Development and Pilot of a Checklist for Management of Acute Liver Failure in the Intensive Care Unit

Introduction Acute liver failure (ALF) is an ideal condition for use of a checklist. Our aims were to develop a checklist for the management of ALF in the intensive care unit (ICU) and assess the usability of the checklist among multiple providers. Methods The initial checklist was developed from published guidelines and expert opinion. The checklist underwent pilot testing at 11 academic liver transplant centers in the US and Canada. An anonymous, written survey was used to assess the usability and quality of the checklist. Written comments were used to improve the checklist following the pilot testing period. Results We received 81 surveys involving the management of 116 patients during the pilot testing period. The overall quality of the checklist was judged to be above average to excellent by 94% of users. On a 5-point Likert scale, the majority of survey respondents agreed or agreed strongly with the following checklist characteristics: the checklist was easy to read (99% agreed/agreed strongly), easy to use (97%), items are categorized logically (98%), time to complete the checklist did not interfere with delivery of appropriate and safe patient care (94%) and was not excessively burdensome (92%), the checklist allowed the user the freedom to use his or her clinical judgment (80%), it is a useful tool in the management of acute liver failure (98%). Web-based and mobile apps were developed for use of the checklist at the point of care. Conclusion The checklist for the management of ALF in the ICU was shown in this pilot study to be easy to use, helpful and accepted by a wide variety of practitioners at multiple sites in the US and Canada

Flunarizine arrests hepatitis C virus membrane fusion.

Written with support from a Senior Research Fellowship from the Wellcome Trust (grant no.: 101908/Z/13/Z) to Y.M. and from grant R01 GM102869 from the National Institutes of Health to Y.M.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/hep.2822

Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure

Background Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF. Method Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls. Results Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups–non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT \u3e2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values Summary/Conclusions While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting

Being an informal caregiver for a relative with liver cirrhosis and overt hepatic encephalopathy : a phenomenological study

Aims and objectives: To explore the experiences of being an informal caregiver for a relative with liver cirrhosis and overt hepatic encephalopathy. Background: Overt hepatic encephalopathy is a common complication in patients with liver cirrhosis. It is associated with decreased quality of life for patients, and presents a major burden for caregivers. The involvement of informal caregivers in medical care is recommended, but it has not been clearly described. An understanding of the experience of caregivers is needed to improve the support provided to them by healthcare professionals. Design: A qualitative, interpretative, phenomenological approach was used. Methods: Twelve informal caregivers participated in qualitative interviews. The analysis followed the six steps of the interpretative phenomenological approach. Results: Caregivers' experiences were described using five themes: (1) feeling overwhelmed by their loved one having unexplainable symptoms and behaviours; (2) learning that this and previous experiences were complications of liver disease; (3) becoming aware of the symptoms of hepatic encephalopathy; (4) having feelings of being tied down and (5) experiencing and overcoming obstacles in working with healthcare professionals. Conclusions: This study provides insight into caregivers' experiences and the consequences for their lives. The first occurrence of symptoms was a shock, but receiving the diagnosis was seen as an important step in understanding and learning. Caregivers provide daily assessments of their relatives' conditions, and they feel responsible for medication management. Over time, the caregivers impressively showed how they were able to incorporate their personal experiences into care-giving and to accept more accountability in managing the disease. Relevance to clinical practice: Nurses should acknowledge caregivers as experts in caring for their loved ones. Nurses can assist caregivers in managing an episode of hepatic encephalopathy and can provide individualised interventions to ease the future burden

All-oral direct-acting Antiviral Therapy Against Hepatitis C Virus (HCV) in Human Immunodeficiency Virus/HCV– Coinfected Subjects in Real-World Practice: Madrid Coinfection Registry Findings

We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)–coinfected patients treated with interferon-free direct-acting antiviral agent–based therapy in hospitals from the region of Madrid between November 2014 and August 2016.We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure.We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention-to-treat analysis was 92.0% (95% confidence interval, 90.9%-93.1%) overall, 93.8% (92.4%-95.0%) for no cirrhosis, 91.0% (88.8%-92.9%) for compensated cirrhosis, and 80.8% (73.7%-86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14-2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12-2.41), a baseline cluster of differentiation 4– positive (CD41) T-cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35-3.92), an HCV RNA load 800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14-2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96-1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76-4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir. Conclusion: In this large real-world study, direct-acting antiviral agent–based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus–related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct-acting antiviral agent–based regimens

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

Cirrhosis and liver transplantation in patients co-infected with HIV and hepatitis B or C: an observational cohort study

This study assessed the likelihood of referral for liver transplantation assessment in a prospective cohort of patients co-infected with HIV and hepatitis B or C with complications of cirrhosis. There were 141 co-infected patients from 11 UK centres with at least one complication of cirrhosis recorded (either decompensation or hepatocellular carcinoma) out of 772 identified with cirrhosis and/or HCC. Only 23 of these 141 (16.3%) were referred for liver transplantation assessment, even though referral is recommended for co-infected patients after the first decompensation episode

An expert consensus for the management of chronic hepatitis B in Asian Americans.

BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels \u3e2000 IU/mL (\u3e10 CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes