Liver transplantation in glycogen storage disease: a single-center experience.

BACKGROUND: Glycogen storage diseases (GSDs) are inherited glycogen metabolic disorders which have various subtypes. GSDs of type I, III, IV, VI, and IX show liver involvement and are considered as hepatic types of GSDs. Thus, liver transplantation (LT) has been proposed as a final therapy for these types of GSD. LT corrects the primary hepatic enzyme defect; however, the long-term outcomes of LT in these patients have not been extensively evaluated so far. There are few reports in the English literature about the outcome of GSD patients after LT. There has been no report from Iran. The present retrospective study aimed to evaluate the long-term outcomes of eight patients with GSD types I, III, and IV who underwent LT in the affiliated hospitals of Shiraz University of Medical Sciences, from March 2013 to June 2021. During this period, there were no patients with GSD VI and IX identified in this center. RESULTS: The median time of diagnosis of the GSDs and at transplant was 1 year and 11 years, respectively. All eight transplanted patients were alive at the time of follow-up in this study. None of them required a re-transplant. All of the patients showed normalized liver enzymes after LT with no sign of hypoglycemia. CONCLUSIONS: LT is an achievable treatment for end-stage hepatic involvement of GSDs with a cure for metabolic deficiency. Our experience in these eight patients shows a favorable outcome with no mortality and no major complication.

Diagnosis of Latent Tuberculosis in Liver Transplant Candidates, a Single Center Experience.

BACKGROUND: Tuberculosis is an important cause of mortality and morbidity in liver transplant patients, so it is valuable to diagnose latent tuberculosis in liver transplant candidates by an accurate screening test prior to transplantation. Tuberculin skin test (TST) is the standard test for the diagnosis of latent tuberculosis. Currently interferon-gamma release assays (QuantiFERON-TB Gold (QFT)) have been proposed as the best screening test, especially in the geographic areas with widespread BCG vaccination. In this research, we will compare these two tests in the largest liver transplant center in the south of Iran. METHODS: Both TST and QFT were performed in 50 liver transplant patients and 50 normal healthy individuals. RESULTS: TST was positive in 6 cases and 4 controls. QFT was positive in 5 cases and 9 controls. Sensitivity and negative predictive value were higher in QFT but the specificity and positive predictive value were higher in TST. CONCLUSIONS: There is no significant difference between QFT and TST in evaluation of latent tuberculosis in liver transplant patients, however TST is less expensive and more feasible in Iran.

Biliary Intraepithelial Neoplasia in Non-biliary Cirrhosis-Report From 100 Explanted Livers: A Single Center Experience.

BACKGROUND: Intrahepatic cholangiocarcinoma is a highly malignant tumor with a very short 5-year survival. Multistep carcinogenesis has been suggested as the main pathway for the development of this tumor. Main suggested precursors have been (1) biliary intraepithelial neoplasia (BilIN) and (2) intraductal papillary neoplasm of bile duct (IPNB). The former is flat and does not produce grossly and radiologically detectable mass lesion, but the latter produces grossly identifiable lesion. OBJECTIVES: The development of bile duct dysplasia (BilIN) in chronic biliary diseases has been investigated and proved, but the incidence of BilIN in non-biliary causes of cirrhosis such as hepatitis B and non-alcoholic steatohepatitis has very rarely been investigated. In this study, we have tried to find out the prevalence of BilIN in non-biliary cirrhosis. PATIENTS AND METHODS: During the study period (2017-2018) in 100 explanted livers with the diagnosis of non-biliary cirrhosis, thorough sampling (at least 20 sections) was performed, and pathologic sections were studied for the presence of BilIN. RESULTS: In the 100 studied livers with different diagnoses of non-biliary causes of cirrhosis, 31% of cases showed BilIN-1 and 2% of cases showed BiliIN-2. No case of BilIN-3 has been identified. DISCUSSION AND CONCLUSIONS: Non-biliary causes of cirrhosis should be considered as precursors of cholangiocarcinoma (BilIN); however, the incidence of this occurrence is low.

Biliary Intraepithelial Neoplasia (BilIN) in Primary Sclerosing Cholangitis: The First Report from Iran.

BACKGROUND: Primary sclerosing cholangitis (PSC) as one of the most common chronic cholestatic liver diseases is a main predisposing factor for the development of cholangiocarcinoma (CCA). Biliary intraepithelial neoplasia (BilIN) is defined as precancerous bile duct epithelial changes, which can be eventually led to cholangiocarcinoma. There are very few studies about the frequency of BilIN in the patients with PSC and its correlation with paraclinical findings. OBJECTIVES: In this study, we tried to find the frequency of BilIN in the patients with PSC and correlate its presence with clinicopathologic factors. METHODS: During two years (2014 - 15) of investigation, 80 explanted livers with the confirmed diagnosis of PSC were studied through precise inspection and thorough sectioning of the explanted livers. These findings were correlated with paraclinical findings to identify any predictor of these neoplastic epithelial changes. RESULTS: During the study period of 2 years, among 80 livers with confirmed diagnosis of PSC, there were 43 cases with different types of metaplasia. The frequency of epithelial changes was as below: 29 (35%) for pyloric metaplasia, 9 (10.8%) for mucinous metaplasia, 3 (3.6%) for intestinal metaplasia, 1 (1.2%) for osteoid metaplasia, and 1 (1.2%) for squamous metaplasia. There was no epithelial dysplasia in the study sample; however, according to the most recent reports, mucinous metaplasia is considered as BilIN 1; therefore, there would be 9 cases of BilIN I. There has been no statistically significant difference between PSC cases and those with BilIN in demographic variables, except for bilirubin and CA19-9 which were higher in the PSC cases with BilIN. CONCLUSIONS: This study showed that the frequency of BilIN was low among Iranian patients with PSC. High bilirubin and CA19-9 can be predictors of the development of bile duct epithelial changes in patients with PSC.

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.

Liver Transplant for Children With Hepatocellular Carcinoma and Hereditary Tyrosinemia Type 1.

OBJECTIVES: This study sought to determine the prevalence of hepatocellular carcinoma and other premalignant lesions in children with hereditary tyrosinemia type 1 who had undergone an orthotopic liver transplant at the Shiraz Transplant Center, in Shiraz, Iran. MATERIALS AND METHODS: Between September 2006, and June 2011, thirty-six patients with hereditary tyrosinemia type 1 received a liver transplant from a deceased (whole or split) or a living-related donor. Clinical records and pathologic specimens, before and after surgery, for each case were reviewed. In addition, ultrasound, abdominal computed tomographic imaging scan findings, and levels of alpha-fetoprotein were recorded. RESULTS: Twenty-two patients with hepatic nodules larger than 10 mm underwent a Tru-Cut needle biopsy before their liver transplant. In 2 patients, a diagnosis of hepatocellular carcinoma was made by pathologic examination; in the other 20, cirrhosis was confirmed with no evidence of malignancy. After pathologic examination of the explanted livers, the largest nodules in the 36 patients were 35 mm. Five cases had at least 1 nodule of hepatocellular carcinoma. Three of the other patients had small cell dysplasia in some of nodules. All 5 cases with hepatocellular carcinoma were patients older than 2 years of age (19 patients were older than 2 years of age). All patients with hepatocellular carcinoma received pretransplant nitisinone treatment. All patients with hepatocellular carcinoma after their liver transplant are alive at the time of this writing. CONCLUSIONS: The prevalence of cell dysplasia and hepatocellular carcinoma in children with hereditary tyrosinemia type 1 in our study is not as high as that reported previously, so it appears that patients older than 2 years of age require a liver transplant.

HLA-G polymorphism (rs16375) and acute rejection in liver transplant recipients.

BACKGROUND: HLA-G molecules exhibit immunomodulatory properties that can delay graft rejection. The 14 bp insertion/deletion polymorphism (INDEL) (rs16375) influences the stability of final HLA-G mRNA and its soluble isoforms. OBJECTIVE: The present study aimed to investigate the possible association between this polymorphism and the incidence of acute rejection in Iranian liver transplant recipients. METHODS: Different genotypes were evaluated by PCR. The patients who had acute rejection within 6 months after transplantation were classified as acute rejection (AR) group, while others were considered as nonacute rejection (NAR) group. RESULTS: Among the recipients, 21 patients (21%) had at least one episode of AR, while the other 79 patients (79%) had normal liver function. No significant differences were found between the two groups regarding sex, MELD score, and primary liver disease. Also, no difference was observed concerning rs16375 genotype and allele frequency (P = 0.44, OR: 0.69; CI: 0.21-2.10). CONCLUSION: The study results revealed no significant difference between the AR and the NAR groups regarding the 14 bp INDEL genotypes and alleles. Further studies are recommended to be conducted on other polymorphic sites as well as monitoring of serum HLA-G concentration in order to ascertain the potential implications of this marker in our population.

Hepatocellular carcinoma in explanted livers of patients with genotype d HBV cirrhosis: report of the first experience from Iran.

BACKGROUND: This study was conducted to determine the impact of hepatitis B virus (HBV) as a cause of hepatocellular carcinoma (HCC) in a single liver transplant center in Iran.  METHODS: We included all hepatectomy specimens from patients with HBV-related cirrhosis who underwent transplants from May 1993 until January 2012 in this study. From these, we determined the number that had HBV-induced HCC. Nested PCR results were used to determine the HBV genotype from sections of the hepatectomy pathology specimens. RESULTS: During this time period there were 1361 cirrhotic livers transplanted in our center. Of these, 249 were attributed to HBV cirrhosis. Overall, HCC was detected in 40 (2.9%) subjects, of which 29 (1.2%) had HBV-related HCC.  Genotype D was only genotype observed in all HBV subjects.  CONCLUSIONS: The results revealed that although HBV-related cirrhosis was the most frequent single cause for liver transplant, the frequency of HBV-induced HCC was very low among transplant recipients. Out of 1361 transplant recipients, only 29 (2.1%) were diagnosed with HBV-related HCC. All HBV subjects had genotype D.

Frequency of HLA-G exon 8 polymorphisms and kidney allograft outcome in Iranian population.

The 14-bp polymorphism in exon 8 of the HLA-G gene is associated with HLA-G mRNA stability and the patterns of alternative isoform splicing and may influence the functionality of the HLA-G molecule. HLA-G expression was related to allograft acceptance and fewer episodes of acute rejection during heart, kidney and liver-kidney transplantation. In order to determine a possible correlation between the 14-bp insertion/deletion polymorphism and kidney allograft outcome in our population, genomic DNA was isolated from 144 patients who had received isolated kidney allografts. The recipients was divided into two groups, grafts presenting features of rejection group and a non-rejection group, and compared them with a control group of 100 healthy subjects. There was no significant difference in allelic frequencies of 14-bp insertion/deletion polymorphism between normal controls and kidney transplant patients. No significant difference was found between the RG and the NRG regarding the 14-bp genotypes and alleles. Therefore, additional studies with more sample size from other populations with analysis of other HLA-G polymorphisms are necessary to define this polymorphism as a valuable clinical marker.