E. Oton

Hepatitis C Recurrence After Liver Transplantation: Viral and Histologic Response to Full‐Dose Peg‐Interferon and Ribavirin

Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48‐weeks of full‐dose peg‐interferon‐α‐2a (n = 4) or α‐2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients ≥12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 ± 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end‐of‐treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV‐RNA (p = 0.005) and a length from LT to therapy between 2–4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease ≥1‐log10 at week 4 and/or 2‐log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg‐interferon withdrawal in 16 (29%) subjects. In 15 patients with post‐treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.

Improved graft function in liver‐transplanted patients after partial splenic embolization: reversal of splenic artery steal syndrome?

Abstract:  Aim:  To describe the functional effect of partial splenic embolization (PSE) in liver‐transplanted (LT) patients with hypersplenism and hepatitis C virus (HCV) recurrence.

Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation

BACKGROUND & AIMS Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients. METHODS Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain. RESULTS In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p=0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT. CONCLUSIONS Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need. LAY SUMMARY Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need.

Partial Splenic Embolization for the Treatment of Hypersplenism in Liver Transplanted Patients with Hepatitis C Virus Recurrence before peg-interferon Plus Ribavirin

Reinfection of the graft follows liver transplantation (LT) patients with HCV, with an accelerated course of the disease due to immunosuppressive treatment (1). Progression to cirrhosis is increased, more than 20% of patients present severe graft damage at 5 years post-LT (2), and the rate of death and allograft failure is increased when compared with other indications (3). The lack of an efficient strategy to prevent graft reinfection and the aggressive course of HCV after LT indicate the need for an effective antiviral therapy able to preserve the viability of the graft. Recent data on the use of peg-IFN plus ribavirin (RBV) after LT are encouraging, with rates of sustained virological response (SVR) over 30%, improved graft function, and a beneficial effect on the histological disease progression (4). Therapy, however, is limited by the high rate of peg-IFN and/or RBV-related hematological toxicity leading to dose reductions and/or administration of hematopoietic growth factors, such as erythropoietin (EPO), or granulocyte-colonies stimulating factor (G-CSF) (5). To date, severe thrombocytopenia remains as an absolute contraindication for HCV therapy. Partial splenic embolization (PSE) seems to be an effective alternative to surgical splenectomy for the treatment of hematologic disorders in cirrhotic patients with hypersplenism, especially against thrombocytopenia (6), and improves liver functions (7). We aimed to evaluate the safety and effectiveness of PSE before peg-IFN/RBV in three liver recipients with HCV recurrence and hypersplenism. After pneumococcal vaccination, PSE was performed under intravenous antibiotic, sedative, and antiemetic therapy. A femoral artery approach was used for superselective distal catheterization of the splenic artery, with injection of polyvinyl-alcohol particles (355 to 500 ) suspended in a solution of penicillin, gentamicin, and non-ionic iodine contrast, to obtain an splenic infarction ratio between 50% and 80%. Contrast-enhanced abdominal CT scan and Doppler ultrasound studies were performed before PSE and during follow-up, to assess the presence of complications. At a mean of 12 weeks after PSE all patients started weight-adjusted RBV plus peg-IFN-2b and were assessed in a monthly basis, including

Is Liver Transplantation Advisable for Isoniazid Fulminant Hepatitis in Active Extrapulmonary Tuberculosis

Antituberculous treatment is a well‐known cause of fulminant hepatic failure (FHF). This could lead to liver transplantation as the only possible treatment, which on the other hand could be contraindicated due to active tuberculosis. The risk of aggressive dissemination of the disease after transplantation is not clearly determined by the current second‐line antituberculous therapies. We report a case of vertebral tuberculosis treated with rifampin, isoniazid and pyrazinamide. He developed an FHF that was treated with urgent liver transplantation. Despite the immunosuppression, the disease was well controlled with ciprofloxacin, ethambutol and streptomycin and the patient is in good health 23 months after transplantation. In conclusion, active extrapulmonary tuberculosis should perhaps be considered for liver transplantation when FHF develops due to anti‐tuberculous drugs.

Chronic intestinal pseudo-obstruction due to lymphocytic leiomyositis: is there a place for immunomodulatory therapy?

There is a rare cause of chronic intestinal pseudo-obstruction (CIPO) characterised by a lymphocytic infiltrate in the muscle of the intestine, which is called idiopathic lymphocytic leiomyositis. Few cases have been reported and prognosis is very poor. We present a case with a comparatively benign evolution, showing good response to immunosuppressive therapy. The patient was a healthy 16 year old female who presented with a crisis of postprandial bloating followed by diarrhoea and vomiting. During the following months she lost 10 kg in weight and any attempt at oral feeding resulted in severe abdominal distension and vomiting. Therefore, total parenteral nutrition was finally prescribed. Plain abdominal film and small bowel follow through indicated huge dilatation of the small intestine with air fluid levels. Gastroscopy and colonoscopy were normal, as were mucosal biopsies. Human immunodeficiency virus, hepatitis …

Hepatitis C Virus Sensitivity to Combined Antiviral Therapy in Liver Transplant Versus Immunocompetent Patients

Recurrent hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) frequently causes allograft failure, because viral aggressiveness has been shown to be increased among immunosuppressed patients. Several studies have reported lower efficacy of antiviral therapy after OLT associated with worse tolerability. The aim of this study was to compare the logarithmic falls in viral loads at 4 and 12 weeks of treatment with pegylated interferon alpha and ribavirin among OLT versus immunocompetent patients. OLT patients (group 1) were recruited from 3 Spanish centers. Two age- and sex-matched controls (group 2) were randomly assigned to each case. We excluded coinfection with human immunodeficiency virus or hepatitis B or cholestatic hepatitis. Among group 1 (n = 66) were 72.7% men with an overall mean age of 52.7 +/- 10.1 years; 90.9% were genotype 1. The mean baseline viral load was 6.0 +/- 0.6 log10 IU/mL, and 19% of patients had cirrhosis. Among group 2 (n = 132) were 72.7% men with an overall mean age of 50.1 +/- 10.1 years; 92.4% were genotype 1. The mean baseline viral load was 5.9 +/- 0.5 log10 IU/mL, and 17% of patients had cirrhosis. There were no significant differences in patient characteristics between the 2 groups. The logarithmic falls in viral loads at 4 weeks of treatment were similar in groups 1 and 2: 2.3 +/- 2.1 vs 2.4 +/- 1.9 log10 IU/mL (P = .49); they were also similar at 12 weeks of treatment: 3.9 +/- 1.9 vs 3.7 +/- 2.4 log10 IU/mL (P = .66). In conclusion, in our study HCV sensitivity to combined antiviral therapy was the same among transplant versus immunocompetent patients.

Severe Hepatitis C Recurrence: Is It a Negative Predictive Factor for Sustained Response to Treatment?

Dear Sir: We read with interest the article by Carrion et al1 entitled “Efficacy of Antiviral Therapy on Hepatitis C Recurrence After Liver Transplantation: A Randomized Controlled Study.” In the transplantation setting this is, to our knowledge, the first controlled and randomized study to explore not only the response to combined treatment for recurrent hepatitis C, but also the benefit in terms of fibrosis and hepatic venous pressure gradient. We are excited to read controlled studies, such as this one, that helps to manage recurrent hepatitis C in transplanted patients. We have one comment in relation to the basal factors found to be predictive of response to treatment. High bilirubin and severe recurrence have resulted as negative prognostic features in terms of sustained viral response. In group C (severe recurrence), out of the 27 patients, 12 were diagnosed with cholestatic hepatitis and 4 with fibrosing cholestatic hepatitis. This entity has been described in the transplantation setting2,3 as a pathogenically different disease with extremely high levels of viral load and direct damage to hepatocytes by the virus itself, and not directed by immunologic mechanisms. This disease frequently results in progressively higher levels of bilirubin and cholestatic enzymes so liver failure occurs in a short period of time if the patient is not treated. It is true that there are patients who have intermediate forms of severe hepatitis without evident histologic signs of fibrosing cholestatic hepatitis, and it is frequently difficult to classify a particular patient as having this or another type of recurrence. However, we also hold that there is a trend toward higher viral loads and higher bilirubin in the group with cholestatic hepatitis. Although cholestatic hepatitis is a type of severe recurrence, it should perhaps be analyzed separately, not mixed with established chronic hepatitis with fibrosis 3 or 4, whose prognosis and response to interferon could be different. High viral load is a recognized factor of worse response, and cholestatic hepatitis usually has much higher viral load than the rest of viral recurrences. So we agree that bilirubin and severe recurrence are predictors of a poor response, but perhaps only for cholestatic hepatitis and not for fibrosis 3 or 4, whose response could be similar to milder forms of recurrent hepatitis.4 We feel that this issue should be taken into account because, otherwise, it seems that very mild hepatitis without fibrosis should be treated very early posttransplantation because later their response will be much worse. This approach could be less than optimal owing to the high incidence of adverse events,4 including acute and chronic rejection.5,6 ELENA OTON Liver Transplantation Unit Hospital Universitario Nuestra Señora de la Candelaria Santa Cruz de Tenerife, Spain