Hemodynamic and Clinical Determinants of Left Atrial Enlargement in Liver Transplant Candidates.

New-onset heart failure is a frequent complication after orthotopic liver transplantation (OLT). Left atrial enlargement (LAE) may be a sign of occult left heart disease. Our primary objective was to determine invasive hemodynamic and clinical predictors of LAE and then investigate its effect on post-transplant outcomes. Of 609 subjects who received OLT between January 1, 2010, and October 1, 2018, 145 who underwent preoperative right-sided cardiac catheterization and transthoracic echocardiography were included. Seventy-eight subjects (54%) had pretransplant LAE. Those with LAE had significantly lower systemic vascular resistance with higher cardiac and stroke volume index (61.0 vs 51.7 ml/m2; p <0.001), but there was no difference in pulmonary artery wedge pressure. There was a linear relation between left atrial volume index and stroke volume index (R2 = 0.490, p<0.001), but not pulmonary artery wedge pressure. The presence of severe LAE was associated with a reduced likelihood (hazard ratio = 0.26, p = 0.033) of reaching the composite end point of new-onset systolic heart failure, heart failure hospitalization, or heart failure death within 12 months post-transplant. There was also a significant reduction in LAE after transplantation (p = 0.013). In conclusion, LAE was common in OLT recipients and was more closely associated with stroke volume than left heart filling pressures. The presence of LAE was associated with a reduced likelihood of reaching composite outcomes and tended to regress after transplant.

Idiopathic Adulthood Ductopenia Causing Cirrhosis.

Idiopathic adulthood ductopenia (IAD) is a chronic small duct cholestatic biliary disease that is characterized by the loss of interlobular bile ducts. It is diagnosed when there is biochemical evidence of cholestatic liver disease, ductopenia on liver biopsy, and no other identifiable cause of cholestasis. We present a patient with 10 days of progressive abdominal pain, jaundice, and worsening liver function tests who advanced to fulminant liver failure with no apparent underlying cause. He was found to have cirrhosis, with biopsy demonstrative of ductopenia, consistent with idiopathic adulthood ductopenia, which is a rare etiology of cirrhosis but should be considered when the typical workup yields no answer.

Validation of blood phosphatidylethanol as an alcohol consumption biomarker in patients with chronic liver disease.

BACKGROUND: Blood phosphatidylethanol (PEth) is a promising biomarker of alcohol consumption. This study was conducted to evaluate its performance in patients with liver disease. METHODS: This study included 222 patients with liver disease. Patient-reported alcohol use was obtained as a reference standard, and PEth was measured by tandem mass spectrometry. Receiver operating characteristic (ROC) and contingency table analyses were used to assess the performance of PEth in detecting any drinking and averaging 4 or more drinks daily in the past 30 days. RESULTS: At the limit of quantitation (20 ng/ml), PEth was 73% sensitive (95% confidence interval [CI] 65 to 80) and 96% specific (95% CI 92 to 100) for any drinking in the past month. Subjects who drank but had a negative PEth result were mainly light drinkers. Subjects who reported 30-day abstinence but with quantifiable PEth either reported heavy drinking within the past 6 weeks or had data that suggested underreported drinking. At the optimal cutoff concentration of 80 ng/ml, PEth was 91% sensitive (95% CI 82 to 100) and 77% specific (95% CI 70 to 83) for averaging at least 4 drinks daily. CONCLUSIONS: PEth is a useful test for detecting alcohol use in patients with liver disease, but cutoff concentrations for heavy drinking will result in misclassification of some moderate to heavy drinkers.

Hair ethyl glucuronide is highly sensitive and specific for detecting moderate-to-heavy drinking in patients with liver disease.

AIMS: Hair ethyl glucuronide (EtG) is a promising biomarker of moderate-to-heavy alcohol consumption and may have utility in detecting and monitoring alcohol use in clinical populations where alcohol use is of particular importance. This study evaluated the relationship between hair EtG and drinking in patients with liver disease. METHODS: The subjects (n = 200) were patients with liver disease who presented for care at a university medical center. Alcohol use during the 3 months preceding participation in the study was assessed, and a sample of hair was obtained for EtG testing. Classification of drinking status (any drinking or averaging at least 28 g per day) by hair EtG was evaluated, as well as the effects of liver disease severity and demographic and hair care factors. RESULTS: The area under the receiver operating characteristic curve for detecting an average of 28 g or more per day during the prior 90 days was 0.93. The corresponding sensitivity and specificity of hair EtG ≥8 pg/mg for averaging at least 28 g of ethanol per day were 92 and 87%, respectively. Cirrhosis and gender may have a modest influence on the relationship between drinking and hair EtG. CONCLUSION: Hair EtG was highly accurate in differentiating subjects with liver disease averaging at least 28 g of ethanol per day from abstainers and lighter drinkers.

Sensitivity and specificity of urinary ethyl glucuronide and ethyl sulfate in liver disease patients.

BACKGROUND: It is important to monitor alcohol use in the care of patients with liver disease, but patient self-report can be unreliable. We therefore evaluated the performance of urine ethyl glucuronide (EtG) and ethyl sulfate (EtS) in detecting alcohol use in the days preceding a clinical encounter. METHODS: Subjects (n = 120) were recruited at a university-based hepatology clinic or during hospitalization. Alcohol consumption was ascertained by validated self-report measures. Urine EtG (cutoff 100 ng/ml) and EtS (cutoff 25 ng/ml) concentrations were assayed by a contracted laboratory using tandem mass spectrometry. The sensitivity and specificity of each biomarker in the detection of drinking during the 3 and 7 days preceding the clinic visit were determined, as well as the influence of liver disease severity on these results. RESULTS: Urine EtG (sensitivity 76%, specificity 93%) and urine EtS (sensitivity 82%, specificity 86%) performed well in identifying recent drinking, and liver disease severity does not affect biomarker performance. After elimination of 1 false-negative self-report, urine EtG > 100 ng/ml was 100% specific for drinking within the past week, whereas 9% of the subjects without evidence of alcohol drinking for at least 1 week had EtS > 25 ng/ml. CONCLUSIONS: Urine EtG and EtS can objectively supplement the detection of recent alcohol use in patients with liver disease. Additional research may determine optimal methods for integrating these tests into clinical care.

Posttransplantation lymphoproliferative disorder--the great mimic in liver transplantation: appraisal of the clinicopathologic spectrum and the role of Epstein-Barr virus.

Case series describing posttransplantation lymphoproliferative disorder (PTLD) after liver transplantation (LTx) have been limited in number because of the rarity of the disorder. The prevalence of Epstein-Barr virus (EBV) infection and its detection, the clinical and histological diversity of disease, and survival have varied. The aim of this study is to define the clinical and pathological spectrum of PTLD after LTx, and evaluate EBV prevalence, impact of infection, and patient survival. A retrospective analysis of all LTx recipients at our institution diagnosed with PTLD from January 1990 until May 2005, recording clinical presentations, times of presentation after transplantation, histological findings, results of EBV assessment, and survival, as well as the interrelationship of these variables. Among 621 LTx recipients were 22 cases of PTLD in 21 patients, of whom 5 were children and 16 were adults. Extranodal disease was present in 17 of 22 cases (77%) involving a wide variety of organ systems, while 5/22 (23%) had lymphadenopathy. The spectrum of PTLD histopathology was equally varied. In situ hybridization for EBV showed negativity in 8 of 13 (62%) and positivity in 5 of 13 (38%) cases tested. Neither time interval from transplantation to presentation (median 33 months) nor mortality (average 32%) was influenced by EBV status. In conclusion, PTLD in LTx recipients is predominantly extranodal and can involve a wide variety of organ systems, which may confound initial diagnosis. The lymphoproliferative histological spectrum is also diverse. Nowadays, PTLD is frequently EBV-negative, and EBV status does not appear to influence clinical or pathological presentation, or survival.

Alcohol and the liver.

PURPOSE OF REVIEW: To highlight salient recent discoveries and results of clinical trials in alcoholic liver disease (ALD). The burden of care for ALD patients is hefty and the prevalence of alcohol abuse may be increasing in both the developed and the underdeveloped world. RECENT FINDINGS: Molecular mechanisms of alcoholism are being identified but not of the predisposition to alcoholic liver injury, except perhaps for polymorphism of a cytotoxic T-cell antigen. The Mayo End-stage Liver Disease (MELD) score performs well in assessing the prognosis of ALD; serological biomarkers for predicting ALD outcome are of uncertain value. Concomitant liver disease (e.g., obesity, hepatitis C, and iron overload) aggravates the severity of ALD; conversely, alcohol abuse may be a cryptic co-factor in some cases of non-alcoholic fatty liver. For alcoholic hepatitis, nutritional support is the mainstay of treatment; steroids are considered by some (but not all) as safe and effective therapy, whereas manipulations of tumor necrosis factor-alpha activity have been disappointing, or of unproven benefit at best. In liver transplantation for ALD, methods are being devised to monitor recidivism and to ameliorate its risk and that of co-morbid psychiatric conditions. SUMMARY: Much of the pathogenesis of ALD has been identified and headway has been made in predicting its prognosis. However, much remains to be done to elucidate the molecular genetics of the risk of developing ALD and in formulating safe, effective therapies for alcoholic hepatitis.

Long-term outcomes for patients with post-liver transplant anastomotic biliary strictures treated by endoscopic stent placement.

BACKGROUND: Biliary stricture is one of the most common complications of liver transplantation. A number of treatment options are available, but a standard approach has not been established. METHODS: A total of 25 patients with post-liver transplantation anastomotic strictures were treated endoscopically by stent placement. Long-term outcomes (bile duct patency, morbidity, and mortality) were reviewed retrospectively. RESULTS: Placement of a stent was attempted in 25 patients with anastomotic stricture. Successful stent placement with stricture resolution at the time of stent removal was noted in 22 patients (technical success 88%). In those 22 patients, long-term success (mean follow-up after all stents removed, 54 months) was observed in 20 patients (90%) and partial success in two (10%). Long term, failure did not occur in any patient. There was no procedure- or disease-related mortally. Three mild episodes of cholangitis occurred during the period while the stents were in place, in relation to 79 endoscopic interventions for a procedure-related complication rate of 3.7%. CONCLUSIONS: The long-term outcome for patients with post-liver transplantation biliary anastomotic strictures treated with endoscopic stent placement is excellent, with no therapy- or disease-associated mortality and minimal morbidity.

Veno-occlusive Disease.

Therapy for veno-occlusive disease of the liver (VOD) occurring after bone marrow transplantation should be directed at those with moderate or severe disease who will not recover on their own. Thrombolytic therapy may have a role in severe VOD as long as there is no renal or lung impairment. However, the risk of bleeding complications, including the risk of cerebral hemorrhage, must be considered in these patients. Defibrotide has shown promise for treatment of severe VOD but is not yet widely available in the United States. Therapy directed at reducing portal hypertension such as transjugular intrahepatic portosystemic shunts helps reduce ascites but has no effect on mortality. Liver transplantation has been reported but should be considered only in patients with severe liver failure who would have a good outcome in the absence of liver disease or have undergone bone marrow transplantation for benign disease. The most important advances in VOD has been in the prevention of this syndrome by recognizing the risk factors for it and changes in conditioning regimens before bone marrow transplantation.

U.S. veterans' experience with rebetron in a nonstudy environment: success or failure?

OBJECTIVE: The aim of this study is to report the clinical response observed in a U.S. veteran population with hepatitis C to combination therapy with Rebetron (interferon/ribavirin) outside of a controlled study environment. METHODS: Ninety-nine consecutive patients with hepatitis C who met the approved guidelines for treatment were offered treatment with Rebetron. Ninety-four patients initiated therapy. All patients received formal instruction on the use of the drug, as well as the side effects and were instructed to report any side effects. Follow-up was scheduled twice a month for the first month, then monthly unless adverse events were observed. RESULTS: Ninety-four of 99 patients initiated therapy. Thirty-two patients were lost to follow-up or did not tolerate therapy. Ethnic distribution comprised 56 whites, 42 African Americans, one Hispanic. Of the 56 whites who started therapy, 39 completed treatment. Sustained viral response (SVR) for all genotypes was observed in 10 of 39 (26%). In the African American patients, 22 of 42 (52%) completed therapy, but a SVR was noted in none. The only Hispanic patient did not respond to therapy. In the veteran population, favorable factors associated with achieving SVR included having genotype other than 1, absence of cirrhosis, and ethnicity. Factors contributing to the low response rates were difficulty in adhering to therapy as well as a predominance of genotype 1. CONCLUSIONS: Using an intention-to-treat analysis, only 10% of veterans achieved SVR. These findings highlight the need to develop a multidisciplinary team to address the complexity of treating the veteran patient with hepatitis C.