Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.

Severe Hepatitis Complicating Olmesartan Enteropathy: A Case Report.

Introduction: Olmesartan, an angiotensin II receptor antagonist, is associated with an uncommon complication of enteropathy that presents insidiously, usually months to years after initial commencement of anti-hypertensive therapy which can be dose-dependent. It has a variable spectrum of clinical presentation but commonly presents as a moderate to severe malabsorptive process with potential severe complications related to poor end-organ perfusion. Lymphocytic gastritis and microscopic colitis are often noted in patients presenting with olmesartan-induced enteropathy; however, hepatic involvement has been less frequently observed. Case Presentation: We illustrate a case of a 43-year-old female presenting with 2 weeks of profuse non-bloody diarrhea in the context of olmesartan enteropathy which was complicated by an acute severe ischemic and enteropathic hepatopathy. Conclusion: Our case prompts clinicians to maintain a high index of suspicion in cases presenting with a seronegative enteropathy and concurrent acute liver injury while on olmesartan therapy. Cessation of olmesartan therapy resulted in prompt resolution of diarrheal symptoms and normalization of the acute transaminitis on subsequent three-week follow-up.

Testosterone is lower in men with non-alcoholic fatty liver disease and alcohol-related cirrhosis and is associated with adverse clinical outcomes.

BACKGROUND/AIMS: Low serum testosterone is common in cirrhotic men, but the impact of disease aetiology remains uncertain. This study compares serum total testosterone (TT) levels by disease aetiology and assesses its prognostic value. METHODS: Single-centre retrospective study of cirrhotic men who had TT levels measured between 2002 and 2020. A cut-off of 12 nmol/L was used to define low TT and 230 pmol/L for calculated free testosterone (cFT). Linear and logistic regression used to adjust for variables known to affect testosterone levels and assess for an association between levels and outcomes. RESULTS: Of 766 cirrhotic men, 33.3% had alcohol-related liver disease (ALD) and 11.9% had non-alcoholic fatty liver disease (NAFLD). The median age was 56 years (interquartile range (IQR) 50-61), and the model for end-stage liver disease (MELD) score 14 (IQR 9-20). TT levels were low in 53.3% of patients, (median 11.0 nmol/L; IQR 3.7-19.8) and cFT low in 79.6% (median 122 pmol/L; IQR 48.6-212). Median TT was lower in men with ALD (7.6 nmol/L; IQR 2.1-16.2) and NAFLD (9.8 nmol/L; IQR 2.75-15.6) compared to other aetiologies (11.0 nmol/L; IQR 3.73-19.8) (p < 0.001 for all), which remained true after adjustment for age and MELD score. TT was inversely associated with 12-month mortality or transplant (381 events, p = 0.02) and liver decompensation (345 events, p = 0.004). CONCLUSIONS: Low serum testosterone is common in cirrhotic men and is associated with adverse clinical outcomes. TT levels are significantly lower in ALD and NAFLD compared to other disease aetiologies. Further large-scale studies are required to assess the potential benefits of testosterone therapy.

A home-based, multidisciplinary liver optimisation programme for the first 28 days after an admission for acute-on-chronic liver failure (LivR well): a study protocol for a randomised controlled trial.

BACKGROUND: Acute-on-chronic liver failure (ACLF) represents a rising global healthcare burden, characterised by increasing prevalence among patients with decompensated cirrhosis who have a 28-day transplantation-free mortality of 33.9%. Due to disease complexity and a high prevalence of socio-economic disadvantage, there are deficits in quality of care and adherence to guideline-based treatment in this cohort. Compared to other chronic conditions such as heart failure, those with liver disease have reduced access to integrated ambulatory care services. The LivR Well programme is a multidisciplinary intervention aimed at improving 28-day mortality and reducing 30-day readmission through a home-based, liver optimisation programme implemented in the first 28 days after an admission with either ACLF or hepatic decompensation. Outcomes from our feasibility study suggest that the intervention is safe and acceptable to patients and carers. METHODS: We will recruit adult patients with chronic liver disease from the emergency departments, in-patient admissions, and an ambulatory liver clinic of a multi-site quaternary health service in Melbourne, Australia. A total of 120 patients meeting EF-Clif criteria will be recruited to the ACLF arm, and 320 patients to the hepatic decompensation arm. Participants in each cohort will be randomised to the intervention arm, a 28-day multidisciplinary programme or to standard ambulatory care in a 1:1 ratio. The intervention arm includes access to nursing, pharmacy, physiotherapy, dietetics, social work, and neuropsychiatry clinicians. For the ACLF cohort, the primary outcome is 28-day mortality. For the hepatic decompensation cohort, the primary outcome is 30-day re-admission. Secondary outcomes assess changes in liver disease severity and quality of life. An interim analysis will be performed at 50% recruitment to consider early cessation of the trial if the intervention is superior to the control, as suggested in our feasibility study. A cost-effectiveness analysis will be performed. Patients will be followed up for 12 weeks from randomisation. Three exploratory subgroup analyses will be conducted by (a) source of referral, (b) unplanned hospitalisation, and (c) concurrent COVID-19. The trial has been registered with the Australian New Zealand Clinical Trials Registry. DISCUSSION: This study implements a multidisciplinary intervention for ACLF patients with proven benefits in other chronic diseases with the addition of novel digital health tools to enable remote patient monitoring during the COVID-19 pandemic. Our feasibility study demonstrates safety and acceptability and suggests clinical improvement in a small sample size. An RCT is required to generate robust outcomes in this frail, high healthcare resource utilisation cohort with high readmission and mortality risk. Interventions such as LivR Well are urgently required but also need to be evaluated to ensure feasibility, replicability, and scalability across different healthcare systems. The implications of this trial include the generalisability of the programme for implementation across regional and urban centres. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001703897 . Registered on 13 December 2021. WHO Trial Registration Data Set. See Appendix 1.

Utility and limitations of Hepascore and transient elastography to detect advanced hepatic fibrosis in HFE hemochromatosis.

Aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 Index (Fib4) have been validated against liver biopsy for detecting advanced hepatic fibrosis in HFE hemochromatosis. We determined the diagnostic utility for advanced hepatic fibrosis of Hepascore and transient elastography compared with APRI and Fib4 in 134 newly diagnosed HFE hemochromatosis subjects with serum ferritin levels > 300 µg/L using area under the receiver operator characteristic curve (AUROC) analysis and APRI- (> 0.44) or Fib4- (> 1.1) cut-offs for AHF, or a combination of both. Compared with APRI, Hepascore demonstrated an AUROC for advanced fibrosis of 0.69 (95% CI 0.56-0.83; sensitivity = 69%, specificity = 65%; P = 0.01) at a cut-off of 0.22. Using a combination of APRI and Fib4, the AUROC for Hepascore for advanced fibrosis was 0.70 (95% CI 0.54-0.86, P = 0.02). Hepascore was not diagnostic for detection of advanced fibrosis using the Fib4 cut-off. Elastography was not diagnostic using either APRI or Fib4 cut-offs. Hepascore and elastography detected significantly fewer true positive or true negative cases of advanced fibrosis compared with APRI and Fib4, except in subjects with serum ferritin levels > 1000 µg/L. In comparison with APRI or Fib4, Hepascore or elastography may underdiagnose advanced fibrosis in HFE Hemochromatosis, except in individuals with serum ferritin levels > 1000 µg/L.

A retrospective case-controlled cohort study of inpatient drug induced liver injury: the RIDDLE study.

BACKGROUND: Identification of risk factors for drug-induced liver injury (DILI) has been hindered by the unpredictable incidence and idiosyncratic nature of DILI. The aim of this study was to identify characteristic host risk factors for DILI. METHODS: A retrospective cohort study was performed examining all patients admitted with a diagnosis of DILI over a 5.5-year period. Cases were compared to a control group non-exposed to DILI using propensity score-derived inverse probability weights. Patients with DILI due to alcohol or paracetamol were excluded from analysis. RESULTS: Seventy-two cases of DILI admitted to hospital were identified. Antimicrobials caused 56.9% of cases, with amoxicillin-clavulanate the single most common agent, responsible for 13.9% of cases. DILI cohort median age (50.2±36 years) was significantly younger than controls (65.0±38 years) (P<0.001). Pre-existing chronic liver disease (OR, 3.44; 95% CI, 1.38-8.59; P=0.008), length of stay (P<0.001) and in-hospital death (P=0.009) were more likely to be associated with DILI cases. There was no correlation with sex (OR male, 0.92; 95% CI, 0.50-1.67; P=0.78), presence of comorbid autoimmune disease (OR, 1.44; 95% CI, 0.68-3.05; P=0.35), past drug allergies (OR, 1.71; 95% CI, 0.92-3.16; P=0.09), or atopy (OR, 0.87; 95% CI, 0.42-1.82; P=0.72). CONCLUSIONS: Younger age and presence of chronic liver disease were associated with an admission with DILI; however, it remains difficult to predict the population at risk of DILI on clinical grounds and putative risk factors such as female gender, and history of other drug allergies and autoimmunity, were not demonstrated in this study.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. AIM: To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care. METHODS: All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012-2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin. RESULTS: 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality. CONCLUSION: Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

Retrospective study of idiosyncratic drug-induced liver injury from infliximab in an inflammatory bowel disease cohort: the IDLE study.

BACKGROUND: Infliximab therapy may be associated with drug-induced liver injury (DILI), often resembling a drug-induced autoimmune hepatitis. However, the prevalence of DILI in patients receiving infliximab is unclear. Abnormal liver biochemistry is common in patients with inflammatory bowel disease (IBD) and definitive diagnosis may be difficult. The aim of this study was to describe the patterns of abnormal liver biochemistry in an IBD cohort. METHODS: In a retrospective cohort study of adult patients with IBD treated with infliximab through a single institution we used the Roussel Uclaf Causality Assessment Method (RUCAM) to evaluate liver biochemistry and possible DILI. All cases of abnormal liver biochemistry were ascribed a presumptive diagnosis from the electronic medical record. RESULTS: Fifty-seven of the 175 patients (149 Crohn's disease, 26 ulcerative colitis) had abnormal liver biochemistry. Of the 57 cases, one had highly probable, and 10 possible DILI due to infliximab. There were no significant differences regarding demographics, concomitant therapy/disease, indication for infliximab or outcomes between patients with normal and abnormal liver biochemistry, except for higher baseline alanine transaminase and alkaline phosphatase in the abnormal biochemistry group (P<0.001). Multivariate logistic regression showed male sex (odds ratio [OR] 2.49, 95% confidence interval [CI] 1.22-5.09; P=0.01) and background liver disease (OR 15.09, 95%CI 4.09-55.69; P<0.001) to be associated with the abnormal liver biochemistry group. CONCLUSIONS: Abnormal liver biochemistry is common in IBD patients on infliximab. Patients who are male, or have abnormal pre-therapy liver biochemistry or background liver disease, are more likely to develop worsening liver biochemistry during infliximab therapy. RUCAM scoring may help identify true cases of DILI.

Hepatitis B virus activity is not associated with degree of liver steatosis in patients with hepatitis B-related chronic liver disease.

BACKGROUND & AIMS: The recently published manuscript by Zhu and colleagues "Hepatitis B virus infection and risk of non-alcoholic fatty liver disease: A population-based cohort study" found no correlation between presence of chronic HBV and presence of common risk factors for non-alcoholic fatty liver disease on primary analysis. A limitation to this study, like most population based research, is the absence of liver histology, which is considered gold standard for assessment of non-alcoholic fatty liver disease. METHODS: Our group studied the association between hepatitis B viral activity and non-alcoholic fatty liver disease activity as measured by grade of steatohepatitis/fibrosis on liver biopsy by analysing consecutive liver histology samples from patients with chronic hepatitis B at a single quaternary liver transplant centre. RESULTS: Linear regression modelling for active viral hepatitis on histological examination against degree of steatohepatitis showed no correlation (r2  = .018, all P> .1). Linear regression of degree of steatohepatitis vs hepatitis B viral load also showed no correlation. CONCLUSIONS: Our work is concordant with the manuscript from Zhu et al; we found no significant correlation between hepatitis B viral activity and degree of steatohepatitis.

Clinical and financial impacts of introducing an endoscopic mucosal resection service for treatment of patients with large colonic polyps into a regional tertiary hospital.

Background and study aims Endoscopic mucosal resection (EMR) of large sessile or laterally spreading colonic lesions is a safe alternative to surgery. We assessed reductions in Surgical Resection (SR) rates and associated clinical and financial benefits following the introduction of an EMR service to a large regional center. Patients and methods Ongoing prospective intention-to-treat analysis of EMR was undertaken from time of service inception in 2009 to 2017. Retrospective data for SR of large sessile/laterally spreading colonic lesions were collected for the period 4 years before commencement of the EMR service (2005 - 2008) and 9 years after its introduction (2009 - 2017). Results From 2005 to 2008, 32 surgical procedures were performed for non-malignant colonic neoplasia (50 % male, median age 68 years, median Length of Stay (LoS) 10 days). Following the introduction of the EMR service, there was a 56 % reduction in the number of patients referred for surgery (32 surgical procedures, 47 % male, median age 70 years, median LoS 8.5 days). During this period, EMR was successfully performed in 183 patients with 216 lesions resected (60 % male, median age 68 years, median LoS 1 day). Compared to the SR group, the EMR cohort had a lower peri-procedural complication rate (7.7 % vs 54.7 %, P  < 0.0001), and shorter average LoS (1 vs 9 days, P  < 0.0001). A cost saving of AUD $ 19 543.5 was seen per lesion removed with EMR compared to SR. Conclusions The introduction of a dedicated EMR service into a large regional center as an alternative to SR can lead to a substantial decrease in unnecessary surgery with subsequent clinical and financial benefits.

Development of Acute Decompensated Heart Failure Among Hospital Inpatients: Incidence, Causes and Outcomes.

BACKGROUND: We aimed to investigate the incidence, precipitants, and outcomes of acute decompensated heart failure (ADHF) that develops during the inpatient stay. METHODS: We undertook a case-control study in the medical, oncology, surgical, and orthopaedic wards of a tertiary referral hospital (February-May, 2016). Patients aged ≥18 years who developed ADHF during their inpatient stay were enrolled as cases. One control patient was matched to each case by age, gender, presenting complaint/surgery performed and co-morbidities. Multivariate regression was employed to determine variables associated with ADHF. RESULTS: The incidence of ADHF was 1.0% of patients. Eighty cases were well-matched to 80 controls (p>0.05). ADHF precipitants comprised infection (30%), inappropriate intravenous (IV) fluid and medication management (23.8% and 8.8%, respectively), tachyarrhythmia (12.5%), ischaemic heart disease (8.8%), renal failure (1.3%), and other/unclear causes (15%). Three variables were associated with ADHF: not having English as the preferred language (OR 3.5, 95%CI 1.2-9.8), a history of ischaemic heart disease (OR 3.3, 95%CI 1.2-9.1), and the administration of >2000ml of IV fluid on the day before the ADHF (OR 8.3, 95%CI 1.5-48.0). The day before the ADHF, cases were administered significantly more IV fluids than controls (median 2,757.5 versus 975ml, p=0.001). Medication errors mostly related to failure to restart regular diuretics. Cases had significantly greater length of stay (median 15 versus 6 days, p<0.001) and mortality (12.5% versus 1.3%, p=0.01). CONCLUSIONS: New onset ADHF is common and a substantial proportion of cases are iatrogenic. Cases experience significantly increased length of hospital stay, morbidity, and mortality.

Hepatocellular Carcinoma Screening Utilising Serum Alpha-Fetoprotein Measurement and Abdominal Ultrasound Is More Effective than Ultrasound Alone in Patients with Non-viral Cirrhosis.

PURPOSE: This study is aimed to determine the performance of alpha-fetoprotein (AFP) as part of hepatocellular carcinoma (HCC) screening in a non-viral cirrhosis population. METHODS: A retrospective audit was conducted of patients with non-viral cirrhosis over a 13 year period managed at a single centre. All patients were investigated routinely for evidence of viral hepatitis; patients with positive results were excluded from analysis. Cirrhosis was defined on basis of clinical, biochemical, and radiological investigations and examinations. All patients underwent HCC screening with 6-monthly AFP measurement and 6-12-monthly upper abdominal ultrasound (US). Diagnosis of HCC was confirmed by biopsy, definitive imaging, or natural disease progression. RESULTS: Sixty-seven patients were included (49 males, average age 58.7 years). Of 14 patients who developed HCC during the study period, 12 patients had HCC detected via screening. Of the screening diagnosed HCC cases, four (33%) patients had a normal AFP with abnormal surveillance US, three (25%) had raised AFP with normal surveillance US, and five (42%) had concurrent AFP elevation and US abnormality. Patients with raised AFP and normal surveillance US had HCC diagnosed after a progressive rise in AFP precipitated imaging with alternative modalities. Within the 53 patients who remained free of HCC, a raised AFP precipitated additional imaging on 10 occasions. HCC was diagnosed in 12 out of 64 patients over a total of 4292 screening months giving an annual incidence of 3.35%. CONCLUSIONS: Twenty-five percent of HCC occurring in non-viral cirrhosis will be detected earlier using a surveillance program incorporating both AFP and US compared to imaging alone programs.