Pre-Transplant Depression Is Associated with Length of Hospitalization, Discharge Disposition, and Survival after Liver Transplantation.

Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort.

Association between opioid use and readmission following liver transplantation.

The aim of this study was to assess the independent association between pre-transplant prescription opioid use and readmission following liver transplantation. We reviewed the medical records of all patients at a single medical center undergoing primary, single-organ, liver transplantation from 2004 to 2014. We assessed factors associated with hospital readmission 30 days and 1 year after hospital discharge using multivariable competing risk regression models. Among 1056 transplant recipients, 49 (4.6%) were prescribed pre-transplant prescription opioids. Readmission occurred in 421 (40%) patients within 30 days and 689 (65%) within 1 year. Patients with pre-transplant opioid use had a significantly higher risk of readmission at 30 days (HR 1.7; 95% CI 1.1-2.5) and a non-significantly elevated risk at 1 year (HR 1.4; 95% CI 1.0-1.9) when controlling for other potential confounders. Although pain was the major reason for readmission in only 12 (3%) patients at 30 days and 33 (6%) patients at 1 year, pre-transplant opioid use was significantly associated with pain-related readmission at both time points. In conclusion, prescription opioid use pre-transplantation was significantly associated with all-cause 30-day readmissions and pain-related readmissions at 30 days and 1 year.

HIV through the looking glass: insights derived from Hepatitis B.

BACKGROUND: Although higher levels of hepatitis B virus (HBV) replication in HIV-HBV co-infection may relate to liver disease progression, this has not been completely elucidated. We used expression of hepatitis B core antigen (HBcAg) in liver biopsies from HIV-HBV co-infected and HBV mono-infected patients as a marker for HBV replication, and related these findings to clinical and histological parameters. METHODS: Data from 244 HBV patients were compared with 34 HIV-HBV patients. Liver biopsies were scored for inflammation, fibrosis, HBcAg, and hepatitis B surface antigen. Univariate and multivariate analyses were performed. RESULTS: HBcAg, but not hepatitis B surface antigen, staining was stronger in HIV co-infected than in HBV mono-infected. Co-infected and HBV mono-infected had similar alanine aminotransferase, inflammatory and fibrosis scores, and hepatitis B e antigen status. HBcAg staining correlated with HIV after correcting for HBV DNA and hepatitis B e antigen. CD4 counts and HIV RNA level did not correlate with intensity of HBcAg staining. HBV DNA levels were higher in HIV co-infected and correlated with HBcAg staining. CONCLUSIONS: By looking at HBcAg as a reflection of HBV replication in HIV-HBV co-infected with controlled HIV, our findings suggest that these patients may have subtle immune function defects, which could lead to adverse liver disease outcomes.

The changing burden of hepatitis C virus infection in the United States: model-based predictions.

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes a substantial health and economic burden in the United States. With the availability of direct-acting antiviral agents, recently approved therapies and those under development, and 1-time birth-cohort screening, the burden of this disease is expected to decrease. OBJECTIVE: To predict the effect of new therapies and screening on chronic HCV infection and associated disease outcomes. DESIGN: Individual-level state-transition model. SETTING: Existing and anticipated therapies and screening for HCV infection in the United States. PATIENTS: Total HCV-infected population in the United States. MEASUREMENTS: The number of cases of chronic HCV infection and outcomes of advanced-stage HCV infection. RESULTS: The number of cases of chronic HCV infection decreased from 3.2 million in 2001 to 2.3 million in 2013. One-time birth-cohort screening beginning in 2013 is expected to identify 487,000 cases of HCV infection in the next 10 years. In contrast, 1-time universal screening could identify 933,700 cases. With the availability of highly effective therapies, HCV infection could become a rare disease in the next 22 years. Recently approved therapies for HCV infection and 1-time birth-cohort screening could prevent approximately 124,200 cases of decompensated cirrhosis, 78,800 cases of hepatocellular carcinoma, 126,500 liver-related deaths, and 9900 liver transplantations by 2050. Increasing the treatment capacity would further reduce the burden of HCV disease. LIMITATION: Institutionalized patients with HCV infection were excluded, and empirical data on the effectiveness of future therapies and on the future annual incidence and treatment capacity of HCV infection are lacking. CONCLUSION: New therapies for HCV infection and widespread implementation of screening and treatment will play an important role in reducing the burden of HCV disease. More aggressive screening recommendations are needed to identify a large pool of infected patients. PRIMARY FUNDING SOURCE: National Institutes of Health.

Predictors of consent to pharmacogenomics testing in the IDEAL study.

INTRODUCTION: Pharmacogenomic testing is important in developing individualized therapeutic approaches. In the phase 3 IDEAL (Individualized Dosing to Assess Optimal Pegylated Interferon Therapy) clinical trial, a subset of patients receiving peginterferon and ribavirin for treatment of chronic hepatitis C agreed to provide blood samples for genetic testing. Genome-wide association studies subsequently identified associations between IL28B polymorphism and sustained virologic response, and ITPA polymorphism and ribavirin-associated anemia. OBJECTIVE: To characterize the groups of patients who accepted or declined pharmacogenomic testing in the IDEAL study. METHODS: Clinical and demographic factors and treatment outcomes were compared at all sites that had approved pharmacogenomic testing. Differences between patients who consented to and declined pharmacogenomic testing were analyzed using Student's t-test and χ²-test. RESULTS: In total, 109 of 118 sites participated in the pharmacogenomic substudy, and 1674 of 2949 (57%) patients enrolled at these sites consented to pharmacogenomic testing. More patients treated in academic medical centers than in community centers (60 vs. 52%, P<0.001) provided consent. More men than women (58 vs. 54%, P=0.04) consented to pharmacogenomic testing. There was no significant difference in pharmacogenomic participation between patients from different racial groups, including whites and African Americans (58 vs. 54%, P=0.07). Treatment outcomes were also similar according to pharmacogenomic participation. CONCLUSION: In the IDEAL study, patient consent to pharmacogenomic testing did not introduce selection bias. Treatment at an academic center and male sex were associated with higher rates of pharmacogenomic testing consent. Efficacy and safety outcomes were similar in patients who accepted and declined pharmacogenomic testing.

Emerging therapies in hepatitis C: dawn of the era of the direct-acting antivirals.

The HCV viral life cycle provides targets for drug development at virtually every step, and many new drugs aimed at these targets are currently being developed. Clinical practice takes a major step forward this year with the arrival of telaprevir and boceprevir, which will be added to the current standard of care of pegIFNα/RBV. Patients will need to be monitored closely and counseled extensively, and clinicians will need to learn the new response-guided therapy algorithms with these therapies. Although there remains work to be done in the field of HCV, these therapies will allow many more patients the opportunity to eradicate HCV infection.

Direct-acting antiviral medications for chronic hepatitis C virus infection.

Treatment of hepatitis C virus has traditionally been difficult because of low rates of treatment success and high rates of treatment discontinuation due to side effects. Current standard therapy consists of pegylated interferon α and ribavirin, both of which have nonspecific and largely unknown mechanisms of action. New therapies are in development that act directly on the hepatitis C virus at various points in the viral life cycle. Published clinical trial data on these therapies are summarized in this paper. A new era of hepatitis C virus treatment is beginning, the ultimate goals of which will be directly targeting the virus, shortening the length of therapy, improving sustained virologic response rates, and minimizing side effects.

Immune reconstitution syndrome in a patient with disseminated histoplasmosis and steroid taper: maintaining the perfect balance.

Immune reconstitution syndrome (IRS) is an increasingly common condition that has been described in immunosuppressed individuals once immune function is restored. In this case, we describe a patient who had a renal transplant and subsequently developed pulmonary histoplasmosis. His course was also complicated by the development of a clinical syndrome that was originally attributed to thrombocytopenic thrombotic purpura (TTP). When he did not improve with plasmapheresis and high dose prednisone, a bone marrow biopsy revealed disseminated histoplasmosis and administration of prednisone was rapidly tapered. While on 5 mg of prednisone, he developed an inflammatory syndrome characterised by haemoptysis and respiratory distress, full work-up with pathology was consistent with immune reconstitution syndrome. Treatment for IRS consists of continuing treatment for the underlying infection and consideration of administering anti-inflammatory medication for supportive care. This syndrome should be considered in patients who develop worsening inflammatory symptoms while receiving appropriate treatment for their fungal infection in the setting of restoration of immune function.

Rates of surveillance and management of hepatocellular carcinoma in patients evaluated at a liver transplant center.

OBJECTIVES: The treatment of choice for HCC with cirrhosis is liver transplantation (LT). We assessed if patients evaluated for hepatocellular carcinoma are being diagnosed by surveillance, the proportion of patients meeting Milan criteria at diagnosis, and rates of liver transplantation. METHODS: All HCC cases in cirrhotic patients at Duke University Medical Center in the MELD era (Feb 2002-Oct 2008) were identified. Surveillance was defined as an imaging exam for detection of HCC in the 12 months prior to diagnosis of HCC. Logistic regression was used to examine predictors of LT. RESULTS: There were 319 cases meeting diagnostic criteria for HCC. Only 30.7% were diagnosed by surveillance and 43.7% met Milan criteria at diagnosis. Patients diagnosed by surveillance were more likely to meet Milan criteria and to receive LT (p < 0.0001 for both outcomes). Surveillance was associated with higher rates of LT with an OR 2.6 (95% CI 1.2-5.7, p = 0.02). Patients managed by a hepatologist were more likely to be diagnosed by surveillance (65.9 vs. 19.0%, p < 0.0001). Patients meeting Milan criteria managed by a hepatologist were more likely to receive LT than those referred from other providers (26.4 vs. 8%, p = 0.009). CONCLUSIONS: A minority of HCC cases in cirrhotic patients were diagnosed by surveillance, and only 12.5% underwent LT. Patients diagnosed by surveillance were more likely to meet Milan criteria and to undergo LT. These findings highlight the need for increased identification of patients with chronic liver disease and for subsequent referral to hepatologists for enrollment in HCC surveillance programs.