Surgery remains the best option for the management of pain in patients with chronic pancreatitis: A systematic review and meta-analysis.

Controversy related to endoscopic or surgical management of pain in patients with chronic pancreatitis remains. Despite improvement in endoscopic treatments, surgery remains the best option for pain management in these patients.

Short and long-term post-operative outcomes of duodenum preserving pancreatic head resection for chronic pancreatitis affecting the head of pancreas: a systematic review and meta-analysis.

BACKGROUND: To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis. METHODS: A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function). RESULTS: Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure. In total, 323 patients underwent surgical procedures for chronic pancreatitis, including Beger (n = 138) and Frey (n = 99), minimal Frey (n = 32), modified Frey (n = 25) and Berne's modification (n = 29). Two studies comparing the Beger and Frey procedure were entered into a meta-analysis and showed no difference in post-operative pain (RD = -0.06; CI -0.21 to 0.09), mortality (RD = 0.01; CI -0.03 to 0.05), morbidity (RD = 0.12; CI -0.00 to 0.24), exocrine insufficiency (RD = 0.04; CI -0.10 to 0.18) and endocrine insufficiency (RD = -0.14 CI -0.28 to 0.01). CONCLUSION: All procedures are equally effective for the management of pain for chronic pancreatitis. The choice of procedure should be determined by other factors including the presence of secondary complications of pancreatitis and intra-operative findings. Registration number CRD42015019275. Centre for Reviews and Dissemination, University of York, 2009.

Analysis of Endoscopic Radiofrequency Ablation of Biliary Malignant Strictures in Pancreatic Cancer Suggests Potential Survival Benefit.

BACKGROUND: Pancreatic carcinoma is often inoperable, carries a poor prognosis, and is commonly complicated by malignant biliary obstruction. Phase I/II studies have demonstrated good safety and early stent patency using endoscopic biliary radiofrequency ablation (RFA) as an adjunct to self-expanding metal stent (SEMS) insertion for biliary decompression. AIM: To analyze the clinical efficacy of endobiliary RFA. METHODS: Retrospective case-control analysis was carried out for 23 patients with surgically unresectable pancreatic carcinoma and malignant biliary obstruction undergoing endoscopic RFA and SEMS insertion and 46 controls (SEMS insertion alone) in a single tertiary care center. Controls were stringently matched for age, sex, metastases, ASA/comorbidities. Survival, morbidity, and stent patency rates were assessed. RESULTS: RFA and control groups were closely matched-ASA 2.35 ± 0.65 versus 2.54 ± 0.50, p = 0.086; metastases 9/23 (39.1%) versus 18/46 (39.1%), p = 0.800; chemotherapy 16/23 (69.6%) versus 24/46 (52.2%), p = 0.203. Median survival in RFA group was 226 days (IQR 140-526 days) versus 123.5 days (IQR 44-328 days) in controls (p = 0.010). RFA was independently predictive of survival at 90 days (OR 21.07, 95% CI 1.45-306.64, p = 0.026) and 180 days (OR 4.48, 95% CI 1.04-19.30, p = 0.044) in multivariate analysis. SEMS patency rates were equivalent in both groups. RFA was well tolerated with minimal side effects. CONCLUSIONS: Endoscopic RFA is a safe and efficacious adjunctive treatment in patients with advanced pancreatic malignancy and biliary obstruction and may confer early survival benefit. Randomized prospective clinical trials of this new modality are mandated.

Diagnostic utility of single-user peroral cholangioscopy in sclerosing cholangitis.

OBJECTIVE: To evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) in patients with sclerosing cholangitis. METHODS: All patients with sclerosing cholangitis who underwent SOC procedures due to suspicious biliary strictures, in one Swedish and four UK tertiary centers in 2008-2012, were retrospectively enrolled. For each SOC procedure in sclerosing cholangitis, another one attempted due to a single biliary stricture in the same center and calendar year was randomly selected as control. Patients were followed up until death or last clinic visit until November 2012. RESULTS: Fifty-four SOC procedures were attempted in 52 sclerosing cholangitis patients (48 with primary sclerosing cholangitis, 4 with IgG4-related sclerosing cholangitis). Cannulation with the SOC system failed more frequently in sclerosing cholangitis (15% vs. 2% in controls; p = 0.015). The sensitivity, specificity, and accuracy of SOC (including tissue sampling) for cancer diagnosis were similar in sclerosing cholangitis and controls (50% vs. 55%, 100% vs. 97%, and 88% vs. 80%, respectively) with largely overlapping confidence intervals. Adverse events were more common in sclerosing cholangitis, due to an increased frequency of cholangitis (11% vs. 2% in controls; p = 0.051). CONCLUSIONS: SOC is equally accurate in cancer diagnosis in sclerosing cholangitis and patients with single biliary strictures. However, cholangioscope insertion may be hampered by bile duct narrowing and post-SOC cholangitis is more common in sclerosing cholangitis.

Endoscopic radiofrequency ablation for cholangiocarcinoma.

PURPOSE OF REVIEW: To describe the use of endobiliary radiofrequency ablation (RFA) in the treatment of malignant disease of the bile duct and offer a comprehensive review of the emerging evidence on the safety and effectiveness of this new technique. RECENT FINDINGS: Ex-vivo and in-vivo porcine studies have been reported, confirming the feasibility of the technique, gathering preliminary safety data and defining appropriate power settings for human studies. Moderate-sized case series have now reported the use of RFA in mixed cohorts of human individuals with pancreatic cancer, cholangiocarcinoma and other malignant diseases of the bile duct. Endoscopic and percutaneous approaches have both been investigated. Small case series of blocked self-expanding metal stent clearance using RFA have been published. SUMMARY: Intraductal RFA, via both endoscopic and percutaneous approaches, is feasible. Complication rates appear to be comparable with the current standard endoscopic and percutaneous approaches to palliation of malignant strictures of the bile duct. The current body of literature is germinal, but warrants the further investigation of planned clinical trials.

The palliation of cholangiocarcinoma.

PURPOSE OF REVIEW: Cholangiocarcinoma is the second most common primary liver tumour, worldwide. Its incidence and mortality are rising, the cause of which is unclear. Cholangiocarcinoma usually presents late, with obstructive jaundice, malaise, weight loss and discomfort. For most patients, complete surgical resection, the only potential cure, is not possible. Survival length and palliation of symptoms become paramount and often this centres on restoration of bile flow to relieve jaundice and improve general well being. There are now multiple options to achieve this goal and emerging evidence supports certain methods over others. RECENT FINDINGS: For advanced cholangiocarcinoma, endoscopic biliary stenting has become an established treatment. Recent evidence supports the use of metal stents over plastic to improve survival and stent patency. Locoregional therapies, such as radiofrequency ablation, transarterial chemoembolisation and radiotherapy have shown promise in preliminary studies. Landmark studies have established the use of cisplatin and gemcitabine as first-line chemotherapy in advanced cholangiocarcinoma. SUMMARY: The rise in incidence of advanced cholangiocarcinoma, has necessitated the development of novel therapies to optimize palliation. This article discusses the current options for palliation of cholangiocarcinoma, including stenting, locoregional therapy, surgery, endoscopic ultrasound and palliative chemotherapy.

Diagnostic and therapeutic utility of single-operator peroral cholangioscopy for indeterminate biliary lesions and bile duct stones.

BACKGROUND AND AIM: We aimed to evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) for indeterminate biliary lesions and its usefulness in electrohydraulic lithotripsy (EHL) of biliary stones not amenable to conventional endoscopic therapy. PATIENTS AND METHODS: All patients undergoing SpyGlass SOC in four UK tertiary centres between 2008 and 2010 were retrospectively enrolled. Patients were followed up until death or the last clinic visit until May 2011. The operating characteristics of SOC for detecting malignant lesions and the stone clearance rate after SOC-guided EHL were calculated. RESULTS: A total of 165 patients underwent 179 SOC procedures. Sixty-six percent were referred for indeterminate biliary strictures, 13% for filling defects and 21% for SOC-guided EHL. Cannulation with the SOC system was successful in 95% but visualization was inadequate in 13%. Primary sclerosing cholangitis was a risk factor for failed cannulation and conscious sedation (vs. general anaesthesia) for inadequate visualization (P<0.05). The accuracy of SOC for diagnosing malignant lesions was 87%. SOC-guided biopsies were adequate in 72%. Obtaining at least four versus less than four biopsy specimens resulted more often in adequate samples (90 vs. 64%, P=0.037). Complete stone clearance could be achieved in 73% of patients. The adverse event rate was 9.6%. Cholangitis was the most common event (56%, one fatal). CONCLUSION: SOC is useful for the differential diagnosis of indeterminate biliary lesions and the treatment of 'difficult' biliary stones. The adequacy of SOC-guided biopsies is related to the number of specimens obtained. Primary sclerosing cholangitis is related to failed cannulation with the SOC system, whereas general anaesthesia is related to adequate visualization.

National survey evaluating service provision for percutaneous endoscopic gastrostomy within the UK.

OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) feeding has a significant morbidity and mortality associated with the procedure. Patient selection, procedural volume, timing of insertion and aftercare may have a direct bearing on mortality. We aimed to establish whether variation in PEG practice exists within the UK. MATERIALS AND METHODS: The British Society of Gastroenterology (BSG) approached all NHS hospitals providing an endoscopy service (n = 260). A custom designed web-based questionnaire was circulated. RESULTS: The response rate was 83% (n = 215); 57% were Joint Advisory Group (JAG) accredited; 33% (70/215) of hospitals inserted more than 75 PEGs a year (4 hospitals inserting >150). Stroke and neurodegenerative conditions were the main indications for PEG insertion. However, 36% (77/215) of hospitals inserted PEGs for dementia. PEG insertion timings varied: 33% (72/215) had a strict policy of waiting more than 2 weeks from referral to insertion, 14% (30/215) performed immediately and 34% (74/215) determined the time delay depending on the underlying condition. Local guidelines for PEG insertion existed in 87% (186/215) of hospitals and 78% (168/215) had access to radiologically inserted gastrostomies. Prophylactic antibiotics were used in 93% (201/215) of hospitals. Only 64% (137/215) had a dedicated PEG aftercare service. This was significantly lower in non-JAG accredited units (p = 0.008). CONCLUSION: This National BSG survey demonstrates variations in practice particularly with regards to PEG insertion in patients with dementia, the timing of PEG insertion and PEG aftercare. These variations in practice may be important factors accounting for the significant morbidity and mortality associated with this procedure.

Elevated levels of neutrophil gelatinase-associated lipocalin in bile from patients with malignant pancreatobiliary disease.

OBJECTIVES: Accurate differentiation between benign and malignant causes of biliary obstruction remains challenging and reliable biomarkers are urgently needed. Bile is a potential source of such biomarkers. Our aim was to apply a proteomic approach to identify a potential biomarker in bile that differentiates between malignant and benign disease, and to assess its diagnostic accuracy. Neutrophil gelatinase-associated lipocalin (NGAL) is multi-functional protein, released from activated neutrophils, with roles in inflammation, immune function, and carcinogenesis. It has not previously been described in bile. METHODS: Bile, urine, and serum were collected prospectively from 38 patients undergoing endoscopic retrograde cholangiopancreatography ("discovery" cohort); 22 had benign and 16 had malignant pancreatobiliary disease. Initially, label-free proteomics and immunoblotting were performed in samples from a subset of these patients. Enzyme-linked immunosorbent assay was then performed for NGAL as a potential biomarker on all samples in this cohort. The diagnostic performance of biliary NGAL was then validated in a second, independent group ("validation" cohort) of 21 patients with pancreatobiliary disease (benign n=14, malignant n=7). RESULTS: NGAL levels were significantly raised in bile from the malignant disease group, compared with bile from the benign disease group in the discovery cohort (median 1,556 vs. 480 ng/ml, P=0.007). Biliary NGAL levels had a receiver operating characteristic area under curve of 0.76, sensitivity 94%, specificity 55%, positive predictive value 60%, and negative predictive value 92% for distinguishing malignant from benign causes. Biliary NGAL was independent of serum biochemistry and carbohydrate antigen 19-9 (CA 19-9) in differentiating between underlying benign and malignant disease. No significant differences in serum and urine NGAL levels were found between benign and malignant disease. Combining biliary NGAL and serum CA 19-9 improved diagnostic accuracy for malignancy (sensitivity 85%, specificity 82%, positive predictive value 79%, and negative predictive value 87%). The diagnostic accuracy of biliary NGAL was confirmed in the second independent validation cohort. CONCLUSIONS: NGAL in bile is a novel potential biomarker to help distinguish benign from malignant biliary obstruction.

Adequacy of flexible sigmoidoscopy with biopsy for diarrhea in patients under age 50 without features of proximal disease.

BACKGROUND: The optimal endoscopic investigation of diarrhea in patients under age 50 without specific features of right-sided colonic/ileal disease is inadequately defined. OBJECTIVE: To assess the potential additional yield of colonoscopy over flexible sigmoidoscopy (FS) in this group. DESIGN: Retrospective cohort study. SETTING: Two teaching hospital endoscopy units. PATIENTS: This study involved all patients under age 50 who had a colonoscopy between 1997 and 2007 to investigate diarrhea, without high-risk features of right-sided colonic/ileal disease, inflammatory bowel disease (IBD), or rectal bleeding. INTERVENTION: Colonoscopy and biopsy. MAIN OUTCOME MEASUREMENTS: Diagnostic yield of colonoscopy over FS with biopsy. RESULTS: Colonoscopic appearances were abnormal in 126 of 625 eligible patients (20%); 72% of abnormalities were within reach of FS. The most common endoscopic abnormality was suspected inflammation in 60 patients (10% overall), reportedly confined to the proximal colon or ileum in 22 patients (37% of this group). Histology from areas of suspected inflammation revealed features of IBD in 68% of patients, but results were normal in the remainder. In the 22 patients with suspected isolated proximal disease, 8 patients (36%) had normal histology results, and a further 6 had left-side colon biopsies demonstrating IBD. In patients with macroscopically normal colons, histological evidence of IBD or microscopic colitis occurred in 14 and 12 patients, respectively, with changes in the left side of the colon in 93% of patients. In this patient group, 85% of IBD or microscopic colitis could have been detected by FS and biopsy. The negative predictive value of FS with biopsy was 98% for IBD and 99% for microscopic colitis. LIMITATIONS: Retrospective study. CONCLUSION: FS is adequate for the investigation of diarrhea in patients under age 50 who lack other features, but its yield depends on biopsy of the left side of the colon.

Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction.

BACKGROUND: In unresectable malignant bile duct obstruction in a patient with a life expectancy longer than 3 months, the use of self-expandable metal stents (SEMSs) is the standard technique to ensure continued biliary drainage. As many as 50% of patients with SEMSs will present with stent occlusion within 6 months. Changes to stent design and composition and concomitant therapy have failed to improve stent patency; therefore, alternative techniques to safely prolong stent patency are required. OBJECTIVE: To demonstrate the safety of endobiliary bipolar radiofrequency ablation (RFA) in patients with malignant biliary obstruction and to report the 90-day biliary patency of this novel procedure. DESIGN: Open-label pilot study. SETTING: Single tertiary care unit. PATIENTS: A total of 22 patients with unresectable malignant bile duct obstruction. INTERVENTIONS: Bipolar RFA within the bile duct. MAIN OUTCOME MEASUREMENTS: Immediate and 30-day complications and 90-day stent patency. RESULTS: A total of 22 patients (16 pancreatic, 6 cholangiocarcinoma) were recruited between January 2009 and April 2010. Deployment of an RFA catheter was successful in 21 patients. SEMS placement was achieved in all cases of successful RFA catheter deployment. One patient failed to demonstrate successful biliary decompression after SEMS placement and died within 90 days. All other patients maintained stent patency at 30 days. One patient had asymptomatic biochemical pancreatitis, 2 patients required percutaneous gallbladder drainage, and 1 patient developed rigors. At 90-day follow-up, 1 additional patient had died with a patent stent, and 3 patients had occluded biliary stents. LIMITATIONS: Cohort study. CONCLUSIONS: Endobiliary RFA treatment appears to be safe. Randomized studies with prolonged follow-up are warranted.

The provision of a percutaneously placed enteral tube feeding service.

There is overwhelming evidence that the maintenance of enteral feeding is beneficial in patients in whom oral access has been diminished or lost. Short-term enteral access is usually achieved via naso-enteral tube placement. For longer term tube feeding there are recognised advantages for enteral feeding tubes placed percutaneously. The provision of a percutaneous enteral tube feeding service should be within the remit of the hospital nutrition support team (NST). This designated team should provide a framework for patient selection, pre-assessment and post-procedural care. Close working relations with community-based services should be established. An accredited therapeutic endoscopist should be a member of the NST and direct the technical aspects of the service. Every endoscopy unit in an acute hospital setting should provide a basic percutaneous endoscopic gastrostomy (PEG) service. This should include provision for fitting a PEG jejunal extension (PEGJ) if required. Specialist units should be identified where a more comprehensive service is provided, including direct jejunal placement (DPEJ), as well as radiological and laparoscopically placed tubes. Good understanding of the indications for percutaneous enteral tube feeding will prevent inappropriate procedures and ensure that the correct feeding route is selected at the appropriate time. Each unit should adopt and become familiar with a limited range of PEG tube equipment. Careful adherence to the important technical details of tube insertion will reduce peri-procedural complications. Post-procedural complications remain relatively common, however, and an awareness of the correct approach to managing them is essential for all clinicians involved in providing a percutaneous enteral tube feeding service. Finally, ethical considerations should always be taken into account when considering long-term enteral feeding, especially for patients with a poor quality of life.

Metabolic profiling of bile in cholangiocarcinoma using in vitro magnetic resonance spectroscopy.

OBJECTIVES: Cholangiocarcinoma (CCA) has a poor prognosis and its aetiology is inadequately understood. Magnetic resonance spectroscopy (MRS) of bile may provide insights into the pathogenesis of CCA and help identify novel diagnostic biomarkers. The aim of this study was to compare the chemical composition of bile from patients with CCA with that of bile from patients with benign biliary disease. METHODS: Magnetic resonance spectra were acquired from the bile of five CCA patients and compared with MRS of control bile from patients with benign biliary disease (seven with gallstones, eight with sphincter of Oddi dysfunction [SOD], five with primary sclerosing cholangitis [PSC]). Metabolic profiles were compared using both univariate and multivariate pattern-recognition analysis. RESULTS: Univariate analysis showed that levels of glycine-conjugated bile acids were significantly increased in patients with CCA, compared with the benign disease groups (P= 0.002). 7 beta primary bile acids were significantly increased (P= 0.030) and biliary phosphatidylcholine (PtC) levels were reduced (P= 0.010) in bile from patients with CCA compared with bile from gallstone patients. These compounds were also of primary importance in the multivariate analysis: the cohorts were differentiated by partial least squares discriminant analysis (PLS-DA). CONCLUSIONS: These preliminary data suggest that altered bile acid and PtC metabolism play an important role in CCA aetiopathogenesis and that specific metabolites may have potential as future biomarkers.

The safety and utility of prophylactic pancreatic duct stents in the prevention of post-ERCP pancreatitis: an analysis of practice in a single UK tertiary referral center.

BACKGROUND: The use of temporary prophylactic pancreatic duct (PD) stents in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in high-risk patients has been shown to be effective in multiple trials. However, there are limited data on the clinical implications of PD stents and their impact on practice outside of the trial setting. METHODS: The utility of prophylactic pancreatic stenting was evaluated in a retrospective analysis of 1,000 consecutive ERCPs performed in a single tertiary referral pancreatobiliary center over a 24-month period, based upon a predetermined protocol to identify patients at high risk of postprocedure pancreatitis. RESULTS: One thousand procedures performed in 688 patients were studied. Sixty-one patients were considered for stent placement and stents were successfully placed in 58 cases. The overall rate of post-ERCP pancreatitis in our study population was 3.6%. The rate of pancreatitis in the stented patients was considered high at 22.4%, but the majority (69%) were classified as mild and there were no reported severe episodes. This compares to pancreatitis in the nonstented group, in whom the majority (73.9%) experienced either moderate or severe episodes. CONCLUSION: A strategy of prophylactic PD stents in this study has eliminated severe post-ERCP pancreatitis in high-risk patients. However, the high pancreatitis rate in stented patients may represent the cost to achieve this, while stent type and size employed are likely contributing factors. To maximize the benefits of PD stenting, there is a need to identify and treat all those considered at high risk.

Symptomatic pancreatitis in patients with cystic fibrosis.

OBJECTIVES: A small group of cystic fibrosis (CF) patients develop symptomatic pancreatitis. The clinical characteristics of these cases are not well documented in the literature. Most cases are in pancreatic sufficient (PS) patients, but it is not clear whether pancreatitis does occur in pancreatic insufficient (PI) patients. There is no information on how the group with PS and pancreatitis differs from the group with PS that does not develop pancreatitis. METHODS: The Royal Brompton Hospital database of adult CF patients was searched to identify all patients with symptomatic pancreatitis. Clinical details were taken from the case notes. PS pancreatitis patients were then compared with an age- and sex-matched PS control group drawn from the database. RESULTS: Sixteen patients (9 males) had suffered symptomatic pancreatitis, representing 1.6% of the total database. The mean age at CF diagnosis was 18.7 years, and at presentation with pancreatitis it was 28.8 years. Twelve were PS at diagnosis of CF. At presentation with pancreatitis, seven patients were PS and at the most recent follow-up or death, two remained PS. There was a median of three hospital admissions with pancreatitis. Eight cases developed pancreatic or hepatobiliary complications. In the comparison of pancreatitis patients with controls, there was no difference in survival but pancreatitis patients were significantly more likely to develop PI status. Mild CF transmembrane conductance regulator mutations in general, and R117H in particular, were found more often in pancreatitis patients. CONCLUSIONS: Symptomatic pancreatitis is a significant problem in 1-2% of patients with CF. These patients are PS at birth but are more likely to develop late PI status than PS patients without pancreatitis. R117H may be associated with this phenotype.

Management of symptomatic esophageal involvement with lichen planus.

AIM: To describe the clinical features and treatment schedules of a series of 5 patients with esophageal lichen planus (LP). To review the literature on esophageal LP. BACKGROUND: LP, a common papulosquamous dermatologic condition, can present to the gastroenterologist with esophageal involvement. This is rare and occurs in a distinct population of LP patients. Disease at this site is frequently refractory to conventional treatment. CASE SERIES: Between 2001 to 2007, 5 female patients were diagnosed with esophageal LP. They all had esophageal strictures which were treated with a combination of balloon dilatation and intralesional triamcinolone. Therapeutic intervention was covered with oral steroids before and after the procedure. Symptoms tended to recur, necessitating repeat procedures. The average interval between treatments was 8.3 months. CONCLUSIONS: Intralesional triamcinolone and balloon dilatation produced good symptomatic relief in these 5 patients with esophageal LP. This was generally maintained for several months. We reviewed 35 cases of symptomatic esophageal LP in the English literature. Esophageal LP seems to have a striking predilection for middle-aged women, particularly those with disease at other mucosal sites. A range of systemic immunosuppressants and esophageal-directed therapies has been tried.

Variceal hemorrhage and cystic fibrosis: outcomes and implications for liver transplantation.

Autopsy and imaging studies show that liver involvement is common in cystic fibrosis. However, complications of chronic liver disease including portal hypertension and variceal bleeding are infrequently encountered, and the degree to which variceal hemorrhage affects prognosis in cystic fibrosis is unclear. This uncertainty has lead to debate as to whether liver transplantation is indicated in these patients. We describe a case series of 18 patients and compare their survival with a control group of cystic fibrosis patients without liver disease. The median age at first bleed was 20.0 years (range 9.7-30.9). The median survival after first bleed was 8.4 years, compared to 13.0 years in the control group (P = 0.15). A total of 14 patients have died, 9 from respiratory disease with no discernable contribution from their liver disease. Liver disease contributed to 4 deaths. Only 1 patient suffered a fatal hemorrhage, which may have been either variceal or bronchial in origin. Long-term survival is a frequent occurrence in patients with cystic fibrosis who suffer variceal hemorrhage, and age at death is comparable to the general cystic fibrosis population. In conclusion, this suggests that liver transplantation is not indicated in these patients without additional features of liver decompensation.