Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments.

Multifocal phaeohyphomycosis caused by Exophiala xenobiotica in a kidney transplant recipient.

In recent years, black fungi have been increasingly reported as causing opportunistic infections after solid organ transplantation. Here, we report a case of insidious, relentless, and multifocal Exophiala xenobiotica infection in a kidney transplant recipient that eventually required multiple surgical excisions along with oral and intravenous antifungal combination therapy using liposomal amphotericin B and posaconazole. We compare the present case with all previously reported cases of Exophiala infection after kidney transplantation.

[Risk of materno-fetal transmission of the HIV infection with antiretroviral therapy and cesarean section: experience of the Parma group]. / Rischio di trasmissione materno-fetale dell'infezione da HIV mediante terapia antiretrovirale e taglio cesareo: esperienza del gruppo di Parma.

Vertical transmission of HIV is by far the most important way of infection in pediatric patients. Transmission rate of infection varies between 15-40% in the absence of antiretroviral prophylaxis. Only 2% of infected pregnant women who underwent caesarean section and zidovudine treatment transmitted the infection to their newborns. From January 1995 to September 2000 twenty seropositive pregnant women and their twenty newborns were followed at the Azienda Ospedaliera of Parma. Nine women (45%) were treated with only zidovudine according to the ACTG 076 protocol; eight women (40%) continued the treatment they were assuming before pregnancy with the eventual addition of zidovudine. 3 women (15%) were not treated because HIV infection was only detected after delivery. 15 women underwent caesarean section, in 13 cases in association to antiretroviral prophylaxis: in the remaining 2 cases no intrapartum treatment was started due to the urgency of delivery. The rate of vertical transmission among the 20 women was 5% (1/20), significantly less then that observed (20.5%) among 31 pregnant HIV women followed in Parma from January 1987 to December 1994 and not treated with antiretroviral prophylaxis and/or cesarean section (Magnani G. Personal data). The only infected baby was born by vaginal delivery. No transmission was observed in the group of pregnant women who underwent the combination of antiretroviral prophylaxis and cesarean section.

Hepatitis C virus viremia following clinical resolution of acute hepatitis C.

Clinical resolution of acute hepatitis C occurs in a limited proportion of cases. However, the rate of hepatitis C virus persistence remains unclear. For this purpose, we conducted a serial study of 60 patients with hepatitis C virus infection from the early stage of the disease for 24 to 80 months (average 50 months). Fourteen cases who recovered from acute hepatitis were selected from this group for prospective analysis of the behavior of liver enzymes, anti-HCV antibodies (RIBA II, Ortho Diagnostic System) and hepatitis C virus-RNA in serum and in peripheral blood lympho-mononuclear cells by nested polymerase chain reaction. Primers were derived from the 5'-untranslated region of the hepatitis C virus genome and the amplified products were detected by gel electrophoresis and a DNA enzyme immunoassay. All patients except two showed early recovery from acute hepatitis that occurred within 3 months from clinical onset. Transaminase normalization was always preceded by clearance of serum hepatitis C virus-RNA, which remained negative throughout follow-up. During the resolution phase of the disease a progressive decline in the antibody response was observed in most of the patients. At the end of the study anti-C100 was negative in half the cases, while anti-C33 and anti-C22 became negative or borderline in five cases. Hepatitis C virus-RNA was found in the peripheral blood lympho-mononuclear cells, but not in the serum, of only one of eight patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up of anti-hepatitis C virus antibodies in patients with acute nonA nonB hepatitis and different outcome of liver disease.

We screened 74 patients with nonA nonB acute hepatitis (37 of post-transfusion PTH, and 37 of non-post-transfusion, NPTH, origin) for the presence of anti-HCV by tests detecting either C100-3 antibodies alone (ELISA I) or C100-3 plus C33c plus C22-3 antibodies (ELISA II). Samples were taken at the onset of disease and then serially for a period of time ranging from 12 to 60 months. An increased number of anti-HCV positive cases (86% vs 69%) and an earlier seroconversion were observed with the second compared to the first generation ELISA. Positive samples were confirmed by recombinant immunoblot assay (RIBA), which was also used to study the kinetics of the antibody response to individual HCV antigens. Anti-C33c and anti-C22-3 antibodies were the first detectable markers of HCV infection in 80% and 20% of the patients, respectively. Thirty-two percent of the patients studied showed complete and persistent biochemical recovery, whereas 68% maintained a chronic elevation of the transaminase values. Among the 20 patients who showed early and persistent normalization of the transaminase values, complete disappearance of all antibody reactivities was limited to five of them, whereas in four cases only anti-C100-3 and anti-5-1-1 became negative.