Cyclosporin in steroid-resistant autoimmune hepatitis and HCV-related liver diseases.

Cyclosporin has been used for many years in transplantation, and in this field its role is widely documented. However, other fields of application merit to be investigated, including the role of cyclosporin in treating autoimmune hepatitis and its possible role as an antiviral agent in hepatitis C virus (HCV) infections in both immunocompetent patients and in recipients of orthotopic liver transplants. Cyclosporin A has given promising results in small studies, and experience in transplantation and other immunological disorders indicates that its side-effects can be adequately managed. Cyclosporin certainly deserves further clinical investigation for first-line therapy in autoimmune hepatitis. Cyclosporin A suppresses the HCV genome dose-dependently in vitro at clinically relevant concentrations (150-250 ng/mL). The maximum effect is similar to that obtained with IFN alpha, and the effects of these two agents are certainly additive, and possibly synergistic. The inhibitory action of cyclosporin A appears to be independent upon its immunosuppressive action. Analysis of indirect endpoints in clinical trials on cyclosporin A for immunosuppression in transplant recipients indicates that cyclosporin A treatment can delay recurrence of HCV. Small, open label studies suggest that the observed anti-HCV activity of cyclosporin A can be translated into a real clinical benefit; nevertheless, these findings need to be confirmed in randomized, controlled clinical trials.

Bronchoalveolar lavage and its role in diagnosing cobalt lung disease.

The bronchoalveolar lavage (BAL) of two groups of hard metal workers (11 subjects) were examined and compared with BALs of 14 unexposed individuals as controls. The first group of workers included five asymptomatic subjects (2 females and 3 males) with normal lung function tests and chest X-rays. All the workers had been exposed daily to hard metal dust for 5 years before fiberoptic bronchoscopy. The second group of workers included six individuals (1 female and 5 males) with cobalt lung disease at biopsy. The BAL's cytology at the deep lung level is in agreement with a possible immunologic pathogenesis of the lung disease, similar to hypersensitivity pneumonitis (lymphocytosis with helper-suppressor ratio reduction). In order to identify diagnostic key-parameters, the data presented here are compared with data reported in literature for workers with a history of hard metal or cobalt (alone) exposure. Although the BAL can be useful, for a better definition of the reaction at the deep lung level, it seems insufficient per se for the diagnosis of hard metal lung disease.

Combined double lung-liver transplantation for cystic fibrosis without cardio-pulmonary by-pass.

Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244-1,533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.