Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Nonalcoholic fatty liver disease and vascular disease:State-of-the-art

Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.

Clinic-pathological features of metabolic associated fatty liver disease with hepatitis B virus infection

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in 2020.AIM To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)infection.METHODS Patients with histopathologically proven MAFLD from a single medical center were included.Patients were divided into MAFLD group(without HBV infection)and HBV-MAFLD group(with HBV infection).Propensity score matching was utilized to balance the baseline characteristics between two groups.RESULTS A total of 417 cases with MAFLD were included,359(86.1%)of whom were infected with HBV.There were significantly more males in the HBV-MAFLD group than in the MAFLD group(P<0.05).After propensity score matching,58 pairs were successfully matched with no significant differences found in gender,age,body mass index,lipid levels,liver enzymes,and the other metabolic associated comorbidities between the two groups(P>0.05).The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group,while the degree of inflammation and fibrosis in the liver was less severe(P<0.05).In multivariate analysis,HBV infection was associated with significantly lower grade of hepatic steatosis[odds ratio(OR)=0.088,95%confidence interval(CI):0.027-0.291]but higher inflammation level(OR=4.059,95%CI:1.403-11.742)and fibrosis level(OR=3.016,95%CI:1.087-8.370)after adjusting for age,gender,and other metabolic parameters.CONCLUSION HBV infection is associated with similar metabolic risks,lower steatosis grade,higher inflammation,and fibrosis grade in MAFLD patients.

Non-alcohol fatty liver disease in Asia:Prevention and planning

AIM:To review all of epidemiological aspects of nonalcoholic fatty liver disease(NAFLD) and also prevent this disease is examined.METHODS:We conducted a systematic review according to the PRISMA guidelines.All searches for writing this review is based on the papers was found in Pub Med(MEDLINE),Cochrane database and Scopus in August and September 2014 for topic of NAFLD in Asia and the way of prevention of this disease,with no language limitations.All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed.RESULTS:NAFLD is the most common liver disorder in worldwide,with an estimated with 20%-30% prevalence in Western countries and 2%-4% worldwide.The prevalence of NAFLD in Asia,depending on location(urban vs rural),gender,ethnicity,and age is variable between 15%-20%.According to the many studies in the world,the relationship between NAFLD,obesity,diabetes mellitus,and metabolic syndrome(MS) is quiet obvious.Prevalence of NAFLD in Asian countries seems to be lower than the Western countries but,it has increased recently due to the rise of obesity,type 2 diabetes and MS in this region.One of the main reasons for the increase in obesity,diabetes and MS in Asia is a lifestyle change and industrialization.Today,NAFLD is recognized as a major chronic liver disease in Asia.Therefore,prevention of this disease in Asian countries is very important and the best strategy for prevention and control of NAFLD is lifestyle modifications.Lifestyle modification programs are typically designed to change bad eating habits and increase physical activity that is associated with clinically significant improvements in obesity,type 2 diabetes and MS.CONCLUSION:Prevention of NAFLD is very importantin Asian countries particularly in Arab countries because of high prevalence of obesity,diabetes and MS.

Autophagy in hepatitis C virus-host interactions:Potential roles and therapeutic targets for liver-associated diseases

Autophagy is a lysosome-associated,degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis.Hepatitis C virus(HCV)is a major cause of chronic hepatitis,which often leads to end-stage liverassociated diseases and is a significant burden on worldwide public health.Emerging lines of evidence indicate that autophagy plays an important role in promoting the HCV life cycle in host cells.Moreover,the diverse impacts of autophagy on a variety of signaling pathways in HCV-infected cells suggest that the autophagic process is required for balancing HCVhost cell interactions and involved in the pathogenesis of HCV-related liver diseases.However,the detailed molecular mechanism underlying how HCV activates autophagy to benefit viral growth is still enigmatic.Additionally,how the autophagic response contributes to disease progression in HCV-infected cells remains largely unknown.Hence,in this review,we overview the interplay between autophagy and the HCV life cycle and propose possible mechanisms by which autophagy may promote the pathogenesis of HCVassociated chronic liver diseases.Moreover,we outline the related studies on how autophagy interplays with HCV replication and discuss the possible implications of autophagy and viral replication in the progression of HCV-induced liver diseases,e.g.,steatosis and hepatocellular carcinoma.Finally,we explore the potential therapeutics that target autophagy to cure HCV infection and its related liver diseases.

Risk factors for de novo hepatitis B infection in pediatric living donor liver transplantation

AIM: To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection.

Epidemiology of fatty liver: An update

We provide a concise review of the main epidemiological literature on fatty liver(FL) published between January 2011 and October 2013. The findings from the literature will be considered in light of the already available knowledge. We discuss the limitations inherent in the categorization of FL into non-alcoholic and alcoholic FL, the potential relevance of FL as an independent predictor of cardiometabolic disease, and recent research addressing the role of FL as an independent predictor of mortality. This review is organized as a series of answers to relevant questions about the epidemiology of FL.

A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia

AIM: To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease (NAFLD) and hyperferritinemia, a frequent feature associated with more severe liver damage, despite at least 6 mo of lifestyle changes.

Nodular liver lesions involving multiple myeloma: A case report and literature review

We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT showed multiple bone lesions and nodular liver lesions. Liver biopsy revealed nodular infiltration of multiple myeloma with positive staining of kappa light chain. Further investigation of bone marrow aspiration, immunofixation and immunoelectrophoresis of serum protein, urine test for Bence-Jones protein, 132-microglobulin in serum and urine confirmed the diagnosis. The patient also coinfected with hepatitis C virus （HCV）. With six cycles of chemotherapy with VAD schedule, she achieved complete remission. In this report, a literature review of liver lesions involving multiple myeloma is also provided.

Clinical implications,diagnosis,and management of diabetes in patients with chronic liver diseases

Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.

T2* magnetic resonance imaging of the liver in thalassemic patients in Iran

AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with beta-thalassemia major having regular blood transfusions were consecutively enrolled. Serum ferritin levels were measured, and all patients underwent MRI T2* of the liver. Liver biopsy was performed in 53 patients at an interval of no longer than 3 mo after the MRIT2* in each patient. The amount of iron was assessed in both MRI T2* and liver biopsy specimens of each patient. RESULTS: Patients’ ages ranged from 8 to 54 years with a mean of 24.59 ± 8.5 years. Mean serum ferritin level was 1906 ± 1644 ng/mL. Liver biopsy showed a moderate negative correlation with liver MRI T2* (r = -0.573, P = 0.000) and a low positive correlation with ferritin level (r = 0.350, P = 0.001). Serum ferritin levels showed a moderate negative correlation with liver MRI T2* values (r = -0.586, P = 0.000). CONCLUSION: Our study suggests that MRI T2* is a non-invasive, safe and reliable method for detecting iron load in patients with iron overload.

Role of Nrf2 in chronic liver disease

Nuclear erythroid 2-related factor 2(Nrf2) is a central regulator of antioxidative response elements-mediated gene expression. It has a significant role in adaptive responses to oxidative stress by interacting with the antioxidant response element, which induces the expression of a variety of downstream targets aimed at cytoprotection. Previous studies suggested oxidative stress and associated damage could represent a common link between different forms of diseases. Oxidative stress has been implicated in various liver diseases, including viral hepatitis, nonalcoholic fatty liver disease/steatohepatitis, alcoholic liver disease and drug-induced liver injury. Nrf2 activation is initiated by oxidative or electrophilic stress, and aids in the detoxification and elimination of potentially harmful exogenous chemicals and their metabolites. The expression of Nrf2 has been observed throughout human tissue, with high expression in detoxification organs, especially the liver. Thus, Nrf2 may serve as a major regulator of several cellular defense associated pathways by which hepatic cells combat oxidative stress. We review the relevant literature concerning the crucial role of Nrf2 and its signaling pathways against oxidative stress to protect hepatic cell from oxidative damage during development of common chronic liver diseases. We also review the use of Nrf2 as a therapeutic target to prevent and treat liver diseases.

Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease

AIM: To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD).METHODS: The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden&#x02019;s index.RESULTS: The mean age of men and women in the study population were 44.8 &#x000b1; 16.8 and 43.78 &#x000b1; 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P &#x0003c; 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P &#x0003c; 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden&#x02019;s index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden&#x02019;s index = 0.5888).CONCLUSION: Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.

On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B

BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.

Development of a novel score for the diagnosis of bacterial infection in patients with acute-on-chronic liver failure

BACKGROUND The diagnosis of bacterial infection is difficult in patients with acute-on-chronic liver failure(ACLF).AIM To evaluate the diagnostic accuracy of widely used parameters for bacterial infection in ACLF and to develop a simple scoring system to improve diagnostic efficiency.METHODS This was a retrospective study.Procalcitonin(PCT),white blood cells(WBC),proportion of neutrophils(N%),and C-reactive protein(CRP)were examined.Logistic regression was used to select variables for the scoring models and receiver operating characteristic curve(ROC)analysis was used to evaluate the diagnostic value of different indices.RESULTS This study included 386 patients with ACLF,169(43.78%)of whom had bacterial infection on admission.The area under the ROC(AUROC)of PCT,CRP,WBC and N%for the diagnosis of bacterial infection ranged from 0.637 to 0.692,with no significant difference between them.Logistic regression showed that only N%,PCT,and CRP could independently predict infection.A novel scoring system(infection score)comprised of N%,PCT and CRP was developed.The AUROC of the infection score was 0.740,which was significantly higher than that for the other four indices(infection score vs N%,PCT,CRP,and WBC,P=0.0056,0.0001,0.0483 and 0.0008,respectively).The best cutoff point for the infection score was 4 points,with a sensitivity of 78.05%,a specificity of 55.29%,a positive predictive value of 57.91%and a negative predictive value of 76.16%.CONCLUSION The infection score is a simple and useful tool for discriminating bacterial infection in ACLF.

Development and validation of a novel model to predict liver-related mortality in patients with idiosyncratic drug-induced liver injury

Background: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury(DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. Methods: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve(AUC). A high-mortality-risk subgroup was identified according to the score. Results: Three independent DILI cohorts, including one derivation cohort( n = 741) and two validation cohorts( n = 650, n = 617) were recruited. The DILI mortality predictive(DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin(mg/d L) + 0.439 × aspartate aminotransferase/alanine aminotransferase – 1.579 × albumin(g/d L) –0.006 × platelet count(109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941(95% CI: 0.922-0.957), 0.931(0.908-0.949) and 0.960(0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. Conclusions: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.

Response-guided treatment of cirrhotic chronic hepatitis B patients: Multicenter prospective study

AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.

Coexistent Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes after pediatric liver transplantation:A case report

BACKGROUND Kaposi sarcoma and post-transplant lymphoproliferative disorder have been occasionally reported in post-liver transplant patients.However,the simultaneous occurrence of these two diseases in the same lymph nodes is very rare.CASE SUMMARY We report the case of a 19-mo-old boy,who presented with intermittent fever and enlarged cervical lymph nodes after liver transplantation.Six cervical lymph nodes were biopsied,and the histopathological examinations revealed multifocal hyperplasia of spindle cells around small blood vessels,extravasated erythrocytes,and heavy infiltration of plasma cells in the cortex and medulla of the lymph nodes.The immunohistochemical analyses of spindle cells revealed positive expression of CD34,CD31,erythroblast transformation-specific-related gene,friend leukemia integration 1,and human herpesvirus-8.The lymphoproliferative lesions expressed CD38,CD138,and multiple myeloma 1.Epstein-Barr encoded RNA in situ hybridization demonstrated Epstein-Barr virus-positive lymphoid cells.Finally,we diagnosed the coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder(plasmacytic hyperplasia)in the same lymph nodes.Treatment strategy included anti-CD20 monoclonal antibody(rituximab)and discontinuation of the immunosuppressant therapies.Lymph node biopsies during follow-up examinations revealed lymphoid hyperplasia.CONCLUSION The rare coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes post-liver transplantation possibly associates with immunodeficiency and Epstein-Barr virus and human herpesvirus-8 coinfection.

Effect of liver transplantation with primary hyperoxaluria type 1:Five case reports and review of literature

BACKGROUND Primary hyperoxaluria type 1(PH1)is a rare autosomal recessive disease stemming from a deficiency in liver-specific alanine-glyoxylate aminotransferase,resulting in increased endogenous oxalate deposition and end-stage renal disease.Organ transplantation is the only effective treatment.However,its approach and timing remain controversial.CASE SUMMARY We retrospectively analyzed 5 patients diagnosed with PH1 from the Liver Transplant Center of the Beijing Friendship Hospital from March 2017 to December 2020.Our cohort included 4 males and 1 female.The median age at onset was 4.0 years(range:1.0-5.0),age at diagnosis was 12.2 years(range:6.7-23.5),age at liver transplantation(LT)was 12.2 years(range:7.0-25.1),and the follow-up time was 26.3 mo(range:12.8-40.1).All patients had delayed diagnosis,and 3patients had progressed to end-stage renal disease by the time they were diagnosed.Two patients received preemptive LT;their estimated glomerular filtration rate was maintained at>120 mL/min/1.73 m2,indicating a better prognosis.Three patients received sequential liver and kidney transplantation.After transplantation,serum and urinary oxalate decreased,and liver function recovered.At the last follow-up,the estimated glomerular filtration rates of the latter 3 patients were 179,52 and 21 mL/min/1.73 m2.CONCLUSION Different transplantation strategies should be adopted for patients based on their renal function stage.Preemptive-LT offers a good therapeutic approach for PH1.