M. Abradelo

Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%[95% CI, 54–80]) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation

Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG‐IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)‐ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG‐IFN (1.5 μg/kg/week) and ribavirin (800‐1,000 mg/day) for 12 months. Follow‐up was based on biochemical (ALT), virological (RNA‐HCV), and histological (liver biopsy) examinations. Follow‐up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low γ‐glutamyltransferase GGT (P = 0.04) and HCV‐RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patients compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG‐IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy. Liver Transpl 12:1805‐1812, 2006.

Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis C virus-coinfected liver transplant recipients: a FIPSE/GESIDA prospective cohort study.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)–infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)–coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV‐coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow‐up was 2.6 years (interquartile range = 1.25‐3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty‐eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty‐three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty‐six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3‐fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5‐5.8]. Independent factors for severe infections included a pretransplant Model for End‐Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70‐7.1), a history of AIDS‐defining events before transplantation (HR = 4.0, 95% CI = 1.9‐8.6), and non–tacrolimus‐based immunosuppression (HR = 2.5, 95% CI = 1.3‐4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV‐coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non–tacrolimus‐based immunosuppression. Liver Transpl 18:70–82, 2012.

Incidence and risk factors for the development of lung tumors after liver transplantation

Tobacco and immunosuppression are risk factors for developing upper aerodigestive and lung tumors after transplantation. This study comprises 701 adult recipients who survived more than 2 months after transplant: 276 patients underwent orthotopic liver transplantation (OLT) for alcoholic cirrhosis (AC) and 425 for nonalcoholic disease. The aim is to analyze the incidence, clinical characteristics, risk factors, and outcome of patients who develop lung malignancies after OLT. Incidence of lung cancer was 2.1% (15 patients): 4.3% (12 patients) in the alcoholic group and 0.7% (three patients) in the nonalcoholic group (P < 0.001). Mean time from OLT to tumor diagnosis was 86 months. Thirteen patients were smokers; 12 patients were heavy drinkers; and 11 were drinkers and smokers. Squamous cell carcinoma was diagnosed in nine patients, large cell carcinoma in three, adenocarcinoma in two, and broncoalveolar in one. Tumor staging: 10 patients at stage IV; three at stage IIIB; and two at stage IIB. Tumor resection was performed in one patient, and three also received chemotherapy. Mean survival after tumor diagnosis was 5.4 months. There is a higher risk of lung cancer in smoker patients who have undergone OLT for AC, and have a very poor prognosis because tumors are diagnosed at advanced stages.

Advantages of the piggy back technique on intraoperative transfusion, fluid compsumption, and vasoactive drugs requirements in liver transplantation: a comparative study

INTRODUCTION The piggyback technique was first described in adult liver transplantation in 1989, although it has been used in conjunction with venous bypass, with cross-clamping the vena cava, or both. In this study, the inferior vena cava was not occluded at any time during the liver transplant. OBJECTIVE We compared the use of intraoperative blood products, fluid requirements, and vasoactive drugs among patients managed with bypass, without bypass, and with the piggyback technique. MATERIAL AND METHODS Between May 1986 and October 2002, 875 liver transplants included 50 patients divided into three groups (cases considered to be the preliminary series on each group): group A/piggyback (17 patients:34%), group B/ bypass (16 patients: 32%), and group C/no bypass (17 patients:34%). There were no differences in mean age, gender, UNOS or Child-Pugh score, and indications for liver transplantation. RESULTS Mean follow up was 134.63+/-32.19 months. At the end of the study, 91.3% of the patients are alive with no operative mortality. There were no differences in postoperative complications, postreperfusion syndrome rate, and postoperative renal failure. However, the number of packed red blood cell units consumed intraoperatively (12+/-7.43 vs 18.03+/-11.46 vs 17.59 +/- 23.8; P =.043), the need for intraoperative crystaloids (3.1 L+/-1.6 vs 6.8+/-4.8 vs 9.1 L+/-3.6; P=.001) and the requirement for vasoactive drugs (18% vs 38% vs 24%; P=.043) was notably lower in group A vs group B vs group C. Operative time was longer in group A (121.54+/-37.77 vs 78.73+/-11.89 vs 87.07+/-14.33 minutes). CONCLUSIONS The piggyback technique requires a longer operative time but offers the advantages of reducing the red blood cell requirements and preventing severe hemodynamic instability by virtue of reducing the need for vasoactive drugs and for a larger volume of intraoperative fluids.

Advanced donor age increases the risk of severe recurrent hepatitis C after liver transplantation

The association between donor age and the severity of recurrent hepatitis C and, whether there is any donor age above which severity of recurrence increases significantly, were analyzed. A total of 131 liver grafts of hepatitis C virus (HCV)‐infected recipients were selected for the study. Distribution of donor age was compared between grafts with and without severe recurrence. The risk of developing severe recurrence as well as the hepatitis‐free, severe hepatitis‐free and HCV‐related graft survival was compared between different donor age groups. Mean donor age was higher for grafts with severe recurrence (P = 0.007). The risk of developing severe recurrence within 2 years post‐transplant increased with donors aged ≥50 years (RR = 1.34) and donors aged ≥70 years (RR = 1.61). Five‐year severe hepatitis‐free survival rates decreased progressively when donor age was over 50 years (P < 0.001). The study shows 50 and 70 years as the donor age cut‐off points above which the evolution of HCV‐infected recipients worsens.

Upper aerodigestive tract and lung tumors after liver transplantation

BACKGROUND The purpose of this study was to analyze the incidence, clinical characteristics, treatment, and outcome of upper aerodigestive (UAD) and lung de novo tumors after ortothopic liver transplantation (OLT). PATIENTS AND METHODS Between April 1986 and June 2002, we performed 851 OLT in 753 patients. We excluded pediatric, partial, and hepatorenal transplants and recipients who died within 2 months after OLT. Thus, we analyzed the incidence and outcome of these tumors in 605 patients after OLT. RESULTS We found 21 (3.5%) tumors in 20 (3.3%) recipients: 14 were UAD tumors (three in floor of the mouth, two in tonsil, one in tongue, one in pharynx, three in larynx, and four in esophagus) and seven were lung tumors. Nineteen patients were men and one was a woman, with a mean age at transplantation of 47.7+/-8.6 years. Mean time from OLT to tumor diagnosis was 61.7+/-35.1 years. As risk factors, 70% were heavy smokers, 75% were heavy drinkers, and 70% developed acute rejection. The incidence of these tumors was significantly higher in transplanted patients for alcoholic cirrhosis compared to the nonalcoholic cirrhosis (8.1% vs 0.8%; P<.0001). After surgical excision in 65% of patients, 1-, 2-, and 3-year patient survival were 47.6%, 37.0%, and 19.7%, respectively. CONCLUSION There is a significantly higher incidence of these tumors in male heavy drinkers and/or smokers who underwent OLT for alcoholic cirrhosis; in spite of aggressive surgical treatment, the prognosis is poor.

Incidence, risk factors, and outcome of chronic rejection during antiviral therapy for posttransplant recurrent hepatitis C

Antiviral therapy for recurrent hepatitis C in liver transplantation has been associated with the development of chronic rejection. The aim of this study was to assess the incidence, evolution, and risk factors associated with the development of chronic rejection during posttransplant hepatitis C virus antiviral therapy. Seventy‐nine patients with posttransplant recurrent hepatitis C who were treated with pegylated interferon and ribavirin were prospectively followed. Liver biopsy was performed before antiviral therapy was initiated and when liver tests worsened during therapy. Pretransplant and posttransplant factors were analyzed as potential risk factors for the development of chronic rejection. Seven of 79 patients (9%) developed chronic rejection during antiviral therapy. The mean time from the start of treatment to the development of chronic rejection was 5.8 months (3–12 months). An analysis of factors associated with the development of chronic rejection showed that the use of cyclosporine as immunosuppression therapy (6 of 19 patients who received cyclosporine developed chronic rejection in comparison with only 1 of 57 patients who received tacrolimus; P = 0.0013), achievement of sustained virological response (P = 0.043), and ribavirin discontinuation (P = 0.027) were associated with the development of chronic rejection. In conclusion, the development of chronic rejection during posttransplant pegylated interferon and ribavirin therapy is a severe complication. The use of cyclosporine, ribavirin discontinuation, and viral infection elimination seem to be associated with the development of this complication. Liver Transpl 15:948–955, 2009.

Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: A prospective cohort study

BACKGROUND & AIMS The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. METHODS This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. RESULTS Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. CONCLUSIONS The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly.

Liver transplantation and transjugular intrahepatic portosystemic shunt

OBJECTIVE Describe the results of liver transplantation after installing Transjugular Intrahepatic Portosystemic Shunt (TIPS) and compare them with those of a control group in a comparative, longitudinal, retrospective study. MATERIALS AND METHODS Between April 1986 and October 2002, we performed 875 liver transplantations. Between January 1996 and October 2002, 26 transplantations were performed on TIPS carriers. This group was compared with a control cohort of 50 randomly selected patients who underwent transplantation in this period (non-TIPS carriers). Both groups were homogeneous with no significant differences between age, sex United Network for Organ Sharing (UNOS) score, Child stage, or etiology. RESULTS Actuarial survival rates at 1 and 3 years: TIPS group 96.15% and 89.29% versus control cohort 87.8% and 81%, respectively. In 73.9%, the TIPS was clearly effective; in 88.9%, a postoperative Doppler revealed normal flow. There were no statistically significant differences compared with time on the waiting list for transplant, duration of the operation, ischemia times, intraoperative consumption of hemoderivates, vascular or nonvascular postoperative complications, duration of stay in the intensive care unit, hospital stay, or retransplantation rate. CONCLUSIONS In our experience, TIPS insertion does not affect either the intraoperative or postoperative evolution and is not associated with an increased time on the liver transplant waiting list.