R Aerts

Clinical models are inaccurate in predicting bile duct stones in situ for patients with gallbladder

BackgroundThe probability that a patient has common bile duct stones (CBDS) is a key factor in determining diagnostic and treatment strategies. This prospective cohort study evaluated the accuracy of clinical models in predicting CBDS for patients who will undergo cholecystectomy for lithiasis.MethodsFrom October 2005 until September 2006, 335 consecutive patients with symptoms of gallstone disease underwent cholecystectomy. Statistical analysis was performed on prospective patient data obtained at the time of first presentation to the hospital. Demonstrable CBDS at the time of endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography (IOC) was considered the gold standard for the presence of CBDS.ResultsCommon bile duct stones were demonstrated in 53 patients. For 35 patients, ERCP was performed, with successful stone clearance in 24 of 30 patients who had proven CBDS. In 29 patients, IOC showed CBDS, which were managed successfully via laparoscopic common bile duct exploration, with stone extraction at the time of cholecystectomy. Prospective validation of the existing model for CBDS resulted in a predictive accuracy rate of 73%. The new model showed a predictive accuracy rate of 79%.ConclusionClinical models are inaccurate in predicting CBDS in patients with cholelithiasis. Management strategies should be based on the local availability of therapeutic expertise.

Drug holiday in patients with polycystic liver disease treated with somatostatin analogues

Background: Somatostatin analogues (SAs) reduce liver volume and relief symptoms in polycystic liver disease (PLD). Its effect wears off after continuing therapy suggesting development of SA tolerance in patients on chronic therapy. We postulate that a drug holiday resensitizes the liver to its acute pharmacological effects. Therefore, this study examines the liver volume-reducing effect of SAs after a drug holiday. Methods: Patients were identified from the International PLD Registry and included in our analysis when (1) treated with SAs during two cycles separated by a drug holiday and (2) height-adjusted total liver volume (hTLV) was available at start and end of each cycle. For our primary outcome we compared the effect of SAs (in % per 6 months) on hTLV between the first and second treatment cycle. Results: In 34 patients, initial liver volume-reducing effect was similar to that after rechallenge [−2.6% per 6 months (interquartile range, −3.8–0.8) versus −1.6% per 6 months (interquartile range, −3.1–1.1), p = 0.510]. Cessation of treatment led to a rebound effect, but liver volume remained stable compared with the baseline with intermittent therapy in responders to SA [−0.6% (interquartile range, −7.4–5.7) after 46.5 months]. Conclusions: PLD patients treated with SAs benefit from retreatment after a drug holiday. The significant increase of liver volume after cessation of treatment complicates widespread use of a drug holiday as new treatment strategy. Our results contribute to a better understanding of the pharmacological effect of SAs and help to identify patients who might benefit.

Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry

Polycystic liver disease (PLD) occurs in two genetic disorders, autosomal‐dominant polycystic kidney disease (ADPKD) and autosomal‐dominant polycystic liver disease (ADPLD). The aim of this study is to compare disease severity between ADPKD and ADPLD by determining the association between diagnosis and height‐adjusted total liver volume (hTLV).

Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease: The DIPAK 1 Randomized Clinical Trial

Importance Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys and loss of renal function, eventually leading to a need for kidney replacement therapy. There are limited therapeutic management options. Objective To examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD. Design, Setting, and Participants An open-label randomized clinical trial with blinded end point assessment that included 309 patients with ADPKD from July 2012 to March 2015 at 4 nephrology outpatient clinics in the Netherlands. Eligible patients were 18 to 60 years of age and had an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2. Follow-up of the 2.5-year trial ended in August 2017. Interventions Patients were randomized to receive either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n = 153) or standard care only (target blood pressure <140/90 mm Hg; n = 152). Main Outcomes and Measures Primary outcome was annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase. Secondary outcomes included change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]). Results Among the 309 patients who were randomized (mean [SD] age, 48.4 [7.3] years; 53.4% women), 261 (85.6%) completed the trial. Annual rate of eGFR decline for the lanreotide vs the control group was −3.53 vs −3.46 mL/min/1.73 m2 per year (difference, −0.08 [95% CI, −0.71 to 0.56]; P = .81). There were no significant differences for incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P = .87), change in eGFR (−3.58 vs −3.45; difference, −0.13 mL/min/1.73 m2 per year [95% CI, −1.76 to 1.50]; P = .88), and change in quality of life (0.05 vs 0.07; difference, −0.03 units per year [95% CI, −0.13 to 0.08]; P = .67). The rate of growth in total kidney volume was lower in the lanreotide group than the control group (4.15% vs 5.56%; difference, −1.33% per year [95% CI, −2.41% to −0.24%]; P = .02). Adverse events in the lanreotide vs control group included injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%). Conclusions and Relevance Among patients with later-stage autosomal dominant polycystic kidney disease, treatment with lanreotide compared with standard care did not slow the decline in kidney function over 2.5 years of follow-up. These findings do not support the use of lanreotide for treatment of later-stage autosomal dominant polycystic kidney disease. Trial Registration ClinicalTrials.gov Identifier: NCT01616927

654 A NEW CLASSIFICATION OF PRIMARY LIVER CARCINOMAS BASED ON THEIR POSSIBLE CELLULAR ORIGIN

universal sustained virological response (SVR), it is eagerly hoped that morbidity and mortality from hepatitis C virus (HCV) will soon disappear. At present, cirrhosis, the predominant risk factor for hepatocellular carcinoma (HCC), is increasing among patients with HCV as they become older and the duration of infection longer. We estimate the impact of DAAs with high SVR rates on the incidence of HCC in the population. Methods: Since the extent to which the risk of HCC decreases in patients with established cirrhosis achieving SVR remains poorly defined, we conducted a simulation experiment in which a cohort of 50 year-old subjects (n = 1,000) with compensated HCV cirrhosis (MELD=6) is followed for 20 years. In a viremic subject, the MELD score, HCC and mortality from end stage liver disease (ESLD) would increase progressively. Once SVR is achieved, MELD would stop increasing and the proportion at risk of HCC decrease over time. Results: The Table summarizes 20-year outcomes in the 50 year-old cohort based on SVR eliminating HCC risk in 3%/year.

970 OCCURRENCE AND CLINICOPATHOLOGICAL RELEVANCE OF PROGNOSTIC MARKERS IN HEPATOCELLULAR CARCINOMA

The threshold annual incidence for efficacy of HCC surveillance in non-HBV liver cirrhosis has been established in 1.5%. Although alcoholic cirrhosis is clearly a risk factor for HCC, the incidence of the tumour in this population is not accurately known. Aim: To determine the annual incidence of HCC in a cohort of patients with alcoholic cirrhosis followed prospectively and to define groups with different risk of tumour development. Methods: We evaluated 450 consecutive patients with alcoholic liver cirrhosis (369 men, mean age 53.9±7.4 years) included in a surveillance program for HCC detection (mean follow-up 59±49 months). All patients were Child–Pugh class A/B. The diagnosis of cirrhosis was supported by liver biopsy in 140 patients and was based on clinical-biological criteria in the rest. Alcoholic etiology was established by history of alcohol consumption and the exclusion of other etiologies. The first 5 years after inclusion in the program were considered to define potential risk factors. Nineteen demographic, clinical and laboratory variables were analysed. Results: During the overall follow-up, 62 patients developed HCC. The annual incidence was 2.6% and the 10-years cumulative incidence was 25.2%. In the first 5 years after inclusion in the program, 43 patients developed HCC. In univariate analysis, age > 58 years, platelets 2mg/dl, albumin 58 (OR 2.91, 95%CI 1.29– 6.57) and platelets <125×103/mm3 (OR 2.40, 95%CI 1.30–4.46) were independently associated with an increased risk of HCC. These two variables allowed us to define 3 different risk groups. The annual incidence of HCC in the group without any of these two factors (n = 109), with one of them (n=249) or with both (n =87) was 0.6%, 2.8% and 5.3% respectively (p < 0.0001). Conclusions: The annual incidence of HCC in patients with alcoholic cirrhosis Child–Pugh class A/B is about 2.5%. Two simple variables, age and platelets, can be used to distribute the patients in different risk groups for HCC development over the next 5 years. A surveillance program for early detection of HCC is probably not justifiable in the low-risk group.

Liver transplantation using livers from septuagenarian and octogenarian donors: an underused strategy to reduce mortality on the waiting list

Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.