Liver stiffness measured by transient elastography in patients with acute pancreatitis

BackgroundAlcohol abuse constitutes a risk factor for acute pancreatitis and liver cirrhosis, and cirrhosis in turn may delay the recovery from pancreatitis. We evaluated the occurrence and significance of liver fibrosis or cirrhosis in patients with acute pancreatitis by applying transient elastography (TE).MethodsTE was carried out in 78 patients with acute pancreatitis. Comparisons were made to the severity and recurrence of pancreatitis, to biological markers for fibrosis (APRI test), alcohol intake (AST/ALT ratio, AUDIT), and prothrombin time (TT-SPA). A cut-off value of ≥7.5 kilopascals (kPa) was set for increased liver stiffness, and ≥10 kPa for significant fibrosis.ResultsThe aetiology of pancreatitis was alcohol intake in 62 patients, gallstones in 11, idiopathic in 3, tumour in 1 and medication in 1. TE was successful in 64 out of 78 patients. The median TE value was 6.5 kPa (range 2.5–61.1); 22 (35%) had values ≥7.5 kPa and 7 (11%) ≥10 kPa. Values ≥7.5 were associated with older age, higher APRI ratio, and lower TT-SPA. It did not predict the length of hospitalization or the recurrence of pancreatitis. Increased AST/ALT ratio was associated with high TE values, whereas AUDIT values were not. Values ≥10 kPa seemed to indicate manifest cirrhosis, hepatitis or subsequent development of diabetes.ConclusionsTE values ≥7.5 kPa did not predict the length of hospital stay or recurrence of pancreatitis but there were some findings of impaired liver function. Values ≥10 kPa may indicate subsequent development of diabetes and a more severe course of acute pancreatitis.     

Abnormal Liver Function in Relation to Hemodynamic Profile in Heart Failure Patients

BackgroundWe studied the relation between liver function abnormalities and hemodynamic profile in patients with heart failure (HF).Methods and ResultsIn 323 HF patients, liver function was determined by aspartate and alanine aminotransferase (AST, ALT), alkaline phosphatase, γ-glutamyl transpeptidase (GGT), lactate dehydrogenase, and direct and total bilirubin (Bili dir, Bili tot). Central venous pressure (CVP) and cardiac index (CI) were determined invasively. Follow-up consisted of time to all-cause mortality. Mean age was 53 ± 15 years, and 60% were male. In multivariable analysis, all liver function tests related to CVP, but higher CVP was predominantly related to GGT (r = 0.336, P < .001) and Bili dir (r = 0.370, P < .001). Only elevated AST (r =?0.177, P < .01), ALT (r = ?0.130, P < .05), and Bili tot (r = ?0.158, P < .01) were associated with both low CI and elevated CVP. The prognostic value of abnormal liver function tests was related to their interaction with CI and CVP.ConclusionsElevated liver function tests mainly indicate higher CVP, whereas only the presence of elevated AST, ALT, or Bili dir may indicate a low CI. The absence of prognostic information in the presence of invasive hemodynamic measurements suggests that abnormal liver function tests in HF reflect a poor hemodynamic status.     

Novel non-invasive score to predict cirrhosis in the era of hepatitis C elimination: A population study of ex-substance users in Singapore

BackgroundChronic hepatitis C infection is common among people with history of substance use. Liver fibrosis assessment is a barrier to linkage to care, particularly among those with history of substance users. The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination, especially in countries where transient elastography (TE) is not available. We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population.MethodsHCV patients with history of substance use between 2011 and 2016 were analyzed. All patients had TE for liver fibrosis assessment. Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared. Youden's index was used to determine optimal cut-off of the novel score.ResultsA total of 579 patients were included. In multivariate logistic regression, cirrhosis on TE was associated with age (P = 0.002), aspartate aminotransferase (AST) (P = 0.004), and platelet count (P < 0.001), but not alanine aminotransferase (ALT) (P = 0.896). These form the components of modified AST-to-platelet ratio index (APRI) score. Modified APRI was superior to APRI in predicting cirrhosis (AUROC, 0.796 vs. 0.770, P = 0.007), but not fibrosis-4 score (FIB-4) (P = 1.00). Modified APRI at cut-off of 4 has sensitivity, specificity and negative predictive value (NPV) of 94.4%, 26.9% and 92.6%, respectively, and at 19, has sensitivity, specificity and positive predictive value (PPV) of 33.3%, 96.2% and 77.1%, respectively. FIB-4 has a NPV and PPV of 88.6%, 41.8% and 78.5%, 77.6%, at cut-off of 1.45 and 3.25, respectively. Using the cut-off of 4 and 14 for modified APRI, 32.5% of patients can be correctly classified and misses out only 5.6% of cirrhosis patients.ConclusionsModified APRI score is superior in predicting cirrhosis in HCV population, with 32.5% of the population being correctly classified using cut-off of 4 and 14. Further studies are required to validate the findings.     

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis

AIM:To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.METHODS:We conducted a study of 63 patients with liver cirrhosis.A control group comprised of 30 age and gender-matched healthy persons.Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made.Estimated glomerular filtration rate from serum creatinine(GFRCr)and cystatin C(GFRCys)was calculated.RESULTS:We confirmed significant differences in val-ues of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh(P=0.01),and a significant correlation with model of end stage liver disease(MELD)score(rs=0.527,P<0.001).More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr(P<0.001).Significantly higher renal resistive index was noted in Child-Pugh C than in A(P<0.001)and B stage(P=0.001).Also,a significant correlation between renal resistive index and MELD score was observed(rs=0.607,P<0.001).Renal resistive index correlated significantly with cystatin C(rs=0.283,P=0.028)and showed a negative correlation with GFRCys(rs=-0.31,P=0.016).CONCLUSION:Cystatin C may be a more reliable marker for assessment of liver insufficiency.Additionally,cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.     

Serum Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients with Chronic Liver Diseases

We meesured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employses, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcohotic liver cirrhosls, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 ± 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 ± 5.1 and 13.7 ± 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty-two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and γ-glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics     

Evaluation of acoustic radiation force impulse imaging for determination of liver stiffness using transient elastography as a reference

AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan^© (FS)] as a reference.METHODS: Six hundred and six patients were enrolled in this study. All patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixty-eight patients underwent liver biopsy.RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs 482/606 (79.5%), P < 0.001]. ARFI-SWV correlated significantly with FS-LS (r = 0.920, P < 0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.09 ± 0.13 m/s for patients with no significant fibrosis (FS-LS < 7.6 kPa); 1.46 ± 0.27 m/s for patients with significant liver fibrosis (7.6 < FS-LS ≤ 13.0 kPa); and 2.55 ± 0.77 m/s for patients with liver cirrhosis (FS-LS > 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations.CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis.     

Relationship between liver function and brain shrinkage in patients with alcohol dependence

Background: Oxidative stress has been proposed as one of the mechanisms of alcohol‐induced brain shrinkage and alcohol‐induced hepatotoxicity. The aim of this study was to assess the correlations between liver function and brain volume (BV) measurements in patients with alcohol dependence. Methods: We recruited 124 patients with alcohol dependence and 111 healthy control subjects from National Institute of Health, National Institute on Alcohol Abuse and Alcoholism inpatient alcohol treatment program. Gamma‐glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as hematocrit (Hct) and albumin were assayed shortly after admission. Magnetic resonance imaging examination was conducted in both groups (after 3‐week abstinence in the patient group). We used stepwise linear regression analyses to determine the variables most strongly correlated with brain shrinkage. Results: Patients with alcohol dependence had lower BV, and greater brain shrinkage as measured by gray matter ratio (GMR), white matter ratio (WMR), brain ratio (BR), and higher cerebrospinal fluid ratio ratio (CSFR) compared with their healthy counterparts. Age and sex were significantly correlated with some BV measurements in both patient and control groups. Body mass index (BMI) was significantly correlated with CSFR, BR, GMR, and WMR; Hct with CSFR and BR; serum GGT level with BV, CSFR, BR, GMR, and WMF in the patient group. No biological variables were correlated with BV indices in the control group. In gender‐stratified analysis, age was significantly correlated with brain shrinkage in male patients but not in female patients. Serum GGT level in male and female patients, Hct in male patients, and AST levels in female patients were significantly correlated with brain shrinkage. Conclusions: Our results showed that the higher levels of liver function indices, especially GGT, correlated with BV shrinkage as measured using CSFR, BR, GMR, and WMR in patients with alcohol dependence but not in controls. Serum GGT level outweighed aging effect on brain shrinkage in female patients.     

Fibrosis staging in chronic hepatitis C: analysis of discordance between transient elastography and liver biopsy

Summary. In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir ≥ F2) is variable. Constitutional and liver disease‐related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)‐RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy‐six of 286 (26.6%) had stage ≥F2 and TE < 7.1 kPa (false negative); 21 of 286 (7.3%) had stage <F2 and TE ≥ 7.1 kPa (false positive). No patient with discordant results had cirrhosis. By Dale model, aspartate aminotransferase (AST) was found to be the unique variable significantly related (P = 0.046) with discordance between biopsy and TE. Discordance rate was 43.4% (82 patients) with AST < 1.5 × UNL vs 25.8% (25 patients) with AST ≥ 1.5 × UNL (P = 0.004). False negative rate was 43.4 (82 patients) with AST < 1.5 × UNL vs 17.1% (13 patients) with AST ≥ 1.5 × UNL (P < 0.001). Areas under the receiver operating characteristic (AUROC) for F ≥ 2, according to AST < 1.5 × UNL vs ≥ 1.5 × UNL were 0.738 (95% CI: 0.683–0.812) and 0.854(95% CI: 0.754–0.907). Transient elastography is not adequate on its own to rule out or to rule in significant fibrosis, as it is influenced by major variations in biochemical activity of liver disease. Liver stiffness, at low levels of AST, can underestimate fibrosis.     

Validation of aspartate aminotransferase to platelet ratio for diagnosis of liver fibrosis and prediction of postoperative prognosis in infants with biliary atresia

AIM: To validate the value of aspartate aminotransferase to platelet ratio index(APRI) in assessment of liver fibrosis and prediction of postoperative prognosis of biliary atresia(BA) infants from Mainland China.METHODS: Medical records of 153 BA infants who were hospitalized from January 2010 to June 2013 were reviewed. The efficacy of APRI for diagnosis of liver fibrosis was assessed using the receiver operator characteristic(ROC) curve compared to thepathological Metavir fibrosis score of the liver wedge specimens of 91 BA infants. The prognostic value of preoperative APRI for jaundice persistence, liver injury,and occurrence of cholangitis within 6 mo after KP was studied based on the follow-up data of 48 BA infants.RESULTS: APRI was significantly correlated with Metavir scores(rs = 0.433; P 0.05). The mean APRI value was 0.76 in no/mild fibrosis group(Metavir score F0-F1), 1.29 in significant fibrosis group(F2-F3), and2.51 in cirrhosis group(F4)(P 0.001). The area under the ROC curve(AUC) of APRI for diagnosing significant fibrosis and cirrhosis was 0.75(P 0.001)and 0.81(P = 0.001), respectively. The APRI cut-off of 0.95 was 60.6% sensitive and 76.0% specific for significant fibrosis diagnosis, and a threshold of 1.66 was 70.6% sensitive and 82.7% specific for cirrhosis.The preoperative APRI in infants who maintained jaundice around 6 mo after KP was higher than that in those who did not(1.86 ± 2.13 vs 0.87 ± 0.48, P 0.05). The AUC of APRI for prediction of postoperative jaundice occurrence was 0.67. A cut-off value of0.60 showed a sensitivity of 66.7% and a specificity of 83.3% for the prediction of jaundice persistence.Preoperative APRI had no significant association with later liver injury or occurrence of cholangitis.CONCLUSION: Our study demonstrated that APRI could diagnose significant liver fibrosis, especially cirrhosis in BA infants, and the elevated preoperative APRI predicts jaundice persistence after KP.     

Minimal Hepatic Encephalopathy in Patients with Cirrhosis by Measuring Liver Stiffness and Hepatic Venous Pressure Gradient

Background/Aim:

Transient elastography (TE) of liver and hepatic venous pressure gradient (HVPG) allows accurate prediction of cirrhosis and its complications in patients with chronic liver disease. There is no study on prediction of minimal hepatic encephalopathy (MHE) using TE and HVPG in patients with cirrhosis.

Patients and Methods:

Consecutive cirrhotic patients who never had an episode of hepatic encephalopathy (HE) were enrolled. All patients were assessed by psychometry (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), critical flicker frequency test (CFF), TE by FibroScan and HVPG. MHE was diagnosed if there were two or more abnormal psychometry tests (± 2 SD controls).

Results:

150 patients with cirrhosis who underwent HVPG were screened; 91 patients (61%, age 44.0 ± 11.4 years, M:F:75:16, Child''s A:B:C 18:54:19) met the inclusion criteria. Fifty three (58%) patients had MHE (Child A (7/18, 39%), Child B (32/54, 59%) and Child C (14/19, 74%)). There was no significant difference between alanine aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin level in patients with MHE versus non MHE. Patients with MHE had significantly lower CFF than non MHE patients (38.4 ± 3.0 vs. 40.2 ± 2.2 Hz, P = 0.002). TE and HVPG in patients with MHE did not significantly differ from patients with no MHE (30.9 ± 17.2 vs. 29.8 ± 18.2 KPas, P = 0.78; and 13.6 ± 2.7 vs. 13.6 ± 3.2 mmHg, P = 0.90, respectively).There was significant correlation of TE with Child''s score (0.25, P = 0.01), MELD (0.40, P = 0.001) and HVPG (0.72, P = 0.001) while no correlation with psychometric tests, CFF and MHE.

Conclusion:

TE by FibroScan and HVPG cannot predict minimal hepatic encephalopathy in patients with cirrhosis.     

Liver injury during antituberculosis treatment: An 11-year study

Setting: Bispebjerg Hospital, Department of Pulmonary Medicine, tuberculosis referral center for the Municipality of Copenhagen.Objective: To evaluate routine procedure for the management of liver injury during antituberculosis treatment.Design: From 1983–1993, 765 patients for whom we could trace 752 files (98%) were treated at our ward with standard Danish treatment for tuberculosis. From 1983–1986 they received a three-drug (9-month) regimen and from 1986–1993 a four-drug (6-month) regimen consisting of isoniazid, rifampicin, ethambutol + pyrazinamide. Data from a retrospective chart review.Results: An increase in aspartate aminotransferase (AST) of more than twice the upper limit of normal (ULN) was recorded in 127 patients (16%). 66 had elevated AST before treatment; most of these were men with a daily alcohol consumption in excess of 60 g. In the remaining 61 patients (8%) AST increased during antituberculosis treatment. 30 of these patients were excessive alcohol consumers, and seven had alcoholic liver cirrhosis. Despite an increase in AST of median 6 × ULN (range 2–25 × ULN), it was possible to continue treatment in 31 (15 excessive alcohol consumers) or reintroduce it fully in 14 (12 excessive alcohol consumers). Only 16 patients (2%), including 11 women with no daily alcohol consumption, needed a modified regimen. These patients were older (P < 0.05), seven were jaundiced, and one had alcoholic liver cirrhosis. Hepatotoxicity was confirmed by challenge with pyrazinamide (n = 7), isoniazid (n = 6) and combined isoniazid/rifampicin (n = 1). No deaths were caused by hepatotoxicity.Conclusion: In spite of an increase in AST levels to approximately 6 × ULN during antituberculosis treatment, the drugs can be continued or reintroduced in full in most cases. Risk factors of hepatotoxicity included old age, female sex and extensive tuberculosis, and not alcohol consumption. Overall, hepatotoxicity during antituberculosis treatment can be monitored and managed easily.     

Point shear wave elastography method for assessing liver stiffness

AIM:To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness.METHODS:This was a single-center,cross-sectional study.Consecutive patients with chronic viral hepatitis scheduled for liver biopsy(LB)(Group 1)and healthy volunteers(Group 2)were studied.In each subject 10 consecutive point shear-wave elastography(PSWE)measurements were performed using the iU22 ultrasound system(Philips Medical Systems,Bothell,WA,United States).Patients in Group 1 underwent PSWE,transient elastography(TE)using FibroScan(Echosens,Paris,France)and ultrasound-assisted LB.For the assessment of PSWE reproducibility two expert raters(rater 1 and rater 2)independently performed the examinations.The performance of PSWE was compared to that of TE using LB as a reference standard.Fibrosis was staged according to the METAVIR scoring system.Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve(AUC)for F≥2,F≥3and F=4.The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin’s concordance correlation coefficient.RESULTS:To assess the performance of PSWE,134consecutive patients in Group 1 were studied.The median values of PSWE and TE(in kilopascals)were 4.7(IQR=3.8-5.4)and 5.5(IQR=4.7-6.5),respectively,in patients at the F0-F1 stage and 3.5(IQR=3.2-4.0)and 4.4(IQR=3.5-4.9),respectively,in the healthy volunteers in Group 2(P<10-5).In the univariate analysis,the PSWE and TE values showed a high correlation with the fibrosis stage;low correlations with the degree of necroinflammation,aspartate aminotransferase and gamma-glutamyl transferase(GGT);and a moderate negative correlation with the platelet count.A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables.The following AUC values were found:0.80(0.71-0.87)for PSWE and 0.82(0.73-0.89)for TE(P=0.42);0.88(0.80-0.94)for PSWE and 0.95(0.88-0.98)for TE(P=0.06);and 0.95(0.89-0.99)for PSWE and 0.92(0.85-0.97)for TE(P=0.30)for F≥2,F≥3 and F=4,respectively.To assess PSWE reproducibility,116 subjects were studied,including 47consecutive patients scheduled for LB(Group 1)and 69 consecutive healthy volunteers(Group 2).The intraobserver agreement ranged from 0.83(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 1 and from 0.84(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 2.The interobserver agreement yielded values from0.83(95%CI:0.78-0.88)to 0.93(95%CI:0.91-0.95).CONCLUSION:PSWE is a reproducible method for assessing liver stiffness,and it compares with TE.Compared with patients with nonsignificant fibrosis,healthy volunteers showed significantly lower values.     

Impacts of common factors of life style on serum liver enzymes

AIM: To investigate the impacts of gender, age and factors of life style (alcohol, overweight, coffee and smoking) on serum liver enzymes.METHODS: Serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were measured from 6269 apparently healthy individuals (2851 men, 3418 women, mean age 45 ± 12 years, range 25-74 years) in a national cross-sectional health survey. All subjects underwent detailed clinical examinations and interviews including the amount and pattern of alcohol use, coffee consumption and smoking habits.RESULTS: In this population with a mean ± SD alcohol consumption of 65 ± 105 g/wk and body mass index (BMI) of 26.1 ± 4.3 kg/m², both ALT and GGT were significantly influenced by alcohol use (P < 0.001) and BMI (P < 0.001), whereas smoking increased only GGT (P < 0.001). A significant effect of age on ALT was seen in men (P < 0.001) whereas not in women. Significant two-factor interactions of alcohol use in men were observed with age (ALT: P < 0.01; GGT: P < 0.001) and BMI (GGT: P < 0.05). For ALT, a significant interaction also occurred between BMI and age (P < 0.005). In contrast, women showed significant interactions of alcohol use with BMI (GGT: P < 0.05), smoking (GGT: P < 0.001), and coffee consumption (GGT: P < 0.001).CONCLUSION: Life-style associated changes in liver enzymes may reflect health risks, which should be considered in the definition of normal limits for liver enzymes.     

Noninvasive assessment of liver damage in chronic hepatitis B

AIM:To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index(APRI)and neutrophillymphocyte(N/L)ratio to predict liver damage in chronic hepatitis B(CHB).METHODS:We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects.Liver biopsy materials were stained with hematoxylin-eosin and Masson’s trichrome.Patients’fibrosis scores and histological activity index(HAI)were calculated according to the Ishak scoring system.Fibrosis score was recognized as follows:F0-1 No/early-stage fibrosis,F2-6 significant fibrosis,F0-4 non-cirrhotic and F5-6 cirrhotic.Significant liver fibrosis was defined as an Ishak score of≥2.APRI and N/L ratio calculation was made by blood test results.RESULTS:The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores(P<0.001).Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count.APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients.However,this significance was not confirmed by multiple logistic regression analysis.The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01with sensitivity,specificity,positive predictive value and negative predictive value of 62%(36%-86%),74%(62%-83%),29%(13%-49%)and 92%(82%-97%),respectively.In addition,correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI(r=-0.218,P=0.041).CONCLUSION:N/L ratio was negatively correlated with HAI.APRI score may be useful to exclude cirrhosis in CHB patients.     

Telaprevir- and boceprevir-based tritherapies in real practice for F3-F4 pretreated hepatitis C virus patients

AIM:To assess,in a routine practice setting,the sus-tained virologic response(SVR) to telaprevir(TPV) or boceprevir(BOC) in hepatitis C virus(HCV) nullresponders or relapsers with severe liver fibrosis.METHODS:One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon(peg-INF) α2a + ribavirin(PR) according to standard treatment schedules without randomization.These patients were treated in routine practice settings in 10 public or private health care centers,and the data were prospectively collected.Only patients with severe liver fibrosis(Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography),genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study.RESULTS:The Metavir fibrosis scores were F3 in 35(28%) and F4 in 90(72%) of the patients.In total,62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy.The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%.The SVR was 65.9% in the TPV group and 44.1% in the BOC group.Independent predictive factors of an SVR included a response to previous treatment,relapsers vs null-responders [OR = 3.9;(1.4,10.6),P = 0.0084],a rapid virological response(RVR) [OR 6.9(2.6,18.2),P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2(2.3,29.5),P = 0.001].During treatment,63 patients(50.8%) had at least one severe adverse event(SAE) of grade 3 or 4.A multivariate analysis identified two factors associated with SAEs:female gender [OR = 2.4(1.1,5.6),P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3(2.3,12.4),P ≤ 0.001].CONCLUSION:More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting.The SVR rate was influenced by the response to previous PR treatment,the RVR and liver stiffness.     

Estimating steatosis and fibrosis: Comparison of acoustic structure quantification with established techniques

AIM:To compare ultrasound-based acoustic structure quantification(ASQ) with established non-invasive techniques for grading and staging fatty liver disease.METHODS:Type 2 diabetic patients at risk of nonalcoholic fatty liver disease(n = 50) and healthy volunteers(n = 20) were evaluated using laboratory analysis and anthropometric measurements, transient elastography(TE), controlled attenuation parameter(CAP), proton magnetic resonance spectroscopy(1H-MRS; only available for the diabetic cohort), and ASQ.ASQ parameters mode, average and focal disturbance(FD) ratio were compared with:(1) the extent of liver fibrosis estimated from TE and nonalcoholic fatty liver disease(NAFLD) fibrosis scores; and(2) the amount of steatosis, which was classified according to CAP values.RESULTS:Forty-seven diabetic patients(age 67.0±8.6 years;body mass index 29.4±4.5 kg/m2)with reliable CAP measurements and all controls(age 26.5±3.2 years;body mass index 22.0±2.7 kg/m2)were included in the analysis.All ASQ parameters showed differences between healthy controls and diabetic patients(P0.001,respectively).The ASQ FD ratio(logarithmic)correlated with the CAP(r=-0.81,P0.001)and 1H-MRS(r=-0.43,P=0.004)results.The FD ratio[CAP250 d B/m:107(102-109),CAP between 250 and 300 d B/m:106(102-114);CAP between 300 and 350 d B/m:105(100-112),CAP≥350 d B/m:102(99-108)]as well as mode and average parameters,were reduced in cases with advanced steatosis(ANOVA P0.05).However,none of the ASQ parameters showed a significant difference in patients with advanced fibrosis,as determined by TE and the NAFLD fibrosis score(P0.08,respectively).CONCLUSION:ASQ parameters correlate with steatosis,but not with fibrosis in fatty liver disease.Steatosis estimation with ASQ should be further evaluated in biopsy-controlled studies.     

Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis

Background and AimsAlcohol-related liver disease is a leading cause of liver-related mortality. The effect of alcohol abstinence on the natural history of alcohol-related cirrhosis across distinct stages of portal hypertension has not been thoroughly investigated. In this study, we assessed the clinical implications of abstinence in patients with alcohol-related cirrhosis and clinically significant portal hypertension.MethodsAlcohol abstinence, hepatic decompensation, and mortality were assessed in patients with alcohol-related cirrhosis who underwent a baseline hepatic venous pressure gradient (HVPG) measurement and were diagnosed with clinically significant portal hypertension (HVPG ≥10 mm Hg).ResultsA total of 320 patients with alcohol-related cirrhosis (median age: 57 [interquartile range (IQR), 49.7-63.1] years; 75.6% male; 87.5% decompensated) and a median HVPG of 20 (IQR, 17-23) mm Hg were followed up for a median of 36 (IQR, 14-80) months. Overall, 241 (75.3%) patients remained abstinent, while 79 (24.7%) patients had active alcohol consumption. Alcohol abstinence was linked to a significantly reduced risk of hepatic decompensation (adjusted hazard ratio [aHR], 0.391; P < .001), as well as liver-related (aHR, 0.428; P < .001) and all-cause (aHR, 0.453; P < .001) mortality, after adjusting for baseline HVPG, MELD, and previous decompensation. Importantly, alcohol abstinence significantly reduced the cumulative incidence of hepatic decompensation in both groups with HVPG 10–19 mm Hg (P < .001) and HVPG ≥20 mm Hg (P = .002). The 3-year decompensation probability was 32.4% vs 60.0% in HVPG 10–19 mm Hg and 57.5% vs 82.6% in HVPG ≥20 mm Hg for abstinent patients vs active drinkers, respectively.ConclusionsAlcohol abstinence improves prognosis across all stages of portal hypertension in alcohol-related cirrhosis, including in patients who have already progressed to high-risk portal hypertension. (ClinicalTrials.gov, Number: NCT03267615).     

A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia

AIM:To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease(NAFLD)and hyperferritinemia,a frequent feature associated with more severe liver damage,despite at least 6 mo of lifestyle changes.METHODS:Eligible subjects had to be 18-75 years old who underwent liver biopsy for ultrasonographically detected liver steatosis and hyperferritinemia,ferritin levels≥250 ng/mL,and NAFLD activity score>1.Iron depletion had to be achieved by removing 350 cc of blood every 10-15 d according to baseline hemoglobin values and venesection tolerance,until ferritin<30 ng/mL and/or transferrin saturation(TS)<25%.Thirty-eight patients were randomized 1:1 to phlebotomy(n=21)or lifestyle changes alone(n=17).The main outcome of the study was improvement in liver damage according to the NAFLD activity score at 2 years,secondary outcomes were improvements in liver enzymes[alanine aminotransferases(ALT),aspartate aminotransferase(AST),and gamma-glutamyl-transferases(GGT)].RESULTS:Phlebotomy was associated with normalization of iron parameters without adverse events.In the21 patients compliant to the study protocol,the rate of histological improvement was higher in iron depleted vs control subjects(8/12,67%vs 2/9,22%,P=0.039).There was a better improvement in steatosis grade in iron depleted vs control patients(P=0.02).In patients followed-up at two years(n=35),ALT,AST,and GGT levels were lower in iron-depleted than in control patients(P<0.05).The prevalence of subjects with improvement in histological damage or,in the absence of liver biopsy,ALT decrease≥20%(associated with histological improvement in biopsied patients)was higher in the phlebotomy than in the control arm(P=0.022).The effect of iron depletion on liver damage improvement as assessed by histology or ALT decrease≥20%was independent of baseline AST/ALT ratio and insulin resistance(P=0.0001).CONCLUSION:Iron depletion by phlebotomy is likely associated with a higher rate of improvement of histological liver damage than lifestyle changes alone in patients with NAFLD and hyperferritinemia,and with amelioration of liver enzymes.     

Transient elastography in the assessment of liver fibrosis in adult thalassemia patients

Transient elastography (TE) is a valuable noninvasive technique of measuring liver stiffness and a reliable tool for predicting hepatic fibrosis in patients with chronic liver disease. The role of TE in patients with β‐thalassemia has not been extensively investigated. The present study aimed to evaluate the role of TE in the assessment of hepatic fibrosis in 115 adult patients with β‐thalassemia major (TM) (#59) or intermedia (TI) (#56). TE was performed according to current practice. Histologic data were obtained in 14 cases. Liver iron concentration was assessed by atomic absorption spectrometry and T2* magnetic resonance. In patients with TM, the proportion of anti‐HCV positive viremic patients, median serum ferritin levels, and TE values were significantly higher than in TI. In the group of 14 patients who underwent liver biopsy, a significant positive correlation was observed between liver stiffness and fibrosis stage (r = 0.73, P = 0.003). Severe fibrosis is diagnosed with a sensitivity of 60% and a specificity of 89%, whereas cirrhosis is detected with a sensitivity of 100% and a specificity of 92%. At multivariate analysis, the variables independently associated with TE were ALT, GGT, and bilirubin levels in both groups and, in patients with TM, HCV RNA positivity. In β‐thalassemia patients, TE is a reliable tool for assessing liver fibrosis even if the influence of iron overload has to be clarified. Am. J. Hematol. 85:564–568, 2010. © 2010 Wiley‐Liss, Inc.     

Noninvasive elastography-based assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis

The development of liver fibrosis markers in primary biliary cirrhosis (PBC) is needed to facilitate the assessment of its progression and the effectiveness of new therapies. Here, we investigated the potential usefulness of transient elastography (TE) in the noninvasive evaluation of liver fibrosis stage and disease progression in PBC. We performed, first, a prospective performance analysis of TE for the diagnosis of METAVIR fibrosis stages in a diagnostic cohort of 103 patients and, second, a retrospective longitudinal analysis of repeated examinations in a monitoring cohort of 150 patients followed-up for up to 5 years. All patients were treated with ursodeoxycholic acid. Diagnostic thresholds of liver stiffness in discriminating fibrosis stages ≥ F1, ≥ F2, ≥ F3, and =F4 were 7.1, 8.8, 10.7, and 16.9 kPa, respectively. TE showed high performance and was significantly superior to biochemical markers (e.g., aspartate aminotransferase [AST]/platelet ratio, FIB-4, hyaluronic acid, AST/alanine aminotransferase ratio, and Mayo score) in diagnosing significant fibrosis, severe fibrosis, or cirrhosis. Analysis of the monitoring cohort data set using generalized linear models showed the following: (1) an overall progression rate of 0.48 ± 0.21 kPa/year (P = 0.02) and (2) no significant progression in patients with F0-F1, F2, or F3 stages, but a significant increase (4.06 ± 0.72 kPa/year; P < 0.0001) in cirrhotic patients. A cut-off value of 2.1 kPa/year was associated with an 8.4-fold increased risk of liver decompensations, liver transplantations, or deaths (P < 0.0001, Cox regression analysis). CONCLUSION: TE is one of the best current surrogate markers of liver fibrosis in PBC. Over a 5-year period, on-treatment liver stiffness appears stable in most noncirrhotic PBC patients, whereas it significantly increases in patients with cirrhosis. Progression of liver stiffness in PBC is predictive of poor outcome.