Cellular Therapy for Liver Disease

Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease.     

Liver Disease as Presenting Manifestation of Hodgkin's Disease

Six patients who were referred to the liver unit on accountof jaundice are described. A different initial diagnosis hasbeen made in each case, these being fulminant hepatic failure,severe hepatitis with renal failure, toxoplasma hepatitis, extrahepaticobstruction, sclerosing cholangitis, and liver abscess. Afterdelays of four weeks to 12 months from the time of first symptomsall six patients were eventually found to have advanced Hodgkin'sdisease (stage 4). In four patients the diagnosis was made duringlife, but in two only at autopsy. In four lymphoma tissue wasfinally demonstrable in the liver, but in two liver biopsy showedonly minor non-specific changes despite grossly abnormal liverfunction tests. Three of the six patients were treated withchemotherapy, and two of these recovered sufficiently to leavehospital. With the encouraging survival figures now being obtainedin Hodgkin's disease, an awareness of the varied hepatic manifestationsof the disease may allow treatment to be instituted at an earlierstage.     

肝病治疗仪对非酒精性脂肪性肝病血液流变学指标的影响（附60例分析）

目的探讨肝病治疗仪对非酒精性脂肪性肝病血液流变学指标的影响。方法选取2009年8月～2010年8月门诊确诊为非洒精性脂肪性肝病60例,所有患者采用肝病治疗仪治疗,观察治疗前后患者血液流变学指标变化,同时检测肝功能、甘油三酯、胆固醇及B超等。结果轻度脂肪肝血液流变学指标治疗前后改变不大（P〉0．05）;而中、重度脂肪肝血液流变学指标在治疗90d后,各项指标改善明显（P〈0．05）。结论肝病治疗仪对非酒精性脂肪性肝病患者血液流变学指标的改善与脂肪肝严重程度及其疗效成正相关。     

降阶梯方案配合营养支持治疗克罗恩病患儿的护理

目的探讨降阶梯方案配合营养支持治疗克罗恩病患儿的护理方法。方法回顾并总结了2009年4月至2010年8月行降阶梯方案及营养支持治疗的11例克罗恩病患儿的临床资料。结果 11例克罗恩病患儿均顺利完成降阶梯方案配合营养支持的治疗,临床症状及体征均得到明显改善,治疗期间患儿未发生严重不良反应。结论切实做好实施降阶梯方案时的用药护理和不良反应的观察,同时配合医生完成对患儿进行的营养支持,有利于促进患儿尽快康复。     

Therapy for Nonalcoholic Fatty Liver Disease: Current Options and Future Directions

PurposeNonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that is driven by the metabolic syndrome. NAFLD encompasses nonalcoholic fatty liver, >5% fat in the liver without inflammation of fibrosis, nonalcoholic steatohepatitis (NASH), fat plus varying degrees of inflammation and fibrosis, and cirrhosis of the liver from NASH. As facets of the metabolic syndrome, particularly diabetes and obesity, become more common worldwide, the incidence of new NAFLD is increasing.MethodsA qualitative systematic review was performed via searches of PubMed and ClinicalTrials.gov for therapeutic interventions for NAFLD.FindingsCurrent therapies rely on metabolic syndrome risk factor control and lifestyle changes to achieve weight loss. Because sustained weight loss is difficult for many patients, there is a critical unmet need for pharmacotherapy to treat NAFLD, especially the progressive form, NASH, to prevent cirrhosis of the liver. New therapies for NAFLD focus on the subset of patients with NASH and some degree of fibrosis. Novel mechanisms of action, including farnesoid X nuclear receptor agonism, C–C motif chemokine receptor 2 and receptor 5 antagonism, stearoyl-CoA desaturase-1, and thyroid hormone receptor β agonism, are currently under investigation as monotherapy. The products also hold potential for use in combination with and without insulin sensitizers and other established drugs in the future.ImplicationsThis review of NASH treatments details the interventions that are currently available as well as those in late-stage clinical trials that may represent the future of NASH therapy.     

慢性肝病住院患者营养筛查评估与管理循证实践

目的 制定慢性肝病住院患者营养不良风险筛查、评估及管理的最佳证据,并应用于临床实践,以规范肝病患者的营养筛查、评估与管理策略,提高患者营养水平。方法 遵循JBI临床证据实践应用模式,将最佳证据本土化后制定慢性肝病患者营养筛查、评估与管理的审查指标,通过培训与考核不断指导并规范临床实践,比较最佳证据实施前后患者营养状况、知信行情况及质量审查指标完成情况。结果 证据应用后,观察组慢性肝病患者营养不良发生率低于对照组,血清白蛋白水平高于对照组（P<0.05）;慢性肝病患者营养知信行水平均有所提高（P<0.05）;证据应用后医护人员对肝病营养筛查、评估及管理相关知识和态度情况优于证据应用前（P<0.05）;证据应用后6项审查指标执行情况优于证据应用前（P<0.05）。结论 通过应用最佳证据,并将证据科学地筛查、评估和管理慢性肝病住院患者营养问题,能改善患者营养水平,提升临床护理质量。     

Effect of Propranolol as Antiadhesive Therapy in Sickle Cell Disease

Sickle red blood cells (SSRBCs) adhere to both endothelial cells (ECs) and the extracellular matrix. Epinephrine elevates cyclic adenosine monophosphate in SSRBCs and increases adhesion of SSRBCs to ECs in a β‐adrenergic receptor and protein kinase A‐dependent manner. Studies in vitro as well as in vivo have suggested that adrenergic stimuli like epinephrine may contribute to vaso‐occlusion associated with physiologic stress. We conducted both animal studies and a Phase I dose‐escalation study in sickle cell disease (SCD) patients to investigate whether systemically administered propranolol inhibits SSRBC adhesion and to document the safety of propranolol in SCD. Systemically administered propranolol prevented SSRBC adhesion and associated vaso‐occlusion in a mouse model. In patients receiving a single oral dose of 10, 20, or 40 mg propranolol, SSRBC adhesion to ECs was studied before and after propranolol, with and without stimulation with epinephrine. Propranolol administration significantly reduced epinephrine‐stimulated SSRBC adhesion in a dose dependent manner (p = 0.03), with maximum inhibition achieved at 40 mg. Adverse events were not severe, did not show dose dependence, and were likely unrelated to drug. No significant heart rate changes occurred. These results imply that β‐blockers may have a role as antiadhesive therapy for SCD. Clin Trans Sci 2012; Volume 5: 437–444     

Cytapheresis as a Non-Pharmacological Therapy for Inflammatory Bowel Disease

SUMMARY: Although inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic recurrent disease with unknown etiology. Recent immunological studies suggest close relation to autoimmune status featured by antibodies against colonic epithelial cells. For patients with IBD, 5-aminosalycilates are often used in case of mild disease, and corticosteroids are standard therapy for moderate-to-severe disease. However, we often encounter patients who are resistant to or dependent of conventional therapy, which are likely to lead to future problems in quality of life due to adverse effects of drugs used, especially corticosteroids. Extracorporeal leukocyte removal therapy (cytapheresis) is one of the adjunctive therapies for IBD patients refractory to steroids. By removing circulating activated leukocytes, especially granulocytes and lymphocytes, impaired immune response is suppressed. In the present article recently published studies are reviewed in order to reflect the current state of the art in the use of cytapheresis for treating IBD, especially UC and CD. Although there are only few randomized controlled trials, clinical experience so far suggests that cytapheresis has superior efficiency than conventional therapies in steroid-resistant moderate-to-severe UC. Moreover, cytapheresis features its safety characteristic compared with other conventional medications for severe UC, cytapheresis is regarded as safe treatment regimen.     

Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review

PurposeParkinson disease (PD) medications are not readily available in all countries. Citicoline increases dopamine synthesis and inhibits dopamine uptake. This systematic review aims to synthesize current existing evidence on the efficacy of citicoline adjunctive therapy in improving PD symptoms.MethodsAn extensive literature search of Scopus, Embase, PubMed, Cochrane Library, and Google Scholar was conducted for articles published on or before December 31, 2019. The studies were screened and selected by 2 independent reviewers. We included all studies that explored the efficacy of citicoline as an adjunct therapy in PD.FindingsA total of 7 studies (2 crossover, 3 randomized controlled, and 2 open prospective studies) were included. Despite the varied outcome tools, this review found that patients with PD who were taking citicoline had significant improvement in rigidity, akinesia, tremor, handwriting, and speech. Citicoline allowed effective reduction of levodopa by up to 50%. Significant improvement in cognitive status evaluation was also noted with citicoline adjunctive therapy.ImplicationsCiticoline adjuvant therapy has beneficial effects as an adjuvant therapy in patients with PD. However, due to the heterogeneity of the studies, there is a need for more high-quality studies.