Histopathology of Post-Transplant Liver Biopsies,the First Report From Iran

Background

Evaluation of a transplanted liver by Imaging techniques and enzyme changes is sensitive to hepatocellular or biliary problems, but in most instances liver allograft biopsies are performed in order to find out the final reason for these changes.

Objectives

It’s been about 17 years (with more than 1326 cases) since the first liver transplantation in the Namazi Hospital of Shiraz University of Medical Sciences while during the last five years the number of post liver transplant biopsies have increased. Until now there has been no report of the pathological results of post liver transplant needle biopsies from Iran.

Materials and Methods

During the last 5 years, there have been 382 post liver transplant biopsies. We studied the clinical charts and pathological results of all needle biopsies.

Results

A total of 382 needle biopsies were performed on 287 patients aged between 1 and 64 years old. The earliest specimen was obtained within the first few hours following transplantation, and the last was gathered 3209 days (261 ± 523) post-transplantation. Acute rejection was the most common diagnosis, which occurred in 180 (47%) of specimens. Among other complications were vascular problems (8.6%), preservation/reperfusion (I/R) injury (7%), chronic rejection (5.2%), biliary injury/obstruction (3.4%), recurrence of primary disease (2.6%), drug-induced hepatic injury (1.8%), cirrhosis (1.6%), sepsis (1.4%), cytomegalovirus hepatitis (1.4%), post-transplantation lymphoproliferative disease (1%) and Venous outflow obstruction (0.5%).

Conclusions

The most common pathological diagnosis of post-transplant liver needle biopsies has been acute rejection, followed by ischemia due to hepatic artery thrombosis, preservation/reperfusion injury, and chronic rejection.     

Management of Hepatitis B Virus Infection in Liver Transplantation Setting; The Rising Concerns and Growing Hopes,Report From 10th Congress of the Iranian Society for Organ Transplantation, 2011, Shiraz,Iran

Hepatitis B infection is the main cause of liver related mortality in many countries including Iran. Liver transplantation in cirrhosis due to HBV infection before 1990 was an absolute contraindication. Recurrent infection was a significant event in post liver transplant setting and resulted in increased risk of graft failure and death except successful transplanted individuals. Advances in antiviral prophylaxis have now made graft reinfection majority patients as a rare event. Graft and patient survival have been improved significantly during the past two decades, and consequences of transplantation for hepatitis B virus are now superior to those achieved for most other indications. This has encouraged many centers including the major liver transplantation center of Iran, in Shiraz, to provide liver transplantation to more patients with HBV related end stage liver disease. Management of these patients begins before transplantation along with special care after transplantation. There are some myths and doubts in the management of these patients and one should always balance the cost and efficiency. One of the major concerns is the high economic and social cost of recurrence and all possible efforts should be performed to avoid the ominous consequences of reinfection. Having a clear scientific grasp on the management of HBV cirrhosis before and after liver transplantation, options and protocols, and changing the concept which HBV infected are contraindicated ones for liver transplantation, and future hopes in increasing patients survival after liver transplantation using the new nucleosides analogues and availability of hepatitis B immunoglobulin in the transplantation setting. This scientific report paper outlines the insights communicated at the HBV and liver transplantation symposium during 10th Congress of the Iranian Society for Organ Transplantation, May 2011, Shiraz, Iran.     

Cholangiocarcinoma Secondary to Primary Sclerosing Cholangitis in Explanted Livers: A Single-Center Study in the South of Iran

Background:

Primary sclerosing cholangitis (PSC) is a chronic disease, characterized by chronic inflammation and fibrosis of bile duct epithelial cells. This is a significant contributory factor to the development of malignancy, most commonly cholangiocarcinoma (CCA), which is the second most common malignant liver tumor.

Objectives:

For the first time in Iran, we intend to describe our experience with cases of PSC, with and without CCA, in explanted livers, and compare our results with those found in other areas of the world.

Patients and Methods:

The study population comprised 181 individuals with a diagnosis of PSC who had undergone liver transplantation in the main liver transplant center of Iran, the largest center of hepatobiliary surgery in the south of that country, over a 3-year period between 2012 and 2014. All explanted livers, with and without CCA, were evaluated.

Results:

Of the 181 patients, 16 were found to have CCA, two of whom had been diagnosed after pathologic study of the explanted livers. Therefore it appeared that 8.8% of the patients with PSC in our center had developed CCA before liver transplantation.

Conclusions:

A comparison of our results with those obtained from other centers in both Western and Asian countries (which reported CCA in 3.6% - 36.5% of patients with PSC), shows that the incidence of CCA in the patients we studied is intermediate.     

Hepatocyte transplantation: State of the art

Advances in biotechnology have allowed hepatocyte transplantation as a relevant proposition to treat liver disease. This procedure may change the crescent mortality in liver transplantation waiting lists due global organ shortage. Recent clinical trials have described promising results of hepatocyte transplantation for acute, acute-on-chronic and metabolic liver disease. In this report, we discuss progresses regarding hepatocyte culture, cryopreservation systems, hepatocyte immortalization, suitable recipient site for hepatocyte engraftment, cell differentiation and fusion into hepatocytes, current clinical trials, and summarize the bioartificial liver systems. These progressions motivate expectation concerning hepatocyte transplantation as a consistent therapy for liver disease.     

Prevalence and Risk Factors for Obesity After Liver Transplantation: A Single-Center Experience

Background

The study of weight gain after transplantation and its associated factors is necessary to propose strategies to prevent and treat this problem.

Objectives

This study aims to investigate factors affecting the development of obesity after liver transplantation (LTx).

Patients and Methods

Medical records of 343 liver transplantation cases, which were followed between January 2001 and January 2010 at Dokuz Eylul University, were retrospectively analyzed. Patient pre-liver transplantation height, body weight, body mass index (BMI) measurements, as well as changes in body weight at the beginning, 6 months, 12 months, and 5 years post-transplantation were observed. BMI measurements with records of immunosuppressive therapies were obtained.

Results

The study was carried out with the records of 226 patients. 151 patients (66.8%) were male; 75 (33.2%) were female. The mean age was 46.19 ± 10.2 years. 123 of these liver transplants were performed from living donors, while 103 were from cadaveric donors. The causes of liver transplantation were hepatitis D virus (HDV) infection (28%), hepatitis B virus (HBV) infection (24%), hepatitis C virus (HCV) infection (24%), alcoholic liver disease (9%), cryptogenic liver disease (9%), autoimmune hepatitis (4%), and other (2%). In this study, the prevalence of obesity was 21% at the end of the second year, decreasing to 14% by the end of the fifth year. The mean BMI gradually increased during the follow-ups, reaching 25.1 kg/m² and 26 kg/m² six months after liver transplantation and at the end of the first year, respectively (P < 0.002). Obesity developed in 18.2% of post-transplant patients who were receiving a calcineurin inhibitor (CNI). Regarding the development of obesity after transplantation, no statistically significant difference was found between patients using cyclosporine (CsA) and tacrolimus (TAC) (P = 0.07). Six months after liver transplantation, the mean body weight gain in the groups receiving steroids and not receiving steroids were 4.71 kg and 2.7 kg, respectively (P = 0.03). In the post-transplant period, there was no significant difference in patients who had received TAC and CsA for development of diabetes mellitus (DM), hypertension (HT), or hyperlipidemia (HL) (P = 0.30).

Conclusions

Obesity prevalence before and after liver transplantation was comparable. Education of obese patients prior to surgery and recommendation of medical nutrition therapy should be appropriate. Similar medical care for the non-obese subjects could prevent increase in obesity prevalence. Non-corticosteroid immunosuppressive agents had no significant effect on the development of weight gain and obesity. Avoiding the use of long-term steroid therapy and obesity education are the key measures for preventing obesity after liver transplantation.     

Risk Factors for Portal Vein Thrombosis in Patients With Cirrhosis Awaiting Liver Transplantation in Shiraz,Iran

Background:

Portal vein thrombosis is a fairly common and potentially life-threatening complication in patients with liver cirrhosis. The risk factors for portal vein thrombosis in these patients are still not fully understood.

Objectives:

This study aimed to investigate the associations between various risk factors in cirrhotic patients and the development of portal vein thrombosis.

Patients and Methods:

In this case-control study performed at the Shiraz organ transplantation center, Iran, we studied 219 patients (> 18 years old) with liver cirrhosis, who were awaiting liver transplants in our unit, from November 2010 to May 2011. The patients were evaluated by history, physical examination, and laboratory tests, including factor V Leiden, prothrombin gene mutation, Janus Kinase 2 (JAK2) mutation, and serum levels of protein C, protein S, antithrombin III, homocysteine, factor VIII, and anticardiolipin antibodies.

Results:

There was no statistically significant difference in the assessed hypercoagulable states between patients with or without portal vein thrombosis. A history of previous variceal bleeding with subsequent endoscopic treatment in patients with portal vein thrombosis was significantly higher than in those without it (P = 0.013, OR: 2.526, 95% CI: 1.200 - 5.317).

Conclusions:

In our population of cirrhotic patients, treatment of variceal bleeding predisposed the patients to portal vein thrombosis, but hypercoagulable disorders by themselves were not associated with portal vein thrombosis.     

Hyponatremia as the Initial Presentation of Cryptococcal Meningitis After Liver Transplantation

Introduction:

Meningoencephalitis is the most common clinical manifestation of cryptococcal infection, as the organism has a propensity to invade the CNS. Patients often present with elevated intracranial pressure, focal motor deficits, altered mentation and internal hydrocephalus. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been reported as a notable cause of euvolemic hyponatremia in immunocompromised patients.

Case Presentation:

A 67-year-old male with liver transplantation due to hepatitis C (HCV) related liver cirrhosis developed severe hyponatremia four months after liver transplantation, which was discovered during routine clinic visit. Patient was referred to the emergency department, treated and discharged with normal serum sodium level. Few days later, he presented with dizziness, confusion, ataxia, abnormal muscle movements and leg pain. Laboratory investigations were consistent with SIADH and revealed a sodium level of 115 mmol/L. Brain MRI showed a leptomeningeal enhancement in the superior cerebellar sulci suspicious for infection. Lumbar puncture was performed and consistent with Cryptococcus neoformans infection; therefore, cryptococcal meningitis was diagnosed. Amphotericin B was started for the patient for six weeks followed by fluconazole for one year. His level of consciousness improved significantly, and his serum sodium level slowly returned to its normal baseline over three weeks after starting amphotericin B.

Conclusions:

Symptomatic hyponatremia secondary to SIADH remains a rare complication of cryptococcal meningitis.     

Organ Allocation for Liver Transplantation According to the Public Opinion

Background

Although liver transplantation is the last resort for treating end stage liver diseases, this medical procedure is not available for all needful patients because of inadequate organ supply. Therefore, guidelines have been developed by medical experts to regulate the process. Some professionals believe that medical criteria are inadequate for organ allocation in all situations and may not secure fairness of organ allocation.

Objectives

The current study has been designed to identify decision criteria about allocation of donated liver to potential recipients from public points of view.

Patients and Methods

This is a qualitative study that was conducted through individual interviews and Focus Group Discussions. Individual interviews were conducted among patients’ companions and nurses in one of the two liver transplant centers in Iran. Group discussions were conducted among groups of ordinary people who had not dealt previously with the subject. Data was analyzed by Thematic Analysis method.

Results

Most of the participants in this study believe that in equal medical conditions, some individual and societal criteria could be used to prioritize patients for receiving donated livers. The criteria include psychological acceptance, ability to pay post-operative care costs, being breadwinner of the family, family support, being socially valued, ability to be instructed, lack of mental disorders, young age of the recipient, being on waiting list for a long time, lack of patient’s role in causing the illness, first time transplant recipient, critical medical condition, high success rate of transplantation, lack of concurrent medical illnesses, not being an inmate at the time of receiving transplant, and bearing Iranian nationality.

Conclusions

Taking public opinion into consideration may smooth the process of organ allocation to needful patients with equal medical conditions. It seems that considering these viewpoints in drafting organ allocation guidelines may increase confidence of the society to the equity of organ allocation in the country. This strategy may also persuade people to donate organs particularly after death.     

Opinion Toward Living Liver Donation of Hospital Personnel From Units Related to Organ Donation and Transplantation: A Multicenter Study From Spain and Latin-America

Background:

Hospital personnel of services related to donation and transplantation process play a fundamental role in the development of transplantation.

Objectives:

The aim of this study was to investigate the attitude toward living liver donation (LLD) among hospital personnel from services related to donation and transplantation in hospital centers in Spain and Latin America.

Materials and Methods:

Eight hospitals within the “International Donor Collaborative Project” were selected, three in Spain, three in Mexico and two in Cuba. The study was performed in transplant-related services, using a randomized sample, which was stratified by the type of service and job category.

Results:

In total, 878 workers were surveyed of which 82% (n = 720) were in favor of related LLD, 10% (n = 90) were against and 8% (n = 68) undecided. Attitudes toward related LLD were more favorable in the following groups: the Latin Americans (86% in favor vs. 77% among the Spanish; P = 0.007); younger people (37 vs. 40 years, P = 0.002); those in favor of either deceased donation (P < 0.001) or living kidney donation (P < 0.001); those who believed that they might need a transplant in the future (P < 0.001); those who would accept a liver from a living donor (P < 0.001); those who discussed the subject of donation and transplantation with their families (P = 0.040); and those whose partner was in favor of donation and transplantation (P = 0.044).

Conclusions:

Personnel from donation and transplantation-related units had a favorable attitude toward LLD. This attitude was not affected by psychosocial factors, although it was influenced by factors directly and indirectly related to the donation and transplantation process.     

Liver Transplantation in the MELD Era: A Single-Center Experience

Model for Endstage Liver Disease (MELD) score has been used to allocate organs since February 2002. This policy allocates organs to candidates with regard to severity of their underlying liver disease except in the case of hepatocellular carcinoma (HCC) patients. The purpose of this study was to determine the impact of MELD on waiting times, dropout rates, and transplantation rates in all patients awaiting liver transplantation at our center. The records of all patients listed for liver transplantation between May 28, 1999, and February 27, 2004, at the Mayo Clinic, Scottsdale, Arizona, were reviewed. Candidates were grouped by two time periods as pre-MELD or post-MELD based on date of MELD implementation (February 27, 2002). The incidence of deceased donor liver transplantation (DDLT), waiting time to DDLT, dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting for or after DDLT were determined for each group. Three hundred fifty-one patients were listed for liver transplantation (195 pre-MELD, 156 post-MELD) during the study period. HCC patients had an improved rate of transplantation after MELD (pre-MELD, 1.39 persons per year; post-MELD, 3.48 persons per year). In all groups, with the exception of hepatitis C virus, the transplantation rates were the same for both categories. The hepatitis C virus group also had improved transplantation rates in the post-MELD period. HCC candidates under the new allocation policy have an increased incidence of DDLT in our institution. However, this has not disadvantaged patients with non-HCC diagnoses. Thus, the new MELD-based allocation policy has benefited all candidates by allowing more timely transplants.     

Liver Transplantation for Alcoholic Liver Disease: Survival of Patients Transplanted with Alcoholic Hepatitis Plus Cirrhosis as Compared with Those with Cirrhosis Alone

From January 1986 through December 1991, a total of 221 patients with alcoholic liver disease received liver transplantation. In 147 of these cases, complete pretransplant histopathologic, demographic, and laboratory data (minimum of CBC, AST, ALT, total bilirubin, albumin, and prothrombin time) were available for review. Forty-five (30%) of the 147 recipients had alcoholic hepatitis plus cirrhosis (AH), whereas 70% had cirrhosis (CIRR) alone. Age and sex were similar in the subgroups, but the patients with CIRR had a greater AST/ALT ratio, longer protime, and lower platelet count (all p < 0.01). Coexistent hepatitis B (4.7%) or hepatitis C (4.1%) was similar in both groups. Current survival is 80% for patients with AH and 84% for those with CIRR (NS). Overall, survivors were younger (43.4 ±1.7 years) than nonsurvivors (53.6 ± 3.2) (p < 0.01), an age influence that was significant in the CIRR group (p <; 0.01) but not in the AH group. Inexplicably, the AST/ALT ratio was greater in AH survivors (1.5 ± 0.2) than it was in nonsurvivors (0.4 ± 0.1) (p < 0.01). In patients with CIRR, the platelet count was greater in survivors (252 ± 29 vs. 86 + 11 ± 10⁹ cells/liter).
The data support the clinical impression that patients with chronic decompensated cirrhosis referred for liver transplantation had more severe complications of their liver disease than did those with AH. Survival in both subgroups was similar, but overall the survivors are nearly a decade younger than the nonsurvivors. Because the diagnosis of AH implies a briefer period of alcohol abstention, it was interesting to note that liver transplantation could be accomplished as successfully with AH as with CIRR.     

Liver transplantation in Japan: Registry by the Japanese Liver Transplantation Society

As of 31 December 2017, a total of 9242 liver transplants have been carried out in 67 institutions in Japan. There were 447 deceased donor transplants (444 from heart‐beating donors and 3 from non‐heart‐beating donors) and 8795 living‐donor transplants. The annual total of liver transplants in 2017 was 416 (69 deceased donor transplants and 347 living‐donor transplants). The most frequent indication was cholestatic disease, followed by neoplastic disease and hepatocellular disease. In terms of hepatocellular disease in 2017, cirrhosis due to hepatitis C and B decreased (13 and 8, respectively), whereas alcoholic cirrhosis markedly increased (32). Patient survival following transplantation from heart‐beating donor (444 transplants: 1 year, 89.1%; 3 years, 85.2%; 5 years, 82.9%; 10 years, 75.4%; 15 years, 70.7%) was similar to that from living‐donor (8794 transplants: 1 year, 85.0%; 3 years, 80.9%; 5 years, 78.5%; 10 years, 73.2%; 15 years, 68.5%; 20 years, 65.7%; 25 years, 64.6%). Graft survival was very much the same as patient survival (heart‐beating donor: 1 year, 88.4%; 3 years, 84.5%; 5 years, 82.2%; 10 years, 74.7%; 15 years, 70.1%; living donor: 1 year, 84.3%; 3 years, 79.9%; 5 years, 77.3%; 10 years, 71.4%; 15 years, 66.3%; 20 years, 63.3%; 25 years, 61.9%). Survival data are reported according to age and sex of recipient, indication, age and sex of donor, ABO compatibility, and other factors.     

Percutaneous Left Atrial Appendage Closure With the Ultraseal Device: Insights From the Initial Multicenter Experience

Objectives

This study sought to evaluate the feasibility, safety, and efficacy of the Ultraseal device for left atrial appendage closure (LAAC) (Cardia, Eagan, Minnesota) in patients with nonvalvular atrial fibrillation at high bleeding risk.

Epidemiology,Risk Factors,and Outcome of Bloodstream Infection Within the First Year After Kidney Transplantation

BackgroundMulti-drug resistant organisms have been emerging among kidney transplant (KT) recipients with bloodstream infections (BSI). The investigation for epidemiology, risk factors and outcome of these infections following KT was initiated.Materials and MethodsA retrospective study of all adult KT recipients who developed a BSI within the first year after KT in 2016 at a single transplant center was conducted. The cumulative incidence of BSI was estimated with Kaplan-Meier methodology. Clinical characteristics and outcome were extracted. Risk factors were analyzed with Cox proportional hazards models.ResultsAmong 171 KT recipients, there were 26 (15.2%) episodes of BSI. Fifty-nine percent were men and the mean ± SD age was 43 ± 12 years. The cumulative incidence of BSIs was 10.1% at 1 month, 13.5% at 6 months, and 15.2% at 12 months. Gram-negative bacteria were responsible for 92% of BSIs, Escherichia coli was the most common pathogen (65%) followed by Klebsiella pneumoniae (11%). Among those, 71% were resistant to extended-spectrum cephalosporins. The genitourinary tracts were the predominant source of BSIs (85%). The second kidney transplantation (HR, 4.55; 95% CI, 1.24–16.79 [P = 0.02]) and receiving induction therapy (HR, 3.05; 95% CI, 1.15‐8.10 [P < 0.03]) were associated with BSI in a multivariate analysis. One patient (4%) developed allograft rejection, allograft failure and death from septic shock.ConclusionsOne out of six KT recipients could develop BSI from gram-negative bacteria within the first year after transplant, particularly in those that received the second transplantation or induction therapy.     

Clinical Features,Image Findings,and Prognosis of Inflammatory Pseudotumor of the Liver: A Multicenter Experience of 45 Cases

Background/Aims

Inflammatory pseudotumor (IPT) of the liver is a rare disease characterized by chronic infiltration of inflammatory cells. However, the clinical characteristics and outcomes of IPT remain uncertain.

Methods

Clinical features, image findings, and outcomes of 55 patients with histologically proven IPT were evaluated.

Results

They consisted of 26 men and 19 women with median age of 65 years. Serum carcinoembryonal antigen and carbohydrate antigen 19-9 levels were normal in 42 patients (93.3%). Enhanced CT scans indicated poorly defined peripheral enhancement (82.5%) at the arterial phase and poorly defined hyperattenuating lesions with internal hypoattenuating areas at the equilibrium phase (77.0%). Gadolinium-enhancement MRI revealed poorly defined peripheral rim-like enhancement (77.8%). Ten patients underwent surgical resection and 35 were treated conservatively with or without antibiotics. No recurrence was noted after surgical resection during follow-up (1 to 48 months). In all patients who received conservative treatment, complete resolution or size reduction was noted during follow-up (1 to 192 months).

Conclusions

CT and MRI provide clues to the diagnosis of IPT in patients with liver masses and normal tumor markers. However, due to the lack of pathognomonic findings, the clinician''s suspicion and histological diagnosis are necessary to make an accurate diagnosis of IPT.