Direct-acting antivirals (DAAs) against HCV have an immune modulatory effect, this could possibly lead to a decreased tumour control. We, therefore, aimed to assess the risk of extrahepatic cancer (EHC) during and the first years after DAA treatment.
This is a nationwide cohort study with prospectively collected data for 19 685 persons with HCV, 4013 DAA treated, 3071 interferon (IFN) treated and 12 601 untreated, from 2008 to 2016. Follow-up time was maximum 3 years. The risk for EHC was compared between the groups using Cox regression analyses, with adjustment for age and Charlson Comorbidity Index (CCI). The HCV-infected groups were also compared with matched cohorts without HCV from the general population. In total 341 EHCs were identified, 84, 43 and 214 EHC in the DAA, IFN and untreated group respectively. The EHC risk in DAA treated compared with IFN treated was doubled, but when adjusted for age and CCI the HR was 1.07 (95% CI 0.74-1.56). Compared with the general population, the HR of EHC for the DAA group was 1.45 (CI 1.13-1.86), with the difference remaining statistically significant after adjusting for CCI.
We found no increased risk for EHC associated with DAA therapy after adjustment for age and CCI. An increased risk of EHC in DAA treated compared with the general population was though seen, and attention should be paid to this association in the ageing population with a history of HCV infection.
Symptoms of chronic hepatitis B (CHB) are not well characterised.
To evaluate CHB symptoms and associations with disease activity and clinical outcomes.
Longitudinal data from 1576 participants in the Hepatitis B Research Network Cohort Study who completed symptom assessments were analysed. A composite symptom score was calculated using a Symptom Checklist (0 = none to 40 = extreme). Multivariable mixed models assessed variables associated with symptom change over time. Latent class symptom trajectories were evaluated. The cumulative probability of long-term clinical outcomes (new onset cirrhosis, hepatic decompensation, hepatocellular carcinoma, liver transplantation, death) was examined by baseline symptom groups.
Participants median age was 42 (range: 18-80), 51% were male, 75% Asian, (68% of whom were born outside North America) with a median follow-up of 4.2 years. On average, symptoms did not significantly change over time. The multivariable model identified several variables associated with higher symptoms during follow-up: being female, non-Asian, born in the United States/Canada, lower education, higher AST, lower platelets and more comorbidities. Two patient subgroups were identified based on longitudinal symptom trajectories: a low symptom group (92%, n = 1451) with symptom scores averaging 2.4 over time and a moderate symptom group (8%, n = 125) with symptom scores averaging 11.5. During follow-up, 7.3% in the moderate symptom group, but only 3.2% of the low symptom group, developed adverse outcomes (P = 0.02).
In this large cohort of CHB patients, symptoms were generally mild and stable over time. However, in some patients with moderate symptoms at baseline, deleterious clinical outcomes were more frequent at follow-up.
ClinicalTrials.gov Identifier: NCT01263587.
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). In patients with UC, associations between endoscopic findings and UC symptoms are not well described.
Post hoc analysis of data from two randomised, placebo-controlled, 8-week, phase 3 studies of tofacitinib for the treatment of patients with UC.
Associations of stool frequency and rectal bleeding subscores with endoscopic improvement (Mayo endoscopic subscore ≤1) were assessed and relationships studied using regression analyses.
Analysis of two-by-two contingency tables showed that dichotomised stool frequency and rectal bleeding were each or both not good predictors of endoscopic improvement. Using stool frequency and/or rectal bleeding as predictors of endoscopic subscore, regression modelling analyses demonstrated a weak relationship between variables. However, a robust relationship was observed with endoscopic subscore as a predictor of stool frequency and rectal bleeding. In OCTAVE Induction 1, normal/inactive disease (endoscopic subscore 0) corresponded to a least-squares mean value of 0.05 for rectal bleeding (no blood), and severe disease (endoscopic subscore 3) corresponded to a value of 1.5 (interpreted as streaks of blood with stool <50% of the time [score of 1] or obvious blood with stool most of the time [score of 2]). OCTAVE Induction 2 results were similar.
Results suggest that the likelihood of endoscopic improvement or normalisation is higher in patients with normal stool frequency and without rectal bleeding, but that these symptoms alone are not predictive of endoscopic improvement or normalisation, and endoscopy is needed for disease assessment.
ClinicalTrials.gov: NCT01465763; NCT01458951.
Acute oesophageal variceal haemorrhage (AOVH) is one of the most common complications of cirrhosis, treated with terlipressin plus endoscopic variceal banding. Identifying patients with a high chance to survive is paramount in order to allocate resources with accuracy. The purpose of this study was to analyse if liver-specific scores are capable of prognosticating mortality for AOVH patients.
Historical cohort study was conducted in a public tertiary care teaching hospital.
Data from medical records from 2010 to 2016 were obtained by searching the hospital electronic database patients who received terlipressin. Charts were reviewed in order to determine the diagnosis of cirrhosis and AOVH. Data in these charts were reviewed and multiple variables were collected. The study included 97 patients. Liver-specific scores were calculated and ROC-curves pairwise comparisons were performed using DeLong test.
Model for End-Stage Liver Disease-Sodium (MELD-Na) was able to predict mortality in 30 and 90-day, with AUROC of 0.76 and 0.78 respectively. Values of MELD-Na above 17 were able to predict higher mortality for all patients, with the sensitivity of 69% and 67% and the specificity of 75% and 77% for 30 and 90-day mortality respectively (P < 0.05). Although, when stratifying for acute-on-chronic liver failure patients, Chronic Liver-Failure-Sequential Organ Failure Assessment (CLIF-SOFA) performed better than other liver-specific scores, whereas Child-Turcotte-Pugh performed better for acute decompensation patients.
MELD-Na score was superior to other liver-specific scores for predicting mortality in a cohort of cirrhotic patients admitted due to AOVH in a tertiary hospital.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), which in males, especially in advanced age, can sometimes evolve into acute respiratory distress syndrome. In addition, mild to moderate alterations in liver function tests (LFTs) have been reported in the worst affected patients. Our review aims to analyse data on the incidence and prognostic value of LFT alterations, the underlying mechanisms and the management of pre-existing liver disease in COVID-19 affected patients.
We searched available literature through online PubMed database using terms as “SARS-CoV-2,” “Liver damage,” “Liver Function tests,” “COVID-19,” “pre-existing liver disease,” “drug-induced liver injury.”
Available evidence suggest that there could be a relationship between SARS-CoV-2 infection and liver damage, although the underlying involved mechanism remains unclear. Cohort studies have shown that high ALT levels, low platelet counts and low albumin levels at admission and during hospitalisation are associated with a high mortality rate. Unfortunately, little is known about the impact of COVID-19 on pre-existing liver damage. While chronic viral infections or NAFLD are associated with an increased risk of COVID-19 progression, patients with cirrhosis may have increased susceptibility to SARS-CoV-2 infection due to their systemic immunocompromised status. DILI seems common among hospitalised patient with severe pneumonia.
Mild to moderate liver impairment during Covid-19 is common, especially in patients with pre-existing liver disease. Further studies should be performed in order to understand how pre-existing liver conditions may influence and worsen progression of liver disease in COVID-19 patients.
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