Effects of Interventions for Improving Awareness and Knowledge of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults for Prevention of Liver Cancer-A Randomized Controlled Trial.

Chinese young adults (CYA), who are at an increasing risk of developing nonalcoholic fatty liver disease (NAFLD), which in turn increases the risk of liver cancer, are an ideal target population to deliver educational interventions to improve their awareness and knowledge of NAFLD and consequently reduce their risk of developing NAFLD. The purpose of this study was to determine the efficacy of two interventions to improve awareness and knowledge of NAFLD among CYA for the prevention of liver cancer. Between May and July 2021, 1373 undergraduate students aged 18 to 25 years in one university in China completed a web-based, self-administered survey distributed through WeChat app. One week after completion of the baseline survey, all eligible participants were randomly assigned to a pamphlet, a video intervention, or no intervention (control group), with follow-up assessments immediately and 1-month post-intervention. The 7-page pamphlet or 6.5-min video had information on NAFLD. Self-assessments included NAFLD awareness, lean NAFLD awareness, and knowledge scores of NAFLD. About 26% of participants had NAFLD awareness at baseline. Compared with controls, participants in both interventions showed significant improvement of awareness of NAFLD (pamphlet, + 46.0%; video, + 44.3%; control, + 18.7%; OR [95% CI], 3.13 [2.19-4.47] and 2.84 [1.98-4.08]), awareness of lean NAFLD (pamphlet, + 41.2%; video, + 43.0%; control, + 14.5%; OR [95% CI], 2.84 [1.62-4.99] and 2.61 [1.50-4.54]), and knowledge score of NAFLD (pamphlet, + 64.2%; video, + 68.9%; control, - 1.0%; OR [95% CI], 1.62 [1.47-1.80] and 1.67 [1.50-1.86]) at immediately post-intervention. Delivering NAFLD education through a pamphlet or video intervention was effective in improving the awareness and knowledge of NAFLD among CYA.

Sustained elimination of parenteral support in adult patients with under 60 cm of small intestine: A case series.

Patients with short bowel syndrome (SBS) are often managed by expert multidisciplinary teams. One of the main goals in the management of SBS is the weaning of parenteral support (PS). Weaning of PS removes the risks associated with long-term central line placement and eliminates the need for intestinal transplant. Whereas several papers detail the ongoing care and management of patients with SBS who are dependent on PS, there are few reports discussing the successful weaning of PS in this patient population. We present five case studies examining weaning of PS in adult patients with <60-cm small bowel and partial or full colon who were enrolled in a multidisciplinary adult intestinal rehabilitation program. The case studies demonstrate weaning can occur >2 years after initial assessment and enrollment in an expert program. The ability of the program to focus on individualized care and frequent patient communication is key to PS weaning in patients with SBS.

Development and Validation of a Questionnaire to Assess Awareness and Knowledge of Nonalcoholic Fatty Liver Disease, a Liver Cancer Etiological Factor, among Chinese Young Adults.

PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of valid, reliable, ready-to-use survey instruments for assessing awareness and knowledge of NAFLD in this population. The aims of this study were to develop, validate, and assess the reliability of a web-based, self-administered questionnaire evaluating awareness and knowledge of NAFLD among CYA. METHODS: Based on review of relevant literature, a draft questionnaire was initially developed. Face and content validity of the questionnaire was evaluated by an expert panel of seven gastroenterologists. The construct validity was tested through item analysis based on item response theory. Reliability assessment included test-retest for stability and test for internal consistency. Two pilot tests were conducted among 60 randomly selected students at Lanzhou University, China, through WeChat App. RESULTS: The content validity and clarity indexes were both greater than 0.85. Face validity was established by concluding that questions had no issue with feasibility, readability, clarity of wording, clarity of layout, and style. Response rates for two pilot tests were 96.7% (58 out of 60) and 98.3% (59 out of 60), respectively. Results testing the construct validity showed estimated amount of information obtained by the test between -3 and +3 range of ability was 97.57%. The test-retest reliability (Pearson's r) was 0.62. The internal consistency (KR20) was 0.92. CONCLUSIONS: This newly developed questionnaire is a reliable and valid instrument for assessing awareness and knowledge of NAFLD among this sample from CYA.

Factors Associated with Awareness and Knowledge of Nonalcoholic Fatty Liver Disease, a Liver Cancer Etiological Factor, Among Chinese Young Adults.

PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of study assessing awareness and knowledge of NAFLD among them. This study aimed to assess awareness and knowledge of NAFLD, and identify the factors associated with awareness and knowledge of NAFLD among CYA. We conducted a survey to assess awareness and knowledge of NAFLD among students who enrolled in one university undergraduate program in 2018, 2019, and 2020 through a newly developed web-based, self-administered questionnaire. The outcomes included awareness of NAFLD and knowledge score of NAFLD. We conducted unadjusted and adjusted analyses of associated factors with these outcomes. A total of 1373 students participated in the survey. Of all participants, 26.2% reported that they had heard of NAFLD, 7.7% reported that they had heard of lean NAFLD, and 11.1% received ≥ 20 points in the knowledge section of NAFLD. The mean and median scores were 9.35 (Std = 7.67) and 9 (range 0-27). Factors associated with having awareness and knowledge (≥ 20 points) of NAFLD included medical background, high medical knowledge level, and family history of NAFLD. There was low NAFLD awareness and knowledge among CYA aged 18 to 25 years. Our findings point to the need to develop an educational intervention for CYA to improve their NAFLD awareness and knowledge. Further studies should include information on physical activity and dietary habits to test whether NAFLD awareness and knowledge impact those habits.

Cholecystectomy prior to short bowel syndrome does not alter nutritional prognosis.

BACKGROUND: Previous cholecystectomy is common in patients with short bowel syndrome (SBS). An intact gallbladder is beneficial in preventing cirrhosis in SBS patients, but the nutritional consequences of cholecystectomy are largely unknown. Our aim was to evaluate the effect of pre-SBS cholecystectomy on need for chronic parenteral nutrition (PN). METHODS: We reviewed 485 adults with SBS: 267 underwent cholecystectomy prior to SBS and 218 patients had an intact gallbladder. Demographic data, intestinal anatomy, and nutritional outcome were compared. RESULTS: Pre-SBS cholecystectomy patients were more likely to have had postoperative SBS and BMI >35. Intestinal remnant length and anatomy type and performance of surgical rehabilitation procedures within the first year were similar. Overall, there was no significant difference in the need for PN > 1year between the two groups. There was also no significant difference in the need for PN > 1year in any specific subgroup of intestinal remnant length or intestinal anatomy. CONCLUSIONS: Cholecystectomy performed prior to the development of SBS does not influence the nutritional prognosis of SBS, regardless of the intestinal remnant length and anatomy type.

Illicit Drug Use and Endoscopy: When Do We Say No?

BACKGROUND: Illicit drug use (IDU) is often encountered in patients undergoing elective ambulatory surgical procedures such as endoscopy. Given the variety of systemic effects of these drugs, sedation and anesthetics are believed to increase the risk of cardiopulmonary complications during procedures. Procedural cancelations are common, regardless of the drug type, recency of use, and total dosage consumed. There is a lack of institutional and society recommendations regarding the optimal approach to performing outpatient endoscopy on patients with IDU. AIM: To review the literature for current recommendations regarding the optimal management of outpatient elective endoscopic procedures in patients with IDU. Secondary aim is to provide guidance for clinicians who encounter IDU in endoscopic practice. METHODS: Systematic review of PubMed, CINAHL, Embase, and Google Scholar for articles presenting data on outcomes of elective procedures in patients using illicit drugs. RESULTS: There are no clinically relevant differences in periprocedural complications or mortality in cannabis users compared to non-users. Endoscopy in patients with remote cocaine use was also found to have similar outcomes to recent use. CONCLUSIONS: Canceling endoscopic procedures in patients with recent IDU without consideration of the type of drug, dosage, and chronicity may lead to unnecessary delays in care and increased patient morbidity. Healthcare systems would benefit from additional guidelines for evaluating the patient with recent illicit drug use for acute intoxication and consider proceeding with procedures in the non-toxic population.

Presentation of preclinical gastrointestinal anatomy via laparoscopic simulation.

In this report, the authors examine the integration of teaching anatomical science with clinical implications in minimally invasive surgery. The authors hypothesized that implementation of integrated laparoscopic simulation during undergraduate medical education would improve student learning of anatomical structures from in situ, laparoscopic orientations; and subsequently improve student preparation for clinical rotations and clerkships. During the fall of 2020 and 2021, 260 (130 students/year) second year medical students at the University of Nebraska Medical Center participated in a six-week gastrointestinal curriculum. Following a traditional anatomy dissection experience, students completed a laparoscopic event consisting of narrated laparoscopic videos and hands-on laparoscopic simulation. To examine the integrated curricular event, outcome measures focused on technical performance using grasping forceps, anatomical knowledge, and perception of the educational innovation. Outcomes were analyzed via timed performance and a pre and post assessment that was designed to assess student anatomical knowledge and perception. Completion of the technical performance assessment ranged from 1 min, 17 s to 6 min. Student knowledge of anatomical structures from in situ, laparoscopic orientations following the laparoscopic simulation sessions was significantly improved (53.3% pre vs 81.0% post), and almost all students (98.9%) agreed that the simulation sessions improved their understanding of laparoscopic anatomy and procedures. This report demonstrates the implementation of a multidisciplinary, integrated simulation that satisfied basic science anatomy teaching objectives, while enhancing student enthusiasm for the content. Future studies will examine the subsequent impact of the innovation on student preparedness for clinical rotations and clerkships.

Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure.

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil-based lipid therapy should be implemented in order to successfully halt and reverse IFALD.

Liver Transplantation in a Patient With Hepatic Angiosarcoma.

Liver transplantation (LT) is an accepted form of therapy for selected cases of malignant tumors of the liver that include primary and fibrolamellar hepatocellular carcinoma, cholangiocarcinoma limited to Klatskin distribution, neuroendocrine tumors, epithelioid hemangioendothelioma, and hepatoblastoma. This is the case of a 61-year-old previously healthy female transferred from an outside hospital for a second opinion for a liver transplant. Computed tomography of the abdomen with contrast showed cirrhosis and multiple masses with arterial enhancement in her liver. She underwent a liver biopsy that showed a low-grade vascular tumor. She underwent an exploratory laparotomy with open liver biopsy which showed no visual evidence of omental spread. The pathology was reported as a low-grade vascular lesion, which was likely a small vessel neoplasm. After denial for LT secondary to an unknown low-grade vascular tumor, she presented to our medical center. Oncology was consulted and diagnosed with her liver vascular tumors as benign with an overall favorable prognosis. She was listed for liver transplant with a model for end-stage liver disease-sodium score of 25 and developed hepatorenal syndrome type 1. She was on hemodialysis for approximately 10 weeks prior to her LT and was eventually listed for simultaneous liver and kidney transplants. She underwent an orthotopic liver transplant 10 weeks after presenting to UNMC. The amount of necrosis and the elevated mitotic rate was sufficient to classify the tumor as a Federation Nationale des Centres de Lutte le Cancer grade 3 of three angiosarcomas. She was scheduled for a living donor kidney transplant three days after her liver transplant, but it was postponed after she continued to have increased urine output that responded to a trial of diuretics with continued improvement in kidney function. She successfully completed 16 months post-LT without any known recurrence of primary angiosarcoma.

Dry Beriberi Manifesting as Acute Inflammatory Demyelinating Polyneuropathy in a Patient With Decompensated Alcohol-Induced Cirrhosis.

Thiamine (vitamin B1) deficiency is uncommon in developed countries and is most commonly seen in patients with poor dietary intake, malabsorption syndromes, and alcoholism. With the increasing rates of alcohol use, thiamine deficiency is likely an under-recognized and potentially reversible cause of sensorimotor dysfunction called dry beriberi. We present a case of profound lower extremity weakness in a 28-year-old female from Nepal with decompensated alcohol-induced cirrhosis. Based on laboratory testing, it was determined that the cause of her neuropathy was dry beriberi. She was subsequently started on thiamine replacement therapy with slow improvement over the next six months.

Impact of sarcopenia on mortality in patients undergoing liver re-transplantation.

BACKGROUND: Sarcopenia, which is a loss of skeletal muscle mass, has been reported to increase post-transplant mortality and morbidity in patients undergoing the first liver transplant. Cross-sectional imaging modalities typically determine sarcopenia in patients with cirrhosis by measuring core abdominal musculatures. However, there is limited evidence for sarcopenia related outcomes in patients undergoing liver re-transplantation (re-OLT). AIM: To evaluate the risk of mortality in patients with pre-existing sarcopenia following liver re-OLT. METHODS: This is a retrospective study of all adult patients who had undergone a liver re-OLT at the University of Nebraska Medical Center from January 1, 2007 to January 1, 2017. We divided patients into sarcopenia and no sarcopenia groups. "TeraRecon AquariusNet 4.4.12.194" software was used to evaluate computed tomography or magnetic resonance imaging of the patients done within one year prior to their re-OLT, to calculate the Psoas muscle area at L3-L4 intervertebral disc. We defined cutoffs for sarcopenia as < 1561 mm2 for males and < 1464 mm2 for females. The primary outcome was to compare 90 d, one, and 5-year survival rates. We also compared complications after re-OLT, length of stay, and re-admission within 30 d. Survival analysis was performed with Kaplan-Meier survival analysis. Continuous variables were evaluated with Wilcoxon rank-sum tests. Categorical variables were evaluated with Fisher's exact tests. RESULTS: Fifty-seven patients were included, 32 males: 25 females, median age 50 years. Two patients were excluded due to incomplete information. Overall, 47% (26) of patients who underwent re-OLT had sarcopenia. Females were found to have significantly more sarcopenia than males (73% vs 17%, P < 0.001). Median model for end stage liver disease at re-OLT was 28 in both sarcopenia and no sarcopenia groups. Patients in the no sarcopenia group had a trend of longer median time between the first and second transplant (36.5 mo vs 16.7 mo). Biological markers, outcome parameters, and survival at 90 d, 1 and 5 years, were similar between the two groups. Sarcopenia in re-OLT at our center was noted to be twice as common (47%) as historically reported in patients undergoing primary liver transplantation. CONCLUSION: Overall survival and outcome parameters were no different in those with and without the evidence of sarcopenia after re-OLT.

Impact of psychosocial comorbidities on clinical outcomes after liver transplantation: Stratification of a high-risk population.

BACKGROUND: Liver transplantation is the accepted standard of care for end-stage liver disease due to a variety of etiologies including decompensated cirrhosis, fulminant hepatic failure, and primary hepatic malignancy. There are currently over 13000 candidates on the liver transplant waiting list emphasizing the importance of rigorous patient selection. There are few studies regarding the impact of additional psychosocial barriers to liver transplant including financial hardship, lack of caregiver support, polysubstance abuse, and issues with medical non-compliance. We hypothesized that patients with certain psychosocial comorbidities experienced worse outcomes after liver transplantation. AIM: To assess the impact of certain pre-transplant psychosocial comorbidities on outcomes after liver transplantation. METHODS: A retrospective analysis was performed on all adult patients from 2012-2016. Psychosocial comorbidities including documented medical non-compliance, polysubstance abuse, financial issues, and lack of caregiver support were collected. The primary outcome assessed post-transplantation was survival. Secondary outcomes measured included graft failure, episodes of acute rejection, psychiatric decompensation, number of readmissions, presence of infection, recidivism for alcohol and other substances, and documented caregiver support failure. RESULTS: For the primary outcome, there were no differences in survival. Patients with a history of psychiatric disease had a higher incidence of psychiatric decompensation after liver transplantation (19% vs 10%, P = 0.013). Treatment of psychiatric disorders resulted in a reduction of the incidence of psychiatric decompensation (21% vs 11%, P = 0.022). Patients with a history of polysubstance abuse in the transplant evaluation had a higher incidence of substance abuse after transplantation (5.8% vs 1.2%, P = 0.05). In this cohort, 15 patients (3.8%) were found to have medical compliance issues in the transplant evaluation. Of these specific patients, 13.3% were found to have substance abuse after transplantation as opposed to 1.3% in patients without documented compliance issues (P = 0.03). CONCLUSION: Patients with certain psychosocial comorbidities had worse outcomes following liver transplantation. Further prospective and multi-center studies are warranted to properly determine guidelines for liver transplantation regarding this high-risk population.

Gigantic Stomach: A Rare Manifestation of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is characterized by degeneration and atrophy of skeletal, cardiac, and smooth muscles after a latent period of apparently normal development and function. The gastrointestinal manifestations start in the second decade of life and are mainly due to atrophy of smooth muscle layers. Refractory gastroparesis and chronic constipation can lead to severe gastric and small bowel dilatation, which can be life threatening. Here, we present a case of a 21-year-old male with a gigantic stomach secondary to DMD resolved with conservative management and no surgical intervention.

Surgical Delay Is Associated with Improved Survival in Hepatocellular Carcinoma: Results of the National Cancer Database.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the fastest growing causes of cancer-related death in the USA. Studies that investigated the impact of HCC therapeutic delays are limited to single centers, and no large-scale database research has been conducted. This study investigated the association of surgical delay and survival in HCC patients. METHODS: Patients underwent local tumor destruction and hepatic resection for stages I-III HCC were identified from the 2004 to 2013 Commission on Cancer's National Cancer Database. Surgical delay was defined as > 60 days from the date of diagnosis to surgery. Generalized linear-mixed model assessed the demographic and clinical factors associated with delay, and frailty Cox proportional hazard analysis examined the prognostic factors for overall survival. RESULTS: A total of 12,102 HCC patients met the eligibility criteria. Median wait time to surgery was 50 days (interquartile range, 29-86), and 4987 patients (41.2%) had surgical delay. Delayed patients demonstrated better 5-year survival for local tumor destruction (29.1 vs. 27.6%; P = .001) and resection (44.1 vs. 41.0%; P = .007). Risk-adjusted model indicated that delayed patients had a 7% decreased risk of death (HR, 0.93; 95% CI, 0.87-0.99; P = .027). Similar findings were also observed using other wait time cutoffs at 50, 70, 80, 90, and 100 days. CONCLUSIONS: A plausible explanation of this finding may be case prioritization, in which patients with more severe and advanced disease who were at higher risk of death received earlier surgery, while patients with less-aggressive tumors were operated on later and received more comprehensive preoperative evaluation.

Intestinal failure-associated liver disease: causes, manifestations and therapies.

PURPOSE OF REVIEW: The goal of this review is to provide updates on the causes, manifestations and therapies IFALD in adults with an emphasis on recent discoveries on pathways of pathogenesis and interventions to reduce the incidence of IFALD. RECENT FINDINGS: IFALD is a multifactorial complication of long-term home parenteral therapy. Although exact pathways are unknown, altered bile acid metabolism, microbiome dysbiosis impact on the gut-liver axis and soybean-based lipid formulations are major drivers of IFALD development. SUMMARY: IFALD contributes to morbidity and mortality in patients on parenteral nutrition. Proactive management by a multidisciplinary team has led to improved outcomes in at-risk patients. Attention to early treatment and prevention of sepsis, introduction of nonsoybean based lipid formulations, surgical procedures such as step enteroplasties and, potentially, microbiome dysbiosis are considerations in IFLAD management.

Prophylactic cholecystectomy in short bowel syndrome: Is it being utilized?

INTRODUCTION: Cholelithiasis is common in patients with short bowel syndrome (SBS). Prophylactic cholecystectomy (PC) of the non-diseased gallbladder has been recommended in SBS patients when laparotomy is being undertaken for other reasons. Our aim was to determine if PC is being utilized. METHODS: 500 adults with SBS were seen over a 25 year period. 215 undergoing cholecystectomy prior to SBS were excluded, leaving 285 patients for evaluation. RESULTS: 151 (53%) SBS patients underwent a subsequent laparotomy. 77 underwent cholecystectomy for cholelithiasis at the 1st opportunity. 27 patients underwent a PC at the 1st opportunity. 47 patients did not undergo PC at the 1st opportunity. 17 (36%) of these 47 patients subsequently developed cholelithiasis with 7 undergoing cholecystectomy. Age, gender, diagnosis and initial BMI and need for longterm parenteral nutrition were similar in patients who had PC or did not. PC patients were more likely to have intestinal remnant length <60 cm (59% vs 21%, p < .05). CONCLUSIONS: Overall 10% of SBS patients underwent PC. However, only 36% of eligible patients undergoing laparotomy had a PC.

Castleman's Disease and Posttransplant Lymphoproliferative Disorder after Liver Transplant: 3-Year Follow-Up.

A 59-year-old male with a history of hepatitis C cirrhosis and history of hepatitis B exposure presented 8 months after orthotopic liver transplant (LT) with fever, fatigue, myalgia, night sweats, nonproductive cough, and shortness of breath. Bone marrow biopsy for pancytopenia was positive for Epstein-Barr virus (EBV) DNA. Lymph node biopsy for lymphadenopathy on imaging showed human herpes virus 8 (HHV8) associated Castleman's disease. Treatment included valganciclovir, rituximab, and prednisone taper with eventual discontinuation. Quantitative HHV8 DNA was initially 611,000 DNA copies/mL and was later undetectable at 6 months following treatment and remained undetectable at 3-year follow-up.

Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B.

BACKGROUND: Globally, of the 248 million people chronically infected with the hepatitis B virus (HBV), 74 million reside in China. Five oral nucleot(s)ide analogs (NUCs) have been approved for the treatment of chronic hepatitis B (CHB) in China. OBJECTIVES: The aims of this study were to determine rates of adherence to NUC therapy in patients with CHB, to identify the self-perceived barriers to adherence, and to examine the factors associated with adherence. METHODS: Questionnaire-based interviews were administered among Chinese patients with CHB at hepatology clinics of a tertiary hospital in the city of Wuhan, China. Adults aged 18 years or older prescribed with NUCs were recruited and interviewed to complete a 27-item questionnaire in a private setting, and adherence was measured using the Morisky Medication Adherence Scale (MMAS-8). RESULTS: Among 369 participants, only 16.5% had high adherence (score of 8), 32.2% had medium adherence (score of 6 to <8), and 51.2% were measured with low adherence (score of <6). A logistic regression model was used to determine the factors associated with medication adherence. Significant predictors of high adherence consisted of urban residency, non-cirrhotic status, not using prescribed pills other than HBV medications, and reminders from family members. The five most common reasons for skipping NUCs were that medication(s) are expensive (48.7%), forgetfulness (45.1%), have experienced or worry about potential side effects (19.8%), do not want others to know about my medication(s) usage (18.5%), and ran out of pills and do not have time to refill (15.9%). CONCLUSIONS: This study revealed that adherence rates to oral antiviral therapy were far from optimal. This finding should generate public attention, and it would be beneficial for interventional programs to target Chinese patients from rural regions, as well as patients with low socioeconomic status, cirrhosis, and taking multiple medications.

Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study.

BACKGROUND: Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. METHODS: The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice-web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39). FINDINGS: Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the seladelpar 200 mg group. Mean changes from baseline in alkaline phosphatase were -2% (SD 16) in the placebo group, -53% (14) in the seladelpar 50 mg group, and -63% (8) in the seladelpar 200 mg group. Changes in both seladelpar groups versus placebo were significant (p<0·0001 for both groups vs placebo), with no significant difference between the two seladelpar groups (p=0·1729). All five patients who received seladelpar for 12 weeks had normal alkaline phosphatase values at the end of treatment, based on a central laboratory ULN for alkaline phosphatase of 116 U/L. The most frequently reported adverse events were pruritus (16%; one patient on placebo, four on seladelpar 50 mg, and one on seladelpar 200 mg), nausea (13%; one patient on placebo, three on seladelpar 50 mg, and one on seladelpar 200 mg), diarrhoea (10%; two patients on placebo, one on seladelpar 50 mg, and one on seladelpar 200 mg), dyspepsia (8%; two patients on seladelpar 50 mg and one on seladelpar 200 mg), muscle spasms (8%; three patients on seladelpar 200 mg), myalgia (8%; one patient on placebo and two on seladelpar 200 mg), and dizziness (8%; one patient on placebo and two on seladelpar 50 mg). INTERPRETATION: Seladelpar normalised alkaline phosphatase levels in patients who completed 12 weeks of treatment. However, treatment was associated with grade 3 increases in aminotransferases and the study was stopped early. The effects of seladelpar should be explored at lower doses. FUNDING: CymaBay Therapeutics.

Practice, Knowledge, and Barriers for Screening of Hepatocellular Carcinoma Among High-Risk Chinese Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the leading causes of cancer deaths in China. Considering its poor prognosis when diagnosed late, Chinese guidelines recommend biannual screening for HCC with abdominal ultrasound and serum α-fetoprotein (AFP) test for high-risk populations. OBJECTIVES: To investigate the practice, knowledge, and self-perceived barriers for HCC screening among high-risk hospital patients in China. METHODS: An interview-based questionnaire was conducted among Chinese patients with chronic hepatitis B and/or chronic hepatitis C infection from outpatient clinics at 2 tertiary medical institutions in Shanghai and Wuhan, China. FINDINGS: Among 352 participating patients, 50.0% had routine screening, 23.3% had irregular screening, and 26.7% had incomplete or no screening. Significant determinants for screening included higher level of education, underlying liver cirrhosis, a family history of HCC, and better knowledge concerning viral hepatitis, HCC, and HCC screening guidelines. Moreover, factors associated with better knowledge were younger age, female gender, urban residency, education level of college or above, annual household income of greater than 150,000 RMB, and longer duration of hepatitis infection. The 3 most common barriers reported for not receiving screening were not aware that screening for HCC exists (41.5%), no symptoms or discomfort (38.3%), and lack of recommendation from physicians (31.9%). CONLUSIONS: Health care professionals and community leaders should actively inform patients regarding the benefits of HCC screening through design of educational programs. Such interventions are expected to increase knowledge about HCC and HCC screening, as well as improve screening adherence and earlier diagnosis.