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Purpose of Review: To give a comprehensive update of the current hepatitis C (HCV) antiviral treatments in the liver transplant setting., Recent Findings: Hepatitis C treatment after liver transplantation with several interferon-free combinations has shown excellent efficacy and safety results, overwhelming interferon-based therapies in this setting. In posttransplant decompensated liver disease, however, efficacy of antiviral therapies seems to be lower, but viral eradication has been associated with an improvement of liver function and clinical status in most cases. Hence, antiviral treatment should be offered before advanced liver disease is reached, in order to prevent graft damage and guarantee the best efficacy rates of therapies., Summary: New interferon-free combinations with potent direct antivirals cure hepatitis C in most of patients after liver transplantation. Hepatitis C after liver transplantation should be treated as early as possible and before advanced liver disease is established in the graft. In patients with graft cirrhosis, eradication of hepatitis C is associated with improved liver function.

Cryoglobulinemia is characterized by a wide range of causes, symptoms, and outcomes. Hepatitis C virus (HCV) infection is detected in 30%-100% of patients with cryoglobulins. Although more than half the patients with cryoglobulinemic vasculitis present a relatively benign clinical course, some may present with potentially life-threatening situations. We conducted the current study to analyze the clinical characteristics and outcomes of HCV patients presenting with life-threatening cryoglobulinemic vasculitis. We evaluated 181 admissions from 89 HCV patients diagnosed with cryoglobulinemic vasculitis consecutively admitted to our department between 1995 and 2010. In addition, we performed a systematic analysis of cases reported to date through a MEDLINE search.The following organ involvements were considered to be potentially life-threatening in HCV patients with cryoglobulinemic vasculitis: cryoglobulinemic, biopsy-proven glomerulonephritis presenting with renal failure; gastrointestinal vasculitis; pulmonary hemorrhage; central nervous system (CNS) involvement; and myocardial involvement. A total of 279 patients (30 from our department and 249 from the literature search) fulfilled the inclusion criteria: 205 presented with renal failure, 45 with gastrointestinal vasculitis, 38 with CNS involvement, 18 with pulmonary hemorrhage, and 3 with myocardial involvement; 30 patients presented with more than 1 life-threatening cryoglobulinemic manifestation. There were 146 (52%) women and 133 (48%) men, with a mean age at diagnosis of cryoglobulinemia of 54 years (range, 25-87 yr) and a mean age at life-threatening involvement of 55 years (range, 25-87 yr). In 232 (83%) patients, life-threatening involvement was the first clinical manifestation of cryoglobulinemia. Severe involvement appeared a mean of 1.2 years (range, 1-11 yr) after the diagnosis of cryoglobulinemic vasculitis. Patients were followed for a mean of 14 months (range, 3-120 mo) after the diagnosis of life-threatening cryoglobulinemia. Sixty-three patients (22%) died. The main cause of death was sepsis (42%) in patients with glomerulonephritis, and cryoglobulinemic vasculitis itself in patients with gastrointestinal, pulmonary, and CNS involvement (60%, 57%, and 62%, respectively). In conclusion, HCV-related cryoglobulinemia may result in progressive (renal involvement) or acute (pulmonary hemorrhage, gastrointestinal ischemia, CNS involvement) life-threatening organ damage. The mortality rate of these manifestations ranges between 20% and 80%. Unfortunately, this may be the first cryoglobulinemic involvement in almost two-thirds of cases, highlighting the complex management and very elevated mortality of these cases., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Considering the impact of recurrent hepatitis C after liver transplantation on patient and graft survival, we examine the current and potential use of protease inhibitors in the prevention and treatment of recurrent hepatitis C., Recent Findings: In genotype-1-infected patients in the waiting list, triple therapy with boceprevir or telaprevir should be considered in compensated cirrhotics. However, tolerability of therapy is low, and side effects are frequent and potentially life-threatening. In posttransplant hepatitis C, available data suggest that triple therapy substantially increases the virological response. Interactions of protease inhibitors with immunosuppressants are considerable, especially between tacrolimus and telaprevir. Anemia seems to be particularly frequent with triple therapy after liver transplantation. Interferon (IFN)-free regimens seem to achieve a high antiviral effect with an excellent safety profile and will probably replace the current IFN-based treatments in a few years from now., Summary: Antiviral therapy with protease inhibitors will substantially increase the number of patients achieving sustained hepatitis C virus eradication, either before or after liver transplantation. However, side effects and drug-drug interactions will possibly hamper their applicability in both settings; thus, a careful selection and management of patients will be crucial. In the near future, combination of direct-acting antivirals will allow shorter, safer, and more effective IFN-free regimens.

The emergence of tumor necrosis factor-α (TNF-α)-targeted therapies as a key therapeutic option for patients with rheumatic, digestive, and dermatologic autoimmune diseases has been associated with increasing reports of liver damage in patients with hepatitis B virus (HBV) infection. We studied the current evidence on the use of anti-TNF agents in patients with HBV through a systematic analysis of cases reported in the MEDLINE and EMBASE databases using the MeSH term "hepatitis B virus" combined with the terms "infliximab," "etanercept," "adalimumab," "certolizumab," "golimumab," and "anti-TNF agents," and summarize the results here. We analyzed 257 patients with positive HBV markers who received anti-TNF therapy (255 identified in the search strategy and 2 new cases), 89 HBsAg+ carriers, and 168 anti-HBc+ persons. HBV reactivation was reported in 35 (39%) HBsAg+ carriers. The percentage of reactivation was higher in patients previously treated with immunosuppressive agents (96% vs. 70%, p=0.033) and lower in those who received antiviral prophylaxis (23% vs. 62%, p=0.003). Acute liver failure was reported in 5 patients, 4 of whom died. Infliximab was associated with a higher rate of induced liver disease (raised transaminase levels, clinical signs, viral reactivation, and acute liver failure) compared with etanercept. In anti-HBc+ persons, reactivation was reported in 9 (5%) cases, including 1 patient who died due to fulminant liver failure.In summary, our search of the current evidence identified 257 reported HBV+ patients treated with anti-TNF agents, with a significant percentage of liver damage in HBsAg+ carriers, including raised transaminase levels (42%), signs and symptoms of liver disease (16%), reappearance of serum HBV-DNA (39%), and death related to liver failure (5%). The rate of reactivation in anti-HBc+ persons was 7-fold lower than in HBsAg+ carriers. The increasing number of reported cases of HBV reactivation following TNF-targeted therapies and the associated morbidity and mortality demand specific preventive strategies.

Background: In the liver transplantation (LTx) setting, there are several situations where measurement of hepatitis C virus (HCV)-RNA concentration may provide relevant information. However, HCV-RNA quantification is expensive and not routinely available in all laboratories. An assay to quantify total HCV core antigen in serum has been recently developed. The aim of this study was to compare the performance of HCV-RNA and HCV core antigen determination in a cohort of 116 HCV-infected patients who underwent LTx., Methods: HCV-RNA and HCV core antigen concentrations were determined in serum samples (n=435) obtained before LTx and at weeks 4, 12, and 48 after LTx., Results: There was an excellent correlation between HCV-RNA and HCV core antigen levels (r=0.802 P<0.001), with an equivalence of 9,900 IU/mL of HCV-RNA per pg/mL of HCV core antigen. The determination of core antigen was linear in samples containing between 20,000 and 2,500,000 IU/mL of HCV-RNA and highly reproducible (mean coefficient of variation, 15%). Overall, HCV core antigen tested positive in 378 (92%) of 410 samples with detectable HCV-RNA (>600 IU/mL); the percentage increased to 98% in samples taken later than 4 weeks after LTx. In fact, almost all samples (369 of 375 [98.4%]) with HCV-RNA levels higher than 20,000 IU/mL were positive for HCV core antigen, whereas 56 of 57 samples with undetectable core antigen had HCV-RNA levels below 50,000 IU/mL., Conclusions: The performance of total HCV core antigen immunoassay is appropriate for monitoring viral load in HCV-infected patients undergoing LTx and might be considered a useful alternative to HCV-RNA testing.

Background: Hepatitis C recurrence after liver transplantation is often associated with accelerated graft fibrosis and progression to cirrhosis. Because drugs blocking the action of angiotensin-II can reduce fibrosis in different human and experimental models, we assessed the possible beneficial effect of these drugs on graft fibrosis in hepatitis C recurrence after liver transplantation., Methods: We retrospectively reviewed the charts of 128 liver-transplant recipients with hepatitis C recurrence. Twenty-seven patients (group I) received angiotensin converting enzyme inhibitors or angiotensin-II receptor antagonists as antihypertensive treatment, and 101 patients (group II) did not receive these drugs., Results: No significant differences were found between groups I and II in demographic, clinical, and laboratory data. In contrast, cirrhosis in the graft was less frequently observed in group I than in group II during postransplant follow-up: 15% versus 35% (P=0.035), respectively, with a probability of cirrhosis of 9% versus 32% at 5 years after transplantation and 35% versus 70% at 10 years (P=0.0049). Furthermore, the fibrosis stage (scored from 0-4) in the liver biopsy obtained at the end of follow-up was significantly lower in group I than in group II (median [and range]: 1 [0-4] vs. 2 [0-4]; P=0.038), and the fibrosis progression index (increase of fibrosis stage per year) was also lower in group I than in group II (0.21 [0-0.45] vs. 0.52 [0-2.58]; P=0.006)., Conclusion: The administration of angiotensin-blocking agents may be beneficial to reduce the development of graft fibrosis in hepatitis C recurrence after liver transplantation.

To determine the clinical characteristics and outcome of patients with chronic hepatitis C virus (HCV) infection presenting severe autoimmune cytopenia unrelated to interferon alpha therapy, we analyzed characteristics and outcomes of 35 patients with HCV (16 from our departments and 19 from the literature). We considered active autoimmune hemolytic anemia (AHA) as a decrease of at least 2 g/dL in hemoglobin levels, an increase of at least 0.6 mg/dL in the serum unconjugated bilirubin level, a reticulocyte count >5%, and a positive direct Coombs test. Severe neutropenia was defined as a neutrophil count <0.5 x 10(9)/L, and severe thrombocytopenia as a platelet count <30 x 10(9)/L. We identified the following cytopenias: AHA (17 cases), severe thrombocytopenia (16 cases), aplastic anemia (2 cases), severe neutropenia (1 case), refractory sideroblastic anemia (1 case), and pure red cell aplasia (1 case). Three patients simultaneously presented 2 types of severe cytopenias. Twenty-seven patients (77%) were female and 8 (23%) male, with a mean age at diagnosis of cytopenia of 51.7 years (range, 18-84 yr). Immunologic markers were detected in 19 (68%) of 28 patients, the most frequent being hypocomplementemia in 16 (57%), cryoglobulins in 15 (54%), antinuclear antibodies in 12 (43%), and rheumatoid factor in 5 (18%). Other associated processes were autoimmune diseases in 14 (50%) of 28 and human immunodeficiency virus (HIV) coinfection in 3 (9%) of 32. We found clinical and immunologic differences between HCV patients with AHA and those with severe thrombocytopenia. Patients with HCV-related AHA showed a higher prevalence of associated autoimmune diseases (71%), cryoglobulins (67%), and cirrhosis (59%). All had a good response to corticosteroids, but a poor prognosis (47% mortality). In contrast, patients with HCV-related severe thrombocytopenia had a lower prevalence of associated autoimmune diseases (11%), a poorer response to corticosteroids (55%), and lower mortality (6%), with HIV/HBV coinfections in some patients. The 35 cases presented demonstrate that different types of immune-mediated cytopenias may be severe and clinically significant in patients with HCV infection. Hemolytic anemia and severe thrombocytopenia were the most frequent cytopenias observed. Most patients responded well to corticosteroids, although a higher rate of mortality was observed in those with liver cirrhosis.