Feasibility and Effectiveness of Norepinephrine Outside the Intensive Care Setting for Treatment of Hepatorenal Syndrome.

Vasoconstrictors are the treatment of choice for hepatorenal syndrome (HRS). We evaluate the real-life effectiveness of a sequential vasoconstrictor regimen of midodrine-octreotide followed by norepinephrine in a nonintensive care unit (non-ICU) setting in the United States, where terlipressin is not available. The diagnosis of HRS and definitions of response to therapy were based on 2015 guidelines from the International Club of Ascites. In adult patients with HRS without partial or full response to oral midodrine and subcutaneous octreotide, norepinephrine was administered at a starting dose of 5 mcg/minute, with a goal to achieve a mean arterial pressure (MAP) of 10 mm Hg above baseline. We assessed predictors of response and treatment outcomes. A total of 61 patients were administered midodrine and octreotide for the treatment of HRS, with a 28% response rate. The median MELD-Na (Model for End-Stage Liver Disease-sodium) score was 30 (interquartile range [IQR] 24-35). Responders were more likely to have alcohol-related liver disease and lower Acute-on-Chronic Liver Failure (ACLF) grade. Of the nonresponders, 20 were then administered norepinephrine, of whom 45% achieved full or partial response. Achieving an MAP increase of ≥10 mm Hg was associated with a greater probability of response. Patients who responded to norepinephrine experienced improved transplant-free survival at 90 days (88% versus 27%; P = 0.02); 5 of 20 patients experienced norepinephrine treatment-related adverse events, namely arrhythmias. Norepinephrine can be effectively used in a non-ICU setting as rescue therapy in patients who have not responded to midodrine and octreotide. Based on these data, we propose a practical stepwise algorithm for vasoconstrictor therapy to manage HRS in situations where terlipressin is not an option.

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.

Changes in Renal Function in Patients With Chronic HBV Infection Treated With Tenofovir Disoproxil Fumarate vs Entecavir.

BACKGROUND & AIMS: It is unclear whether drugs used to treat chronic hepatitis B virus (HBV) infection cause significant renal impairment. We compare adjusted mean estimated glomerular filtration rates (eGFR; mL/min/1.73 m2) of patients with chronic HBV infection treated with tenofovir disoproxil fumarate (TDF) vs patients treated with entecavir. METHODS: We performed a retrospective study of patients with chronic HBV infections treated with TDF (n = 239) or entecavir (n = 171), from 2000 through 2016, followed for a mean time of 43-46 months. Levels of serum creatinine were measured ≥12 months while patients received treatment. Patients did not have prior exposure to adefovir or HCV, HDV, or HIV co-infection. We performed propensity score matching (PSM) for age, sex, presence of hypertension, diabetes mellitus, baseline eGFR, cirrhosis, and follow-up duration. We performed multivariate generalized linear modeling, adjusting for cirrhosis, diabetes, and hypertension, to estimate adjusted mean eGFR for matched and unmatched cohorts. Cox regression was used to identify predictors of renal impairment. RESULTS: eGFRs were ≥60, after PSM, in 116 patients given entecavir and in 116 patients given TDF; eGFRs were <60 in 32 patients given entecavir and 26 patients given TDF. Multivariate generalized linear modeling of the unmatched overall and <60 eGFR cohorts revealed significantly lower adjusted mean eGFRs in patients given TDF (all P < .001). However, in the eGFR ≥60 PSM cohort, the adjusted mean eGFR was similar between patients receiving either treatment. In Cox regression analysis, TDF was not associated with mild or moderate renal impairment compared with entecavir. CONCLUSION: In a retrospective study of patients with chronic HBV infections treated with TDF vs entecavir, we found that TDF was not associated with higher risk of worsening renal function during short- or intermediate-term follow-up periods, among patients without significant renal impairment. Additional studies, with longer follow-up periods, are needed because treatment for chronic HBV infection is generally long term or life-long. For patients with baseline renal impairment, significant renal decline was among patients given TDF compared to patients given entecavir.

Dextromethorphan abuse in adolescence: an increasing trend: 1999-2004.

OBJECTIVES: To analyze the trend of dextromethorphan abuse in California and to compare these findings with national trends. DESIGN: A 6-year retrospective review. SETTING: California Poison Control System (CPCS), American Association of Poison Control Centers (AAPCC), and Drug Abuse Warning Network (DAWN) databases from January 1, 1999, to December 31, 2004. PARTICIPANTS: All dextromethorphan abuse cases reported to the CPCS, AAPCC, and DAWN. The main exposures of dextromethorphan abuse cases included date of exposure, age, acute vs long-term use, coingestants, product formulation, and clinical outcome. Main Outcome Measure The annual proportion of dextromethorphan abuse cases among all exposures reported to the CPCS, AAPCC, and DAWN databases. RESULTS: A total of 1382 CPCS cases were included in the study. A 10-fold increase in CPCS dextromethorphan abuse cases from 1999 (0.23 cases per 1000 calls) to 2004 (2.15 cases per 1000 calls) (odds ratio, 1.48; 95% confidence interval, 1.43-1.54) was identified. Of all CPCS dextromethorphan abuse cases, 74.5% were aged 9 to 17 years; the frequency of cases among this age group increased more than 15-fold during the study (from 0.11 to 1.68 cases per 1000 calls). Similar trends were seen in the AAPCC and DAWN databases. The highest frequency of dextromethorphan abuse occurred among adolescents aged 15 and 16 years. The most commonly abused product was Coricidin HBP Cough & Cold Tablets. CONCLUSIONS: Our study revealed an increasing trend of dextromethorphan abuse cases reported to the CPCS that is paralleled nationally as reported to the AAPCC and DAWN. This increase was most evident in the adolescent population.

Efficacy and effectiveness of anti-HBV therapy with early withdrawal of HBIG prophylaxis to prevent HBV recurrence following liver transplantation.

INTRODUCTION: The traditional regimen for prophylaxis of hepatitis B recurrence post-liver transplantation is to use hepatitis B immune globulin (HBIG) along with oral antiviral therapy; however, it is unclear when it is safe to discontinue HBIG after certain time point and to maintain patients with only oral antiviral therapy. Several studies have suggested that maintenance with oral anti-hepatitis B virus (HBV) therapy following short-term or no HBIG following the immediate post-transplantation period may also be safe and effective in prevention of HBV recurrence. AREAS COVERED: We reviewed relevant literature to determine the effectiveness of early withdrawal of HBIG after liver transplantation and its effect on prevention of HBV recurrence. We used PubMed to search for any studies that used HBIG-free or short-term HBIG protocols with continued anti-HBV therapy. Short-term is defined as 12 months or less, and it is an evolving concept as new data on shorter and shorter duration becomes available. Additionally, a mini-quantitative analysis of the studies was performed using studies that involved the use of entecavir and tenofovir as anti-HBV therapy with or without HBIG. EXPERT OPINION: Patients who are considered low risk for HBV recurrence at the time of liver transplant may safely be able to utilize a short-term duration of HBIG with indefinite antiviral maintenance therapy afterwards, whereas high-risk patients will likely need long-term HBIG in combination with antiviral therapy.