Scientific corner

Sequential therapy consisting of glucocorticoid infusions followed by granulocyte-monocyte absorptive apheresis in patients with severe alcoholic hepatitis.

Kazuhiro Watanabe 1Yoshihito Uchida 1Kayoko Sugawara 1Kayoko Naiki 1Mie Inao 1Nobuaki Nakayama 1Satoshi Mochida 2 , J Gastroenterol 2017 Jul;52(7):830-837.

Sequential therapy combining glucocorticoid infusion and GMA was useful for attenuating liver injuries in patients with severe alcoholic hepatitis by preventing rebound increases in inflammatory reactions after discontinuation of glucocorticoid infusions, except in patients with bacterial infections and/or multiple organ failure.

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Ulcerative colitis with hepatitis B virus infection treated successfully by granulocyte monocyte apheresis.

Hisako Saito 1Norio Hanafusa 1Junko Kishikawa 2Eisei Noiri 1Eiji Sunami 2Soichiro Ishihara 2Toshiaki Watanabe 2Masaomi Nangaku 1 , J Clin Apher. 2016 Dec;31(6):584-586.

Results show that GMA is a safe and efficacious strategy against UC complicated by HBV without affecting hepatitis because GMA had no remarkable effect on HBV activity.

Scientific corner

Granulocytapheresis for the Treatment of Severe Alcoholic Hepatitis: A Case Series and Literature Review.

Kenya Kamimura 1Michitaka ImaiAkira SakamakiShigeki MoriMasaaki KobayashiKen-Ichi MizunoManabu TakeuchiTakeshi SudaMinoru NomotoYutaka Aoyagi, Dig Dis Sci. 2014 Feb;59(2):482-8.

Severe alcoholic hepatitis has a high mortality rate due to limited therapeutic methods. Although corticosteroids have been used to control the inflammatory response, the outcomes vary and no standardized therapy has been established. Novel therapeutic approaches, such as anti-TNF-α, pentoxifilline, and others have been tested clinically on the basis of their cytokinemic pathophysiology with limited success. However, treatment of leukocytosis that causes cytokinemia and hepatic inflammation in patients via granulocytapheresis and leukocytapheresis showed promising results in a number of reports. Here, we report two cases of severe alcoholic hepatitis treated with granulocytapheresis. The liver function and inflammation recovered after the therapy. A review of 35 cases treated with granulocytapheresis and leukocytapheresis demonstrated their efficacy in treating alcoholic hepatitis by controlling leukocytosis as well as cytokines such as IL-8. Multidisciplinary treatment for severe alcoholic hepatitis should be considered case by case on the basis of the complexity and severity of the condition.

Scientific corner

Management of hepatitis C virus infection in liver transplantation with adacolumn apheresis.

G Novelli 1M RossiV MorabitoG FerrettiR PretagostiniF RubertoF PuglieseN GuglielmoP B Berloco , Transplant Proc. 2012 Sep;44(7):1946-52.

Recurrent hepatitis C virus (HCV) is a major cause of liver transplant loss, hepatic failure, and retransplantation need. Posttransplantation antiviral therapy in patients with evidence of recurrent disease is the mainstay of management. Although HCV is a hepatocellular pathogen, there is increasing evidence that the virus can infect and persist in other cells. In particular, granulocytes and monocytes/macrophages are known to constitute extrahepatic sites for HCV replication and dissemination. The aim of this study was to apply Adacolumn apheresis as a possible therapeutic alternative to conventional drug therapy to manage HCV infections. Seven patients who underwent liver transplantation for HCV-related cirrhosis were eligible for the study. The patients underwent 5 1-hour sessions for 5 consecutive days. The first treatment was performed in the anhepatic phase of liver transplantation with the intent to early reduce infected granulocytes and monocytes/macrophages. The patients were evaluated over the 5 days after inclusion with 3- and 6-months follow-ups. Early apheresis treatments in the anhepatic phase and over the following 4 days after transplantation produced low viral loads in 4 patients, negative viral loads in 2 patients, and increased viremia in 1 patient. At follow-up, the viremia load was stable in 6 patients without increased transaminase levels. At the end of the treatment cycle, almost all immune cells of the 6 patients maintained CD4+/CD8+ T-cell ratios. The optimal timing of treatment initiation is unknown, but early preemptive therapy is recommended to decrease the risk for recurrent infection. Although this study investigated the responses among a small number of patients, it documented that the Adacolumn changed cellular immunity, promoting early virologic responses.

Scientific corner

Adacolumn apheresis for hepatitis C virus in patients waiting for kidney transplant. Preliminary study.

Gilnardo Novelli 1Giancarlo FerrettiVincenzo MorabitoPaola CintiLuca PoliRenzo PretagostiniPasquale B Berloco, G Ital Nefrol. Jan-Feb 2012;29 Suppl 54:S109-13.

Hepatitis C virus (HCV) infection occurs much more frequently in the hemodialysis population than in the general population. Patients with chronic kidney disease with persistent HCV infection may develop serious and progressive chronic liver disease, with associated long-term morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Monocytes and macrophages are known to produce extrahepatic breeding sites and spread the disease. Our aim was to lower the levels of macrophages, granulocytes, monocytes, proinflammatory cells and viremia using an extracorporeal device: the Adacolumn ® leukocyte apheresis system (Otsuka). The Adacolumn is a direct hemoperfusion-type leukapheresis device. The column is a single-use (disposable) polycarbonate column with a capacity of about 335 mL, filled with 220-g cellulose acetate beads of 2 mm in diameter bathed in physiological saline. The carriers adsorb ”activated” granulocytes and monocytes/macrophages that bear Fc and complement receptors. The patients underwent five 1-hour sessions for five consecutive days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. A reduction of viremia was observed in all patients in association with a decrease in cytokine levels and a proportional decrease in immune cells. Although this study investigated responses in a small number of patients, it was shown that the Adacolumn changed the cellular immunity and promoted early viral response.

Scientific corner

Granulocytapheresis and plasma exchange for severe alcoholic hepatitis.

Yoshinori Horie 1 , J Gastroenterol Hepatol. 2012 Mar;27 Suppl 2:99-103.

Our perception is that, patients with elevated myeloid leucocytes benefit most from GMA, while plasma exchange appears to support patients with coagulation deficiency or high plasma bilirubin and HD has indication in patients with high Cr.

Scientific corner

Beneficial effects of neutrophil-targeted therapy for pyoderma gangrenosum associated with ulcerative colitis

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Leukocyte apheresis in the management of ulcerative colitis

Ahmed HelmyMaheeba AbdullaIngvar Kagevi, and Khalid Al Kahtani, Saudi J Gastroenterol. 2009 Oct; 15(4): 283–287.

The goal of this concise report is to present the available data on the efficacy, safety, and applicability of cytapheresis in patients with UC.

Scientific corner

Cytomegalovirus disappearance after treatment for refractory ulcerative colitis in 2 patients treated with infliximab and 1 patient with leukapheresis

Scientific corner

Cytapheresis in patients with severe ulcerative colitis after failure of intravenous corticosteroid: a long-term retrospective cohort study

Ken Fukunaga 1Kazuko NagaseTakeshi KusakaNobuyuki HidaYoshio OhdaKoji YoshidaKatsuyuki TozawaKoji KamikozuruM IimuroShiro NakamuraHiroto MiwaTakayuki Matsumoto, Gut Liver. 2009 Mar;3(1):41-7. doi: 10.5009/gnl.2009.3.1.41

This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC.

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