Liver International ISSN 1478-3223
VIRAL HEPATITIS
Histological features of chronic hepatitis C in haemodialysis patients Stratigoula Sakellariou1, John N. Boletis 2, Vana Sypsa3, Mina Psichogiou4, Dina Tiniakos5,6 and Ioanna Delladetsima1 1 2 3 4 5 6
First Department of Pathology, Medical School, University of Athens, Athens, Greece Department of Nephrology and Renal Transplantation Unit, Medical School, University of Athens, Laiko General Hospital, Athens, Greece Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece First Department of Internal Medicine, Propaedeutic, Medical School, University of Athens, Laiko General Hospital, Athens, Greece Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Keywords bile ducts – HCV – haemodialysis – histology – lymphoid aggregates – steatosis
Correspondence Sakellariou Stratigoula, First Department of Pathology, Medical School, University of Athens, 75 Mikras Asias Str, Goudi, 11527, Athens, Greece Tel: +30 210 7462 174 Fax: +30 210 7462 157 e-mail: [email protected] Received 7 July 2013 Accepted 16 November 2013 DOI:10.1111/liv.12413 Liver Int. 2014: 34: e56–e61
Abstract Background & Aims: HCV infection in haemodialysis (HD) patients is still a matter of investigation. The aim of this study was to determine the histology of chronic hepatitis C (CHC) in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. The relative importance of virological, demographic and clinical parameters on disease manifestation was examined. Methods: Sixty-one consecutive liver biopsies from HD patients and 326 from non-uraemic patients with chronic HCV infection were comparatively evaluated. Results: Haemodialysis patients with CHC were older than control subjects (P = 0.031), showing a similar HCV genotype distribution (P = 0.328) and lower viral load (P = 0.001). CHC in HD patients was significantly milder according to stage (P = 0.033), grade and its parameters (periportal activity, portal inflammation and lobular activity) (P < 0.001). The frequency of lymphoid aggregates (10.2% vs 50%, P < 0.001), bile duct lesions (1.7% vs 22.1%, P < 0.001) and extent of steatosis (P = 0.022) in HD group was significantly reduced. Multivariate analysis showed that non-uraemic patients had 2.3 times higher risk of developing steatosis independently of genotype distribution and age. In HD group, genotype 3, longer HD duration and age at infection were significantly associated with steatosis, while older age at infection correlated with advanced fibrosis. Conclusions: Chronic hepatitis C in HD patients is usually very mild, losing its diagnostic histological features while patient’s age and age at infection retain their prognostic significance. The weak inflammatory response, probably because of immunocompromised status and low viral load, may present a beneficial factor in the natural course of the disease.
The natural outcome of CHC in the general population is well established, prognostic factors have been thoroughly investigated and histopathology has been elucidated. It usually runs an asymptomatic clinical course and leads to cirrhosis in about 20% of the patients within an interval of 15–20 years. Μild chronic hepatitis is the predominant histological pattern while individual features such as lymphoid aggregates/follicles, steatosis and bile duct lesions are of relative diagnostic significance (1). In specific CHC settings such as HIV-coinfected and transplant patients, hepatitis severity and course are modified because of alterations mainly in host immune response and viral factors (2–4). HCV infection in haemodialysis (HD) patients with end-stage renal disease (ESRD), despite a declined incidence in the last decade, remains the
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major cause of chronic liver disease. Its prevalence ranges between 3 and 80% (5) depending on the geographical region. Information regarding hepatitis outcome is controversial (6–8) with cirrhosis incidence ranging from 0 to 24% in uraemic patients (9), while the impact of haemodialysis and ERSD on the natural course of the disease is still unclear. HCV-infected HD patients have been reported to show higher mortality compared to non-infected HD subjects (8, 10) and faster progression to cirrhosis compared to patients with normal renal function (11). In parallel, there is growing evidence that chronic hepatitis C (CHC) in ESRD and HD patients is milder than in non-uraemic individuals (12–17). However, information regarding the impact of prognostic parameters is limited and data referring to the histological spectrum Liver International (2014) © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Sakellariou et al.
of CHC in relation to virus and host-related factors are almost missing. The main aim of this study was to determine the histology of CHC in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. Furthermore, the relative importance of virological, demographic and clinical parameters on disease manifestation and possible modification was investigated. Patients and methods
We examined a series of 61 consecutive liver biopsies from 61 HCV-infected haemodialysis patients. Their mean (standard deviation-SD) age was 45.7 (11.7) years (range 21–69 years) and thirty-seven patients (60.7%) were men. Median haemodialysis time was 4.2 years (25th, 75th percentiles: 2.3, 6.8 years). Renal failure resulted from glomerulopathy in 17 patients, from pyelonephritis and/or lithiasis in five and from diabetes mellitus in four patients. Four subjects suffered from polycystic kidney disease, two from vesicoureteral reflux and four had severe hypertension. In the remaining 25 patients, the cause of renal impairment was unknown or inconclusive. Three hundred and twenty-six biopsies from 326 consecutive non-uraemic patients (creatinin
VIRAL HEPATITIS
Histological features of chronic hepatitis C in haemodialysis patients Stratigoula Sakellariou1, John N. Boletis 2, Vana Sypsa3, Mina Psichogiou4, Dina Tiniakos5,6 and Ioanna Delladetsima1 1 2 3 4 5 6
First Department of Pathology, Medical School, University of Athens, Athens, Greece Department of Nephrology and Renal Transplantation Unit, Medical School, University of Athens, Laiko General Hospital, Athens, Greece Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece First Department of Internal Medicine, Propaedeutic, Medical School, University of Athens, Laiko General Hospital, Athens, Greece Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Keywords bile ducts – HCV – haemodialysis – histology – lymphoid aggregates – steatosis
Correspondence Sakellariou Stratigoula, First Department of Pathology, Medical School, University of Athens, 75 Mikras Asias Str, Goudi, 11527, Athens, Greece Tel: +30 210 7462 174 Fax: +30 210 7462 157 e-mail: [email protected] Received 7 July 2013 Accepted 16 November 2013 DOI:10.1111/liv.12413 Liver Int. 2014: 34: e56–e61
Abstract Background & Aims: HCV infection in haemodialysis (HD) patients is still a matter of investigation. The aim of this study was to determine the histology of chronic hepatitis C (CHC) in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. The relative importance of virological, demographic and clinical parameters on disease manifestation was examined. Methods: Sixty-one consecutive liver biopsies from HD patients and 326 from non-uraemic patients with chronic HCV infection were comparatively evaluated. Results: Haemodialysis patients with CHC were older than control subjects (P = 0.031), showing a similar HCV genotype distribution (P = 0.328) and lower viral load (P = 0.001). CHC in HD patients was significantly milder according to stage (P = 0.033), grade and its parameters (periportal activity, portal inflammation and lobular activity) (P < 0.001). The frequency of lymphoid aggregates (10.2% vs 50%, P < 0.001), bile duct lesions (1.7% vs 22.1%, P < 0.001) and extent of steatosis (P = 0.022) in HD group was significantly reduced. Multivariate analysis showed that non-uraemic patients had 2.3 times higher risk of developing steatosis independently of genotype distribution and age. In HD group, genotype 3, longer HD duration and age at infection were significantly associated with steatosis, while older age at infection correlated with advanced fibrosis. Conclusions: Chronic hepatitis C in HD patients is usually very mild, losing its diagnostic histological features while patient’s age and age at infection retain their prognostic significance. The weak inflammatory response, probably because of immunocompromised status and low viral load, may present a beneficial factor in the natural course of the disease.
The natural outcome of CHC in the general population is well established, prognostic factors have been thoroughly investigated and histopathology has been elucidated. It usually runs an asymptomatic clinical course and leads to cirrhosis in about 20% of the patients within an interval of 15–20 years. Μild chronic hepatitis is the predominant histological pattern while individual features such as lymphoid aggregates/follicles, steatosis and bile duct lesions are of relative diagnostic significance (1). In specific CHC settings such as HIV-coinfected and transplant patients, hepatitis severity and course are modified because of alterations mainly in host immune response and viral factors (2–4). HCV infection in haemodialysis (HD) patients with end-stage renal disease (ESRD), despite a declined incidence in the last decade, remains the
e56
major cause of chronic liver disease. Its prevalence ranges between 3 and 80% (5) depending on the geographical region. Information regarding hepatitis outcome is controversial (6–8) with cirrhosis incidence ranging from 0 to 24% in uraemic patients (9), while the impact of haemodialysis and ERSD on the natural course of the disease is still unclear. HCV-infected HD patients have been reported to show higher mortality compared to non-infected HD subjects (8, 10) and faster progression to cirrhosis compared to patients with normal renal function (11). In parallel, there is growing evidence that chronic hepatitis C (CHC) in ESRD and HD patients is milder than in non-uraemic individuals (12–17). However, information regarding the impact of prognostic parameters is limited and data referring to the histological spectrum Liver International (2014) © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Sakellariou et al.
of CHC in relation to virus and host-related factors are almost missing. The main aim of this study was to determine the histology of CHC in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. Furthermore, the relative importance of virological, demographic and clinical parameters on disease manifestation and possible modification was investigated. Patients and methods
We examined a series of 61 consecutive liver biopsies from 61 HCV-infected haemodialysis patients. Their mean (standard deviation-SD) age was 45.7 (11.7) years (range 21–69 years) and thirty-seven patients (60.7%) were men. Median haemodialysis time was 4.2 years (25th, 75th percentiles: 2.3, 6.8 years). Renal failure resulted from glomerulopathy in 17 patients, from pyelonephritis and/or lithiasis in five and from diabetes mellitus in four patients. Four subjects suffered from polycystic kidney disease, two from vesicoureteral reflux and four had severe hypertension. In the remaining 25 patients, the cause of renal impairment was unknown or inconclusive. Three hundred and twenty-six biopsies from 326 consecutive non-uraemic patients (creatinin
