.001). PRO-C3 was associated with NAFLD activity score and fibrosis. ADAPT outperformed other non-invasive scores for detecting NASH. These data support the use of PRO-C3 and ADAPT as diagnostic tools to identify patients with NASH eligible for inclusion in clinical trials. NCT02217475 LAY SUMMARY: PRO-C3 is a serological biomarker associated with liver disease activity and fibrosis. Its performance for the detection of disease activity and fibrosis is improved when it is incorporated into the ADAPT score. Herein, we showed that ADAPT was better at selecting patients with non-alcoholic steatohepatitis for inclusion in clinical trials than other non-invasive scores.

A Multi-Center Study Exploring the Association of Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease in Cuban Patients

Aim: There is a paucity of data on Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Syndrome (MetS) among native Cubans. We aimed to assess the prevalence of MetS in Cubans with NAFLD and the outcomes and predictors for advanced fibrosis. Methods: A multicenter (outpatient clinics of nine hospitals in seven Cuban provinces) cross-sectional study of adults with NAFLD between September 2018 and May 2019. MetS was defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP: ATPIII) criteria. Advanced fibrosis was defined using AST to Platelet Ratio Index (APRI) ≥1 and Fibrosis-4 score (FIB-4) ≥2.67. Results: 819 patients enrolled, 563 (68.7%) had MetS; mean age 54.9 years, 60.3% female, 65.8% white, 95.1% from urban residency, mean BMI 30.7 kg/m². Fibrosis was present in 114 (13.9%); 94 (82.5%) had APRI ≥1; 77 (67.5%) had FIB-4 ≥ 2.67; 57 (50%) both scores were elevated. MetS group had significantly more fibrosis than no MetS, [17% vs. 7% (p=0.0001)]. Patients with fibrosis were older (57.7 vs. 54.5, P=0.0015), of Mestizos ethnicity (36.8% vs. 16.9%, P&lt;0.0001), and from rural residency (17.5% vs. 2.8%, P&lt;0.0001). MetS was independently associated with fibrosis: Odds Ratio (OR) = 2.05 (95% CI 1.10-3.81) (p=0.024), but, rural residency was the strongest fibrosis predictor [OR: 5.30 (95% CI 2.45-11.47, (P&lt;0.0001)]. Other fibrosis predictors were male gender, sedentary life-style, NAFLD family history, and lower estimated glomerular filtration rate (p&lt;0.05). Risk of fibrosis was not associated with age, ethnicity, or smoking (all p&gt;0.05). Conclusion: Cuban NAFLD patients with MetS have substantial clinical impairment and a higher risk for fibrosis.

Attenuated effect of PNPLA3 on hepatic fibrosis by HSD17B13 in Japanese patients with non-alcoholic fatty liver disease.

PNPLA3 rs738409 has been associated with increased risks of fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Recently, carriage of the rs6834314 G allele, which is in high linkage with rs72613567 of 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13), was reported to be associated with a reduced risk of liver injury in NAFLD patients. We estimated the impact of these genetic variants on hepatic fibrosis in Japanese patients with NAFLD. We analysed the associations of these genetic variants with liver histology in 290 Japanese patients with biopsy-proven NAFLD diagnosed during 2002-2019. During follow-up, 14 patients (4.8%) developed hepatocellular carcinoma. Prevalences of the PNPLA3 rs738409 genotypes were 0.17 for CC, 0.41 for CG, 0.42 for GG, and those for HSD17B13 rs6834314 were 0.54 for AA, 0.39 for AG and 0.07 for GG. There was no significant interaction between the PNPLA3 and HSD17B13 genotypes. Prevalences of advanced fibrosis according to PNPLA3/HSD17B13 genotypes were 0.16 for CC,CG/AG,GG, 0.20 for CC,CG/AA, 0.30 for GG/AG,GG and 0.37 for GG/AA. Multivariate analysis identified PNPLA3 GG as a predictor of advanced fibrosis (stage 3/4) in carriers of HSD17B13 AA (odds ratio 2.4, P=.041), but not HSD17B13 AG/GG (P=.776). The HSD17B13 genotype G was significantly associated with lower prevalences of severe inflammation and ballooning and tended to be associated with a higher prevalence of advanced steatosis. In Japanese patients with NAFLD, carriage of the HSD17B13 rs6834314 G allele attenuated the effect of the PNPLA3 rs738409 GG genotype on advanced hepatic fibrosis.

Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis

BackgroundHepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration.MethodsSHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a digitized image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA.ResultsNotably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p < 0.0001), steatosis grade (rho = 0.554, P < 0.001), Mallory-Denk bodies (rho = 0.54, P < 0.001), pericellular fibrosis (rho = 0.527, P < 0.001), and lymphocytic infiltration (rho = 0.435, P < 0.0002). Additionally, hepatic SHH expression correlated with circulating M65 (rho = 0.588, p < 0.0001), and circulating M30 (rho = 0.375, p = 0.001), as well as AST and ALT (rho = 0.43, p = 0.0004, and rho = 0.27, p = 0.03, respectively). Further, serum M30 was almost twice as high in NASH patients compared to non-NASH (539.1 ± 290.8 U/L vs. 287.6 ± 190.5 U/L; p = 0.0002), while M65 was almost three times higher in NASH patients compared to non-NASH (441.2 ± 464.2 U/L vs. 162.8 ± 353.1 U/L, P = 0.0006). Logistic modeling indicates hepatic SHH expression and presence of type 2 diabetes as independent predictors of advanced fibrosis (defined as portal and pericellular fibrosis > 2: OR = 1.986, p = 0.01, and OR = 3.280, p = 0.03, respectively).ConclusionThus, our findings show quantitation of SHH expression by CAM can provide a tool for quantifying changes in hepatocyte injury and assist in unambiguous staging/grading of NASH. Our study showed minimal interobserver variability using CAM based quantification. Once validated, CAM assessment of hepatic SHH could benefit clinical trials or long term outcomes studies of NASH subjects.

Combination of PNPLA3 and TLL1 polymorphism can predict advanced fibrosis in Japanese patients with nonalcoholic fatty liver disease.

Hepatic fibrosis is an independent risk factor for mortality and liver-related events in patients with nonalcoholic fatty liver disease (NAFLD). PNPLA3 rs738409 has been associated with fibrosis in viral and non-viral hepatitis. TLL1 rs17047200 also has been associated with developing hepatocellular carcinoma probably via hepatic fibrogenesis. We estimated the impact of these genetic polymorphisms on hepatic fibrosis in Japanese patients with NAFLD. We analyzed the association between these genetic variants and the backgrounds of 817 individuals who received health checkups (health check cohort) from 2012 to 2014. Then, we investigated the relationship between genetic variants and liver histology in 258 consecutive patients with biopsy-proven NAFLD in Japan (NAFLD cohort) from 2012 to 2017 (UMIN000027399). The prevalence of PNPLA3 CG/GG in the NAFLD cohort was higher than that in the health check cohort (p<0.001). The prevalence of patients with advanced fibrosis (stages 3-4) was higher for PNPLA3 genotype CG/GG than CC (p=0.048) and for TLL1 genotype AT/TT than AA (p=0.044). The high-risk group which had at least two risk alleles of these variants was more likely to have advanced fibrosis (p=0.004). Multivariate analysis identified body mass index [odds ratio (OR) 1.123, serum AST (OR 1.037, p=0.004], serum albumin (OR 0.247, p=0.032), and genetic high risk (OR 2.632, p=0.026) as predictors of advanced fibrosis. In Japanese patients with NAFLD, individuals with risk alleles of PNPLA3 and TLL1 may have a risk of advanced fibrosis.

Predictors for advanced fibrosis in morbidly obese non-alcoholic fatty liver patients

AIMTo investigate predictors for fibrosis specifically in a high risk population of morbidly obese patients, including detailed evaluation of lifestyle.METHODSWe conducted a cross-sectional study among morbidly obese patients attending the bariatric clinic at the Tel-Aviv Medical Center between the years 2013-2014 with body mass index (BMI) above 40 or above 35 with co-morbidity. Patients with serum hepatitis B surface antigen or anti-hepatitis C virus antibodies, genetic liver diseases, autoimmune disease or high alcohol intake (≥ 30 g/d in men or ≥ 20 g/d in women) were excluded from the study. Liver fibrosis was estimated by transient elastography (FibroScan®), using the ‘‘XL’’ probe. We collected data on age and gender, education, smoking status and amount, medical history, nutrition and lifestyle habits. All these data were collected using structured and validated questionnaires. Fasting blood test were available for a subsample.RESULTSFibroscan was performed on a total of 91 patients, of which 77 had a valid examination according to the accepted criteria. Of those, 21% had significant fibrosis (F2) and 39% had advanced or severe fibrosis (F3 or F4). In multivariate analysis, male gender and BMI had a positive association with advanced fibrosis; the OR for fibrosis F ≥ 2 was 7.93 (95%CI: 2.36-26.64, P = 0.001) for male gender and 1.33 (1.11-1.60 kg/m2, P = 0.002) for BMI. The OR for fibrosis F ≥ 3 was 2.92 (1.08-7.91, P = 0.035) for male gender and 1.17 (1.03-1.33, P = 0.018) for BMI. Subjects were categorized to subgroups based on the combination of male gender and BMI of 40 and above. A significant dose response association with stiffness level was noted across these categories, with the highest stiffness among men with a higher BMI (P = 0.001). In addition, a significant positive correlation between pack-years cigarette smoking and liver stiffness was demonstrated among men (r = 0.54, P = 0.012).CONCLUSIONIn the morbidly obese population, a higher BMI, male gender and degree of smoking in men bears a greater risk for advanced nonalcoholic fatty liver disease.

Incidence and Predictors of Advanced Liver Fibrosis by a Validated Serum Biomarker in Liver Transplant Recipients.

Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the liver transplant (LT) population. We employed a simple serum biomarker to elucidate incidence and predictors of advanced fibrosis after LT over a long follow-up period. Methods. We included 440 consecutive patients who underwent LT between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond 12 months after LT. Results. Over 2030.5 person-years (PY) of follow-up, 189 (43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95% confidence interval [CI], 8.1–10.7). Advanced fibrosis was predicted by chronic HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92–5.36, p < 0.001), hypoalbuminemia (aHR = 2.31, 95% CI 1.72–3.09; p < 0.001), and hyponatremia (aHR = 1.48, 95% CI 1.09–2.01; p = 0.01). LT recipients with more than 1 predictor had a higher incidence of advanced fibrosis, the highest being when all 3 predictors coexisted (log-rank: p < 0.001). Conclusions. Chronic HCV infection, hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis following LT. Patients with these risk factors should be serially monitored using noninvasive fibrosis biomarkers and prioritized for interventions.

Phase angle is associated with advanced fibrosis in patients chronically infected with hepatitis C virus

AimsThe objective of this study was to evaluate the association of phase angle (PhA) with advanced liver fibrosis in patients chronically infected with hepatitis C virus (HCV). Main methodsOne hundred sixty consecutive patients chronically infected with HCV were treated at the Hepatitis C outpatient care setting of our hospital from April 2010 to May 2011 and prospectively evaluated. Bioelectrical impedance analysis measurements were performed during the first hospital visit. Biochemical measurements and liver biopsy data were collected from the patients' medical records and included in the analysis only if they were performed within three months of the inclusion of the patient in the study. Key findingsOne hundred sixty consecutive patients were evaluated and 25 patients were excluded. A total of 135 patients with 49.8±11.4years old were studied. Among these patients, 60% were male and the PhA was 6.5±0.8°. Regarding the stage of fibrosis, patients with advanced fibrosis were older and had more insulin resistance and more inflammation compared with patients that had mild fibrosis. Logistic regression analysis revealed that PhA was a predictor of advanced fibrosis even when adjusted for gender, age, HOMA-IR, HDL-cholesterol and AST (OR: 0.227; CI 95%: 0.090–0.569; p: 0.013). The best PhA cut-off points associated with advanced fibrosis for the combined data, for females and for males were 6.43°, 5.94° and 6.72°, respectively. SignificancePhA was predictor of advanced liver fibrosis in patients chronically infected with HCV. In the sample evaluated, for each one-degree decrease in PhA, the risk of advanced fibrosis increased more than four-fold.

Clinical Presentation, Treatment Outcome and Predictors of Severity in Autoimmune Hepatitis: A Retrospective, Multicenter Experience

AIM: Autoimmune Hepatitis (AIH) is a chronic hepatitis of unknown etiology. It affects adults and children and can progress to cirrhosis. We aim to investigate the mode of presentation, predictors of severity and treatment outcome of AIH in Saudi patients. METHODS: This is a multicenter retrospective study that involved patients diagnosed with AIH from 3 tertiary hospitals. Clinical, biochemical, radiological and histopathological data were collected and treatment outcomes were reported. RESULTS: A total of 212 patients were included. Female: male ratio was 3:2 and the mean age was 36.2 ± 16.8 years while 50 patients (23.6%) were above age of 50. Abnormal liver function tests (LFTs) were found in (45%). Presentation was chronic in 37.7%, acute in 30.7%, with evidence of liver cirrhosis in 28.8% and with a fulminant disease in 2.8%. Antinuclear antibody (ANA) and Anti-smooth muscle antibody (ASMA) were negative in 65 (30.6%) and 74 (35%) patients respectively. Pre-treatment liver biopsies in 166 patients showed advanced fibrosis (stage 3 and 4) in 63.3%. On multivariate analysis, platelets, alanine transaminase (ALT) level and immunoglobulin G (IgG) level were predictors of fibrosis. Complete response was achieved in 74.5% while 9% had partial response and 16.5% had no response to treatment. CONCLUSION: The majority of AIH patients had advanced fibrosis at the time of diagnosis and liver cirrhosis was found in nearly one-third of cases. IgG, ALT, and platelet were predictors of advanced fibrosis. Complete response to treatment was achieved in two-third of patients. Relying on autoimmune markers for diagnosis can be misleading.

Usefulness of ultrasonographic estimation of preperitoneal and subcutaneous fat thickness in the diagnosis of nonalcoholic fatty liver disease in diabetic patients.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have been regarded as the hepatic manifestation of metabolic syndrome. Abdominal wall fat index (AFI), defined as the ratio of preperitoneal and subcutaneous fat thickness in the abdomen estimated by ultrasonography (US), has been shown to be useful in screening for disorders related to metabolic syndrome. We investigated the relation between AFI and NAFLD/NASH in diabetic patients. The degree of fat accumulation in the liver and the thickness of preperitoneal and subcutaneous fat were determined by US in 340 diabetic patients. An NAFLD fibrosis score (NAFLD-FS) was used to assess the advancement of hepatic fibrosis in NAFLD patients. Of all 340 subjects, 209 (61 %) were diagnosed with NAFLD by US. AFI of NAFLD subjects was significantly higher than that of non-NAFLD subjects. Of the 209 subjects with NAFLD, 31 (15 %) were shown to have advanced NASH fibrosis according to NAFLD-FS. Multivariate analysis identified AFI as a significant predictor of advanced fibrosis. AFI easily obtained by US was significantly related to the presence of NAFLD and/or advanced hepatic fibrosis in diabetic patients.

Assessment of Liver Function and Liver Fibrosis with Dynamic Gd-EOB-DTPA–Enhanced MRI

To evaluate the ability of segmental linear fitting analysis of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid liver perfusion magnetic resonance imaging (MRI) to assess liver function and liver fibrosis. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid liver perfusion MRI was performed in 41 patients, and perfusion estimates were generated by segmental linear fitting analysis of the time-intensity curves. The relationships of Tin, Tout, Kup, and the ratio between the signal intensities of the peak and the last phase with liver fibrosis stage and laboratory measurements of liver function were evaluated. Serum prealbumin concentration was significantly positively correlated with Kup and the signal intensity ratio and was significantly negatively correlated with Tin and Tout. Tin and Tout were significantly higher and Kup and the signal intensity ratio were significantly lower in patients with advanced fibrosis than those without. Tout was the best predictor of advanced fibrosis, with an area under the receiving operating characteristic curve of 0.843, a sensitivity of 100%, and a specificity of 80%. A new procedure of quantifying the hepatocyte-specific uptake of a T1-enhancing contrast agent can be used to assess impaired hepatobiliary function. The parameters obtained from perfusion MRI have the potential to predict advanced fibrosis.

Interleukin-28B rs12979860 C allele: Protective against advanced fibrosis in chronic hepatitis C genotype 1 infection.

Background and Aim: While genetic polymorphisms upstream of the interleukin-28B(IL28B) gene are associated with necroinflammatory activity grade in chronic hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is less definitive. Pretreatment liver biopsies in a cohort of treatment-naïve patients with HCV-1 were analyzed to evaluate associations between liver histology, and the rs12979860 and rs8099917 IL28B single nucleotide polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high activity grade (A2/3) were identified using multivariable logistic regression analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141 patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P = 0.03), with an increasing number of Talleles associated with a higher frequency of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97–0.99; P < 0.0001), high activity grade (OR 5.68, 95% CI% 1.86–17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36, 95% CI 0.14–0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00–1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be independently associated with a lower prevalence of advanced fibrosis stage in HCV-1 infection. This association warrants further evaluation.

Acoustic radiation force impulse imaging as noninvasive marker of hepatic fibrosis

Background: Acoustic Radiation Force impulse Imaging (ARFI) is a novel non-invasive technique studying the localized mechanical properties of tissue by utilizing short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response(tissue displacement), providing a measure of tissue elasticity. Aims: To investigate the feasibility of ARFI imaging as a noninvasive method for assessing liver fibrosis compared to liver biopsy scores in patients with suspected chronic liver disease. Method: A prospective comparison study of ARFI elastography (Virtual Touch imaging, ACUSON S2000 ultrasound unit, Siemens) in a consecutive series of patients who underwent liver biopsy for assessment of liver stiffness was measured in meters per second. Mean ARFI velocities were compared with Modified Ishak scores and Brunt score for fibrosis in liver biopsy findings. Results: Study included 40 patients of suspected chronic liver disease who underwent liver biopsy and ARFI Elastography from the same segment of liver between the age group of 38.7 ± 14.4 years with predominant male gender (80%) over a period of 1 year. Cryptogenic cause for chronic hepatitis (32.5%) was the leading cause followed by NASH (22.5%) and then contributed equally by viral etiology of HCV and HBV (20%) each. The median ARFI value is 1.55mt/sec and there is an increasing trend of ARFI values as Childs score increases. ARFI proved to be a better predictor of advanced fibrosis (F3 or F4). The spearman rho correlation coefficients between median values of ARFI measurements and the histological fibrosis stage of the Metavir score and Brunt score were both highly significant (P< 0.01) with rho of 0.523 and 0.69 respectively. Conclusion: Our study showed that ARFI sonoelastography stands out on account of its very good correlation with liver biopsy (gold standard for evaluating liver fibrosis).

Serum connective tissue markers as predictors of advanced fibrosis in patients with chronic hepatitis B and D

Liver biopsy to assess fibrosis is invasive and prone to sampling error. While algorithms of serum markers to predict fibrosis stage have been described for chronic hepatitis C, these cannot be applied equally well to hepatitis B. We therefore determined 9 serum fibrosis markers, liver biochemical tests and ultrasound parameters in 109 consecutive adult patients with chronic hepatitis B and D. All patients had compensated liver disease. Using the METAVIR score, advanced disease was defined as fibrosis stage ≥F2, and active inflammation as grade ≥A2. A gold standard was created considering splenomegaly and/or platelets <150,000 as indicators of advanced fibrosis irrespective of histology. Area under receiver operating characteristics curves was used for assessment of single markers and odds ratio for their combinations. Patients with advanced disease were older, had lower albumin, higher gamma glutamyl transferase and lower platelet. Levels of 6 of the 9 fibrosis markers, tissue inhibitor of metalloproteinases-1, procollagen type III aminoterminal propeptide, matrix metalloproteinase-2, laminin, hyaluronan and collagen IV correlated with advanced fibrosis. Markers useful for fibrosis prediction also predicted marked inflammation. Using the gold standard, age, prothrombin time, gamma glutamyl transferase and albumin were independent predictors of fibrosis with odds ratio's of 3.11, 4.18, 3.35 and 5.25, respectively. Their combined use predicted fibrosis with an odds ratio of 228.8. Tissue inhibitor of metalloproteinases-1 and hyaluronan were powerful predictors of fibrosis (Odds ratio's of 8.65 and 8.38). Their combined use revealed an odds ratio of 28.6, when compared with the gold standard. In conclusion, advanced liver fibrosis in chronic hepatitis B and D may be predicted with use of these two fibrosis markers.

Explanted liver inflammatory grade predicts fibrosis progression in hepatitis C recurrence

Factors present prior to liver transplantation (LT) that predict fibrosis progression in recurrent hepatitis C infection (HCV) after LT would be important to identify. This study sought to determine if histologic grade of HCV in the explant predicts fibrosis progression in recurrent HCV. The clinical and histologic data of all 159 patients undergoing their first LT for HCV at our center from 1998 to 2001 were retrospectively reviewed with follow-up through June 2008. Twenty-five cases were excluded for: non-HCV-related graft loss <90 days (19), recidivism (4), or unavailable explant or follow-up biopsies (2). A single pathologist scored (Ishak) explants in a blinded fashion. Patients were grouped by explant inflammatory grade ≤ 4 (group1) and >4 (group 2). Prospectively scored liver biopsies (protocol months 1 and 4, annually, and as indicated clinically) were reviewed for development of advanced fibrosis (bridging or cirrhosis). Cox proportional hazard regression was used to analyze the association of explant grade, donor, viral and LT factors with progression to advanced fibrosis. The groups were well-matched for patient, viral, donor, and transplant factors. Five-year advanced fibrosis-free survival in group 1 versus group 2 was 63% versus 28%, P < 0.001. Explant grade >4 was associated with increased HCV-related graft loss at 1 (6% versus 3%) and 5 (36% versus 14%) years post-LT (P = 0.003). On univariate and multivariate Cox regression analysis, predictors of advanced fibrosis were explant grade >4 (hazard ratio [HR] = 3.3, 95% confidence interval [CI] = 1.9-5.6, P < 0.001) donor age >50 (HR = 3.3, 95% CI = 1.9-5.7, P < 0.001) and viral load at LT of >158,730 IU/mL (HR = 1.8, 95% CI = 1.05-3.1, P = 0.03). Explant histologic grade can identify patients requiring more aggressive monitoring and intervention for HCV recurrence post-LT.