Liu-Jun-Zi decoction alleviates chemotherapy-induced anorexia by regulating gut microbiota and TLR4/MyD88/NF-κB p65 signaling pathway

Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-induced anorexia was discussed from the aspects of regulating gut microbiota,repairing intestinal barrier injury and inhibiting inflammatory pathways.Methods:A rat model of chemotherapy-induced anorexia was established using cisplatin.The study evaluated the therapeutic effects of LJZD by observing the weight,food intake,and intestinal pathology of rats.The impact of LJZD on gut microbiota and metabolites,specifically short-chain fatty acids,was investigated through gut microbiota analysis and targeted metabolomics.The anti-inflammatory and intestinal protective effects of LJZD were assessed by examining the expression of intestinal tight junction proteins associated with the inflammatory pathway.Results:LJZD alleviated cisplatin-induced inflammation and intestinal barrier disruption,as evidenced by upregulated expression of tight junction protein 1(TJ-1)and occludin,along with reduced serum levels of interleukin 6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and lipopolysaccharide.Additionally,LJZD alleviated microbiota imbalance and regulated the levels of short-chain fatty acids,especially increased the relative abundance of Coriobacteriales Incertae Sedis,Lactabacillus johnsonii F19785,Parasutterella,and reduced the Tyzzerella.In the hypothalamus,LJZD exerts suppressive effects on the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)p65 signaling pathway,leading to a downregulation in the transcriptional activity of IL-6 and IL-1β,as well as Interleukin 6 receptors(IL-6R)and Interleukin-1βreceptors(IL-1R1)mRNA expression levels.Conclusion:In summary,LJZD alleviate chemotherapy-induced anorexia by modulating the gut microbiota,repairing the intestinal mechanical barriers,and suppressing the TLR4/MyD88/NF-κB p65 signaling pathway.

Guicao Baidu decoction in mitigating chemotherapy-induced myocardial injury:case report and mechanism investigation

To observe the effects of GuiCaoBaiDu Decoction(GCBD)on chemotherapy especially doxorubicin(DOX)-induced myocardial cardiotoxicity(DIC)and explore the mechanisms.The present study presents a case demonstrating the preventive and therapeutic effects of GCBD on myocardial injury following chemotherapy.Then network pharmacology was employed to predict the targets of GCBD.Subsequently,a DOX-induced apoptosis model of H9C2 cardiomyocytes was established and co-cultured with serum containing GCBD serum.The viability and myocardial enzyme levels were evaluated using CCK8 assay and ELISA assay,TUNEL was using for apoptosis test.The GCBD effect was confirmed by tests of ROS andα-actinin levels,evaluation of mitochondrial morphology,and BAX co-localization with mitochondria.Furthermore,the expression levels of apoptosis-related molecules were determined via Western blotting.Additionally,a mouse model exhibiting DOX-induced cardiac functional impairment was generated and subsequently treated with GCBD.Myocardial enzyme level was tested at first,then echocardiography was tested,myocardial apoptosis in mice was observed through HE staining while related proteins were detected using IHC.Network pharmacological analyses revealed that GCBD exerts its effects on BAX,Caspase7,and other related molecules.Initially,we demonstrated the effective amelioration of DIC in cardiomyocyte viability,LDH/CK levels,α-actinin and ROS levels,and apoptosis by GCBD through improvements in TUNEL test,mitochondrial morphology and WB.The efficacy of GCBD in enhancing cardiac function in DIC mice has been validated through animal experiments.Taken together,our study showed that GCBD could significantly alleviate DOX induced myocardial injury by regulating mitochondrial apoptosis.The utilization of GCBD can effectively contribute to the prevention and treatment of chemotherapy-induced myocardial injury when anthracycline chemotherapy is employed in clinical practice.

Patterns of antiemetic prophylaxis for chemotherapy-induced nausea and vomiting in China

Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current guidelines. Methods： We searched the China Health Insurance Research Association （CHIRA） Database to identify patients with cancer who were 〉 18 years old and received either moderately or highly emetogenie chemotherapy （MEC and HEC, respectively） between 2008 and 2012. Patients＇ characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics. Results： Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC （59.4% vs. 81.3 %; P〈0.001）. The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group （P〈0.012）; however, a higher proportion received a mixed regimen containing eorticosteroids （P≤0.007）. Although more than half of the patients in the HEC group took three antiemeties to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group （both P〈0.001）. Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic. Conclusions： These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen.

Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects

Chemotherapy-induced diarrhoea (CID) is a common side-effect experienced by patients being treated with a variety of antineoplastic agents. Approximately 80% of patients undergoing chemotherapeutic treatment for colorectal and other gastrointestinal cancers present with CID;moreover, about 5% of early deaths associated with combination anti-cancer chemotherapy are due to CID. Chronic post-treatment diarrhoea amongst cancer survivors can persist for more than 10 years greatly effecting long-term quality of life. Gastrointestinal toxicities such as diarrhoea and vomiting are amongst the primary contributors to dose reductions and delays throughout anti-cancer treatment, presenting a significant hurdle in clinical management of anti-cancer regimes and often result in sub-optimum treatment. However, little is known about pathophysiological mechanisms underlying CID. This work provides a review of chemotherapy-induced diarrhoea, current management guidelines, and shortcomings of current treatments as well as emerging and already existing anti-diarrhoeal treatments potentially suitable for CID.

Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers:State of art and an innovative approach for prevention

Chemotherapy-induced peripheral neuropathy(CIPN)is a common side effect that occurs in 20%of ovarian cancer patients treated with the combination of carboplatin/paclitaxel(CP).This toxicity is directly correlated with the dose of paclitaxel administered.Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate,but,unfortunately,no significant improvement was obtained.CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment.Neuropathy can last for months and even years after its onset.Moreover,patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs,and residual neuropathy can affect the continuation of treatment.There are no approved drugs that mitigate or prevent the onset of CIPN.In this review,we summarize the evidence regarding the incidence of CIPN with different taxane formulations,regimen schedules and prevention systems.In particular,the Hilotherm®Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries.We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN.Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated;only two patients(4.5%)stopped hilotherapy because of cold intolerance,and only one patient(2.2%)experienced grade≥2 CIPN.

Psychosocial adaptation and influencing factors among patients with chemotherapy-induced peripheral neuropathy

BACKGROUND Chemotherapy-induced peripheral neuropathy(CIPN)is a severe and longlasting side effect caused by various anticancer agents that damage sensory,motor and autonomic nerves.It can cause maladaptive behaviors,including disease severity,anxiety,depression,sleep disorders,falls,and social impairment.These disorders have physical,psychological and social effects on patients and can seriously influence their quality of life.AIM To investigate the current situation of psychosocial adaptation to the disease and its influencing factor in patients with CIPN.METHODS A convenience sampling method was used to select 233 patients with CIPN in our hospital from February to August 2021.In addition,a cross-sectional survey was conducted using a sociodemographic questionnaire,the Self-Report Psychosocial Adjustment to Illness Scale,and the European Organisation for the Research and Treatment of Cancer Quality of Life CIPN20(QLQ-CIPN20).Factors influencing psychosocial adaptation in patients with CIPN were analyzed by t-test or one-way analysis of variance,correlation analysis,multiple stepwise regression analysis,and structural equation models.RESULTS The psychosocial adaptation score of patients with CIPN was 52.51±13.18.Multivariate analysis showed that autonomic nerves,tumor stage,motor nerves,education level,availability of caregivers,semi-retirement status,CIPN grade were independent risk factors for patients with CIPN(P<0.05).Structural equation models showed that QLQ-CIPN20 mediated the relationship between CIPN grade,tumor stage,and psychosocial adaptation.CONCLUSION Patients with CIPN have poor psychosocial adaptation and are affected by a variety of physiological,psychological,and social factors.Patients’adaptive responses should be assessed,and targeted interventions implemented.

Sigma-1 receptor: a new player in neuroprotection against chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy is a very frequent neurological complication in cancer. Oxaliplatin（OXA） is a platinum analogue used as a first-line agent in the treatment of colorectal cancer. OXA induced peripheral neuropathy（OIN） is the main toxicity both during and after the completion of chemotherapy that presents as two distinct syndromes： acute and chronic neuropathy. None of the neuroprotective agents previously tested had prevented or limited the acute and/or chronic OIN. MR309（previously developed as E-52862） is a novel selective sigma-1 receptor（S1R） antagonist with preclinical analgesic activity in OXA-induced neuropathic pain in animal models. This review analyzes the results of the recently published phase Ⅱ, randomized, double-blind, placebo-controlled clinical trial including 124 patients with colorectal cancer（CRC） treated with MR309. This study shows encouraging findings in the setting of neuroprotection against OIN with an acceptable safety profile. The study demonstrated MR309 usefulness in decreasing acute OIN, by reducing cold hypersensitivity experienced by patients, and pointed to the amelioration of chronic OIN by lowering the proportion of patients who developed severe chronic OIN. In addition, we provide a summary and discussion on the pathways that can be modulated by the S1R to explain the observed clinical benefits in the OIN.

Albumin–bilirubin grade as a predictor of survival in hepatocellular carcinoma patients with thrombocytopenia

BACKGROUND The models for assessing liver function,mainly the Child–Pugh(CP),albuminbilirubin(ALBI),and platelet–ALBI(PALBI)classifications,have been validated for use in estimating the prognosis of hepatocellular carcinoma(HCC)patients.However,thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC.AIM To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients.METHODS A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed.Preoperative scores on the CP,ALBI and PALBI classifications were estimated accordingly.Kaplan–Meier curves with logrank tests and Cox regression models were used to explore the significant factors associated with overall survival(OS)and recurrence-free survival(RFS).RESULTS The preoperative platelet counts were significantly different among the CP,ALBI and PALBI groups.After a median follow-up of 28 mo,39.3%(53/135)of the patients experienced postoperative recurrence,and 36.3%(49/135)died.Univariate analysis suggested thatα-fetoprotein levels,tumor size,vascular invasion,and ALBI grade were significant predictors of OS and RFS.According to the multivariate Cox regression model,ALBI was identified as an independent prognostic factor.However,CP and PALBI grades were not statistically significant prognostic indicators.CONCLUSION The ALBI grade,rather than CP or PALBI grade,is a significant prognostic indicator for thrombocytopenic HCC patients.

Study on the mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacology and molecular docking

Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP,and the target of chemotherapy-induced diarrhea were screened by the GeneCards.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.8.0 software.The string datebase was used to draw the protein interaction(PPI)network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets.Result:The result showed that 216 components were screened and 276 effective targets were screened.There were 1764 chemotherapy-induced diarrhea targets.The 173 common targets were obtained through venn diagram.The GO function analysis found 2427 items of biological process,168 items of molecular function and 79 items of cellular component.The KEGG pathway analysis found 169 items.Conclusion:The PPI network found that STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6、etc.may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapy-induced diarrhea.GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress and so on.The KEGG pathways involved mainly include Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway、hepatitise B signaling pathway and other pathways,that Play the role of anti-inflammatory and repair barrier.

Review of the mechanisms of TCM in relieving the chemotherapy-induced diarrhea

With the clinical application of various chemotherapeutic drugs,the side effects are also followed.Diarrhea is one of the most serious side effects of chemotherapy.A large number of clinical and experimental studies have proven that traditional Chinese medicine has great prospects in relieving chemotherapy-related diarrhea.The article mainly discusses the mechanism of chemotherapy-related diarrhea and the prospect of traditional Chinese medicine in relieving the mechanism of chemotherapy-related diarrhea.

Non-pharmacological management for chemotherapy-induced nausea and vomiting in patients with cancer:a scoping review

Objective:This review aimed to map and summarize published studies that tested non-pharmacological management for chemotherapyinduced nausea and vomiting(CINV).Methods:We searched for eligible studies in 5 electronic databases and screened the retrieved studies using the inclusion and exclusion criteria.Data were then collated according to the types of interventions,measurement tool,and outcomes.Results:The search yielded 2343 records,of which 11 were included.Four categories of non-pharmacological CINV management were made;manipulative and body-based therapy(n=5 studies);mind–body therapy(n=3 studies);biologically based practice(n=1 study),and energy therapy(n=2 studies).Seven different scales were used to measure CINV.Nine studies repor ted improvement in CINV.Conclusions:This scoping review demonstrates the breadth of non-pharmacological management to address CINV.Various types of CINV scales were used to measure CINV severity.The management and scale can be utilized to improve nursing care,par ticularly in cancer care.

Risk Factors for Chemotherapy-Induced Leukopenia in Patients with Lung Cancer

Objective: This analysis was conducted to clarify risk factors for chemotherapy-induced leukopenia (CIL) in lung cancer. Methods: A retrospective study was conducted on data from 358 patients with lung cancer who received chemotherapy. Results: Among 358 cases of lung cancer who received chemotherapy, a total of 240 patients experienced CIL, rate was 67%. The demographic data including gender (P = 0.795), age (P = 0.134), presence of selected chronic comorbidities (P = 0.23) were not significantly different in the two groups. The weight loss rate, PS score, sub-normal pre-WBC level, sub-normal pre-PLT level, and the cycle of chemotherapy were significantly different between the groups (P < 0.05). Multivariate analysis revealed that the weight loss rate ≥5% (OR = 0.503), sub-normal pre-WBC level (OR = 11.807), the cycle of chemotherapy ≥3 (OR = 3.100) were main risk factors for CIL in lung cancer. Conclusion: Before treatment, weight loss rate is 5% or higher, chemotherapy has a cycle of 3 or more and sub-normal WBC level is independent risk factor of lung cancer after chemotherapy-induced leucopenia.

Controlling Chemotherapy-Induced Nausea and Vomiting with Neurokinin-1 Receptor Antagonists in Patients on AC-Based Chemotherapy—Are We There Yet?

Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens;as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.

Predictive value of thrombocytopenia for bloodstream infection in patients with sepsis and septic shock

BACKGROUND Thrombocytopenia is common in patients with sepsis and septic shock.AIM To analyse the decrease in the number of platelets for predicting bloodstream infection in patients with sepsis and septic shock in the intensive care unit.METHODS A retrospective analysis of patients admitted with sepsis and septic shock in Xingtai People Hospital was revisited.Patient population characteristics and laboratory data were collected for analysis.RESULTS The study group consisted of 85(39%)inpatients with bloodstream infection,and the control group consisted of 133(61%)with negative results or contamination.The percentage decline in platelet counts(PPCs)in patients positive for pathogens[57.1(41.3-74.6)]was distinctly higher than that in the control group[18.2(5.1–43.1)](P<0.001),whereas the PPCs were not significantly different among those with gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.Using receiver operating characteristic curves,the area under the curve of the platelet drop rate was 0.839(95%CI:0.783-0.895).CONCLUSION The percentage decline in platelet counts is sensitive in predicting bloodstream infection in patients with sepsis and septic shock.However,it cannot identify gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.

Angiotensin II administration in severe thrombocytopenia and chronic venous thrombosis:A case report

BACKGROUND The initial trials on angiotensin II(AT II)administration indicated a high incidence of thrombocytopenia and thrombosis,as well as a positive correlation between hyperreninemia and response to the medication.CASE SUMMARY We describe a case of a patient presenting with catecholamine resistant septic shock,thrombocytopenia,deep vein thrombosis,and normal renin concentration who responded immediately to AT II treatment.We observed no worsening of thrombocytopenia and no progression of thrombosis or additional thromboses during treatment.CONCLUSION Our case underscores the need for individualized assessment of patients for potential therapy with AT II.

Establishment of a Mouse Thrombocytopenia Model Induced by Cyclophosphamide

An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route that could cause stable thrombocytopenia. A suitable drug dosage that could induce thrombocytopenia in mouse efficiently with the definite administration route was then investigated. BALB/c mice were randomly divided into Normal, Model A and Model B groups. To Model A, 200 mg/kg of cyclophosphamide was given by vena caudalis injection as first dose and 30 mg/kg as maintenance dose by intraperitoneal injection at the following 6 days. To Model B, 150 mg/kg of cyclophosphamide was given by subcutaneous injection once a day for consecutive 3 days. All groups were under investigation for 15 days. The result suggested that a decrease in the number of blood platelets of Model B at the 7th day were significantly than that of Normal. Other platelet related indices like platelet distribution width, mean platelet volume and platelet-large cell ratio of Model B increased significantly in comparison with those of Normal group. The platelets count was reduced but fluctuated greatly, and more than half of the mice died in Model A. Therefore, subcutaneous injection of cyclophosphamide for 3 days was used for the cyclophosphamide dosage test. BALB/c mice were randomly divided into Normal, cyclophosphamide low dose （100 mg/kg）, medium dose （120 mg/kg） and high dose （140 mg/kg） groups. All groups were under investigation for 11 days. Though all 3 dosages successfully initiated thrombocytopenia as the platelets number dropped at the 7th day, the low dose was considered to be a suitable one that was of high efficacy and low toxicity. Thus, BALB/c mice challenged by subcutaneous injection of cyclophosphamide 100 mg/kg per day for 3 consecutive day is one simple, feasible and stable mouse thrombocytopenia model that could be used for pharmacodynamic test of the drugs which are supposed to have platelets increasing effect.

Successful Treatment of Severe Heparin-induced Thrombocytopenia with Intravenous Immunoglobulin, Platelet Transfusion and Rivaroxaban: A Case Report

Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.

Management of thrombocytopenia due to liver cirrhosis:A review

Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis,limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding.Multiple factors,including splenic sequestration,reduced activity of the hematopoietic growth factor thrombopoietin,bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents,and antiviral treatment with interferon-based therapy,can contribute to the development of thrombocytopenia in cirrhotic patients.Of these factors,the major mechanisms for thrombocytopenia in liver cirrhosis are(1)platelet sequestration in the spleen;and(2)decreased production of thrombopoietin in the liver.Several treatment options,including platelet transfusion,interventional partial splenic embolization,and surgical splenectomy,are now available for severe thrombocytopenia in cirrhotic patients.Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis,their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials.In this review,we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume,and we describe the current management of thrombocytopenia due to liver cirrhosis.

Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection

We report the first case of a patient with hepatitis C virus(HCV) infection and idiopathic thrombocytopenic purpura(ITP), who later developed acquired amegakaryocytic thrombocytopenia(AAMT), with autoantibodies to the thrombopoietin(TPO) receptor(c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.