Naaventhan Palaniyappan

A study of T1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors

Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non‐invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the liver. Here, we extend this work to measure T1 of the whole liver and investigate the effects of additional histological factors such as steatosis, inflammation and iron accumulation on the relationship between liver T1 and fibrosis. We prospectively enrolled patients who had previously undergone liver biopsy to have MR scans. A non‐breath‐holding, fast scanning protocol was used to acquire MR relaxation time data (T1 and T2*), and blood serum was used to determine the enhanced liver fibrosis (ELF) score. Areas under the receiver operator curves (AUROCs) for T1 to detect advanced fibrosis and cirrhosis were derived in a training cohort and then validated in a second cohort. Combining the cohorts, the influence of various histology factors on liver T1 relaxation time was investigated. The AUROCs (95% confidence interval (CI)) for detecting advanced fibrosis (F ≥ 3) and cirrhosis (F = 4) for the training cohort were 0.81 (0.65–0.96) and 0.92 (0.81–1.0) respectively (p < 0.01). Inflammation and iron accumulation were shown to significantly alter T1 in opposing directions in the absence of advanced fibrosis; inflammation increasing T1 and iron decreasing T1. A decision tree model was developed to allow the assessment of early liver disease based on relaxation times and ELF, and to screen for the need for biopsy. T1 relaxation time increases with advanced fibrosis in liver patients, but is also influenced by iron accumulation and inflammation. Together with ELF, relaxation time measures provide a marker to stratify patients with suspected liver disease for biopsy. Copyright

Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging

Graphical abstract

The Utility of Scoring Systems in Predicting Early and Late Mortality in Alcoholic Hepatitis: Whose Score Is It Anyway?

Background. Alcoholic hepatitis (AH) is a distinct clinical entity in the spectrum of alcoholic liver disease with a high short-term mortality. Several scoring systems are being used to assess the severity of AH but the ability of these scores to predict long-term survival in these patients is largely unknown. Aims. We aim to assess the utility of five different scoring systems Child Pugh (CP), model for end-stage liver disease (MELD), Maddreys discriminant function (mDF), Glasgow AH score (GAHS), and age-bilirubin-INR-creatinine (ABIC) score in predicting shot-term and long-term survival in patients with AH. Methods. Patients with histological evidence of AH were identified from our database. The clinical and biochemical parameters were used to calculate the 5 different scores. The prognostic utility of these scores was determined by generating an ROC curve for survival at 30 days, 90 days, 6 months, and 1 year. Results and Conclusions. All 5 scores with the exception of CP score have a similar accuracy in predicting the short-term prognosis. However, they are uniformly poor in predicting longer-term survival with AUROC not exceeding 0.74. CP score is a very poor predictor of survival in both short and long term. Abstinence from alcohol was significantly (P < 0.05) associated with survival at 1 year.

Development and evaluation of a nurse-led transient elastography service for the staging of hepatic fibrosis in patients with suspected chronic liver disease

BACKGROUND AND AIMS Establishing the presence of fibrosis and cirrhosis is an essential step in the management of patients with chronic liver diseases (CLD). Liver stiffness measurement (LSM) based on transient elastography (TE) correlates well with the stages of liver fibrosis and has been developed as a non-invasive alternative to liver biopsy. The studies performed to date have used physician operators. With the potential use of TE for screening of community-based populations for liver disease, we aimed to evaluate the performance of nurse operators. DESIGN Retrospective analysis. METHODS We reviewed the reliability and accuracy of LSMs performed by the nurse-led TE service at Queens Medical Centre, Nottingham between May 2009 and January 2011. Consecutive patients with suspected CLD who underwent LSM were included. RESULTS Over the study period 585 LSMs were performed. Analysis was performed on the 208 patients where LSM could be compared with liver biopsy findings. Of these 11 (5.3%) had unreliable LSM results (less than 10 valid shots or success rate <60%). There were no LSM failures. Inadequate liver biopsy specimen led to exclusion in 26 (12.5%) patients. For the detection of significant fibrosis (Ishak stage >2), a sensitivity of 0.78 and specificity of 0.81 was obtained, with a cut-off value of 8 kPa. Using a cut-off value of 13 kPa for detection of cirrhosis, a sensitivity and specificity of 0.8 and 0.92 was obtained. CONCLUSION We have demonstrated that a nurse-led TE service can produce a low level of unreliable results and LSM failures, with comparable sensitivity and specificity for detecting significant fibrosis and cirrhosis to those reported in the literature. The demands on the use of TE could potentially be eased through the introduction of nurse-led service delivery.

Magnetic Resonance Imaging Methods for Assessing Cirrhosis and Portal Hypertension

Magnetic resonance imaging (MRI) has been widely used for the detection and characterisation of focal lesions of the liver. Its ability to distinguish the physical properties of the tissue as well as the vasculature with contrast enhancement has made MRI the gold-standard test for the diagnosis of hepatocellular carcinoma. Both of these properties should make MRI an attractive imaging modality in assessing chronic liver disease and hence, MRI methodologies for the evaluation and stratification of chronic liver disease are being developed recently. MRI permits assessment of the whole liver in contrast to the 1 /50,000th portion of the organ obtained by liver biopsy, the current gold standard for the evaluation of the degree of liver injury, inflammation or scarring. Routine liver biochemistry or ultrasound examinations that have been used for decades lack sensitivity to estimate the degree of liver pathology, therefore aren’t useful in patient stratification, prognostication or monitoring. MRI is non-invasive, widely available technology with the most potential to develop further in the future. MRI does not involve ionising radiation, which makes it a preferable, especially for repeated assessments in surveillance. In this chapter, we discuss the advances in MRI in diagnosing and assessing cirrhosis and portal hypertension. The role of magnetic resonance elastography (MRE) is discussed separately.

Using MRI to study the alterations in liver blood flow, perfusion, and oxygenation in response to physiological stress challenges: Meal, hyperoxia, and hypercapnia: Modulating Liver Blood Flow and Oxygen

Noninvasive assessment of dynamic changes in liver blood flow, perfusion, and oxygenation using MRI may allow detection of subtle hemodynamic alterations in cirrhosis.

OC-019 The evaluation of portal hypertension using quantitative magnetic resonance imaging (MRI)

Introduction The majority of complications in liver cirrhosis results from portal hypertension. The hepatic venous pressure gradient (HVPG) is the gold standard measure to assess portal pressure but this requires hepatic vein catheterisation which is an invasive procedure and available in only a few specialised liver units. We aim to develop a novel non-contrast quantitative MRI methodology to estimate portal pressure. Method We prospectively recruited patients undergoing HVPG measurement for clinical indications and MRI was performed within 6 weeks. A respiratory-triggered inversion recovery scheme was used to measure the longitudinal (T1) relaxation time of the liver and spleen employing a fat suppressed Echo Planar Imaging-acquisition. Phase-contrast (PC)-MRI was used to assess the velocity, area and bulk flow in the splanchnic circulation without any intravenous contrast agents. Results 33 patients [alcoholic, 10 (30.3%); non-alcoholic fatty liver disease, 11 (33.3%); and autoimmune hepatitis, 5 (15.2%)], aged 55 ± 12 years (mean ± SD) were enrolled in this study. 4 patients were excluded due to claustrophobia (3) and non-cirrhotic portal hypertension (1). Liver and spleen T1relaxation time correlated significantly with HVPG (R = 0.797, p < 0.001; R = 0.383, p = 0.037 respectively) (Figure 1). The correlation of HVPG with splanchnic and collateral haemodynamics is shown in Table 1.Abstract OC-019 Figure 1Abstract OC-019 Table 1 Vessel Correlation coefficient, R Significance, p Superior mesenteric artery Flow 0.30 0.11 Velocity 0.53 0.003* Splenic artery Flow 0.41 0.04* Velocity 0.61 0.001* Azygous vein Flow 0.72 <0.001* Velocity 0.44 0.018* Conclusion We have demonstrated that parameters related to both hepatic architecture and splanchnic haemodynamics derived from non-contrast quantitative MR imaging techniques correlate significantly with HVPG. In future studies, these MRI techniques will be utilised for the non-invasive evaluation of portal hypertension. Disclosure of interest None Declared.

PTU-121 Monitoring changes in hepatic architecture and haemodynamics with quantitative magnetic resonance imaging (MRI) following directly-acting antiviral therapy in hepatitis C patients with decompensated cirrhosis

Introduction Directly-acting antiviral (DAA) therapy achieves sustained virological response (SVR) in over 90% of those with chronic hepatitis C (CHC), but even in those with SVR, the risk for liver related morbidity and mortality persists albeit at a lower level. It is hypothesised that the residual risk of liver related outcome in those with SVR is related to the progression or non-regression of structural and haemodynamic changes of advanced liver disease at the time of HCV therapy. Here, we investigate the effect of DAAs on the hepatic architecture and splanchnic haemodynamics in patients with decompensated cirrhosis, using quantitative MRI techniques. Method We prospectively recruited patients receiving DAAs for CHC related decompensated cirrhosis from the East Midlands hub of the Early Access Programme commissioned by NHS England. MRI was performed before and at the end of a 12-week treatment with Daclatasvir, Sofosbuvir and Ribavarin. A respiratory-triggered inversion recovery scheme was used to measure the longitudinal (T1) relaxation time of the liver employing a fat suppressed Echo Planar Imaging-acquisition. Phase-contrast (PC)-MRI was used to assess the velocity, area and bulk flow in the splanchnic circulation without any intravenous contrast agents. Results 9 patients have undergone baseline and post-treatment MR scans and end-of-treatment response (EOTR) was achieved in all 9 patients, but one patient has had virologic relapse. There was a significant reduction in the T1 relaxation time in patients with SVR (baseline T1: 765 ± 112 ms; post-treatment 737 ± 118 ms; p = 0.043) (Figure 1). There were no significant changes in the hepatic artery, portal vein, superior mesenteric artery and splenic artery flow. The changes in the Model for End-Stage Liver Disease (MELD) and United Kingdom Model for End-Stage Liver Disease (UKELD) score are shown in Table 1.Abstract PTU-121 Table 1 Baseline Post-treatment Paired t-test MELD 8.1 ± 1.9 9.4 ± 2.4 p = 0.07 UKELD 49.0 ± 3.8 47.6 ± 4.5 p = 0.05Abstract PTU-121 Figure 1 Conclusion Treatment of decompensated CHC related cirrhosis with DAA is associated with early improvement in the MR markers of liver architecture. These early changes are likely to reflect the reduction in the inflammation associated with EOTR and is evident before any improvement in conventional liver function tests. This novel quantitative MR methodology will allow us to non-invasively monitor HCV related liver disease. Disclosure of interest None Declared.

PTU-120 Quantitative Magnetic Resonance Imaging (MRI) in the Evaluation of the Degree of Steatosis, Iron Accumulation and Fibrosis in Chronic Liver Diseases (Mrker Study): Abstract PTU-120 Table 1

Introduction Half of all the liver biopsies performed are to assess the severity of pathology including grading of fat, iron accumulation as well as fibrosis. Liver biopsies are invasive tests associated with sampling errors; the coefficient of variation for fibrosis measurement is 45% even with 25mm long specimens. We aimed to develop and validate non-contrast, non-breath-holding, quantitative MRI methodology to estimate the amout of fibrosis, fat and iron accumulation within the whole liver. Methods MRI relaxation time data (T1, T2and T2*) were acquired (over 15–20 minutes) using a novel Echo Planar Imaging technique with a respiratory-triggered (r.t.) acquisition method. 1H MR spectra were acquired (r.t.) using a multiple echo PRESS acquisition which allowed for individual T2correction to the spectrum for accurate quantification of the fat fraction in a 30x30x30mm3voxel. Results 115 patients (67 Training; 48 Validation cohort) with suspected chronic liver disease aged 19 to 72 years [alcoholic (13%), non-alcoholic (56%) fatty liver disease, chronic viral hepatitis (21%) and haemochromatosis (3%)] who had a liver biopsy ≥25 mm were included in the study. The diagnostic accuracy of the T1 parameter in the detection of different histological stages of fibrosis, using receiver operator curves and areas under the curve (AUC), in the training and validation cohort are summarised in Table 1. There were also significant correlations between MR measures of fat fraction and staging of steatosis with a Spearman’s correlation coefficient of 0.760 (p < 0.001) and T2* with hepatic iron staging with Spearman’s correlation coefficient of –0.588 (p < 0.001). The T1 relaxation time of the liver correlated with the percentage of fibrosis measured as a continous variable on morphometry within the entire study population (Pearson correlation coefficient of 0.712, p < 0.001). Abstract PTU-120 Table 1 Fibrosis stage (0–4) detected AUC Training AUC Validation Cirrhosis (stage 4 vs. 0–3) 0.91 0.83 Advanced fibrosis (stage 3/4 vs. 0/1/2) 0.81 0.78 Mild fibrosis (stage 2/3/4 vs. 0/1) 0.67 0.70 Conclusion Across a range of chronic liver diseases, MR measures of fat fraction, hepatic iron content and fibrosis of the whole liver correlate well with related histological measures. Disclosure of Interest None Declared

Hepatobiliary surgeryPortal hypertension and ascites

Portal pressure is the product of portal blood flow and resistance; an increase in either leads to increased portal pressure. Cirrhosis is the underlying cause in most cases, but portal hypertension can develop due to pre-, intra- and post-hepatic obstruction to the flow, secondary to a variety of causes. Diagnosis can be established by a combination of non-invasive imaging or portal vasculature and clinical or serological markers for the cause underlying cirrhosis. Development of gastro-oesophageal varices and ascites are the most important clinical manifestation of portal hypertension. Non-selective β-blockers and endoscopic band ligation are effective in primary and secondary prevention of variceal bleeding. Active variceal haemorrhage is managed using a combination of vasoactive drug (e.g. terlipressin) and endoscopic band ligation. If these measures fail, transjugular intrahepatic portosystemic shunt (TIPS) insertion achieves haemostasis. Diuretic therapy with spironolactone and furosemide are the mainstays of management of ascites. If ascites becomes refractory, repeat large volume paracentesis and TIPS in selected cases help to control symptoms. Development of ascites is an important landmark in the natural history of cirrhosis and liver transplantation should be considered definitive treatment.