Hepatitis B virus infection and renal transplantation

Although the prevalence of chronic hepatitis B virus (HBV) infection has declined in renal transplant recipients (RTRs), it remains a relevant clinical problem with high morbidity and mortality in long-term follow up. A thorough evaluation, including liver biopsy as well as assessment of HBV replication in serum (i.e. hepatitis B e antigen and/or HBV DNA) is required before transplantation. Interferon should not be used in this setting because of low efficacy and precipitation on acute allograft rejection. The advent of effective antiviral therapies offers the opportunity to prevent the progression of liver disease after renal transplantation. However, as far as we are aware, no studies have compared prophylactic and preemptive strategies. To date, the majority of RTRs with HBV-related liver disease have had a high virological and biochemical response to lamivudine use. However, lamivudine resistance is frequent with a prolonged course of therapy. Considering long-term treatment, antiviral agents with a high genetic barrier to resistance and lack of nephrotoxicity are suggested. The optimal strategy in RTRs with HBV infection remains to be established in the near future.

Impact of high dose vitamin C on platelet function

AIM To examine the effect of high doses of vitamin C(VitC) on ex vivo human platelets(PLTs).METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to:(1) normal saline(control);(2) 0.3 mmol/L VitC(Lo VitC); or(3) 3 mmol/L VitC(Hi VitC, final concentrations) and stored appropriately. The Vit C additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of Vit C used here correspond to plasma Vit C levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography(TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate(ATP) secretion in response to collagen or adenosine diphosphate(ADP); and flow cytometry, for changes in expression of CD-31, CD41 a, CD62 p and CD63. In addition, PLT intracellular Vit C content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time(PT), partial thrombplastin time(PTT), functional fibrinogen] and Lipidomics analysis(UPLC ESI-MS/MS).RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L(Lo VitC) and 15.7 mmol/L(Hi VitC, P < 0.05). VitC supplementation did not significantly change PT and PTT values, or functional fibrinogen levels over the 8 d exposure period(P > 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle(P < 0.05). There was also a fall of 20 mm in maximum amplitude associated with the Hi VitC compared to both baseline and day 8 saline controls. Platelet aggregation studies, showed uniform declines in collagen and ADP-induced platelet aggregations over the 8-d study period in all three groups(P > 0.05). Collagen and ADP-induced ATP secretion was also not different between the three groups(P > 0.05). Finally, VitC at the higher dose(3 mmol/L) also induced the release of several eicosanoids including thromboxane B2 and prostaglandin E2, as well as products of arachidonic acid metabolism via the lipoxygenases pathway such as 11-/12-/15-hydroxyicosatetraenoic acid(P < 0.05).CONCLUSION Alterations in PLT function by exposure to 3 mmol/L VitC for 8 d suggest that caution should be exerted with prolonged use of intravenous high dose VitC.

Running in the family:MALT lymphoma and autoimmune disease in mother and daughter

Gastric B-cell lymphoma of the mucosa associated lym-phoid tissue(MALT) lymphoma is one of the most com-mon forms of extranodal lymphoma.In addition to in-fection with Helicobacter pylori(H.pylori),the presence of an underlying autoimmune disease has also been associated with MALT lymphoma development.To date,no familial predisposition for MALT lymphomas has been reported as opposed to other types of lymphoma.A 65-year-old woman was admitted at our institution in 1998 with a diagnosis of H.pylori positive gastric MALT lymphoma and the presence of chronic autoim-mune thyroiditis was established on further work-up.H.pylori eradication did not result in regression of the lymphoma and RT-PCR showed the presence of the t(11;18)(q21;q21) translocation.About 1.5 years after H.pylori eradication,chemotherapy with cladribine resulted in complete remission.Due to lymphoma re-currence 13 mo later,radiotherapy to the stomach(46 Gy) resulted in minimal residual disease without further progression.The patient developed a second malig-nancy(Epstein-Bar virus-associated anaplastic large cell lymphoma in the mediastinum) in 2004 which initially responded to two courses of chemotherapy,but she re-fused further therapy and died of progressive lympho-ma in 2006.In 2008,her 55 years old daughter with a long standing Sj gren's syndrome was diagnosed with MALT lymphoma of the right parotid,but no evidence of gastric involvement or H.pylori infection was found.Currently,she is alive without therapy and undergoing regular check-ups.To our knowledge,this is the first report of MALT lymphoma in a f irst-degree relative of a patient with gastric MALT lymphoma in the context of two autoimmune diseases without a clearly established familial background.

Physician’s Awareness of Home Blood Pressure in the Treatment of Hypertensive Patients with Chronic Kidney Disease

Aim: The majority of guidelines recommended the significance of home-based blood pressure (home-BP) measurement. The present study explored that to what extent, general practitioners (GPs) were aware of the importance of home-BP in the daily clinical practice. Method: We sent out questionnaires to GPs who had been specialized in nephrology and hypertension. The questions focused on the awareness of home-BP and the selections of antihypertensive agents for refractory hypertension in chronic kidney disease (CKD) patients. Results: 1) The majority (95.9%) of the responding GPs had utilized home-BP in their clinical practice. 2) When prescribing a single agent for hypertensive CKD patients, the majority of GPs (87.3%) chose ARB for the first line drug, and Ca channel blockers (CCB) were the second. 3) As an add-on drug to the pre-treatment with an angiotensin receptor blocker (ARB), the majority preferred CCB (82.7%) to diuretics (21.8%). In addition, a fixed combination formula of antihypertensive medication consisting of ARB plus diuretic was accepted by the majority of GPs (78.7%). 4) To improve morning hypertension in patients treated with two or more drugs, 87.8% of the doctors agreed that additional night-time dosing could be useful. The choices of the agents given at night-time varied, mainly with α1-blockers (40.6%), followed by α-blockers (30.5%) and α-methyldopa (19.8%). Conclusion: The majority of GPs in Japan are aware of the importance of the home-BP-based management of CKD. They mainly chose ARB as a first line drug, and ARB plus CCB as an add-on therapy.

慢性丙型肝炎患者肝脏中8-硝基鸟嘌呤的蓄积

Background/Aims: Nucleic acid damage by reactive nitrogen and oxygen species may contribute to inflammation- related carcinogenesis. To investigate the extent of nucleic acid damage in hepatitis C virus infection and its change after interferon treatment, we measured 8- nitrogua- nine and 8- hydroxy- 2’ - deoxyguanosine (8- OHdG) in the liver of patients with chronic hepatitis C (CHC) before and after interferon therapy. Methods: Hepatic accumulation of 8- nitroguanine and 8- OHdG was immunohistochemically evaluated in 20 CHC patients and 7 control patients with non- alcoholic fatty liver. Results: Immunoreactivities of 8- nitroguanine and 8- OHdG were strongly detected in the liver from patients with CHC, but not in control livers. 8- Nitroguanine accumulation was found not only in infiltrating inflammatory cells, but also hepatocytes particularly in the periportal area. The accumulation of 8- nitroguanine and 8- OHdG increased with inflammatory grade (8- nitroguanine; P=0.0019, 8- OHdG; P=0.0009). In the sustained virological responder group after interferon therapy, 8- nitroguanine and 8- OHdG accumulationweremarkedly decreased in the liver (8- nitroguanine; P=0.018, 8- OHdG; P=0.018). Conclusions: In this study,we demonstrated for the first time that 8- nitroguanine accumulated in the liver of patients with CHC. 8- Nitroguanine is a useful biomarker to evaluate the severity of HCV- induced chronic inflammation in relation to hepatocellular carcinoma.

Sending an SOS: Healing the Liver with the Bone Marrow

Citation of this article:Ayares G,Arab JP,Singal AK.Sending an SOS:Healing the Liver with the Bone Marrow.J Clin Transl Hepatol 2022;10(1):1-3.doi:10.14218/JCTH.2021.00557.Cirrhosis,an end stage of any chronic liver disease is a form of impaired regeneration leading to progressive dif-fuse hepatic fibrosis.The healthcare burden of cirrhosis is increasing,and it is currently the 13th leading cause of death globally.The progression of liver injury and fibrosis results in portal hypertension and hepatic insufficiency.