Eyob Feyssa

Operative Start Times and Complications After Liver Transplantation

The recent national focus on patient safety has led to a re‐examination of the risks and benefits of nighttime surgery. In liver transplantation, the hypothetical risks of nighttime operation must be weighed against either the well‐established risks of prolonging cold ischemia or the potential risks of strategies to manipulate operative start times. A retrospective review was conducted of 578 liver transplants performed at a single institution between 1995 and 2008 to determine whether the incidence of postoperative complications correlated with operative start times. We hypothesized that no correlation would be observed between complication rates and operative start times. No consistent trends in relative risk of postoperative wound, vascular, biliary, or other complications were observed when eight 3‐h time strata were compared. When two 12‐h time strata (night, 3 p.m.–3 a.m., and day, 3 a.m.–3 p.m.) were compared, complications were not significantly different, but nighttime operations were longer in duration, and were associated a twofold greater risk of early death compared to daytime operations (adjusted OR 2.9, 95% CI 1.16–7.00, p = 0.023), though long‐term survival did not differ significantly between the subgroups. This observation warrants further evaluation and underscores the need to explore and identify institution‐specific practices that ensure safe operations regardless of time of day.

MELD score less than 15 predicts prolonged survival after transjugular intrahepatic portosystemic shunt for refractory ascites after liver transplantation.

Background. Transjugular intrahepatic portosystemic shunt (TIPS) is used in the management of refractory ascites (RA) and variceal bleeds. Little data exist on TIPS safety, efficacy, and survival after liver transplantation (LT). Methods. We conducted a retrospective analysis of patients who underwent TIPS placement after LT for RA. Clinical success was defined as a reduction of portosystemic gradient (PSG) and resolution of RA. Results. Twenty-six patients underwent TIPS. The most common indication for LT was hepatitis C virus (88%). Median time from LT to TIPS was 17 months (1–89 months). Median pre-TIPS model for end-stage liver disease (MELD) score was 15 (7–33). The median pre-TIPS PSG was 18 mm Hg (7–38 mm Hg). Median change in the PSG after TIPS was 11 mm Hg (1–27 mm Hg). Fifty-eight percent (15/26) of TIPS were considered clinically successful. Median post-TIPS patient survival was 15 months (1–109 months). Cumulative 1-year post-TIPS patient survival was 50%. On multivariate analysis, pre-TIPS MELD was a significant and independent predictor of patient survival (P<0.01). The 3- and 6-month patient mortality and graft loss for patients with a pre-TIPS MELD of more than or equal to 15 were significantly higher than those with a pre-TIPS MELD score of less than 15 (P<0.01). The overall median survival for patients with a pre-TIPS MELD score of more than or equal to 15 was 3 months (1–59 months) compared with 45 months (2–109 months) for patients with pre-TIPS MELD score of less than 15. Conclusions. TIPS after LT can be clinically effective in patients with RA with a MELD score less than 15. This suggests that TIPS could be used as a means to extend posttransplant survival but should be carefully individualized in patients with a MELD score more than or equal to 15.

Evaluating safety and efficacy of rabbit antithymocyte globulin induction in elderly kidney transplant recipients.

OBJECTIVESnThe optimal immunosuppression regimen for elderly kidney transplant recipients is poorly defined. We sought to evaluate the short-term efficacy and safety of thymoglobulin in geriatric recipients of deceased-donor kidneys.nnnMATERIALS AND METHODSnA single-center, retrospective analysis was undertaken between elderly (≥ 65 years) (n=137) and nonelderly (n=276) kidney transplant recipients who received rabbit antithymocyte globulin induction and calcineurin inhibitor, mycophenolic acid, and prednisone maintenance.nnnRESULTSnThe mean age was 70 versus 52 years. Fewer elderly patients had an earlier transplant or panel reactive antibodies > 20%, but had more machine perfused, older, and extended criteria donor kidneys. Elderly patients received lower rabbit antithymocyte globulin (5.4 vs 5.6 mg/kg; P = .04) and initial mycophenolic acid doses (1620 vs 1774 mg; P = .002), and experienced less delayed graft function (31.1% vs 50.0%; P < .001). Death-censored graft survival and graft function at 3 years and biopsy-proven acute rejection at 1 year were comparable; however, there was lower 3-year patient survival in elderly patients. Donor age was the only factor associated with reduced patient survival. Rates of malignancy, infection, or thrombocytopenia were similar; however, leukopenia occurred less frequently in elderly patients (11.7% vs 19.9%; P = .038).nnnCONCLUSIONSnElderly kidney transplant recipients receiving rabbit antithymocyte globulin did not experience different short-term graft survival, graft function or rates of infection, malignancy or hematologic adverse reactions than did nonelderly patients; they experienced fewer episodes of delayed graft function, but had lower 3-year patient survival.

Operative start times and complications after kidney transplantation.

The worldwide focus on work hour regulations and patient safety has led to the re‐examination of the merits of night‐time surgery, including kidney transplantation. The risks of operating during nontraditional work hours with potentially fatigued surgeons and staff must be weighed against the negative effects of prolonged cold ischemic time with resultant graft compromise. The aim of this study was to evaluate the impact of performing renal transplantation procedures during evening versus day time hours. The main outcome measures assessed between the day and night cohorts included comparisons of the postoperative complication rates and survival outcomes for both the renal allograft and the patient. A retrospective review of 633 deceased donor renal transplants performed at a single institution was analyzed. Three statistically significant results were noted, namely, a decrease in vascular complications in the nighttime cohort, an increase in urologic complications on subgroup analysis in the 3 AM to 6 AM cohort, and the 12 AM to 3 AM subgroup had the greatest odds of any complication. There was no statistical difference in either patient or graft survival over a twelve month period following transplantation. We conclude that although the complication rate varied among cohorts this was clinically insignificant and there was no overall clinically relevant impact on patient or graft survival.

Guillain-Barre syndrome associated with peginterferon alfa- 2a for chronic hepatitis C: A case report

The recommended therapy for chronic hepatitis C (CHC) infection is the combination of a Pegylated interferon and Ribavirin. Almost all such patients on combination therapy experience one or more adverse events during the course of treatment. Significant neurological side effects are rare. A few cases of Bells Palsy, chronic inflammatory demyelinating polyneuropathy and even one case of acute demyelinating polyneuropathy with atypical features for Guillain-Barre syndrome (GBS) associated with Interferon therapy have been reported but no report of GBS with typical features has been published. We present a case report of typical GBS associated with Peginterferon alfa-2a and Ribavirin used for treatment of CHC infection.

An extended treatment protocol with pegylated interferon and ribavirin for hepatitis C recurrence after liver transplantation

AIMnTo evaluate the efficacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).nnnMETHODSnBetween August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 fibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV undetectability.nnnRESULTSnExtended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatment response and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not significant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not increased.nnnCONCLUSIONnRecurrent HCV after LT can be safely treated with extended virological response-guided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.

Tc-99m-BrIDA hepatobiliary (HIDA) scan has a low sensitivity for detecting biliary complications after orthotopic liver transplantation in patients with hyperbilirubinemia

BackgroundTc-99m-BrIDA hepatobiliary scans are noninvasive tests for detecting biliary leaks and obstructions. However, there is low sensitivity and specificity in patients with hyperbilirubinemia. Biliary complications (BC) are the Achilles heel of orthotopic liver transplantation (OLT). We questioned whether hyperbilirubinemia in liver transplant recipients rendered HIDA scanning less dependable.MethodsHIDA findings were compared to endoscopic retrograde cholangiopancreatography, laparotomy, and clinical course. Results were categorized as follows: true positive (TP), true negative (TN), false positive (FP), false negative (FN), or nondiagnostic/inconclusive. We searched for variables associated with erroneous or nondiagnostic tests which we defined as all examinations determined to be FP, FN and/or nondiagnostic/inconclusive.ResultsThirty-four patients underwent a HIDA scan. The sensitivity and specificity were 70 and 100%. The sensitivity of HIDA improved to 100% in patients with a total bilirubin (TB) <5xa0mg/dl. Inconclusive and FN patients had a total bilirubin >5xa0mg/dl. One FN had a TB <5xa0mg/dl, but was determined inconclusive due to the roux-en-Y.ConclusionHIDA scans performed when the total bilirubin was <5xa0mg/dl had a high sensitivity and specificity for detecting biliary complications after OLT. However, when the total bilirubin exceeded 5xa0mg/dl, the specificity was still 100% but the numbers of nondiagnostic/inconclusive and FN exams were increased.

All Those Liver Masses are not Necessarily from the Liver: A Case of a Giant Adrenal Pseudocyst Mimicking a Hepatic Cyst

Patient: Male, 50 Final Diagnosis: Adrenal pseudocys Symptoms: Abdominal pain • fever Medication: — Clinical Procedure: — Specialty: — Objective: Unusual clinical course Background: Most abdominal cysts, including adrenal pseudocysts, are benign and asymptomatic. Rapid enlargement, hemorrhage, infection, rupture with leakage of cyst contents, or pressure on adjacent organs can cause symptoms. Although usually diagnosed incidentally on imaging, determining the origin of a cyst can sometimes be challenging. In these situations, surgical excision and pathological analysis is crucial to diagnosis and management. We report here a case of a giant symptomatic adrenal pseudocyst that closely mimicked a hepatic cyst at presentation. Case Report: A 50-year-old man, with a history of an incidentally detected hepatic cyst, presented with severe abdominal pain, fevers, leukocytosis, and mildly abnormal liver function tests. CT scan revealed a large well defined cystic space-occupying lesion within the liver, with findings suggesting cyst rupture and possible infection. Early laparotomy was performed, and the origin was determined intraoperatively to be right adrenal, which was later confirmed by pathology. Conclusions: Contrast-enhanced CT scan is the criterion standard for evaluation for abdominal cystic masses. Precise diagnosis of a giant abdominal cyst can be challenging. Surgery is both diagnostic and curative in such situations. We also discuss the specific situations in which surgery should be considered in cases of adrenal cystic masses.

Overcoming a treatment barrier in treating hepatitis C in dialysis patients

To the Editor I read the recent review article by Davis et al. with great interest. The authors raised the important issue of HCV treatment by nephrologists. Since direct-acting antiviral therapies were approved, the sustained virologic response (SVR) has reached 90%. However, the “population” SVR is still very low; i.e treatment is not widely provided. We agree that the next step to eradicate HCV is to expand the delivery of treatment and to decrease treatment barriers. In our institution, we have been using a new approach in which the primary care physician starts the HCV treatment. This approach has significantly decreased the delay in initiating treatment from 273 to 77 days. The program was first implemented to increase screening, diagnosis, and treatment of HCV by actively incorporating primary care providers (PCP) at every step of the HCV care process. We believe this multidisciplinary team approach for the HCV treatment will improve the quality of care for HCV patient. A second issue relates to the method of determining advanced liver fibrosis/cirrhosis. The authors state that transient elastography is a preferred approach and recommend that the test be performed after dialysis because central venous pressure can affect the result. Indeed, the few articles on the subject show conflicting data and this question still requires more research to answer. Keller et al. found a significant decrease in liver stiffness after hemodialysis only if predialysis liver stiffness is above 7.1 kPa. They recommended doing transient elastography before dialysis to increase detection of liver fibrosis. Liu et al. have proposed optimized liver stiffness values offering high accuracy for detecting liver fibrosis in hemodialysis patients using transient elastography 1 day after hemodialysis. To routinely obtain transient elastography after hemodialysis may not be feasible. We agree that the test should be done when the patient is euvolemic. However, hemodialysis units are unlikely to have elastography machines at the center, at least for nonhospital based programs. The appropriate timing for elastography in hemodialysis patient still needs further investigations.

Emricasan (IDN‐6556) Lowers Portal Pressure in Patients with Compensated Cirrhosis and Severe Portal Hypertension

Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan‐caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open‐label study enrolled 23 subjects with compensated cirrhosis and PH (hepatic vein pressure gradient [HVPG] >5 mm Hg). Emricasan 25 mg twice daily was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings. Median age was 59 (range 49‐80); 70% were male. Cirrhosis etiologies were nonalcoholic steatohepatitis and hepatitis C virus. Subjects were Child class A (87%) with a median Model for End‐Stage Liver Disease score of 8 (range 6‐15). Twelve had severe PH (HVPG ≥12 mm Hg). Overall, there was no significant change in HVPG after emricasan (mean [standard deviation, SD] –1.1 [4.57] mm Hg). HVPG decreased significantly (mean [SD] –3.7[4.05] mm Hg; P = 0.003) in those with severe PH: 4/12 had a ≥20% decrease, 8/12 had a ≥10% decrease, and 2/12 HVPG decreased below 12 mm Hg. There were no significant changes in blood pressure or heart rate. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased significantly in the entire group and in those with severe PH. Serum cleaved cytokeratin 18 and caspase‐3/7 decreased significantly. Emricasan was well tolerated. One subject discontinued for nonserious adverse events. Conclusion: Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH; an effect upon portal venous inflow is likely, and concomitant decreases in AST/ALT suggest an intrahepatic anti‐inflammatory effect.