Interactions between virus-related factors and post-transplant ascites in patients with hepatitis C and no cirrhosis: role of cryoglobulinemia

Abstract

SummaryRefractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post-transplant cryoglobulinemia could be a predisposing factor for ascites in this population. Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than 1 year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had 1-year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis, and centrolobular necrosis. Additional biopsies were performed when needed. Fourteen of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0-F1 in 36% and F2-F3 in 57%. Factors independently associated with post-transplant ascites were pretransplant refractory ascites (P = 0.001), fibrosis ≥stage 2 at 1 year (P = 0.002), perisinusoidal fibrosis at 1 year (P = 0.02), and positive cryoglobulinemia (P = 0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites. Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at 1 year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV-related ascites.

Five myths about variable selection

“…Then, nonsignificant predictor variables were sequentially eliminated and models re‐estimated until all variables remaining in the model show significant association with the outcome. The technique of backward selection is sometimes also applied directly to a set of predictor variables , or the process of variable selection is reversed by “forward selection” , meaning that candidate predictors are sequentially included in a model if their association with the outcome variable, on top of the set of variables already in the model, is significant. Box provides an overview of the most common approaches of variable selection and explains some statistical notions commonly used in this context.…”

Ascites After Liver Transplantation

“…5,9 Positive cryoglobulinemia in HCV-positive patients was also found to be predictive of ascites development. 9 There are limited data on ascites resolution after HCV treatment, particularly with use of DAAs. However, in our experience, ascites generally resolves after HCV treatment if advanced fibrosis is not present.…”

“…HCV recurrence after liver transplantation can result in ascites even in the absence of significant fibrosis. According to two retrospective studies, ascites was found in patients with stage 0, 1, or 2 fibrosis on allograft biopsy 5,9 . Positive cryoglobulinemia in HCV‐positive patients was also found to be predictive of ascites development 9 .…”

“…According to two retrospective studies, ascites was found in patients with stage 0, 1, or 2 fibrosis on allograft biopsy 5,9 . Positive cryoglobulinemia in HCV‐positive patients was also found to be predictive of ascites development 9 . There are limited data on ascites resolution after HCV treatment, particularly with use of DAAs.…”

Approach to persistent ascites after liver transplantation

“…In the study by Lan et al [ 18 ] among 173 hepatitis C virus (HCV) transplants, 18 patients (10%) developed posttransplant ascites, with two-thirds of ascites episodes occurring without significant fibrosis. In the retrospective study of 82 liver transplant recipients with HCV recurrence, 17% of patients developed refractory ascites, and in some patients, refractory ascites occurred in the absence of advanced fibrosis[ 19 ]. In the same study, positive cryoglobulinemia that was systematically tested (P = 0.02) and perisinusoidal fibrosis at 1 year ( P = 0.02) were independently associated with posttransplant ascites[ 19 ].…”