Graft dysfunction associated with autoimmune phenomena has been recently described in liver transplant recipients without previous autoimmune disease. However, the natural history, diagnostic criteria, and definitive therapeutic approach of de novo autoimmune hepatitis (de novo AIH) are poorly understood. We report 12 cases of de novo AIH 27.9 ؎ 24.5 months after liver transplantation: the outcome of 7 patients treated with steroids is compared with a group of 5 nontreated patients. Nontreated patients lost the graft after 5.8 ؎ 2.6 months from de novo AIH onset. All treated patients were alive after 48.4 ؎ 14 (29-65) months from de novo AIH onset, and none of them lost the graft. However, 5 patients relapsed in relation to steroid tapering. All patients presented an atypical antiliver/ kidney cytosolic autoantibody, associated to classical autoantibodies in 10 cases. Histological study showed several degrees of lobular necrosis and inflammatory infiltrate. HLA antigen frequencies and matching were compared with 2 control groups (16 orthotopic liver transplantation [LTX] patients without de novo AIH and 929 healthy blood donors); de novo AIH patients showed a higher prevalence of HLA-DR3 (54.5% vs. 25.9%, P ؍ .04) than healthy controls, which was not observed in LTX patients without de novo AIH. In conclusion, this new disease should be included in the differential diagnosis of unexplained graft dysfunction. In addition, treatment with steroids results in a dramatically improved outcome. However, maintenance therapy is usually required. (HEPATOLOGY 2002;35:349-356.)
Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m ) or 5 (eGFR<15 mL/min/1.73m or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.
SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.
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