Comparative Analysis of Outcomes in Living and Deceased Donor Liver Transplants for Primary Sclerosing Cholangitis

Introduction  Primary sclerosing cholangitits (PSC) is a progressive fibrosing cholangiopathy eventually leading to end-stage liver disease (ESLD). While literature for deceased donor liver transplantation (DDLT) for PSC abounds, only a few reports describe live donor liver transplant (LDLT) in the setting of PSC. We present a single-center experience on survival outcomes and disease recurrence for LDLT and DDLT for ESLD secondary to PSC. Aim  The aim of this study was to analyze survival outcomes and disease recurrence for LDLT and DDLT for ESLD secondary to PSC. Patients and Methods  A retrospective review of 58 primary liver transplants for PSC-associated ESLD, performed between May 1995 and January 2007, was done. Patients were divided into two groups based on donor status. Group 1 (n = 14) patients received grafts from living donors, while group 2 (n = 44) patients received grafts from deceased donors. An analysis of survival outcomes and disease recurrence was performed. Recurrence was confirmed based on radiological and histological criteria. Results  Recurrence of PSC was observed in four patients in LDLT group and seven in DDLT group. Retransplantation was required in one patient in LDLT group and nine patients in DDLT group. One patient (7%) among LDLT and six patients (14%) among DDLT died. The difference in patient and graft survival was not statistically significant between the two groups (patient survival, p = 0.60; graft survival, p = 0.24). Conclusion  This study demonstrates equivalent survival outcomes between LDLT and DDLT for PSC; however, the rate of recurrence may be higher in patients undergoing LDLT.     

Posterior reversible encephalopathy syndrome in a patient with lupus nephritis

Posterior reversible encephalopathy syndrome (PRES) is characterized by acute onset of headache, nausea, focal neurological deficits or seizures along with radiological findings of white matter defects in the parietal and occipital lobes. Causes of PRES include uremia, hypertensive encephalopathy, eclampsia and immunosuppressive medications. Usually, the treatment of choice involves correcting the underlying abnormality. We describe an unusual case of recurrent PRES caused by uremia during a lupus flare in a patient with biopsy-proven Class IV Lupus Nephritis (LN) with vasculitis. PRES in systemic lupus erythematosis (SLE) is a rare clinical phenomenon and, when reported, it is associated with hypertensive encephalopathy. Our patient did not have hypertensive crisis, but had uremic encephalopathy. The patient's PRES-related symptoms resolved after initiation of hemodialysis. The temporal correlation of the correction of the uremia and the resolution of the symptoms of PRES show the etiology to be uremic encephalopathy, making this the first reported case of uremia-induced PRES in Class IV LN with vasculitis.     

Urinary organ specific neoantigen

Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A₄₀₅:0.717±0.500) vs 27 controls [0.121 ±0.273 (P<0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N=13), adenomas (N=26), inflammatory bowel disease (N=8), or having a normal colonoscopic examination (N=24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P<0.05). The presence of the Mr 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.The work reported in this paper was supported in part by a grant from the Israeli Cancer Association and Tel Aviv University, and in part by grants from the Israel Cancer Association and the Sackler School of Medicine, Tel Aviv, Israel.     

Risk of cardiovascular disease in HIV,hepatitis C,or HIV/hepatitis C patients compared to the general population

Background: As a result of effective antiretroviral therapy HIV patients are living longer, and their risk of cardiovascular disease (CVD) is a growing concern. It remains unknown whether coinfection with hepatitis C (HCV) changes an HIV person’s CVD risk, and how the risks compare to the general population. The objective of this study was to compare the Framingham Risk Score (FRS) and vascular age differences in persons with HIV, HCV or HIV/HCV disease to the general population. Methods: HIV, HCV, and HIV/HCV patients with clinic visits between 2004 and 2009 were sampled from medical clinics in Rochester, NY. Uninfected persons were randomly selected from the National Health and Nutrition Examination Survey (NHANES), and individually matched on gender, race, and age. We stratified by infection group and conducted separate multivariable linear regression analyses between each infection group and the gender, race, and age matched participants from NHANES. Results: Rochester patients (HIV = 239, HCV = 167, HIV/HCV = 182) were compared 3 : 1 with the NHANES participants. After controlling for weight, marital status, current pharmacotherapies and the matching variables of gender, race, and age, HIV/HCV patients had a 2% higher general FRS compared with the general population (p = 0.03), and vascular age differences that were 4.1 years greater (p = .01). HCV patients had a 2.4% higher general FRS than the general population (p < .001), and vascular age differences that were 4.4 years greater (p < .001). CVD risk was elevated but not significantly different between HIV patients and the general population. Conclusion: Cardiovascular disease risk is elevated among HIV/HCV and HCV infected persons compared with the general population.     

Gender-Specific Differences in Baseline,Peak, and Delta Serum Creatinine: The NACSELD Experience

Digestive Diseases and Sciences - Women have lower serum creatinine values than men for similar renal function. We aimed to determine the differential effect of baseline, peak, and delta creatinine...     

Ribavirin induced hemolysis: A novel mechanism of action against chronic hepatitis C virus infection

Hepatitis C virus(HCV)is not usually cleared by our immune system,leading to the development of chronic hepatitis C infection.Chronic HCV induces the production of various cytokines,predominantly by Kupffer cells(KCs),and creates a pro-inflammatory state in the liver.The chronic dysregulated production of interferon(IFN)and other cytokines by KCs also promotes innate immune tolerance.Ribavirin(RBV)monotherapy has been shown to decrease inflammation in liver of patients with chronic hepatitis C.Sustained virological response(SVR)is significantly higher when IFN is combined with RBV in chronic HCV(c HCV)infection.However,the mechanism of their synergy remains unclear.Previous theories have attempted to explain the anti-HCV effect based on direct action of RBV alone on the virus or on the immune system;however,these theories have serious shortcomings.We propose that hemolysis,which universally occurs with RBV therapy and which is considered a limiting side effect,is precisely the mechanism by which the anti-HCV effect is exerted.Passive hemolysis results in anti-inflammatory/antiviral actions within the liver that disrupt the innate immune tolerance,leading to the synergy ofRBV with IFN-α.Ribavirin-induced hemolysis floods the hepatocytes and KCs with heme,which is metabolized and detoxified by heme oxygenase-1(HMOX1)to carbon monoxide(CO),biliverdin and free iron(which induces ferritin).These metabolites of heme possess anti-inflammatory and antioxidant properties.Thus,HMOX1 plays an extremely important anti-oxidant,anti-inflammatory and cytoprotective role,particularly in KCs and hepatocytes.HMOX1 has been noted to have anti-viral effects in hepatitis C infected cell lines.Additionally,it has been shown to enhance the response to IFN-αby restoring interferon-stimulated genes(ISGs).This mechanism can be clinically corroborated by the following observations that have been found in patients undergoing RBV/IFN combination therapy for c HCV:(1)SVR rates are higher in patients who develop anemia;(2)once anemia(due to hemolysis)occurs,the SVR rate does not depend on the treatment utilized to manage anemia;and(3)ribavirin analogs,such as taribavirin and levovirin,which increase intrahepatic ribavirin levels and which produce lesser hemolysis,are inferior to ribavirin for treating c HCV.This mechanism can also explain the observed RBV synergy with direct antiviral agents.This hypothesis is testable and may lead to newer and safer medications for treating c HCV infection.     

Risk of contrast-induced nephropathy in hospitalized patients with cirrhosis

AIM： TO evaluate the incidence of contrast-induced nephropathy （CIN） in cirrhotic patients and to identify risk factors for the development of CIN.
METHODS： We performed a retrospective review of 216 consecutive patients with cirrhosis who underwent computed tomography （CT） with intravenous contrast at the University of Rochester between the years 2000-2005. We retrospectively examined factors associated with a high risk for CIN, defined as a decrease in creatinine clearance of 25% or greater within one week after receiving contrast.
RESULTS： Twenty-five percent of our patients developed CIN, and 74% of these patients had ascites seen on CT. Of the 75% of patients who did not develop CIN, only 46% had ascites. The presence of ascites was a significant risk factor for the development of CIN （P = 0.0009, OR 3.38, 95% CI 1.55-7.34） in multivariate analysis. Patient age, serum sodium, Model for End-stage Liver Disease score, diuretic use, and the presence of diabetes were not found to be significant risk factors for the development of CIN. Of the patients who developed CIN, 11% developed chronic renal insufficiency, defined as a creatinine clearance less than baseline for 6 wk.
CONCLUSION： Our results suggest that in hospitalized cirrhotic patients, especially those with ascites, the risk of CIN is substantial.     

Taurine deficiency after intensive chemotherapy and/or radiation.

Taurine, a nonessential amino acid (AA), is the most abundant free AA in the intracellular space. We measured plasma AA concentrations in 36 patients 7-28 d after intensive chemotherapy and/or radiation. Plasma taurine concentrations were uniformly low in all patients (20.0 +/- 6.4 mumol/L, mean +/- SD). Plasma taurine in 11 healthy volunteer control subjects was 45.0 +/- 20.3 mumol/L (P less than 0.001). Other AA concentrations, specifically those of precursor AAs methionine and cystine, were normal. We prospectively measured plasma AA concentrations in 12 patients before starting and 6-10 d after completing intensive cytotoxic treatment. Values before treatment were 37.2 +/- 11.6, 109.6 +/- 30.7, and 18.5 +/- 4.8 for taurine, cystine, and methionine, respectively, and were 24.3 +/- 6.0, 111.2 +/- 23.8, and 24.0 +/- 14.5 after treatment. Pretreatment plasma taurine correlated directly with the magnitude of decrease in plasma taurine during cytotoxic treatment (n = 12, r = 0.85, P less than 0.01). Intensive cytotoxic chemotherapy and/or radiation leads to a reduction in plasma taurine concentrations without any change in its precursor AAs, methionine and cystine. The clinical relevance of plasma taurine depletion will need further study.