Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.

Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma

BACKGROUND Overexpression of heat shock proteins(HSPs) is associated with several malignancies and contributes to the development, progression, and metastasis of cancer, in addition to the inhibition of cellular death. In recent years, there has been active research into using HSP inhibitors in several malignancies. Due to the poor prognosis of esophageal adenocarcinoma(EAC), it would be valuable to find new biomarkers for the development of cancer treatments.AIM To evaluate the expressions of HSP27 and HSP70 and their effect on survival in EAC.METHODS Immunohistochemical analyses and evaluations of HSP27 and HSP70 expression were performed on all available samples from 93 patients diagnosed with EACbetween 1990 and 2007 at two university hospitals. Fifteen cases with Barrett's metaplasia and 5 control cases from the same patient population were included in the analysis. HSP expression was quantitatively assessed and classified as high or low. Kaplan-Meier analyses and Cox regression models adjusting for age and sex as well as tumor site, stage, and grade were used to evaluate the effect on survival.RESULTS Tumor stage and surgical treatment were the main prognostic factors. High HSP27 expression in cancer cases was a strong negative predictive factor, with a mean survival of 23 mo compared to the 49 mo in cases with a low expression(P= 0.018). The results were similar for HSP70, with a poorer survival of 17 mo in cases with high HSP70 expression, in contrast to 40 mo(P = 0.006) in cases with a low expression. A Cox regression survival analysis was performed, adjusting for possible confounding factors, and higher HSP27 and HSP70 expressions remained an independent negative prognostic factor. The HSPs' correlation with survival was not affected by cancer treatments. When the analysis was adjusted for all factors, the odds ratios for HSP27 and HSP70 were 3.3(CI: 1.6–6.6, P =0.001) and 2.2(CI: 1.2–3.9, P = 0.02), respectively.CONCLUSION HSP27 and HSP70 overexpression is associated with poor survival in EAC, which is, to the best of our knowledge, reported for the first time.

Differential impact of aging and gender on lipid and lipoprotein profiles in a cohort of healthy Chinese Singaporeans

Aim： To evaluate the impact of age and gender on lipid and lipoprotein profiles and the burden of dyslipidemia in a cohort of healthy Chinese Singaporean. Methods： A total of 1 775 healthy Chinese, 536 men and 1 239 women aged between 30 and 70 years old were involved in the present study. Results： Gender differences in all lipid and lipoprotein levels were clearly evident. Singaporean Chinese men have significantly higher levels of total cholesterol （TC）, triglyceride （TG）, low density lipoprotein-cholesterol （LDL-C） and total cholesterol/high density lipoprotein-cholesterol （TC/HDL-C）, and lower levels of HDL-C than women. Although lipid and lipoprotein levels in men did not change in the different age groups, those in women, especially TC, LDL-C and TC/HDL-C, were significantly higher in older women （〉 50 years old） than corresponding levels in younger women （30-46 years old）. Furthermore, TG was significantly correlated with lipids and lipoproteins differently in men and women. If 100 mg/dL of LDL-C were to be adopted as the therapeutic cut-off level, then the burden of care will be huge as approximately 90% of both Chinese men and women have LDL-C greater than 100 mg/dL. Condusion： In light of the findings of the present study, we suggest that preventive measures to promote the reduction in risk of coronary heart disease （CHD） must address the high proportion of men and women with high LDL-C, and that these measures should take into account both the gender and age factors. For men, reduction of high cholesterol must start early in life, whereas for women, steps must be taken earlier to mitigate the anticipated sharp increase in risk, especially after menopause.

The contribution of Asian scientists to global research in andrology

Aim: To present a personal account of the involvement of the World Health Organization (WHO) in the collaborativedevelopment in Asia of those areas of andrology concerned with male contraception and reproductive health.Methods: The andrology training through workshops and institution support undertaken by the WHO HumanReproduction Programme (HRP) and how they contributed to the strengthening of andrology research in Asia aresummarised. Results: The author's experience and the Asian scientific contributions to the global research in thefollowing areas are reviewed: the safety of vasectomy and the development of new methods of vas occlusion; gossypoland its failure to become a safe, reversible male antifertility drag; Tripterygium and whether its pure extracts will passthrough the appropriate toxicology and phased clinical studies to become acceptable contraceptive drugs; hormonalmethods of contraception for men. Conclusion: The WHO policy of research capacity building through training andinstitution strengthening, together with the collaboration of Asian andrologists, has created strong National institutionsnow able to direct their own programmes of research in clinical and scientific andrology.

Gastrointestinal dysbiosis and the use of fecal microbial transplantation in Clostridium difficile infection

The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections(CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation(FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities.

Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis:Insights into mechanisms,pathophysiology,and treatment options

BACKGROUND Autoimmune gastritis(AIG)is a progressive,chronic,immune-mediated inflammatory disease characterized by the destruction of gastric parietal cells leading to hypo/anacidity and loss of intrinsic factor.Gastrointestinal symptoms such as dyspepsia and early satiety are very common,being second in terms of frequency only to anemia,which is the most typical feature of AIG.AIM To address both well-established and more innovative information and knowledge about this challenging disorder.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 10 years.RESULTS A total of 125 records were reviewed and 80 were defined as fulfilling the criteria.CONCLUSION AIG can cause a range of clinical manifestations,including dyspepsia.The pathophysiology of dyspepsia in AIG is complex and involves changes in acid secretion,gastric motility,hormone signaling,and gut microbiota,among other factors.Managing dyspeptic symptoms of AIG is challenging and there are no specific therapies targeting dyspepsia in AIG.While proton pump inhibitors are commonly used to treat dyspepsia and gastroesophageal reflux disease,they may not be appropriate for AIG.Prokinetic agents,antidepressant drugs,and non-pharmacological treatments may be of help,even if not adequately evidence-based supported.A multidisciplinary approach for the management of dyspepsia in AIG is recommended,and further research is needed to develop and validate more effective therapies for dyspepsia.

Vocational Rehabilitation after Acquired Brain Injury: A Swedish Study of Benefits and Costs

Purpose: To examine the benefits from a vocational rehabilitation program for patients suffering from Acquired Brain Injury (ABI) in terms of quality of life, and overall health. In addition, to examine the direct societal costs of healthcare interventions related to vocational rehabilitation and indirect societal costs related to production loss. Method: Identified interventions in 45 patients with ABI who were discharged from a vocational rehabilitation program between 2010 and 2011 were documented, classified and translated into costs. Expenses associated with production loss were calculated by comparing sick leave production loss at first contact with the team, with sick leave production loss at discharge. Health related QoL and overall health, was measured at first contact and at discharge by using the EQ5D. Results: For vocational rehabilitation interventions, mean costs were €6303/individual/month. At first contact with the team, mean production loss was estimated to be €4409/individual/month compared;at discharge to be €2446. QoL ratings increased from first contact to discharge, although estimated health did not change. At discharge, significant correlations were found between QoL ratings and estimated health and the extent of production loss

Molecular pathobiology of scleritis and its therapeutic implications

Scleritis and other autoimmune diseases are characterized by an imbalance in the levels of pro-inflammatory and anti-inflammatory molecules with the balance tilted more towards the former due to the failure of recognition of self. The triggering of inflammatory process could be ascribed to the presence of cytoplasmic DNA/chromatin that leads to activation of cytosolic DNA-sensing c GAS-STING(cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway and enhanced expression of NF-κB that results in an increase in the production of pro-inflammatory bioactive lipids. Bioactive lipids gamma-linolenic acid(GLA), dihomoGLA(DGLA), prostaglandin E1(PGE1), prostacyclin(PGI2) and lipoxin A4, resolvins, protectins and maresins have antiinflammatory actions, bind to DNA to render it non-antigenic and are decreased in autoimmune diseases. These results suggest that efforts designed to enhance the production of anti-inflammatory bioactive lipids may form a new approach to autoimmune diseases. Local injection or infusion of lipoxins, resolvins, protectins and maresins or their precursors such as arachidonic acid may be exploited in the prevention and management of autoimmune diseases including scleritis, uveitis and lupus/rheumatoid arthritis.

Role of leptin in the progression of psoriatic,rheumatoid and osteoarthritis

Leptin,an adipokine responsible for body weight regulation,may be involved in pathological processesrelated to inflammation in joint disorders including rheumatoid arthritis(RA),osteoarthritis,and psoriatic arthritis(PsA).These arthropathies have been associated with a wide range of systemic and inflammatory con-ditions including cardiovascular disease,obesity,and metabolic syndrome.As a potent mediator of immune responses,leptin has been found in some studies to play a role in these disorders.Furthermore,current potent biologic treatments effectively used in Ps A including ustekinumab(an interleukin 12/23 blocker) and ada-limumab(a tumor necrosis factor-alpha blocker also used in RA) have been found to increase leptin receptor expression in human macrophages.This literature review aims to further investigate the role leptin may play in the disease activity of these arthropathies.

The Differential Effects of Chronic Alcohol and Cigarette Smoke Exposures on Cognitive-Behavioral Dysfunction in Long Evans Rats

Background and Objective: Chronic heavy alcohol consumption and daily cigarette smoking are the most prevalent substance use problems in the U.S., including Veterans. Excessive alcohol use causes neurocognitive and behavioral deficits that can be linked to neurodegeneration. Similarly, preclinical and clinical data suggest that smoking also leads to brain atrophy. This study examines the differential and additive effects of alcohol and cigarette smoke (CS) exposures on cognitive-behavioral function. Methods: A 4-way experimental model of chronic alcohol and CS exposures was generated using 4-week-old male and female Long Evans rats that were pair-fed with Lieber-deCarli isocaloric liquid diets containing 0% or 24% ethanol for 9 weeks. Half of the rats in the control and ethanol groups were exposed to CS for 4 hours/day and 4 days/week for 9 weeks. All rats were subjected to Morris Water Maze, Open Field, and Novel Object Recognition testing in the last experimental week. Results: Chronic alcohol exposure impaired spatial learning as shown by significantly increased latency to locate the platform, and it caused anxiety-like behavior marked by the significantly reduced percentage of entries to the center of the arena. Chronic CS exposure impaired recognition memory as suggested by significantly less time spent at the novel object. Combined exposures to alcohol and CS did not show any significant additive or interactive effect on cognitive-behavioral function. Conclusion: Chronic alcohol exposure was the main driver of spatial learning, while the effect of secondhand CS exposure was not robust. Future studies need to mimic direct CS exposure effects in humans.

Intratumoral Bacteria Dysbiosis Is Associated with Human Papillary Thyroid Cancer and Correlated with Oncogenic Signaling Pathways

Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological thresholds.Mild hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate intake.Severe hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left untreated.Individuals with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

Era of universal testing of microsatellite instability in colorectal cancer

Colorectal cancer (CRC) incidence and mortality are constantly decreasing, but CRC still remains the third most prevalent cancer and the third most common cause of cancer death in both males and females in the United States. Recent rapid declines in CRC incidence rates have largely been attributed to increases in screening that can detect and remove precancerous polyps, and the decrease in death rates for CRC largely reflects improvements in early detection, treatment and the understanding of molecular/genetic basis of CRC. One of the important molecular/genetic findings is the presence of microsatellite instability (MSI) in CRCs. Many studies have shown the importance of MSI testing in diagnosing Lynch syndrome and predicting prognosis and response to chemotherapeutic agents in CRCs. Increased emphasis has been placed on the importance of MSI testing for all newly diagnosed individuals with CRCs. Both immunohistochemical staining (IHC) and polymerase chain reaction (PCR)-based MSI testing show high sensitivity and specificity in detecting MSI. The current clinical guidelines and histopathology features are indicative of, but not reliable in diagnosing Lynch syndrome and CRCs with MSI. Currently, there are evidences that universal testing for MSI starting with either IHC or PCR-based MSI testing is cost effective, sensitive, specific and is getting widely accepted.

Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic manifestations.Thus,HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection.Although the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established.In addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance.In order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc supplements.Little is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported.On the other hand,insulin-sensitizing agents are reported to improve sustained virologic response rates.In this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin resistance.Furthermore,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCVassociated insulin resistance.

WJG 20^(th) Anniversary Special Issues(1): Hepatocellular carcinoma Risk prediction of hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy

Chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC)is a major health problem in AsianPacific regions.Antiviral therapy reduces,but does not eliminate the risk of HCC.It would be a heavy financial burden in most low and middle economic countries if all CHB patients received antiviral therapy and HCC surveillance.Thus,there is a need for accurate risk prediction to assist prognostication,decisions on the need for antiviral therapy and HCC surveillance.A few wellestablished risk factors for HCC,namely advanced age,male gender,high viral load,cirrhosis etc.,are the core components of three HCC risk scores:CU-HCC,GAGHCC and REACH-B scores.These 3 scores were confirmed to be accurate in predicting HCC up to 10 years in treatment-na ve patients.Their validity and applicability have recently been demonstrated in a large cohort of entecavir treatment patients.A decrease in risk scores after antiviral therapy translates to a lower risk of HCC.These findings support the application of HCC risk scores in all CHB patients.Different levels of care and different intensities of HCC surveillance should be offered according to the risk profile of patients.Patients at risk of HCC should undergo regular HCC surveillance,even when they are receiving antiviral treatment.

Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

The outcome after curative resection for hepatocellular carcinoma(HCC)remains unsatisfactory due to the high recurrence rate after surgery.In patients with hepatitis B virus(HBV)-related HCC,which is the majority of patients with HCC in Asia,a high viral load is a strong risk factor for HCC recurrence.It is logical to believe that antiviral therapy may improve the postoperative outcome by promoting viral clearance and hepatocyte regeneration,as well as improving residual liver volume in HCC patients with hepatitis B.However,the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be established.There are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and interferon.Interferon treatment reduces the overall incidence of HBV-related HCC in sustained re-sponders.However,side effects may limit its long-term clinical application.Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver diseases.They may also improve the outcome after curative resection for HBV-related HCC.There are increasing evidence to suggest that antiviral therapy could suppress HBV,decrease the perioperative reactivation of viral replication,reduce liver injury,preserve the liver function before and after operation,and may lower the risk of HCC recurrence.After all,antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus,resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.

Epigenetic dysregulation in Epstein-Barr virus-associated gastric carcinoma: Disease and treatments

Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predominance,lower rates of lymph node involvement,and better prognosis.EBVaGC is further characterised by abnormal hypermethylation of tumour suppressor gene promoter regions,causing down-regulation of their expression.In the present review,we critically discuss the role of EBV in gastric carcinogenesis,summarising the role of viral proteins and microRNAs with respect to aberrant methylation in EBVaGC.Given the role of epigenetic dysregulation in tumourigenesis,epigenetic modifiers may represent a novel therapeutic strategy.

IGF1-PI3K-induced physiological cardiac hypertrophy:Implications for new heart failure therapies,biomarkers,and predicting cardiotoxicity

Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.

Klebsiella pneumoniae invasive liver abscess syndrome with purulent meningitis and septic shock: A case from China's Mainland

We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient’s condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in China's Mainland. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.