Early Liver Transplant In Patients With Liver Cirrhosis Recovered From COVID-19 Infection.

OBJECTIVES: Coronavirus disease 2019 has resulted in significant morbidities and mortalities in nearly all parts ofthe world. There remain major concerns about management, timing, and safety of liver transplant in patients who have recovered from COVID-19. We aimed to study the clinical course and outcomes of patients with liver cirrhosis who recovered from COVID-19 and underwent liver transplant from deceased donors. MATERIALS AND METHODS: A retrospective study was conducted on liver transplant recipients who underwent liver transplant from April 1, 2020, to January 30, 2021. We evaluated all recipients of liver transplantfrom deceased donors during this period in the COVID-19 pandemic. RESULTS: There were 14 patients with decompensated liver cirrhosis who had recovered from COVID-19 as documented by reverse transcription-polymerase chain reaction test for SARS-CoV-2. Mean duration from COVID-19 to transplant surgery was 56.14 ± 29.96 days. Mortality occurred in 3 patients, and of whom 2 had been hospitalized and received medications for COVID-19 before transplant. Five patients had positive reverse transcription-polymerase chain reaction results for SARS-CoV-2 after liver transplant. CONCLUSIONS: This is a large reported series of patients with liver cirrhosis who have received liver transplant after recovery from COVID-19. We provided evidence that liver transplant from deceased donors should be considered in patients recovered from COVID-19, especially in those with deterioration of clinical status.

Nonalcoholic Steatohepatitis Is the Most Rapidly Growing Indication for Liver Transplantation in Iranian Patients.

OBJECTIVES: Nonalcoholic fatty liver disease is a rapidly growing disease and is hypothesized to become the most common cause of liver cirrhosis in the near future. This study aimed to investigate trends of nonalcoholic steatohepatitis as an indication for liver transplant in Iranian patients. MATERIALS AND METHODS: Liver transplant data from all adult patients (age > 18 y) who had undergone liver transplant between 1993 and 2017 at the Shiraz Organ Transplant Center (Shiraz, Iran) were reviewed. Underlying liver diseases leading to liver transplant were stratified according to year of transplant, and trends of increase or decline were analyzed. Kaplan-Meier curves were used for analysis of posttransplant survival of patients with nonalcoholic steatohepatitis and patients with modified nonalcoholic steatohepatitis. RESULTS: We evaluated 3184 liver transplant patients. Of these, 112 patients with biopsy-proven nonalcoholic steatohepatitis underwent liver transplant up to the end of 2017. Mean age of patients was 52.86 ± 9.01 years in those with nonalcoholic steatohepatitis and 51.73 ± 7.91 years in those with modified nonalcoholic steatohepatitis (P > .05).The prevalence of nonalcoholic steatohepatitis as an indication for liver transplant was 0.8% in 2011, 0.36% in 2012, 1.9% in 2013, 4.01% in 2014, 2.89% in 2015, 6.65% in 2016, and 9.97% in 2017. The prevalence of modified nonalcoholic steatohepatitis was 2.4% in 2011, 2.88% in 2012, 2.71% in 2013, 2% in 2014, 2.17% in 2015, 2.13% in 2016, and 2.28% in 2017. We found that nonalcoholic steatohepatitis as a cause of liver transplant increased significantly during recent years (P < .001). CONCLUSIONS: Nonalcoholic steatohepatitis is a rapidly growing indication for liver transplant among Iranian patients. Health care providers should consider programs for prevention and early diagnosis of patients with nonalcoholic steatohepatitis for proper treatment.

Retransplant of the Liver: 12-Year Experience of the Shiraz Organs Transplantation Center.

OBJECTIVES: Liver transplant is the most effective treatment modality for patients with end-stage liver disease, metabolic disorders, hepatic malignancy, and acute liver failure. When a graft fails after primary liver transplant, retransplant of the liver remains the only option. Here, we report the past 12-year experience of the Shiraz Transplant Center regarding liver retransplant. MATERIALS AND METHODS: This is a retrospective cohort study of a 12-year period (2004-2015) of the Shiraz Center in Iran. RESULTS: Of the 3107 patients who had a liver transplant during the study period, 58 retransplants were performed (1.86%) in 57 patients. The leading cause of retransplant was primary nonfunction in 24 patients (41.4% of retransplant cases and 0.77% of all liver transplant cases). The second leading cause of retransplant was vascular complications in 25 patients (23 with hepatic artery thrombosis and 2 with portal vein thrombosis), accounting for 43.1% of retransplant cases and 0.80% of all liver transplant cases. In addition, 5 patients (8.6%) had retransplant for rejection, which accounted for 0.16% of all liver transplant cases. Four patients with retransplant (6.9%) had recurrence of primary disease, which accounted for 0.12% of all liver transplant cases. Most liver retransplants occurred early (≤ 30 days after primary transplant) at the Shiraz Transplant Center. Five-year survival rate after retransplant was 35%, and retransplant for hepatic artery thrombosis was more common in children. CONCLUSIONS: Because most patients required retransplants in the early period after primary transplant, the decision for retransplant must be considered carefully with full multidisciplinary evaluation and only in skilled hands. Retransplant in subgroups of patients with little chance of a successful outcome should be avoided.

Liver Transplant for Primary Hyperoxaluria Type 1: Results of Sequential, Combined Liver and Kidney, and Preemptive Liver Transplant.

OBJECTIVES: Primary hyperoxaluria type 1 is an autosomal recessive disorder that causes overproduction and urinary excretion of oxalate. Liver transplant has been suggested as a treatment for primary hyperoxaluria type 1 since the defective enzyme is expressed in the liver. This study aimed to investigate results of combined liver and kidney, sequential, and preemptive livertransplantin patients with primary hyperoxaluria type 1. MATERIALS AND METHODS: In this cohort study, we followed patients with primary hyperoxaluria type 1 who underwent liver transplant at our centerin Shiraz, Iran. Clinical and laboratory data of patients were gathered, and major outcomes, including renal failure after liver transplant, rejection, and mortality were recorded. Survival of patients was analyzed by the Kaplan-Meier method. RESULTS: Our study included 24 patients. There were 16 male (66.6%) and 8 female (33.33%) patients. Thirteen patients were in the pediatric age group (age < 18 y), and 11 patients were adults (age ≥ 18 y). Thirteen patients underwent sequential transplant, 8 patients underwent combined liver and kidney transplant, and 3 patients underwent preemptive transplant. All patients received organs from deceased donors. There were no statistically significant differences in mortality, rejection, and hemodialysis after transplant between those with sequential transplant and those with combined liver and kidney transplant (P > .05). CONCLUSIONS: Liver transplant can be considered a treatment for patients with primary hyperoxaluria type 1. Combined liver and kidney transplant and preemptive liver transplant could be proper options for these patients.

A Report of 85 Cases of COVID-19 and Abdominal Transplantation From a Single Center: What Are the Associated Factors With Death Among Organ Transplantation Patients.

BACKGROUND: In this study, we report the epidemiology of COVID-19 among recipients of organ transplantation and evaluate associated factors with death. METHODS: We screened 6969 patients who had organ transplantations in our center for COVID-19. Specific data on presentation, clinical course, treatment, and prognosis were acquired. RESULTS: We found 85 patients (66 liver, 16 kidney, 2 kidney-pancreas, and 1 liver-kidney recipient) who acquired COVID-19. Most common symptoms included fever (48.2%), cough (41.2%), myalgia (41.2%), and fatigue (40%). Dyspnea developed in 33% of patients. Overall, one-third of patients had an oxygen saturation of below 90% on admission. Patients were hospitalized for a median (interquartile range) of 9 (5, 13.7) days and had a 33.9% intensive care unit admission rate. Overall, 17 patients (20%) died, which included 31.3% of patients with kidney transplantations and 18.2% of patients with liver transplantations. All 4 pediatric patients in our series died. In our univariate analysis among adults, rates of leukopenia (38.4% versus 13.2%; P = 0.04), low albumin levels (53.8% versus 10.2%; P = 0.001), and shorter duration between transplantation and COVID-19 (P = 0.02), were higher among patients who died. In our least absolute shrinkage and selection operator regression model, low albumin levels (OR, 4.48; 95% confidence interval, 1.16-17.27) were associated with higher risk of death. CONCLUSIONS: This is the largest single-center report on abdominal transplantations and COVID-19. Liver and kidney transplant recipients have an increased risk of mortality compared with the general population due to COVID-19. More specifically, pediatric patients and those with low albumin levels are at higher risks of death due COVID-19.

The Largest Single Center Report on Pediatric Liver Transplantation: Experiences and Lessons Learned.

OBJECTIVE: We described our experiences on pediatric liver transplantation (LT) from the largest LT center in the world termed the Shiraz Transplant Center. BACKGROUND: After the first successful pediatric LT in 1967, pediatric LT has become the routine treatment for children with liver failure worldwide. METHODS: Data on a total of 1141 pediatric cases of LT were collected. Specifics on baseline and anthropometric characteristics, clinicopathology, prognosis of recipients of LT, and donor characteristics are reported. RESULTS: Mean age of patients was 7.83 ±â€Š5.55 years old. Most common etiologies for LT were biliary atresia (15.9%), progressive familial intrahepatic cholestasis (13.4%), and Wilson's disease (13.3%), respectively.Whole organs, living donor grafts, and split grafts were used in 47.9%, 41%, and 11.1% of patients, respectively. In-hospital complications were seen among 34.7% of patients and the most common complications were infections (26.8%), bleeding (23.4%), and vascular complications (18%).Median (interquartile range) model for end stage liver disease score was 20 (15, 25). Main causes of death among patients were sepsis (35.2%), followed by post-transplantation lymphoproliferative diseases (10.5%), and primary nonfunction of liver (9%).Patient survival showed improvement over the years (1-year survival of 73.1%, 83.4%, and 84.4%, 2-year survival of 65.2%, 77.1%, and 78.7%, 5-year survival of 58.2%, 72%, and 77.8% for 1997-2007, 2007-2013, and 2013-2019, respectively; P < 0.001). CONCLUSIONS: This is the largest single-center report on pediatric LT in literature which provides valuable experiences in pediatric LT.

Single Center Long-Term Results of Pediatric Liver Transplantation.

OBJECTIVES: Liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the rare donor organs, complex surgical demands, and the necessity to prevent long-term complications. Our objectives were to analyze 16 years of experience in the Shiraz University Organ Transplant Center. MATERIALS AND METHODS: We retrospectively analyzed the records of 752 patients (< 18 years old) who underwent orthotopic liver transplant at our center over a 16-year period. Mean age was 90 months, and male-to-female ratio was 1.25. Of the 752 transplants, 354 were whole organs, 311 were from living related donors, and 87 were in situ split liver allografts. Patient and graft survival rates were determined at 1, 3, and 5 years, and results between groups were compared. RESULTS: Overall mortality was 31.8%. The 1-, 3-, and 5-year patient survival rates were 77%, 69%, and 66%, respectively, whereas the respective graft survival rates were 75%, 68%, and 65%. We observed significant differences in survival according to graft type (log-rank test, P < .001). We also observed significant differences in survival probabilities according to age (log-rank test, P < .001). Cox regression was used to simultaneously analyze effects of age and graft type on survival. Both graft type and age significantly affected survival (P < .001). The 1-, 3, and 5-year survival rates for patients having whole organ transplants were 88%, 81%, and 78%. Patients who received living donor grafts had respective survival rates of 66%, 60%, and 58%, with rates of 65%, 47%, and 47% for patients who received split grafts. CONCLUSIONS: Our results were similar to those observed in the literature in terms of indication for transplant and posttransplant survival.

Gastrocolic Fistula Presented as an Early Complication of Gastric Surgery in a 42-year-old Man.

Currently, surgery is less needed for the treatment of refractory peptic ulcer disease (PUD) or its complications. So, the complications of PUD surgery have been clearly declined. Here in, we present a 42-year-old man with chronic watery diarrhea and significant weight loss during 2 years after gastrojejunostomy for the treatment of obstructive PUD. Small bowel gastrointestinal series showed rapid transit without passage of contrast in the parts of small bowel. The patient was scheduled for exploratory laparotomy. During the surgery a large fistula was detected between the stomach and transverse colon, which was repaired. At the follow-up 6 months after the surgery, the patient did not have any history of recurrence of diarrhea and had 10 kg weight gain. Gastrocolic fistula is a very rare complication of surgical management of PUD. Barium enema is the most helpful imaging procedure for the diagnosis of gastrocolic fistula and surgery after correction of nutritional status is suggested especially for malnourished patients.

A New Consideration in Hepatic Artery Reconstruction in Adult Liver Transplant: Arterial Transposition Versus Extra-Anatomic Jump Grafts.

OBJECTIVES: In some cases of liver transplant, standard hepatic artery reconstruction may be difficult or impossible due to inadequate flow of the recipient's hepatic artery, as a result of stenosis, intimal dissection, or anomalies of the hepatic artery. We compared splenic artery transposition with extra-anatomic jump graft as 2 alternative methods for hepatic artery reconstruction in these situations. MATERIALS AND METHODS: We reviewed the files of 2135 liver transplant recipients from March 2011 to February 2016 at the Shiraz Transplant Center. Data of 93 patients with unusual hepatic artery reconstruction were analyzed to assess outcomes, morbidity, mortality, and pre- and posttransplant parameters (both clinical and paraclinical). Patients were divided into 2 groups: 17 with splenic artery transposition (splenic artery group) and 76 with extra-anatomic jump grafts (control group). RESULTS: There was only 1 occurrence (5.8%) of hepatic artery thrombosis in the splenic artery group causing extra-anatomic jump graft. However, in the control group, there were 4 occurrences (5.2%) of hepatic artery thrombosis, causing 1 revision of anastomosis and 3 retransplant procedures. No deaths due to hepatic artery complications were reported in the 2 groups. Three-year survival rate was 87.5% in the splenic artery group and 68.9% in the control group. CONCLUSIONS: Splenic artery transposition is an acceptable method for hepatic artery reconstruction in deceased-donor liver transplant procedures with no greater rates of complication or morbidity than extra-anatomic jump grafts. Less operation time and better exposure during surgery are advantages of this method.

The incidence rate of inflammatory bowel disease in an urban area of iran: a developing country.

BACKGROUND The incidence of inflammatory bowel disease (IBD) varies among different societies. The aim of this study is to determine the incidence rate of IBD in Kerman, a city in Southeast Iran. METHODS All medical records that indicated a new diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) were retrieved from the gastrointestinal endoscopy and pathology departments of 12 centers from October 2011 to September 2012. RESULTS The incidence rate of UC in Kerman was estimated at 4.98/100,000 (95% CI: 2.44-6.94). The mean age of patients was 39.4 years and male to female ratio was 0.89:1.0. UC patients had the following prevalence: cigarette smoking (30%), appendectomy (36%) and oral contraceptive (OCP) use (78.9%). The incidence rate of CD was 0.8/100,000 (95% CI: 0.6 4-1.14). The mean age at diagnosis was 33.3 years and male to female ratio was 0.5:1.0. Cigarette smoking was reported in 33.3%, appendectomy in 66.6% and OCP useing in 75% of CD patients. Rectal and distal colitis, left side colitis and extensive colitis was seen in 20 (55.4%), 12 (33.3%) and 4 (11.1%) of patients with UC, respectively. All patients with CD had large intestinal involvement and one case (16.6%) had ileocolonic disease. CONCLUSION Our study has shown that the incidence rate of both UC and CD in Kerman is lower than Western populations but it is the same as some Asian countries. Characteristics of disease involvement in this study are similar to other studies that have been conducted in Iran and elsewhere.

Blue Rubber Bleb Nevus Syndrome as a rare Cause of Iron Deficiency Anemia: a Case Report and Review of Literature.

Blue Rubber Bleb Nevus Syndrome is a rare disorder that is characterizedby multiple recurrent vascular malformations of skin and gastrointestinal tract.The affected patients may present with diverse manifestations including irondeficiency anemia. We report this syndrome in a 22-year-old man that was referred to our hospitalfor iron deficiency anemia with unknown cause and vascular malformationsin the skin and gastrointestinal tract. Because of stable hemoglobin level,we decided to treatment him by iron supplementation and close follow up. Wereport this case along with a review of literature.

Is perioperative intravesically applied antibiotic solution effective in the prophylaxis of urinary tract infections after renal transplantation?

OBJECTIVES: To evaluate the efficacy of intravesically applied amikacin for the prophylaxis of urinary tract infections (UTIs) occurring in the first 3 months after kidney transplantation. METHODS: In a prospective, randomized, controlled trial, 200 consecutive renal transplant recipients were randomly divided into two equal groups. The bladders of the first group, the amikacin group, were filled with saline solution containing amikacin (1 g in adults and 30 mg/kg in pediatric patients) whereas the bladders of the patients of the second group, the control group, were filled with saline solution. Patients were followed up for 3 months after transplantation with urine cultures to evaluate the prevalence of posttransplantation UTIs in both groups. RESULTS: The overall incidence of UTIs was found to be significantly lower in the amikacin group (25 vs. 49%; p = 0.0007). In addition, male patients, patients with end-stage renal disease due to glomerulonephritis, patients receiving renal transplantation for the first time, or those from the amikacin group receiving a living-related graft had a significantly lower incidence of UTIs than their counterparts in the control group (p < 0.05). UTIs were most frequently caused by Escherichia coli (28.9%). CONCLUSIONS: Perioperative bladder irrigation with amikacin solution significantly decreases the overall incidence of UTIs in the first 3 months after kidney transplantation.

Effects of surgical technique on postoperative renal function after orthotopic liver transplant.

OBJECTIVES: The classic technique for orthotopic liver transplant consists of the total excision of the retrohepatic inferior vena cava during native hepatectomy. Controversy about the effects of the classic technique on postoperative renal function continues. The aim of this study was to evaluate the effects of the chosen hepatectomy technique on postoperative renal function. MATERIALS AND METHODS: Of 253 patients who received an orthotopic liver transplant between June 2006 and July 2008 in the Shiraz transplant unit, only 15 underwent operation with the classic technique. Patient demographics and factors including cold ischemic time, warm ischemic time, operative time, transfusions, blood loss, and early postoperative renal function were assessed retrospectively. The criteria for acute renal failure were a serum creatinine level of > 133 micromol/L (1.5 mg/dL), an increase in the baseline serum creatinine level by 50%, or oliguria requiring renal replacement therapy. RESULTS: All patients received a liver from a deceased donor, and none required venovenous bypass during the operation. The minimum mean arterial blood pressure value of the patients during clamping was 65 -/+ 19 mm Hg. The mean preoperative plasma creatinine level was 87.51 -/+ 39.78 micromol (0.99 -/+ 0.45 mg/dL). During the first week after transplant, 7 patients (46.6%) experienced acute renal failure, and 3 of those 7 required renal replacement therapy. By the sixth postsurgical month, 4 of those 7 patients had died (1 from adult respiratory distress syndrome, 2 from sepsis, and 1 from recurrent cholangiocarcinoma). In all other patients, the plasma creatinine level had returned to the normal range by the third postsurgical week 3 or during short-term follow-up. CONCLUSIONS: Use of the classic technique for orthotopic liver transplant may increase the rate of postoperative renal failure, but that complication usually resolves during short-term follow-up.

Pancreas transplantation in shiraz organ transplant center; the first Iranian experience.

BACKGROUND: Pancreas transplantation is the treatment of choice for selected patients with type 1 diabetes mellitus. We reviewed our first 40 patients who underwent pancreas transplantation in Shiraz Organ Transplant Center. METHODS: Between April 2006 and April 2008, we performed pancreas transplantation on 40 recipients. The operation included portal venous drainage and exocrine enteric drainage. Immunosuppressive therapy included prednisolone, tacrolimus, and mycophenolate mofetil. Ganciclovir was administered as prophylaxis for cytomegalovirus. Peri-operative and regular follow up data on survival and complication were gathered and analyzed. RESULTS: The mean follow-up was 10.1+/-6.5 months (range: 1 - 24 months). Mean age of donors and recipients was 23.6+/-8.2 and 32.30+/-8.9 years, respectively. The mean pretransplant insulin consumption was 43.75+/-17.4 IU. Fasting blood glucose before transplantation was 275.5+/-72.3 mg/dL that decreased to 95.6+/-7.01 at six months follow-up (P<0.001). Complications were as follows: re-exploration (n=9), gastrointestinal complications (n=10), acute rejection episodes (n=12), and chronic rejection (n=4). We lost one patient due to diffuse cytomegalovirus and aspergillus infection three months after the operation with a functioning graft. Overall graft survival was 84.9% and patient survival 97.5%. CONCLUSION: Good patient and graft survival in these series encouraged us to continue the program with all its difficulties.

Outcome of bowel perforation after pediatric liver transplantation.

Bowel perforation is one of the causes of mortality after pediatric liver transplantation. The aim of this study was to evaluate the incidence, risk factors, clinical presentations, and outcomes of bowel perforation in pediatric liver recipients. This is a retrospective analysis of all pediatric patients who underwent liver transplantation at a single liver transplant center in Iran between 1999 and 2006. During this period 72 liver transplantations were performed in children <18 yr. Twenty-two children underwent 33 re-explorations after liver transplantation. Five bowel perforations occurred in four children (incidence, 6.9%). One patient required two re-explorations. The median time between liver transplantation and the diagnosis of the bowel perforation was seven days. All patients had abdominal distention before re-exploration. The sites of perforation were jejunum (n = 3) and ileum (n = 2), and simple repair was performed in all cases. Three children had a history of prior Kasai operation. One of them received high dose of methylprednisolone before bowel perforation. Two children expired after bowel perforation (mortality rate, 50%). Bowel perforation is relatively frequent after pediatric liver transplantation. Among risk factors, prior Kasai operation may have a role. We observed that abdominal distention is a sign of bowel perforation and a high index of suspicion is required for rapidly diagnosis of this complication. The outcome of bowel perforation is poor and its mortality is high. Further studies are needed to establish real risk factors for this complication.

Effect of D-penicillamine on liver fibrosis and inflammation in Wilson disease.

BACKGROUND: Wilson disease is a disorder of copper metabolism characterized by copper overload. A mutation in the ATP7B gene causes dysfunction of ATP7B protein and a reduction in copper excretion into the bile in hepatocytes. Excess copper accumulation leads to liver injury. D-penicillamine primarily can inhibit fibrogenesis and prevent the appearance of scar lesions in the liver. We studied this phenomenon in our patients. MATERIALS AND METHODS: Pathology slides from the explanted livers of 26 patients diagnosed as having Wilson disease with hepatoneurologic manifestations between 2000 and 2008 who had undergone a liver transplant were investigated retrospectively. Patients were divided into 2 groups according to their history of D-penicillamine use before transplant. The degree of fibrosis and inflammation were classified as mild (1), moderate (2), and severe (3), and were reviewed by an impartial hepatopathologist. RESULTS: Of 26 patients (20 male, 6 female) who had Wilson disease with a mean age of 17.6 -/+ 8.6 years, 69% (18/26) had a history of D-penicillamine use before liver transplant from 6 months to 9 years (mean, 3.4 -/+ 2.7 years). In the D-penicillamine group, 14 patients (77%) had grade 1 fibrosis. Grade 2 and 3 fibrosis was seen in 5.6% and 16% of patients, respectively. In the D-penicillamine group, inflammation was grade 3 in 44% (8/18), grade 2 in 44% (8/18), and grade 1 in 11% of the patients (2/18). In the non- D-penicillamine group (8 patients), grades of fibrosis were grade 3 (62%), grade 2 (25%), and grade 1 (12%); 87% of the patients had grade 2 and 3 inflammation. The degree of fibrosis was significantly lower in the D-penicillamine group than it was in the non-D-penicillamine group (P < .05). CONCLUSION: D-penicillamine may reduce the rate of liver fibrogenesis in patients with Wilson disease.