Acute Kidney Injury in Cirrhosis

( Florence Wong ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

The Diagnosis of Acute Kidney Injury in Cirrhosis: The Reasonable Cut-off Serum Creatinine Value

( Florence Wong ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Traditionally, the diagnosis of acute renal failure in cirrhosis is made using the conventional criterion of a 50% increase in serumcreatinine (SCr) with the final SCr reaching ≥1.5 mg/dL. The recent recognition that even small increases in SCr irrespective ofthe final SCr level can have a negative impact on survival in cirrhosis has led to refinement of the definition of acute renal failure,or more commonly known as acute kidney injury (AKI) nowadays. The severity of AKI is then defined by different stages. Thusstage 1 AKI represents a small but acute increase in SCr by 0.3 mg/dL or 26.4μmol/L in < 48 hours, or 1.5-2 times increase inSCr from baseline. Stages 2 and 3 AKI represent 2.1-3 times and >3 times of increase in SCr respectively, without a cut-off SCrthreshold. There followed a flurry of studies that used this new definition of AKI and many reported the utility of the new definitionand staging system in predicting prognosis of cirrhotic patients with AKI. However, many were not convinced that this new systemadds any information to what we already know about the prognosis of advanced cirrhosis. In 2 recent articles, which evaluatedthe impact of AKI on short-term mortality in patients with decompensated cirrhosis admitted to the hospital for various reasons,both the new AKI criteria with the conventional criteria for the diagnosis of AKI were applied. The first study reported that patientswith stage 1 AKI and a peak SCr of ≤1.5 mg/dL had a very good survival, similar to that of non-AKI patients. Therefore, a thresholdof SCr of 1.5 mg/dL should be retained in the determination of prognosis for these patients. The second study found that theconventional diagnostic criteria with a cut-off SCr of 1.5 mg/dL was better than the new AKI criteria in the prediction of survival.Furthermore, a SCr of ≥1.5 mg/dL was able to predict progression of AKI. However, a larger study of infected cirrhotic patientsfound that the new AKI diagnostic criteria were accurate in predicting survival. These desperate results therefore fuel an ongoingdebate as to whether the conventional or the new AKI diagnostic criteria are better in the prognostication of these cirrhoticpatients. In advocating for a cut-off SCr of 1.5 mg/dL, there is a concern that treatment for AKI may be delayed till the thresholdis reached. Conversely, if a threshold SCr for the diagnosis of AKI is not set, patients may start expensive pharmacological treatmentfor AKI when it may not be required. Therefore, the International Ascites Club, in setting a compromise, suggested that the newdiagnostic AKI criteria should remain, as there is sufficient evidence to support their application in cirrhosis as accurate. However,pharmacological therapy should not be started until AKI has progressed to at least stage 2. These guidelines will need to be validatedin further studies before they can be generally applied to all cirrhotic patients.

Acute kidney injury in liver cirrhosis: new definition and application

( Florence Wong ) 대한간학회 2016 Clinical and Molecular Hepatology(대한간학회지) Vol.22 No.4

The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 μmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression. (Clin Mol Hepatol 2016;22:415-422)

Efficacy and Safety of Tenofovir DF (TDF) in Chronic Hepatitis B Patients (CHB) with Lamivudine Resistance (LAM-R): 5-year Results

( Florence Wong ),( Scott Fung ),( Hie-won Hann ),( Magdy Elkhashab ),( Thomas Berg ),( Milotka J. Fabri ),( Andrzej Horban ),( Mijomir Pelemis ),( Ioan Sporea ),( John F. Flaherty ),( Benedetta Masse 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: In CHB patients with LAM-R, TDF has shown efficacy comparableto FTC/TDF and no detectable TDF resistance at 2 years. The final5 year efficacy and safety results from this trial are presented.Methods: CHB patients on LAM with HBV DNA >3 log10 IU/mL andwith documented LAM-R were randomized (1:1) to TDF or FTC/TDFand followed for 5 years.Results: Two hundred eighty patients were randomized; 232 (83%)completed 5 years of treatment. At baseline, mean age was 47 years,most were male (75%) and non-Asian (66%); 53% were HBeAgnegative. Mean HBV DNA was 5.7 log10 IU/mL and 42% had ALT≤ULN at baseline. At Year 5, virologic, serologic, and biochemicalresponses were similar among groups, and remained stable. Ninepatients (4-TDF, 5-FTC/TDF) discontinued due to an adverse event,including increased serum creatinine in 1 patient. For both groupscombined, confirmed renal safety endpoints over 5 years were: CrCL<50 mL/min in 19 (6.8%) patients (12 requiring dose modification),increases in serum creatinine of ≥0.3 and ≥0.5 mg/dL from baselinein 21 (7.5%) and 2 (0.7%) patients, respectively, and serum phosphorus<2 mg/dL in 3 (1.1%) patients. Mean declines in BMD (g/cm2)from baseline for hip and spine BMD, respectively, were 1.7% and1.5% at Year 2, and 2.5%, and 1% at Year 5. Seven patientsexperienced fracture (all except 1 were trauma-related). No TDF resistancewas detected through 5 years by population sequencing.Conclusions: In LAM R patients with CHB treated for 5 years withTDF, a high rate of HBV DNA suppression was achieved and maintainedwith no detectable TDF resistance. There is no apparent ad advantageof combination FTC/TDF in this population. Renal eventsassociated with TDF occurred in up to 7.5% of patients, and averagelosses in bone mineral density of 1 2.5% were observed.

Breast Cancer Screening Practice and Associated Factors in Menopausal and Postmenopausal Women

Florence Mei Fung Wong,Winnie Lai Sheung Cheng 대한폐경학회 2019 대한폐경학회지 Vol.25 No.1

Objectives: This study examined breast cancer screening (BCS) practices and its associated factors among menopausal and postmenopausal women. Methods: A cross-sectional design was conducted using convenience sampling at a community center. The modified Chinese BCS Belief questionnaire was used to understand BCS practice. Results: A total of 144 eligible women presented better knowledge and perceptions about breast cancer (mean, 11.46; standard deviation [SD], 3.65) and barriers to achieving mammographic screening (mean, 14.75; SD, 3.70). Participants aged ≥ 50 years had a negative association with the attitudes towards general health check-ups (B = –1.304, standard error [SE] = 0.65, P = 0.046). In this context, having regular physical exercise had a positive association with attitudes towards general health check ups (B = 1.458, SE = 0.06, P = 0.017), and knowledge and perceptions about breast cancer (B = 1.068, SE = 0.62, P = 0.086). Being employed had a positive associated with barriers to achieving mammographic screening (B = 1.823, SE = 0.51, P < 0.001). Conclusions: The women had better knowledge and perception about breast cancer and fewer barriers to mammographic screening. However, attitudes towards general health check-ups were relatively poor. It is noteworthy that women who aged ≥ 50 years and had insufficient physical exercise had poor attitudes. Those who were employed had fewer barriers, and those who had regular physical exercise had better knowledge on the benefits of the BCS practice. Importantly, women who aged ≥ 50 years and lack physical exercise need education about breast cancer to increase their awareness of breast wellness.

Management of refractory ascites

Florence Wong 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.1

The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.

Improvement in Renal Parameters in CHB Patients Treated with Tenofovir Alfenamide (TAF) versus Tenofovir Disoproxil Fumarate (TDF) over 96 Weeks

( Hyung Joon Kim ),( Wan Long Chuang ),( Kosh Agarwal ),( Jae Seok Hwang ),( Florin Caruntu ),( Florence Wong ),( Hie Won Hann ),( John Flaherty ),( Audrey Lau ),( Anuj Gaggar ),( Vithika Suri ),( Shu 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: In Phase 3 studies in CHB patients the efficacy of TAF was found smaller changes in renal parameters compared with TDF treatment. This benefit was particularly evident in patients with risk factors for renal impairment.Here, we present renal safety results after 96 weeks of treatment. Methods: In Phase 3 studies (HBeAg positive patients [N=873] and HBeAg negative patients [N=425]), patients were randomized 2:1 to TAF 25 mg QD or TDF 300 mg QD, and treated for 144 weeks. Renal parameters including estimated glomerular filtration rate (eGFR) calculated by the Cockcroft-Gault method were evaluated. Chronic kidney disease (CKD) staging was categorized by the National Kidney Foundation KDOQI guidelines. Evaluated risk factors for kidney disease included older age (age ≥ 50), female gender, renal impairment (eGFR <90mL/min) and presence of comorbidities (hypertension, cardiovascular disease and diabetes). Urine markers of renal glomerular dysfunction (urine protein and albumin to creatinine ratio) and tubular dysfunction (retinol binding protein (RBP) and beta-2 microglobulin [B2M] to creatinine ratio) were serially assessed. Results: Patients treated with TAF continued to show smaller changes in serum creatinine (p=0.001) and eGFRCG (p<0.001) at 96 weeks. Similarly, median percentage changes in renal tubular markers, were also smaller in TAF-treated patients compared with TDF patients at Week 96; RBP/Cr (p<0.0001) and B2M/Cr (p<0.0001). A lower percentage of patients experienced ≥1 stage worsening in NKF CKD stage when treated with TAF compared with TDF at Week 96 overall and when evaluated by risk factors for kidney disease.Furthermore, CKD stage progression increased disproportionately in the TDF group in patients with ≥2 risk factors (Table). Conclusions: Treatment with TAF for 96 weeks continued to be associated with smaller changes in renal parameters compared with TDF treatment. The benefits of TAF are particularly evident in patients with risk factors for kidney disease.