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Patients with cirrhosis account for 3% of intensive care unit admissions with hospital mortality exceeding 50%; however, improvements in survival among patients with acutely decompensated cirrhosis and organ failure have been described when treated in specialized liver transplant centers. Acute-on-chronic liver failure is a distinct clinical syndrome characterized by decompensated cirrhosis associated with one or more organ failures resulting in a significantly higher short-term mortality. In this review, we will discuss the management of common life-threatening complications in the patient with cirrhosis that require intensive care management including neurologic, cardiovascular, gastrointestinal, pulmonary, and renal complications.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.

Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials Introduction Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin. Aim We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients. Methods We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1st December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed. Results A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I2=0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I2=0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I2=0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I2=0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02). Conclusion Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit.

Effective immunosupression management is central to achieving optimal outcomes in liver transplant recipients. Current immunosuppression regimens and agents are highly effective in minimizing graft loss due to acute and chronic rejection but can also produce a substantial array of toxicities. The utilization of immunosuppression varies widely, contributing to the wide disparities in posttransplant outcomes reported between transplant centers. The International Liver Transplantation Society (ILTS) convened a consensus conference, comprised of a global panel of expert hepatologists, transplant surgeons, nephrologists, and pharmacologists to review the literature and experience pertaining to immunosuppression management to develop guidelines on key aspects of immunosuppression. The consensus findings and recommendations of the ILTS Consensus guidelines on immunosuppression in liver transplant recipients are presented in this article.

Biliary mucoceles after deceased donor liver transplantation are a rarity, and mucoceles mimicking a gallbladder from the recipient remnant cystic duct have not been described until this case. We describe a 48-year-old male who presented with right upper quadrant pain and was found to have a recipient cystic duct mucocele 3 mo after receiving a deceased donor liver transplant. We describe the clinical presentation, laboratory and imaging findings (including the appearance of a gallbladder), multidisciplinary approach and surgical resolution of this mucocele originating from the recipient cystic duct, and a review of the literature.

Indications for liver transplant have been extended, and older and sicker patients are undergoing transplantation. Infectious, malignant, and cardiovascular diseases account for the most posttransplant deaths. Cirrhotic patients can develop heart disease through systemic diseases affecting the heart and the liver, cirrhosis-specific heart disease, or common cardiovascular. No single factor can predict posttransplant cardiovascular complications. Patients with history of cardiovascular disease, and specific abnormalities on echocardiography, electrocardiography, or serum markers of heart disease seem to be at increased risk of complications. Pretransplant cardiovascular evaluation is essential to detecting these risk factors so their effects can be mitigated through appropriate intervention.

Biliary tract cancers (BTC) including, cholangiocarcinoma (CC) and gallbladder cancer (GBC), are rare and highly fatal malignancies. The etiology and inherited susceptibility of both malignancies are poorly understood. We quantified the risk of BTC in first-degree (FDR), second-degree (SDR), and first cousin (FC) relatives of individuals with BTC, stratified by tumor subsite. BTC diagnosed between 1980 and 2011 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and gender-matched BTC-free controls were selected to form the comparison group for determining BTC risk in relatives using Cox regression analysis. Of the 1302 index patients diagnosed with BTC, 550 (42.2 %) were located in the gallbladder and 752 (57.8 %) were cholangiocarcinomas. There was no elevated risk of BTC (all subsites combined) in FDRs (HR 0.94, 95 % CI 0.29–3.0), SDRs (HR 0.25, 95 % CI 0.06–1.03), and FCs (HR 0.96, 95 % CI 0.61–1.51) of BTC cases compared to cancer-free controls. Similarly, no increased familial risk of GBC or CC was found in relatives of BTC patients stratified by tumor subsite compared to relatives of controls. Relatives of BTC patients are not at an increased risk of GBC or CC in a statewide population. This suggests that biliary tract cancer risk is not associated with a familial predisposition and may be mitigated more strongly by environmental modifiers.

Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation.

Through detailed analyses of the National Health and Nutrition Examination Survey, the Nationwide Inpatient Sample, and the United Network for Organ Sharing registry, the authors provide a view of the epidemiology of the spectrum of alcohol liver disease (ALD) in the United States. Although the prevalence of ALD among the general population has been relatively stable at 8%, over the last decade, there has been an increase in ALD with advanced fibrosis, including increased hospitalizations for liver cirrhosis and its complications, and an increase in ALD as a cause for liver transplant listing, as well as a greater proportion of liver cancer cases associated with ALD.

Background Due to donor organ shortage, the number of patients listed for transplant greatly exceeds the supply of available heart allografts Recent approval of direct-acting antiviral (DAA) agents for HCV provides an opportunity to expand the donor pool through the use of organs from HCV NAT+ donors and offering highly-effective anti-HCV therapy to organ recipients who develop HCV infection Methods A heart transplant nurse coordinator identified an opportunity to increase donor pool by utilizing HCV NAT + donors The nurse coordinator researched and reviewed other national heart transplant programs’ experiences to support the model of accepting HCV NAT+ donors A review of our local Organ Procurement Organization (OPO) identified that approximately 4 to 6 HCV NAT+ donors may be available locally for transplant annually, with additional donors potentially available through distant procurement The nurse coordinator advocated for a change by first identifying a physician mentor and champion Next, key players needed to successfully launch the proposal were recruited as the core team Results A multidisciplinary task force was formed and included members from Transplant Infectious Diseases, Hepatology, Pharmacy, Cardiology, Cardiac Surgery, Quality, OPO, Administration and Risk Management The task force members conceptualized and executed a guideline for the use of HCV NAT+ donors The guideline addressed patient education, informed consent, co-infection testing, discharge treatment plan, therapy algorithm based on viral genotype, concomitant medications, financial support and outcome monitoring Next, patient consent form and practice guideline were approved by the hospital Patient Safety Committee and the transplant team Finally, the HCV NAT+ Protocol was fully implemented, 11 months after the initial decision to modify donor acceptance criteria Conclusion A nurse coordinator directed initiative for a major practice change was successfully implemented by collaborative coordination with key stakeholders in the Heart Transplant Program Quality and process improvement is an excellent way for a nurse coordinator to positively impact their program and patients This report identifies the resources and key steps needed to successfully implement guidelines for HCV NAT+ donor organ use in a heart transplant program.

Introduction: Hepatitis C virus (HCV) infection in kidney transplant (KTX) patients reduces long-term patient and graft survival. Direct-acting antivirals (DAA) are > 90% effective in achieving sustained viral response (SVR); however, DAAs are not routinely available to patients with end-stage renal disease (ESRD). The University of Utah Transplant Program developed a protocol to allow HCV-positive potential KTX recipients to accept HCV-positive donors' kidneys. Three months after successful KTX, they were eligible for DAA therapy. Methods: HCV-positive patients approved for KTX by the University of Utah Transplant Selection Committee were eligible to be enrolled in this study. Patients consented for the use of HCV-positive donor organs. Three to six months after successful KTX, these patients were treated for HCV with interferon-free direct-acting antiviral regimens according to viral genotype and prior treatment experience. Results: Between 2014-2015, 12 HCV-positive patients were listed for KTX. Eight patients were kidney only eligible, seven patients received HCV-positive deceased donor kidneys, and one received an HCV-negative organ. Currently, six patients have completed treatment, all have achieved sustained viral response (SVR), and one patient is currently awaiting treatment. All seven patients have functioning kidney grafts. Wait time for KTX was reduced amongst all blood groups from an average of 1,350 days to only 65 days. Conclusions: HCV-positive patients with ESRD can successfully receive an HCV-positive donor's kidney. Once transplanted, these patients can receive DAA therapy and achieve SVR. Use of HCV-positive organs reduced time on the waitlist by greater than three years and expanded the donor organ pool.

Constipation is one of the most frequent gastrointestinal disorders encountered in clinical practice in Western societies. Its prevalence increases with age and is more frequently reported in female patients. Chronic constipation has been associated with considerable impairment in quality of life, can result in large individual healthcare costs, and represents a burden to healthcare delivery systems. This review will focus on the definition, epidemiology, diagnostic approach, and non-pharmacologic as well as pharmacologic management of chronic constipation in the elderly, including an overview of new medications currently under clinical investigation.

Pituitary incidentalomas and non-functioning pituitary adenomas have fairly rare complications that may be more common when lesions are large (> 10 mm) and solid.

Summary Background Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta-analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision. Methods We searched MEDLINE, EMBASE and Cochrane CENTRAL, queried experts and reviewed the reference list of included publications. Eligible studies were comparative and noncomparative longitudinal studies that enroled patients with NFPA who underwent surgery (alone or in combination with other therapies). Reviewers, working independently and in duplicate, determined study eligibility with adequate reproducibility and extracted descriptive, quality and outcome data. Risks, relative risks (RR) and 95% confidence intervals (CIs) were estimated from each study and pooled using random-effects meta-analysis. Results Most included studies were uncontrolled case series in which patients received a combination of surgery and radiotherapy. The overall quality of the evidence was very low. Median follow-up was 4·29 years. When surgery was not combined with radiotherapy, there was an increased risk of tumour recurrence (RR 1·97; 95% CI, 1·15–3·35). Complications were more likely with the transcranial than with the transsphenoidal approach (mortality RR 4·89; 95% CI, 3·15–6·47; new anterior pituitary deficits RR 4·90; 95% CI, 2·94–7·82; and persistent diabetes insipidus RR 2·50; 95% CI, 1·05–5·35). Overall, transsphenoidal surgery had fairly low perioperative mortality (≤1%) and low complication rate (≤5% for all patient-important outcomes), but only less than a third of the patients had improvement in pituitary function. Conclusions Observational evidence supports the association between a combined approach of transsphenoidal surgery with radiotherapy and improvements in visual field defects and reduction in tumour recurrence.

Context: Treatment for patients with congenital adrenal hyperplasia (CAH) may affect the final height of these patients. Objective: Our objective was to determine the distribution of achieved height in patients with classic CAH diagnosed at infancy or early childhood and treated with glucocorticoids. Data Sources: We searched MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, and Scopus through September 2008; the reference sections of included studies; and expert files. Study Selection: Eligible studies included patients diagnosed with CAH before age 5 and followed to final height. Data Extraction: Reviewers working in duplicate independently extracted data on study characteristics and outcomes and determined each study’s risk of bias. Data Synthesis: The sd score (SDS) for final height and corrected height (defined as final height SDS − midparental height SDS) were estimated from each study and pooled using random-effects metaanalysis. The I2 statistic was used to assess inconsistency in results acr...

Context: The risks of testosterone therapy in men remain poorly understood. Objective: The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. Data Sources: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. Study Selection: Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. Data Extraction: Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. Data Synthesis: The methodological quality of the 51 included studies varied from low to medium, and...

Our aim was to assess long-term survival in patients transplanted for HCV-related end-stage liver disease (ESLD) and evaluate potentially modifiable predictors of survival. We performed a retrospective analysis of adult liver transplants (LT) at our institution for HCV-related ESLD since the program's inception. Pertinent demographic, clinical, and biochemical information was retrieved from electronic medical records and histological data from 990 per-protocol liver biopsies were collected. Three hundred eighty LT were performed at our institution during the study period, 206 patients were transplanted for HCV-related ESLD; 6 died within 30 days of transplantation and were not included. The remaining 200 recipients (DDLT 168 LDLT 32) constituted the evaluable population. The demographics were as follows: 150 males, median age 53 years; median donor age 39 years; hepatocellular carcinoma (HCC) in 26%. Overall 1-, 5-, and 7-year survival: 95%, 81%, and 79%; median survival 43 months, mortality 15%. Significant HCV recurrence (HAI ≥6 and/or fibrosis ≥2) was present in 49%, “early recurrence” (within 1 year of LT) in 30.5% and biopsy-proven acute rejection was present in 27%. Factors with a significant negative impact on patient survival included: fibrosis stage ≥2 at 12-month biopsy, advanced donor age, history of HCC and early acute rejection. Survival was similar regardless of the donor type (DDLT vs. LDLT). Early and aggressive HCV recurrence has a very heavy toll on patient survival. Prompt recognition and treatment of “rapid fibrosers” may impart benefit. As has been described before, avoidance of rejection and selection of young donors for HCV-positive recipients will also improve survival in this population. On the basis of our findings, LDLT is a good option for HCV-positive recipients. Liver Transpl 15:1872–1881, 2009. © 2009 AASLD.

SUMMARY Improved outcomes and increased availability have made liver transplantation thedefinitivetherapeuticoptionforpatientswithend-stageliverdisease.Asmostpatientswith liver disease are cared for by primary care providers, it is important for cliniciansto be aware of the main indications and contraindications to transplantation, havea general understanding of the pretransplant evaluation process, and be able to referpatients to a transplant center in a timely fashion.In recent years the organ allocation system in the United States has undergonemodifications that have benefited patients awaiting liver transplantation. Furtherresearch in this area will certainly result in improvements in the current system. Livingdonor liver transplantation is now carried out in many transplant centers as a way todecrease mortality on the waiting list for selected candidates. This procedure posesunique clinical, technical, and ethical problems that will have to be resolved by themedical community. REFERENCES

Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

Summary. Background: Hepatitis C virus (HCV) translation is initiated in a cap-independent manner by an internal ribosome entry site (IRES) located within the 5′ untranslated region (5′UTR). Sequence changes in this region could affect translation efficiency and presumably viral replication. Aim: To determine translation efficiency of 5′UTR variants developing during post-transfusion hepatitis C in two immunocompetent subjects and in two immunosuppressed liver recipients with recurrent HCV. Methods: Sequential samples were screened for 5′UTR changes by single-strand conformation polymorphism followed by cloning and sequencing whenever band pattern suggested sequence changes. 5′UTR variants were tested for IRES activity using a bicistronic dual luciferase expression plasmid transfected into HepG2 and Huh7 cell-lines. Results: In the transfused patients, translation efficiency of 5′UTR variants from early post-transfusion samples was 5.1- to 13.7-fold higher than that of predominant variants found in late follow-up samples. Post-transplant variants in the other two patients had 2.6- to 5.9-fold higher translation efficiency than those present only in pretransplant samples. Conclusion: In the immunocompetent host there may be selection of low translation efficiency HCV variants over the course of infection. However, in immunosuppressed subjects the opposite seems to be true as low translation efficiency variants are superseded by high translation efficiency variants.

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease of uncertain etiology. However, the histologic features of PSC liver disease can resemble those in cystic fibrosis (CF), an inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to determine if PSC patients have a higher frequency of common CF alleles than disease controls.DNA was extracted from peripheral lymphocytes of patients with end-stage liver disease. Samples were obtained before liver transplantation from 59 PSC patients and from three groups of control patients (20 each with primary biliary cirrhosis, autoimmune hepatitis, or hepatitis C). DNA samples were genotyped for 32 common CF mutations, the intron 8 T tract variants, and the M470V variant.One of 59 PSC patients (1.7%) had the common CF mutation (DeltaF508) in one CFTR gene. Two controls (3.3%) carried a single CF mutation (DeltaF508 in one primary biliary cirrhosis patient; W1282X in one hepatitis C patient). These rates do not differ from expected in the general population. The frequency of CFTR variants (5T and M470V) was also similar between PSC patients and controls.Despite anatomical similarities between CF liver disease and PSC, we could not confirm that PSC patients carried common CF mutations or common CFTR variants in higher than expected frequencies. These data suggest that CFTR dysfunction does not influence the pathogenesis of PSC.

Background: Interferon-based therapy induces changes in viral dynamics in chronic hepatitis C (CHC) patients. Aims: The aim of this study was to assess early hepatitis C virus (HCV)-RNA changes and evaluate its predictive value to achieve sustained viral response (SVR) in patients with CHC treated with peginterferon α-2b weekly plus ribavirin daily for 48 weeks. Methods: HCV-RNA was measured at baseline, 48 h, 4, 12, 24 and 48 weeks of treatment and 24 weeks after treatment. Results: Eighteen HCV genotype 1 patients were included (13 male, five female) with a mean age of 44.4±11.9 years. Nine patients achieved SVR (50%). Viral decline occurred as early as 48 h; the magnitude of decline was statistically different between both groups (P

Despite increasing success in the management of the most common causes of chronic liver disease, there are still many patients who go on to develop terminal liver failure and for whom the only definitive therapy is liver transplantation (LT). In most industrialized countries the main barrier to timely LT is the number of available liver donors. It has become apparent that as the procedure has become more widely available the number of patients awaiting LT has increased exponentially, while the number of donors has remained relatively constant. This is clearly illustrated by data from the United Network for Organ Sharing (UNOS) in the United States. The number of yearly registered candidates for LT grew from 2217 in 1992 to 18,505 in 2001; while the number of liver transplants has remained relatively stable since 1998 at a mean of 4921 per year, representing a deficit greater than 12,000 donors per year [1,2]. This ever-growing gap between patients requiring a liver transplant and potential donors has led to the development of strategies to increase the donor pool, such as adult living donor liver transplantation (LDLT), split-liver transplantation, and the use of non-heart beating donors. The use of so-called ‘marginal donors’, such as older donors, those with increased steatosis, and donors with evidence of prior exposure to hepatitis B or C viruses, has increased. The latter practice has evolved in parallel with our understanding of the pathobiology of hepatitis B and C, resulting in the development of more efficacious treatment modalities. The current review will focus on this subject with special emphasis on the most current information.

Background & Aims: Studies on hepatitis C virus (HCV) quasispecies dynamics in the natural course of infection are rare owing to difficulties in obtaining samples from the early phase of infection. Methods: We studied 15 patients from the Transfusion-Transmitted Viruses Study who seroconverted to anti-HCV after receiving infected blood. Follow-up serum samples were collected every 2–3 weeks for 6 months, at 10 months, and at 11–16 years. Viral quasispecies in the second envelope hypervariable region 1 (E2/HVR1) and 5′ untranslated region (5′UTR) were analyzed with single-strand conformation polymorphism (SSCP) and heteroduplex mobility assay (HMA). Results: Seven patients cleared infection within 7–24 weeks (mean, 14.0 wk) and 3 patients eventually became anti-HCV negative. In 6 patients with resolving hepatitis the SSCP band pattern remained stable, whereas in one patient minor changes appeared before clearance. In contrast, in all 8 patients progressing to chronicity, major changes in the E2/HVR1 quasispecies developed at 8–22 weeks (mean, 13.1 wk). Shannon entropy and medium mobility shift values derived from HMA gels remained stable in patients with resolving hepatitis but changed in those who developed chronic infection. Only 2 patients showed minor changes in 5′UTR. A decrease in E2/HVR1 complexity at the time of transmission (bottleneck) was found in 5 patients altogether. Conclusions: Changes in E2/HVR1 quasispecies 8–22 weeks after infection, likely caused by mounting immune pressure, were predictive of ensuing chronic infection, whereas stability was associated with resolution. Our study also showed that composition of HCV quasispecies may be preserved during transmission from host to host.

The aim of this study was to define liver shear stiffness by magnetic resonance elastography (MRE) that distinguishes normal from abnormal liver biopsy, especially when steatosis ≥20%, among potential live liver donors. Baseline clinical, laboratory, imaging, MRE, and liver biopsy results were recorded. Using MRE, hepatic shear stiffness in kilopascals (kPa) was measured and compared to liver biopsy. Comparison between groups was done using χ 2 or Fisher’s exact test for categorical variables and Wilcoxon test for continuous variables. Receiver operating characteristic (ROC) curve was calculated to assess diagnostic accuracy. Statistical significance was set at p

The classic hepatotropic viruses, hepatitis A through E, are not the only viral agents able to infect the liver. Other systemic viruses may cause hepatic injury that can range from mild and transient elevation of aminotransferases to acute hepatitis and occasionally acute liver failure and fulminant hepatitis. The clinical presentation may be indistinguishable from that associated with classic hepatotropic viruses. These agents include cytomegalovirus; Epstein-Barr virus; herpes simplex virus; varicella-zoster virus; human herpesvirus 6, 7, and 8; human parvovirus B19; adenoviruses among others. Wide spectrums of clinical syndromes are associated with cytomegalovirus disease. Unique clinical syndromes may present in neonates, young adults and immunocompromised hosts infected with cytomegalovirus. Cases of fulminant hepatitis have been reported in both immunocompromised and immunocompetent hosts infected with Epstein Barr virus. Occasionally, these patients with acute hepatic failure may need liver transplantation. Herpes simplex viruses may involve the liver in neonatal infections, pregnancy, immunocompromised hosts and occasionally, immunocompetent adults. Varicella-Zoster virus has also been associated with severe acute hepatitis and fulminant hepatitis in adults. The drug of choice for these conditions is intravenous acyclovir. These may also need liver transplantation in the more severe forms of clinical presentation. Typical liver biopsy findings can be useful in determining the diagnosis of these viral infections. Human herpesviruses 6, 7, and 8, human parvovirus B19, and adenoviruses can also be present with features of acute liver injury and occasionally as fulminant hepatitis. The clinical syndromes are less well delineated than those associated with herpesviruses. It is important to consider these viruses as possible etiologic agents in patients who have acute liver injury and their serologic markers for the classic hepatotropic viruses are not indicative of an active infection.

Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta-analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision.We searched MEDLINE, EMBASE and Cochrane CENTRAL, queried experts and reviewed the reference list of included publications. Eligible studies were comparative and noncomparative longitudinal studies that enroled patients with NFPA who underwent surgery (alone or in combination with other therapies). Reviewers, working independently and in duplicate, determined study eligibility with adequate reproducibility and extracted descriptive, quality and outcome data. Risks, relative risks (RR) and 95% confidence intervals (CIs) were estimated from each study and pooled using random-effects meta-analysis.Most included studies were uncontrolled case series in which patients received a combination of surgery and radiotherapy. The overall quality of the evidence was very low. Median follow-up was 4·29 years. When surgery was not combined with radiotherapy, there was an increased risk of tumour recurrence (RR 1·97; 95% CI, 1·15-3·35). Complications were more likely with the transcranial than with the transsphenoidal approach (mortality RR 4·89; 95% CI, 3·15-6·47; new anterior pituitary deficits RR 4·90; 95% CI, 2·94-7·82; and persistent diabetes insipidus RR 2·50; 95% CI, 1·05-5·35). Overall, transsphenoidal surgery had fairly low perioperative mortality (≤ 1%) and low complication rate (≤ 5% for all patient-important outcomes), but only less than a third of the patients had improvement in pituitary function.Observational evidence supports the association between a combined approach of transsphenoidal surgery with radiotherapy and improvements in visual field defects and reduction in tumour recurrence.

Treatment for patients with congenital adrenal hyperplasia (CAH) may affect the final height of these patients.Our objective was to determine the distribution of achieved height in patients with classic CAH diagnosed at infancy or early childhood and treated with glucocorticoids.We searched MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, and Scopus through September 2008; the reference sections of included studies; and expert files.Eligible studies included patients diagnosed with CAH before age 5 and followed to final height.Reviewers working in duplicate independently extracted data on study characteristics and outcomes and determined each study's risk of bias.The sd score (SDS) for final height and corrected height (defined as final height SDS - midparental height SDS) were estimated from each study and pooled using random-effects metaanalysis. The I(2) statistic was used to assess inconsistency in results across studies.We found 35 eligible studies, most of which were retrospective single-cohort studies. The final height SDS achieved by CAH patients was -1.38 (-1.56 to -1.20; I(2) = 90.2%), and the corrected height SDS was -1.03 (-1.20 to -0.86; I(2) = 63.1%). This was not significantly associated with age at diagnosis, gender, type and dose of steroid, and age of onset of puberty. Mineralocorticoid users had a better height outcome in comparison with the nonusers (P = 0.02).Evidence derived from observational studies suggests that the final height of CAH patients treated with glucocorticoids is lower than the population norm and is lower than expected given parental height.

By interrupting the adenoma-carcinoma sequence, endo-scopic polypectomy can prevent the development of colorectal cancer (CRC). Endoscopic polypectomy has, therefore, become an accepted screening and surveillance modality for CRC and has been widely adopted by clinicians, policymakers, and professional organizations as an effective screening tool. Most gastroenterologists are adequately trained to endoscopically excise the majority of polyps found in a routine colonoscopy. However, some polyps, due to their size, location, or configuration, are considered more technically challenging or are associated with an increased risk of complications (such as bleeding or perforation) and, hence, are not routinely resected. These so-called complex polypectomies are the focus of this paper.

Summary Context Prenatal treatment with dexamethasone to prevent virilization in pregnancies at risk for classical congenital adrenal hyperplasia (CAH) remains controversial. Objective To conduct a systematic review and meta-analyses of studies that evaluated the effects of dexamethasone administration during pregnancies at risk for classical CAH because of 21-hydroxylase deficiency (CYP21A2). Data Sources We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception through August 2009. Review of reference lists and contact with CAH experts further identified candidate studies. Study Selection Reviewers working independently and in duplicate determined trial eligibility. Eligible studies reported the effects on either foetal or maternal outcomes of dexamethasone administered during pregnancy compared to a control group that did not receive any treatment. Data Extraction Reviewers working independently and in duplicate determined the methodological quality of studies and collected data on patient characteristics, interventions, and outcomes. Data Synthesis We identified only four eligible observational studies (325 pregnancies treated with dexamethasone). The methodological quality of the included studies was overall low. Meta-analysis demonstrates a reduction in foetus virilization measured by Prader score in female foetuses treated with dexamethasone initiated early during pregnancy (weighted mean difference, −2·33, 95% CI, −3·38, −1·27). No deleterious effects of dexamethasone on stillbirths, spontaneous abortions, foetal malformations, neuropsychological or developmental outcomes were found although these data are quite sparse. There was increased oedema and striae in the mothers treated with dexamethasone. There were no data on long-term follow-up of physical and metabolic outcomes in children exposed to dexamethasone. Conclusions The observational nature of the available evidence and the overall small sample size of the whole body of the literature significantly weaken inferences about the benefits and harms of dexamethasone in this setting. Dexamethasone seems to be associated with reduction in foetus virilization without significant maternal or foetal adverse effects. However, this review underscores the current uncertainty and further investigation is clearly needed. The decision about initiating treatment should be based on patients’ values and preferences and requires fully informed and consenting parents.

The risks of testosterone therapy in men remain poorly understood.The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men.We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies.Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility.Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data.The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes.The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.

Our aim was to assess long-term survival in patients transplanted for HCV-related end-stage liver disease (ESLD) and evaluate potentially modifiable predictors of survival. We performed a retrospective analysis of adult liver transplants (LT) at our institution for HCV-related ESLD since the program's inception. Pertinent demographic, clinical, and biochemical information was retrieved from electronic medical records and histological data from 990 per-protocol liver biopsies were collected. Three hundred eighty LT were performed at our institution during the study period, 206 patients were transplanted for HCV-related ESLD; 6 died within 30 days of transplantation and were not included. The remaining 200 recipients (DDLT 168 LDLT 32) constituted the evaluable population. The demographics were as follows: 150 males, median age 53 years; median donor age 39 years; hepatocellular carcinoma (HCC) in 26%. Overall 1-, 5-, and 7-year survival: 95%, 81%, and 79%; median survival 43 months, mortality 15%. Significant HCV recurrence (HAIor=6 and/or fibrosisor=2) was present in 49%, "early recurrence" (within 1 year of LT) in 30.5% and biopsy-proven acute rejection was present in 27%. Factors with a significant negative impact on patient survival included: fibrosis stageor=2 at 12-month biopsy, advanced donor age, history of HCC and early acute rejection. Survival was similar regardless of the donor type (DDLT vs. LDLT). Early and aggressive HCV recurrence has a very heavy toll on patient survival. Prompt recognition and treatment of "rapid fibrosers" may impart benefit. As has been described before, avoidance of rejection and selection of young donors for HCV-positive recipients will also improve survival in this population. On the basis of our findings, LDLT is a good option for HCV-positive recipients.

The aim of this paper was to assess the persistence of hepatitis C virus (HCV) among patients successfully treated with peginterferon and ribavirin. The persistence of viral RNA was evaluated in the serum and peripheral blood mononuclear cells (PBMCs) of 25 chronic hepatitis C patients with sustained viral response to peginterferon and ribavirin treatment up to 56 months after the completion of therapy. Viral RNA was detected in the peripheral blood mononuclear cell cultures of five patients (20%), but none had detectable serum HCV RNA. At present, the clinical relevance of this finding is unclear. It is possible that viral persistence and, specifically, the presence of HCV RNA in PBMCs may lead to HCV reactivation under special circumstances, such as immunosuppression.

Since the introduction of liver transplantation as a routine surgical procedure for the treatment of end-stage liver disease, there has been an increasing gap between the number of available grafts and the number of patients on the waiting list. This has led transplant centers to expand the donor pool by different means. One of them has been the introduction of living donor liver transplantation. Other strategies include using less than optimal allografts from deceased donors, the so-called marginal donors, which include the use of grafts from older subjects, livers with moderate amounts of steatosis, or from donors with markers of past or current infection with hepatitis viruses who have absent or minimal liver biochemical or histologic injury. In this review, we will focus on the current use of allografts from donors with antihepatitis B core antibody and/or antibodies against hepatitis C virus in cadaveric and living donor liver transplantation.