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Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary microvasculature dilatation that causes intrapulmonary shunting and leads to a gas exchange abnormality in the presence of liver diseases, which is the most common cause of respiratory insufficiency in these patients. HPS doubles the risk of death, and liver transplantation (LT) is the only curative therapeutic option so it should be considered in patients with severe HPS, with excellent survival rates post-LT. However, pretransplant Pao 2  <45 mm Hg has been associated with an increase in post-transplant morbidity and mortality, but it does not imply a contraindication for LT. The resolution of HPS usually occurs within 6 months post-LT, but it can take 1 year. Portopulmonary hypertension (PoPH) is defined as pulmonary arterial hypertension (PAH) that develops in the setting of portal hypertension with or without liver disease in the absence of other causes of PAH. The prevalence of PoPH is 5% to 10% among liver transplant (LT) candidates. The impact of LT on PoPH is unpredictable. Therefore, despite conferring a high morbidity and mortality, PoPH itself is not an indication for liver transplantation. It may be considered a contraindication for LT in severe cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus (HCV) still has significant prevalence in kidney transplant (KT) recipients and is related to poor recipient and graft survival. New direct-acting antivirals (DAA) are leading to a radical change in the problem., Methods: We studied HCV prevalence at the time of transplantation and in follow-up patients, the way cases are handled, and the results of DAA., Results: A total of 2,001 KT had been performed in our center since 1978. Pre- or post-transplantation HCV serology was present in 1,880 cases and was positive in 13.4%. A total of 1,195 transplant recipients were still being monitored by us, with only 60 (5%) HCV+ and 45 (3.6%) RNA+ cases. Of these 45 HCV+/RNA+, 25 had been or were being treated, 7 were about to begin treatment, 1 was awaiting new DAA treatment owing to low glomerular filtration rate (GFR), 3 were being evaluated, 2 had been excluded owing to high comorbidity, 2 refused to be treated, 2 needed to return to hemodialysis, and 1 was lost to follow-up. Except 1 case where Viekira Pak was used because of low GFR, all cases included sofosbuvir as the main drug associated with either ledipasvir (70%) or daclatasvir (25%). Ribavirin was added as coadjuvant in 35% of cases. Twenty-one patients had completed treatment (84%). Two patients had to interrupt DAA therapy (8%), one because of hepatotoxicity and the other as a result of a liver transplantation. In every case, the graft maintained function and negativization of viral replication occurred., Conclusions: Side effects have been low, anemia related to ribavirin being the main one. Just one case needed to be interrupted at the 7th week of DAA therapy due to hepatotoxicity. It has frequently been necessary to adjust immunosuppression treatment with the use of higher doses of tacrolimus., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The reported incidences of de novo malignancy following orthotopic liver transplantation (OLT) are significantly greater than those in the general population. We have analyzed the efficacy of mammalian target of rapamycin inhibitor (mTORi) as immunosuppressant therapy in patients with de novo malignancies or those engrafted because of a primary liver cancer., Methods: We performed a case-control study of patients with hepatocellular carcinoma (HCC; n = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven patients with these tumors were treated with mTORi, and 167, with calcineurin inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the CNI over 15 days, until obtaining levels of 5-10 ng/dL., Results: No incidence of rejection, serious adverse events, or death was observed with an overall actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group. Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05). Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05)., Discussion: Surprising differences in survival and tumor recurrence rates were observed among the mTORi-treated group compared with controls. Switching from CNI to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable to employ this strategy in liver transplant patients with primary hepatic or "de novo" neoplasms., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: We assessed whether trough anti-hepatitis B surface antigen (HBs) serum levels considered to be protective (>100 IU/L) were maintained in liver transplanted patients after 6 months of uninterrupted treatment with Niuliva, a new intravenous HBIg., Methods: Twenty patients, aged 18-70 years, who had undergone liver transplantation due to HBV-related liver disease at least 1 year before inclusion were enrolled in a prospective, open-label, uncontrolled, multicenter clinical study. A fixed monthly dose of 5,000 IU of study medication was administered intravenously for 6 months., Results: After the second infusion, all mean values of anti-HBs and 95% CIs were above the limit of 100 IU/L considered to be protective. The percentages of success ranged between 95% (95% CI 75.1%-99.9%) and 100% (95% CI 86.1%-100%). Mean values and 95% CI of in vivo recovery of anti-HBs at 15-30 minutes after each infusion showed overlaps between all intervals, which indicated that significant differences were not present in the recovery of post infusion anti-HBs in vivo. There were no recurrences of HBV infection during the study. There were no seroconversions in patients previously negative to hepatitis C virus or HIV. No serious adverse events related to the study medication were observed., Conclusions: Serum levels of anti-HBs after using Niuliva in patients who had undergone liver transplantation were protective in 95%-100% of cases after the study period. This new HBIg showed the expected pharmacokinetic profile and was well tolerated and safe.

Background: Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants which have the advantages, with respect to calcineurin inhibitors (CNI: cyclosporine or tacrolimus), of no nephrotoxicity and inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias., Materials and Methods: Twenty-two liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 7 hepatocellular carcinomas; 5 de novo malignancies; 4 renal insufficiencies; 4 chronic rejections; and 2 acute rejection episodes., Results: There were 16.7% tumor recurrences, and 25% improvements in renal function, 75% in chronic rejection, and 50% in acute rejection. There was no incidence of rejection, kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. We observed incidences of 50% for hypercholesterolemia, 31.8% for hypertriglyceridemia, 22.7% for thrombocytopenia, 18.2% for leukopenia, and 9.1% for anemia. The intercurrent infection rate was 13.6%, including oral thrush in 13.6%. Lower limb edema occurred in 13.6%, with 1 case of facial edema and 1 of alopecia., Conclusions: mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with no incidence of rejection. Their effectiveness to control chronic rejection seems significant, but it is doubtful for steroid-resistant acute rejection episodes.

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (-), 11.5%; anti-HBc (-)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients

We conducted a retrospective study to evaluate the response to recombinant hepatitis B vaccine after 4 intramuscular doses (40 microg) administered at 0, 1, 2, and 6 months in 157 cirrhotic patients who were liver transplant candidates. Seventeen nonresponders were revaccinated with the same schedule. We studied the association between the following variables and the vaccine response: age, gender, etiology of cirrhosis, diabetes, severity of liver disease (Child-Pugh class and Model for End-Stage Liver Disease [MELD] score), and the number of administered doses. The response rates were: 1 dose, 40% (2/5); 2 doses, 0% (0/7); 3 doses, 32.7% (16/49); and 4 doses, 31.3% (30/96) of patients. The median hepatitis B surface antibody (anti-HBs) titer was 45 mU/mL (range, 11-620 mU/mL). The response rate to revaccination was 41.2% (median anti-HBs titer, 88 mU/mL; range, 18-190 mU/mL). Diabetics showed a lower response rate than nondiabetic patients (17.2% vs 35.3%; P = .046). No association was observed between the response rate to vaccine and the other variables. In conclusion, the response rate to hepatitis B vaccine reached a little more than 30% in cirrhotic patients who received 3 or 4 doses. No higher response rate was observed among patients who received 4 doses. Diabetes was associated with a lower response rate. Anti-HBs seroconversion rates were not associated with the other variables. Revaccination may significantly increase the response rate to hepatitis B vaccine in cirrhotic patients, and may be considered in nonresponders after the third dose. Early vaccination against HBV should be considered in such patients.

Hepatocellular carcinoma is the most prevalent primary hepatic tumor. Early diagnosis and staging is of paramount importance to obtain favorable survivals. So far, there is no general agreement on the most appropriate imaging technique to detect the tumor for correlation between pretransplant radiologic and pathologic size of the tumor, which remains inadequate. With greater clinical experience and increasing accuracy of imaging methods, magnetic resonance (MR) appears to be the most accurate method, yielding a correlation in 67% of cases.

Hepatitis B virus (HBV) recurrence and de novo HBV infection are frequent events in liver transplantation recipients. Treatment with lamivudine is initially efficient in both infections but the incidence of lamivudine-resistant HBV emergence increases over time. Adefovir appears to be promising in post-liver transplantation patients with recurrent HBV infection and lamivudine-resistant HBV. This study analyzed adefovir treatment in 42 post-liver transplantation patients who developed recurrent HBV or de novo HBV infection with lamivudine-resistant HBV (54.8% HCV-coinfected). Patients received 10 mg of oral adefovir once daily for a mean period of time of 21.5 months (range from 12 to 31 months). In 62.9% of patients, ALT levels decreased significantly. Serum HBV-DNA was undetectable in 64% of the cases. Twenty percent of patients lost HBeAg marker and 13.3% of them developed anti-HBe. In 9.5% of recipients, HBsAg became negative. There was no significant change in serum creatinine levels. In only one patient was worsening of the renal function detected, making dose adjustment necessary. No other side effects were reported. Our results confirm the efficacy and safety of adefovir treatment in post-liver transplantation patients with lamivudine-resistant HBV, neither were adefovir-resistant mutations identified in patients after 21 months of therapy, nor were there adverse events, especially renal toxicity.

Glutathione S-transferase T1 (GSTT1) is a drug metabolizing enzyme abundantly expressed in liver and kidney cells; it is encoded by a single gene that is absent in 20% of the Caucasian population. Our group found that some liver transplantation patients developed de novo immune hepatitis (IH) and that all of them had anti-GSTT1 antibodies. The main objective of this study was to analyze the influence of a GSTT1 mismatch between donor and recipient in the immune response and the outcome of the graft. We confirmed that only under one of the four possible genetic combinations (null recipient/positive donor) is an alloimmune response triggered with production of anti-GSTT1 antibodies. Therefore, we conclude that this genetic mismatch can be considered a risk factor for de novo IH.