mtDNA content analysis could serve as a noninvasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the nonsignificant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the gray zone created by the use of alpha-fetoprotein in some cirrhotic patients.
Background
Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation.
Objective
This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs.
Patients and methods
This study included 24 patients with HCV-related cirrhosis, Child–Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence.
Results
DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals.
Conclusion
Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.
BSG abstracts increasingly being used for post-operative pain and pyrexia 2. There is a lack of awareness that paracetamol should be prescribed by weight when used in certain higher risk groups 1,2 ; including those weighing less than 50kilos and in malnourished patients 3. This study assessed iv paracetamol prescribing in patients at increased risk of hepatotoxicity. Methods Drug charts and medical records from 5 wards (3 surgical and 2 medical including 1 gastroenterology ward) were assessed prospectively over 3 days. All patients prescribed paracetamol were identified; those receiving iv preparations were included. The age, sex and weight were recorded in conjunction with the dose, route and number of paracetamol doses received by each patient. Intravenous doses were identified by countersignatures on drug charts or where iv was the only route indicated. Medical records were reviewed for a history of alcohol excess, chronic liver disease, chronic kidney disease (CKD), eating disorders, and those taking CYP450 inducing medications. Results 59 patients were receiving paracetamol via any route. The average age was 74.6 years old (range 32-86). 25 patients had received iv paracetamol with 12/25 (48%) receiving the drug only via the iv route. The mean number of consecutive doses was 4.44 (range 1-28). 3 patients had CKD, 3 patients were on the CYP450 inducer Rifampicin and 1 patient had an eating disorder and CKD. 2 patients receiving iv doses were under 50 kg, one of which had CKD. Of the 9 patients deemed to be at risk of iatrogenic paracetamol induced hepatotoxicity, 0% had paracetamol prescribed at the recommended reduced dose of 3g per day. Conclusion This study demonstrates that intravenous paracetamol was not being prescribed appropriately. Intravenous paracetamol should be reduced in high risk groups to 3g per day (15mg/kg/24 hours). With 25-37% of all hospital inpatients being deemed at risk of malnourishment 4 a large patient cohort is at risk of paracetamol induced liver injury. Assessment of nutritional status and improved awareness of higher risk patients is needed to avoid iatrogenic paracetamol induced hepatotoxicity through poor prescribing.
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