Efficacy and Safety of Anti-TNF-α Agents in Inflammatory Bowel Disease After Liver Transplant: A Case Series.

BACKGROUND: Ulcerative colitis (UC) and Crohn disease (CD) can appear de novo or worsen after liver transplant. Our aim was to assess the efficacy and safety of anti-tumor necrosis-alpha (anti-TNF-α) agents after transplantation. METHODS: We reviewed the clinical database of our center searching for all liver transplant patients with inflammatory bowel disease who were treated with anti-TNF-α agents between 1997 and 2017. Clinical response was assessed from clinical activity indices 12 weeks after starting treatment. The median age of the 6 patients (3 women) was 37 years. Four patients were diagnosed before transplantation (2 UC and 2 CD), and in the other 2 the disease appeared de novo (1 UC and 1 CD). The indications for transplant were primary sclerosing cholangitis (n = 3), cryptogenic cirrhosis (n = 2), and hepatitis C virus cirrhosis (n = 1). RESULTS: Clinical response was seen in 3 of the 6 patients and, in the 3 cases for whom endoscopic data were available, no mucous healing was seen. The only adverse effects noted over a mean follow-up of 15 months were 1 cytomegalovirus infection and 1 severe infusion reaction to infliximab. No patients had recurrence of primary sclerosing cholangitis in the graft, and none of the patients died. CONCLUSION: Use of an anti-TNF-α agent in a liver transplant patient with inflammatory bowel disease may be an effective option, with an acceptable risk-benefit ratio. Further studies are required to confirm their use in this context.

Retransplant Due to Fulminant Hepatic Failure From Hepatitis E Virus: A Case Report.

Hepatitis E virus (HEV) usually causes self-limiting acute liver infections from fecal or oral transmission, though other routes of infection exist (vertical transmission, blood transfusion, zoonosis). It may give rise to fulminant hepatic failure in 1% of cases. Cases have recently been reported of chronic infection evolving to cirrhosis in immunosuppressed patients, such as those with a liver or kidney transplant. Nonetheless, development of acute liver failure in these patients is exceptional, with few cases published. We present a case of acute liver failure due to HEV in a liver transplant patient who required a liver retransplant 9 years after receiving the original transplant.

Interstitial pneumonitis associated with sirolimus in liver transplantation: a case report.

Sirolimus is a powerful immunosuppressive drug initially used in kidney transplant patients but now increasingly employed in recipients of other types of solid organ transplants, such as liver, heart, lung, or pancreas. Sirolimus is indicated for rescue therapy and to reduce the toxic side effects of calcineurin inhibitors. However, its use has been associated with an uncommon but important pulmonary toxicity. Reports have described interstitial pneumonitis, bronchiolitis obliterans, organizing pneumonia, and alveolar proteinosis. We present the case of a liver transplant patient with interstitial pneumonitis associated with sirolimus.

Efficacy and safety of monotherapy with mycophenolate mofetil in liver transplantation.

AIM: To analyze the efficacy and safety of mycophenolate mofetil (MMF) as monotherapy in liver transplant patients who have adverse effects associated with calcineurin inhibitors (CNIs). PATIENTS AND METHODS: Seventeen patients, 13 men and four women, mean age 62 years, who received a liver transplant between 1998 and 2003 and initial immunosuppressive therapy with CNIs (10 tacrolimus and seven cyclosporine), were converted to monotherapy with MMF due to adverse events associated with CNIs: chronic renal failure in 16 patients (four with diabetes mellitus and seven with hypertension) and neurotoxicity in one patient. The mean time between transplant and starting monotherapy was 32 months (range: 18 to 70) and the mean follow-up time on monotherapy was 20 months (range: 8 to 39). MMF was introduced gradually at the same time as the CNIs were reduced. RESULTS: There was a progressive decrease in creatinine during the initial months. Compared with baseline levels, the differences at 3 and 6 months of monotherapy were significant (P < .001), remaining so throughout the follow-up period. Renal function improved in 15 of 17 patients (88%) and normalized in 10 of 17 (60%). The patient with neurotoxicity due to CNI improved. One patient (6%) had moderate rejection that was corrected after reintroducing tacrolimus. In two patients it was necessary to suspend MMF, one due to gastrointestinal intolerance and the other due to severe myelotoxicity and Pneumocystis jiroveci infection. Other, minor adverse events were corrected by adjusting the dose: one herpes zoster, two diarrhea, and two anemia. CONCLUSIONS: Monotherapy with MMF efficiently and safely corrected renal dysfunction associated with CNIs, with few side effects and a low incidence of rejection.

Endoscopic Management of Post-Liver Transplantation Biliary Strictures With the Use of Fully Covered Metallic Stents.

OBJECTIVE: The aim of this work was to evaluate the safety and efficacy of a fully covered self-expandable metal stent (FCSEMS) in the treatment of post-liver transplantation biliary strictures. METHODS: From October 2009 to October 2014, 44 patients with post-liver transplantation biliary stenosis were treated with the use of endoscopic retrograde cholangiography and placement of FCSEMS after informed consent. The FCSEMS was scheduled to remain in situ for 3-6 months. Patients were followed at regular intervals to evaluate for symptoms and liver function tests. Technical success, complications, and patient outcome were analyzed. RESULTS: All of the strictures were anastomotic, 52% having occurred within the 1st year following the transplantation. Placement of the FCSEMS was possible on the 1st attempt in 54% of patients. Stricture resolution at the time of stent removal was seen in 100% of the cases. During an average follow-up of 27.83 ± 18.3 months after stent removal, stenosis recurred in 9 out of 41 patients (21.9%). The average time of recurrence was 11.78 ± 13.3 months. In all of these cases, the recurrence was resolved by means of placement of another FCSEMS. In 4 cases, the recurrence was associated with a migration of the prosthesis, partial in 2 cases and total in 2 cases. Stent migration occurred in a total of 17 of the 41 patients (41.4%), in 13 of the 32 (40.6%) who had no recurrence of stenosis and in 4 of the 9 (44.4%) of those who experienced recurrence. The average numbers of endoscopic retrograde cholangiography studies required per patient were 2.8 in those with no recurrence and 3.3 in those with recurrence. No death was associated with the process. CONCLUSIONS: FCSEMS is a safe effective alternative to plastic stents in the treatment of post-transplantation biliary strictures, resulting in a lower risk of complications and better patient acceptance.

Everolimus plus mycophenolate mofetil as initial immunosuppression in liver transplantation.

BACKGROUND: The purpose of this study was to assess the efficacy and safety of a de novo immunosuppressive regimen with everolimus (EVL) plus mycophenolate mofetil (MMF) without calcineurin inhibitors (CNI) for liver transplantation. The secondary purpose was to compare the renal function with a control group of patients treated with tacrolimus plus MMF. METHODS: Sixteen male and 4 female liver transplant patients received immunosuppression with EVL plus MMF without CNI, with induction with steroids and 16 with basiliximab also. In 10 cases it was indicated as induction immunosuppression without CNI as prevention against nephrotoxicity and neurotoxicity or recurrence of hepatocarcinoma in predisposed patients and in another 10 after withdrawing CNI during the immediate post-transplant period, before hospital discharge, as the result of toxicity, mainly nephrotoxicity and neurotoxicity or the presence of hepatocarcinoma with a high risk of recurrence. A control group comprising 31 patients taking tacrolimus plus MMF was included to compare the renal function. RESULTS: The mean follow-up time was 24 months. One patient had a recurrence of hepatocarcinoma at 8 months after transplant. The cases of nephrotoxicity and neurotoxicity resolved favorably. There were 7 rejections (35%); 2 evolved to chronic rejection with both needing retransplantation, 2 resolved with dose adjustment, and 3 required conversion to CNI. The side effects were hyperlipidemia (25%), wound dehiscence (10%), lymphedema (10%), cytomegalovirus infection (25%), myelotoxicity (25%) and proteinuria >1 g in 1 case (5%). No differences were found in renal function between the two groups. CONCLUSIONS: This regimen was proven to be efficient to prevent and treat nephrotoxicity and neurotoxicity with an acceptable tolerability profile. However, the high associated rejection rate indicates that great caution is required in its use during the immediate post-transplant period. It is advisable to associate the regimen with low doses of CNI and to have agile methods available to monitor EVL to enable rapid dose adjustment.

Efficacy and safety of entecavir and/or tenofovir for prophylaxis and treatment of hepatitis B recurrence post-liver transplant.

AIMS: To establish the efficacy and safety of entecavir (ETV) and/or tenofovir (TDF) in the treatment and prevention of hepatitis B virus (HBV) recurrence after liver transplantation. PATIENTS AND METHODS: Eight patients (four men) received treatment with ETV and/or TDF after liver transplantation as prophylaxis for HBV recurrence or as posttransplant treatment of HBV. Four liver transplants were in patients with HBV-associated cirrhosis who had received prior nucleos(t)ide analogue treatment until HBV DNA became undetectable. After transplantation, two of these four were treated with ETV + TDF and the other two with just TDF. All received intramuscular hepatitis B immunoglobulins. The reasons for the other four liver transplants were primary biliary cirrhosis in two cases, alcoholic cirrhosis, and hepatitis C virus. Two of the patients were donor anti-HBcAb-positive/recipient anti-HBcAb-negative. They received no anti-HBV prophylaxis so they had a recurrence of HBV. These four patients required treatment with ETV+TDF for the HBV DNA to become negative. RESULTS: The mean age was 60 (39-67) years. The mean follow-up was 9.5 (3-20) months. The mean follow-up of the patients who received prophylaxis was 8.2 (3-19) months. These had no HBV recurrence. The mean follow-up of the patients who received treatment for HBV recurrence was 12 (3-19) months. ETV combined with TDF was necessary for the HBV DNA to become undetectable because this was not possible using different nucleos(t)ide analogues. There were no significant adverse effects from these drugs and no alteration of renal function during the follow-up period. CONCLUSIONS: Therapy with ETV and/or TDF seems to be efficient and safe when used in the prophylaxis and treatment of HBV recurrence after liver transplantation. They are well tolerated and seem to have no interactions with immunosuppressive medication.

Hepatitis C virus recurrence after liver transplantation: analysis of factors related to sustained viral response.

OBJECTIVES: To determine the efficacy and safety of pegylated interferon (peg-IFN) plus ribavirin to treat hepatitis C virus (HCV) recurrence, analyzing possible factors associated with sustained viral responses (SVR). PATIENTS AND METHODS: Forty-one patients (25 men and 16 women) of overall mean age of 50 years (range, 33-60) with recurrent HCV were treated with peg-IFN plus ribavirin including 33 (80%) subjects displayed genotype 1. The following variables were analyzed: gender, donor and recipient ages, immunosuppressant, genotype, treatment duration, early viral response (EVR), pretreatment viral load, degree of fibrosis, levels of alanine aminotransferase and gamma-glutamyltransferase (IU/L), time since liver transplantation (OLT), use of stimulating factors (epoetin and granulocyte colony stimulating factor [G-CSF]) and side effects, and their association with SVR. The time from OLT to the start of treatment was 29 months (range, 6-90). Seventy-one percent of patients received cyclosporine and 29% tacrolimus. RESULTS: The mean treatment duration was 31 (range, 4-72) months with an EVR achieved in 12/38 (31.5%) of patients and a SVR in 16/41 (39%). Treatment was discontinued in 23 patients due to side effects. Epoetin was necessary in 29% and G-CSF in 10%. There were 3 cases of rejection (1 mild and 2 severe culminating in death). On univariate analysis genotype non-1B (P < .02), pretherapy RNA (P < .02), complete treatment, and EVR (P < .005) were the only variables associated with SVR. The mean donor age of 43 years showed no statistical significance. CONCLUSION: Therapy with peg-IFN plus ribavirin achieves an acceptable SVR, although not entirely free from severe side effects. Ensuring completion of the full treatment course is fundamental to achieve SVR.