A one-week internal medicine procedure rotation designed to increase procedural opportunities and competency.

Background: Mounting literature describes increased procedure volume and improvement in procedural skills following implementation of procedural curricula and standardized rotations, generally requiring at least two weeks and incorporating dedicated lecture and didactic efforts. It is unknown whether shorter rotations that feature self-directed curricula can achieve similar outcomes.Methods: House staff participated in a one-week procedure rotation that coincided with preexisting non-clinical blocks ('jeopardy'). It provided an online curriculum as well as opportunities to perform procedures under interprofessional supervision. Inpatient procedure volumes were tallied before and after implementation of the rotation. During the first year of the rotation (academic year 2013-2014), house staff completed a knowledge-based quiz and a Likert-based survey (range 1-5) addressing confidence in performing procedures and satisfaction in procedural training. Results: Ninety-five of 99 house staff participated in the intervention (96% response rate). The total number of procedures performed by the Division of Hospital Medicine increased from an average of 74 per year over the four years prior to the introduction of the rotation to 291 per year during the third year of the rotation. The knowledge-based quiz score improved from a pre-intervention mean value of 50% to a post-intervention mean value of 61% (P = 0.020). Confidence in performing procedures improved from a pre-intervention mean value of 2.37 to a post-intervention mean value of 2.59 (P < 0.001). Satisfaction with procedural training improved from a pre-intervention mean value of 2.48 to a post-intervention mean value of 2.69 (P < 0.001).Conclusions: A one-week procedure rotation with a self-directed curriculum was introduced into the curriculum of an internal medicine residency program and was associated with increased procedure volume and sustained improvement in house staff knowledge, confidence, and satisfaction with procedural training.

Effect of relaxing hepatitis C treatment restrictions on direct-acting antiviral use in a Medicaid program: an interrupted time series analysis.

BACKGROUND: Although direct-acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C virus (HCV), many state Medicaid programs have limited coverage because of their expense. In 2015, the Centers for Medicare & Medicaid Services (CMS) notified states about the legality of Medicaid coverage limitations, particularly within managed care programs. OBJECTIVES: To (1) examine how relaxation and alignment of hepatitis C policies within the Oregon Medicaid program affected DAA utilization and (2) describe changes in DAA coverage policies and patient characteristics of treated individuals over time. METHODS: We manually collected DAA Medicaid drug policies in the state of Oregon before and after the CMS notification was released. After categorizing DAA policies into 2 groups based on baseline prior authorization criteria (restrictive and permissive), we evaluated how changes in these DAA policies affected utilization over 3 time periods (pre-CMS period, post-CMS period, and fibrosis policy alignment). Immediate and gradual changes in trend were assessed using an interrupted time series regression model. Finally, we examined patient characteristics and liver disease complications over time as policy restrictions were removed and aligned with one another. RESULTS: From 2014 to 2018, Oregon's coordinated care organizations and fee-for-service drug policies relaxed liver fibrosis and substance abstinence coverage criteria leading to immediate increases in DAA use in 2016 (0.62 prescriptions per 10,000 enrollees per month; 95% CI = 0.17 to 1.08) and 2018 (1.07 prescriptions per 10,000 enrollees per month; 95% CI = 0.63 to 1.51) among more restrictive coordinated care organizations at baseline. This was followed by a decrease in trend after the 2016 and 2018 impact (-0.05; 95% CI = -0.11 to -0.001 and -0.07; 95% CI = -0.13 to -0.02, respectively). Over the 3 periods, there was a decrease in treated individuals with liver-related complications (P < 0.0001) and an increase in those with a substance use diagnosis (P = 0.0013). CONCLUSIONS: Reducing coverage limitations resulted in treatment of patients with fewer liver-related complications and more substance use disorders. Expanding access to treatment did not result in sustained increases in utilization, and additional interventions may be necessary to meet HCV elimination goals. DISCLOSURES: This study was funded in part by AbbVie Pharmaceuticals, which did not have any role in the study design, collection, analysis and interpretation of data, writing the report, or the decision to submit the report for publication. Hartung received support for his work on this study via a grant from AbbVie Pharmaceuticals. The other authors did not receive any financial support for their contributions to this study. The authors have no other financial disclosures to report. This study was presented at the Academy Health Annual Research Meeting in Washington, DC, on June 3, 2019.

Clinical Outcome Event Adjudication in a 10-Year Prospective Study of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B.

Background and Aims: In the REALM (Randomized, Observational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%; hepatocellular carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.

Thromboelastography Better Reflects Hemostatic Abnormalities in Cirrhotics Compared With the International Normalized Ratio.

GOAL: The goal of this study was to describe potential key differences in thromboelastography (TEG) variables in hospitalized cirrhotics compared with a healthy population, identify patterns of hematologic disturbance with disease progression, and assess the value of traditional tests such as international normalized ratio (INR) and platelet count to determine coagulopathy in cirrhotics. BACKGROUND: TEG, a functional assay of coagulation, has emerged as a useful tool for predicting bleeding risk in cirrhosis. STUDY: Hospitalized cirrhotics who received a TEG before any blood products between January 2017 and February 2018 at a liver transplant center were included. Reaction time (r-time), coagulation time (k-time), angle-rate of clot polymerization (α) and maximum clot strength (maximum amplitude) were measured with kaolin-activated citrated blood TEG assays. RESULTS: A total of 106 cirrhotic patients (Child-Turcotte-Pugh A, B, C; n=25, 25, 56) were identified for comparison against data from 53 healthy controls. TEG parameters in cirrhotics were statistically different from controls. Mean INR and platelet count for all cirrhotics were largely outside the normal reference range, contrary to TEG parameters which demonstrated parameters mostly within the normal reference ranges. The r-time, k-time, and α values in the cirrhotics progressively increased and maximum amplitude values progressively decreased as the liver disease progressed. Regression analysis showed no significant correlations between INR and r-time across any Child-Turcotte-Pugh class (r=0.01, 0.18, 0.23; P=0.95, 0.39, 0.08, respectively). CONCLUSIONS: Although cirrhotics had TEG parameters within normal ranges, there was a propensity for decreased clot formation as liver function worsened. Importantly, the INR did not correlate with TEG parameters in cirrhotic patients, and given the precarious hemostatic balance in these patients, a TEG may be a better predictor of bleeding risk.

Life projects: the transformative potential of direct-acting antiviral treatment for hepatitis C among people who inject drugs.

BACKGROUND AND OBJECTIVES: People who inject drugs (PWID) are disproportionately affected by chronic hepatitis C (HCV) in high-income countries. The advent of direct-acting antivirals (DAAs) makes treatment of this underserved population more possible than ever. The dearth of programs adapted to the needs of PWID and stigma associated with drug use and chronic HCV pose significant barriers to the effective uptake of treatment among this population. We employed "life projects" as a conceptual framework to examine the social incentives of PWID being treated for HCV. This study advances the existing literature on the transformative potential of HCV treatment among PWID, explores how these transformations may affect treatment success, and discusses implications for decisions around whether and when to treat PWID. METHODS: We conducted in-depth interviews with participants of a pilot clinical trial testing the effective delivery of DAA treatment to PWID within two healthcare for the homeless clinic settings - one group receiving opioid agonist therapy (OAT) and another group frequenting a needle and syringe exchange program (NSP). A purposive sample of 27 participants was selected based on place of care. Interviews were transcribed, coded, and analysed for patterns using a priori domains and emergent themes. RESULTS: Participants in both treatment groups described significant life projects that motivated them to complete HCV treatment. These projects included social redemption, strengthening of relationships, pursuit of abstinence from substance use, and harm reduction. These themes were consistent between treatment groups, though more participants in the syringe exchange group relied on harm reduction than on pursuing abstinence to prevent reinfection after achieving virologic cure. CONCLUSION: Understanding the incentives that propel PWID to complete HCV treatment could help to enhance treatment uptake and adherence through dedicated programs that address current barriers to care.

Influence of spontaneous splenorenal shunts on clinical outcomes in decompensated cirrhosis and after liver transplantation.

Cirrhosis and portal hypertension can lead to the formation of a spontaneous splenorenal shunt (SSRS) that may divert portal blood flow to the systemic circulation and reduce hepatic perfusion. Our aims were to evaluate SSRSs as an independent prognostic marker for mortality in patients with decompensated cirrhosis and the influence of SSRSs on liver transplantation (LT) outcomes. We retrospectively analyzed adult patients with decompensated cirrhosis undergoing LT evaluation from January 2001 to February 2016 at a large U.S. center. All patients underwent liver cross-sectional imaging within 6 months of evaluation, and images were reviewed by two radiologists. Clinical variables were obtained by electronic health record review. The cohort was followed until death or receipt of LT, and the subset receiving LT was followed for death after LT or graft failure. Survival data were analyzed using multivariable competing risk and Cox proportional-hazards regression models. An SSRS was identified in 173 (23%) of 741 included patients. Patients with an SSRS more often had portal vein thrombosis and less often had ascites (P < 0.01). An SSRS was independently associated with a nonsignificant trend for reduced mortality (adjusted subhazard ratio, 0.81; Gray's test P = 0.08) but had no association with receipt of LT (adjusted subhazard ratio, 1.02; Gray's test P = 0.99). Post-LT outcomes did not differ according to SSRS for either death (hazard ratio, 0.85; log-rank P = 0.71) or graft failure (hazard ratio, 0.71; log-rank P = 0.43). Conclusion: Presence of an SSRS does not predict mortality in patients with decompensated cirrhosis or in LT recipients. (Hepatology Communications 2018;2:437-444).

Susceptibility profile of methicillin-resistant Staphylococcus aureus to linezolid in clinical isolates.

OBJECTIVE: To determine the resistance and sensitivity pattern of methicillin-resistant Staphylococcus aureus (MRSA) isolates to linezolid (LZD) along with its prevalence in a tertiary care hospital of Karachi, Pakistan. MATERIALS AND METHODS: A cross-sectional study was carried out. This study lasted for about 1 year. Prevalence and sensitivity of LZD, vancomycin, and oxacillin was tested against isolates of MRSA. RESULTS: Out of total 369 specimens 165 were found to be MRSA making the prevalence in our study 44.7%. All of the isolates which were tested positive for MRSA were susceptible to LZD and no resistance was noted when compared with previous studies performed in Europe and USA. CONCLUSION: Stringent implementation of infection control measures along with screening for resistance in patients on prolonged LZD therapy or who previously went under LZD therapy should be performed, coupled with judicious usage of the aforementioned antibiotic should be undertaken, as sufficient data is not available at this point for the clinical spectrum of LZD resistant S. aureus, antimicrobial resistance.

Outcomes in Adults With Acute Liver Failure Between 1998 and 2013: An Observational Cohort Study.

BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. OBJECTIVE: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. DESIGN: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440). SETTING: 31 liver disease and transplant centers in the United States. PATIENTS: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). MEASUREMENTS: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). RESULTS: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. LIMITATIONS: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. CONCLUSION: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study. PRIMARY FUNDING SOURCE: National Institutes of Health.

Occupational health related concerns among surgeons.

The surgeon's daily workload renders him/her susceptible to a variety of the common work-related illness. They are exposed to a number of occupational hazards in their professional work. These hazards include sharp injuries, blood borne pathogens, latex allergy, laser plumes, hazardous chemicals, anesthetic gases, equipment hazards, static postures, and job related stressors. However, many pay little attention to their health, and neither do they seek the appropriate help when necessary. It is observed that occupational hazards pose a huge risk to the personal well-being of surgeons. As such, the importance of early awareness and education alongside prompt intervention is duly emphasized. Therefore, increased attention to the health, economic, personal, and social implications of these injuries is essential for appropriate management and future prevention. These risks are as great as any other occupational hazards affecting surgeons today. The time has come to recognize and address them.

Symptom distress in patients with end-stage liver disease toward the end of life.

Research on symptom distress experienced by patients with end-stage liver disease at the end of life is limited. The aims of the study were to describe presence, frequency, severity, and distress of symptoms in patients with end-stage liver disease toward the end of life and to describe the variability in psychological and physical symptom distress between and within patients over time. This study used a prospective, longitudinal descriptive design. Data were collected from 20 patients once a month for up to 6 months. Participants completed the Memorial Symptom Assessment Scale, which reports a total score, a Global Distress Index score, and a psychological and a physical distress score. Patients reported lack of energy, pain, difficulty sleeping, and feeling drowsy as the most frequent, severe, and distressing symptoms. Global Distress Index mean scores (measured on a 1-4 scale) ranged from 2.6 to 2.9 across time. There was notable variability in psychological and physical distress scores between and within patients across time. Gaining knowledge about the prevalent symptoms experienced by patients with end-stage liver disease and the trajectory of these symptoms is crucial for designing interventions that optimize well-being in patients with end-stage liver disease as they are approaching death.

Malignant infiltration of the liver presenting as acute liver failure.

There have been few reports of acute liver failure (ALF), with encephalopathy and coagulopathy, caused by infiltration of the liver by malignant cells. We describe a case series of 27 patients with ALF caused by malignancy. We examined a large, multicenter ALF registry (1910 patients; mean age, 47.1 ± 13.9 y) and found only 27 cases (1.4%) of ALF attributed to malignancy. Twenty cases (74%) presented with abdominal pain and 11 presented with ascites. The most common malignancies included lymphoma or leukemia (33%), breast cancer, (30%), and colon cancer (7%); 90% of the patients with lymphoma or leukemia had no history of cancer, compared with 25% of patients with breast cancer. Overall, 44% of the patients had evidence of liver masses on imaging. Diagnosis was confirmed by biopsy in 15 cases (55%) and by autopsy for 6 cases. Twenty-four patients (89%) died within 3 weeks of ALF.

Hepatitis C treatment eligibility among HIV-hepatitis C virus coinfected patients in Oregon: a population-based sample.

Approximately 287,000 individuals in the USA are coinfected with HIV and hepatitis C. Recently, new hepatitis C regimens have become available, increasing rates of sustained virologic response in the monoinfected, with studies evaluating their success in the coinfected under way. Previous investigators estimated eligibility for hepatitis C therapy among the coinfected patients, but all had significant methodological limitations. Our study is the first to use a multi-year, statewide, population-based sample to estimate treatment eligibility, and the first to estimate eligibility in the setting of an interferon-free regimen. In a population-based sample of 161 patients infected with HIV and hepatitis C living in Oregon during 2007-2010, 21% were eligible for hepatitis C therapy. Despite the anticipation surrounding an interferon-sparing regimen, eligibility assuming an interferon-free regimen increased only to 26%, largely due to multiple simultaneous contraindications. Obesity was described for the first time as being associated with decreased eligibility (OR: 0.11). Active alcohol abuse was the most common contraindication (24%); uncontrolled mental health (22%), recent injection drug use (21%), poor antiretroviral adherence (22%), and infection (21%) were also common excluding conditions. When active drug or alcohol abuse was excluded as contraindications to therapy, the eligibility rate was 34%, a 62% increase. Assuming an interferon-free regimen and the exclusion of active drug or alcohol abuse as contraindications to therapy, the eligibility rate increased to 42%. Despite the availability of direct-acting anti-viral regimens, eligibility rates in HIV-hepatitis C virus (HCV) coinfection are modest. Many factors precluding hepatitis C therapy are reversible, and targeted interventions could result in increased eligibility.

Guideline adherence and outcomes in esophageal variceal hemorrhage: comparison of tertiary care and non-tertiary care settings.

BACKGROUND: Implementation of consensus guidelines for esophageal variceal hemorrhage yields improved outcomes. We evaluated guideline adherence and outcomes after variceal hemorrhage at a university hospital (UH) and a staff-model health maintenance organization (HMO). STUDY: Factors associated with short-term bleeding, infection, and death were retrospectively identified in UH (n=160) and HMO (n=123) patients with esophageal variceal hemorrhage from January 2000 to December 2006. A second analysis of factors associated with long-term rebleeding was conducted in patients who survived ≥14 days without rebleeding. RESULTS: UH patients were younger, with more severe liver disease and overall illness (P<0.01). UH patients more often received vasoactive agents and prophylactic antibiotics (P<0.01), however the rate of endoscopic therapy did not differ. Infections at 14-days were similar (18.2% vs. 13.0%, P=0.25), but UH patients had greater in-hospital rebleeding (16.4% vs. 5.7%, P<0.01) and mortality (15.2% vs. 4.1%, P<0.01). Poor liver function and overall illness predicted infection, rebleeding, and death (adjusted odds ratio 2.75 to 13.39). Long-term rebleeding occurred in 36.1% of UH patients and 25.9% of HMO patients. Secondary prophylaxis reduced late rebleeding (hazard ratio 0.37 to 0.41). Poor liver function did not predict late rebleeding. Adherence to secondary prophylaxis was greater at the HMO (P<0.05), but late rebleeding did not differ (36% vs. 26%, P=0.13). CONCLUSIONS: Irrespective of practice setting, poor liver function and critical illness predicted short-term bleeding, infection, and death after esophageal variceal hemorrhage, and secondary prophylaxis prevented long-term rebleeding. Differing guideline adherence did not influence outcomes between tertiary care and non-tertiary care centers.

Subtle hepatocellular carcinoma: a persisting role for alpha-fetoprotein monitoring in high-risk patients with cirrhosis.

Hepatocellular carcinoma (HCC) is a common, aggressive malignancy that usually develops in a background of liver cirrhosis. Practice guidelines recommend screening of cirrhotic patients with ultrasound and more detailed imaging (computed tomography or magnetic resonance imaging) if abnormalities are detected. The utility of alpha-fetoprotein levels in HCC surveillance is controversial. Although HCC risk differs by etiology of cirrhosis, screening and surveillance guidelines are uniform after cirrhosis is established. We report a case of rapidly progressive HCC occurring in a cirrhotic patient with multiple unique risk factors for neoplasia, detected by a rising alpha-fetoprotein level without imaging features of liver cancer.

Novel biomarker candidates to predict hepatic fibrosis in hepatitis C identified by serum proteomics.

BACKGROUND: Liver biopsy remains the gold standard to assess hepatic fibrosis. It is desirable to predict hepatic fibrosis without the need for invasive liver biopsy. Proteomic techniques allow unbiased assessment of proteins and might be useful to identify proteins related to hepatic fibrosis. AIMS: We utilized two different proteomic methods to identify serum proteins as candidate biomarkers to predict hepatic fibrosis stage in patients with chronic hepatitis C virus (HCV) infection. METHODS: Serum was obtained from 24 people with chronic HCV at time of liver biopsy and from 6 normals. Liver biopsy fibrosis was staged 1-4 (Batts-Ludwig). Pooled serum samples (six in each of four fibrosis groups and controls) were analyzed with 4- and 8-plex isobaric tags for relative and absolute quantitation (iTRAQ), determining protein identification (ID) and ratios of relative protein abundance. Nonpooled samples were analyzed with two-dimensional (2-D) gels and difference in gel electrophoresis (DIGE) comparing different samples on the same gel and across gels. Spots varying among groups were measured with densitometry, excised, digested, and submitted for tandem mass spectrometry (MS/MS) protein ID. RESULTS: iTRAQ identified 305 proteins (minimum 99% ID confidence); 66 were increased or decreased compared with controls. Some proteins were increased or decreased for specific fibrosis scores. From 704 DIGE protein spots, 66 were chosen, 41 excised, and 135 proteins identified, since one gel spot often identified more than one protein. CONCLUSIONS: Both proteomic methods identified two proteins as biomarker candidates for predicting hepatic fibrosis: complement C4-A and inter-alpha-trypsin inhibitor heavy chain H4.

Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection.

UNLABELLED: Interferon lambda 1 (IFN-lambda1) is a type III IFN that produces intracellular responses similar to those of IFN-alpha but in fewer cell types because of differences in the receptor distribution pattern, and this could potentially result in an improved safety profile. This was an open-label three-part study of patients with chronic hepatitis C virus (HCV) genotype 1 infection. Part 1 evaluated single-agent pegylated interferon lambda (PEG-IFN-lambda) at 1.5 or 3.0 microg/kg administered every 2 weeks or weekly for 4 weeks in patients who had relapsed after previous IFN-alpha-based treatment. Part 2 evaluated weekly doses of PEG-IFN-lambda ranging from 0.5 to 2.25 microg/kg in combination with ribavirin (RBV) for 4 weeks in treatment-relapse patients. Part 3 evaluated weekly PEG-IFN-lambda at 1.5 microg/kg in combination with RBV for 4 weeks in treatment-naive patients. Fifty-six patients were enrolled: 24 patients in part 1, 25 patients in part 2, and 7 patients in part 3. Antiviral activity was observed at all PEG-IFN-lambda dose levels (from 0.5 to 3.0 microg/kg). Two of seven treatment-naive patients (29%) achieved rapid virological response. Treatment was well tolerated with minimal flu-like symptoms and no significant hematologic changes other than RBV-associated decreases in hemoglobin. The most common adverse events were fatigue (29%), nausea (12%), and myalgia (11%). Six patients experienced increases in aminotransferases that met protocol-defined criteria for dose-limiting toxicity (DLT) or temporarily holding therapy with PEG-IFN-lambda. Most DLT occurred in patients with high PEG-IFN-lambda exposure. CONCLUSION: Weekly PEG-IFN-lambda with or without daily RBV for 4 weeks is well tolerated with minimal adverse events and hematologic effects and is associated with clear antiviral activity across a broad range of doses in patients with chronic HCV.

Prevalence and impact of manic traits in depressed patients initiating interferon therapy for chronic hepatitis C infection.

GOALS: To evaluate the impact of manic traits on adverse events in depressed hepatitis C patients initiating interferon therapy. BACKGROUND: Interferon alpha therapy for hepatitis C can exacerbate preexisting depression. Bipolar disorder frequently presents as depressive symptoms that are indistinguishable from or misdiagnosed as major depressive disorder. The impact of bipolar disorder on adverse psychiatric events during therapy is unknown. STUDY: A retrospective study was performed on consecutive patients initiating interferon therapy in the Hepatology clinic at a tertiary-care center between December 2004 and October 2007. All patients completed the Physicians Health Questionnaire (PHQ-9), a validated survey for major depressive disorder. Patients with a positive PHQ screen completed the Mood Disorders Questionnaire (MDQ), a validated screening tool for manic traits. Patients with a negative PHQ served as controls. All adverse psychiatric events were documented through retrospective record review for 6 months after interferon initiation. RESULTS: A total of 165 patients were treated with interferon alpha. One hundred thirty-two (80%) had a negative PHQ (controls) and 33 had a positive PHQ. Forty-one (30%) of the control patients had adverse psychiatric events. Psychiatric events occurred in 8 of 22 (36%) patients with positive PHQ but negative MDQ; 8 of 11 (73%) with positive PHQ and positive MDQ had psychiatric adverse events. This finding was statistically significant compared with the control group (P=0.007). The overall sustained viral response rate was 58% and was not statistically significant among groups. CONCLUSIONS: Baseline manic traits, as detected by the MDQ, were associated with high rates of adverse psychiatric events among individuals receiving antiviral therapy.

Hepatic and cardiac iron overload among patients with end-stage liver disease referred for liver transplantation.

BACKGROUND: Iron overload is associated with fatal cardiovascular events following liver transplantation. Myocardial iron deposits were observed post-mortem in patients who died of cardiac events after transplantation at our institution. This observation prompted testing to exclude cardiac iron in subsequent transplant candidates. AIMS: To assess the results of testing for iron overload in liver transplant candidates at our institution. METHODS: Ferritin, TIBC, and serum iron were measured in cirrhotics referred for transplantation. Patients with transferrin saturation ≥50% and ferritin ≥250 ng/mL underwent liver biopsy graded for iron. Patients with 3-4+ hepatic iron deposits underwent HFE mutation analysis and endomyocardial biopsy with iron staining. RESULTS: Eight hundred and fifty-six patients were evaluated for liver transplantation between January 1997 and March 2005. Two hundred and eighty-seven patients (34%) had transferrin saturation ≥50% and ferritin ≥250 ng/mL. Patients with markers of iron overload had more advanced liver disease than those with normal iron indices. One hundred and fifty-three patients underwent liver biopsy. Twenty-six patients (17%) had 3-4+ hepatic iron staining. One patient was a C282Y heterozygote. Endomyocardial biopsy was performed in 14 patients of whom nine had cardiac iron deposition. CONCLUSIONS: Non-HFE-related cardiac iron overload can occur in advanced liver disease We therefore recommend screening for cardiac iron prior to liver transplantation.

The epidemiology and clinical characteristics of patients with newly diagnosed alcohol-related liver disease: results from population-based surveillance.

GOALS: We describe the epidemiology of outpatients newly diagnosed with chronic alcoholic liver disease and describe predictors of cirrhosis and referral for specialty care. BACKGROUND: Alcohol is a major cause of liver disease in the United States. Most previous work has described hospitalized patients. STUDY: Participants were identified through prospective population-based surveillance in gastroenterology practices Multnomah County, Oregon and New Haven County, Connecticut; and primary care and gastroenterology practices from Kaiser Permanente Northern California in Alameda County during 1999 to 2001. Patients were interviewed, a blood specimen obtained, and their medical record reviewed. RESULTS: We identified 82 patients from gastroenterology practices with newly diagnosed alcoholic liver disease. Their median age was 50.0 years. 72.0% were male and 79.3% were White. The median age at initiation of alcohol use was 17.0 years. 43.9% of patients had evidence of cirrhosis at the time of diagnosis. Only 40.2% reported alcohol as the cause of their liver disease. Patients with cirrhosis were more likely to be older, have a higher median number of years of heavy alcohol consumption, and to have been hospitalized for a liver-related complication than noncirrhotic patients. An additional 83 primary care patients were more likely to be older, to be drinking alcohol at study interview, and to not have cirrhosis than patients referred for gastroenterology care. CONCLUSIONS: Patients with alcoholic liver disease may present at a late stage and may not identify alcohol as a cause for their liver disease. Improved patient screening and education may limit morbidity and mortality.