Severe Liver Disease (severe + liver_disease)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Liver disease as risk factor for cystic fibrosis-related diabetes development

ACTA PAEDIATRICA, Issue 5 2007
L Minicucci
Abstract Aim: To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. Methods: Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. Results: Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43,93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1= 58.4 ± 27% predicted versus 67.4 ± 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. Conclusion: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance. [source]


Hepatitis B and C virus coinfection: A novel model system reveals the absence of direct viral interference,

HEPATOLOGY, Issue 1 2009
Pantxika Bellecave
Coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) has been associated with severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests reciprocal replicative suppression of the two viruses, or viral interference. However, interactions between HBV and HCV have been difficult to study due to the lack of appropriate model systems. We have established a novel model system to investigate interactions between HBV and HCV. Stable Huh-7 cell lines inducibly replicating HBV were transfected with selectable HCV replicons or infected with cell culture,derived HCV. In this system, both viruses were found to replicate in the same cell without overt interference. Specific inhibition of one virus did not affect the replication and gene expression of the other. Furthermore, cells harboring replicating HBV could be infected with cell culture,derived HCV, arguing against superinfection exclusion. Finally, cells harboring replicating HBV supported efficient production of infectious HCV. Conclusion: HBV and HCV can replicate in the same cell without evidence for direct interference in vitro. Therefore, the viral interference observed in coinfected patients is probably due to indirect mechanisms mediated by innate and/or adaptive host immune responses. These findings provide new insights into the pathogenesis of HBV,HCV coinfection and may contribute to its clinical management in the future. (HEPATOLOGY 2009.) [source]


Risk of severe liver disease in NAFLD with normal ALT levels: A pediatric report,

HEPATOLOGY, Issue 6 2008
Melania Manco M.D., Ph.D.
No abstract is available for this article. [source]


Risk of severe liver disease in nonalcoholic fatty liver disease: Role of insulin resistance,

HEPATOLOGY, Issue 6 2008
Anna Ludovica Fracanzani
No abstract is available for this article. [source]


Identification of hepatocytic and bile ductular cell lineages and candidate stem cells in bipolar ductular reactions in cirrhotic human liver,

HEPATOLOGY, Issue 3 2007
Hongchao Zhou
Hepatocyte function and regeneration are severely compromised in severe liver disease, and a common sequela is cirrhosis. Structural changes caused by cirrhosis create a cellular environment conducive to the formation of ductular reactions (DRs). Ductular reactions are primarily composed of oval cells also known as "intermediate hepatobiliary cells". We have conducted single, double, and triple staining to study lineages of oval cells present in DRs. Staining with NCAM, CK19, and HepPar1 has revealed a distinctly bipolar structure to DRs that are embedded in cirrhotic tissue. Spatial analysis of cells that are singly HepPar1-positive, or CK19-positive, has revealed hepatocytic and biliary poles, respectively, in the DRs. Also, the location of singly NCAM-positive cells in DRs suggests that they may be bipotent liver stem/progenitor cells. The locations of other intermediate hepatobiliary cells, which have combinations of markers, suggest that CK19+/NCAM+ cells are transitional cells in the biliary lineage and that rare cells that are negative for all three markers are transitional cells in the hepatocytic lineage. A working cell lineage model for DRs is presented. (HEPATOLOGY 2007;45:716,724.) [source]


Natural history of hepatic fibrosis progression in chronic hepatitis C virus infection in India

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009
Syed S Hissar
Abstract Background and Aim:, The rate of fibrosis progression per year can predict the time for the development of cirrhosis in chronic hepatitis C (CHC). We assessed the rate of fibrosis progression and the predictors of disease severity in Indian CHC patients. Methods:, Of the 355 treatment-naïve, histologically-proven CHC patients, the precise duration of infection (from the time of exposure to HCV until liver biopsy) could be determined in 213 patients (age = 41.6 ± 14.7 years, male : female = 139 : 74, genotype 3 = 75%). The rate of fibrosis progression per year was calculated. The correlation of the advanced degree of fibrosis and age, duration of infection, age at the onset of infection, sex, mode of infection, hepatitis C virus (HCV) genotype, histological activity index (HAI), and the presence of diabetes mellitus were studied. Results:, The median rate of fibrosis progression per year was 0.25 (0.0,1.5) fibrosis units. The fibrosis progression rate was higher in patients who acquired infection at > 30 years of age, those < 30 years (0.33 vs 0.15; P < 0.001), and those who acquired HCV infection with a history of blood transfusion than with other modes of transmission (0.25 vs 0.19; P = 0.04). The median time to progress to cirrhosis was 16 years. The multivariate analysis found that the HAI score (odds ratio [OR]= 14.03; P < 0.001) and the duration of infection > 10 years (OR = 4.83; P < 0.001) correlated with severe liver disease (fibrosis , 3). Conclusion:, The median rate of fibrosis progression per year in Indian CHC patients is 0.25 fibrosis units. A higher HAI and longer duration of infection are associated with a significant risk of advanced liver disease, and merit early therapeutic interventions. [source]


Chronic hepatitis B virus infection in Asian countries

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2000
I Merican
Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5,10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8,10% of males and 6,8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50,75% of those with HCC. In Taiwan, 75,80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14,35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8,4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC. [source]


Hepatitis B virus X mutations occurring naturally associated with clinical severity of liver disease among Korean patients with chronic genotype C infection,

JOURNAL OF MEDICAL VIROLOGY, Issue 8 2008
Hyun-Ju Kim
Abstract Few reports have detailed mutation frequencies and mutation patterns in the entire X region according to clinical status. The aims of this study were to elucidate the relationships between mutation patterns and their frequencies in the X region and clinical status in a Korean cohort and determine specific X mutation types, related closely with liver disease progression. All X mutations were determined by direct sequencing in 184 patients with different clinical features. Mutation rates in the X region in patients with more severe liver disease, hepatocellular carcinoma (HCC) (3.6%) or liver cirrhosis (4%) were always significantly higher than in patients with corresponding less severe forms, chronic hepatitis (2.9%) or asymptomatic carriers (2.1%), but no significant difference in mutation rates was found in terms of HBeAg serostatus. All five mutation types (V5M/L, P38S, H94Y, I127T/N, and K130M and V131I) affecting the six codons were found to be related significantly to clinical severity. Among these, two mutation types (V5M/L and K130M and V131I) were observed more frequently in HBeAg negative patients than in HBeAg positive patients. In conclusion, the results suggest that an accumulation of mutations in the X region contributes to disease progression in chronic patients, at least Korean patients with genotype C. Specific mutation types appears to be related more to severe liver diseases such as HCC or liver cirrhosis. In particular, a novel mutation type (V5M/L) discovered firstly during the present study was found to be associated significantly with HCC. J. Med. Virol. 80:1337,1343, 2008. © 2008 Wiley-Liss, Inc. [source]


Hepatitis C in ethnic minority populations in England

JOURNAL OF VIRAL HEPATITIS, Issue 6 2008
A. G. Mann
Summary., The aim of the study was to investigate the differing epidemiology of hepatitis C-related end-stage liver disease in ethnic minorities in England. We used Hospital Episode Statistics from 1997/98 to 2004/05 to directly age-standardize numbers of episodes and deaths from hepatitis C-related end-stage liver disease in ethnic groups using the white English population as standard and the age-structured population by ethnic group from the 2001 Census. We estimated the odds of having a diagnosis of end-stage liver disease amongst hepatitis C-infected individuals in each ethnic group compared with whites using logistic regression. The main outcome measures were age-standardized morbidity and mortality ratios and morbidity and mortality odds ratios. Standardized ratios (95% confidence interval) for hepatitis C-related end-stage liver disease ranged from 73 (38,140) in Chinese people to 1063 (952,1186) for those from an ,Other' ethnic group. Amongst individuals with a diagnosis of hepatitis C infection, the odds ratios (95% CI) of severe liver disease were 1.42 (1.13,1.79), 1.57 (1.36,1.81), 2.44 (1.85,3.22), 1.73 (1.36,2.19) and 1.83 (1.08,3.10) comparing individuals of Black African, Pakistani, Bangladeshi, Indian and Chinese origin with whites, respectively. Ethnic minority populations in England are more likely than whites to experience an admission or to die from severe liver disease as a result of hepatitis C infection. Ethnic minority populations may have a higher prevalence of hepatitis C or they may experience a poorer prognosis because of differential access to health services, longer duration of infection or the prevalence of co-morbidities. [source]


Characteristics of HCV positive subjects referring to hospitals in Italy: a multicentre prevalence study on 6 999 cases

JOURNAL OF VIRAL HEPATITIS, Issue 5 2006
T. Stroffolini
Summary., In 2001, 6 999 anti-HCV positive subjects referred to 79 Italian hospital in a 6 months enrolment period were evaluated. Of them, 5 632 (80.5%) tested anti-HCV positive alone, 1 163 (16.6%) reported also an excessive alcohol intake, and 204 (2.9%) were also HBsAg positive. Normal biochemistry was observed in 7.8% of cases, chronic hepatitis in 67.9% of cases, liver cirrhosis in 18.9% of cases, and hepatocellular carcinoma in 3.6% cases. HCV positive subjects with excessive alcohol intake were statistically significantly younger, of male sex, and having more severe liver disease than those without excessive alcohol intake. Adjusting for the confounding effect of age and sex by multiple logistic regression analysis, HCV positive chronic hepatitis cases drinking more than four alcoholic drinks daily were 2.2-fold (CI 95% = 1.3,4.0) more likely to progress to liver cirrhosis than teetotallers. These findings indicate that nearly a quarter of HCV positive subjects referred to hospitals in Italy have a severe liver disease causing a remarkable impact on the national health system. Excessive alcohol intake in HCV chronic hepatitis cases increases the risk of progression to liver cirrhosis. [source]


Apoptotic cell death does not parallel other indicators of liver damage in chronic hepatitis C patients

JOURNAL OF VIRAL HEPATITIS, Issue 3 2000
Rodrigues
The mechanisms of hepatocyte damage and the events that lead to high rates of chronic liver disease in hepatitis C virus (HCV) infection remain unclear. Recent in vitro studies have suggested that the HCV core protein may disrupt specific signalling pathways of apoptosis. This prompted us to study patients with chronic HCV infection to: determine the extent of apoptosis in the liver; evaluate whether clinical and biochemical data are correlated with histological findings; and to investigate if apoptosis is related to the histological activity of the disease. Twelve patients with chronic hepatitis C were included in the study. Liver histology was scored by using the histological activity index (HAI) of Knodell et al. DNA fragmentation was assessed in liver tissue by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) assay. Routine methods were used to determine serum markers of liver disease. Bile acids were measured in serum and liver by gas chromatography. Patients were placed, according to their HAI score, into group A (3.8 ± 0.3) or group B (7.8 ± 0.8) (P < 0.01). Liver enzymes tended to be higher in group B patients than in patients of group A. Levels of toxic bile acids in serum were greater in patients than in controls (P < 0.01). Chenodeoxycholic acid values were slightly higher in serum and liver of patients in group A. Liver biopsies with low HAI scores showed an increased rate of apoptosis (18.0 ± 4.0 apoptotic cells per field) compared to those with higher HAI scores (6.6 ± 2.1, P < 0.05) or to controls (3.5 ± 0.4, P < 0.01). Hence, less severe liver disease, associated with lower histological grades and biochemistries, as well as increased levels of chenodeoxycholic acid, induces an expanded apoptotic response. The lower apoptotic rate in advanced liver disease may be associated with the high incidence of hepatocellular dysplasia/neoplasia. [source]


A virological perspective on the need for vaccination

JOURNAL OF VIRAL HEPATITIS, Issue 2000
S. Locarnini
Superinfecton of chronic carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV) with hepatitis A virus (HAV) is often associated with more severe liver disease than infection with HAV alone. Superinfection commonly causes markers of HBV and HCV replication to fall to significantly lower levels. The pathogenesis of acute liver damage characteristic of viral hepatitis is thought to be mediated by host cytotoxic T-lymphocytes (CTLs) directed against virus-infected hepatocytes. It has been proposed that the more aggressive liver disease observed in individuals infected with HAV in addition to chronic HBV/HCV is a result of the induction of interferon (IFN)-, during acute HAV infection. This accounts for the antiviral effect on the active markers of HBV/HCV replication, and the enhanced CTL response against HBV/HCV-infected hepatocytes. Alternatively, HAV may indirectly stimulate the T helper 1 (Th1)-type cytokine responses, such as interleukin (IL)-2, IFN-, and tumour necrosis factor (TNF)-,, which directly promote the antiviral CTL response. Clearance of HBV infection, and possible HAV and HCV, is associated with a specific CTL response, while viral persistence in chronic HBV and HCV infection has been attributed to an imbalance in the Th1,Th2 arms of the immune response. Vaccination against hepatitis A should be considered for patients with chronic HBV/HCV infection, to minimize the risk of exacerbating underlying liver disease. [source]


Review article: the treatment of non-alcoholic steatohepatitis with thiazolidinediones

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2005
H. REYNAERT
Summary It is generally accepted that non-alcoholic fatty liver disease will be the most frequent liver disease in the near future and that the management of patients with non-alcoholic fatty liver disease will be a challenge for hepatologists in the next decades. Non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome, in which insulin resistance plays a crucial role. Although steatosis will often not progress to severe liver disease, in some patients, it results in cirrhosis and even hepatocellular carcinoma. Therefore, it is important to identify those patients at risk for developing fibrosis. Age, diabetes, obesity and hypertriglyceridaemia are independent risk factors for fibrosis in patients with elevated serum alanine aminotransferase levels and steatosis on ultrasound. The presence of multiple metabolic disorders increases the risk. Apart from diet, exercise and correction of underlying metabolic abnormalities, no specific treatment is available at the moment. Theoretically, thiazolidinediones are an attractive way to treat non-alcoholic fatty liver disease, because they improve insulin resistance. Some preliminary studies with thiazolidinediones were encouraging, as steatosis, inflammation and fibrosis improved in a substantial number of patients. Although no serious side effects occurred in the pilot studies, we should look vigilantly for hepatotoxicity, as the first generation thiazolidinediones proved to be toxic for the liver. [source]


A comparison of liver transplantation outcomes in the pre- vs.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2005
post-MELD eras
Summary Background:, The model for end stage liver disease (MELD)-based organ allocation system is designed to prioritize orthotopic liver transplantation (OLT) for patients with the most severe liver disease. However, there are no published data to confirm whether this goal has been achieved or whether the policy has affected long-term post-OLT survival. Aim:, To compare pre-OLT liver disease severity and long-term (1 year) post-OLT survival between the pre- and post-MELD eras. Methods:, Using the United Network of Organ Sharing database, we compared two cohorts of adult patients undergoing cadaveric liver transplant in the pre-MELD (n = 3857) and post-MELD (n = 4245) eras. We created multivariable models to determine differences in: (i) pre-OLT liver disease severity as measured by MELD; and (ii) 1-year post-OLT outcomes. Results:, Patients undergoing OLT in the post-MELD era had more severe liver disease at the time of transplantation (mean MELD = 20.5) vs. those in the pre-MELD era (mean MELD = 17.0). There were no differences in the unadjusted patient or graft survival at 1 year post-OLT. This difference remained insignificant after adjusting for a range of prespecified recipient, donor, and transplant centre-related factors in multivariable survival analysis. Conclusions:, Although liver disease severity is higher in the post- vs. pre-MELD era, there has been no change in long-term post-OLT patient or graft survival. These results indicate that the MELD era has achieved its primary goals by allocating cadaveric livers to the sickest patients without compromising post-OLT survival. [source]


Protection from phototoxic injury during surgery and endoscopy in erythropoietic protoporphyria

LIVER TRANSPLANTATION, Issue 9 2008
Staffan Wahlin
Erythropoietic protoporphyria is an inherited condition characterized by pronounced solar photosensitivity and in a minority of patients severe liver disease that necessitates liver transplantation for survival. Phototoxic injury to abdominal organs and skin has been reported in several cases of liver transplantation surgery, including a few transplants in which protective light filters were used. This study discusses the optimal characteristics of light filters used during liver transplantation surgery. An experimental model is used to evaluate the relative protection of different filters, and the results are compared with theoretical calculations regarding the risk for phototoxic injury from light sources in health-care procedures. Whether protective measures are warranted in other illuminated procedures besides liver transplantation has been discussed often but never studied. This study elucidates the risk for phototoxic injury in endoscopy, laparoscopy, and non,liver transplant surgery. A theoretical model and epidemiological data are considered. Our findings indicate that endoscopy, laparoscopy, and surgical procedures other than liver transplantation are safe in the noncholestatic protoporphyria patient and that general recommendations for using filters in these situations are not warranted. Among the tested filters, a flexible yellow filter omitting wavelengths below 470 nm is recommended for liver transplant surgery. This filter has been readily accepted by surgeons and offers a good balance between protection and altered visual color perception. The experimental model, using hemolysis of protoporphyrin-loaded erythrocytes as a measure of phototoxicity, has substantiated theoretical findings on relative filter protection. Liver Transpl 14:1340,1346, 2008. © 2008 AASLD. [source]


Vitamin A toxicity: When one a day doesn't keep the doctor away

LIVER TRANSPLANTATION, Issue 12 2006
Rekha Cheruvattath
Vitamin A toxicity has been reported to cause severe liver disease and, occasionally, liver failure. Herein we present the case of a 60-year-old male with symptoms of muscle soreness, alopecia, nail dystrophy, and ascites. He continued to deteriorate with the development of refractory ascites, renal insufficiency, encephalopathy, and failure to thrive. A liver biopsy demonstrated presence of Ito cells and vacuolated Kupffer cells without the presence of cirrhosis. His clinical history revealed ingestion of large doses of vitamin A. His worsening clinical situation ruled out the possibility of a transjugular intrahepatic portosystemic shunt. The patient underwent orthotopic liver transplantation with resolution of symptoms. Vitamin A toxicity should be considered in the differential diagnosis of noncirrhotic portal hypertension. In conclusion, liver transplantation is a valid option if no improvement occurs in spite of cessation of the medication. Liver Transpl 12:1888,1891, 2006. © 2006 AASLD. [source]


Sexual functioning in patients with end-stage liver disease before and after transplantation

LIVER TRANSPLANTATION, Issue 10 2006
James H. Sorrell
The effects of end-stage liver disease (ESLD) on sexual functioning are complex and often overlooked in the context of chronic illness and the transplantation evaluation. The aim of the present study is to report on the prevalence of sexual dysfunction in patients with ESLD presenting for liver transplantation evaluation, as well as to examine a cohort after transplantation. Participants included 173 consecutive adult outpatients with ESLD who presented for orthotopic liver transplantation evaluation. All transplant candidates underwent a psychiatric evaluation, and a sexual history was taken by the transplant psychiatrist. Patients who received a liver transplant were contacted by telephone for follow-up (n = 39). The following domains were explored: sexual frequency, satisfaction, ability to orgasm, sexual interest, and, for men, erectile dysfunction. Before transplantation, high levels of sexual dysfunction were found, with women showing higher levels of dysfunction than men. Increased age and more severe liver disease were related to lower sexual frequency and satisfaction. Contrary to previous work, the cause of disease (alcoholic liver disease) was not related to sexual functioning before transplantation. Those with erectile dysfunction before transplantation showed continued dysfunction after transplantation. An additional finding was an age and gender bias against taking a sexual history from older women. Overall, for both men and women, the findings point to continued and persistent sexual dysfunction after transplantation. Findings may help transplant teams routinely inquire into the sensitive domain of sexual functioning early on and thereby provide an opportunity for treatment. Liver Transpl 12:1473-1477, 2006. © 2006 AASLD. [source]


MELD,Moving steadily towards equality, equity, and fairness

LIVER TRANSPLANTATION, Issue 5 2005
James Neuberger
Background and aims: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list. Methods: The MELD model predicts liver disease severity based on serum creatinine, serum total bilirubin, and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis. In this study, we prospectively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant candidates with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November, 1999, and December, 2001. Results: In this study cohort with chronic liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list mortality increased directly in proportion to the listing MELD score. Patients having a MELD score <9 experienced a 1.9% mortality, whereas patients having a MELD score > or =40 had a mortality rate of 71.3%. Using the c-statistic with 3-month mortality as the end point, the area under the receiver operating characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh (CTP) score (P < 0.001). Conclusions: These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers.(Gastroenterology 2003;124:91,96.) Context: The Model for Endstage Liver Disease (MELD) score serves as the basis for the distribution of deceased-donor (DD) livers and was developed in response to "the final rule" mandate, whose stated principle is to allocate livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area. However, in selected areas of the United States, organs are kept in organ procurement organizations (OPOs) with small waiting lists and transplanted into less-sick patients instead of being allocated to sicker patients in nearby transplant centers in OPOs with large waiting lists. Objective: To determine whether there is a difference in MELD scores for liver transplant recipients receiving transplants in small vs large OPOs. Design and setting: Retrospective review of the US Scientific Registry of Transplant Recipients between February 28, 2002, and March 31, 2003. Transplant recipients (N = 4798) had end-stage liver disease and received DD livers. Main outcome measures: MELD score distribution (range, 6,40), graft survival, and patient survival for liver transplant recipients in small (<100) and large (> or =100 on the waiting list) OPOs. RESULTS: The distribution of MELD scores was the same in large and small OPOs; 92% had a MELD score of 18 or less, 7% had a MELD score between 19 and 24, and only 2% of listed patients had a MELD score higher than 24 (P = .85). The proportion of patients receiving transplants in small OPOs and with a MELD score higher than 24 was significantly lower than that in large OPOs (19% vs 49%; P<.001). Patient survival rates at 1 year after transplantation for small OPOs (86.4%) and large OPOs (86.6%) were not statistically different (P = .59), and neither were graft survival rates in small OPOs (80.1%) and large OPOs (81.3%) (P = .80). Conclusions: There is a significant disparity in MELD scores in liver transplant recipients in small vs large OPOs; fewer transplant recipients in small OPOs have severe liver disease (MELD score >24). This disparity does not reflect the stated goals of the current allocation policy, which is to distribute livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area. (JAMA 2004;291:1871,1874.) [source]


Combined orthotopic heart and liver transplantation: The need for exception status listing1,

LIVER TRANSPLANTATION, Issue 12 2004
Paige M. Porrett
Through May 2004, 33 combined orthotopic heart-liver transplants (OHT/OLT) have been performed nationwide. No published data exist to date regarding outcomes of patients awaiting such transplants, although progression of two organ disease processes may contribute to premature death for waiting patients. Retrospective data were collected on patients listed for combined OHT/OLT from both an individual tertiary care transplant center and the national UNOS registry to delineate listing criteria and evaluate patient outcomes in both the pre- and post-MELD eras. All patients who survived to transplantation or died on the waiting list were included in the analysis. Results show that 29.6% of patients registered nationally and 42% of patients listed institutionally survived to transplantation. Survival to transplantation was associated with less severe liver disease, though patients with MELD scores ranging from 19 to 26 had significantly higher wait list mortality than expected when compared to single-organ liver transplants. Following combined orthotopic heart-liver transplantation, 80% and 70% of patients survive 1 and 3 years, respectively. In conclusion, combined OHT/OLT is a successful therapy, but current organ allocation policies may not ensure expeditious transplantation in critically ill patients with dual vital organ failure. Providing exception status listing to these patients would ensure more expeditious transplantation and potentially contribute to improved survival. (Liver Transpl 2004;10:1539,1544.) [source]


Liver Transplantation from Deceased Donors Serologically Positive for Chagas Disease

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2007
L. A. C. D'Albuquerque
The high mortality rates among patients waiting for liver transplantation has motivated the use of ,marginal livers', among which are included livers from deceased donors serologically positive for Chagas disease (CD). The present work describes the outcome of orthotopic liver transplantation in six patients with severe liver disease (Child Pugh C), with livers from donors serologically positive for CD. Transplantations were performed from November 2000 to January 2005, and the patients received prophylactic treatment with benznidazole for 60 days, as a recommended by the Brazilian Consensus in Chagas Disease. The transplantation procedures presented no technical problems, and all the patients were discharged from hospital. Five of them did not present side effects demanding interruption of the prophylactic treatment. Four of the patients were clinically well over 1 year after transplantation (mean follow-up of 42.1 months), with negative serological results for CD. Two patients died, one of them 6 months post surgery of sepsis due to biliary complication and other one due to pulmonary (tuberculosis) complications. They were both serologically negative for CD. These results suggest that liver transplantation from CD donors, followed by benznidazole prophylactic treatment, is an important therapeutic alternative for severe liver disease. [source]


The increasing problem of hepatitis C virus infection

AUSTRALIAN DENTAL JOURNAL, Issue 1 2001
EA Coates
Abstract The widespread incidence of hepatitis C (HCV) infection throughout the community is of concern. Although many of those infected will not suffer significantly from their infection, up to one-third will have liver disease, fatigue and oral health problems. General dental practitioners need to be aware of the precautions necessary in traeating people with severe liver disease. This paper discusses the issues associated with treating patients who have HCV infection including the importance of preventive programs to reduce dental pathology and maximise oral health. [source]


Liver disease as risk factor for cystic fibrosis-related diabetes development

ACTA PAEDIATRICA, Issue 5 2007
L Minicucci
Abstract Aim: To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. Methods: Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. Results: Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43,93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1= 58.4 ± 27% predicted versus 67.4 ± 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. Conclusion: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance. [source]