A prospective study on the prevalence of MASLD in people with type-2 diabetes in the community. Cost effectiveness of screening strategies.

BACKGROUND AND AIMS: As screening for the liver disease and risk-stratification pathways are not established in patients with type-2 diabetes mellitus (T2DM), we evaluated the diagnostic performance and the cost-utility of different screening strategies for MASLD in the community. METHODS: Consecutive patients with T2DM from primary care underwent screening for liver diseases, ultrasound, ELF score and transient elastography (TE). Five strategies were compared to the standard of care: ultrasound plus abnormal liver function tests (LFTs), Fibrosis score-4 (FIB-4), NAFLD fibrosis score, Enhanced liver fibrosis test (ELF) and TE. Standard of care was defined as abnormal LFTs prompting referral to hospital. A Markov model was built based on the fibrosis stage, defined by TE. We generated the cost per quality-adjusted life year (QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) over a lifetime horizon. RESULTS: Of 300 patients, 287 were included: 64% (186) had MASLD and 10% (28) had other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287) and 3% (8/287), respectively. Among those with significant fibrosis classified by LSM≥8.1 kPa, false negatives were 54% from ELF and 38% from FIB-4. On multivariate analysis, waist circumference, BMI, AST levels and education rank were independent predictors of significant and advanced fibrosis. All the screening strategies were associated with QALY gains, with TE (148.73 years) having the most substantial gains, followed by FIB-4 (134.07 years), ELF (131.68 years) and NAFLD fibrosis score (121.25 years). In the cost-utility analysis, ICER was £2480/QALY for TE, £2541.24/QALY for ELF and £2059.98/QALY for FIB-4. CONCLUSION: Screening for MASLD in the diabetic population in primary care is cost-effective and should become part of a holistic assessment. However, traditional screening strategies, including FIB-4 and ELF, underestimate the presence of significant liver disease in this setting.

Androgenic anabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature.

BACKGROUND: Anabolic androgenic steroids (AAS) usage is widespread and increasing. AAS drug-induced liver injury (DILI) is recognised but its clinical course and management is poorly described. We report 2 cases of AAS DILI with associated renal dysfunction, managed successfully with oral corticosteroids. METHODS: A comprehensive review identified 50 further cases to characterise the clinical and biochemical course. Causality grading was calculated using the updated Roussel Uclaf Causality Assessment Method (RUCAM) score. Data are presented as median values. RESULTS: The most common AAS taken was methyldrostanolone. Patients commonly present with jaundice and pruritus but may exhibit other constitutional symptoms. Patients presented 56 days after starting, and bilirubin peaked 28 days after stopping, AAS. Causality assessment was 'unlikely' in 1 (2%), 'possible' in 31 (60%) and 'probable' in 20 (38%). Peak values were: bilirubin 705 µmol/L, alanine transaminase 125 U/L, aspartate transaminase 71 U/L, alkaline phosphatase 262 U/L, gamma-glutamyl transferase 52 U/L, international normalised ratio 1.1. Liver biopsies showed 'bland' canalicular cholestasis. 43% of patients developed kidney injury (peak creatinine 225 µmol/L). Therapies included antipruritics, ursodeoxycholic acid and corticosteroids. No patients died or required liver transplantation. CONCLUSIONS: Physicians are likely to encounter AAS DILI. Causality assessment using the updated RUCAM should be performed but defining indications and proving efficacy for therapies remains challenging.

Hepatic steatosis and fibrosis: Non-invasive assessment.

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.

Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial.

BACKGROUND: Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery. OBJECTIVES: The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches. DESIGN: Pilot parallel three-arm randomised controlled trial nested within feasibility work. SETTING: Two UK NHS departments of upper gastrointestinal surgery. PARTICIPANTS: Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy. INTERVENTIONS: Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access. MAIN OUTCOME MEASURE: The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited. RESULTS: During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the hybrid procedure and 20 to totally minimally invasive surgery. Recruitment is continuing, allowing a seamless transition into the definitive trial. Consequently, the database is unlocked at the time of writing and data presented here are for patients recruited by 31 August 2014. Random allocation achieved a good balance between the arms of the study, which, as a high proportion of patients underwent their allocated surgery (69/79, 87%), ensured a fair comparison between the interventions. Dressing patients with large bandages, covering all possible incisions, was successful in keeping patients blind while pain was assessed during the first week post surgery. Postsurgical length of stay and risk of adverse events were within the typical range for this group of patients, with one death occurring within 30 days among 76 patients. There were good completion rates for the assessment of pain at 6 days post surgery (88%) and of the patient-reported outcomes at 6 weeks post randomisation (74%). CONCLUSIONS: Rapid recruitment to the pilot trial and the successful refinement of methodology indicated the feasibility of a definitive trial comparing different approaches to oesophagectomy. Although we have shown a full trial of open compared with minimally invasive oesophagectomy to be feasible, this is necessarily based on our findings from the two clinical centres that we could include in this small preliminary study. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59036820. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 48. See the NIHR Journals Library website for further project information.

Accuracy and reliability of microbubble ultrasound measurements for the non-invasive assessment of hepatic fibrosis in chronic hepatitis C.

AIM: Contrast-enhanced ultrasound can be used to assess liver disease severity non-invasively by observing intra- and extrahepatic hemodynamic changes. Transit times are calculated to include intra- and extrahepatic components (hepatic vein transit time, HVTT) or the intrahepatic component (hepatic transit time, HTT), but these have not been compared directly. We aimed to compare diagnostic accuracy of HVTT and HTT in gauging the severity of chronic hepatitis C (CHC) and to assess inter- and intra-observer reliability. METHODS: Recorded ultrasound scans performed on 75 patients with biopsy-staged CHC, using the microbubble contrast agent Sonovue were analyzed. RESULTS: Diagnostic accuracy of HTT and HVTT for diagnosis of cirrhosis was 0.78 and 0.71 (P = 0.24). Diagnostic accuracy of HTT and HVTT for diagnosis of fibrosis stage >2 was 0.76 and 0.72 (P = 0.23). Negative predictive value for cirrhosis using this cut-off was high for both techniques (HVTT, 88%; HTT, 92%), suggesting utility for exclusion of cirrhosis. Inter-observer reliability for HTT and HVTT were 0.92 and 0.94, respectively. Intra-observer reliability for HTT and HVTT were 0.98 and 0.99. CONCLUSION: In this cohort, reliability exceeded 90% while diagnostic accuracy was in keeping with previous studies of microbubble transit time analysis. Despite higher numerical diagnostic accuracy for HTT, no significant difference was demonstrated between the techniques, suggesting that both methods can be used reliably.

31P MR spectroscopy in assessment of response to antiviral therapy for hepatitis C virus-related liver disease.

OBJECTIVE: An increase in the ratio of phosphomonoester (PME) to phosphodiester (PDE) during 31P MR spectroscopy of the liver has been observed with increasing severity of hepatitis C-related liver disease. The purpose of this study was to investigate the utility of 31P MR spectroscopy as a biomarker of response to interferon and ribavirin treatment. SUBJECTS AND METHODS: Forty-seven patients with biopsy-proven hepatitis C undergoing viral eradication treatment with interferon and ribavirin underwent hepatic 31P MR spectroscopy at 1.5 T (voxel size, 70 x 70 x 70 mm; TR, 10,000; number of signals averaged, 48). All underwent baseline imaging before treatment and repeated imaging at 6-month intervals after the start of treatment. RESULTS: All patients underwent follow-up imaging 6 months after the start of treatment; 25 patients, 12 months; and 10 patients, 18 months after the start of treatment. According to the Ishak histologic scoring system, nine patients had mild hepatitis; 30 patients, moderate to severe hepatitis; and eight patients, cirrhosis. Thirty-two patients responded to antiviral treatment. Among these patients, 25 had a decrease in PME/PDE ratio on follow-up imaging. Among responders the mean baseline PME/PDE ratio decreased from 0.27 +/- 0.02 (standard error) to 0.16 +/- 0.01 after treatment (paired Student's t test, p < 0.001). Among the 15 virologic nonresponders, the ratios were similar in six patients; six other patients had an increase on follow-up imaging. In the latter nonresponder group, the mean baseline PME/PDE ratio was 0.21 +/- 0.03 compared with 0.31 +/- 0.08 after treatment (paired Student's t test, p =0.24). CONCLUSION: The in vivo hepatic PME/PDE ratio decreased in patients with hepatitis C who responded to antiviral treatment and remained similar or increased in patients without a virologic response. These results suggest that PME and PDE can be used as biomarkers in a noninvasive test of response to treatment.

Quantitative versus morphological assessment of liver fibrosis: semi-quantitative scores are more robust than digital image fibrosis area estimation.

BACKGROUND/AIM: Digital image analysis (DIA) allows quantitative assessment of fibrosis on liver biopsy. Accurate determination of a threshold greyscale level representing fibrous tissue is critical. This method has not been fully evaluated in clinical practice. METHODS: Digital images of stained liver biopsy sections were captured by microscopy and converted to greyscale. A novel method of determining the threshold greyscale value at which to measure fibrosis area was developed (peak proportion area change (PPAC)). Reproducibility was tested in comparison with standard interactive thresholding and with semi-quantitative scoring using the Histological activity index (HAI) system by a histopathologist. Fibrosis areas for different sections from the same biopsy core were also compared by each method. RESULTS: Comparison between PPAC and interactive thresholding method demonstrated superior reproducibility of the PPAC method: r > 0.7, P < 0.001 compared with r = 0.19-0.64 (not all reaching significance). On a single section, reproducibility was similar for PPAC and the modified HAI system. When different sections from the same core were compared, the HAI system was more robust. CONCLUSIONS: The PPAC method is superior to standard interactive thresholding. However, variability in DIA scores between sections invalidates the technique for clinical use and semi-quantitative scoring systems remain the gold standard for fibrosis assessment.