Showing papers by "Stuart McPherson published in 2022"

Viral hepatitis in 2021: The challenges remaining and how we should tackle them

Abstract: Viral hepatitis results in 1.4 million deaths annually. The World Health Organization (WHO) set an ambitious target to eliminate viral hepatitis by 2030, but significant challenges remain. These include inequalities in access to healthcare, reaching at risk populations and providing access to screening and effective treatment. Stigma around viral hepatitis persists and must be addressed. The WHO goal of global elimination by 2030 is a worthy aim, but remains ambitious and the coronavirus 2019 pandemic undoubtedly has set back progress. This review article will focus on hepatitis A to E, highlighting problems that have been resolved in the field over the past decade, those that remain to be resolved and suggest directions for future problem solving and research.

COVID-19 and liver cancer: lost patients and larger tumours

Abstract: Background Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. Objective To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. Design We prospectively audited our service for the first year of the pandemic (March 2020–February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019–February 2020). Results We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. Conclusion The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)

Abstract: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy‐proven cirrhosis in NAFLD.

Identification of liver disease: why and how

Abstract: Mortality from chronic liver disease (CLD) in the UK has increased by over 400% since 1970, driven by alcohol, non-alcoholic fatty liver disease and hepatitis C virus, the natural histories of which can all be improved by early intervention. Patients often present with advanced disease, which would be preventable if diagnosed earlier and lifestyle change opportunities offered. Liver function tests (LFTs) are very commonly measured. Approximately 20% are abnormal, yet the majority are not investigated according to guidelines. However, investigating all abnormal LFTs to identify early liver disease would overwhelm services. Recently, several diagnostic pathways have been implemented across the country; some focus on abnormal LFTs and some on stratifying at-risk populations. This review will collate the evidence on the size of the problem and the challenges it poses. We will discuss the limitations and restrictions within systems that limit the responses available, review the current pathways being evaluated and piloted in the UK, and explore the arguments for and against LFT-based approaches and ‘case-finding strategies’ in the community diagnosis of liver disease. Furthermore, the role of fibrosis assessment methods (including scoring systems such as Fibrosis-4 (FIB-4) index, the enhanced liver fibrosis test and elastography) within these pathways will also be discussed. In conclusion, this review aims to establish some principles which, if adopted, are likely to improve the diagnosis of advanced liver disease, and identify the areas of contention for further research, in order to establish the most effective community detection models of liver disease.

Systematic review and meta‐analysis: Associations between metabolic syndrome and colorectal neoplasia outcomes

Abstract: Metabolic syndrome (MetS) is a cluster of factors including obesity, hypertension, diabetes, hypercholesterolemia and hyperlipidaemia. It has been associated with an increased risk of colorectal neoplasia. This systematic review and meta‐analysis assessed the association between MetS and (i) recurrence of adenomas or occurrence of CRC in patients with prior adenomas, and (ii) survival in patients with CRC.

ASEPTIC: primary antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis—study protocol for an interventional randomised controlled trial

Abstract: Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites.The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients' health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events.This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis.ClinicalTrials.gov NCT043955365 . Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central - Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).

I-COPTIC: Implementation of community pharmacy-based testing for hepatitis C: Delphi consensus protocol.

Abstract: OBJECTIVE The World Health Organisation aims to eliminate Hepatitis C (HCV) by 2030. To achieve this, targeted testing needs to be widely available. Studies have demonstrated that community pharmacies can deliver effective targeted testing for HCV and the National Health Service in England has commissioned a national service. However, a recent survey of HCV operational delivery networks has shown limited uptake of this service. The objective of this protocol is to guide the formation of a consensus statement to facilitate the widespread implementation of community pharmacy-based targeted testing for HCV. METHOD We will use a modified Delphi method. A purposive selection of panel participants will be identified and recruited from a national survey and via chain-referral sampling. The main inclusion criteria for selection is direct involvement in the implementation of an HCV testing service in pharmacies. We aim for a heterogenous group, encompassing all aspects of the testing service. We will conduct a three round Delphi. The first round will consist of open questions which will be qualitatively analysed using thematic analysis with a framework method based on the WHO Health Systems Framework. This analysis will generate statements, that will be sent to the participants in the second round. A third round will be used where consensus is not reached. CONCLUSIONS The findings from this Delphi consensus study will facilitate the widespread implementation of targeted testing for HCV in community pharmacies.

Determining the frequency and characteristics of Hepatitis C reinfections in North East England

Abstract: Hepatitis C virus infection (HCV) is common, and injecting drug use is the major risk factor for acquisition. Understanding HCV reinfection following treatment is an important consideration for HCV elimination programmes. The aim of this work was to assess the frequency and patterns of HCV reinfection in our region to develop avoidance strategies. All individuals who completed anti‐HCV treatment with a known outcome in Tyne and Wear, England between January 2016 and May 2021 were included. This was a retrospective analysis of prospectively collected data. HCV reinfection was defined as positive HCV RNA after achieving sustained virological response 12 (SVR12). 788 of 840 patients (76% male; mean age 45.7 ± 11.9 years; 47% Genotype 1; 11% Cirrhosis; 20% started in prison) achieved SVR (94%). 443 patients (56%) had HCV RNA testing post‐SVR after a median 0.82 (range 0.1–5.2) years. 56 reinfections (7.1% of all SVRs and 12.6% of SVRs who had post‐SVR testing) were diagnosed. The median time to reinfection was 1.37 (range 0.1–4.0) years and the rate of reinfection was 10.5 /100 person years. 45 (80%) reinfections became chronic, 17 of whom were retreated and achieved SVR. 5 individuals developed a second reinfection. Younger age was the only factor independently associated with reinfection (HR 0.91 [0.88–0.94] p < .001). In conclusion, HCV reinfection is common and may slow our HCV elimination efforts. In order to address high reinfection rates, harm minimization approaches need improved, and we have implemented an ‘HCV track and trace’ pilot to try to reduce onwards HCV transmission.

P85 Successful implementation of case finding for hepatitis C in people detained in police custody

Abstract: Introduction As part of the national Hepatitis C (HCV) elimination strategy, NHS England aims to eliminate HCV by 2025. As part of this programme, identifying undiagnosed cases through HCV testing is critical. Unfortunately, the global COVID 19 pandemic led to a reduction in HCV testing in England, potentially slowing progress towards elimination. To mitigate the impact of this, innovative ways of increasing HCV testing are required. Individuals detained in police custody have higher rates of injecting drug use than the general population and may therefore be at risk of HCV transmission. Police custody suites may therefore provide an opportunity to offer HCV testing to 'at risk' individuals. In collaboration with local police custody healthcare staff, we developed a pilot of HCV testing for individuals in police custody. Here we describe the outcomes of this pilot Methods Since 01/07/2021, all individuals presenting to Northumbria police custody suites who were reviewed by a healthcare professional were offered Dried Blood Spot test (DBS) for HCV Antibody/RNA, HIV and HBsAg. Individuals were excluded if they were <16 years of age or alleged perpetrators of sexual violence. The Newcastle HCV team were responsible for informing people of their results and establishing those with a positive HCV result on a treatment pathway. Results Of the 3116 people in police custody identified as eligible to be offered BBV testing (See figure 1), 193 accepted (6%). A total of 19 were HCV Ab positive (10% of total individuals tested) and of these 12 were HCV RNA detected (63.0% of HCV Ab positive and 6% of total individuals tested). No cases of HIV or hepatitis B were identified. 137 (71.0%) individuals were negative for all BBV's. Unfortunately, 37 (19%) samples could not be processed by the lab due to insufficient samples (19.0%). This was identified as a training issue and addressed by senior custody suite staff. of the 12 cases of active HCV identified, 5 have commenced HCV antiviral treatment, 6 are awaiting treatment and 1 person is awaiting retesting as the result was 'weak positive'. of the 7 individuals who were HCV Antibody positive but RNA negative, 3 had self-cleared, 3 were known to have received antiviral treatment and achieved a sustained virological response and 1 patient was currently on treatment. Conclusions The pilot demonstrated that HCV screening can successfully be implemented into the police custody suites, leading to a diagnosis of active HCV in 6%. Wider implementation of this strategy could help progress towards HCV elimination.

P52 How can we use liver ultrasound more efficiently with rising demands?

Abstract:

Background

Given the large burden of undiagnosed liver disease in the community, there are calls to improve early detection to permit treatment and/or surveillance for complications. Ultrasound forms part of the work up for patients with suspected liver disease, but may not add much diagnostic value for some patients, such as those with fatty liver without advanced fibrosis/cirrhosis. With expansion of liver disease early detection programmes there is potential to overwhelm existing ultrasound services, reducing access to those with strong indications (e.g. HCC surveillance). The aim of this work was to review the indications for patients referred for outpatient liver ultrasound scans (USS) in our Trust to identify where the scans may not add significant additional diagnostic information, ultimately to create capacity for those with strong indications.

Methods

All outpatient liver USS performed in October 2021 in our Trust were retrospectively reviewed looking at the indication and result. Scans were excluded if they were not targeted on the liver or were for abdominal pain or gallstones.

Results

From a total of 1295 abdominal USS performed, 471 were liver targeted (314 [75%] secondary care [SC] and 157 primary care [PC]). Of the SC scans 138 (44%) were for HCC surveillance, 48 (15%) for investigation of suspected advanced fibrosis/cirrhosis, 34 (11%) for investigation of raised liver enzymes, 11 (4%) for suspected fatty liver and 83 (26%) other indications (e.g. HBV, HCV, PSC). Of the PC scans, 73 were to investigate raised liver enzymes (38 [52%] hepatitic, 31 cholestatic, 3 mixed, 1 isolated raised bilirubin), 34 were suspected fatty liver, 18 were for suspected advanced fibrosis/cirrhosis and 32 were for other indications. Of the 34 PC scans carried out for primarily for suspected fatty liver, 27 had a FIB-4 calculated and 23 (85%) had a FIB-4 <1.45. Of these, 22 had fatty liver confirmed on USS and 1 was normal. There were no other significant findings on any of these scans. Additionally, of the 38 patients with hepatitic blood tests, 20 patients had fatty liver on USS and only 4 had FIB-4 score >1.45.

Conclusions

A significant number of USS from primary care were for patients with suspected fatty liver with low FIB-4 and ultrasound yielded no additional findings in these patients. To help create capacity in ultrasound we plan to modify our regional guidance to advise against routine ultrasound for patients with suspected fatty liver with low FIB-4 and no additional symptoms.

Letter: non‐invasive prediction models to exclude cirrhosis in NAFLD—not everyone fits the mould. Authors' reply

Abstract: We thank Giri et al for their interest in our recent manuscript.1 They raised some interesting points regarding our study sample and the generalizability of our proposed cutoffs for FIB4 and the NAFLD Fibrosis Score (NFS) in different patient populations.2 We agree that nonalcoholic fatty liver disease (NAFLD) is a dynamic disease that can improve over time with dietary change, exercise and weight loss and that these changes may have occurred in the time interval between the liver biopsy and entry into the cohort. The amount of weight loss that has been associated with improvement in the fibrosis stage is 10%.3 Unfortunately, no more than 10%– 12% of patients will successfully experience this degree of weight loss, even in the setting of a structured weightloss program.3,4 We expect that very few patients would experience substantial weight loss, therefore, few would be reclassified from having cirrhosis to lower fibrosis stages in the year between liver biopsy and cohort enrollment. Giri et al are correct in noting that older age and diabetes may influence the performance of FIB4 and NFS. However, we observed that the AUROC, sensitivity and specificity in the UK cohort were almost identical to the US cohort for FIB4 (0.87 vs 0.86, 0.78 vs 0.80 and 0.76 vs 0.78) and NAFLD fibrosis score (0.89 vs 0.84, 0.68 vs 0.70, and 0.89 vs 0.86) despite the UK cohort having an older mean age and higher prevalence of diabetes. PPV were slightly higher for NAFLD fibrosis score (0.46 in UK vs 0.35 in US) and similar for FIB4 (0.31 vs 0.29). Whilst some studies have reported decreased accuracy of FIB4 in patients with diabetes,5 FIB4 has been associated with an increased risk of liverrelated morbidity and mortality in a cohort of patients with an even higher prevalence of diabetes than in our study.6 In our derivation and validation cohorts, the mean BMI was 34–­35 kg/m2,­ with­most­ patients­ having­ BMI > 30­ and­ ~15% with BMI >40, which is representative of the general NAFLD population. Our study was not powered to investigate the performance of our cutoffs in subgroups such as patients with diabetes or class III obesity. We recognise age is an important predictor of cirrhosis in patients with NAFLD, and that accurate identification of highrisk patients is imperative. Shah et al7 reported a FIB4 cutoff of 1.3 as having 90% sensitivity to rule out cirrhosis. Our newly identified cutoff of 1.67 is in fact higher, yet lower than the suggested 2.0 cutoff in patients who are older than 65.8 Further work must be done to identify the most appropriate FIB4 cutoff in older patients, as the cutoff of 2.0 has not yet been wellvalidated. The use of a single cutoff, as proposed in our study, allows us to confidently rule out cirrhosis, but emphasises the need for additional testing to diagnose cirrhosis. Giri et al's comments highlight the need for further validation of our newly proposed cutoffs, particularly in patients older than 65, as well as those with diabetes and/or class III obesity.

Risk factors for decompensation and death following umbilical hernia repair in patients with end-stage liver disease

Abstract: Introduction Symptomatic umbilical hernias are a common cause of morbidity and mortality in patients with cirrhosis and end-stage liver disease (ESLD). This study set out to characterise the factors predicting outcome following repair of symptomatic umbilical hernias in ESLD at a single institution. Methods A retrospective review was performed of all patients with ESLD who underwent repair of a symptomatic umbilical hernia between 1998 and 2020. Overall survival was predicted using the Kaplan–Meier method. Logistic regression was used to determine predictors of decompensation and 30-day, 90-day and 1-year mortality. Results One-hundred-and-eight patients with ESLD underwent umbilical hernia repair (emergency n = 78, 72.2%). Transjugular shunting was performed in 29 patients (26.9%). Decompensation occurred in 44 patients (40.7%) and was predicted by emergency surgery (OR, 13.29; P = 0.001). Length of stay was shorter in elective patients compared to emergency patients (3-days vs. 7-days; P = 0.003). Thirty-day, 90-day and 1-year survival was 95.2, 93.2 and 85.4%, respectively. Model for ESLD score >15 predicted 90-day mortality (OR, 18.48; P = 0.030) and hyponatraemia predicted 1-year mortality (OR, 5.31; P = 0.047). Transjugular shunting predicted survival at 1 year (OR, 0.15; P = 0.038). Conclusions Repair of symptomatic umbilical hernias in patients with ESLD can be undertaken with acceptable outcomes in a specialist centre, however, this remains a high-risk intervention. Patients undergoing emergency repair are more likely to decompensate postoperatively, develop wound-related problems and have a longer length of stay. Transjugular shunting may confer a benefit to survival, but further prospective trials are warranted.