Lower Rates Of Naturally Occurring Resistance-Associated Substitutions (RASs) In Hepatitis C Virus (HCV)-Infected Chronic Kidney Disease (CKD) Patients Than In HCV-Infected Patients With Only Liver Disease.

PURPOSE: Baseline viral load and existence of resistance-associated substitutions (RASs) are associated with direct-acting antiviral agent (DAA) treatment failure in patients with chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: This study was done on HCV-infected patients with different clinical conditions, group 1 included HCV-infected patients with only liver disease (n= 24) and group 2 had HCV-infected patients with coexisting chronic kidney disease (CKD) (n =26). Baseline RAS in the viral genome, before treatment initiation, was examined in both the groups to understand the host disease status on their occurrence. RESULTS: Predominant genotype (gt) differed in both the groups, in group 1 it was gt3 while it was gt1 in group 2. Overall, the occurrence of RASs at baseline was seen in 10 patients (20%); in group 1 it was seen in 8 (33.3%) as compared to only 2 (7.6%) in group 2; p < 0.001. RAS in both NS5a and NS5b regions of the virus was seen in group 1 while in group 2, RASs were seen only in the NS5a region of the virus at 30K position. In group 1, multiple RASs were also seen. The existence of RAS at baseline in both the groups did not affect the attainment of post-treatment cure for the virus in terms of sustained virological response (SVR). CONCLUSION: Host disease status influences the occurrence of baseline RAS in the virus.

Detection of Coagulopathy in Chronic Renal Disease using Thromboelastography and its comparison with Conventional Tests.

PURPOSE OF THE STUDY: Thromboelastography provides a holistic picture of blood coagulation including fibrin formation, cross, linking and fibrinolysis. Coagulaopathy in end stage renal disease (ESRD) is multifactorial. The present evaluated the thromboelastographic profile of ESRD patients and compared it to conventional tests of coagulation. STUDY DESIGN: In this observational case control study, fifty ESRD patients and 50 controls were recruited. Venous samples were withdrawn and platelet count, International Normalization Ratio and fibrinogen levels were measure. Simultaneously a thromboelastography (TEG) was performed. All samples were drawn prior to initiation of dialysis. RESULTS: The fibrinogen concentration was higher in the ESRD group compared to control (455.51±83.39 vs. 233.84±71.71 mg/dl, P<0.05). The maximum amplitude in ESRD group was 76.94 ± 15.11 mm, which was significantly higher than control group 65.10±10.31 mm (P<0.05).Out of 50 ESRD patients,39 had maximum amplitude (MA) >73mm, 3 had MA <55 mm while 8 patients had normal MA. Further, it was seen that in four out if the five patients whose INR was greater than 1.5. TEG was hypercoaguable. Also, three patients whose platelet count was less than x105/dl had normal thromboelastographs. Two patients with normal platelet count, fibrinogen and INR had hypercoaguable thromboelastographs. Thromboelastography could detect fibrinolysis in 5 patients of end stage renal disease. CONCLUSION: The present study demonstrated that INR, platelet count and fibrinogen levels do not reflect the actual coagulation status in patients of ESRD. Thromboelastography is a better tool to detect coagulopathy in this group of patients.

Combined Fluoroscopy and Ultrasound-Guided Transjugular Kidney Biopsy in Cirrhotic Patients.

PURPOSE: To evaluate the safety and diagnostic yield of combined fluoroscopy and ultrasound-guided transjugular kidney biopsy (TJKB) in cirrhotic patients with suspected renal parenchymal disease. MATERIALS AND METHODS: A retrospective review was made of 27 patients (21 men; overall mean age 44.7 y) who underwent TJKB from June 2013 to June 2016; 21 patients had coagulopathy and/or thrombocytopenia, 4 underwent simultaneous TJKB with transjugular liver biopsy, and 1 patient each had severe obesity and gross ascites. All procedures were performed with the use of fluoroscopy and simultaneous transabdominal ultrasound guidance. The data were analyzed for number of passes taken, number of glomeruli in the tissue cores, adequacy of tissue core for histopathologic diagnosis, and incidence and severity of complications. RESULTS: The average number of passes per case was 3.6 (range 2-6). The total length of tissue cores ranged from 0.4 cm to 2.5 cm. The mean numbers of glomeruli per procedure on light microscopy were 6.7 (range 0-17). Diagnostic biopsy specimens were obtained in 23 out of 27 patients (85%). Eleven patients had minor complications. One patient had major complication in the form of hemoglobin drop of 2.1 mg/dL which required embolization and blood transfusion. CONCLUSIONS: Combined use of fluoroscopy and ultrasound guidance for TJKB yielded adequate tissue samples with fewer passes and a low rate of complications in high-risk patients with cirrhosis.

Bile Cast Nephropathy in Patients with Acute Kidney Injury Due to Hepatorenal Syndrome: A Postmortem Kidney Biopsy Study.

Background and Aims: The role of bile cast nephropathy (BCN) in pathogenesis of hepatorenal syndrome (HRS) in decompensated cirrhosis and acute on chronic liver failure (ACLF) is unknown. This study aimed to determine the frequency of BCN detected on postmortem renal biopsy among patients with decompensated cirrhosis and ACLF who had been admitted with acute kidney injury due to HRS (HRA-AKI) and expired during that hospitalization. Methods: One-hundred-twenty-seven postmortem renal biopsies with adequate size (>1 cm in length) were included for analysis. These were obtained from 84 patients with decompensated cirrhosis and 43 patients with ACLF. Results: BCN was detected in 57 of the total 127 (44.8%) renal biopsy specimens. Patients with BCN had significantly higher levels of serum total bilirubin, total leukocyte count and model for end-stage liver disease score, as compared to those without BCN. BCN was detected in 32/43 (74.4%) of the patients with ACLF, as compared to 25/84 (29.7%) of the patients with decompensated cirrhosis (p < 0.001). On multivariate analysis, direct bilirubin (OR (95% CI): 1.27 (1121-1.698); p < 0.001) and presence of ACLF (OR (95% CI): 2.603 (1.054-7.111); p = 0.041) were found to be significant predictors of BCN on postmortem renal biopsy. Conclusion: BCN was found in 72.1% of patients with ACLF and 27.4% patients with decompensated cirrhosis who had been hospitalized with an admitting diagnosis of HRS-AKI and who expired during that hospitalization and underwent postmortem renal biopsy. Direct serum bilirubin and presence of ACLF were found to be significant predictors of BCN on postmortem renal biopsy.

Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure.

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. CONCLUSIONS: The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure.

Surgical illustration of en-bloc (dual) kidney transplant from a 16-month old brain-dead donor to an adult recipient.

Transplantable organs from pediatric donors have been contributing significantly to donor pool worldwide. Pediatric donors are excellent resources that should be procured whenever available, and with the recent increase in deceased donations in India, more pediatric donors will be available for organ harvesting. We share a rare instance of multi-organ harvesting from a 16-month old brain dead donor and implanting both kidneys en-bloc in an adult male, while liver went to a 4-year old child. The report provides the surgical illustration of salient steps of transplanting both kidneys from pediatric donor into an adult, in an en-bloc manner.

Liver dialysis in acute-on-chronic liver failure: current and future perspectives.

Patients with acute-on-chronic liver failure (ACLF) are known to have a very high mortality rate as the majority of these patients succumb to multiorgan failure. Liver transplant remains the only option for these patients; however, there are problems with its availability, cost and also the complications and side effects associated with immunosuppression. Unlike advanced decompensated liver disease, there is a potential for hepatic regeneration and recovery in patients with ACLF. A liver support system, cell or non-cell based, logically is likely to provide temporary functional support until the donor liver becomes available or the failing liver survives the onslaught of the acute insult and spontaneously regenerates. Understanding the pathogenesis of liver failure and regeneration is essential to define the needs for a support system. Removal of hepatotoxic metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell-based hepatic support, could help to provide a suitable microenvironment and support the failing liver. The current systems, i.e., MARS and Prometheus, have failed to show survival benefits in patients with ACLF based on which newer devices with improved functionality are currently under development. However, larger randomized trials are needed to prove whether these devices can enable restoration of the complex dysregulated immune system and impact organ failure and mortality in these patients.

Management of acute kidney injury in cirrhosis.

Acute kidney injury (AKI) is a relatively frequent problem, occurring in approximately 20 % of hospitalized patients with cirrhosis. Although serum creatinine (S Cr) is the most commonly used method to determine AKI because of easy availability and low cost, practically it underestimates the extent of kidney injury in patients with chronic liver disease. AKI is defined as an abrupt rise in S Cr of 0.3 mg/dl or more (>26.4 mmol/l) or an increase of 150 % or more (1.5-fold) from baseline. The cause of AKI in cirrhosis is multifactorial and is unique in terms of pathogenesis. The most common causes of AKI in cirrhosis can be subdivided into either functional or structural. The functional group includes volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal syndrome). Volume responsive is the most common type of AKI due to frequent use of diuretics, large volume abdominal paracentesis and gastrointestinal bleeding in patients with liver disease. The structural causes include acute tubular necrosis, tubulointerstitial and glomerular diseases. Patients with decompensated cirrhosis are in a vasodilatory state leading to a decrease in effective arterial blood volume, predisposing to AKI. Therefore, management of AKI depends on the underlying cause, and therapy should be directed toward removal of the cause. The outcome in cirrhosis when patients are on dialysis is very dismal. Every effort should be made to prevent AKI.