Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

BACKGROUND AND AIMS: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. APPROACH AND RESULTS: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. CONCLUSIONS: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.

PHOTOSTENT-02: porfimer sodium photodynamic therapy plus stenting versus stenting alone in patients with locally advanced or metastatic biliary tract cancer.

BACKGROUND: Endobiliary stenting is standard practice for palliation of obstructive jaundice due to biliary tract cancer (BTC). Photodynamic therapy (PDT) may also improve biliary drainage and previous small studies suggested survival benefit. AIMS: To assess the difference in outcome between patients with BTC undergoing palliative stenting plus PDT versus stenting alone. METHODS: 92 patients with confirmed locally advanced or metastatic BTC, ECOG performance status 0-3 and adequate biliary drainage were randomised (46 per group) to receive porfimer sodium PDT plus stenting or stenting alone. The primary end point was overall survival (OS). Toxicity and progression-free survival (PFS) were secondary end points. Treatment arms were well balanced for baseline factors and prior therapy. RESULTS: No significant differences in grade 3-4 toxicities and no grade 3-4 adverse events due to PDT were observed. Thirteen (28%) PDT patients and 24 (52%) stent alone patients received subsequent palliative chemotherapy. After a median follow-up of 8.4 months, OS and PFS were worse in patients receiving PDT compared with stent alone group (OS median 6.2 vs 9.8 months (HR 1.56, 95% CI 1.00 to 2.43, p=0.048) and PFS median 3.4 vs 4.3 months (HR 1.43, 95% CI: 0.93 to 2.18, p=0.10), respectively). CONCLUSION: In patients with locally advanced or metastatic BTC, PDT was associated with worse outcome than stenting alone, explained only in part by the differences in chemotherapy treatments. We conclude that optimal stenting remains the treatment of choice for malignant biliary obstruction and the use of PDT for this indication cannot be recommended outside of clinical trials. TRIAL REGISTRATION NUMBER: ISRCTN 87712758; EudraCT 2005-001173-96; UKCRN ID: 1461.

Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data.

BACKGROUND & AIMS: Cirrhosis, the prevalence of which is increasing, is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. METHODS: We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients vs. controls, adjusted for age, sex and comorbidity. RESULTS: The five-year hip fracture risk was raised both in England (2.9% vs. 0.8% for controls) and Denmark (4.6% vs. 0.9% for controls). With confounder adjustment, patients with cirrhosis had fivefold (adjusted HR 5.5; 95% CI 4.3-6.9), and 8.5-fold (adjusted HR 8.5; 95% CI 7.8-9.3) increased rates of hip fracture, in England and Denmark, respectively. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p <0.001), being stronger in younger age groups (under 45 years, HR 17.9 and 16.6 for English and Danish patients, respectively) than in patients over 75 years (HR 2.1 and 2.9, respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. CONCLUSIONS: Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population. These findings support the need for more effort towards fracture prevention in this population, to benefit individuals and reduce the societal burden. LAY SUMMARY: Alcoholic cirrhosis creates a large public health burden and is a risk factor for bone fractures. Based on data from England and Denmark, we found that hip fractures occur more than five times more frequently in people with alcoholic cirrhosis than in people without the disease. Additionally, the aftermath of the hip fracture is severe, such that up to 11% of patients with alcoholic cirrhosis die within 30 days after their hip fracture. These results suggest that efforts directed towards fracture prevention in people with alcoholic cirrhosis could be beneficial.

Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: a cross-sectional survey.

OBJECTIVE: Guidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of the Liver-European Association for the study of Diabetes-European Association for the study of Obesity. Prior to publication of these guidelines, we performed a cross-sectional survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and management. DESIGN: An online survey was circulated to members of British Association for the Study of the Liver and British Society of Gastroenterology between February 2016 and May 2016. RESULTS: 175 gastroenterologists/hepatologists responded, 116 completing the survey, representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300 referrals per year from primary care for investigation of abnormal liver function tests (LFTs). Clinical assessment tended to be performed in secondary rather than primary care including body mass index (82% vs 26%) and non-invasive liver screen (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive fibrosis risk stratification were aspartate transaminase (AST)/alanine transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%). 78% considered liver biopsy in selected cases. 50% recommended 10% weight loss target as first-line treatment. Delivery of lifestyle interventions was mostly handed back to primary care (56%). A minority have direct access to community weight management services (22%). Follow-up was favoured by F3/4 fibrosis (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%). CONCLUSIONS: The survey highlights areas for improvement of service provision for NAFLD assessment including improved recognition of non-alcoholic steatohepatitis in people with type 2 diabetes, streamlining abnormal LFT referral pathways, defining non-invasive liver fibrosis assessment tools, use of liver biopsy, managing metabolic syndrome features and improved access to lifestyle interventions.

The communication of a secondary care diagnosis of autoimmune hepatitis to primary care practitioners: a population-based study.

BACKGROUND: Autoimmune Hepatitis is a chronic liver disease which affects young people and can result in liver failure leading to death or transplantation yet there is a lack of information on the incidence and prevalence of this disease and its natural history in the UK. A means of obtaining this information is via the use of clinical databases formed of electronic primary care records. How reliably the diagnosis is coded in such records is however unknown. The aim of this study therefore was to assess the proportion of consultant hepatologist diagnoses of Autoimmune Hepatitis which were accurately recorded in General Practice computerised records. METHODS: Our study population were patients with Autoimmune Hepatitis diagnosed by consultant hepatologists in the Queens Medical Centre, Nottingham University Hospitals (UK) between 2004 and 2009. We wrote to the general practitioners of these patients to obtain the percentage of patients who had a valid READ code specific for Autoimmune Hepatitis. RESULTS: We examined the electronic records of 51 patients who had biopsy evidence and a possible diagnosis of Autoimmune Hepatitis. Forty two of these patients had a confirmed clinical diagnosis of Autoimmune Hepatitis by a consultant hepatologist: we contacted the General Practitioners of these patients obtaining a response rate of 90.5% (39/42 GPs). 37/39 of these GPs responded with coding information and 89% of these patients (33/37) used Read code J638.00 (Autoimmune Hepatitis) to record a diagnosis. CONCLUSIONS: The diagnosis of Autoimmune Hepatitis made by a Consultant Hepatologist is accurately communicated to and electronically recorded by primary care in the UK. As a large proportion of cases of Autoimmune Hepatitis are recorded in primary care, this minimises the risk of introducing selection bias and therefore selecting cases using these data will be a valid method of conducting population based studies on Autoimmune Hepatitis.