Impact of the COVID-19 pandemic on patients with hepatocellular carcinoma in the West of Scotland: a cohort study.

OBJECTIVE: The COVID-19 pandemic had an undoubted impact on the provision of elective and emergency cancer care, including the diagnosis and management of patients with hepatocellular carcinoma (HCC). Our aim was to determine the effects of the COVID-19 pandemic on patients with HCC in the West of Scotland. DESIGN: This was a retrospective audit of a prospectively collated database of patients presented to the West of Scotland Multidisciplinary Team (MDT) between April and October 2020 (during the pandemic), comparing baseline demographics, characteristics of disease at presentation, diagnostic workup, treatment and outcomes with patients from April to October 2019 (pre pandemic). RESULTS: There was a 36.5% reduction in new cases referred to the MDT during the pandemic. Patients presented at a significantly later Barcelona Cancer Liver Clinic stage (24% stage D during the pandemic, 9.5% pre pandemic, p<0.001) and with a significantly higher Child-Pugh Score (46% Child-Pugh B/C during the pandemic vs 27% pre pandemic, p<0.001). We observed a reduction in overall survival (OS) among all patients with a median OS during the pandemic of 6 months versus 17 months pre pandemic (p=0.048). CONCLUSION: The impact of the COVID-19 pandemic is likely to have contributed to a reduction in the presentation of new cases and survival among patients with HCC in the West of Scotland. The reason for this is likely multifactorial, but disruption of standard care is likely to have played a significant role. Resources should be provided to address the backlog and ensure there are robust investigation and management pathways going forward.

Hepatocellular Carcinoma Risk Scores Predict Patients Under Surveillance at Low Risk of Benefit and High Risk of Harm.

AIMS: Surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. Multiple risk scores aim to stratify HCC risk, potentially allowing individualized surveillance strategies. We sought to validate four risk scores and quantify the consequences of surveillance via the calculation of numbers needed to benefit (NNB) and harm (NNH) according to classification by risk score strata. METHODS: Data were collected on 482 patients with cirrhosis during 2013-2014, with follow-up until 31/12/2019. Risk scores (aMAP, Toronto risk index, ADRESS HCC, HCC risk score) were derived from index clinic results. The area under the receiving operating characteristic curve (AUC) was calculated for each. Additionally, per-risk strata, NNB was calculated as total surveillance ultrasounds per surveillance diagnosed early HCC (stage 0/A) and NNH as total ultrasounds performed per false positive (abnormal surveillance with normal follow-up imaging). RESULTS: 22 (4.6%) patients developed HCC. 77% (17/22) were diagnosed through surveillance, of which 13/17 (76%) were early stage. There were 88 false positives and no false negatives (normal surveillance result however subsequent HCC detection). Overall NNB and NNH were 241 and 36, respectively. No score was significantly superior using AUC. Patients classified as low risk demonstrated no surveillance benefit (AMAP, THRI) or had a high NNB of > 300/900 (ADRESS HCC, HCC risk score), with low NNH (24-38). CONCLUSION: Given the lack of benefit and increased harm through false positives in low-risk groups, a risk-based surveillance strategy may have the potential to reduce patient harm and increase benefit from HCC surveillance. CLINICAL TRIALS REGISTRATION: This was not a clinical trial and the study was not pre-registered.

The association between deprivation and the incidence and survival of patients with hepatocellular carcinoma in the West of Scotland.

INTRODUCTION: This study set out to examine the association between deprivation and the incidence of HCC and survival following diagnosis in the West of Scotland. METHODS: Data were gathered on patients from the prospective West of Scotland regional HCC database from November 2014 to August 2017. Patients were included if they had a new diagnosis of HCC. Data on deprivation were taken from the Scottish Index of Multiple Deprivation (SIMD) 2016. RESULTS: 357 patients were included in the study. There was a higher incidence rate in patients in SIMD quintile 1 (most deprived) compared with quintile 5 (least deprived) (8.4 vs 4.3 per 100,000, respectively, p < 0.0002). There was no difference in stage at diagnosis, treatment intent, or survival, between patients in the most deprived and least deprived quintiles (median survival 368 days vs 325 days, p = 0.8). CONCLUSION: Living in the most deprived areas of the West of Scotland was associated with approximately a twofold increase in the incidence of HCC. However, in contrast to previous research, there was no difference in survival following diagnosis between patients living in the most and least deprived areas.

Eight weeks of sofosbuvir/velpatasvir for genotype 3 hepatitis C in previously untreated patients with significant (F2/3) fibrosis.

Twelve weeks sofosbuvir/velpatasvir (SOF/VEL) is a highly effective pan-genotypic regimen for hepatitis C. Phase 2 data suggest 8 weeks of treatment may be sufficient for previously untreated noncirrhotic patients with genotype 3 (GT3) infection. To maximize the number of patients potentially cured within a fixed treatment budget, we elected to treat such patients locally eligible for treatment (F2/3), with 8 weeks of SOF/VEL. By local protocol, treatment-naive patients with F2 (LSM > 6.9kPa < 9.5kPa) or F3 fibrosis (≥9.5kPa < 12.5kPa) were eligible for 8-week SOF/VEL treatment. Patients commencing treatment before 1 Oct 2017 were identified from the Scottish HCV database. Baseline and treatment outcome data obtained. Ninety patients were included for analysis (72 (80%) male, mean age 45 (IQR ± 8.4), 28 (31.1%) F3 fibrosis). Opioid agonist therapy (OAT) was prescribed in 82 (91.1%) patients. Of 49 patients attending Glasgow city Alcohol and Drug Services, 27 (55.1%) had evidence of recent drug use (< 3 months) including 8 (16.3%) with self-reported intravenous drug use. On an intention-to-treat basis, SVR rates were 86/90 (95.6%, 95% CI 89.0-98.8). Excluding those who prematurely discontinued treatment (n = 4), died prior to SVR testing (n = 1) or whom experienced reinfection (n = 1), per-protocol SVR rate was 84/84 (100%, 95% CI 95.7-100.0). In conclusion, eight-week SOF/VEL is highly effective in treatment-naive GT3 patients with significant fibrosis. This offers a non-protease inhibitor-based 8-week regimen which may be useful for complex drug interactions or where time-limited opportunity for treatment. In limited resource settings, reduction in drug acquisition costs may help achieve progress towards the goal of HCV elimination.

Efficacy of direct-acting antivirals: UK real-world data from a well-characterised predominantly cirrhotic HCV cohort.

Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C virus (HCV) infection. We describe UK real-world DAA experience. Individuals commencing HCV treatment containing a DAA regimen (Mar 2014-Nov 2016), participating in the National HCV Research UK (HCVRUK) Cohort Study were recruited from 33 UK HCV centers. The data were prospectively entered at sites onto a centralised database. The data were reported as median (Q1-Q3). Of the 1448 treated patients, 1054 (73%) were males, the median age being 54 years (47-60), 900 (62%) being genotype 1 and 455 (31%) genotype 3. The majority, 887 (61%) had cirrhosis, and 590 (41%) were treatment-experienced. DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). Overall, 1321 (91%) achieved sustained virological response (SVR12), genotype 1 vs 3, 93% vs 87%, P < .001. Prior treatment, presence of cirrhosis and treatment regimen did not impact SVR12. Predictors of treatment failure were genotype 3 infection, OR, 2.015 (95% CI: 1.279-3.176, P = .003), and male sex, OR, 1.878 (95% CI: 1.071-3.291, P = .028). Of those with hepatic decompensation at baseline (n = 39), 51% (n = 20) recompensated post-treatment, lower baseline serum creatinine being associated with recompensation (P = .029). There were two liver-related deaths, both having decompensated disease. This real-world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post-treatment. Genotype 3 infection was a predictor of treatment failure.

Successful infliximab treatment for steroid-refractory celiac disease: a case report.

Celiac disease is a T cell-mediated enteropathy induced by gluten in genetically predisposed individuals. The majority of patients responds to a gluten-free diet but a small number do not. After the exclusion of gluten in the diet, ulcerative jejunititis, and an enteropathy-associated T-cell lymphoma, another treatment modalities, such as systemic steroids and immunosuppressives, may be necessary. This article reports the case of a 47-year-old white woman with immunoglobulin A deficiency. She was diagnosed with celiac disease with subtotal villous atrophy on jejunal biopsy together with positive antiendomysium and antigliadin immunoglobulin G antibodies. Despite close adherence to a gluten-free diet, her weight continued to decrease, she had diarrhea, and her distal duodenal histology showed no improvement. Some improvement in her symptoms was observed with cyclosporine and systemic steroids, but this was not sustained. Recent evidence has suggested that anti-tumor necrosis factor alpha antibodies have a role in the amelioration of an animal model of villous atrophy, and after careful consideration, she was treated with infliximab. There was a dramatic improvement in her weight, symptoms, and distal duodenal histology. The response has been maintained for 18 months while on azathioprine therapy. It is concluded that infliximab is an effective treatment that may be considered in a small number of patients with refractory celiac disease, resistant to other therapy.