Background:

Although the precipitating events of hepatorenal syndrome (HRS) development have been well characterized, the actual baseline risk of these events resulting in HRS is much less studied.

Aim:

To assess the predictive value of hyponatremia in the development of HRS.Patients and methods: We performed a retrospective observational cohort study including consecutive patients with decompensated liver cirrhosis and normal creatininemia admitted to tertiary center in Slovakia. Patients were censored at two months, development of renal failure, classified either as HRS or renal failure not fulfilling criteria of HRS, was the main outcome.

Results:

Out of 202 patients 18 developed HRS and 14 renal failure not fulfilling the HRS criteria. A significant difference was found between patients with and without HRS in serum sodium (135.76 ± 5.01 vs. 130.78 ± 3.574 mmol/l; p < 0.0001), creatinine, (81 ± 20.11 vs. 98.18 ± 25.032 µmol/l; p = 0.006), bilirubin (90.4 ± 104.82 vs.175.42 ± 174.12 µmol/l; p < 0.0001), MELD (15.17 ± 5.52 vs. 21.61 ± 6.0; p < 0.0001) and MELD-Na score (19.96 ± 6.0 vs. 25.89 ± 4.96; p < 0.0001). Sodium, creatinine, bilirubin, MELD, MELD-Na score were found to be significant predictors of HRS in univariate analysis. Multivariate analysis two prediction models (Model 1: Bilirubin, creatinin, sodium and Model 2: Sodium, MELD) showed that sodium together with creatinine are the strongest HRS predictors, followed by bilirubin or MELD score.

Conclusion:

Serum levels of sodium, creatinine and parameters of liver function are important predictors of hepatorenal syndrome.

Insufficient is the evidence defining the safe minimal remnant volume after living donor hepatectomy. The aim of this study was to evaluate the outcomes of living donors with a remnant-to-total volume ratio (RTVR) less than 30% after right hepatectomy by the selection criteria: preservation of middle hepatic vein (MHV), age<50 years, and no or mild fatty change in healthy adults. All living donors who underwent right hepatectomy saving MHV at the authors' institution between January 2005 and September 2011 were divided into 2 groups: group A with an RTVR < 30% and group B with an RTVR ≥ 30%. Perioperative data, complications by the Clavien classification, and the outcomes with at least 15 months follow-up were compared. Twenty-eight donors were enrolled in group A and 260 in group B. The estimated liver volume was strongly correlated with the actual graft weight (R(2) =0.608, p<0.001). The calculated donation liver volume and RTVR made significant differences between the two groups (p=0.034 and p<0.001, respectively). The peak postoperative AST, ALT, and INR levels made no difference between the two groups. The peak total bilirubin level was higher in group A than in group B (p=0.039). The hospital stay was longer in group A than in group B (p<0.001). All donors recovered completely with no significant difference in overall complications between the two groups. Right hepatectomy saving MHV with an RTVR less than 30% could be safely indicated in carefully selected living donors under 50 years old with no or mild fatty change. Liver Transpl, 2013. © 2013 AASLD.

Background:

Silibinin has been reported to be a promising compound for hepatitis C treatment of non-responders to standard treatment. Although administered silibinin is well tolerated, increased serum bilirubin levels have been observed during high dose intravenous silibinin therapy. The mechanism of silibinin induced hyperbilirubinemia in humans is, however, not identified so far.

Aim:

The aim of this study was to investigate the effect of silibinin on hepatocellular uptake and efflux transport systems for organic anions to elucidate the cause of silibinin induced hyperbilirubinemia. Therefore, the effect of silibinin on transport activity of the hepatocellular uptake transporters organic anion transporting polypeptide (OATP) OATP1B1, OATP1B3, and OATP2B1 as well as Na(+)-taurocholate co-transporting polypeptide (NTCP) and of the efflux transporters multidrug resistance associated protein 2 (MRP2) and bile salt export pump (BSEP) was studied.

Methods:

The effect of silibinin on OATPs and NTCP function was studied in stable transfected CHO cells using the radiolabelled model substrates estrone-3-sulfate and dehydroepiandrosteronesulfate for OATPs and taurocholate for NTCP. Interaction of silibinin with MRP2 and BSEP was measured in vesicles isolated from Sf21 or Sf9 insect cells expressing these transporters using either estradiol-17β-glucuronide or taurocholate as substrates.

Results:

OATP1B1, OATP1B3, and OATP2B1 were inhibited by silibinin, with OATP1B1 being inhibited by (a) complex mechanism(s). An inhibitory effect was also seen for MRP2. Contrary, the bile acid transporters NTCP and BSEP were not affected by silibinin.

Conclusion:

Silibinin induced hyperbilirubinemia may be caused by an inhibition of the bilirubin transporting OATPs and the efflux transporter MRP2.

In severe and rapidly increasing jaundice, the use of intensive phototherapy provides greater effectiveness and a faster decrement in bilirubin levels compared to conventional phototherapy. The aim of this study was to compare the effectiveness of two types of intensive phototherapy: intensive compact fluorescent tube (CFT) and intensive light-emitting diode (LED) phototherapy. Forty-three infants over 35 weeks of gestation with severe non-hemolytic hyperbilirubinemia were enrolled in the prospective study. All infants received multidirectional (circular-shaped) intensive phototherapy. Of these, 20 infants received CFT while 23 infants received LED phototherapy. Bilirubin levels and body temperatures were measured periodically, and the rates of bilirubin decrement were calculated. Mean serum bilirubin level of the 43 infants was 20.5±1.5 mg/dl at the beginning of the therapy and mean duration of phototherapy was 20.6±1.1 hours. The rate of mean bilirubin decline was 47.2% and the decrease was more prominent in the first four hours (0.84 ± 0.41 mg/dl/h). The rates of bilirubin decrement were comparable between the LED and CFT groups. Slightly elevated mean body temperature (37.1ºC) was determined in the CFT group (p<0.05). Intensive phototherapy units with both LED and CFT were effective, showing a decline of half the initial value of bilirubin during the study period in infants with non-hemolytic jaundice. This study shows that intensive phototherapy with either CFT or LED can provide rapid decrease in bilirubin levels in the first few hours. This rapid decline is important in cases that have high risk of bilirubin encephalopathy.

Exchange transfusion is the standard method for treatment of severe hyperbilirubinemia. Our goal was to determine the indications for exchange transfusion (ECT) and the rates of ECT-related adverse events. A retrospective descriptive investigation was performed in newborns that underwent ECT at 17 Shahrivar Pediatric Hospital, Rasht, Guilan province during the period April 2008 to April 2011. Of the 69 patients, 2 (2.9%) required more than one ECT. The mean total serum bilirubin before ECT was 21.55±5.12 mg/dl. The most common cause of ECT was ABO incompatibility (26.1%). ECT complications occurred in 9 neonates (13.0%), the most common being sepsis (7.4%). No case of ECTrelated mortality was observed. All the adverse events resolved completely before discharge. ABO isoimmunization was the most common cause of ECT in this study. The majority of adverse events associated with ECT are asymptomatic and reversible.

A severe increase in total bilirubin coincided with a decline in neurologic status to comatose in a 9 yr old spayed female mixed-breed dog being treated for immune-mediated hemolytic anemia. MRI of the brain was performed to investigate potential causes for the neurologic signs. MRI revealed bilaterally symmetrical hyperintensities within the caudate nuclei, globus pallidus, thalamus, deep cerebellar nuclei, and cortical gray matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, which coincided with areas of bilirubin deposition and neuronal necrosis (kernicterus) identified on necropsy examination. This is the second case report of an adult dog exhibiting kernicterus, and the first report to document MRI findings associated with that condition. Kernicterus is an uncommonly reported complication of hyperbilirubinemia in dogs, but is potentially underreported due to difficulties in recognizing subtle lesions and distinguishing kernicterus from other potential causes of neurologic abnormalities with readily available antemortem tests. MRI may be helpful in supporting the diagnosis of kernicterus.

BackgroundAtazanavir (ATV) causes an elevation of unconjugated hyperbilirubinaemia (HBR) as a result of UDP glucuronyltransferase (UGT) 1A1 inhibition. Zinc sulphate (ZnSO4) reduces unconjugated hyperbilirubinemia in individuals with Gilbert's syndrome. We assessed the changes in total, conjugated and unconjugated bilirubin and the effect on ATV pharmacokinetics (PK) following single and 14 day dosing of ZnSO4.MethodsHIV patients, stable on ATV/ritonavir (r) containing regimens with total bilirubin level >25mmol/L received 125mg daily of ZnSO4 as Solvazinc© tablets for 14 days. ATV/r and bilirubin concentrations were measured pre-ATV/r-dose and 2, 4, 6, 8 and 24hours post-ATV/r-dose; before ZnSO4 initiation (phase 1), after a single dose (phase 2) and following 14 days (phase 3). Changes in bilirubin and ATV/r concentrations in the absence/presence of ZnSO4 were evaluated by geometric mean ratios (GMR) and 90% confidence intervals (CI, phase 1 as reference).ResultsSixteen male patients completed the study maintaining virologic suppression; ZnSO4 was well tolerated. Statistically significant declines in total bilirubin Cmax and AUC0-24 of 16% and 17% were seen in phase2 and 20% in phase3. Whilst there were no significant changes in conjugated bilirubin, unconjugated bilirubin Cmax and AUC0-24 of were lower (17% and 19% - phase 2; 20% and 23% during phase 3). Atazanavir GMR (90% CI) for Ctrough, Cmax and AUC0-24 were 0.74 (0.62-0.89), 0.82 (0.70-0.97), 0.78 (0.70-0.88).ConclusionsIntake of ZnSO4 decreases total and unconjugated bilirubin and causes modest declines in ATV exposure. ZnSO4 supplementation may be useful in management of ATV-related HBR in selected patients.

BACKGROUND::

Breast milk has been shown to be associated with greater success with regards to weaning children with intestinal failure off of parenteral nutrition [PN]. There are only a few studies investigating the role of breast milk in decreasing PNALD.

METHODS::

We conducted a retrospective analysis of newborns requiring prolonged parenteral nutrition. We divided the sample into three different groups [exclusive breast feeding, exclusive formula feeding and mixed feeding].We compared baseline characteristics, feeding profiles and liver function tests and liver enzymes amongst the three groups.

RESULTS::

Among infants on PN for greater than 4 weeks, we found that infants who were only fed breast milk were significantly less likely to develop PNALD [34.6%] compared to those who were only fed formula milk [72.7%] {P = 0.008}. The mean maximum conjugated bilirubin {P = 0.03} and the mean maximum AST were significantly lower in the breast fed group {P = 0.04} compared to the formula fed group. Among the mixed feeding group, infants who received a higher percentage of breast milk showed a significant negative correlation with the mean maximum conjugated bilirubin. {Pearson Correlation = -0.517, P = 0.027}. The mean number of days on PN and the average daily lipid intake in the two groups were not significantly different.

CONCLUSION:

: As a modality for early enteral nutrition, breast milk is protective against the development of PNALD in infants on PN for more than 4 weeks.

Patients with dilated common bile duct (CBD) (>7mm) and/or pancreatic duct (PD) on abdominal imaging are often referred for endoscopic ultrasound (EUS). In many cases, the EUS shows no obvious etiology for the dilated ducts.Find clinical factors that may predict which patients are more likely to have positive findings on EUS to explain the etiologies for the dilated ducts.Retrospective database analysis.Tertiary-care university hospital.Patients referred for EUS for dilated CBD and/or PD from January 2004 to February 2010 were included in this study. Only patients without an obvious etiology for the dilated ducts on abdominal imaging were included.An EUS was performed by using either a radial echoendoscope or a linear endoscope to evaluate the common bile duct and/or the pancreatic duct. When appropriate fine needle aspiration of the mass or cyst was performed.The characteristics of patients who had positive findings on EUS to explain the etiology of their dilated PD and/or CBD.A total of 140 patients were included in the study with a mean age of 64 years, 51 (36%) male and 115 (82%) white. The majority of our patients had a presenting symptom of abdominal pain 105 (75%). 49 (36%) had elevated AST or ALT, 25 (8%) had an elevated bilirubin and 13 (23%) had an elevated lipase. EUS findings explained the dilated ducts in 54 (39%) of our patients, most common diagnoses included: CBD stone in 11 (8%), non-calcific chronic pancreatitis in 9 (6%), pancreatic mass in 8 (6%), IPMN in 7 (5%). On bivarate analysis patients who were older (p = 0.006), male (p = 0.001), had elevated LFTs (p = <0.001), had elevated lipase (p = 0.021) or had dilated CBD and PD (p = 0.007) were more likely to have an etiology for their dilated duct(s) discovered on EUS.A retrospective study with a small number of patients.Older patients, males and those patients presenting with concurrent elevations in the AST/ALT and/or lipase were more likely to have an underlying etiology discovered on EUS. Furthermore, EUS may detect an undiagnosed pancreatic malignancy in patients presenting with unexplained duct dilation.

Hypertensive disorders complicating pregnancy seriously endanger the safety of the mother and fetus during pregnancy. Very few studies have explored hypertensive disorders of pregnancy in India, even though this disease has been associated with adverse maternal and perinatal outcomes. This study aimed to analyze the disease pattern and risk factors associated with the disorder and assess the maternal and fetal outcomes in cases of hypertensive disorders of pregnancy.This case-control study was carried out over 1 year from 2011 to 2012 at the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, Uttar Pradesh, India. A total of 149 patients were enrolled in the study. As seven were lost to follow-up, analysis was carried out on 142 cases. Patients were further classified according to the National High Blood Pressure Education Program Working Group (2000) as having mild preeclampsia (65 cases), severe preeclampsia (32 cases), or eclampsia (45 cases). Thirty-one healthy pregnant non-hypertensive women were enrolled into the study as controls.The most common manifestation was edema, seen in 90% of cases. Proteinuria was also relatively common, 26.76% of patients with proteinuria of ≥300 mg/24 hours, 47.88% with proteinuria of ≥2 g/24 hours, and 25.35% with a urinary protein excretion of 3-5 g/24 hours. Central nervous system involvement was observed in 42.2% of cases, elevated bilirubin levels in 47.0%, visual symptoms in 6.4%, vaginal bleeding in 11.3%, and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome was reported in 2.80%. Maternal deaths occurred in 2.8% of cases, all of which were from the eclampsia group. Stillbirths occurred in 16.9% of cases, and overall neonatal death observed in 4.23% of cases.Women with hypertensive disorders of pregnancy were more prone to adverse maternal and fetal outcomes than normotensive pregnant women, but we observed a decreasing trend in the present study compared with that reported in other studies, which might be due to the increased number of hospital deliveries that occurred in our study.