Orthotopic liver transplantation in U.S. veterans under primary tacrolimus immunosupression.

The evolution and refinement of surgical techniques, per ioperative patient care, and immunosuppression hav~ estab~ished orthoto~ic li~er transplantation (OLTX) as a ~ighly successful therapeutic modality for patients wrth end-stage hver disease. In February 1989,Tacrohmus (Prograf®, formerly FK 506)was first used successfully at the University of Pittsburgh Medical Center to treat patients with rejection refractory to cyclosporine-based immunosuppression." Clinical trials utilizing Tacrolimus in solid organ transplantation followed, and in April of 1994 it was approved for use by the Food and Drug Administration

Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects

Cryoglobulinaemia may cause cutaneous vasculitis and glomerulonephritis, potentially leading to end stage renal failure. An important proportion of cryoglobulinaemias are secondary to hepatitis C virus infection. Emerging antiviral treatment options offer a chance for causal therapy of these cases of cryoglobulinaemia. This review summarises the classification and clinical and therapeutic aspects of cryoglobulinaemic vasculitis and glomerulonephritis

Clinical-evolutional particularities of the cryoglobulinemic vasculitis in the case of a patient diagnosed with hepatitis C virus in the predialitic phase

Hepatitis C virus (HCV) represents a fundamental issue for public health, with long term evolution and the gradual appearance of several complications and associated pathologies. One of these pathologies is represented by cryoglobulinemic vasculitis, a disorder characterized by the appearance in the patient’s serum of the cryoglobulins, which typically precipitate at temperatures below normal body temperature (37°C) and dissolve again if the serum is heated. Here, we describe the case of a patient diagnosed with HCV that, during the evolution of the hepatic disease, developed a form of cryoglobulinemic vasculitis. The connection between the vasculitis and the hepatic disorder was revealed following treatment with interferon, with the temporary remission of both pathologies and subsequent relapse at the end of the 12 months of treatment, the patient becoming a non-responder. The particularity of the case is represented by both the severity of the vasculitic disease from its onset and the deterioration of renal function up to the predialitic phase, a situation not typical of the evolution of cryoglobulinemia. Taking into account the hepatic disorder, the inevitable evolution towards cirrhosis, and the risk of developing the hepatocellular carcinoma, close monitoring is necessary

Renal transplantation in patients with hepatitis C virus antibody. A long national experience

Background. Renal transplantation is the best therapy for patients with hepatitis C virus (HCV) infection with end-stage renal disease. Patient and graft survival are lower in the long term compared with HCV-negative patients. The current study evaluated the results of renal transplantation in Spain in a long period (1990–2002), focusing on graft failure

Era of direct acting anti-viral agents for the treatment of hepatitis C.

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents (DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article

New Perspectives on Treatment of Hepatitis B Before and After Liver Transplantation

open5noThe hepatitis B virus (HBV) infects more than 260 million people globally, with increasing incidence, especially in developing countries. Despite antiviral therapies, HBV-related end-stage liver disease remains one of the most important indications for liver transplantation worldwide. Although new available treatments have improved the outcome of patients with both compensated and decompensated liver disease in some specific clinical settings as acute-on-chronic liver failure mortality is still high. Moreover, the incidence of HBV-related hepatocellular carcinoma (HCC) seems to be increasing and represents a major challenge for the transplant team. In the post-transplant setting, combination of anti-HBV immunoglobulins and oral nucleos(t)ides provided significant improvement on graft and patient survival. Furthermore, recent data suggested the possibility of personalized therapeutic algorithms based on pre and post-transplant viral and host risk factors. Finally, liver grafts from HBV core antibody (anti-HBc) positive or hepatitis B surface antigen (HBsAg) donors can be safely used in order to expand the donor pool, considering adequate allocation and tailored prophylaxis after LT. In this review we have focused on the evolution of antiviral therapy for HBV, highlighting useful information to aid the transplant hepatologist in clinical practice.ReviewopenZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, Francesco PaoloZanetto, Alberto; Ferrarese, Alberto; Bortoluzzi, Ilaria; Burra, Patrizia; Russo, FRANCESCO PAOL

Curing Hepatitis C in Liver Transplant Recipients Is Associated with Changes in Immunosuppressant Use.

Background and aimsAll-oral interferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients. The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).MethodsWe compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with all-oral direct acting agents.ResultsWe identified 52 liver LT treated recipients who achieved a SVR. The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most recipients received tacrolimus (TAC) for their immunosuppressant regimen. After achieving SVR, there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05). However, there was a statistically significant decrease in daily dose of TAC adjusted per weight, serum levels of TAC, and the product of glomerular filtration rate and TAC. No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.ConclusionsImmunosuppression needs were increased for those patients treated with TAC but not cyclosporine. LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection

Liver transplantation for viral hepatitis in 2015

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release

Role of antiviral therapy in the natural history of hepatitis B virus-related chronic liver disease

Hepatitis B virus (HBV) infection is a dynamic state of interactions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B (CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma (HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation