Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

Systematic Review and Meta-Analysis on the Effects of Lactulose and Rifaximin on Patient-Reported Outcomes in Hepatic Encephalopathy.

INTRODUCTION: Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs. RESULTS: We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin. DISCUSSION: Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies.

Active coping, resilience, post-traumatic growth, and psychiatric symptoms among early and late liver transplant survivors.

Understanding survivorship experiences at different stages postliver transplantation (poat-LT) is essential to improving care. Patient-reported concepts including coping, resilience, post-traumatic growth (PTG), and anxiety/depression, have been implicated as important predictors of quality of life and health behaviors after LT. We aimed to descriptively characterize these concepts at different post-LT survivorship stages. This cross-sectional study featured self-reported surveys measuring sociodemographic, clinical characteristics, and patient-reported concepts including coping, resilience, PTG, anxiety, and depression. Survivorship periods were categorized as early (1 y or below), mid (1-5 y), late (5-10 y), and advanced (10 y or above). Univariable and multivariable logistic and linear regression modeling examined factors associated with patient-reported concepts. Among 191 adult LT survivors, the median survivorship stage was 7.7 years (interquartile range: 3.1-14.4) and median age was 63 years (range: 28-83); most were male (64.2%) and Caucasian (84.0%). High PTG was more prevalent in the early survivorship period (85.0%) than late survivorship (15.2%). High trait resilience was only reported by 33% of survivors and associated with higher income. Lower resilience was seen among patients with longer LT hospitalization stays and late survivorship stages. About 25% of survivors had clinically significant anxiety and depression, which was more frequent among early survivors and females with pre-LT mental health disorders. In multivariable analysis, factors associated with lower active coping included survivors ≥65 years, non-Caucasian race, lower levels of education, and nonviral liver disease. In a heterogeneous cohort including early and late LT survivors, there was variation in levels of PTG, resilience, anxiety, and depression at different survivorship stages. Factors associated with positive psychological traits were identified. Understanding determinants of LT survivorship has important implications for how we should monitor and support LT survivors.

Successful liver transplantation in patients with active SARS-CoV-2 infection.

The Coronavirus Disease 2019 (COVID-19) pandemic has substantially impacted solid organ transplantation, including temporary inactivation of waitlist candidates with COVID-19 infection. We report two cases of liver transplantation (LT) in individuals with asymptomatic COVID-19 infection. The first patient is a 68-year-old female with decompensated cirrhosis complicated by worsening frailty and sarcopenia. The second patient is a 22-year-old female with acute liver failure likely secondary to drug/toxin exposure. Both patients were treated with COVID-19-directed therapies and neither patient developed symptomatic disease. These cases demonstrate that LT can be safely performed in select patients with asymptomatic COVID-19 infection at the time of transplant.

Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma.

BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment.

Speech patterns and enunciation for encephalopathy determination-A prospective study of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a complication of cirrhosis that benefits from early diagnosis and treatment. We aimed to characterize speech patterns of individuals with HE to investigate its potential to diagnose and monitor HE. This was a single-center prospective cohort study that included participants with cirrhosis with HE (minimal HE [MHE] and overt HE [OHE]), cirrhosis without HE, and participants without liver disease. Audio recordings of reading, sentence repetition, and picture description tasks were obtained from these groups. Two certified speech-language pathologists assessed speech rate (words per minute) and articulatory precision. An overall severity metric was derived from these measures. Cross-sectional analyses were performed using nonparametric Wilcoxon statistics to evaluate group differences. Change over time in speech measures was analyzed descriptively for individuals with HE. The study included 43 total participants. Speech results differed by task, but the overall pattern showed slower speech rate and less precise articulation in participants with OHE compared to other groups. When speech rate and precision ratings were combined into a single speech severity metric, the impairment of participants with OHE was more severe than all other groups, and MHE had greater speech impairment than non-liver disease controls. As OHE improved clinically, participants showed notable improvement in speech rate. Participants with OHE demonstrated impaired speech rate, precision, and speech severity compared with non-liver disease and non-HE cirrhosis. Participants with MHE had less pronounced impairments. Speech parameters improved as HE clinically improved. Conclusion: These data identify speech patterns that could improve HE diagnosis, grading, and remote monitoring.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021.

BACKGROUND & AIMS: Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. METHODS: We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH). RESULTS: Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020. CONCLUSIONS: Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Early Survivorship After Liver Transplantation: A Qualitative Study Identifying Challenges in Recovery From the Patient and Caregiver Perspective.

Survivorship after liver transplantation (LT) is a novel concept providing a holistic view of the arduous recovery experienced after transplantation. We explored components of early survivorship including physical, emotional, and psychological challenges to identify intervention targets for improving the recovery process of LT recipients and caregivers. A total of 20 in-person interviews were conducted among adults 3 to 6 months after LT. Trained qualitative research experts conducted interviews, coded, and analyzed transcripts to identify relevant themes and representative quotes. Early survivorship comprises overcoming (1) physical challenges, with the most challenging experiences involving mobility, driving, dietary modifications, and medication adherence, and (2) emotional and psychological challenges, including new health concerns, financial worries, body image/identity struggles, social isolation, dependency issues, and concerns about never returning to normal. Etiology of liver disease informed survivorship experiences including some patients with hepatocellular carcinoma expressing decisional regret or uncertainty in light of their post-LT experiences. Important topics were identified that framed LT recovery including setting expectations about waitlist experiences, hospital recovery, and ongoing medication requirements. Early survivorship after LT within the first 6 months involves a wide array of physical, emotional, and psychological challenges. Patients and caregivers identified what they wish they had known prior to LT and strategies for recovery, which can inform targeted LT survivorship interventions.

Roux-en-Y Gastric Bypass Is Associated With Increased Hazard for De Novo Alcohol-related Complications and Liver Disease.

GOAL: The goal of this study was to determine if bariatric surgeries are associated with de novo alcohol-related complications. BACKGROUND: Bariatric surgery is associated with an increased risk of alcohol use disorders. The effect of bariatric surgeries on other alcohol-related outcomes, including liver disease, is understudied. MATERIALS AND METHODS: Using the IMS PharMetrics database, we performed a cohort study of adults undergoing bariatric surgery or cholecystectomy, excluding patients with an alcohol-related diagnosis within 1 year before surgery. The primary outcome was any alcohol-related diagnosis after surgery. We fit a multivariable Cox proportional hazards model to determine independent associations between bariatric surgeries [Roux-en-Y gastric bypass (RYGB); adjustable gastric band; sleeve gastrectomy] versus cholecystectomy and the development of de novo alcohol-related outcomes. We further fit complication-specific models for each alcohol-related diagnosis. RESULTS: RYGB was significantly associated with an increased hazard of any de novo alcohol-related diagnosis [adjusted hazard ratio (AHR)=1.51, 95% confidence interval (CI): 1.40-1.62], while adjustable gastric band (AHR=0.55, 95% CI: 0.48-0.63) and sleeve gastrectomy (AHR=0.77, 95% CI: 0.64-0.91) had decreased hazards. RYGB was associated with a 2- to 3-fold higher hazard for alcoholic hepatitis (AHR=1.98, 95% CI: 1.17-3.33), abuse (AHR=2.05, 95% CI: 1.88-2.24), and poisoning (3.14, 95% CI: 1.80-5.49). CONCLUSIONS: RYGB was associated with higher hazards of developing de novo alcohol-related hepatitis, abuse, and poisoning compared with a control group. Patients without a history of alcohol use disorder should still be counseled on the increased risk of alcohol use and alcohol-related complications, including alcohol-related liver disease, following RYGB, and should be monitored long term for the development of alcohol-related complications.

"If I Get Cured, My Whole Quality of Life Will Change": Patients' Anticipated and Actualized Benefits Following Cure from Chronic Hepatitis C.

BACKGROUND: Patients' motivations for undergoing direct-acting antiviral (DAA) therapy for chronic hepatitis C may include anticipation of treatment benefits not well described in the literature. AIMS: Evaluate patients' anticipated and actualized improvements in several domains of functioning before and after viral cure. METHODS: Pre-post-study utilizing in-depth interviews with 28 patients prior to, and several months after, DAA therapy. Interviews were audio-recorded, transcribed, coded, and analyzed by two qualitative experts. RESULTS: Patients had a median age of 54 years, 43% were male, 57% white, 25% had cirrhosis, and 71% were treated with sofosbuvir/ledipasvir. Pre-treatment, patients hoped for improvements in several domains including psychological, emotional, physical, social, and occupational functioning. After viral cure, increased energy and less fear of transmission were pathways to better quality of life. Psychological and emotional improvements positively affected physical, social, and occupational functioning. Social improvements were due to better mood and motivation, fewer symptoms, and reduced fear of stigma and transmission. Occupational benefits were linked to increased stamina, self-confidence, and less pain, anxiety, and stigma. Reduced fear of stigma had a pervasive impact on all life improvements after cure. Patient characteristics such as the presence of cirrhosis or psychiatric issues influence treatment motivations. Qualitative data correspond with change in pre-post-survey scores. CONCLUSIONS: Tremendous hope is placed on the ability of DAA therapy to bring about substantial improvements in life functioning after viral cure. Highly interconnected effects on quality of life worked synergistically through improved physical and psychological well-being. Stakeholders should appreciate the multi-dimensional benefits that viral eradication bestows upon individuals and society.

Liver biopsy in the real world-reporting, expert concordance and correlation with a pragmatic clinical diagnosis.

BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis. Aims To investigate the completeness of real-world NASH-related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy-diagnosed NASH and a pragmatic clinical definition of NASH. METHODS: Liver pathology reports from 222 patients across 38 TARGET-NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over-read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET-NASH clinically defined NASH: elevated ALT, hepatic steatosis on biopsy or imaging and ≥1 of the following: BMI ≥30 kg/m2 , type 2 diabetes mellitus and dyslipidaemia. RESULTS: Documentation of steatosis, lobular inflammation, portal inflammation and ballooning were missing from 21%, 35%, 46% and 40% of reports, respectively. There was slight-to-fair concordance (weighted kappa 0.01-0.35) between site and central pathologists for inflammatory features, and moderate concordance (weighted kappa 0.56-0.57) for fibrosis staging. Clinical definition of NASH was 75%-91% concordant (94%-95% sensitive) with biopsy-diagnosed NASH. CONCLUSIONS: There is substantial variability in reporting and grading NASH and fibrosis staging in clinical practice. This heterogeneity may adversely impact patient assessment and translation of practice guidelines into reality. The TARGET-NASH pragmatic clinical definition may serve as a valuable tool to accurately identify NASH patients in clinical practice.

What Survivorship Means to Liver Transplant Recipients: Qualitative Groundwork for a Survivorship Conceptual Model.

Survivorship is a well-established concept in the cancer care continuum with a focus on disease recurrence, quality of life, and the minimization of competing risks for mortality; however, survivorship has not been well studied in liver transplantation (LT). We investigated what survivorship means to LT patients and identified motivations and coping strategies for overcoming challenges after LT. A total of 20 in-depth home interviews were conducted among adults 3 to 6 months after LT. Interviews were conducted by trained qualitative research experts and coded and analyzed using an inductive approach. A majority of LT recipients (75%) identified themselves as survivors. Integral to the definition of survivorship was overcoming hardship (including experiences on the waiting list) and the unique experience of being given a "second chance" at life. Motivations to survive included a new chance at life (55%), family (40%), spirituality/faith (30%), and fear of rejection (15%). LT recipients and caregivers identified multiple strategies to cope with post-LT challenges, including relying on a large network of community, spiritual, and virtual support. These findings informed a conceptual model of LT survivorship based on socioecological theory, which identified the following variables influencing survivorship: (1) pretransplant experiences, (2) individual attributes and challenges, (3) interpersonal relationships with caregivers and other social support, (4) community relationships, and (5) large-scale factors including neighborhood and financial issues. LT recipients identified themselves as survivors, and post-LT identities were greatly influenced by pre-LT experiences. These perspectives informed an in-depth conceptual model of survivorship after transplantation. We identified sources of motivation and coping strategies used in LT recovery that could be targets of survivorship interventions aimed at improving post-LT outcomes.

The Clinical Spectrum and Diagnosis of Oxaliplatin Liver Injury in the Era of Nonalcoholic Fatty Liver Disease.

Oxaliplatin is an alkylating agent given with fluorouracil and leucovorin as a mainstay adjuvant chemotherapy for stage III colorectal cancer (CRC). Liver injury from oxaliplatin ranges from mild liver enzyme increases in 42% to 57% of patients in clinical trials1 to rare severe injury leading to acute liver failure.2 Chronic injury from endothelial cell damage and architectural distortion may manifest years later with nodular regenerative hyperplasia (NRH), portal sclerosis, and noncirrhotic portal hypertension (NCPH).2,3 Chronic subclinical injury occurs in up to 78% of patients.3 Diagnosis may be confounded by nonalcoholic fatty liver disease (NAFLD), and long-term outcomes from chronic injury are unclear.

A Systematic Review of Patient-Reported Outcomes in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with decreased health-related quality of life and debilitating symptoms. These experiences can be defined as patient-reported outcome (PRO) concepts and measured using PRO instruments. We identified all PRO concepts and instruments used in the PBC and PSC literature. This systematic review identified PBC and/or PSC studies from January 1, 1990, to May 6, 2019, that measured at least one PRO concept. Study population, design, PRO concept, PRO instrument, and validation data for PRO instruments were investigated. We provided descriptive statistics of PRO concepts and instruments used, stratified by population type. Use of PRO concepts and instruments were assessed over time. The search yielded 318 articles (69% in PBC, 18% in PSC, 13% in both, and 24% in drug trials). Forty-nine unique PRO concepts were identified. The five most common PRO concepts included pruritus (25%), fatigue (19%), broad health-related quality of life (16%), gastrointestinal adverse events (6%), and physical adverse events (6%). Only 60% of PRO concepts were measured with a PRO instrument, most of which were nonvalidated visual analogue or numeric rating scales. Only three of 83 PRO instruments were developed with feedback from the target populations (one for PBC, one for PSC, and one for both), and only six documented any psychometric testing in the target populations. Use of PRO instruments increased over time from 30% in the 1990s to 67% by 2019. Conclusion: The overwhelming majority of PRO instruments used in PBC/PSC were nonspecific and lacked patient validation or empirical justification. Significant opportunities exist to use qualitative methods to better understand patient experiences, and translate this knowledge into meaningful, patient-driven study outcomes.

A Quality Improvement Initiative Results in Improved Rates of Timely Postvariceal Bleeding Surveillance Endoscopy.

OBJECTIVES: We performed a study to assess the effects of a quality improvement (QI) initiative on the rates of postvariceal bleeding surveillance upper endoscopy (EGD). METHODS: We identified patients with cirrhosis hospitalized with variceal bleeding and assessed the rates of timely (≤4 weeks) EGD before and after a QI initiative. RESULTS: Preintervention: 16% (5 of 32) of patients underwent timely surveillance EGD. We developed a standardized ordering template for gastroenterology fellows and reserved postvariceal EGD scheduling slots. Postintervention: 43% (12 of 28) of patients underwent timely surveillance EGD. DISCUSSION: A QI intervention was associated with a 27% absolute increase in timely surveillance EGDs.

An Evolving Approach to the Diagnosis of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic/ immune-mediated esophageal disease. Knowledge related to the clinical presentation, pathogenesis, epidemiology, natural history, treatment, and outcomes of EoE has rapidly evolved over the past 2 decades. This article focuses on the similarly evolving diagnostic framework for EoE. In the initial clinical guidelines, diagnosis of EoE was based on symptoms of esophageal dysfunction; at least 15 eosinophils per high-power field (eos/hpf) on esophageal biopsy; and either a lack of response to high-dose proton pump inhibitor (PPI) therapy, or normal pH monitoring. The first 2 criteria have remained largely unchanged; however, the role of PPIs has been controversial, particularly due to the recognition of PPI-responsive esophageal eosinophilia (PPI-REE), in which patients with suspected EoE experience resolution of symptoms and esophageal eosinophilia with PPI therapy. A quickly expanding evidence base has found that most adult patients with EoE and PPI-REE share similar clinical, endoscopic, histologic, immunologic, and molecular characteristics prior to the use of PPIs. Because of this, the most recent diagnostic guidelines have removed the lack of response to PPIs as a diagnostic criterion; PPIs are now better considered as a treatment for esophageal eosinophilia. EoE should currently be suspected on a clinical basis when there are symptoms of esophageal dysfunction and at least 15 eos/hpf on esophageal biopsies. A history of atopy and endoscopic signs of EoE are strongly supportive of the diagnosis. However, the diagnosis cannot be confirmed until a thorough evaluation of other potential causes of esophageal eosinophilia has been performed.