Outcomes of National Survey of the Practice of Hepatocellular Carcinoma Surveillance.

Background & Aim: HCC has significantly improved outcomes when detected early. Guidelines recommend biannual surveillance with ultrasound (US) and/or AFP in at-risk individuals. This survey aimed to describe HCC surveillance adherence/practices amongst the NHS hospitals in the UK. Methods: An electronic survey was sent to 79 NHS hospitals via the British Association for the Study of the Liver distribution list. The responses were captured from July 2021 to January 2022. Centres were divided into hepato-pancreato-biliary (HPB) and non-HPB centres, depending on whether the hospital undertakes major liver surgeries. Results: A total of 39 (49.3%) centres responded: 15 HPB and 24 non-HPB centres from across the UK. HCC surveillance eligibility criteria were universally applied, but heterogeneous approaches occur outside these criteria. Eighty per cent of patients undergoing surveillance were estimated to have cirrhosis. Eighty-five per cent of centres do 6-monthly US and AFP requested by clinicians and liver clinical nurse specialists. Compliance was estimated at 80% but not routinely audited. In most centres, general sonographers and/or radiologists perform surveillance US scans without a standard reporting template, although structured reporting was viewed as desirable by the majority. Poor views on US are approached heterogeneously, with patients variably offered ongoing US, CT, or MRI with different protocols. Conclusion: Most responding NHS hospitals follow 6-monthly HCC surveillance guidance. Data recording is variable, with limited routine data collection regarding compliance, yield, and quality. Surveillance US is mostly performed by non-HPB specialists without standardised reporting. There is an inconsistent approach to poor views with US surveillance. Even in a universal healthcare system such as NHS, which is free at the point of care, delivery of HCC surveillance has not improved over the last decade and remains variable.

Cost of hepatocellular carcinoma to the national health service in England: a registry-based analysis.

OBJECTIVE: Hepatocellular carcinoma (HCC) incidence in the UK trebled between 1997 and 2017. With increasing numbers requiring treatment, understanding the likely impact on healthcare budgets can inform service planning and commissioning. The aim of this analysis was to use existing registry data to describe the direct healthcare costs of current treatments for HCC and estimate the impact on National Health Service (NHS) budgets. DESIGN: A retrospective data analysis based on the National Cancer Registration and Analysis Service cancer registry informed a decision-analytic model for England comparing patients by cirrhosis compensation status and those on palliative or curative treatment pathways. Potential cost drivers were investigated by undertaking a series of one-way sensitivity analyses. RESULTS: Between 1 January 2010 and 31 December 2016, 15 684 patients were diagnosed with HCC. The median cost per patient over 2 years was £9065 (IQR: £1965 to £20 491), 66% did not receive active therapy. The cost of HCC treatment for England over 5 years was estimated to be £245 million. CONCLUSION: The National Cancer Registration Dataset and linked data sets have enabled a comprehensive analysis of the resource use and costs of secondary and tertiary healthcare for HCC, providing an overview of the economic impact to the NHS England of treating HCC.

Major variation in hepatocellular carcinoma treatment and outcomes in England: a retrospective cohort study.

Objective: Hepatocellular carcinoma (HCC) is increasingly incident in England, while survival remains poor with regional disparities. We aimed to explore the differences in HCC treatment across different geographical regions and to examine the impact on cancer survival. Methods: Incident HCC cases and treatment were identified from the English Hospital Episode Statistics (2016-2017) and then a subset by National Health Service (NHS) regions. Treatment was grouped into curative, palliative and untreated. Median survival was estimated to date of death in the national statistics. Results: The median observed survival was 8.6 months (95% CI 7.5 to 9.9) across all 2160 HCC cases, 52.1 months (CI 50.5, not reached) in 449 (20.8%) treated with curative intent, 21.0 months (CI 18.5 to 24.5) after other cancer-specific treatment in 449 (20.8%), and 2.3 months (CI 2.1 to 2.6) in 1262 (58.4%) untreated. Across NHS regions, <50% of cases received treatment (30.4%-49.6%), while between 14.2% and 27.7% had curative treatment. The 3-year survival was similar (23.5%-29.7%), except in the London region (40.0%). Conclusion: Majority of HCC cases in England are untreated and survival remains low, with variation in outcomes in regions with similar incident rates. A deeper exploration of regional treatments and screening practice is required to improve early detection and survival.

Primary liver cancer in the UK: Incidence, incidence-based mortality, and survival by subtype, sex, and nation.

BACKGROUND & AIMS: The incidence of primary liver cancer (PLC) is increasing in Western Europe. To understand trends over time and the current burden in the UK, a detailed analysis of the epidemiology of PLC and its subtypes was conducted. METHODS: Data on PLCs diagnosed during 1997-2017 were obtained from population-based, nationwide registries in the UK. European age-standardised incidence (ASR) and incidence-based mortality rates (ASMR) per 100,000 person-years were calculated overall and by sex and UK-nation. Annual percentage change in rates was estimated using Joinpoint regression. One-, 2-, and 5-year age-standardised net survival was estimated. RESULTS: A total of 82,024 PLCs were diagnosed. Both hepatocellular carcinoma (HCC) incidence and mortality rates trebled (ASR 1.8-5.5 per 100,000, ASMR 1.3-4.0). The rate of increase appeared to plateau around 2014/2015. Scottish men consistently had the highest HCC incidence rates. PLC survival increased, driven by a substantial increase in the proportion that are HCC (as prognosis is better than other PLCs) and in HCC survival (change in 1-year survival 24-47%). Intrahepatic cholangiocarcinoma was the most common PLC in women and 1-year survival improved from 22.6% to 30.5%. CONCLUSIONS: PLC incidence has been increasing rapidly but, as most risk factors are modifiable, it is largely a preventable cancer. This rate of increase has slowed in recent years, possibly attributable to effective treatment for hepatitis C. As other risk factors such as obesity and diabetes remain prevalent in the UK, it is unlikely the considerable burden of this disease will abate. While improvements in survival have been made, over half of patients are not alive after 1 year, therefore further progress in prevention, early detection, and treatment innovation are needed. LAY SUMMARY: Many more people are getting liver cancer, particularly the subtype hepatocellular carcinoma, than 20 years ago. Men in Scotland are most likely to get liver cancer and to die from it. Survival after liver cancer diagnosis is getting longer but still less than half are alive after 1 year.

The importance of steatosis in chronic hepatitis C infection and its management: A review.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease with approximately 180 million people infected worldwide. Hepatic steatosis is a frequent histological finding in chronic hepatitis C (CHC) infection and is 2- to 3-fold more common than would be expected by chance alone. A high body mass index with excess visceral fat distribution is associated with steatosis in patients infected with HCV genotype 1 but not genotype 3, re-enforcing the concept that in patients with CHC, some have "metabolic steatosis", predominantly HCV genotype 1, and others "viral steatosis", mainly HCV genotype 3. Accumulating evidence suggests that steatosis may contribute to progression of fibrosis in CHC. Hepatic insulin resistance appears to play a role through the pro-fibrogenic effects of compensatory hyperinsulinemia. The aim of this review was to assess the effect host and viral factors play in steatosis development in patients with CHC infection and its possible relationship with hepatocellular carcinoma. The review examines the mechanisms by which CHC infection causes hepatic steatosis, the impact hepatic steatosis has on the natural history of the disease and finally, explores if treatments leading to a reduction in the amount of steatosis might lead to improved treatment outcomes. The basic medical science of steatosis in CHC will be discussed including proposed models of steatogenesis and the influence of viral and metabolic factors at the molecular level and how these might impact on current and future therapies.

King's Score: an accurate marker of cirrhosis in chronic hepatitis C.

OBJECTIVES: Histological assessment of patients with chronic hepatitis C infection is no longer performed routinely; consequently, a simple test is needed to identify patients with significant hepatic fibrosis. METHODS: Data were collected, retrospectively, on 923 consecutive patients undergoing percutaneous liver biopsy for chronic hepatitis C at King's College Hospital between 1 January 2000 and 30 June 2006; 602 patients were accepted to form the training set and a further 105 patients to form the validation set. RESULTS: On liver biopsy, 132 (22%) had cirrhosis (Ishak F5-6) in the training set and 19 (18%) in the validation set. Factors found by multivariate analysis to be associated with fibrosis in the training set were used to construct the King's Score: age x aspartate aminotransferase x international normalized ratio / platelets. Area under receiver operating characteristic curves for predicting cirrhosis and significant fibrosis (F3-6) were 0.91 and 0.79, respectively. A King's Score of greater than or equal to 16.7 predicted cirrhosis in 34% of patients (odds ratio 36.2, 95% confidence interval, 22.0-59.6; P<0.0001) with sensitivity 86%, specificity 80% and a high negative predictive value of 96%; a score greater than or equal to 12.3 predicted F3-6 (odds ratio 33.9, 95% confidence interval, 15.2-34.4; P<0.001). The validation set confirmed the utility of this index, area under receiver operating characteristic curves 0.94 and 0.89 for cirrhosis and F3-6, respectively. CONCLUSION: The King's Score is a simple and accurate index for predicting cirrhosis in chronic hepatitis C. Patients with a score of less than 16.7 have a low risk of cirrhosis.

Outcome after wait-listing for emergency liver transplantation in acute liver failure: a single centre experience.

BACKGROUND/AIMS: Though emergency liver transplantation (ELT) is an established treatment for severe acute liver failure (ALF), outcomes are inferior to elective surgery. Despite prioritization, many patients deteriorate, becoming unsuitable for ELT. METHODS: We examined a single-centre experience of 310 adult patients with ALF registered for ELT over a 10-year period to determine factors associated with failure to transplant, and in those patients undergoing ELT, those associated with 90-day mortality. RESULTS: One hundred and thirty-two (43%) patients had ALF resulting from paracetamol and 178 (57%) from non-paracetamol causes. Seventy-four patients (24%) did not undergo surgery; 92% of these died. Failure to transplant was more likely in patients requiring vasopressors at listing (hazard ratio 1.9 (95% CI 1.1-3.6)) paracetamol aetiology (2.5 (1.4-4.6)) but less likely in blood group A (0.5 (0.3-0.9)). Post-ELT survival at 90-days and one-year increased from 66% and 63% in 1994-1999 to 81% and 79% in 2000-2004 (p<0.01). Four variables were associated with post-ELT mortality; age >45 years (3 (1.7-5.3)), vasopressor requirement (2.2 (1.3-3.8), transplantation before 2000 (1.9 (1.1-3.3)) and use of high-risk grafts (2.3 (1.3-4.2). CONCLUSIONS: The data indicate improved outcomes in the later era, despite higher level patient dependency and greater use of high-risk grafts, through improved graft/recipient matching.

The increasing prevalence of hepatitis delta virus (HDV) infection in South London.

On the basis of historical studies, hepatitis delta virus (HDV) infection is considered uncommon in the United Kingdom (UK) and mainly confined to intravenous drug users. In order to assess the current prevalence of HDV co-infection in patients with chronic hepatitis B (HBV), a retrospective analysis was performed of 962 consecutive HBV-infected adult patients referred to King's College Hospital between January 1st 2000 and March 31st 2006. The 82 subjects positive for HDV antibody (8.5%) had a similar age to those without HDV (median 36 years, interquartile range 30-47, vs. 35 years, 29-43). Excluding non-UK residents, the prevalence of HDV Antibody was 7.1%. Most HDV-infected subjects were born in regions where HDV is endemic, for example, Southern or Eastern Europe (28.1%), Africa (26.8%) or Middle-East (7.3%). Forty one (50%) were considered to have acquired HDV infection via intra-familial transmission but intravenous drug use was still a common route of transmission (24.4%). Comparing HBV/HDV co-infected to HBV mono-infected patients, a higher proportion were hepatitis C antibody positive (25.6% versus 3.8%; odds ratio 8.89, 95% confidence interval 4.4-17.9; P < 0.00001) and more had cirrhosis (26.8% vs. 12.9%; odds ratio 2.64, 95% confidence interval 1.55-4.49; P < 0.0001) but, despite this, the risk of hepatocellular carcinoma was similar (odds ratio 1.34, 95% confidence interval 0.62-2.91). Although HDV infection is reportedly declining in some endemic regions, our data demonstrate a high prevalence in South London. HDV co-infection is associated with increased morbidity and patients with HBV should be tested for HDV infection.

Actin-free Gc globulin: a rapidly assessed biomarker of organ dysfunction in acute liver failure and cirrhosis.

Reductions in serum levels of Gc globulin, a hepatically synthesized component of the extracellular actin scavenger system responsible for complexing circulating actin and attenuating intravascular microthrombus formation, are associated with poor outcome in acute liver failure. Clinically applicable assays of the important actin-free fraction (Af-Gc) have not been available until now. We measured actin-free Gc globulin levels with a novel, rapid assay in 61 cases of acute liver failure (ALF) and in 91 patients with cirrhosis (40 of whom were clinically unstable with extrahepatic organ dysfunction), and studied associations with liver dysfunction, extrahepatic organ dysfunction, indices of disseminated coagulation, and outcome. Reductions in Af-Gc levels mirrored hepatic dysfunction and organ dysfunction in both groups, and discriminated patients with poor prognosis from those with good prognosis in the ALF cohort. Levels were lowest in patients with ALF (10% of control values), but levels were also markedly reduced in both unstable (28%) and stable (44%) patients with cirrhosis. Associations with markers of disseminated intravascular coagulation were seen in both groups, most notably in the cirrhosis cohort, supporting a pathophysiological role for reduced Af-Gc in the evolution of organ dysfunction. In acetaminophen-induced ALF, Af-Gc identified patients with poor prognosis as well as did the Acute Physiology and Chronic Health Evaluation (APACHE II) score (area under the receiver operating characteristic curve, 0.7), and in cirrhosis, Af-Gc was an independent predictor of mortality by multifactorial analysis. In conclusion, the importance of Af-Gc reductions in the development of multiple organ dysfunction in ALF and cirrhosis is highlighted, probably resulting from reduced hepatic production and peripheral exhaustion of this arm of the extracellular actin scavenger system.