Liver Transplant for Hepatocellular Carcinoma in Post-Milan Criteria Era: A Long-Term Single-Center Experience.

OBJECTIVES: We investigated the outcomes of liver transplant in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Prospectively, recipients of deceased donor liver transplants from 2007 to 2021 at Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, were enrolled into the study. The Milan criteria were applied for selection of liver transplant candidates diagnosed with hepatocellular carcinoma. Patients with diagnosis of acute liver failure and who underwent secondary liver transplant were excluded. All patients diagnosed with hepatocellular carcinoma were given mechanistic target of rapamycin inhibitor with calcineurin inhibitor minimization 4 weeks after liver transplant. Patients were assigned to the experimental group (with hepatocellular carcinoma; n = 82) or the control group (without hepatocellular carcinoma; n = 1076). We recorded the etiologies of liver cirrhosis in the experimental group, demographic data from all patients, and postoperative complications. RESULTS: Of 1158 total patients, mean age was 44.15 ± 14.71 years (range, 1-73 years) and 712 were male patients (61.5%). In the experimental group (n = 82), there were 76 patients (92.68%) who were within the Milan criteria; others were excluded intraoperatively. All patients were followed for a median of 65.3 ± 40.8 months (range 10-197 months). Patient survival rates in the experimental group and control group at 3 months, 1 year, and 3 years were 89%, 80%, and 78% versus 84%, 81%, and 70%, respectively (P = .742). Hepatocellular carcinoma reoccurred in 6 patients (7.31%) at mean of 16.83 months postoperatively. CONCLUSIONS: Liver transplant for patients with hepatocellular carcinoma in the post-Milan criteria era is associated with acceptable outcomes.

Liver Transplant in Patients With Autoimmune Hepatitis: A Large Single-Center Study.

OBJECTIVES: Autoimmune hepatitis is a rare indication for liver transplant in Western countries. Our goal was to identify characteristics and long-term outcomes of patients who underwent liver transplant for autoimmune hepatitis-related end-stage liver disease at our center. MATERIALS AND METHODS: Adult patients who underwent primary liver transplant from January 2007 to March 2022 at Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran, were enrolled in our study. RESULTS: Among 1107 patients enrolled in our study, mean age was 45.94 ± 12.43 years (range, 16-73 years) and 423 (38.2%) female patients were included. Autoimmune hepatitis was the underlying cause of cirrhosis in 177 patients (experimental group); the other 930 patients did not have autoimmune hepatitis (control group). All patients were followed for a median of 60 ± 40.3 months (range, 3-187 months) after transplant. In the experimental group, patient survival rates at 1 month, 1 year, and 3 years were 87%, 81%, and 78%, which were not significantly different between the 2 groups (P = .445). Recurrence of autoimmune hepatitis was detected in 8 patients (4.5%) in the experimental group. Acute allograft rejection was more significantly detected in the patients with recurrence of autoimmune hepatitis than in patients without recurrence of autoimmune hepatitis. CONCLUSIONS: Liver transplant in patients with autoimmune hepatitis is safe and is associated with good outcomes.

Enhanced recovery after hepatopancreaticobiliary surgery: A single-center case control study.

BACKGROUNDS/AIMS: The aim of this study was to find the safety and effectiveness of enhanced recovery after surgery (ERAS) in patients who undergo hepatopancreaticobiliary (HPB) surgeries and its association with the postoperative complications and survival rate of the patients. METHODS: This study was conducted on patients who underwent HPB surgeries in Imam Khomeini Hospital Complex, Iran from 2018 to 2020. Patients who underwent surgery after from 2019 to February 2020 considered as the ERAS group (n=47) in which ERAS was implemented postoperatively including removing nasogastric tube and initiating surgical diet at 6 hours post operation, and removing intraabdominal drains and Foley catheter at postoperative day one. Other patients (n=43) were considered as the control group in which conventional postoperative care was implemented. RESULTS: Ninety patients with the mean age of 47.3±13.3 yrs/old (range= 17-76) including 39 females were enrolled into the study. There were no significant differences between the demographic and preoperative comorbidities between the two groups. Pain severity of the patients in the ERAS group was significantly lower than the control group (visual analogue scales of 3.4±0.77 vs. 4.47±0.88, p<0.001). However, there were no significant differences between the other postoperative data between the two groups. One patient in each group died during hospitalization period due to myocardial infarction. CONCLUSIONS: ERAS may be safe and effective in patients who undergo HPB surgery and may be associated with less severe postoperative pain.

Value of Ultrasonography in Detection of Diaphragmatic Injuries Following Thoracoabdominal Penetrating Trauma; a Diagnostic Accuracy Study.

INTRODUCTION: Diagnosis of diaphragmatic rupture following thoracoabdominal penetrating trauma is very challenging in asymptomatic patients with stable vital signs. This study aimed to evaluate the diagnostic accuracy of focused assessment with sonography for trauma (FAST) in this regard. METHODS: This cross-sectional study was performed on patients referring to emergency department due to left thoracoabdominal stab wound during 2 years. All patients initially underwent ultrasonography and the screening performance characteristics of FAST in detection of diaphragmatic injuries were calculated, considering the findings of diagnostic laparoscopy as the gold standard test. RESULTS: Twenty-four patients with the mean age of 33 ± 10.64 years (16-61 years) were studied (100% male). The mean chest wall laceration size was 2.7 ± 2.7 cm (1-10 cm) and the most frequent location of wounds was posterior chest wall (42%) and in the 6th and 7th intercostal space (50%). Diaphragmatic rupture was seen in 4 (16.7%) patients based on diagnostic laparoscopy. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratio of FAST in detection of diaphragmatic raptures were 50% (95% CI: 9.18 - 90.8), 100% (95% CI: 79.9 - 100.0), 100% (95% CI: 19.8 - 100.0), 9.1% (95% CI: 1.5 - 30.6), Infinity, and 0.1 (95% CI: 0.02 - 0.37), respectively. The overall accuracy of FAST in this regard was 75.0% (95% CI: 42.3 - 100.0). CONCLUSION: In patients with penetrating trauma to the left thoracoabdominal region, FAST cannot be the definitive alternative to diagnostic laparoscopy to detect diaphragm rupture.

The diagnostic values of procalcitonin and interleukin 6 in acute appendicitis.

OBJECTIVE: Despite the recent use of computed tomography scan and diagnostic laparoscopy, acute appendicitis is still highly misdiagnosed. Timely diagnosis of acute appendicitis is more crucial in children and elderly patients because of vague symptoms and rapid progression to perforation in these age groups, which may result in high rates of morbidity and mortality. The aim of the present study was to find the diagnostic values of procalcitonin and interleukin 6 (IL-6) for diagnosing acute appendicitis in our center. MATERIAL AND METHODS: Patients who were suspected of acute appendicitis and who were referred to the emergency department of a tertiary care urban hospital in 2016 were enrolled in the study. A 5 mL blood sample was obtained from each patient before appendectomy and was examined for procalcitonin and IL-6. Then, the resected specimen of the appendix was studied by a pathologist, and a definite diagnosis was made. RESULTS: Eighty patients including 53 (66.3%) men who underwent appendectomy were enrolled in the study. The diagnosis of acute appendicitis was histopathologically confirmed in 60 (75%) patients including 18, 20, and 22 patients with inflammatory, suppurative, and gangrenous/perforated appendicitis, respectively. The sensitivity and specificity of procalcitonin versus IL-6 for diagnosing acute appendicitis were 65% and 80% vs. 76% and 55%, respectively. The sensitivity and specificity of concurrent procalcitonin and IL-6 for diagnosing acute appendicitis were 95% and 55%, respectively. CONCLUSION: Our study suggests that parallel measurement of procalcitonin and IL-6 decreases unnecessary negative appendectomies.

Evaluation of the effectiveness of sodium hyaluronate, sesame oil, honey, and silver nanoparticles in preventing postoperative surgical adhesion formation. An experimental study.

PURPOSE:: To evaluate the effectiveness of sodium hyaluronate, sesame oil, honey, and silver nanoparticles in preventing of postoperative surgical adhesion formation. METHODS:: Forty male Wistar rats were randomly assigned into five groups with eight rats in each group including control, hyaluronate, sesame, honey and silver groups. After two weeks the animals underwent laparotomy and were evaluated by two different blinded surgeons for severity of adhesions based on the two different classification scoring systems including Nair classification and cumulative adhesion scoring scale. RESULTS:: The scores of severity of adhesions in the hyaluronate and sesame groups were significantly lower than the control group based on the Nair classification (both P-values = 0.02), however based on the cumulative adhesion scoring scale just the score of severity of adhesions in the hyaluronate group was significantly lower than the control group (P-value = 0.02). In the hyaluronate group the severity of adhesions was decreased by 48% based on the cumulative adhesion scoring scale. CONCLUSIONS:: Sodium hyaluronate and sesame oil may have a significant effect in preventing postoperative surgical adhesion formation.

Evaluation of the effectiveness of sodium hyaluronate, sesame oil, honey, and silver nanoparticles in preventing postoperative surgical adhesion formation. An experimental study

Abstract Purpose: To evaluate the effectiveness of sodium hyaluronate, sesame oil, honey, and silver nanoparticles in preventing of postoperative surgical adhesion formation. Methods: Forty male Wistar rats were randomly assigned into five groups with eight rats in each group including control, hyaluronate, sesame, honey and silver groups. After two weeks the animals underwent laparotomy and were evaluated by two different blinded surgeons for severity of adhesions based on the two different classification scoring systems including Nair classification and cumulative adhesion scoring scale. Results: The scores of severity of adhesions in the hyaluronate and sesame groups were significantly lower than the control group based on the Nair classification (both P-values = 0.02), however based on the cumulative adhesion scoring scale just the score of severity of adhesions in the hyaluronate group was significantly lower than the control group (P-value = 0.02). In the hyaluronate group the severity of adhesions was decreased by 48% based on the cumulative adhesion scoring scale. Conclusions: Sodium hyaluronate and sesame oil may have a significant effect in preventing postoperative surgical adhesion formation.

The effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats.

PURPOSE:: To assess the effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative adhesion in animal models. METHODS:: Sixty males Albino Wistar rats aged 5 to 6 weeks were classified into five groups receiving none, heparin, PRP, silver nanoparticles, PRP plus silver nanoparticles intraperitoneally. After 2 weeks, the animals underwent laparotomy and the damaged site was assessed for peritoneal adhesions severity. RESULTS:: The mean severity scores were 2.5 ± 0.9, 2.16 ± 0.7, 1.5 ± 0.5, 2.66 ± 0.88, and 2.25 ± 0.62 in the control, heparin, PRP, silver and PRP plus silver groups, respectively with significant intergroup difference (p = 0.004). The highest effective material for preventing adhesion formation was PRP followed by heparin and PRP plus silver. Moreover, compared to the controls, only use of PRP was significantly effective, in terms of adhesion severity (p = 0.01) . CONCLUSION:: Platelet-rich plasma alone may have the highest efficacy for preventing postoperative peritoneal adhesions in comparison with heparin, silver nanoparticles and PRP plus silver nanoparticles.

The effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats

Purpose: To assess the effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative adhesion in animal models. Methods: Sixty males Albino Wistar rats aged 5 to 6 weeks were classified into five groups receiving none, heparin, PRP, silver nanoparticles, PRP plus silver nanoparticles intraperitoneally. After 2 weeks, the animals underwent laparotomy and the damaged site was assessed for peritoneal adhesions severity. Results: The mean severity scores were 2.5 ± 0.9, 2.16 ± 0.7, 1.5 ± 0.5, 2.66 ± 0.88, and 2.25 ± 0.62 in the control, heparin, PRP, silver and PRP plus silver groups, respectively with significant intergroup difference (p = 0.004). The highest effective material for preventing adhesion formation was PRP followed by heparin and PRP plus silver. Moreover, compared to the controls, only use of PRP was significantly effective, in terms of adhesion severity (p = 0.01) . Conclusion: Platelet-rich plasma alone may have the highest efficacy for preventing postoperative peritoneal adhesions in comparison with heparin, silver nanoparticles and PRP plus silver nanoparticles.

The effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats

Abstract Purpose: To assess the effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative adhesion in animal models. Methods: Sixty males Albino Wistar rats aged 5 to 6 weeks were classified into five groups receiving none, heparin, PRP, silver nanoparticles, PRP plus silver nanoparticles intraperitoneally. After 2 weeks, the animals underwent laparotomy and the damaged site was assessed for peritoneal adhesions severity. Results: The mean severity scores were 2.5 ± 0.9, 2.16 ± 0.7, 1.5 ± 0.5, 2.66 ± 0.88, and 2.25 ± 0.62 in the control, heparin, PRP, silver and PRP plus silver groups, respectively with significant intergroup difference (p = 0.004). The highest effective material for preventing adhesion formation was PRP followed by heparin and PRP plus silver. Moreover, compared to the controls, only use of PRP was significantly effective, in terms of adhesion severity (p = 0.01) . Conclusion: Platelet-rich plasma alone may have the highest efficacy for preventing postoperative peritoneal adhesions in comparison with heparin, silver nanoparticles and PRP plus silver nanoparticles.

Transplantation of Deceased Donor Livers With Elevated Levels of Serum Transaminases at Shiraz Transplant Center.

BACKGROUND: The current organ shortage has prompted the use of marginal organs. We conducted this retrospective study to present our experience with transplanting deceased donor livers with elevated levels of serum transaminases and to explain whether elevated levels of serum transaminases in donors affect allograft function and survival of the recipients. METHODS: Data of deceased donor livers and patients, who underwent liver transplantation from March 2013 to March 2015 at Shiraz center for organ transplantation, was reviewed. Liver donors with aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) level of more than 500 IU/l and their related recipients were considered as the case group (n = 24) and the others were considered as the control group (n = 834). RESULTS: In the case group, the medians of levels of serum AST and ALT of donors were 834 ± 425 IU/L (range: 250 - 2285) and 507 ± 367 IU/L (range: 100 - 1600), respectively. Recipients were followed for a median of 13.6 ± 9 months (range: 7 - 28.4). Post-transplant complications were acute rejection (n = 5), infection (n = 3), portal vein thrombosis (n = 3), bile duct stricture (n = 1), and hepatic artery stenosis (n = 1). The one-year survival rate of the patients was 91.7%. Demographics, post-transplant complications and one-year survival rates were not significantly different between the two study groups. CONCLUSIONS: Transplanting deceased donor livers with markedly elevated liver enzymes may be an acceptable choice for expanding the donor pool.

HBIG Remains Significant in the Era of New Potent Nucleoside Analogues for Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

Advent of hepatitis B immunoglobulin (HBIG) as the mainstay of prophylaxis against hepatitis B recurrence after liver transplantation with antiviral drugs has resulted in excellent outcomes for liver transplantation in hepatitis B virus (HBV)-related cirrhosis in the last two decades. However, there is no consensus on a gold standard prophylaxis protocol and several controversies over the duration, dose, and route of administration of HBIG with or without different antivirals exist among liver transplantation centers. We present this review of different prophylaxis regimens including HBIG and antiviral monotherapy, combination of HBIG with antivirals, and withdrawal of HBIG and whole prophylaxis. HBIG monotherapy in either the intramuscular or the subcutaneous form is an accepted choice for prevention of HBV re-infection after liver transplantation in low risk patients. Withdrawal of HBIG monotherapy may be considered but should only occur after transitioning to an oral antiviral therapy such as adefovir, tenofovir, or entecavir. Lamivudine monotherapy may be associated with a higher recurrence rate compared to more potent antivirals. In high risk patients, intramuscular or subcutaneous HBIG in combination with an antiviral, most commonly lamivudine, is currently considered the standard of care. Complete discontinuation of all preventative therapy cannot be recommended at this time and should only be performed in the setting of a clinical trial.

Efficacy and safety of lamivudine or tenofovir plus intramuscular hepatitis B immunoglobulin in prevention of hepatitis B virus reinfection after liver transplant.

OBJECTIVES: Hepatitis B immunoglobulin prophylaxis in combination with antiviral drugs is recommended for prevention of hepatitis B virus reinfection after liver transplant. However, there is no consensus on a standard prophylactic method, and controversy exists over the duration, dose, and route of administration. We conducted a prospective study to evaluate the safety and effectiveness of intramuscular hepatitis B immunoglobulin in combination with lamivudine and/or tenofovir and discontinuation of hepatitis B immunoglobulin after 1 year for prevention of hepatitis B virus reinfection. MATERIALS AND METHODS: Patients with hepatitis Brelated liver cirrhosis who had undergone primary liver transplants were enrolled. The prophylactic protocol involved intraoperative intramuscular hepatitis B immunoglobulin at 10 000 IU, tapering to 5000 IU daily for the first 6 days, weekly for a month, every 2 weeks for the next month, and monthly for a year after liver transplant, in combination with antiviral drugs. RESULTS: From January 2002 until March 2014, two hundred sixty-eight liver transplants were performed. Forty-four patients (16.4%) who underwent liver transplants due to hepatitis B-related liver failure were enrolled. Five patients had hepatocellular carcinoma; 20 had both hepatitis D and hepatitis B virus infection. The median age was 47 years (range, 26-59 y) with a median model for end stage liver disease score of 20. Thirty-three patients were men (76%). Sixty-one percent of patients were negative for hepatitis B virus DNA at the time of transplant. The median follow-up was 13.6 months (range, 0-142 mo). Only 1 patient (2.3%) experienced hepatitis B virus reinfection (at 44.7 months posttransplant), which was successfully treated with tenofovir. Five patients died (11.4%) during the follow-up from nonhepatitis B causes. CONCLUSIONS: Intramuscular hepatitis B immunoglobulin in combination with lamivudine or tenofovir and discontinuation of hepatitis B immunoglobulin after 1 year posttransplant may provide safe and cost-effective protection against posttransplant hepatitis B reinfection.

Cytomegalovirus reactivation and preemptive therapy after liver transplant.

OBJECTIVES: Cytomegalovirus is the most common viral infection after orthotopic liver transplant. The purpose of the present study was to determine the incidence of cytomegalovirus reactivation in Iranian liver transplant recipients at our center and to evaluate outcomes with preemptive therapy with ganciclovir for pp65 antigenemia. MATERIALS AND METHODS: There were 145 patients who had liver transplant and who survived > 2 weeks after transplant. All patients were evaluated for pp65 antigenemia weekly until 90 days after transplant. The diagnosis of cytomegalovirus reactivation was made when a recipient had pp65 antigenemia ≥ 1/50,000 leukocytes. In patients who had cytomegalovirus infection, preemptive therapy with ganciclovir (5 mg/kg, intravenous, twice daily) was started immediately after diagnosis and continued for ≥ 21 days and until cytomegalovirus antigen became undetectable on 2 consecutive tests. RESULTS: All patients in our study were seropositive for cytomegalovirus before transplant. Follow-up at mean 27 ± 20 months (range, 5.2 to 80.6 mo) after transplant showed that 46 patients (32%) had cytomegalovirus reactivation at mean 56 ± 67 days after transplant (range, 12 to 445 d). There was a higher frequency of female patients in the cytomegalovirus reactivation than non-reactivation group (odds ratio, 2.3; P ≤ .02). The most common causes of liver failure in the cytomegalovirus reactivation group were autoimmune hepatitis, cryptogenic cirrhosis, and hepatitis B virus cirrhosis. There was no significant relation between cause of liver failure, use of steroids before or after transplant, and frequency of acute rejection and cytomegalovirus reactivation. Only 1 patient (2%) developed cytomegalovirus disease at 22 days after transplant, and this patient was treated successfully. There were 6 patients (13%) who developed a second episode of cytomegalovirus reactivation at median 43 days (range, 10 to 176 d) after the first episode; all 6 patients were treated successfully with ganciclovir. CONCLUSIONS: Preemptive treatment with ganciclovir may be an effective approach against cytomegalovirus in seropositive recipients after liver transplant.

Patient outcomes in a liver transplant program in Iran.

OBJECTIVES: The first liver transplant program in Tehran was started at Tehran University of Medical Sciences in 2002. The purpose of this study was to evaluate patient outcomes in this program. MATERIALS AND METHODS: From January 2002 to February 2013, there were 172 deceased-donor orthotopic liver transplants performed in 166 patients, including revision transplant in 6 patients. Outcomes were evaluated for 4 phases of the program: (1) phase 1 (2002 to 2005; 9 transplants); (2) phase 2 (2006 to 2009; 41 transplants); (3) phase 3 (2010 to 2011; 49 transplants); and (4) phase 4 (2012 to 2013; 73 transplants). RESULTS: The most frequent indications for liver transplant included cryptogenic cirrhosis, autoimmune hepatitis, and hepatitis B and C cirrhosis. During the progression from phase 1 to 4, there were significant decreases in median cold ischemia time, operative time, and transfusions (platelets, packed red blood cells, and fresh frozen plasma). The most frequent complications included infection and acute rejection. The overall median follow-up for all patients was 26 months (range, 9-144 mo). Frequency of 1-month, 3-month, 1-year, and 2-year survival increased from phase 1 to 4. Kaplan-Meier plots showed significant improvement in patient survival from phase 1 to 4 (P ≤ .001). The most common causes of death were sepsis and bleeding. CONCLUSIONS: Clinical outcomes with deceased-donor liver transplant may be improved with a cooperative multidisciplinary team, coordinated care from different specialties, increased experience, and modifications of anesthetic and surgical techniques. Comprehensive unified written protocols for preoperative, perioperative, and postoperative treatment may help improve outcomes after sufficient experience is achieved.

Revision liver transplant for persistent infection and localized aspergillosis after hepatic artery thrombosis.

Early hepatic artery thrombosis after liver transplant may be complicated by aggressive aspergillosis and bacterial infections that may cause morbidity and mortality. The definitive treatment of hepatic artery thrombosis is revision transplant. However, sepsis may be a contraindication to revision transplant. A 37-year-old man developed hepatic artery thrombosis at 3 days after liver transplant. During the treatment of hepatic artery thrombosis, he developed multiple biliary, bacterial, and fungal infections. Evaluation showed aspergillosis with multiple intrahepatic abscesses. He was treated with antibiotic and antifungal drugs. Despite active sepsis, revision transplant was performed and the infection resolved. Although sepsis may be a contraindication for transplant surgery, revision transplant was successful, probably because the primary transplanted liver was the source of infection.

Establishing a liver transplantation program at Tehran University of Medical Sciences, Iran: a report of ten years of experience.

In 2001, a Liver Transplantation (LT) program was commenced in Imam Khomeini Hospital Complex as the first one in the capital city of Tehran which is the second liver transplantation center in Iran. This study presents the results of our 10-year experience with LT.