End Stage Liver Disease

Objectives: To describe the patterns of growth, nutritional status, body composition, and resting energy expenditure (REE) in prepubertal children with Alagille syndrome (AGS) before the onset of end-stage liver disease. Study design: Thirteen prepubertal subjects with AGS (8 male; mean age, 6.8 ± 2.8 years) were evaluated for growth parameters, body composition by skinfolds and by dual-energy x-ray absorptiometry, and REE by indirect calorimetry. The children with AGS were compared with a healthy, agematched reference group of 37 prepubertal children. Results: Compared with healthy children, children with AGS had significantly reduced (P < .05) growth (weight, weight z score, height, height z score), nutritional status (midarm circumference, triceps skinfold, and midarm muscle area), and body composition (fat mass and fat-free mass). Subscapular thickness, percent body fat, and REE were not different. The AGS subgroup (n = 4) with REE greater than 110% predicted value had a reduced percent body fat (P < .02).

Background: Regional citrate anticoagulatio∂n (RCA) is being used increasingly in critically ill patients who require continuous renal replacement therapy (CRRT). RCA may be avoided in patients with liver disease because of perceived increased risk of metabolic complications. The study compares the circuit lifespan and metabolic complications using RCA for CRRT at varying levels of liver dysfunction. Methods: Data was collected retrospectively including the number of days on CRRT, number of circuit (re)initiations within that time and serum ionized and total calcium, bicarbonate, and sodium, repeatedly during treatment. Model for end-stage liver disease (MELD) scores were calculated and patients were divided into 4 groups according to MELD score quartiles. Results: A total of 697 patients were included in the present study. The median circuit survival time was not different between groups. The median minimum serum ionized calcium levels during treatment were significantly lower in groups 3 and 4 (p<0.001), but by the last day of treatment, mean serum ionized calcium levels were not different between groups. The median minimum bicarbonate levels were significantly lower in groups 3 and 4 compared with groups 1 and 2 (p<0.01), but this is not considered clinically significant. The median maximum and mean serum bicarbonate levels were not significant between groups. Total to ionized calcium ratio levels were similar in groups 1, 2 and 3, but significantly higher in group 4 compared with other groups. Conclusion: RCA is a reasonably safe form of anticoagulation for maintaining efficiency and patency of the dialyzer in critically ill patients with liver dysfunction.

Background/Aims-A total of 213 patients with compensated cirrhosis, portal hypertension and no varices were included in a trial evaluating beta-blockers in preventing varices. Predictors of the development of hepatocellular carcinoma (HCC), including hepatic venous pressure gradient (HVPG) were analyzed. Methods-Baseline laboratory tests, ultrasound and HVPG measurements were performed. Patients were followed prospectively every three months until development of varices or variceal bleeding or end of the study in 09/02. The endpoint was HCC development according to standard diagnostic criteria. Univariate and multivariate Cox regression models were developed to identify predictors of HCC. Results-In a median follow-up of 58 months 26/213 (12.2%) patients developed HCC. Eight patients were transplanted and 28 patients died without HCC. Twenty-one (84%) HCC developed in patients with HCV. On multivariate analysis HVPG (HR 1.18; 95%CI 1.08-1.29), albumin (HR 0.34; 95%CI 0.14-0.83) and viral etiology (HR 4.59; 95%CI 1.51-13.92) were independent predictors of HCC development. ROC curves identified 10 mmHg of HVPG as the best cutoff; those who had an HVPG above this value had a 6-fold increase in the HCC incidence. Conclusions-Portal hypertension is an independent predictor of HCC development. An HVPG >10 mmHg is associated with a 6-fold increase of HCC risk.

Background Gut microbiota modifiers may have beneficial effects of non-alcoholic fatty liver disease (NAFLD) but randomised controlled trials (RCT) are lacking in children. Aim We performed a double-blind RCT of VSL#3 vs. placebo in obese children with biopsy-proven NAFLD. Methods Of 48 randomised children, 44 (22 VSL#3 and 22 placebo) completed the study. The main outcome was the change in fatty liver severity at 4 months as detected by ultrasonography. Secondary outcomes were the changes in triglycerides, insulin resistance as detected by the homoeostasis model assessment (HOMA), alanine transaminase (ALT), body mass index (BMI), glucagon-like peptide 1 (GLP-1) and activated GLP-1 (aGLP-1). Ordinal and linear models with cluster confidence intervals were used to evaluate the efficacy of VSL#3 vs. placebo at 4 months. Results At baseline, moderate and severe NAFLD were present in 64% and 36% of PLA children and in 55% and 45% of VSL#3 children. The probability that children supplemented with VSL#3 had none, light, moderate or severe FL at the end of the study was 21%, 70%, 9% and 0% respectively with corresponding values of 0%, 7%, 76% and 17% for the placebo group (P < 0.001). No between-group differences were detected in triglycerides, HOMA and ALT while BMI decreased and GLP-1 and aGLP1 increased in the VSL#3 group (P < 0.001 for all comparisons). Conclusions A 4-month supplement of VSL#3 significantly improves NAFLD in children. The VSL#3-dependent GLP-1 increase could be responsible for these beneficial effects. Trial identifier: NCT01650025 (www.clinicaltrial.gov

Concerns have been raised that optimized redistricting of liver allocation areas might have the unintended result of shifting livers from better-performing to poorer-performing OPOs. We used the Liver Simulated Allocation Model to simulate a 5-year period of liver sharing within either 4 or 8 optimized districts. We investigated whether each OPO's net liver import under redistricting would be correlated with two OPO performance metrics (observed to expected liver yield and liver donor conversion ratio), along with two other potential correlates (eligible deaths and incident listings above MELD 15). We found no evidence that livers would flow from betterperforming OPOs to poorer-performing OPOs in either redistricting scenario. Instead, under these optimized redistricting plans, our simulations suggest that livers would flow from OPOs with more-than-expected eligible deaths toward those with fewer-than-expected eligible deaths, and that livers would flow from OPOs with fewer-than-expected incident listings to those with morethan-expected incident listings, the latter a pattern already established in the current allocation system. Redistricting liver distribution to reduce geographic inequity is expected to align liver allocation across the country with the distribution of supply and demand, rather than transferring livers from better-performing OPOs to poorer-performing OPOs.

Non selective beta blockers (NSBBs) are used in primary and secondary prophylaxis of portal hypertension-related bleeding in patients with cirrhosis. The efficacy of NSBBs treatment is predicted by hemodynamic response in term of reduction of the hepatic venous pressure gradient (HVPG) below 12 mmHg or at least 20% of the basal value. Nevertheless a relevant number of patients who do not achieve this HVPG reduction during NSBBs therapy do not bleed during follow up; this evidence suggests an additional non-hemodynamic advantage of NSBBs treatment to modify the natural history of cirrhosis. Recent studies have questioned the efficacy and safety of NSBBs in patients with advanced stage of liver disease characterized by refractory ascites and/or spontaneous bacterial peritonitis. These studies have suggested the existence of a defined and limited period to modify the natural history of cirrhosis by NSBBs: the &quot;window hypothesis&quot;. According with this hypothesis, patients with ...

Background. Non-alcoholic steatohepatitis is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. Aims. To investigate the insulin resistance in patients with non-alcoholic steatohepatitis who have no other causes of insulin resistance such as obesity, diabetes mellitus, and hyperlipidaemia. Patients. Thirteen patients (7 male, 6 female] with non-alcoholic steatohepatitis and 12 16 male, 6 female] healthy volunteers. Methods. All patients and healthy volunteers were submitted to biochemical tests and hyperinsulinaemic euglycaemic insulin clamp technique. Results. Basal insulin levels and C-peptide levels were significantly higher in non-alcoholic steatohepatitis group than in controls [p<O. 001 and p<O. 001, respectively]. Hyperinsulinaemic euglycaemic insulin clamp technique revealed lower glucose utilization in the non-alcoholic steatohepatitis group and the difference was statistically significant (P<O. 00 7). Conclusions. Our study revealed marked hyperinsulinaemia and insulin resistance in patients with non-alcoholic steatohepatitis. Hyperinsulinaemia and insulin resistance may contribute to pathogenesis of nonalcoholic steatohepatitis.

BACKGROUND: Liver transplantation is performed at large transplant centers worldwide as a therapeutic intervention for patients with end-stage liver diseases. AIM: To analyze the outcomes and incidence of liver transplantation performed at the University of São Paulo and to compare those with the State of São Paulo before and after adoption of the Model for End-Stage Liver Disease (MELD) score. METHOD: Evaluation of the number of liver transplantations before and after adoption of the MELD score. Mean values and standard deviations were used to analyze normally distributed variables. The incidence results were compared with those of the State of São Paulo. RESULTS: There was a high prevalence of male patients, with a predominance of middle-aged. The main indication for liver transplantation was hepatitis C cirrhosis. The mean and median survival rates and overall survival over ten and five years were similar between the groups (p&gt;0.05). The MELD score increased over the course of...

Gastrointestinal stromal tumors (GISTs) are the most common non-epithelial (mesenchymal) tumors of the gastrointestinal tract. Although GISTs appear as solid and well-circumscribed lesions in most patients, they may also appear as solid- cystic (mixed) or pure cystic lesions due to reasons like intra-tumor hemorrhage and necrosis in a very small percentage of patients. Hence, cystic GISTs mostly lead to a diagnostic dilemma. In this paper we aimed to report a case of pure cystic giant GIST that was drained percutaneously twice after being misdiagnosed as a mesenteric cyst. An 83-yearold man was operated for a pre-diagnosis of a recurrent mesenteric cyst. The operation was started with the three-trocar laparoscopic technique. Six thousand milliliters of purulent fluid were drained from the cystic lesion. Then, a mini incision was performed above the umbilicus and the cyst and the distal ileal segment where it was originated were removed from the abdominal cavity. After the resection of a 15-cm ileal segment together with the cystic lesion, an intestinal anastomosis was performed. The histopathological and immunohistochemical findings showed that the mass was a GIST (size: 20 cm, mitosis: 3/50 HPF, Ki 67: %15, CD117: positive, DOG-1: positive). The patient was closely followed without imatinib therapy. KEY WORDS: Abscess, Cystic Degeneration, GIST, Mistreatment.

h i g h l i g h t s Congenital absence of the infrahepatic inferior vena cava (IVC) amongst adult liver transplant recipients is rare. Radiological identification of vascular anomalies by routine pre-transplant imaging (CT/MRI) during transplant assessment work up is essential to plan appropriate strategies. Preservation of adequate length of native hepatic veins as they join the right atrium allows satisfactory outflow reconstruction with classic piggyback technique.

During the study period 47 patients underwent cadaveric LT. The mean age of the donors and recipients was 45 years (range: 5¬-72 years) and 46 years (range: 4-66 years), respectively. In all, there were 15 marginal donors and 18 donors with a DRI >1.7. In total, 4 LT patients that received livers from marginal donors and 5 that received livers from donors with a DRI ≥1.7 had EGD. Among the recipients of marginal livers, 5 died, versus 4 of the recipients of standard livers. There was no significant difference in EGD or mortality rate between the patients that received livers from marginal donors or those with a DRI ≥1.7 and patients that received standard donor livers. Conclusion: Marginal and DRI ≥1.7 donors negatively affected LT outcomes, but not significantly.

The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies and is presently being evaluated as an HCV vaccine candidate. HCV binds to human cells through the interaction of E2 with the tetraspanin CD81, a putative viral receptor component. We have analyzed four different E2 proteins from 1a and 1b viral isolates for their ability to bind to recombinant CD81 in vitro and to the native receptor displayed on the surface of Molt-4 cells. A substantial difference in binding efficiency between these E2 variants was observed, with proteins derived from 1b subtypes showing significantly lower binding than the 1a protein. To elucidate the mechanism of E2-CD81 interaction and to identify critical regions responsible for the different binding efficiencies of the E2 variants, several mutants were generated in E2 protein regions predicted by computer modeling to be exposed on the protein surface. Functional analysis of these E2 derivatives revealed that at l...

Objective:The objective  of this  study was  to evaluate the low bone mineral  density (BMD) in patients with liver cirrhosis.Methodology:This cross sectional study on 151 Liver cirrhotic patients was conducted at Liaquat University  Hospital  Hyderabad/Jamshoro.This  study duration  was 6  months,July  2015  to December 2015. The Assessment of bone mineral density (BMD) for each relevant patient was done using ultrasound impedance Dual Energy X-ray Absorptiometry  (DEXA) by senior pathologist having ≥05 yearsofexperience, across the calcaneum, at lumbar spine  (LS) and femur neck (FN),  were computedby using computer supporteddevice.The BMD wasexpressedin terms of T score. The WHO standardvalue was utilized to define the low BMD / osteoporosis is T score -1.5.Original ResearchArticle

This chapter discusses the most common biliary tract diseases, with particular emphasis on biliary strictures, primary sclerosing cholangitis, and cholangiocarcinoma. The aim is to provide an overview of disease epidemiology, genetic and non genetic risk factors, clinical presentation, treatment options, prognosis and impact on quality of life for each of these conditions. In total, this chapter identifies critical areas for clinicians to recognize a cluster of relatively rare conditions and provides guidance on management, including newly emerging technologies.

In July 2005, Argentina switched from a categorical liver allocation system to a MELD/PELD‐based policy for patients with CLD. To analyze WL outcomes and survival after LT in children. From January 2000 to December 2010, 923 children were registered. Two consecutive five‐yr periods were analyzed and compared: Era I (January 2000–July 2005) (n = 379) and Era II (July 2005–December 31, 2010) (n = 544). All data were prospectively collected and analyzed using the Kaplan–Meier method. After adopting the MELD/PELD system, WL registrations increased by 44% (from 379 to 544) and the number of LT increased by only 24% (from 278 to 365). However, three‐month WL mortality rate (32% to 18%, p &lt; 0.0001, HR 2.002 CI 95% 1.5–2.8) decreased significantly. No significant differences were observed between Era 1 and II in one‐yr post‐LT survival (77.5% vs. 84.1%, p = 0.3053) and in acute re‐LT rate (9% vs. 5%, p = 0.1746). Under the MELD/PELD‐based allocation system in Argentina, mortality on the ...

Ceruloplasmin (Cp) is a serum ferroxidase that plays an essential role in iron metabolism. It is routinely tested by immunoturbidimetric assays that quantify the concentration of the protein both in its active and inactive forms. Cp activity is generally analyzed manually; the process is time-consuming, has a limited repeatability, and is not suitable for a clinical setting. To overcome these inconveniences, we have set the automation of the o-dianisidine Cp activity assay on a Cobas Mira Plus apparatus. The automation was rapid and repeatable, and the data were provided in terms of IU/L. The assay was adapted for human sera and showed a good precision [coefficient of variation (CV) 3.7 %] and low limit of detection (LoD 11.58 IU/L). The simultaneous analysis of Cp concentration and activity in the same run allowed us to calculate the Cp-specific activity that provides a better index of the overall Cp status. To test the usefulness of this automation, we tested this assay on 104 healthy volunteers and 36 patients with Wilson's disease, hepatic encephalopathy, and chronic liver disease. Cp activity and specific activity distinguished better patients between groups with respect to Cp concentration alone, and providing support for the clinical investigation of neurological diseases in which liver failure is one of the clinical hallmarks.

Late allocation of organs for transplant impairs post liver transplant (LT) survival. Cardiac dysfunction, especially diastolic and autonomic dysfunction, is frequent and plays an important role in the prognosis of cirrhotic patients. However, the role of myocardial contractility is unexplored and its prognostic value is controversially discussed. This study analyses the role of myocardial contractility assessed by speckle tracking echocardiography in LT allocation. 168 cirrhotic patients (training cohort: 111, validation cohort: 57) awaiting LT in two centers were included in this retrospective study. 51 patients from the training and all patients from the validation cohort were transplanted; 36 patients of the training and 38 of the validation cohort were alive at the end of follow-up; 21 non-transplanted patients died. Contractility of the left ventricle increased with severity of the Child-Pugh score. Interestingly, higher left ventricular contractility in the training cohort pa...

In order to define factors which are important for the development of hepatitis C virus (HCV) infection and disease in transplant patients, we examined the role of class II MHC antigen restriction in viral antigen presentation to support a hypothesis of the association of this disease with an autoimmune pathogenesis. A greater degree of histocompatibility match between these donors and their HCV-negative recipients was associated with a greater predisposition to recipient HCV liver disease (ALT elevation) posttransplant. The HCV carrier state could be identified with significant amplification of autologous mixed lymphocyte reactivity (AMLR) in both long-term hemodialysis and long-term renal transplant patients, but the AMLR was absent in end-stage liver disease patients with HCV-associated cirrhosis and was insignificantly elevated in these patients with persistent infection in the first 2 years after a new liver was transplanted. There was also a moderate reduction in autologous reactivity as well as serum HCV titers among renal transplant patients who displayed biochemical evidence of chronic liver disease as opposed to those who did not. This appeared later in the course of the disease. HCV RNA could be detected in peripheral blood mononuclear cells (PBMC) of only a portion of HCV-infected renal transplant patients and these showed significantly higher autologous reactivity. In contrast, despite the fact that observations were earlier after de novo liver transplantation, HCV RNA (i.e., earlier in the course of a new or recurrent disease process) was found in PBMC of all liver transplant recipients tested. The

Background. Renal failure (RF) is reported to occur in 11-49% of the patients with decompensated end-stage liver disease (ESLD) and has been associated with increased mortality, particularly in the occurrence of hepatorenal syndrome (HRS) type 1. Aims. To evaluate the frequency and outcome of RF in patients admitted to the hospital due to decompensated ESLD and to assess the impact of the underlying cause of RF on survival. Material and methods. Four hundred and six patients (65% males, mean age 62 ± 12 years) with decompensated ESLD were evaluated for the occurrence of RF (defined as serum creatinine ³ 1.5 mg/mL). The underlying cause of RF was reckoned in each subject and compared to outcome. Results. Renal failure was observed in 39% of the patients at admission and in 10% of the subjects during hospitalization. Mortality was significantly higher in subjects with RF (26 vs. 1%, p < 0.000001). Hypovolemia, bacterial infections, parenchymal kidney diseases and HRS were identified as causes of RF in, respectively, 40, 32, 15 and 12% of the cases. Mortality was significantly higher in those subjects with HRS type 1 and bacterial infections, when compared to other causes of RF. Conclusions. Renal failure occurs in nearly half of the patients with decompensated ESLD. It is most commonly caused by hypovolemia and bacterial infections. Occurrence of RF has an adverse impact in patient survival, particularly in those subjects with bacterial infections and HRS type 1, prone to develop progressive renal dysfunction despite intensive medical care.

Liver transplantation has become the standard treatment for acute failure and end-stage liver disease, but there are fewer donor organs available than patients on the waiting list. The donor pool may be increased by using marginal donor candidates. Some infectious and metabolic diseases have been transmitted to the recipient via marginal donor grafts. Hydatid cyst disease is rarely transmitted to a recipient from the donor graft. A literature search showed only 2 previous cases of liver transplantation using a donor graft that contains a hydatid cyst. We treated a 19-year-old woman who experienced acute on chronic end-stage liver failure secondary to cryptogenic cirrhosis. The liver graft from a 97-year-old marginal cadaveric donor contained a calcified hydatid cyst. No complication was associated with the hydatid cyst at 3 years after transplantation. The present case shows that donor livers with an inactive, calcified hydatid cyst may be used for emergency liver transplantation after considering the location, size, and relation of the cyst to vascular and biliary structures. The cyst may be resected on the back table with a successful treatment outcome.

Background and objectives In ANCA-associated GN, severe renal dysfunction portends a poor prognosis for renal recovery and patient survival. This study evaluated the prognostic factors affecting renal and patient outcomes in patients presenting with severe kidney failure to guide immunosuppressive therapy. Design, setting, participants, & measurements This study retrospectively evaluated clinical and histopathologic characteristics of 155 patients who underwent biopsy between October 1985 and February 2011 (median eGFR at presentation, 7.1 ml/min per 1.73 m 2 ; 87% required hemodialysis), all treated with immunosuppressive medications. Three outcomes of interest were measured: patient survival, renal survival, and treatment response (defined as dialysis-free survival without active vasculitis by 4 months after biopsy). Competing risk, Cox, and logistic regression analyses were conducted for each outcome measure. Results Within 4 months after biopsy, treatment response was attained in 51% of patients, 35% remained on dialysis, and 14% died. In a competing risk analysis, estimated cumulative incidence rates of ESRD and diseaserelated mortality were 26% and 17% at 1 year and 32% and 28% at 5 years, respectively. Cyclophosphamide therapy and treatment response by 4 months were independently associated with patient and renal survival, adjusting for the percentage of normal glomeruli, histopathologic chronicity index score, and baseline clinical characteristics. Only 5% of patients still dialysis dependent at 4 months subsequently recovered renal function. Low chronicity index score (odds ratio [OR], 1.16; 95% confidence interval [95% CI], 1.04 to 1.30, per unit decrease) and baseline eGFR.10 ml/min per 1.73 m 2 (OR, 2.77; 95% CI, 1.09 to 7.01) were significantly associated with treatment response by 4 months. Among cyclophosphamide-treated patients, the likelihood of treatment response was .14% even with highest chronicity index score and eGFR,10 ml/min per 1.73 m 2. Conclusions Although low baseline renal function and severe renal scarring are associated with lower treatment response rate, no "futility" threshold could be identified. Conversely, continued immunosuppressive therapy beyond 4 months is unlikely to benefit patients who remain dialysis dependent.

Background/Aims-Lamivudine has been shown to improve liver disease and survival of hepatitis B (HBV) patients on the liver-transplant (OLT) waiting list, but liver failure may worsen in patients with drug resistance. Use of antiviral salvage therapy may decrease this risk. Methods-We analyzed data from patients enrolled in the NIH HBV OLT cohort to study the effects of pre-transplant antiviral therapy on transplant-free survival and survival without transplant. We also compared the clinical outcomes of those who did or did not develop antiviral failure (virologic breakthrough or genotypic resistance) while awaiting transplant. Results-One hundred twenty-two eligible patients received antiviral therapy pre-OLT and were followed for a median of 40.5 months (0.4-123.0) after initiation of antiviral therapy. Forty-four (36.1%) patients developed antiviral failure; all had lamivudine monotherapy as initial treatment. Forty-two patients started salvage therapy a median of 5 months after lamivudine failure; the median MELD score was 12. Twenty-one (50%) patients had a full response to salvage therapy. Eleven (26.2%) patients had a suboptimal virologic response but remained clinically compensated. Antiviral failure was not a significant predictor of transplant or death (p=0.

Aim: The aim of this study was to compare the different phases of chronic Hepatitis B virus (HBV) infection with different values for normal ALT. Background: For many years, the upper limit of 40 IU was considered normal for ALT for both sexes, but in recent years this value is challenged and some guidelines have lowered their limit. Methods: In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital, Tehran, Iran, from 2011 through 2018 were classified in four groups according to American Association of the study of the liver disease (AASLD), European Association of the study of the liver (EASL) /Asian-Pacific Association of the study of the liver (APASL) and American Collage of Gastroenterology (ACG) guidelines. The frequency of each group based on 3 different guidelines was compared. Results: In HBeAg positive patients (n=100), the percentage of immune tolerance phase was 43% according to AASLD cutoff for normal ALT (35 IU for men, 25 IU for women), while it was 68% and 28% with regard to EASL/APASL and ACG (30 IU for men, 19 IU for women) cutoffs respectively. In HBeAg negative patients (n=1900), 66.68% were inactive carriers according to AASLD, but the percentage changed to 82.89% and 52.42% considering EASL/APASL and ACG values, respectively. Conclusion: Using ACG and to a lesser extent AASLD cutoff for ALT, many patients shift from immune tolerance and inactive carrier state into the immune active phase. Thus, more patients are candidates for treatment or intensive workup to determine the extent of liver damage.

Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid-polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29 (+/2) /MxCre (+/2) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-a and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine.

During the study period 47 patients underwent cadaveric LT. The mean age of the donors and recipients was 45 years (range: 5¬-72 years) and 46 years (range: 4-66 years), respectively. In all, there were 15 marginal donors and 18 donors with a DRI >1.7. In total, 4 LT patients that received livers from marginal donors and 5 that received livers from donors with a DRI ≥1.7 had EGD. Among the recipients of marginal livers, 5 died, versus 4 of the recipients of standard livers. There was no significant difference in EGD or mortality rate between the patients that received livers from marginal donors or those with a DRI ≥1.7 and patients that received standard donor livers. Conclusion: Marginal and DRI ≥1.7 donors negatively affected LT outcomes, but not significantly.

OBJECTIVE: To evaluate the frequency of recurrence of spontaneous bacterial peritonitis (SBP) in patients with end stage liver disease and the factors responsible for it.STUDY DESIGN: Descriptive study.PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from November 2008 till November 2009.METHODOLOGY: Patients with cirrhosis who were admitted at AKUH with diagnosis of SBP during the study period

Bone marrow reconversion (BMR) is a replacement of yellow bone marrow for red bone marrow in adults. It can have numerous causes, including malignancy, edema, infection, anemia, and other diseases. We report a case in which BMR was found incidentally on MRI of the knee. The initial complaint in our patient was right knee pain, which led to the early diagnosis of gastrointestinal stromal tumor (GIST). Upper endoscopy and examination of CT revealed a polypoid mass in the antrum of the stomach. The patient underwent atypical gastrectomy with pathologic confirmation of GIST. We would like to emphasise that incidental findings on MRI should not be dismissed and that findings such as BMR can lead to early cancer detection.

In the absence of antiviral treatment, chronic hepatitis C virus (HCV) infection is a liver disease characterized by the development of necroinflammatory changes and progressive liver fibrosis, leading to cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). The approval of ribavirin in combination therapy regimens with interferon (IFN) dramatically improved therapy. Another advance was the introduction of pegylated IFNs, which allow a once-weekly subcutaneous administration and show more favorable pharmacokinetics and greater efficacy. Two forms are available: pegylated IFN alpha-2b (12 kDa) (1.5 g/kg) and pegylated IFN alpha-2a (40 kDa) (fixed dosage of 180 g). Ribavirin is administered orally, at doses ≥10.6 mg/kg, resulting in higher sustained virological responses (SVR) than IFN monotherapy. The highest SVR rates are attained with pegylated IFNs in combination with ribavirin. Factors associated with treatment outcome include HCV genotype, viral load, body weight, age, cirrhosis or bridging fibrosis, coinfection with HIV or hepatitis B virus, and treatment adherence and tolerance. Currently, the main therapeutic challenges ahead are: (a) the dosage optimization of pegylated IFNs and ribavirin according to the patients' characteristics; and (b) to evaluate the efficacy and safety of this combination therapy for difficult-to-treat patients, such as nonresponders, cirrhotics, transplant recipients, renal disease patients or those coinfected with HIV.

Objectives: Most infants with biliary atresia (BA) require liver transplantation (LT) after hepatoportoenterostomy (HPE), including those who initially clear jaundice. The aim of the present study was to identify clinical and routine laboratory factors in infants with BA post-HPE that predict native liver survival at 2 years. Methods: A retrospective cohort study was conducted in 217 patients with BA undergoing HPE in Sydney, Australia and Toronto, Canada between January 1986 and July 2009. Univariate and multivariate logistic regression using backwards-stepwise elimination identified variables at 3 months after HPE most associated with 2-year native liver survival. Results: Significant variables (P < 0.05) on univariate analysis included serum total bilirubin (TB) and albumin at 3 months post-HPE, bridging fibrosis or cirrhosis on initial liver biopsy, ascites of <3 months post-HPE, type 3 BA anatomy, age at HPE of >45 days, change in length z scores within 3 months of HPE, and center. On multivariate analysis, TB (P < 0.0001) and albumin (P ¼ 0.02) at 3 months post-HPE, and center (P ¼ 0.0003) were independently associated with native liver survival. Receiver operating characteristic analysis revealed an optimal cutoff value of TB <74 mmol/ L (4.3 mg/dL; area under the receiver operating characteristic curve 0.8990) and serum albumin level >35 g/L (3.5 mg/dL; area under the receiver operating characteristic curve 0.7633) to predict 2-year native liver survival. TB and albumin levels 3 months post-HPE defined 3 groups (1: TB 74 mmol/L, albumin >35 g/L; 2: TB 74 mmol/L, albumin 35 g/L; 3: TB >74 mmol/L) with distinct short-and long-term native liver survival rates (log-rank P < 0.001). Length z scores 3 months post-HPE were poorer for group 2 than group 1 (À0.91 vs À0.30, P ¼ 0.0217) with similar rates of coagulopathy. Conclusions: Serum TB and albumin levels 3 months post-HPE independently predicted native liver survival in BA when controlling for center. Serum albumin level <35 g/L in infants with BA who were no longer jaundiced at 3 months post-HPE was a poor prognostic indicator. Poorer linear growth and absence of significant coagulopathy suggest a role for early aggressive nutritional therapy in this group.

• Expect severe malnutrition requiring immediate treatment; • Protein malnutrition and hypermetabolism are associated with a poor prognosis; • Ensure adequate energy intake (total energy 30-35 kcal. kgBW-1. d-1 ; non-protein energy 25 kcal. kgBW-1. d-1); • Use indirect calorimetry if available; • Provide enough protein (1.2-1.5 g. kgBW-1. d-1); • Use BCAA after gastrointestinal bleeding and in hepatic encephalopathy grades III°/IV°; • Use fat as fuel (recommended fatty acid ratio n6:n3 = 2:1); • Use enteral tube or sip feeding; • Use parenteral nutrition if enteral feeding alone is not sufficient; • Avoid refeeding syndrome and vitamin/trace element deficiencies.

Background Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from hepatic steatosis to end-stage liver disease. It is the most common liver disease and its prevalence is increasing worldwide. In the present study, the effect of whey proteins on some parameters of NAFLD was investigated. Results Oral administration of the studied whey proteins products reduced the final body weight of rats. There was a significant reduction effect (P &lt; 0.05) of the tested proteins on hepatic triglycerides, liver enzymes (ALT and AST), lipid peroxidation (malondialdehyde level) and serum glucose. Feeding on whey proteins caused an increase in the reduced glutathione. Hepatic content of reduced glutathione was not affected by any of the used whey proteins, but it showed an increasing tendency (P &gt; 0.05). Liver histology showed an improvement of fatty infiltration in hepatocytes from whey protein groups and gives the histology of liver a n...

Background/Aims: The model for end-stage liver disease (MELD) has been used to prioritize cirrhotic patients awaiting liver transplantation. The change in MELD score over time (DMELD) may have additional prognostic value. We investigated the ability of DMELD to predict the outcome of advanced cirrhosis and prospectively assessed the factors associated with increasing DMELD. Methods: Risk factors were determined in 58 prospectively followed-up patients. The predictive power of DMELD, initial MELD and Child-Turcotte-Pugh (CTP) score was compared by using c-statistic in 351 patients. Results: Ascites (PZ0.020) and hepatic encephalopathy (PZ0.023) were significantly associated with increasing MELD score at 3 months. The area under receiver operating characteristic (ROC) curve for DMELD/month was 0.779 compared with 0.718 for MELD (PZ0.130) and 0.528 for CTP score (P!0.001) at 6 months; the area was 0.822, 0.744 and 0.528, respectively (PZ0.018 and !0.001, respectively) at 12 months. DMELD/month O2.5 was the only significant prognostic predictor at 6 (odds ratio: 9.8, P!0.001) and 12 months (odds ratio: 16.3, P!0.001) in multivariate logistic analysis. Conclusions: Increasing MELD score is associated with the onset of ascites and encephalopathy. DMELD is superior to initial MELD and CTP scores to predict intermediate term outcome in patients with advanced cirrhosis.