906. Characteristics of Chronic Hepatitis B Patients with Severe Outcomes in a Large Integrated Healthcare System - 2008-2019

Background It is estimated that there are 1.59 million cases of chronic hepatitis B virus (HBV) infection (CHB) in the United States. HBV infection is highest among men and non-Hispanic Asian adults. CHB can lead to liver damage, cirrhosis, hepatocellular carcinoma, or death. However, the population that is most likely to develop severe outcomes is not as well-defined. Methods We evaluated electronic health record data from Kaiser Permanente Southern California adult members from 2008-2019 with at least 1 year of continuous membership, and with 2 successive, positive HBV lab results (HBV DNA, or HBsAg, or HBeAg) at least 6 months apart (indicative of CHB). Severe outcomes included incident hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant and death, and prevalent and incident liver cirrhosis. For each outcome, we estimated the distribution of characteristics including age, sex, race/ethnicity, and lab values (alanine aminotransferase [ALT], alpha-fetoprotein [AFP], MELD score). Results Our final study population included 5,427 CHB-diagnosed patients with 411 (7.6%) cases of liver cirrhosis, 123 (2.3%) of hepatic decompensation, 65 (1.2%) of HCC, 8 (0.1%) of liver transplant, and 164 (3.0%) deaths. Compared to the total cohort, those who developed severe outcomes were older (median age for each outcome >50 years vs. 47 years in total CHB population). Among those with severe outcomes, the majority were male ( >56%) and Asian. Diabetes was more prevalent in patients with hepatic decompensation, HCC, and death versus the entire cohort (25% vs. 8%, respectively, P< 0.0001), and twice as prevalent among those with cirrhosis. All severe outcomes were associated with >2 x upper limit of normal ALT levels. Conclusion The characteristics of those with severe outcomes were consistent with those of overall CHB, although there was a 2-3 times higher prevalence of diabetes in those with severe outcomes. Identifying characteristics that are more prevalent in those with severe outcomes can help inform screening and management of CHB. Disclosures Ana Florea, PhD MPH, Gilead Inc. (Grant/Research Support) Prabhu Gounder, MD, Gilead Inc. (Grant/Research Support) Amandeep Sahota, MD, MS, Gilead Inc (Grant/Research Support) Katherine J. Pak, MS, Gilead (Grant/Research Support) Vennis Hong, MPH, Gilead Inc. (Research Grant or Support) Theresa M. Im, MPH, Gilead Inc. (Grant/Research Support) Sara Tartof, PhD, Gilead (Grant/Research Support, Scientific Research Study Investigator)

Predictors of residual hepatic reserve and hepatic decompensation in cirrhotic patients after ablated hepatocellular carcinoma treated by DDAs or systemic therapy

Background Therapeutic interventions for hepatocellular carcinoma (HCC) particularly in patients with advanced liver disease may lead to more aggravation of clinical and biochemical parameters of liver functions. We aimed to assess the utilization of easily applied variables which evaluate residual hepatic reserve to predict liability for complications and hepatic decompensation in cirrhotic patients with ablated HCC particularly when these patients were exposed to specific medical treatment such as DAAs and systemic therapy for HCC such as sorafenib. This study included 3 groups with HCC. Group 1: patients with ablated HCC and Child-Turcotte-Pugh (CTP) class A, who received Sofosbuvir (SOF)-based treatment (n = 250), group 2: HCC patients CTP (A), managed with sorafenib after transarterial chemoembolization (TACE) (n = 250) and group 3 as a control group of non-cirrhotic patients (n = 176). Evaluation for all patients was done by routine laboratory investigations including liver and kidney functions, complete blood count, platelet indices and plasma ammonia, upper gastrointestinal (GI) endoscopy and estimation of liver volume by ultrasound and liver stiffness (LS) by Fibroscan. Results Unfavorable outcome and increased incidence of complications during DAAs were independently associated with severity of thrombocytopenia (p = 0.001) at a cut-off 78,000/μl, LS > 20 kPa (p = 0.001), liver volume < 500 ml (p = 0.002), and gamma globulin levels > 4 gm/dl (p = 0.004). In the sorafenib group, unfavorable outcome and complications were independently associated with PDW/MPV ratio > 2.74 (p = 0.001), level of ammonia > 87 μg/dl (p = 0.001), LS > 25 kPa (p = 0.001), and liver volume < 490 ml (p = 0.001). Conclusion Non-invasive parameters of residual hepatic reserve are promising tools to guide therapy and avoid further complications in patients with liver cirrhosis and ablated HCC.

Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade

Background Albumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC. Methods Patients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as ≤ −2.60 score and a grade of 2 as a score of > −2.60 to ≤ −1.39. Results Cabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio [HR] [95% CI]: 0.63 [0.46–0.86] and 0.42 [0.32–0.56]) and ALBI grade 2 (HR [95% CI]: 0.84 [0.66–1.06] and 0.46 [0.37–0.58]) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup. Discussion These results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2. Trial registration number ClinicalTrials.gov number, NCT01908426.

Evaluation of Transient Elastography in Prediction Of De novo Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation

Background Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and it is also a common cause of death in patients with chronic liver disease. The curative treatment options for HCC that are currently available are surgical resection, liver transplantation and radiofrequency ablation .Despite progressive improvements in the efficacy of RFA, the survival of patients with HCC who undergo RFA remains disappointing, mainly due to frequent intrahepatic recurrence of HCC after RFA. Aim of the work To evaluate the role of transient elastography (as an indirect indicator to degree of liver fibrosis) in prediction of denovo recurrence of hepatocellular carcinoma after radiofrequency ablation in hepatitis C related hepatocellular carcinoma .And to compare between transient elastography and other non invasive fibrosis indices in prediction of denovo recurrence of hepatocellular carcinoma after radiofrequency ablation hepatitis C related hepatocellular carcinoma Patients and methods This prospective cohrt study was conducted on hepatocellular carcinoma patient, who underwent radiofrequency ablation in Tropical Medicine Department in Eldemerdash and Ain Shams Specialized Hospital, HCC clinic Ain Shams University Hospitals, Cairo, Egypt between march, 2017 and May, 2019. Data of the patient, who underwent radiofrequency ablation during the study period, were reviewed and the patients who fulfilled the inclusion criteria were enrolled into this study. The patients who fulfilled the inclusion criteria and underwent radiofrequency ablation were followed up for 12 months. Results TE revealed 28 patients with F4 and only 2 patients with F3, the mean measurement of liver stiffness was (22.45 ± 10.36) KPa. There was a significant negative correlation between LS and denovo recurrence of HCC (mean of LS in patients with complete response was 17.19 ± 3.32 and the mean of LS in patient with denovo recurrence was 36,94 ± 5.93,with the The best cut off value ≥24.65 (p value &lt; 0.001)). There was no significant correlation between CDC, FIB4, API scores and denovo recurrence of HCC. Also it was found that the LS was significantly associated with prediction of manifestation of hepatic decompensation after RFA (means of LS in patient without manifestation decompensation after RFA (p value &lt;0.001) .Regarding prediction of mortality, LS at cut off value &gt; 42 .75 (p value = 0,031) was significantly associated with prediction of mortality after one year of RFA. As regard serum non invasive fibrosis indices our results showed correlation between FIB4 score and hepatic decompensation after one year of intervention (the mean of FIB4 score in patients ascites and jaundice was 6.05 ± 4.71 (p value = 0.05) ).Therewas no statistically significant correlation between CDS and API with hepatic decompensation after RFA .As regard role of serum non invasive fibrosis indices in prediction of mortality after RFA, FIB4 score, CDS and API were statistically non significant. Conclusion Our data suggest that LS measurement is a useful predictor of HCC de novorecurrence overall survival and possibility of hepatic decompensation after RFA

Persistent homology approach distinguishes potential pattern between “Early” and “Not Early” hepatic decompensation groups using MRI modalities

Primary sclerosis cholangitis (PSC) predisposes individuals to liver failure, but it is challenging for radiologists examining radiologic images to predict which patients with PSC will ultimately develop liver failure. Motivated by algebraic topology, a topological data analysis - inspired framework was adopted in the study of the imaging pattern between the “Early Decompensation” and “Not Early” groups. The results demonstrate that the proposed methodology discriminates “Early Decompensation” and “Not Early” groups. Our study is the first attempt to provide a topological representation-based method into early hepatic decompensation and not early groups.

Clinical profile and outcome among patients with acute-on-chronic liver failure admitted in the intensive care unit

Background Acute-on-chronic liver failure (ACLF) has been recently defined as a clinical form including acute hepatic decompensation and high 28-day mortality. ACLF usually follows a precipitating event on the background of established cirrhosis. ACLF is considered the most frequent indication for admission to the ICU among cirrhotic patients. Our research aimed to reveal the clinical profile and outcome among patients with ACLF to detect an allocation system of these patients to the intensive care unit (ICU), and a decision tool for clinical practice. It is a prospective study of 60 patients with ACLF. Patients are divided into group A that included 30 patients with ACLF admitted to the hepatology and gastroenterology ward and group B that also included 30 patients with ACLF admitted to the ICU. Each group is subdivided into subgroups regarding the grade of ACLF. Results The most common precipitating factor of ACLF is SBP 78.3% (80% in ICU, 73.6% inward). Renal failure is the most common organ failure in ACLF in both groups. CLIF-C ACLF is assumed to be a highly prognostic score for mortality in ACLF patients better than other scores. ROC curve of CLIF-C ACLF with AUC: 0.972 and CI: 0.919, 1.025 showed a cutoff point = 57.0 above which intensive care admission does not seem to benefit ACLF patients. The sensitivity at the optimal cut point is 88.89% and the specificity is 100%. There is a significant difference between the 3 ACLF groups regarding 1-month and 3-month mortalities in patients admitted to the ICU. ACLF1 shows the least 1-month and 3-month mortality rates while ACLF3 shows the highest mortality rates in ICU patients ((1-month mortality: 20%, 60%, 100% in ACLF1, 2, 3 respectively), (3-month mortality: 50%, 80%, 100% in ACLF1, 2, 3 respectively)). Conclusion Mortality is high in ACLF and increases with the number of organ failures (40% in ACLF1 to 100% in ACLF3). CLIFC-ACLF is the most prognostic scoring system with a cut-off value of 57; above this value, mortality is a fact.

Effectiveness of Direct-Acting Antivirals in Treatment of Elderly Egyptian Chronic Hepatitis C Patients

Background: Hepatitis C virus treatment has dramatically improved by direct-acting antiviral (DAA) therapy. The aim of this study was to assess the efficacy and safety of DAA in elderly Egyptian chronic hepatitis C (CHC) patients. Methods: The study was carried out on 327 CHC elderly patients >60 years; patients were divided into 3 age subgroups (<65, 65–75 and >75 years) on DAA therapy for 12 weeks. Ninety-one patients (27.8%) were treated with dual therapy, 234 patients (71.6%) with triple therapy and 2 patients (0.6%) with quadrable therapy. Results: All patients achieved end-of-treatment virological response (100%). ALT levels normalized during therapy. The follow-up rate of sustained virological response at 12 weeks after the end of treatment (SVR12) was 100%. One hundred and two patients had missed SVR12 data due to being lost tofollow-up. Two hundred twenty-two adverse events were reported (67.8%), including anemia in 30 patients (9.1%), leucopenia in 129 patients (39.4%) and thrombocytopenia in 63 patients (19.2%). No serious side effects led to discontinuation of therapy. No hepatic decompensation was observed, and no patients died. Conclusion: Age does not influence the success of DAA treatment and all DAA regimens are well tolerated, safe and highly efficacious, even in those aged 75 years or older.

Variceal Bleeding in Patients with Initation of Sofosbuvir and Ribavirin – Case Reports

Sofosbuvir is an oral nucleoside analogue and potent inhibitor of the Hepatitis C virus (HCV) RNA polymerase that is used in combination with other antiviral agents to treat chronic Hepatitis C Nevertheless, and for unknown reasons, successful antiviral therapy of Hepatitis C with Sofosbuvir and other direct acting agents in patients with cirrhosis is occasionally complicated by hepatic decompensation. Here we describe 2 case report of upper gi bleed at initial days of treatment with Sofosbuvir and Ribavirin. Keywords: Variceal bleeding , Sofosdbuvir, Ribavirin, Heptitis C, Nucleoside analogue, Antiviral.