Liver-related Events In Patients Research Articles

Combined Liver Stiffness and Α-fetoprotein Further beyond the Sustained Virologic Response Visit as Predictors of Long-Term Liver-Related Events in Patients with Chronic Hepatitis C.

Aims Long-term risk stratification using combined liver stiffness (LS) and clinically relevant blood tests acquired at the baseline further beyond the sustained virologic response (SVR) visit for chronic hepatitis C (CHC) has not been thoroughly investigated. This study retrospectively investigated the prognostics of liver-related events (LREs) further beyond the SVR visit. Methods Cox regression and random forest models identified the key factors, including longitudinal LS and noninvasive test results, that could predict LREs, including hepatocellular carcinoma, during prespecified follow-ups from 2010 to 2021. Kaplan–Meier survival analysis estimated the significance of between-group risk stratification. Results Of the entire eligible cohort (n = 520) of CHC patients with SVR to antiviral therapy, 28 (5.4%) patients developed post-SVR LREs over a median follow-up period of 6.1 years (interquartile range = 3.5–8.7). The multivariate Cox regression analysis identified two significant predictors of LREs after the year 3 post-SVR (Y3PSVR) baseline (LRE, n = 15 of 28, 53.6%, median follow-up = 4.1 [1.6–6.4] years after Y3PSVR): LS at Y3PSVR (adjusted hazard ratio [aHR] = 3.980, 95% confidence interval [CI] = 2.085–7.597, P < 0.001), and α-fetoprotein (AFP) at Y3PSVR (aHR = 1.017, 95% CI = 1.001–1.034, P=0.034). LS ≥1.45 m/s and AFP ≥3.00 ng/mL for Y3PSVR yielded positive likelihood ratios of 4.24 and 2.62, respectively. Kaplan–Meier analysis revealed that among the stratified subgroups, the subgroup with concurrent LS ≥1.45 m/s and AFP ≥3.00 ng/mL at Y3PSVR exhibited the highest risk of LREs after Y3PSVR (log-rank P < 0.001). Conclusion We recommend the combined use of concurrent LS and AFP in future prediction models for LREs in CHC. Patients with concurrently high LS and AFP values further beyond the SVR visit may require a recall policy involving intense surveillance.

OS043 - Young-onset diabetes mellitus increases the risk of liver-related events in patients with non-alcoholic fatty liver disease

OS043 - Young-onset diabetes mellitus increases the risk of liver-related events in patients with non-alcoholic fatty liver disease

FRI101 - Diagnostic performance of AGILE 3+ score for identification of advanced fibrosis and prediction of liver-related events in patients with non-alcoholic fatty liver disease

FRI101 - Diagnostic performance of AGILE 3+ score for identification of advanced fibrosis and prediction of liver-related events in patients with non-alcoholic fatty liver disease

Risk of liver-related events by age and diabetes duration in patients with diabetes and nonalcoholic fatty liver disease.

Several guidelines recommend screening for NAFLD in patients with type 2 diabetes (T2D). We aimed to determine if there is a threshold of age and duration of T2D for liver-related event development to guide screening strategies. We conducted a territory-wide retrospective cohort study of adult patients with NAFLD and T2D diagnosed between 2000 and 2014 in Hong Kong to allow for at least 5 years of follow-up. The primary endpoint was liver-related events, defined as a composite of HCC and cirrhotic complications. This study included 7028 patients with NAFLD with T2D (mean age, 56.1 ± 13.3 years; 3363 male [47.9%]). During a follow-up of 77,308 person-years, there was a threshold effect with 1.1%, 4.9%, and 94.0% of patients developing liver-related events at the age of <40, 40-50, and ≥50 years, respectively. Similarly, 3.1%, 5.1%, and 91.8% of patients developed cirrhosis at the age of <40, 40-50, and ≥50 years, respectively. In contrast, liver-related events increased linearly with diabetes duration, with no difference in the annual incidence rate between the first 10 years of T2D diagnosis and subsequent years (0.06% vs. 0.10%; p = 0.136). On multivariable analysis, baseline age ≥50 years (adjusted HR [aHR] 2.01) and cirrhosis (aHR 3.12) were the strongest risk factors associated with liver-related events. Substitution of cirrhosis with the aspartate aminotransferase-to-platelet ratio index or the Fibrosis-4 index yielded similar results. Age rather than duration of T2D predicts liver-related events in patients with NAFLD and T2D. It is reasonable to screen patients with NAFLD and T2D for advanced liver disease starting at 50 years of age.

Multiinstitutional Evaluation of the Liver Surface Nodularity Score on CT for Staging Liver Fibrosis and Predicting Liver-Related Events in Patients With Hepatitis C.

BACKGROUND. In single-institution multireader studies, the liver surface nodularity (LSN) score accurately detects advanced liver fibrosis and cirrhosis and predicts liver decompensation in patients with chronic liver disease (CLD) from hepatitis C virus (HCV). OBJECTIVE. The purpose of this study was to assess the diagnostic performance of the LSN score alone and in combination with the (FIB-4; fibrosis index based on four factors) to detect advanced fibrosis and cirrhosis and to predict future liver-related events in a multiinstitutional cohort of patients with CLD from HCV. METHODS. This retrospective study included 40 consecutive patients, from each of five academic medical centers, with CLD from HCV who underwent nontargeted liver biopsy within 6 months before or after abdominal CT. Clinical data were recorded in a secure web-based database. A single central reader measured LSN scores using software. Diagnostic performance for detecting liver fibrosis stage was determined. Multivariable models were constructed to predict baseline liver decompensation and future liver-related events. RESULTS. After exclusions, the study included 191 patients (67 women, 124 men; mean age, 54 years) with fibrosis stages of F0-F1 (n = 37), F2 (n = 44), F3 (n = 46), and F4 (n = 64). Mean LSN score increased with higher stages (F0-F1, 2.26 ± 0.44; F2, 2.35 ± 0.37; F3, 2.42 ± 0.38; F4, 3.19 ± 0.89; p < .001). The AUC of LSN score alone was 0.87 for detecting advanced fibrosis (≥ F3) and 0.89 for detecting cirrhosis (F4), increasing to 0.92 and 0.94, respectively, when combined with FIB-4 scores (both p = .005). Combined scores at optimal cutoff points yielded sensitivity of 75% and specificity of 82% for advanced fibrosis, and sensitivity of 84% and specificity of 85% for cirrhosis. In multivariable models, LSN score was the strongest predictor of baseline liver decompensation (odds ratio, 14.28 per 1-unit increase; p < .001) and future liver-related events (hazard ratio, 2.87 per 1-unit increase; p = .03). CONCLUSION. In a multiinstitutional cohort of patients with CLD from HCV, LSN score alone and in combination with FIB-4 score exhibited strong diagnostic performance in detecting advanced fibrosis and cirrhosis. LSN score also predicted future liver-related events. CLINICAL IMPACT. The LSN score warrants a role in clinical practice as a quantitative marker for detecting advanced liver fibrosis, compensated cirrhosis, and decompensated cirrhosis and for predicting future liver-related events in patients with CLD from HCV.

Angiotensin-converting enzyme inhibitors prevent liver-related events in nonalcoholic fatty liver disease.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can inhibit liver fibrogenesis in animal models. We aimed to evaluate the impact of ACEI/ARB use on the risk of liver cancer and cirrhosis complications in patients with NAFLD. We conducted a retrospective, territory-wide cohort study of adult patients with NAFLD diagnosed between January 2000 and December 2014 to allow for at least 5 years of follow-up. ACEI or ARB users were defined as patients who had received ACEI or ARB treatment for at least 6 months. The primary endpoint was liver-related events (LREs), defined as a composite endpoint of liver cancer and cirrhosis complications. We analyzed data from 12,327 NAFLD patients (mean age, 54.2±14.7 years; 6163 men [50.0%]); 6805 received ACEIs, and 2877 received ARBs. After propensity score weighting, ACEI treatment was associated with a lower risk of LREs (weighted subdistribution hazard ratio [SHR], 0.48; 95% CI, 0.35-0.66; p<0.001), liver cancer (weighted SHR, 0.46; 95% CI, 0.28-0.75; p=0.002), and cirrhosis complications (weighted SHR, 0.42; 95% CI, 0.27-0.66; p<0.001), but ARB was not. In subgroup analysis, ACEI treatment was associated with greater reduction in LREs in patients with chronic kidney diseases (CKDs) than those without (CKD-weighted SHR, 0.74; 95% CI, 0.52-0.96; p=0.036; non-CKD-weighted SHR, 0.15; 95% CI, 0.07-0.33; p<0.001). ACEI, rather than ARB, treatment is associated with a lower risk of LREs in NAFLD patients, especially among those with CKD.

Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis.

Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the impact of DAA therapy on liver-related events in patients with cirrhosis is unclear. A total of 350 patients with compensated and decompensated cirrhosis administered DAA therapy at 29 Japanese hospitals were enrolled (Child-Pugh class A [CP-A]: 195 patients, CP-B: 131 patients and CP-C: 24 patients). The SVR rates of patients with CP-A, CP-B and CP-C were 96.9%, 93.1% and 83.3%, respectively (p = 0.006). Seventy patients developed hepatocellular carcinoma (HCC), and male sex, previous HCC treatment, platelet counts < 10.0 × 104/µl, alpha-fetoprotein levels ≥ 5.0ng/ml and CP-C were identified as significant factors in the multivariate analysis. The cumulative HCC occurrence/recurrence rates at 1year were 6.6%/45.2%. The cumulative rate of decompensated cirrhotic events requiring hospital admission at 1year was 9.1%. In the multivariate analysis, CP-B and CP-C were identified as significant factors. During the median observation period of 14.9months, 13 patients died and one patient received liver transplant. The overall survival rates at 1year were 98.4% in patients with CP-A, 96.4% in those with CP-B and 85.6% in those with CP-C (CP-A vs. CP-B: p = 0.759, CP-A vs. CP-C: p = 0.001 and CP-B vs. CP-C: p = 0.005). HCC development and mortality in patients with CP-B were not different from those with CP-A. On the other hand, in patients with CP-C, the development of HCC and decompensated cirrhotic events requiring hospital admission, and death were frequent. University Hospital Medical Information Network (UMIN000036150).

Incidence and predictors of liver-related events in patients with non-alcoholic fatty liver disease

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LRE) and mortality in NAFLD patients.

PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD

BackgroundReliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined.MethodsWe retrospectively investigated the incidence of three complications [CVDs, malignancy (except for liver cancer), and liver-related events] in 477 Japanese patients with histo-pathologically confirmed NAFLD for a median follow-up of 5.9 years. In addition to histological findings, we also investigated noninvasive predictors.ResultsA score of ≥ 2.67 for the noninvasive diagnosis of stage 4 fibrosis based on the Fibrosis-4 (FIB-4) index indicated a high level area under the receiver operating characteristic (AUROC) curve (0.90), sensitivity (82.9%), specificity (86.4%), and negative predictive value [(NPV) of 98.5%]. The yearly incidence rates of CVDs, malignancies, and liver-related events were found to be 1.04%, 0.83%, and 0.30%, respectively. Multivariate analysis identified a FIB-4 index ≥ 2.67 score as a significant and independent, noninvasive predictor of these three complications. Furthermore, the cumulative incidence rates of CVDs were significantly different among the three genotypes of PNPLA3. PNPLA3 genotype CC, chronic kidney disease (CKD), and FIB-4 index ≥ 2.67 was could be attributed to these three significant CVD risk factors. The rates of CVDs were significantly different among the three subgroups based on the combination of risk factors. In malignancy (except for liver cancer), the incidence rate of colon cancer was 25.0%; in particular, the rate in females was 53.8%.ConclusionsOur results highlighted the importance of the PNPLA3 genotype and FIB-4 index ≥ 2.67 on the incidence of complications in Japanese patients with NAFLD, especially the incidence of CVDs. Early diagnosis, based on the presence of one or more risk factors, and early treatment might improve the prognosis for NAFLD patients.

A Cholestatic Pattern Predicts Liver-Related Events in Patients with Nonalcoholic Fatty Liver Disease

Background & Aims: Liver test alteration patterns can be categorized as: predominantly hepatocellular(H), with an ALT/ALP ratio>5; predominantly cholestatic pattern(C) with a ratio < 2; mixed(M), with a ratio between 2 and 5. NAFLD usually has an H pattern, but a C pattern can also be observed. We aimed to assess in subjects with NAFLD the impact of the C pattern on the likelihood of developing of liver-related events(LRE). Methods: 582 consecutive patients with biopsy-proven NAFLD or a clinical diagnosis of NAFLD-related compensated cirrhosis were classified as H, C are M patterns, by using the formula (ALT/ALT Upper Limit of Normal-ULN)/(ALP/ALP ULN). LRE were recorded during follow-up. An external cohort of 1281 biopsy-proven NAFLD patients was enrolled as validation set. Results: H, M and C patterns were found in 153(26.3%), 272(46.7%) and 157(27%) patients, respectively. During a median follow-up of 78 months, only 1(0.6%) patient with H pattern experienced LRE, while 15(5.5%) and 38(24.2%) patients in M and C group had LRE. At multivariate Cox regression analysis, age>55 years(HR2.55,95%C.I.1.17-5.54;p=0.01), platelets<150,000/mmc(HR0.14,95%C.I.0.06-0.32;p<0.001), albumin<4g/L(HR0.62,95%C.I.0.35-1.08;p=0.09), C vs M pattern(HR7.86,95%C.I.1.03-60.1;p=0.04), C vs H pattern(HR12.1,95% C.I.1.61-90.9;p=0.01) and fibrosis F3-F4(HR35.8,95%C.I.4.65-275.2;p<0.001) were independent risk factors for LRE occurrence. C vs M pattern(HR14.3,95%C.I.1.90-105.6;p=0.008) and C vs H pattern(HR15.6,95%C.I. 2.10-115.1;p=0.0068) were confirmed independently associated with LRE occurrence in the validation set. Immunohistochemical analysis found a significant higher prevalence of moderate-high grade ductular metaplasia combined with low grade ductular proliferation in C pattern when compared with biochemical H pattern. Gene expression analysis showed a lower expression of NR1H3, RXRα, VCAM1 in patients with the C pattern. Conclusions: The presence of a cholestatic pattern in patients with NAFLD predicts a higher risk of LRE independently from other features of liver disease. Funding: GS is supported by a Senior Salary Award from Fonds de la Recherche en Sante du Quebec (FRQS) (#296306). Declaration of Interest: GS has acted as speaker for Pfizer, Merck, Novonordisk, Novartis, Gilead, and AbbVie, served as an advisory board member for Merck, Gilead, Pfizer, Allergan, Novonordisk, Intercept and Novartis and has received research funding from Merck and Theratec. All others have nothing to declare. Ethical Approval: Approval was obtained by the Ethical Committee of the University Hospital “Paolo Giaccone” in Palermo.

OC-06A cholestatic pattern predicts liver-related events in patients with nonalcoholic fatty liver disease

Background&Aims: Liver tests alteration patterns can be categorized as: predominantly hepatocellular(H), with an ALT/ALP ratio>5; predominantly cholestatic pattern (C) with a ratio < 2; mixed(M), with a ratio between 2 and 5. NAFLD has usually an H pattern, but a C pattern can also be observed. We aimed to assess in subjects with NAFLD the impact of the C pattern on the likelihood of developing of liver-related events(LRE).

Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis.

BACKGROUNDLiver fibrosis leads to liver-related events in patients with chronic hepatitis C (CHC) infection. Although non-invasive tests (NITs) are critical to early detection of the development of liver fibrosis, the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies.AIMTo determine the prognostic value of NITs for risk stratification in CHC patients.METHODSThe protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019128176). The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25, 2020. We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma, decompensation, or mortality. Pooled hazard ratios (HR) and area under the receiver operating characteristic (AUROC) for each NIT were estimated using a random effects model. Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response (SVR), treatment with either pegylated interferon and ribavirin or direct acting antiviral, Eastern or Western countries, and different cutoff points.RESULTSThe present meta-analysis included 29 cohort studies, enrolling 69339 CHC patients. Fibrosis-4 (FIB-4) index, aspartate aminotransferase to platelet ratio (APRI) score, and liver stiffness measurement (LSM) were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48 [95% confidence interval (CI): 1.91-3.23, I2 = 96%], 4.24 (95%CI: 2.15-8.38, I2 = 20%) and 7.90 (95%CI: 3.98-15.68, I2 = 52%) and AUROCs of 0.81 (95%CI: 0.73-0.89, I2 = 77%), 0.81 (95%CI: 0.75-0.87, I2 = 68%), and 0.79 (95%CI: 0.63-0.96, I2 = 90%), respectively. Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22 (95%CI: 2.32-4.47, I2 = 80%). Pooled adjusted HRs for post-treatment with SVR FIB-4, APRI, and LSM were 3.01 (95%CI: 0.32-28.61, I2 = 89%), 9.88 (95%CI: 2.21-44.17, I2 = 24%), and 6.33 (95%CI: 2.57-15.59, I2 = 17%), respectively. Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55 (95%CI: 1.47-21.02, I2 = 36%). Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75 (95%CI: 0.55-0.95, I2 = 88%) and 0.84 (95%CI: 0.66-1.03, I2 = 88%), respectively. Additionally, FIB-4 and LSM were associated with overall mortality, with pooled adjusted HRs of 2.07 (95%CI: 1.49-2.88, I2 = 27%) and 4.04 (95%CI: 2.40-6.80, I2 = 63%), respectively. CONCLUSIONFIB-4, APRI, and LSM showed potential for risk stratification in CHC patients. Cutoff levels need further validation.

Risk assessment of hepatocellular carcinoma and liver-related events using ultrasonography and transient elastography in patients with chronic hepatitis B.

Cirrhosis has prognostic value. We investigated whether the combined use of ultrasonography (US) and transient elastography (TE) to diagnose cirrhosis is beneficial for the risk assessment of hepatocellular carcinoma (HCC) and liver-related events in patients with chronic hepatitis B (CHB). A total of 9300 patients with CHB who underwent US and TE in two institutions between 2006 and 2018 were enrolled. TE value ≥13kPa was set to indicate cirrhosis. Patients were divided into four groups: US(+)TE(+) (cirrhosis by US and TE), US(+)TE(-) (cirrhosis by US, but not by TE), US(-)TE(+) (cirrhosis by TE, but not by US) and US(-)TE(-) (non-cirrhosis by US and TE).The patients were predominantly male (n=5474, 58.9%) with a mean age of 47.5years. The proportions of patients with cirrhosis diagnosed by US and TE were 17.2% (n=1595) and 13.2% (n=1225), respectively. The proportion of patients with discordant results in diagnosing cirrhosis by US and TE was 18.7% (n=1740). During follow-up (median: 60.0months), HCC and liver-related events developed in 481 (5.2%) and 759 (8.2%) patients, respectively. The cumulative incidence rates of HCC and liver-related events were highest in the US(+)TE(+) group, intermediate-high in the US(-)TE(+) group, intermediate-low in the US(+)TE(-) group and lowest in the US(-)TE(-) group (overall p<.001). Cirrhosis assessed using US and TE was a major predictor of HCC and liver-related event development in patients with CHB. Cirrhosis assessed using TE seemed better in predicting HCC or liver-related events than using US, when cirrhosis diagnosis was discordant by US and TE.

Early Normalization of Alanine Aminotransferase during Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in HBV Patients.

Potent antiviral agents effectively reduce liver-related events in patients with chronic hepatitis B. This study aimed to determine whether alanine aminotransferase normalization using potent antiviral agents was related to hepatocellular carcinoma development. From 2007 to 2017, we included 610 patients with chronic hepatitis B who received entecavir or tenofovir disoproxil fumarate. The patients were divided into the alanine aminotransferase normalization group (Gr.1) and non-normalization group (Gr.2) within a year of potent antiviral treatment. Liver-related events included hepatic encephalopathy, variceal bleeding, and ascites. The mortality rate and hepatocellular carcinoma incidence were investigated for each group. The patients who showed ALT normalization at 1 year of treatment were 397 (65.1%) of 610. During a median follow-up period of 86 months, 65 (10.7%) patients developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma was significantly lower in Gr.1 than in Gr.2 (p < 0.001). Risk factors for alanine aminotransferase non-normalization were body mass index, cholesterol, and liver cirrhosis at baseline. Male sex, age, platelet level, alcohol use, presence of cirrhosis at baseline, and non-normalization after 1 year of treatment were independent risk factors for hepatocellular carcinoma. Alanine aminotransferase normalization within 1 year of initiating antiviral agents reduces the risk of hepatocellular carcinoma development.

Prediction of liver-related events in patients with compensated HBV-induced cirrhosis receiving antiviral therapy.

Many models have been developed to predict liver-related events (LRE) in chronic hepatitis B, few focused on compensated HBV-induced cirrhosis. We aimed to describe the incidence of LRE and to determine independent risk predictors of LRE in compensated HBV-induced cirrhosis patients receiving antiviral therapy using routinely available parameters. Prospective cohorts of treatment-naïve adults with compensated HBV-induced cirrhosis were enrolled. Patients were treated with entecavir (ETV) or ETV + thymosin-alpha1 (Thy-α1) or lamivudine (LAM) + adefovir (ADV). Data were collected at baseline and every 6months. LRE was defined as development of decompensation, HCC or death. Totally 937 patients were included, 608 patients treated with ETV, 252 with ETV + Thy-α1, and 77 with LAM + ADV. After a median follow-up of 4.5years, 88 patients developed LRE including 48 with HCC. The cumulative incidence of LRE at year 1, 3, and 5 was 2.1%, 7.0%, and 12.7%, respectively, and was similar for three treatment groups. All models using variables at month 6 or 12 had better fit than models using baseline values. The best model for prediction of LRE used PLT, GGT, and AFP at month 6 [AUC: 0.762 (0.678-0.814)], for hepatic decompensation-PLT, LSM and GGT at month 12 (AUC: 0.834 (0.675-0.919)), and for HCC-AFP and GGT at month 6 [AUC 0.763 (0.691-0.828)]. All models had negative predictive values of 94.0-98.8%. Models using on-treatment variables are more accurate than models using baseline variables in predicting LRE in patient with compensated HBV-induced cirrhosis receiving antiviral therapy. ClincialTrials.gov number NCT01943617, NCT01720238, NCT03366571, NCT02849132.

Issue Highlights

Although the introduction of biologics for the treatment of Crohn’s in 1998 revolutionized our approach to this disease, primary non-response and secondary loss of response remain vexing problems for a large subset of patients in clinical practice. For anti-TNF agents, common reasons for loss of response include subtherapeutic drug concentrations and development of neutralizing anti-drug antibodies. Therapeutic drug monitoring, dose escalation and interval shortening are approaches with demonstrated effectiveness recapturing response to these agents and are commonly employed in clinical practice. 1 Papamichael K. Cheifetz A.S. Melmed G.Y. et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019; 17: 1655-1668.e3 Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar Shortening the dose interval or dose intensification for Vedolizumab has also been shown to permit recapturing of response in some patients, 2 Peyrin-Biroulet L. Danese S. Argollo M. et al. Loss of response to vedolizumab and ability of dose intensification to restore response in patients with crohn's disease or ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019; 17: 838-846.e2 Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar but whether this approach can be extrapolated to Ustekinumab remains unclear. This retrospective study by Ollech et al 3 Ollech J.E. Normatov I. Peleg N. et al. Effectiveness of Ustekinumab dose escalation in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2021; 19: 104-110 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar is the first to evaluate real-world effectiveness of interval shortening from 8- to 4-week dosing for Ustekinumab. The authors describe pre- and post-dose escalation parameters including Harvey Bradshaw Index (HBI), C-reactive protein (CRP), and fecal calprotectin for a subset of 110 patients not responding to Ustekinumab every 8 weeks. Although not all patients in the subset had all parameters pre- and post-dose increase, of the 78 patients (71%) with pre-and post-HBI metrics, the median HBI decreased from 4.5 to 3 (P = .002). Of 60 patients (55%) with CRP measurements, median CRP decreased from 8 mg/L to 3 mg/L (P = .031). Among patients with HBI >4, CRP ≥5 mg/L, fecal calprotectin >250 μg/g, or endoscopic evidence of active disease, 28% achieved clinical remission (HBI<4), 22% normalized CRP, and 36% endoscopic remission with a median follow up of 9 months post-dose increase. 38% of patients on steroids were able to discontinue, and 45% with active perianal disease reported resolution within 6 months of dose-escalation. Twenty-three patients (20.9%) discontinued therapy following dose escalation, most (78%) due to lack of response; only 1 due to side effects (rash). This is the first study to demonstrate improvement in objective measures of Crohn’s disease activity with dose-intensification of Ustekinumab from 8- to 4-week intervals. Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn’s DiseaseClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewA subset of patients with Crohn’s disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses. Full-Text PDF Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Nonalcoholic Steatohepatitis–Related, Child–Pugh A CirrhosisClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewFactors that affect outcomes of patients with nonalcoholic steatohepatitis (NASH)-related cirrhosis are unclear. We studied associations of type 2 diabetes, levels of hemoglobin A1c (HbA1c), and use of antidiabetic medications with survival and liver-related events in patients with NASH and compensated cirrhosis. Full-Text PDF Intragastric Balloon Placement Induces Significant Metabolic and Histologic Improvement in Patients With Nonalcoholic SteatohepatitisClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewObese patients with nonalcoholic steatohepatitis (NASH) are at risk for cirrhosis if significant weight loss is not achieved. The single fluid-filled intragastric balloon (IGB) induces meaningful weight loss and might be used in NASH treatment. We performed an open-label prospective study to evaluate the effects of IGB placement on metabolic and histologic features of NASH. Full-Text PDF Serum Levels of α-Fetoprotein Increased More Than 10 Years Before Detection of Hepatocellular CarcinomaClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewUltrasound (US)-based screening has been recommended for patients with an increased risk of hepatocellular carcinoma (HCC). US analysis, however, is limited in patients who are obese or have small tumors. The addition of serum level of α-fetoprotein (AFP) measurements to US analysis can increase detection of HCC. We analyzed data from patients with chronic liver disease, collected over 15 years in an HCC surveillance program, to develop a model to assess risk of HCC. Full-Text PDF

Point Shear-Wave Elastography Using Acoustic Radiation Force Impulse Imaging for the Prediction of Liver-Related Events in Patients With Chronic Viral Hepatitis.

Chronic viral hepatitis is associated with substantial morbidity and mortality worldwide. The aim of our study was to assess the ability of point shear-wave elastography (pSWE) using acoustic radiation force impulse imaging for the prediction of the following liver-related events (LREs): new diagnosis of HCC, liver transplantation, or liver-related death (hepatic decompensation was not included as an LRE). pSWE was performed at study inclusion and compared with liver histology, transient elastography (TE), and serologic biomarkers (aspartate aminotransferase to platelet ratio index, Fibrosis-4, FibroTest). The performance of pSWE and TE to predict LREs was assessed by calculating the area under the receiver operating characteristic curve and a Cox proportional-hazards regression model. A total of 254 patients with a median follow-up of 78 months were included in the study. LRE occurred in 28 patients (11%) during follow-up. In both patients with hepatitis B virus and hepatitis C virus (HCV), pSWE showed significant correlations with noninvasive tests and TE, and median pSWE and TE values were significantly different between patients with LREs and patients without LREs (both P<0.0001). In patients with HCV, the area under the receiver operating characteristic curve for pSWE and TE to predict LREs were comparable: 0.859 (95% confidence interval [CI], 0.747-0.969) and 0.852 (95% CI, 0.737-0.967) (P=0.93). In Cox regression analysis, pSWE independently predicted LREs in all patients with HCV (hazard ratio, 17.9; 95% CI, 5.21-61-17; P<0.0001) and those who later received direct-acting antiviral therapy (hazard ratio, 17.11; 95% CI, 3.88-75.55; P=0.0002). Conclusion: Our study shows good comparability between pSWE and TE. pSWE is a promising tool for the prediction of LREs in patients with viral hepatitis, particularly those with chronic HCV. Further studies are needed to confirm our data and assess their prognostic value in other liver diseases.

Different Performance of Liver Stiffness Measurement According to Etiology and Outcome for the Prediction of Liver-Related Events

Liver stiffness measurement (LSM) by transient elastography (TE) has shown promising results for prediction of hepatocellular carcinoma (HCC) and hepatic decompensation in patients with chronic liver disease (CLD). However, whether prognostic performance of TE differs according to etiology or type of outcome remains further clarification. Performance of LSM for the prediction of HCC and hepatic decompensation was analyzed in a cohort of 4026 patients with asymptomatic CLD. During median 4.5years of follow-up (range 3.0-6.2years), liver-related events (LRE) were observed in 196 patients (166 with HCC, 45 with hepatic decompensation, and 15 with both). In the multivariate analysis, LSM was independent factor associated with LRE and showed high AUROC (0.78). When stratified by type of outcome and etiology of liver disease, LSM showed high AUROC for the prediction of HCC for patients with non-viral hepatitis (0.89), while it showed relatively low AUROC for the prediction of HCC for patients with viral hepatitis (0.75). For the prediction of hepatic decompensation, LSM showed high AUROC for patients with both viral- and non-viral hepatitis (0.90, 0.90, respectively). LSM showed powerful prognostic role for the prediction of LRE in patients with CLD. Notably, HCC risk was not negligible in patients with viral hepatitis who showed LSM value < 10kPa, indicating watchful attention for HCC is still needed for viral hepatitis patients with low LSM.

Enhanced Liver Fibrosis Score Can Be Used to Predict Liver-Related Events in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis

There is a growing need for a noninvasive tool to identify patients at higher risk of hepatic decompensation among individuals with compensated nonalcoholic steatohepatitis (NASH) cirrhosis.1 Hepatic venous pressure gradient (HVPG) has value in risk stratification2 and prediction of mortality among cirrhotics3 but has limitations of being invasive, costly, and a requirement for expertise.4 The Enhanced Liver Fibrosis (ELF) score is based on circulating markers of hepatic matrix turnover and consists of hyaluronic acid, TIMP-1 (tissue inhibitor of metalloproteinases-1), and PIIINP (propeptide of type III collagen). It identifies nonalcoholic fatty liver disease (NAFLD) patients with advanced fibrosis quite reliably.5,6 However, its utility as a prognostic biomarker among individuals with compensated cirrhosis due to NASH is unclear. This study evaluated the prognostic significance of the ELF score for predicting short-term liver-related outcomes among patients with compensated NASH cirrhosis.

Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Nonalcoholic Steatohepatitis–Related, Child–Pugh A Cirrhosis

Factors that affect outcomes of patients with nonalcoholic steatohepatitis (NASH)-related cirrhosis are unclear. We studied associations of type 2 diabetes, levels of hemoglobin A1c (HbA1c), and use of antidiabetic medications with survival and liver-related events in patients with NASH and compensated cirrhosis. We collected data from 299 patients with biopsy-proven NASH with Child-Pugh A cirrhosis from tertiary hospitals in Spain, Australia, Hong Kong, and Cuba, from April 1995 through December 2016. We obtained information on the presence of type 2 diabetes, level of HbA1c, and use of antidiabetic medications. Cox proportional and competing risk models were used to estimate and compare rates of transplant-free survival, hepatic decompensation, and hepatocellular carcinoma (HCC). A total of 212 patients had type 2 diabetes at baseline and 8 of 87 patients developed diabetes during a median follow-up time of 5.1 years (range, 0.5-10.0 y). A lower proportion of patients with diabetes survived the entire follow-up period (38%) than of patients with no diabetes (81%) (adjusted hazard ratio [aHR], 4.23; 95% CI, 1.93-9.29). Higher proportions of patients with diabetes also had hepatic decompensation (51% vs 26% of patients with no diabetes; aHR, 2.03; 95% CI, 1.005-4.11) and HCC (25% vs 7% of patients with no diabetes; aHR, 5.42; 95% CI, 1.74-16.80). Averaged annual HbA1c levels over time were not associated with outcomes. Metformin use over time was associated with a significant reduction in risk of death or liver transplantation (aHR, 0.41; 95% CI, 0.26-0.45), hepatic decompensation (aHR, 0.80; 95% CI, 0.74-0.97), and HCC (aHR, 0.78; 95% CI, 0.69-0.96). Metformin significantly reduced the risk of hepatic decompensation and HCC only in subjects with HbA1c levels greater than 7.0% (aHR, 0.97; 95% CI, 0.95-0.99 and aHR, 0.67; 95% CI, 0.43-0.94, respectively). In an international cohort of patients with biopsy-proven NASH and Child-Pugh A cirrhosis, type 2 diabetes increased the risk of death and liver-related outcomes, including HCC. Patients who took metformin had higher rates of survival and lower rates of decompensation and HCC.