Hepatitis: Lumbreras C

Miró JM, Torre-Cisnero J, Moreno A, Tuset M, Quereda C, Laguno M, Vidal E, Rivero A, Gonzalez J, Lumbreras C, Iribarren JA, Fortún J, Rimola A, Rafecas A, Barril G, Crespo M, Colom J, Vilardell J, Salvador JA, Polo R, Garrido G, Chamorro L, Miranda B. · AIDS Study Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). · Enferm Infecc Microbiol Clin. · Pubmed #15970168 links to  free full text

Abstract: Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at http://www.gesidaseimc.com.

Fernández I, Rubio R, Lumbreras C. · Department of Gastroenterology and Hepatology, HIV Unit, Department of Internal Medicine, and Unit of Infectious Diseases, Hospital 12 de Octubre, Madrid, Spain. · Clin Microbiol Infect. · Pubmed #11952720 No free full text.

Abstract: The use of highly active antiretroviral therapy (HAART) has extended the lifespan of patients infected with human immunodeficiency virus (HIV). As the prognosis of HIV infection has improved, liver disease associated with hepatitis C virus (HCV) has become clinically significant in patients with HIV, liver failure being a frequent cause of death in this population. HIV infection may accelerate the course of liver disease in patients co-infected with HCV, so infection with HCV should be treated like any other opportunistic disease in these patients. Nowadays, combination therapy with interferon-alpha and ribavirin is the standard treatment for chronic hepatitis C in HIV-negative patients. Preliminary results of combination therapy in HIV/HCV co-infected patients have been promising, showing a sustained response rate in 40% of these patients. Patients with higher CD4 counts and lower HCV/HIV viral load and those infected with HCV genotype 3a have a better response to therapy. Potential drug interactions between HAART therapy and interferon and ribavirin treatment emphasize the importance of initiating treatment of HCV infection in HIV-positive individuals as soon as possible and ideally before the need for anti-HIV therapy. Recent case reports have suggested that liver transplantation might be an appropriate procedure in HIV patients with undetectable HIV viral load, high CD4 counts and HCV advanced liver disease. However, the limited amount of available information and the complexities of drug interactions between HAART therapy and immunosuppressive drugs oblige us to be prudent within considering such a procedure.

Fernández I, Meneu JC, Colina F, García I, Muñoz R, Castellano G, Fuertes A, Abradelo M, Lumbreras C, Moreno E, Solís-Herruzo JA. · Gastroenterology Department, Hospital Universitario "12 de Octubre," Madrid, Spain. · Liver Transpl. · Pubmed #17133585 links to  free full text

Abstract: 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 microg/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 gamma-glutamyltransferase GGT (P = 0.04) and HCV-RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patient's 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.

Alonso O, Loinaz C, Moreno E, Jiménez C, Abradelo M, Gómez R, Meneu JC, Lumbreras C, García I. · Department of Surgery and Abdominal Organ Transplantation, Hospital '12 de Octubre', Universidad Complutense de Madrid, Madrid, Spain. · Transpl Int. · Pubmed #16008738 No free full text.

Abstract: 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 > or =50 years (RR = 1.34) and donors aged > or =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.

Loinaz C, Lumbreras C, Moreno E, Colina F, Fuertes A, Gómez R, Jiménez C, González-Pinto I, García I, Rojas J, Bellorín C. · Department of Surgery, Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain. · Hepatogastroenterology. · Pubmed #11677981 No free full text.

Abstract: BACKGROUND/AIMS: Hepatitis C-related liver disease is the main indication for liver transplantation in many centers. Viral RNA remains after transplantation in almost 100% of the patients, and more recent reports show a graft hepatitis rate of about 90%. The progression of this hepatitis seems to be quicker than in the nontransplant setting. METHODOLOGY: From June 1989 to October 2000, 197 adult patients had 213 for HCV-related liver disease at our institution. Basal immunosuppression consisted of a triple therapy with cyclosporine, azathioprine and steroids, or dual therapy with tacrolimus and steroids. None of the patients was treated with antivirals after liver transplantation. RESULTS: Pure HCV-related cirrhosis was the indication for liver transplantation in 114 patients, another 14 with hepatocellular carcinoma, 8 associated metabolic diseases, 43 high alcohol intake, 4 hepatitis B, 5 cholestatic diseases, and 3 other diseases. Six patients out of the 197 transplanted in this period were already grafted before this time, and had their first retransplantation of the liver after 1989 (their first liver transplantation was done when HCV was not known). Sixteen additional retransplantation procedures were done in the period considered. Hepatitis was diagnosed in 84.3% of the grafts biopsied later than 90 days after liver transplantation (118/140), and in 92.9% if it was done after one year (92/99). Cirrhosis was diagnosed in 21 grafts at a mean time of 1004.7 days, 21.2% of the grafts biopsied after 1 year and 28.6% after 2 years. Nine grafts in 8 patients were diagnosed as fibrosing cholestatic hepatitis. Patient actuarial survival was 80.9%, 69.7%, 67.5% and 50.6% at 1, 3, 5 and 10 years. Liver failure and hepatoma recurrence were the cause of death in 42.4% of the patients. Actuarial graft survival was 75.2%, 64.9%, 63.5% and 48.6% at 1, 3, 5 and 10 years, and was significantly affected by Child stage (B vs. C, P = 0.004). When compared to 228 non-HCV- infected patients with chronic parenchymatous disease, these had an almost significantly better patient survival (P = 0.0577), but a nonsignificant difference in graft survival. Graft loss related to liver causes was 17.6% in HCV+ patients 14.6% in HCV- patients. Liver causes of death were 14.0% in HCV+ patients and 4.8% in HCV-patients (P = 0.002). CONCLUSIONS: HCV infected liver transplantation recipients present very often graft hepatitis, which may progress to advanced stages in a quite short interval. Mid-term patient and graft survival is comparable to those of non-HCV recipients, but causes of death related directly to liver disease are more common in HCV+. This makes one think that long-term prognosis (more than 10 or 15 years) will be worse in HCV patients.