Indication For Orthotopic Liver Transplantation Research Articles

Post-transplant lymphoproliferative disorder associated Epstein-Barr virus DNAemia after liver transplantation in children: Experience from single center.

The most prevalent malignancy that complicates both adult and pediatric solid organ transplantation is post-transplant lymphoproliferative disorder (PTLD). This study aimed to analyze the clinical and pathological characteristics, treatments, and outcomes of Epstein-Barr virus (EBV) DNAemia and PTLD in pediatric liver transplant recipients. A retrospective chart review was performed on 112 patients less than 18 years of age who underwent isolated orthotopic liver transplantation (OLT) between 2010 and 2022 at Ege University Children's Hospital. Data gathered for 1-year post-OLT included age at OLT, EBV, immunoglobulin (Ig)M/IgG status of the donor and recipient, indication for OLT, induction regimen, all immunosuppression levels, date and result of EBV polymerase chain reaction testing, rejection episodes documented by liver biopsy, and the development of PTLD. Forty-nine patients (43.75%) developed EBV DNAemia (median interval from surgery: 2 months, min-max: 2-36), of which 43 (87.8%) grafts came from living donors, and 6 (12.2%) came from deceased donors. Nine (18.4%) patients died during follow-up, and eight (16.3%) developed PTLD. Of these 8 patients; five patients developed EBV-related disease, one child developed hemophagocytic lymphohistiocytosis, one developed aplastic anemia, and one child developed B cell lymphoma. When PTLD patients and without-PTLD patients were compared, pediatric intensive care unit hospitalization, abnormal bone marrow biopsy findings, lymphadenopathy, age at diagnosis of EBV DNAemia, EBV viral load, tacrolimus (FK 506) pre-infection, were higher and tacrolimus 1-month levels were lower in patients with PTLD (p < 0.05). In logistic regression analysis, we showed that the age at diagnosis of EBV DNAemia was significantly higher in children with PTLD (p = 0.045; OR: 1.389; 95% CI: 1.007-1.914). PTLD is a rare but severe complication associated with EBV after OLT. This study demonstrated that PTLD is associated with older age, higher tacrolimus blood levels before EBV DNAemia, and higher peak EBV viral load at 1 month of EBV DNAemia.

Liver transplantation for biliary cysts: perioperative and long-term outcomes

BackgroundBiliary cysts (BC) is a rare indication for orthotopic liver transplantation (OLT). MethodsWe queried the UNOS dataset to identify patients who underwent OLT for Caroli's disease (CD) and choledochal cysts (CC). All patients with BC (CD + CC) were compared to a cohort of patients transplanted for other indications. Patients with CC were also compared to those with CD. Cox proportional hazard model was performed to assess predictors of graft and patient survival. Results261 patients underwent OLT for BC. Patients with BC had better pre-operative liver function compared to those transplanted for other indications. 5-year graft and patient survival were 72% and 81%, respectively, similar to those transplanted for other indications after matching. Patients with CC were younger and had increased preoperative cholestasis compared to those with CD. Donor age, race, and gender were predictors of poor graft and patient survival in patients transplanted for CC. ConclusionsPatients with BC have similar outcomes to those transplanted for other indications and more frequently require MELD score exception. In patients transplanted for choledochal cysts, female gender, donor age, and African-American race were independent predictors of poor survival. Pediatric patients transplanted for Caroli's disease had better survival compared to adults.

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.

Long Graft Artery and Arterial Anomalies Are Associated with Hepatic Artery Thrombosis after Orthotopic Liver Transplantation

Introduction: Hepatic artery thrombosis is one of the most feared surgical complications after orthotopic liver transplantation (OLT). The aim of this study was to analyse factors involved in global, early (less than a month) and late (more than a month) hepatic artery thrombosis (HAT) after OLT. Methods: Inclusion criteria: patients who underwent OLT between November 2001 and December 2018. Exclusion criteria: liver retransplantation. Several preoperative and intraoperative variables were analysed. Graft artery was classified as long or short when the section was located distal or proximal to the proper/common hepatic artery bifurcation. In the same way, recipient patch for arterial anastomosis was classified as distal or proximal to the proper/common hepatic artery bifurcation. Student's T for continuous variables and Chi-Square for discrete variables were used for univariate analysis. Logistic regression was used for multivariate analysis (MVA). Results: Finally, 588 patients were eligible for statistical analysis. Global, early and late HAT appeared in 53 (9.01%), 35 (5.95%) and 18 (3,06%) patients, respectively. For global HAT, two variables proved to be significant after MVA: hepatocellular carcinoma as indication for OLT (p=0.035) and long graft artery (p=0.007). For early HAT, two variables turned out to be significant after MVA: hepatocellular carcinoma as indication for OLT (p=0.012) and arterial anomalies (p=0.036). For late HAT, only long graft artery reached statistical significance after MVA (p=0.026). Conclusion: Technical factors involving arterial anastomosis, as the presence of arterial anomalies and the length of the graft artery, seem to be essential risk factors for HAT after OLT.

Metabolic syndrome following liver transplantation in nonalcoholic steatohepatitis.

Metabolic syndrome is a major clinical disorder involving metabolic dysregulation characterized clinically with features of central obesity, insulin resistance (IR), type 2 diabetes, hypertension, and dyslipidemia. Metabolic syndrome is strongly associated with the rising prevalence nonalcoholic steatohepatitis, a leading indication for orthotopic liver transplantation in the Western world. The presence or recurrence of metabolic syndrome following liver transplantation can contribute to the development and recurrence of nonalcoholic fatty liver disease (NAFLD) in the liver allograft. In this review, we discuss the endogenous and exogenous drivers of post-transplant metabolic syndrome, role of chronic immunosuppression, and the prevalence and clinical significant of post-transplant metabolic syndrome on nonalcoholic steatohepatitis.

Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study

Introduction and objectivesHepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called "Brazilian Milan Criteria" (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. Materials and MethodsWe conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. ResultsPost-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. ConclusionsIn a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used.

Long-term Outcome of Orthotopic Liver Transplantation in Patients With Hemochromatosis: A Summary of a 30-year Transplant Program.

Background.Hemochromatosis (HC) is an autosomal recessive disease characterized by impaired iron metabolism and a rare indication for orthotopic liver transplantation (LT). Data about iron reaccumulation and remodeling of the liver graft after LT are limited. Therefore, we performed an evaluation of the histopathologic changes during long-term follow-up in patients with HC.Methods.A retrospective analysis of patients undergoing LT at our center between 1990 and 2016 identified 29 patients with HC. End points were the evaluation of post-LT iron reaccumulation and the stage of fibrosis as well as the degree of inflammation of the liver graft. Secondary end points were patient survival and postoperative complications.Results.The median age was 52.7 y, and there were more male (82.8%) than female patients (17.2%). Post-LT serum ferritin values (>1000 μg/L) were only temporarily elevated in 2 patients. The median estimated survival after LT was 45.5 mo (0.1–285.9 mo). Twenty patients (69%) died during follow-up of 10 y. The survival of patients with HC was significantly worse (P = 0.001) when compared with the overall cohort of patients undergoing LT because of to other causes.Conclusions.There was no significant iron overload detected in patients with HC after LT, and only minimal iron deposits were described in liver biopsies. Nevertheless, patients suffering from HC show a lower post-LT survival when compared with patients without iron storage disease but mostly because of extrahepatic causes.

Effect of Hepatitis C Virus Treatment on Rejection Incidence and Severity in Post-Liver Transplant Recipients

Abstract Background and Aims HCV is a worldwide cause of chronic liver disease, particularly in Egypt where the most prevalent is genotype 4. HCV-associated cirrhosis is the most common indication for orthotopic liver transplantation (OLT) among adults. HCV infection remains a problem after transplantation, and recurrent hepatic infection is the leading cause of graft failure. Little is known about the long-term effects of direct acting antiviral therapy in patients after liver transplantation. We examined the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with DAAs relative to the incidence and severity of liver transplantation rejection in patients treated for HCV, post liver transplantation, with Interferon based therapy and patients who didn’t receive any treatment for HCV after transplantation. Patients and Methods The study was conducted on 90 patients who had underwent liver transplantation between 2010 and 2017 at Ain Shams Center for Organ Transplantation (ASCOT) with a minimum follow up period of 6 months. Patients were divided into three groups: group I included 16 patients that didn’t receive antiviral treatment after liver transplantation, group II included 20 patients that had received interferon based therapy after liver transplantation and group III included 54 patients that had received direct acting antivirals after liver transplantation. Results Amongst group I, 2 patients (12.5%) developed acute graft rejection while in group II 2 patients (10%) developed chronic graft rejection and in group III 6 patients (11.11%) developed chronic rejection. In group I, all the patients (100%) had developed rejection that was diagnosed within one year of liver transplantation. In group II, 2 patients (100%) developed chronic graft rejection which occurred after one year of liver transplantation, one of them was on treatment with peg interferon and the other had already completed treatment. In group III, 2 patients (40%) had developed chronic rejection within one year of transplantation, while 4 patients (60%) had developed chronic rejection after one year of transplantation. One patient (16.67%) had developed rejection on treatment while 5 patients (83.33%) had developed rejection after the end of treatment. Conclusion It was found that the incidence of chronic rejection was more in patients that had received antiviral treatment after liver transplantation, however no difference was noted between DAAs and peg-interferon. Chronic rejection was found to be more common when treatment was given over one year after liver transplantation (6 cases) as compared to within the 1st year (2 cases). This may be related to the withdrawal of immunosuppression treatment after one year of transplantation and maintenance on monotherapy.

A study of critical care issues in pediatric liver transplantation

Objective: The objective is to study the intra- and postoperative cardiopulmonary complications, metabolic derangements, and mortality in the recipients of orthotopic liver transplantation (OLT). Materials and Methods: Medical records of all children who underwent OLT at our institution from January 2003 to December 2019 were reviewed, and the clinical and laboratory data were collected. Results: Eighty-two patients (48 males) underwent living-related OLT and one received cadaveric liver. The median age of recipients was 6 years (range: 4 months–16 years). The two common indications for OLT were biliary atresia (n = 27, 32.9%) and Wilson's disease (n = 20, 24.3%). Common metabolic problems during intraoperative phase included hypokalemia (43.9%) and hyperglycemia (57.3%). The mean duration of postoperative ventilation was 35.8 ± 51.4 h. Fifty-two patients were extubated within 24 h of surgery. Pleural effusion was most common present in 52 patients postoperatively. It did not interfere with mechanical ventilation. Hypertension, hypotension, and oliguria were recorded in 28, 31, and 22 patients, respectively. There were 11 graft rejection episodes. Ten children required re-operations. There were 4 (4.8%) early deaths, aged ≤1 year, in the first 2 weeks of transplantation. Conclusion: Medical and surgical complications are common in patients after liver transplantation. Intensive monitoring and laboratory workup help in detection of these complications. Early and 1-year survival rates are comparable to that in the developed world.

Molecular insights into the role of mitochondria in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of fatal liver diseases such as cirrhosis, liver cancer, and indications for orthotopic liver transplantation. Given its high prevalence, the absence of FDA-approved drugs for NAFLD is noticeable. In the pathogenesis of NAFLD, it is well known that mitochondrial dysfunction arises as a result of changes in ETC complexes and the membrane potential (Δψm), as well as decreased ATP synthesis. Due to their fundamental role in energy metabolism and cell death decision, alterations in mitochondria are considered to be critical factors causing NAFLD. Reduced levels of β-oxidation, along with increased lipogenesis, result in lipid accumulation in hepatocytes, and the subsequent production of reactive oxygen species and hepatocyte injury, which contribute to hepatic inflammation and fibrosis through the activations of Kupffer cells and hepatic stellate cells. Here, we review the latest findings describing the involvement of mitochondrial processes in the development of NAFLD and discuss the potential targets against which therapeutics for this disease can be developed.

Role of Transplant in Biliary Disease.

Orthotopic liver transplantation (OLT) has many roles in biliary disease. OLT provides excellent results for patients with unresectable hilar cholangiocarcinoma. OLT prolongs survival in primary biliary cirrhosis not responsive to therapy and improves quality of life. OLT remains the durable option for patients with primary sclerosing cholangitis and complications of end-stage liver disease or recurrent cholangitis secondary to biliary obstruction. Indications for OLT after bile duct injury are chronic liver disease secondary to biliary cirrhosis and acute liver failure from associated vascular injury. OLT is treatment of choice for Caroli disease and syndrome when fibrosis leads to portal hypertension and esophageal varices.

Increasing Incidence of Nonalcoholic Steatohepatitis as an Indication for Liver Transplantation in Australia and New Zealand.

The worldwide increase in obesity and diabetes has led to predictions that nonalcoholic steatohepatitis (NASH) will become the leading indication for orthotopic liver transplantation (OLT). Data supporting this prediction from outside the United States are limited. Thus, we aimed to determine trends in the frequency of NASH among adults listed and undergoing OLT in Australia and New Zealand (ANZ) from 1994 to 2017. Data from the ANZ Liver Transplant Registry were analyzed with patients listed for fulminant liver failure, retransplantation, or multivisceral transplants excluded. Nonparametric trend, Spearman rank correlation, and regression analysis were used to assess trends in etiologies of liver disease over time. Of 5016 patient wait-list registrants, a total of 3470 received an OLT. The percentage of patients with NASH activated for OLT increased significantly from 2.0% in 2003 to 10.9% in 2017 (trend analyses; P < 0.001). In 2017, NASH was the third leading cause of chronic liver disease (CLD) among wait-list registrants behind chronic hepatitis C virus (HCV; 29.5%) and alcohol (16.1%). Similarly, significant increases over time in the percentage of patients undergoing OLT were observed for HCV and NASH (all trend analyses; P < 0.001) but with significant reductions in primary sclerosing cholangitis and cryptogenic cirrhosis (both P < 0.05). By 2017, NASH was the third leading cause of liver disease among patients undergoing OLT (12.4%) and behind chronic HCV (30.2%) and alcohol (18.2%). NASH also became the third most frequent etiology of CLD in patients transplanted (13.8%) with concomitant hepatocellular carcinoma by 2017. In conclusion, NASH is increasing as a primary etiology of liver disease requiring listing and liver transplantation in ANZ.

Síndrome de superposición: hepatitis autoinmune y colangitis biliar primaria. Resultados a largo plazo de una cohorte retrospectiva en un hospital universitario

BackgroundAutoimmune hepatitis (AIH) with characteristics of primary biliary cholangitis (PBC) is known as overlap syndrome. Its prevalence and prognosis have not yet been determined comparatively with AIH. MethodsA retrospective cohort study was conducted comparing patients diagnosed with AIH and AIH-PBC overlap syndrome, followed-up for seven years in a university hospital in Colombia, until 31 December 2016. ResultsA total of 210 patients were included (195 women, mean age 48.5years). Of these, 32 (15.2%) had AIH-PBC overlap syndrome. At diagnosis, no significant differences were found by demographic profile, positive autoantibodies (ANA, ASMA), except AMA (81.2% vs 3.9%, P<.001), and histological grade of fibrosis. The most frequent clinical presentations were nonspecific symptoms in AIH-PBC and acute hepatitis in AIH. Although there were no significant differences, AIH showed a greater biochemical response to immunosuppressive management (87.3% vs 74.2%, P=.061) and a greater number of relapses in those who achieved partial or complete remission during treatment (12.4% vs 7.63%; P=.727). Patients with AIH-PBC had greater progression to cirrhosis (22.2% vs 13.1%, P=.038), even in those who achieved partial or complete biochemical remission without relapse, with greater indication of orthotopic liver transplantation (P=.009), but not retransplantation (P=.183); there were no differences in mortality. ConclusionsAIH-PBC overlap syndrome accounts for a significant proportion of patients with AIH, with greater progression to cirrhosis, indication of liver transplantation and possibly retransplantation. This higher risk of adverse outcomes suggests closer monitoring, probably with follow-up until confirmed histopathological remission.

PSC-IBD: specifický fenotyp idiopatického střevního zánětu asociovaný s primární sklerózující cholangitidou

Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary tree which represents one of the most frequent indications for orthotopic liver transplantation (OLTx) in developed countries. LTx is currently the only curative procedure for PSC. Concomitant inflammatory bowel disease (IBD) is present in approximately 70 % of patients with PSC. Such colitis in PSC has specific clinical and etiological features and is considered as a distinct phenotype of IBD often referred to as "PSC-IBD". The phenotype usually manifests as mild extensive colitis with right-sided predominance. Other morphological features, such as back- wash ileitis and rectal sparing, are also increasingly prevalent in PSC-IBD. Moreover, patients with PSC-IBD have increased risk towards developing colorectal neoplasia which tend to be highly progressive. Therefore, total colonoscopy employing multiple random biopsies or chromoendoscopy should be performed every 1-2 years once PSC-IBD is diagnosed. Even detection of low-grade dysplasia in colonic mucosa should lead towards prophylactic colectomy consideration in patients with PSC-IBD. Recommendations regarding pharmacological therapy are based on the similar principles as in Crohn´s disease and ulcerative colitis. However, status of the liver disease should always be taken into account. Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is a method of choice in the field of surgical therapy of PSC-IBD. The clinical course of PSC-IBD may deteriorate after OLTx despite immunosuppressive therapy administration. IBD can even develop de-novo after OLTx and may significantly influence the risk ratio for PSC recurrence in the liver graft. Key words: inflammatory bowel disease - primary sclerosing cholangitis - PSC-IBD.

Contemporary Policies Regarding Alcohol and Marijuana Use Among Liver Transplant Programs in the United States.

Alcoholic liver disease is a common indication for orthotopic liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period before OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in the United States. This survey of liver transplant programs was conducted to evaluate current policies regarding alcohol, marijuana and methadone use. A questionnaire was distributed to 100 United Network for Organ Sharing-approved liver transplant programs in North America that have performed at least 30 liver transplants/year in the last 5 years. Forty-nine programs responded. Only 43% of the programs required a specific period of abstinence before transplant for alcoholic liver disease and only 26% enforced 6-month abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors, such as family support, patient's motivation, or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of the programs. Policies regarding alcohol use have become more flexible particularly toward patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs.

The use of sofosbuvir for the treatment of recurrent hepatitis C after liver transplantation

The article presents the experience of direct-acting antiviral (DAA) drug treatment for hepatitis C in the patients after liver transplantation. The end-stage liver disease caused by hepatitis C is the main indication for orthotopic liver transplantation (OLT). In 2013, the first agent in the class of antiviral drugs directly acting on hepatitis C virus (HCV) was introduced into clinical practice. That was sofosbuvir, a HCV polymerase inhibitor, that could be used without interferon alfa. Materials and methods . The study enrolled 33 liver transplant recipients with recurrent hepatitis C. Thirty-five courses of antiviral therapy (AT) were conducted with sofosbuvir being one of AT components. Results. By the time of analysis, 21 patients had completed the antiviral therapy. All the patients showed an initial response to the antiviral therapy, HCV aviremia was achieved. In 3 patients, with the evaluable sustained virologic response (SVR), a renewed HCV replication was observed in the first weeks after the AT completion. Conclusion. The new direct-acting antiviral drugs offer an effective antiviral therapy to all liver graft recipients with recurrent HCV.

Bleeding and liver transplantation outcomes in haemophilia.

Hepatitis C is the major cause of end-stage liver disease and the major indication for orthotopic liver transplantation (OLTx) in individuals with haemophilia. To assess the epidemiology and outcomes of OLTx in U.S. haemophilia patients. We investigated haemophilia liver transplant recipients between 1993 and 2012, using the Nationwide Inpatient Sample, identified by ICD9 code 50.59. Of the 11 267 (weighted n = 54 691) patients undergoing OLTx, 44 (0.4%; weighted n = 213) had haemophilia. Those with haemophilia were more likely than non-haemophilic OLTx recipients to have bleeding complications (45.3% vs. 31.5%, P = 0.009) and hypovolemic shock (7.0% vs. 1.1%, P < 0.0001). They also had a significantly higher incidence of HIV (24.8% vs. 0.5%, P < 0.005), hepatitis B (16.2% vs. 7.9%, P = 0.04) and vitamin K deficiency (2.1% vs. 0.02%, P < 0.001). In spite of these differences, there was no difference in in-hospital mortality between haemophilic and non-haemophilic recipients (6.8% vs. 6.2%, P = 0.9). In multivariate logistic regression, bleeding complications in haemophilia increased the risk of in-hospital mortality by more than 3-fold (P < 0.0001), and disseminated intravascular coagulation increased the risk of bleeding complications in haemophilic recipients by over 10-fold (P < 0.0001). Bleeding complications are common in haemophilia OLTx recipients. Thus, aggressive correction of coagulation defects in this group may be a medically sound approach to reduce complications and mortality associated with OLTx.

Long-Term Outcomes of Liver Transplantation for Hepatic Sarcoidosis: A Single Center Experience

Hepatic sarcoidosis is a rare indication for orthotopic liver transplantation (OLT). Hence, studies evaluating these patients are scarce. We present a single center experience with OLT for hepatic sarcoidosis in a case-control study. A retrospective chart review was performed on 970 patients with OLT at our center, and 13 patients (1.3%) were identified who underwent 14 OLTs for hepatic sarcoidosis. For each case, two controls matched for etiology of liver disease, recipient age (±5 years), and duration since transplant (within 5 years) were selected. For the 13 patients transplanted for sarcoidosis, the median age was 46 years. The majority were women (62%) and African-American (85%). Cholestatic liver disease was the primary manifestation. Portal hypertensive complications were present in 11 patients (84%). The median MELD score at transplantation was 19. Extra-hepatic manifestations were present in ten patients (77%). All patients received whole deceased 14 donor allografts. Six patients remain alive with a median post-OLT follow-up of 8.4 years. The 1-, 3-, 5-, and 10-year patient survival rates were 84.6%, 76.9%, 61.1%, and 51.3%, respectively for the sarcoidosis group and 82.1%, 78.6%, 78.6%, and 61.9%, respectively for the matched PSC/PBC group (P=0.739). Re-graft free survival for sarcoidosis patients was 84.6%, 76.9%, 61.5%, and 51.3% for 1-, 3-, 5-, and 10-years and for the matched control group re-graft free survival was 78.6% at 1-, 3-, 5-years, and 64.8% at 10-years (P=0.661). Recurrence of hepatic sarcoidosis was found in 4 patients at 11 days, 112 days, 222 days, and 6.6 years. Our study depicts the long-term benefit of liver transplantation in patients with end stage liver disease secondary to sarcoidosis. It shows statistically comparable graft and patient survival for such patients when compared to other cholestatic diseases. Disease recurrence, although possible, has not been shown to cause allograft dysfunction.

Management of hepatitis c genotype 4 in the liver transplant setting.

End-stage liver disease secondary to hepatitis C virus (HCV) infection is the major indication for orthotopic liver transplantation (OLT) worldwide. The percentage of HCV patients infected with genotype 4 (G4) among recipients of OLT varies depending on geographic location. In the Middle East, including Saudi Arabia, G4 infection is the most common genotype among transplant recipients. Due to the low prevalence of HCV-G4 in Europe and the United States, this genotype has not been adequately studied in prospective trials evaluating treatment outcomes and remains the least studied variant. The aim of this review is to summarize the natural history and treatment outcome of HCV-G4 following liver transplantation, with particular attention to new HCV therapies. This review incorporates all published studies and abstracts including HCV-G4 patients.

Molecular Mechanisms to Control Post-Transplantation Hepatitis B Recurrence.

Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed.