Summary
Background
Hepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver ...disease or immunocompromised states.
Aims
To record the morbidity and mortality of HEV in Scotland.
Methods
Demographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018.
Results
Five hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre‐existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV‐related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40‐782.83, P = 0.005), cirrhosis (OR 41.85, 95% CI 2.85‐594.16, P = 0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01‐1.02, P = 0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02‐0.28, P < 0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty‐five (6.7%) patients developed acute or acute‐on‐chronic liver failure with two requiring transplant. Thirty‐seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain‐Barré and 2 encephalitis. Forty‐four (8.6%) patients developed acute kidney injury.
Conclusion
In Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.
Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and ...replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DILI at onset (NDO; n = 63) and follow-up (n = 42), and healthy volunteers (HV; n = 104). Area under the receiver operating characteristic curve (AUC) for cytoplasmic aconitate hydratase, argininosuccinate synthase, carbamoylphosphate synthase, fumarylacetoacetase, fructose-1,6-bisphosphatase 1 (FBP1) across cohorts achieved near complete separation (range: 0.94-0.99) of DO and HV. In addition, we show that FBP1, alone or in combination with glutathione S-transferase A1 and leukocyte cell-derived chemotaxin 2, could potentially assist in clinical diagnosis by distinguishing NDO from DO (AUC range: 0.65-0.78), but further technical and clinical validation of these candidate biomarkers is needed.
The Glasgow Blatchford Score (GBS) is a validated risk assessment tool in primary upper gastrointestinal haemorrhage, which accurately predicts the need for intervention (endoscopic therapy, blood ...transfusion or surgery) or death.
To identify the GBS that predicts lack of intervention or death and to apply this to clinical practice by managing low-risk patients in the community.
GBSs prospectively calculated on 232 patients with upper gastrointestinal haemorrhage to identify low-risk score. Patients with low-risk of requiring intervention (GBS <or=2, age <70 years) from a further 304 patients were considered for management in the community.
Fifty-two of 232 patients in the first cohort had a GBS <or=2 and were aged less than 70 years: none of these required intervention or died. In the second cohort 104 of 304 (34.2%) patients had a GBS <or=2 and were aged less than 70 years, none of whom died or required endoscopic therapy, blood transfusion, surgery or died. Thrity-two of 104 (10.5% of total cohort) were safely managed in the community.
Using the criteria of a GBS <or=2, aged less than 70 years to define patients at 'low risk' allows 10.5% of patients with primary upper gastrointestinal haemorrhage to be safely managed in the community.
Idiosyncratic drug induced liver injury (DILI) is rare, with an incidence of approximately 19 per 100,000 treated individuals.
An update on the epidemiology, pathogenic mechanisms, diagnosis, ...outcome, risk factors for idiosyncratic drug-induced hepatotoxicity, specific classes of drug hepatotoxicity and biomarkers to predict DILI are covered. Cumulative drug exposure and HLA phenotypes play an important role in the pathogenesis of DILI. Patients who present with suspected DILI and jaundice should have biliary obstruction and acute viral hepatitis, including hepatitis E excluded. Immune-mediated DILI will respond to steroid therapy. Patients with an elevated bilirubin and a hepatocellular pattern of liver function tests have severe liver injury with a mortality of greater than 10% and a risk of acute liver failure. Women have an increased risk of hepatocellular DILI. Antibiotics, anticonvulsants, and antidepressant therapy remain the commonest causes of DILI in the Western Hemisphere. Statin therapy rarely causes severe liver injury.
The establishment of prospective registries for DILI has provided valuable data on the pathogenesis and outcome of DILI. Drug-specific computerised causality assessment tools should improve the diagnosis of DILI. The clinical utility of genetic polymorphisms associated with drug-specific DILI is limited.
Acute upper gastrointestinal haemorrhage is a common medical emergency, initially managed with inpatient care. Bleeding stops spontaneously in over 80% of cases, indicating that patients with ...low-risk upper gastrointestinal haemorrhage may be more optimally managed in the community, without the need for admission to hospital.
To assess the safety of managing patients with low-risk upper gastrointestinal haemorrhage without admission to hospital.
Prospective/retrospective study of all patients presenting to a UK teaching hospital with low-risk upper gastrointestinal haemorrhage who were managed without admission to hospital over 5 years. Low risk was defined as Glasgow Blatchford Score of 2 or less, age below 70 years, no other active medical problems, not taking warfarin and suspected nonvariceal bleed. Outcome measures were the need for intervention (blood transfusion, endoscopic therapy or surgery) and death.
One hundred and forty-two patients fulfilled the inclusion criteria, and were managed without admission to hospital. No patients required endoscopic intervention, blood transfusion or surgery. The 28-day mortality was nil. Forty-one patients had normal endoscopic examination and 11 had significant endoscopic findings (peptic ulceration=10, oozing Mallory-Weiss tear=1) but did not require intervention.
Patients presenting with a primary upper gastrointestinal haemorrhage aged below 70 years with a Glasgow Blatchford Score of 2 or less are at a low risk, and can be safely managed in the community.
Drug-induced liver injury (DILI) encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure. The majority of adverse liver reactions are ...idiosyncratic, occurring in most instances 5-90 days after the causative medication was last taken. The diagnosis of DILI is clinical, based on history, probability of the suspect medication as a cause of liver injury and exclusion of other hepatic disease. DILI can be hepatocellular (predominant rise in alanine transaminase), cholestatic (predominant rise in alkaline phosphatase) or mixed liver injury. An elevated bilirubin level more than twice the upper limit of normal in patients with hepatocellular liver injury implies severe DILI, with a mortality of approximately 10% and with an incidence rate of 0.7-1.3 per 100,000. Although acute liver failure is rare, 13-17% of all acute liver failure cases are attributed to idiosyncratic drug reactions. Response to drug withdrawal may be delayed up to 1 year with cholestatic liver injury with occasional subsequent progressive cholestasis known as the vanishing bile duct syndrome. Overall, chronic disease may occur in up to 6% even if the offending drug is withdrawn. Antibiotics and NSAIDs are the most common cause of DILI. Statins rarely cause significant liver injury whereas antiretroviral therapy is associated with hepatotoxicity in 10% of treated patients. Multiple mechanisms of DILI have been implicated, including TNF-alpha-activated apoptosis, inhibition of mitochondrial function and neoantigen formation. Risk factors for DILI include age, sex and genetic polymorphisms of drug-metabolising enzymes such as cytochrome P450. In patients with human immunodeficiency virus, the presence of chronic viral hepatitis increases the risk of antiretroviral therapy hepatotoxicity. Over the next decade, the combination of accurate case ascertainment of DILI via clinical networks and the application of genomics and proteomics will hopefully lead to accurate prediction of risk of DILI, so that pharmacotherapy can be optimised with avoidance of adverse hepatic events.
To report the natural history of autochthonous hepatitis E and hepatitis E virus (HEV) IgG seroprevalence in Southwest England.
Patients with unexplained hepatitis were tested for hepatitis E and ...cases followed until recovery or death. Five hundred blood donors, 336 individuals over the age of 60 years and 126 patients with chronic liver disease were tested for HEV IgG.
Forty cases of autochthonous hepatitis E (genotype 3) were identified. Hepatitis E was anicteric in 25% of cases and usually caused a self-limiting hepatitis predominantly in elderly Caucasian males. Six of 40 had a significant complication and three patients died, two of who had previously undiagnosed cirrhosis. Hepatitis E shows a seasonal variation with peaks in the spring and summer and no cases in November and December. HEV IgG prevalence increases with age, is more common in men and is 16% in blood donors, 13% in patients with chronic liver disease and 25% in individuals over 60 years.
Autochthonous hepatitis E is more common than previously recognized, and should be considered in the differential diagnosis in patients with hepatitis, whatever their age or travel history. It carries a significant morbidity and when seen in the context of chronic liver disease carries an adverse prognosis.
Upper gastrointestinal hemorrhage (UGIH) is a common cause of hospital admission. The Glasgow Blatchford score (GBS) is an accurate determinant of patients' risk for hospital-based intervention or ...death. Patients with a GBS of 0 are at low risk for poor outcome and could be managed as outpatients. Some investigators therefore have proposed extending the definition of low-risk patients by using a higher GBS cut-off value, possibly with an age adjustment. We compared 3 thresholds of the GBS and 2 age-adjusted modifications to identify the optimal cut-off value or modification.
We performed an observational study of 2305 consecutive patients presenting with UGIH at 4 centers (Scotland, England, Denmark, and New Zealand). The performance of each threshold and modification was evaluated based on sensitivity and specificity analyses, the proportion of low-risk patients identified, and outcomes of patients classified as low risk.
There were differences in age (P = .0001), need for intervention (P < .0001), mortality (P < .015), and GBS (P = .0001) among sites. All systems identified low-risk patients with high levels of sensitivity (>97%). The GBS at cut-off values of ≤1 and ≤2, and both modifications, identified low-risk patients with higher levels of specificity (40%-49%) than the GBS with a cut-off value of 0 (22% specificity; P < .001). The GBS at a cut-off value of ≤2 had the highest specificity, but 3% of patients classified as low-risk patients had adverse outcomes. All GBS cut-off values, and score modifications, had low levels of specificity when tested in New Zealand (2.5%-11%).
A GBS cut-off value of ≤1 and both GBS modifications identify almost twice as many low-risk patients with UGIH as a GBS at a cut-off value of 0. Implementing a protocol for outpatient management, based on one of these scores, could reduce hospital admissions by 15% to 20%.
Background. Through migration, diversity of chronic hepatitis B virus (HBV) infection has changed, affecting disease burden and control. We describe clinical and viral characteristics of chronic HBV ...in the United Kingdom. Methods. A total of 698 individuals with chronic HBV infection were recruited from referral liver centers. Demographic, clinical, and laboratory data were collected. Results. Sixty-one percent of patients were male, 80% were not born in the United Kingdom, and the largest ethnicity was East/Southeast Asian (36%). Twenty-two percent were hepatitis B e antigen (HBeAg) seropositive; 20.4% (59/289) had cirrhosis and 10 (1.7%) had hepatocellular carcinoma. Genotype D was most common (31%) followed by A, C, B, and E (20%, 20%, 19%, and 9%, respectively). Genotype was significantly associated with country of birth, length of time in the United Kingdom, HBeAg status, and precore and basal core promoter mutations. One-third were on treatment, with men independently more likely to be treated. Only 18% of those on treatment were on recommended first-line therapies, and 30% were on lamivudine monotherapy. Among treated individuals, 27% had antiviral drug resistance. Testing rates for human immunodeficiency virus, hepatitis C virus, and delta coinfections were low. Conclusions. We demonstrated diversity of chronic HBV infections in UK patients, suggesting that optimal management requires awareness of the variable patterns of chronic HBV in countries of origin. We also found less-than-optimal clinical management practices, possible gender-based treatment bias, and the need to improve testing for coinfections.
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