Shifting perspectives in liver diseases after kidney transplantation

Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis.The causes are diverse and mainly associated with hepatotropic viruses,drug toxicity and metabolic disorders.Over the past decade,the aetiology of liver disease in kidney recipients has changed significantly.These relates to the use of direct-acting antiviral agents against hepatitis C virus,the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity.In addition,the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients.This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.

Impact of bariatric surgery on glucose and lipid metabolism and liver and kidney function in food-induced obese diabetic rats

BACKGROUND Obesity usually causes diabetes mellitus(DM)and is a serious danger to human health.Type 2 DM(T2DM)mostly occurs along with obesity.Foodborne obesityinduced DM is caused by an excessive long-term diet and surplus energy.Bariatric surgery can improve the symptoms of T2DM in some obese patients.But different types of bariatric surgery may have different effects.AIM To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats.METHODS Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery(RYGB),sleeve gastrectomy(SG),or gastric banding(GB).Glucose and insulin tolerance tests,analyses of biochemical parameters,histological examination,western blot,and quantitative real-time polymerase chain reaction were conducted.RESULTS In comparison to the sham operation group,the RYGB,SG,and GB groups had decreased body weight and food intake,reduced glucose intolerance and insulin insensitivity,downregulated biochemical parameters,alleviated morphological changes in the liver and kidneys,and decreased levels of protein kinase Cβ/P66shc.The effect in the RYGB group was better than that in the SG and GB groups.CONCLUSION These results suggest that RYGB,SG and GB may be helpful for the treatment of foodborne obesity-induced DM.

Liver or kidney:Who has the oar in the gluconeogenesis boat and when?

Gluconeogenesis is an endogenous process of glucose production from noncarbohydrate carbon substrates.Both the liver and kidneys express the key enzymes necessary for endogenous glucose production and its export into circulation.We would be remiss to add that more recently gluconeogenesis has been described in the small intestine,especially under high-protein,lowcarbohydrate diets.The contribution of the liver glucose release,the net glucose flux,towards systemic glucose is already well known.The liver is,in most instances,the primary bulk contributor due to the sheer size of the organ(on average,over 1 kg).The contribution of the kidney(at just over 100 g each)to endogenous glucose production is often under-appreciated,especially on a weight basis.Glucose is released from the liver through the process of glycogenolysis and gluconeogenesis.Renal glucose release is almost exclusively due to gluconeogenesis,which occurs in only a fraction of the cells in that organ(proximal tubule cells).Thus,the efficiency of glucose production from other carbon sources may be superior in the kidney relative to the liver or at least on the level.In both these tissues,gluconeogenesis regulation is under tight hormonal control and depends on the availability of substrates.Liver and renal gluconeogenesis are differentially regulated under various pathological conditions.The impact of one source vs the other changes,based on post-prandial state,acid-base balance,hormonal status,and other less understood factors.Which organ has the oar(is more influential)in driving systemic glucose homeostasis is still inconclusive and likely changes with the daily rhythms of life.We reviewed the literature on the differences in gluconeogenesis regulation between the kidneys and the liver to gain an insight into who drives the systemic glucose levels under various physiological and pathological conditions.

Synergistic Mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera Aqueous Extract: Its Liver and Kidney Benefits in Male Albino Rat Model

Background: The synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract is a common drink in Port Harcourt, Nigeria. It is assumed to have various health benefits. However, the synergistic mixture of the content has not been studied scientifically, hence the need to evaluate its effect on the liver and kidney being part of the body’s metabolic organs. Aim: This study evaluated the synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract in male albino rats. Methods: Acute toxicity LD50 of STCD was carried out, afterwards, fifteen male albino rats were grouped into three groups with 5 rats in each group;Control, 200 mg/kg, 400 mg/kg STCD. The rats were administered STCD orally 24 hourly, for 21 days, with feed and water ad libitum. At the end of the experiment, blood samples were collected for biochemical analysis of the liver and kidney biomarkers, while the liver and kidney tissues were harvested for histopathological examination using standard laboratory methods. Descriptive statistics were computed and expressed as Mean ± SD. One-way ANOVA and Turkeys test was performed. P value ≤0.05 was considered statistically significant. Results: Acute toxicity LD50 of STCD was observed to be ≥2404.2 mg/kg body weight. An increase in the percentage body weight difference of 8.39% and 2.86% was observed for 200 and 400 mg/kg STCD groups. Also, the liver weight was observed to increase in 400 mg/kg (3.92 ± 1.42) in comparison to the control group (3.48 ± 1.61), a decrease in the kidney weight was observed in all groups administered STCD in comparison to the control group. Administration of STCD at both 200 and 400 mg/kg revealed a decrease in the concentration of the hepatic biomarkers AST, ALT, ALP, TP, Albumin, Total and conjugated bilirubin. The kidney biomarker Urea was observed to decrease in concentration for 200 mg/kg STCD (4.60 ± 1.83) and 400 mg/kg STCD (4.76 ± 0.74) when compared to the control group (6.32 ± 2.74). A decrease in Creatinine was observed in 200 mg/kg (91.80 ± 34.69) and 400 mg/kg (98.60 ± 15.53) in comparison to the control group (117.60 ± 42.88). The histological examination of the liver of rats administered STCD revealed structural normal central vein, hepatocytes and portal tract. The kidney examination revealed normal glomeruli and normal tubule. Conclusion: The findings of this study opine that STCD improved the health of both the liver and kidney as evidenced via the biomarkers and histological examinations of the liver and kidney. This study therefore recommends the intake of STCD at moderate doses for improved liver and kidney function due to its bioactive compounds and nutritional content.

Polycystic Ovary Syndrome-Related Infertility Based on the Theory of“Liver and Kidney Homology”

Polycystic ovary syndrome(PCOS)is an endocrine disorder caused by hypothalamic-pituitary-ovarian(HPO)axis dysfunction.In the field of gynecology and reproduction,PCOS has emerged as both a research hot spot and a challenging area of study.According to Chinese medicine,this disease is related to kidney deficiency,phlegm and dampness obstruction,blood stasis and interconnection,Chong pulse impassability,the lack of Ren pulse,and the loss of uterine nourishment,all of which affect the normal development and maturation of eggs as well as the duration at which menstrual blood stores.In this paper,based on the theoretical basis of“liver collects blood,regulates the flow of qi,and is the master of drainage,”we explore the rationality of the treatment of this disease from the perspective of“liver and kidney have the same origin”and the development of PCOS-related infertility in relation to dysfunctional internal organs.We also explore the feasibility of treatment from the perspective of“liver and kidney homology,”expand the ideas for treatment,as well as develop and innovate the application of organ identification in PCOS in relation to infertility.

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(<1.2 mg/dL in men,or<1.1 mg/dL in women)were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012.Thirty patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also included.Measurement of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system.The ACLF patients were followed during their hospitalization period.RESULTS:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed AKI.Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L.The baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.CONCLUSION:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.

Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis

AIM To evaluate the differences in acute kidney injury(AKI) between acute-on-chronic liver failure(ACLF) and decompensated cirrhosis(DC) patients. METHODS During the period from December 2015 to July 2017, 280 patients with hepatitis B virus(HBV)-related ACLF(HBV-ACLF) and 132 patients with HBV-related DC(HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin(NGAL), interleukin-18(IL-18), liver-type fatty acid binding protein(L-FABP), cystatin C(CysC), and kidney injury molecule-1(KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively(25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers(NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI(ACLF-AKI), compared with that in patients with HBV-DC and AKI(DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients(49.3% vs 17.9%, P = 0.013). Fortythree patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLFAKI patients was significantly lower than that of patients with DC-AKI(32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups(P < 0.001).CONCLUSION AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.

Acute kidney injury and post-reperfusion syndrome in liver transplantation

In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death(DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease(CKD). Acute kidney injury(AKI) post-LT has been recently recognized as an important risk factor for the occurrence of denovo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome(PRS) that can influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since preLT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A Pub Med search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on Pub Med search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRSinduced AKI, avoiding confounding factors, we have limited our study to "acute kidney injury AND DCD AND liver transplantation". Accordingly, three out of five studies were selected for our purpose.

MRI-determined fat content of human liver,pancreas and kidney

AIM:To assess and correlate the lipid content of various organs in obese subjects and in persons with a normal body weight.METHODS:Magnetic resonance spectroscopy and a previously validated gradient echo magnetic resonance imaging method with Dixon's two point technique were used in this study to quantify fat in liver,pancreas as well as kidney.RESULTS:In 36 volunteers with body mass index(BMI) ranging from 20.0 to 42.9 kg/m2,the median fat content of liver,pancreas and kidney was 2.3%(interquartile range:0.2%-7.8%),2.7%(1.0%-6.5%) and 0.7%(0.1%-1.4%),respectively.BMI and subcutaneous fat correlated significantly with liver and pancreas fat content.We show for the first time the significant correlation of liver and pancreas fat content in healthy controls(r = 0.43,P < 0.01).These observations are related to body weight as measured by BMI and the amount of subcutaneous fat.Kidney fat content is very low and correlates with none of the other fat depots.CONCLUSION:Renal lipid accumulation,unlike the coupled accumulations of fat in liver and pancreas,is not observed in obese subjects.Unlike suggestions made in previous studies,renal lipid accumulation appears not to be involved in the pathogenesis of renal disease in humans.

An effective model for predicting acute kidney injury after liver transplantation

BACKGROUND: Acute kidney injury (AKI) is a common complication in the early period after liver transplantation (LT), posing an enormous obstacle to treatment efficiency and patient survival. However, the exact influencing factors of AKI are still unclear and a predictive model is desperately required in the clinic. METHODS: Data of 102 consecutive LTs were reviewed. A model for predicting AKI was established and further validated in a prospective study of 44-patients receiving LT. RESULTS: The incidence of AKI was 32.4%. AKI patients showed a significantly lower survival rate than non-AKI patients. Multivariate analysis demonstrated the independent influencing factors of AKI were preoperative serum creatinine >1.2 mg/dl, intraoperative urine output <= 60 ml/h, intraoperative hypotension status, and intraoperative use of noradrenaline. A model was then established and showed a sensitivity of 75.0%, a specificity of 93.8%, and an accuracy of 88.6% in predicting AKI. CONCLUSIONS: High preoperative serum creatinine, low intraoperative urine output, and intraoperative hypotension contribute to the development of AKI, and intraoperative use of noradrenaline serves as a protective factor. The predictive model could potentially facilitate early prediction and surveillance of AKI. (Hepatobilinty Pancreat Dis Int 2010; 9:259-263)

Prophylaxis of chronic kidney disease after liver transplantation-experience from west China

AIM： TO evaluate the prophylaxis of chronic kidney dis- ease （CKD） after liver transplantation （LT） with low-dose calcineurin inhibitor （CNI） and mycophenolate mofetil （MMF）.

Kidneys in chronic liver diseases

Acute kidney injury(AKI),defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL,occurs in about 20% of patients hospitalized for decompensating liver cirrhosis.Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state,reduced effective blood volume and stimulation of vasoconstrictor hormones.The most common causes of AKI in cirrhosis are pre-renal azotemia,hepatorenal syndrome and acute tubular necrosis.Differential diagnosis is based on analysis of circumstances of AKI development,natriuresis,urine osmolality,response to withdrawal of diuretics and volume repletion,and rarely on renal biopsy.Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients.AKI is one of the last events in the natural history of chronic liver disease,therefore,such patients should have an expedited referral for liver transplantation.Hepatorenal syndrome(HRS) is initiated by progressive portal hypertension,and may be prematurely triggered by bacterial infections,nonbacterial systemic inflammatory reactions,excessive diuresis,gastrointestinal hemorrhage,diarrhea or nephrotoxic agents.Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy.The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion,which is effective in about 50% of patients.The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt,renal vasoprotection or systems of artificial liver support.

A successful case of combined liver and kidney transplantation for autosomal dominant polycystic liver and kidney disease

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Diabetes mellitus is a risk factor of acute kidney injury in liver transplantation patients

Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate(e GFR), the model for end-stage liver disease(MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients(35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of e GFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of e GFR within the first year after surgery.

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.

Combined liver and kidney transplantation in Guangzhou,China

BACKGROUND: When liver or kidney transplant can respectively cure end-stage liver or kidney disease, neither hepatic graft nor renal transplant alone can be used as a radical therapy for diseases which involve both liver and kidney. Combined liver and kidney transplantation commenced late in China, and the number of transplants has been limited. This study was designed to assess the effects of simultaneous combined liver and kidney transplantation (SLKT) on end-stage liver and kidney diseases. METHODS: Fifteen patients who had received SLKT from 1996 to 2006 in the First Affiliated Hospital of Sun Yat-Sen University were reviewed. They included 5 patients with polycystic liver and kidney, 5 patients with hepatic cirrhosis and renal failure, and 5 patients with fulminant hepatic failure and hepatorenal syndrome (11 men and 4 women; average age 43.5 years). All patients had combined liver and kidney transplantation. RESULTS: The 5 patients with polycystic liver and kidney have survived for more than one year after SLKT, and the longest survival has been 5 years. Three of the 5 patients with hepatic cirrhosis and renal failure have survived more than two years; one died perioperatively and the other died from recurrence of hepatitis B 18 months after the operation. Three of the 5 patients with fulminant hepatic failure and hepatorenal syndrome have survived for two years, and 2 died of multiple organ failure during the operation. CONCLUSIONS: SLKT is an effective therapy for end-stage liver and kidney disease but the indications of SLKT for hepatorenal syndrome should be strict. SLKT may immunologically protect the renal graft.

Alpha-tocopherol supplementation on chromium toxicity: a study on rat liver and kidney cell membrane

Membrane damage is one of the important consequence of chromium, an environmental toxicant, to produce cytotoxicity. α-tocopherol, a membrane protectant can be used to reduce the chromium-induced membrane damage. In the present study, the impact of chromium in presence and absence of α-tocopherol was studied on plasma membrane of liver and kidney in male Wistar rats (80—100 g body weight). Significant increase in membrane cholesterol level as well as significant decrease in membrane phospholipid level in chromium exposed ( 0.8 mg /100 g body weight/d, i.p., for 4 weeks) animals suggest structural alteration of both liver and kidney plasma memebrane. The alkaline phosphatase, total ATPase and Na +-K +-ATPase activities of plasma membrane were significantly decreased in both liver and kidney after chromium treatment. However, α-tocopherol (30 mg/100 g diet) supplementation can restrict the changes in these membrane-bound enzyme activities. Thus, the usefulness of dietary supplementation of α-tocopherol to restrain the chromium-induced membrane damage is suggested.

Application of machine learning models for predicting acute kidney injury following donation after cardiac death liver transplantation

Background: Acute kidney injury(AKI) is a common complication after liver transplantation(LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. Methods: A total of 493 patients with donation after cardiac death LT(DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes(KDIGO). The clinical data of patients with AKI(AKI group) and without AKI(non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve(AUC). Results: The incidence of AKI was 35.7%(176/493) during the follow-up period. Compared with the nonAKI group, the AKI group showed a remarkably lower survival rate( P<0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval(CI): 0.794–0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models( P<0.001). Conclusions: The random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.

Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μmol/L±270.09μmol/L vs 176.13μmol/L±185.70μmol/L,P=0.014).Serum albumin levels were significantly increased in both the"TQD"group and"TTK"group as compared with the MMC group(31.30 g/L±4.77g/L,30.72 g/L±2.89 g/L vs 28.57 g/L±4.56 g/L,P<0.05).There were no significant differences in levels of alanine transaminase among the three groups(P>0.05).Safety data showed that there was one case of stomachache in the"TQD"group and one case of gastrointestinal side effect in the"TTK"group.CONCLUSION:Treatment with"TTK"improved the survival rates of patients with liver failure due to chronic hepatitis B.Additionally,liver tissue was regenerated and liver function was restored.

Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.