Browsing by Author "Phillips, A"
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- Presence of Multilobular Necrosis on Liver Biopsy Identifies Corticosteroid Responsiveness in Acute Indeterminate HepatitisPublication . Lin, S; Araújo, C; Hall, A; Kumar, R; Phillips, A; Hassan, M; Engelmann, C; Quaglia, A; Jalan, RBackground and aims: Treatment of patients with severe indeterminate hepatitis (IAH) is an unmet need. Corticosteroids are often used in the management of these patients but criteria for the selection of patients for this intervention are arbitrary. The aims of this study were to analyse the clinical and pathological features of patients with IAH to define predictors of corticosteroid responsiveness. Methods: This study included consecutive patients with acute indeterminate hepatitis admitted to a single hospital and underwent a liver biopsy. The clinical manifestation and histopathological features of steroid and non-steroid groups were compared and their relationship with corticosteroids response was evaluated. Results: Forty-eight patients were included, 24 (50%) recovered and the other half underwent liver transplantation or died within 3-months. Of the 48 cases, 24 received corticosteroids (initial dose of 45 ± 12 mg prednisolone). Corticosteroids were initiated 2.7 ± 3.8 days after admission. Liver biopsy was performed 2-days (median, IQR 1-3) after admission. Fifteen (62.5%) patients receiving corticosteroids survived without transplantation compared with 9 (37.5%) that did not receive steroids (P = .149). In those with multilobular necrosis, 50% reduction in the death/transplantation rate was observed after steroid treatment (P = .018). In patients without multilobular necrosis and with or without perivenulitis, corticosteroids did not impact the outcome. Response to corticosteroids was independent of the MELD score. Conclusions: The presence of multilobular necrosis on liver biopsy helps identify a subgroup of IAH cases who may benefit from the administration of corticosteroids.
- Prognostic Role of Liver Biopsy in Patients With Severe Indeterminate Acute HepatitisPublication . Lin, S; Araujo, C; Hall, A; Kumar, R; Phillips, A; Hassan, M; Engelmann, C; Quaglia, A; Jalan, RBackground and aims: Severe indeterminate acute hepatitis (sIAH) is a poorly understood rare disease with no specific therapy. This study aims to define the clinicopathological characteristics of sIAH and the role of liver biopsy in determining prognosis. Methods: Patients with sIAH admitted to a single center between 2010 and 2019 were included. Histopathological patterns of liver biopsies were reviewed by 2 histopathologists, and key findings further were specified by multiplex immunofluorescence. Patients that died or underwent liver transplantation were analyzed as nonsurvivors. Results: Of 294 patients with acute hepatitis, 43 with sIAH were included. Seventeen (39.5%) underwent liver transplantation and 7 (16.2%) died within 3 months. Multilobular necrosis was the predominant histopathological feature, being significantly more frequent in nonsurvivors (62.5% vs 21.1%; P = .016). Necrotic areas showed low HNF4α and Ki67 expression but high expression of CK19 and cell death markers identifying areas of severe tissue injury and inadequate regenerative response. Patients with multilobular necrosis had higher international normalized ratio, Model for End-Stage Liver Disease, and Model for End-Stage Liver Disease-Sodium scores compared with those without (P values for all markers <.05). Multivariate Cox analysis revealed that multilobular necrosis (hazard ratio, 3.675; 95% confidence interval, 1.322-10.211) and lower body mass index (hazard ratio, 0.916; 95% confidence interval, 0.848-0.991) independently predicted death or transplantation. Conclusions: The results of this study provide novel insights into the important role of liver biopsy in sIAH patients, suggesting that the presence of multilobular necrosis is an early indicator of poor prognosis.
- The Association Between Hepatitis B Virus Infection and Nonliver Malignancies in Persons Living with HIV: Results from the EuroSIDA StudyPublication . Mocroft, A; Miro, J; Wandeler, G; Llibre, J; Boyd, A; van Bremen, K; Beniowski, M; Mikhalik, J; Cavassini, M; Maltez, F; Duvivier, C; Uberti Foppa, C; Knysz, B; Bakowska, E; Kuzovatova, E; Domingo, P; Zagalo, A; Viard, JP; Degen, O; Milinkovic, A; Benfield, T; Peters, L; Harxhi, A; Losso, M; Kundro, M; Schmied, B; Zangerle, R; Karpov, I; Vassilenko, A; Mitsura, V; Paduto, D; Clumeck, N; De Wit, S; Delforge, M; Florence, E; Vandekerckhove, L.; Hadziosmanovic, V; Begovac, J; Machala, L; Sedlacek, D; Kronborg, G; Gerstoft, J; Katzenstein, T; Pedersen, C; Johansen, I; Ostergaard, L; Wiese, L; Moller, N; Nielsen, L; Zilmer, K; Smidt, J; Aho, I; Lacombe, K; Pradier, C; Fontas, E; Rockstroh, J; Behrens, G; Hoffmann, C; Stellbrink, H; Stefan, C; Bogner, J; Fätkenheuer, G; Chkhartishvili, N; Sambatakou, H; Adamis, G; Paissios, N; Szlávik, J; Gottfredsson, M; Devitt, E; Tau, L; Turner, D; Burke, M; Shahar, E; Wattad, L; Elinav, H; Haouzi, M; Elbirt, D; D’Arminio Monforte, A; Esposito, R; Mazeu, I; Mussini, C; Mazzotta, F; Gabbuti, A; Lazzarin, A; Castagna, A; Gianotti, N; Galli, M; Ridolfo, A; Uzdaviniene, V; Matulionyte, R; Staub, T; Hemmer, R; Dragas, S; Stevanovic, M; vd Valk, M; Trajanovska, J; Reikvam, D; Maeland, A; Bruun, J; Szetela, B; Inglot, M; Flisiak, R; Grzeszczuk, A; Parczewski, M; Maciejewska, K; Aksak‐Was, B; Mularska, E; Jablonowska, E; Kamerys, J; Wojcik, K; Mozer‐Lisewska, I; Rozplochowski, B; Mansinho, K; Radoi, R; Oprea, C; Gusev, D; Trofimova, T; Khromova, I; Borodulina, E; Ranin, J; Tomazic, J; Miró, J; Laguno, M; Martinez, E; Garcia, F; Blanco, J; Martinez‐Rebollar, M; Mallolas, J; Callau, P; Rojas, J; Inciarta, A; Moreno, S; del Campo, S; Clotet, B; Jou, A; Paredes, R; Puig, J; Santos, J; Gutierrez, M; Mateo, G; Sambeat, M; Laporte, J; Svedhem, V; Thalme, A; Sönnerborg, A; Brännström, J; Flamholc, L; Kusejko, K; Braun, D; Calmy, A; Furrer, H; Battegay, M; Schmid, P; Kuznetsova, A; Sluzhynska, M; Johnson, A; Simons, E; Edwards, S; Phillips, A; Johnson, M; Orkin, C; Winston, A; Clarke, A; Leen, C; Karpov, I; Losso, M; Lundgren, J; Rockstroh, J; Aho, I; Rasmussen, L; Svedhem, V; Pradier, C; Chkhartishvili, N; Matulionyte, R; Oprea, C; Kowalska, J; Begovac, J; Miró, J; Guaraldi, G; Paredes, R; Paredes, R; Larsen, J; Bojesen, A; Neesgaard, B; Jaschinski, N; Fursa, O; Sather, M; Raben, D; Hansen, E; Kristensen, D; Fischer, A; Jensen, S; Elsing., T; Phillips, A; Reekie, J; Cozzi‐Lepri, A; Amele, S; Pelchen‐Matthews, A; Roen, A; Tusch, E; Bannister., WObjectives: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non-liver malignancies in people living with HIV (PLWH). Methods: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. Results: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person-years of follow-up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94-8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47-12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV-positive versus HBV-negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00-1.51]. Compared to HBV-negative individuals, HBsAg-positive/HBV-DNA-positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00-1.89) and NHL (aIRR 2.57; 95% CI 1.16-5.68). There was no significant association between HBV and lung or anal cancer. Conclusions: We found increased rates of nonliver malignancies in HBsAg-positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV-positive subjects with chronic HBV infection.