Common Underlying Liver Diseases Research Articles

Systemic Treatment of Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Multicenter Trial

Introduction: The tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib represent the first-line systemic therapy of choice for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Under sorafenib and lenvatinib, HCC patients have shown increasingly improved overall survival in clinical studies over the years. In contrast, data on overall survival for patients with HCC recurrence after LT under TKIs are scarce and limited to small retrospective series. In this retrospective, multicenter study, we investigated the efficacy of TKI therapy and the influence of immunosuppression in patients with HCC recurrence after LT. Methods: Retrospective data were collected from four transplant centers from Germany and Austria. We included patients with HCC recurrence after LT between 2007 and 2020 who were treated with a TKI. Results: In total, we analyzed data from 46 patients with HCC recurrence after LT. The most common underlying liver disease was hepatitis C, accounting for 52.2%. The median time to relapse was 11.8 months (range 0–117.7 months). The liver graft was affected in 21 patients (45.7%), and 36 patients (78.3%) had extrahepatic metastases at initial diagnosis of recurrence, with the lung being the most commonly affected (n = 25, 54.3%). Of the total, 54.3% (n = 25) of the patients were initially treated locally; 39 (85.8%) and 7 (15.2%) patients received sorafenib and lenvatinib, respectively, as first-line systemic therapy. Median overall survival of the whole cohort was 10.9 months (95% confidence interval (95% CI) 6.9–14.9 months) and median progression free survival was 5.7 months (95% CI 2.0–9.4 months) from treatment initiation. Conclusion: Since history of liver transplantation is considered a contraindication for immunotherapy, prognosis of patients with HCC recurrence after LT remains poor.

Adult-to-adult right lobe graft living donor liver transplantation for acute-on-chronic liver failure: a single-centre retrospective study in Vietnam.

Acute-on-chronic liver failure (ACLF) has a high mortality rate, and liver transplantation is considered a definite treatment for patients with this condition. This study aims to evaluate the outcomes of living donor liver transplantation (LDLT) in ACLF patients in a single centre in a lower middle-income country, Vietnam. This was a retrospective study at the 108 Military Central Hospital (Hanoi, Vietnam), enroling 51 patients diagnosed with ACLF based on Asian Pacific Association for the Study of the Liver (APASL) criteria who underwent LDLT with a right lobe graft from December 2019 to December 2022. The authors utilize the model for end-stage liver disease (MELD) and APASL ACLF Research Consortium (AARC) scores to evaluate and stratify the severity of ACLF. The average age of all patients was 47.27±13.61, with 88.24% being male. The average BMI was 22.78±2.61. The most common underlying liver disease was chronic viral hepatitis B (88.2%). The average MELD score of the patients was 34.90±5.61, with 33.3% having MELD score greater than or equal to 40. In terms of ACLF severity, five patients (9.8%) had grade I ACLF, 35 patients (68.6%) had grade II ACLF, and 11 patients (21.6%) had grade III ACLF. The average AARC score was 9.43±1.68. The duration of treatment in the ICU was 8.59±7.27 days, and the length of hospital stay was 28.02±13.45 days. The most common post-transplant complication was biliary complication (19.61%). Death occurred in 7 patients (13.7%). The survival rates at 6 months, 1 year, and 3 years were 84%, 81.7%, and 81.7%, respectively. Living donor liver transplantation for ACLF patients is safe and has a high post-transplant survival rate. Multidisciplinary care before, during, and after surgery, and the decision to do a liver transplant early, is essential in saving the lives of ACLF patients.

Metabolic-associated fatty liver disease and hepatocellular carcinoma: a prospective study of characteristics and response to therapy.

The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population. Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period. Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n=77), MAFLD plus other liver disease (n=57) (the "mixed" group), and non-MAFLD (n=179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73years vs 67years vs 63years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate. Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration.

Asymptomatic Allograft Fibrosis in Pediatric Liver Transplantation: Potential Clinical Implications.

Asymptomatic Allograft Fibrosis in Pediatric Liver Transplantation: Potential Clinical Implications.

Rs708113 in WNT3A-WNT9A and hepatocellular carcinoma risk.

Hepatocellular carcinoma is the most frequent primary liver malignancy and fourth most common cause of cancer-related mortality worldwide. 1 Global Burden of Disease Cancer CollaborationGlobal, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017; 3: 524-548 Crossref PubMed Scopus (2549) Google Scholar Although chronic viral hepatitis, particularly due to hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to hepatocellular carcinoma in southeast Asia, alcohol-related liver disease and non-alcoholic fatty liver disease are the predominant causes in Europe and North America. Alcohol-related liver disease and non-alcoholic fatty liver disease are expected to become the leading causes of hepatocellular carcinoma in the future, with HBV and hepatitis C virus infections declining as a result of effective vaccination strategies and treatments. With few exceptions, most hepatocellular carcinoma cases in high-income countries develop in patients with established cirrhosis; alcohol-related cirrhosis is the second most common risk factor for hepatocellular carcinoma in high-income countries, 2 West J Card TR Aithal GP Fleming KM Risk of hepatocellular carcinoma among individuals with different aetiologies of cirrhosis: a population-based cohort study. Aliment Pharmacol Ther. 2017; 45: 983-990 Crossref PubMed Scopus (40) Google Scholar with an annual risk of hepatocellular carcinoma of up to 2·5%. 3 Mancebo A González-Diéguez ML Cadahía V et al. Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups. Clin Gastroenterol Hepatol. 2013; 11: 95-101 Summary Full Text Full Text PDF PubMed Scopus (108) Google Scholar Alcohol-related hepatocellular carcinoma is a complex disease, but easily discernible clinical risk factors include type 2 diabetes, obesity, and older age. 4 Llovet JM Kelley RK Villanueva A et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021; 7: 6 Crossref PubMed Scopus (708) Google Scholar Sequence variations in specific genes that modify the risk of alcohol-related hepatocellular carcinoma have been identified, mostly by means of candidate gene case-control studies, which either enhance or alleviate the risk of developing hepatocellular carcinoma. However, the genetic risk loci recognised until now only represent a fraction of the heritability risk, suggesting that additional genetic modulators might exist. 5 Stickel F Buch S Nischalke HD et al. Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis. Am J Gastroenterol. 2018; 113: 1475-1483 Crossref PubMed Scopus (56) Google Scholar The involvement of the rs738409 locus (in the gene coding for PNPLA3) is widely supported by numerous case-control studies, which show the largest effect size among all previously identified genetic risk variants. Additional loci in genes coding for TM6SF2 (rs58542926) and HSD17B13 (rs72613567:TA) were found to increase and alleviate the risk of hepatocellular carcinoma, respectively. 5 Stickel F Buch S Nischalke HD et al. Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis. Am J Gastroenterol. 2018; 113: 1475-1483 Crossref PubMed Scopus (56) Google Scholar , 6 Stickel F Lutz P Buch S et al. Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers. Hepatology. 2020; 72: 88-102 Crossref PubMed Scopus (52) Google Scholar However, unlike in viral hepatitis-associated hepatocellular carcinoma, 7 Jiang DK Sun J Cao G et al. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet. 2013; 45: 72-75 Crossref PubMed Scopus (242) Google Scholar , 8 Kumar V Kato N Urabe Y et al. Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet. 2011; 43: 455-458 Crossref PubMed Scopus (303) Google Scholar a comprehensive and hypothesis-free genome-wide study to detect risk loci that might have remained unidentified for alcohol-related hepatocellular carcinoma so far has been lacking. Common genetic variation in alcohol-related hepatocellular carcinoma: a case-control genome-wide association studyWNT3A-WNT9A is a susceptibility locus for alcohol-related hepatocellular carcinoma, suggesting an early role of the Wnt–β-catenin pathway in alcohol-related hepatocellular carcinoma carcinogenesis. Full-Text PDF

Liver transplantation for acute on chronic liver disease; when and how?

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%-50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. When evaluating prognosis in patients with ACLF, it should be noted that this is a dynamic syndrome that may improve or worsen during hospitalization. Therefore, the ideal scoring system should be able to reflect the dynamic nature of the disease and the responsiveness to medical treatment. Considering the scoring systems and recent data indicating that sequential assessment of prognosis seems to have higher accuracy than prognosis evaluated at the diagnosis of ACLF, stepwise algorithms have been proposed to assess prognosis and help decision making in ACLF patients.

Hepatocellular Carcinoma in Patients Without Cirrhosis: The Fibrosis Stage Distribution, Characteristics and Survival.

The data on hepatocellular carcinoma (HCC) patients without liver cirrhosis is scarce. To study the epidemiology, underlying etiology and fibrosis distribution in noncirrhotic HCC and compare the survival outcomes to cirrhotic HCC. We conducted a retrospective study including all adult patients diagnosed with HCC at two US tertiary academic centers from 2000 to 2015. Univariable and multivariable Cox regression analyses were performed to evaluate the variables associated with patient survival. Two thousand two hundred and thirty-seven HCC patients were included in the final analysis, of which, 13% had no liver cirrhosis. The most common underlying liver disease in non-cirrhotic patients was cryptogenic cause (40%), followed by nonalcoholic fatty liver disease (NAFLD) (25.2%) and hepatitis C (19%). The percentage of F0-F1, F2, and F3 was 72%, 17%, and 11% (cryptogenic cause); 69%, 12%, and 19% (NAFLD); 50%, 17%, and 33% (alcohol); 33%, 39%, and 28% (hepatitis B); 20%, 40%, and 40% (hemochromatosis); and 12%, 40%, and 48% (hepatitis C), respectively. In non-cirrhotic compared to cirrhotic patients, the tumor was more likely to be larger and fell outside Milan criteria (all p < 0.001). Cirrhotic patients had significant shorter survival than non-cirrhotic patients (p < 0.001). On the multivariable analysis, having liver cirrhosis (HR 1.48; 1.21-1.82, p < 0.001), combined viral hepatitis and alcohol use (HR 1.51; 1.23-1.88, p < 0.001), morbid obesity (HR 1.31; 1.01-1.69, p = 0.040) and underweight (HR 2.06; 1.27-3.34, p = 0.004) were associated with worse patient survival. The fibrosis distribution in non-cirrhotic HCC differed among each etiology of liver diseases. Despite more advanced HCC, patients without cirrhosis had significantly longer survival than those with cirrhosis.

Diagnostic Performance of Liver Imaging Reporting and Data System Version 2017 Versus Version 2018 for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Comparative Studies.

The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing liver imaging in patients at risk for hepatocellular carcinoma (HCC). To systematically compare the performance of computed tomography (CT)/MRI LI-RADS category 5 (LR-5) for diagnosing HCC between versions 2017 and 2018. Systematic review and meta-analysis. Six articles with 1181 lesions. 1.5 T and 3.0 T. Data extraction was independently performed by two reviewers who identified and reviewed articles comparing the performance of LR-5 for diagnosing HCC between CT/MRI LI-RADS versions 2017 and 2018. Study and patient characteristics, index test characteristics, reference standards, and study outcomes were extracted from included studies. Risk of bias and concerns regarding applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects models were used to calculate the pooled per-observation sensitivity and specificity of LR-5 using both versions. The summary receiver operating characteristic curves were plotted. Meta-regression analysis was performed to explore heterogeneity. A P-value <0.05 was considered to be statistically significant for all analyses other than heterogeneity, where the significance threshold was 0.1. The pooled per-observation sensitivity of LR-5 for diagnosing HCC did not show statistically significant difference between versions 2017 (60%; 95% confidence interval [CI], 49%-70%) and 2018 (67%; 95% CI, 56%-76%; P=0.381). The pooled per-observation specificities of LR-5 were not significantly different between versions 2017 (92%; 95% CI, 90%-95%) and 2018 (91%; 95% CI, 88%-93%; P=0.332). Meta-regression analyses revealed that the most common underlying liver disease (hepatitis B or hepatitis C) was a significant factor contributing to the heterogeneity of sensitivities among studies for both versions. In this meta-analysis using intraindividual paired comparisons, the pooled sensitivity and pooled specificity of LR-5 were not significantly different between 2017 and 2018 LI-RADS versions. 3 TECHNICAL EFFICACY: Stage 2.

Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death in Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2015. Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative sample of patients newly diagnosed with HCC in Korea, were analyzed. A total of 1,558 patients with HCC registered in the KPLCR in 2015 were investigated. The median age was 61.0 years (interquartile range, 54.0-70.0 years), and men accounted for 79.7% of the subjects. Hepatitis B virus infection was the most common underlying liver disease (58.1%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stage 0, A, B, C, and D HCCs accounted for 14.2%, 31.5%, 7.6%, 39.0%, and 7.8% of patients, respectively. Transarterial therapy (32.1%) was the most commonly performed initial treatment, followed by surgical resection (23.2%), best supportive care (20.2%), and local ablation therapy (10.7%). Overall, 34.5% of patients were treated in accordance with the BCLC guidelines: 59.2% in stage 0/A, 48.4% in stage B, 18.1% in stage C, and 71.6% in stage D. The 1-, 3-, and 5-year OS rates were 67.1%, 50.9%, and 27.0%, respectively. In 2015, approximately 45% of Korean HCC cases were diagnosed at a very early or early stage, and 35% of patients underwent potentially curative initial treatment. BCLC guidance was followed in 34.5% of patients; in patients with stage B or C disease, there was relatively low adherence.

Circulating Cancer Stem Cells in Hepatocellular Carcinoma: A Pilot Study of Prediction for Tumor Recurrence after Living Donor Liver Transplantation

Introduction: The optimal indication of LT in HCC patients has evolved from Milan criteria to morphologic criteria with biologic markers. The role of circulating cancer stem cells has not been reported in patients who underwent LT for HCC. Method: From April 2014 to March 2017, 25 patients who underwent LDLT for HCC were prospectively enrolled. EpCAM, CD90 and EpCAM/CD90 were sorted by FACS and mRNA expression of EPCAM, KRT19, THY1 were analyzed by RT-PCR in peripheral blood at preoperative, postoperative day 1 and 7, respectively. The median follow-up duration was 40 months. Results: The mean age was 55.9 years, and HBV was the most common underlying liver disease (88%). 10 patients were above Milan criteria at diagnosis. HCC recurred in 4 patients. The detected numbers of EpCAM (+) cells and CD90 (+) cells were well correlated with mRNA expression levels in the peripheral blood (P< 0.05). EpCAM protein in HCC tissue was highly expressed in patients with recurrence (66% vs. 20%). (p=0.172). HCCs with EpCAM (+) protein expression showed more detection of EpCAM (+) circulating cells than EpCAM (-). The detection of EpCAM (+) or EpCAM(+)/CD90(+) cells before surgery and at postoperative day 1 were significantly associated with HCC recurrence after LT (p< 0.05 for all). Conclusion: Detection of EpCAM (+) or EpCAM(+)/CD90(+) cells in the peripheral blood before surgery and at postoperative day 1 was the only variable significantly associated with HCC recurrence after LDLT but should be validated in a large-scale prospective study.

The Liver Imaging Reporting and Data System tumor-in-vein category: a systematic review and meta-analysis.

We aimed to systematically determine the etiology of the Liver Imaging Reporting and Data System (LI-RADS) tumor-in-vein category (LR-TIV) on contrast-enhanced CT or MRI and to determine the sources of heterogeneity between reported results. Original studies reporting the etiology of LR-TIV were identified in MEDLINE and EMBASE up until July 7, 2020. The meta-analytic pooled percentages of HCC and non-HCC in LR-TIV were calculated. Subgroup analyses were performed according to the type of reference standard and the most common underlying liver disease. Meta-regression analysis was performed to explore study heterogeneity. Sixteen studies reported the etiology of a total of 150 LR-TIV, of which 98 (65%) were HCC and 52 (35%) were non-HCC. The meta-analytic pooled percentages of HCC and non-HCC in LR-TIV were 70.9% (95% confidence interval [CI], 55.7-82.5%; I2 = 59%) and 29.2% (95% CI, 17.5-44.4%; I2 = 59%), respectively. The meta-analytic pooled percentage of HCC was lower in studies using only pathology as a reference standard (67.1%; 95% CI, 49.3-81.1%), but higher in studies in which hepatitis C was the most common underlying liver disease (81.9%; 95% CI, 11.3-99.4%) than that in the total 16 studies. Study type (cohort study versus case-control study) was significantly associated with study heterogeneity (p = 0.04). The most common etiology of LR-TIV was HCC. It might be important to understand the percentage of HCC and non-HCC in LR-TIV in consideration of the type of reference standard, geographic differences, and study design. • The most common etiology of Liver Imaging Reporting and Data System (LI-RADS) tumor-in-vein category (LR-TIV) was hepatocellular carcinoma (HCC). • The percentage of HCC in LR-TIV was relatively low in studies using only pathology as a reference standard, but high in studies in which hepatitis C was the most common underlying liver disease. • Study type was a factor significantly influencing study heterogeneity.

S1106 Early Detection of Hepatocellular Carcinoma Recurrence in the Post-Transplant Population: A Comparison of RETREAT and Cleveland Clinic Florida Scoring System

INTRODUCTION: Liver transplantation (LT) for hepatocellular carcinoma (HCC) is curative in most cases, however, recurrence is observed in some patients. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score is an externally-validated scoring system for prediction of post-LT HCC recurrence. The Cleveland Clinic Florida Scoring System (CCFSS) is a potential new scoring system for prediction of HCC recurrence. Our study aimed to compare the RETREAT and CCFSS. METHODS: We conducted a retrospective cohort study of adult patients with HCC who underwent LT. The RETREAT score was classified as follows: low risk (scores 0-3), moderate risk (score 4), and high risk (score 5 or higher). The CCFSS is based on explant pathology and categorized as: low (score 1), moderate (score 2), and high risk (score 3). Mantel- Haenzsel chi-square analyses were conducted to compare the RETREAT and CCFSS classifications for detecting HCC recurrence. RESULTS: A total of 52 patients with HCC underwent LT. The median follow-up period was 37 months. The median age of the patient population was 65.5 years (range 30-74 years) and 75% were male. The most common underlying liver disease was hepatitis C (n = 29, 55.8%), followed by fatty liver disease (n = 13, 25%). On explant pathology, 41 patients (78.8%) had viable tumor size <5 cm, two patients (3.8%) had ≥5 cm tumor size and the rest had a complete pathological response. Sixteen patients (31%) showed microvascular invasion. In 14 patients (31%), the tumors were poorly differentiated. Thirty-four patients (65.4%) had only one or no HCC lesions on explant pathology. Four patients had post-LT HCC recurrence, all within 2 years of LT (Table 1). Both risk scores had a sensitivity of 75%; the specificity of RETREAT score was 95.8% while the specificity of CCFSS was 60.4%. The RETREAT score was better able to detect low, moderate and high levels of risk (P < 0.001), compared to the CCFSS score (P = 0.480). AFP levels at the time of LT were associated with HCC recurrences (P = 0.014). Patient age, gender, ethnicity, liver disease etiology, MELD scores, HCC lesions at the time of diagnosis, and number/type of locoregional therapy (LRT), were not predictive of HCC recurrence. CONCLUSION: This is the first study to evaluate the CCFSS as a potential new scoring system to predict HCC recurrence after LT. The RETREAT score is more specific than CCFSS. The incorporation of AFP levels at the time of LT improves the estimation of HCC recurrence in the post-LT period.Table 1

Cabozantinib in advanced hepatocellular carcinoma: Efficacy and safety data from an international multicenter real-world cohort.

e16668 Background: The multikinase inhibitor cabozantinib has been approved by the European Medicines Agency in November 2018 for hepatocellular carcinoma (HCC) prior treated with sorafenib. We report, to our knowledge, for the first time safety and efficacy data of an international, multicenter, real-world cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 10 centers in Austria and Germany. Patients´ characteristics, side effects, duration of treatment and survival data were analyzed until January 17, 2020. Results: 74 patients were identified of whom 65 patients were male (88%) and 9 were female (12%). The median age at the start of cabozantinib treatment was 66 years. The most common underlying liver diseases included hepatitis C in 15 (20%), hepatitis B in 6 (8%), alcohol in 17 (23%) and NAFLD/NASH in 20 (27%) patients, respectively. 64 patients (86%) had BCLC stage C and 43 patients (58%) were Child Pugh A. Cabozantinib was used as systemic second- and third-line treatment in 37 (50%), and 25 (34%) patients, respectively. In the remaining patients cabozantinib was used in further lines. The median starting dose was 40 mg (20-60 mg). In 26 patients (35%) a dose reduction due to side effects was performed. Following best responses under cabozantinib were documented: partial response in 4 (5%), stable disease in 22 (30%), and progressive disease in 24 (32%) patients, respectively. 24 patients (32%) had not yet been evaluable. The median duration of cabozantinib treatment was 4.4 months. 35 patients (47%) had died at day of data analysis. The median overall survival from start of cabozantinib treatment was 7.7 months. Most common adverse events were fatigue and diarrhea. Conclusions: Cabozantinib treatment was effective, safe and feasible in patients with advanced HCC. Patients in the real life setting had more advanced liver disease – only 58% of patients were Child A. Duration of treatment was similar to the phase 3 trial (CELESTIAL). However, overall survival was shorter, probably due to more advanced liver disease.

Effect of baseline medications on response to immunotherapy in hepatocellular carcinoma.

484 Background: Immunotherapy (IO) response rates in advanced hepatocellular carcinoma (HCC) are less than 20%. The microbiome has been shown to mediate IO response in experimental models, and clinical studies have observed that antibiotics, especially prior to IO initiation, are associated with reduced IO response. We reasoned that commonly prescribed antacid medications, such as proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), which are known to influence the microbiome, may also influence IO response. Methods: This is a retrospective chart review-based study of 95 patients with advanced HCC treated with IO at a single academic medical center. The primary outcome was overall survival (OS). The secondary outcome was overall response rate (ORR). The primary predictors were antibiotic or antacid exposure in the 60 days prior to IO. A secondary predictor was antibiotic or antacid exposure in the 30 days prior to IO. Results: The cohort was predominantly male (84%), was racially diverse (31% White, 23% Black, 23% Asian, 13% Hispanic), and had a median age of 65 years. There were 49 deaths with a median follow up of 0.96 years. The most common underlying liver diseases were HCV (49%), HBV (31%), and NASH (11%). The majority of patients had cirrhosis (80%), with a median Child Pugh score of 6. Within 60 days before IO, 25 patients received antibiotics, 40 received PPIs and 5 received H2RAs. Most patients receiving antibiotics also received a PPI (92%). The median duration of antibiotics was 5 days. Neither antibiotic nor antacid exposure within 60 or 30 days prior to IO was significantly correlated with OS in univariate or multivariate analyses, nor were they correlated with ORR. Conclusions: No significant associations between baseline exposure to antibiotics and antibiotics and OS or ORR were identified in this single-institution study. Larger observational studies or mechanistic studies are needed to clarify interactions between medications, the microbiome, and IO response. [Table: see text]

Liver disease referrals to an urban, hospital-based hepatology outpatient clinic over the past 25 years.

BackgroundAdditional hepatologists are required to manage the rapidly increasing number of patients with liver disease. One disincentive to trainees considering a career in hepatology is the longstanding perception that outpatient hepatology consists largely of managing patients with alcohol‐induced liver disease (ALD).ObjectivesTo document the types of liver diseases and changes in liver disease referrals to an urban outpatient liver disease clinic over the past 25 years.MethodsThe nature of the liver disorder, age, gender, and socioeconomic status of patients referred to an urban, hospital‐based, liver diseases outpatient program were documented from 1992 to 2017. Joinpoint analysis was performed to identify significant trends in referral prevalence rates of various disorders.ResultsIn 1992/1993, hepatitis C virus (HCV), followed by hepatitis B virus (HBV), “other”, non‐alcoholic fatty liver disease (NAFLD), and primary biliary cholangitis (PBC) were the most common underlying liver diseases in referred patients (39, 36, 12, 4.5, and 3.5% respectively), whereas in 2016/2017, NAFLD, HBV, HCV, “other,” and ALD were most common (60, 15, 12, 8.7, and 3.3%, respectively). Aside from NAFLD referrals, which consistently increased over the 25‐year period, the prevalence of all other liver disease referrals fluctuated but generally declined. Recently referred patients were significantly older (38 ± 13 years in 1992/1993 and 49 ± 15 years in 2016/2017, P < 0.0001), while gender and socioeconomic status have not changed.ConclusionsHepatology is a diverse, dynamic subspecialty where ALD continues to constitute less than 5% of all patient referrals.

Sensitivity of ultrasound in detecting hepatocellular carcinoma in obese patients compared to explant pathology as the gold standard.

Background/AimsThe American Association for the Study of Liver Diseases recommends ultrasound (US) screening for hepatocellular carcinoma (HCC) among cirrhotic patients, regardless of body mass index (BMI), every 6 months. We examined US sensitivity for diagnosis of HCC in obese patients. MethodsLiver transplant patients data with HCC in explant was used (January 2012-December 2017). All patients underwent liver US within 3 months of diagnosis of HCC. Number/size of HCC lesions were extracted from radiologic and pathologic reports. Obesity was defined as BMI ≥30 kg/m2. ResultsOne hundred sixteen patients were included. 80% were male, with mean BMI of 31 kg/m2. The most common underlying liver disease was hepatitis C virus (62%). At the time of diagnosis, median number of HCC lesions was 2 (interquartile range [IQR], 1–3), and median size of the largest lesion was 2.5 cm (IQR, 1.75–3.9). Overall sensitivity of US study for detection of HCC was 33% (95% confidence interval [CI], 29–48%). Sensitivity was 77% (95% CI, 62–93%) in patients with BMI<30 and 21% (95% CI, 11–30%) in patients with BMI≥30 (P<0.001). Size of the largest HCC lesion (P=0.290) and number of lesions (P=0.505) were not different between groups. Computed tomography (CT) scan detected HCC in 98% of the obese patients with negative US.ConclusionsSensitivity of US for detection of HCC is significantly lower among obese patients compared to overweight and normal weight patients. These patients may benefit from alternating between US and a different imaging modality.

Trends and Characteristics of Hepatocellular Carcinoma in Individuals Without Cirrhosis: A Cancer Registry Linked Large Center Study: 2017 Presidential Poster Award

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in patients with chronic liver disease and cirrhosis. Historically an estimated 10-20% of HCC develops in the absence of cirrhosis. The burden of liver disease has increased over time and the prevalence of underlying liver diseases has also changed. However, the characteristics of non-cirrhotic HCC are not well-described. The aims of this study were to (i) determine the contribution of non-cirrhotic HCC relative to all HCC seen at our center over time, and (ii) to compare patient and tumor characteristics in non-cirrhotic vs cirrhotic HCC. Methods: Using the State Cancer Registry, we identified all patients with HCC seen at a large academic health center from 2000-2014. Demographic, clinical and tumor characteristics were collected. Patients were categorized as non-cirrhotic (when ascertained with high probability), or as confirmed cirrhotics. The number of non-cirrhotic and cirrhotic HCC cases was determined over 5-year intervals (2000-2004, 2005-2009, and 2010-2014). Patient and tumor characteristics were compared between the groups. Results: During the 15-year study period, 4977 cases of HCC were reported to the Indiana State Cancer Registry, including 1250 subjects seen at least once at our institution. The presence or absence of cirrhosis could not be ascertained in 61 cases. Of the remaining 1189 cases, 135 (11.4%) were non-cirrhotic and 1054 (88.6%) had confirmed cirrhosis. The number of non-cirrhotic HCC cases did not change during the study period, but cirrhotic HCC increased over time (Table 1). Noncirrhotics were older, more frequently female and had more advanced HCC at diagnosis (Table 2). Non-cirrhotics underwent resection rather than liver transplantation more frequently compared to cirrhotics (Table 2). The most common underlying liver disease etiologies in non-cirrhotic HCC were unclear/cryptogenic (42%) and fatty liver (30%). Their frequency did not change over 2000-2004 (43.6% and 33.3%), 2005-2009 (47.4% and 22.8%) and 2010-2014 (30.8% and 38.5%), respectively (p=0.15).Table: Table. Trend of overall, non-cirrhotic and cirrhotic HCC over the study period.Table: Table. Comparison of selected patient and tumor characteristics in non-cirrhotic vs. cirrhotic HCC. Values are shown as mean (standard deviation) or number (percentage).Conclusion: The frequency of non-cirrhotic HCC was unchanged over the last 15 years, while cirrhotic HCC more than doubled. The lack of a screening strategy may explain the advanced stage at diagnosis in non-cirrhotic HCC. However; the association of non-cirrhotic HCC with unclear/cryptogenic or fatty liver disease supports the need for further study of HCC risk factors in patients with metabolic syndrome/fatty liver.

Liver Transplantation for Hepatocellular Carcinoma in Young Adults: A United Network for Organ Sharing Study.

Orthotopic liver transplantation (OLT) is curative for hepatocellular carcinoma (HCC). HCC is typically a disease of older adults (OAs); therefore, characteristics and outcomes of OLT for young adults (YAs) (ages 18-40) are not described. The objective of this study was to assess the characteristics and outcomes of YAs with HCC receiving OLT and compare these to OAs (ages >40 years). YAs with HCC who had OLT from the United Network for Organ Sharing (UNOS) database were included in this study. As a comparison group, OAs with HCC were matched 4:1 to the YA group. Descriptive statistics of demographics, comorbidities, and outcomes were generated. Kaplan-Meier product limit estimates were used to assess patient and graft survival. Conditional logistic regression and Cox proportional hazards frailty models were used to compare the groups. A total of 464 YAs received OLT for HCC. The most common underlying liver diseases were hepatitis C virus (21.3%), hepatitis B virus (HBV, 15.5%), and autoimmune/cholestatic disease (12.3%). An increased number of YAs received OLT for HCC after implementation of model for end-stage liver disease scoring. One thousand two hundred eighty OAs served as the comparison group. Post-transplant 5-year survival was 73.1% in YAs with a retransplantation rate of 7.8%. In OAs, survival and retransplantation rates were lower (68.6% p = 0.093; 4.3% p = 0.001). Four hundred sixty-four YAs with HCC received OLT in the UNOS database. Compared to the older population, survival and retransplantation rates were higher. HBV, which is vaccine preventable, is a frequent contributor to HCC in YAs.

Liver transplantation in Iceland: a retrospective study of indications and results

Liver transplantation is an important treatment option for end-stage liver disease. Since liver transplantation is not performed in Iceland, patients are sent abroad for this procedure. The aim of this study was to investigate indications and results of liver transplantations for Icelandic patients. The study was retrospective and included all patients in Iceland who had undergone liver transplantation from the first transplantation in 1984 to the end of 2012. Information was gathered from medical records. The study period was divided into three subperiods in order to evaluate changes in frequency of transplantation and survival. During the period, 45 liver transplantations, thereof five retransplantations, were performed. Of 40 patients 16 were males, 18 females, mean age 40 years. There were six children, 2 girls and 4 boys with an age range of 0.4-12 years. Number of transplantation per million inhabitants increased significantly (2.40 during 1984-1996; 5.18 during 1997-2006 and 8.90 during 2007-2013; p<0.01). The main indication for transplantation was cirrhosis with complications in 26 patients (65%), acute liver failure in 6 (15%), cirrhosis and hepatocellular carcinoma in three (8%), and hemangioendothelioma in two (5%). The most common underlying liver diseases were primary biliary cirrhosis in 8 (20%), autoimmune hepatitis in four (10%), alcoholic cirrhosis in three (7.5%) and primary sclerosing cholangitis in three (7.5%). The mean waiting time for transplantation was 5.9 months (median 3.2). Survial was 84% in one year and 63% in 5 years. Survival increased during the study period. The number of liver transplantations has increased significantly in recent years. Survival has improved and is comparable to survival in countries where liver transplantations are performed.

Current status of deceased donor split liver transplantation in Japan.

The aim of this study was to analyze the outcomes of deceased donor split liver transplantation (LT) in Japan. Among 257 deceased donor LTs, 36 recipients underwent split LT until the end of 2014. The clinical data of donors and recipients were collected from the national organ transplant network and 11 liver transplant institutions, and the outcomes of split LT were evaluated. Most of the whole livers were divided using the ex-situ splitting technique. Twelve livers were divided to left lateral segment/extended right lobe grafts and six livers to left lobe/right lobe grafts. The common underlying liver diseases consisted of graft failure in 11 patients, followed by acute liver failure in nine. Seventeen cases (48.6%) suffered from surgical complications, including biliary complications in six, all of which occurred in the cases receiving right-sided lobe grafts; intra-abdominal hemorrhage in five; and vascular complications in four. The overall graft 1-year and 3-year survival rates were 91.0% and 87.1%, respectively. An initial experience of deceased donor split LT in Japan shows acceptable outcomes despite the high incidence of surgical complications. Further advances in the development of the splitting technique are necessary to expand the application of split LT.