Position statement on the diagnosis and management of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.

Liver Transplantation in the Obese Cirrhotic Patient.

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.

Readability of Healthcare Literature for Hepatitis B and C.

BACKGROUND: Patients increasingly use the Internet for educational material concerning health and diseases. This information can be utilized to teach the population of hepatitis B and C if properly written at the necessary grade level of the intended patient population. AIM: We explored the readability of online resources concerning hepatitis B and C. METHODS: Google searches were performed for "Hepatitis B" and "Hepatitis C." The Internet resources that were intended for patient education were used with specific exclusions. Articles were taken from 19 and 23 different websites focusing on the symptoms, diagnosis, and treatment of hepatitis B and C, respectively. The articles were analyzed using Readability Studio Professional Edition (Oleander Solutions, Vandalia, OH) using 10 different readability scales. The results were compared and averaged to identify the anticipated academic grade level required to understand the information. RESULTS: The average readability scores of the 10 scales had ranges of 9.7-16.4 for hepatitis B and 9.2-16.4 for hepatitis C. The average academic reading grade level for hepatitis B was 12.6 ± 2.1 and for hepatitis C was 12.7 ± 2.1. There was no significant discrepancy between the hepatitis B and C Internet resource averaged grade levels. CONCLUSION: The resources accessed by patients are higher than the previously determined necessary grade level for patients to properly understand the intended information. The American Medical Association recommends material should be simplified to grade levels below the sixth grade level to benefit the ideal proportion of the patient population.

Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). METHODS: Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. RESULTS: N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. CONCLUSION: N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.

Approach to the management of portal hypertensive gastropathy and gastric antral vascular ectasia.

Gastric antral vascular ectasia (GAVE) and portal hypertensive gastropathy (PHG) are important causes of chronic gastrointestinal bleeding. These gastric mucosal lesions are mostly diagnosed on upper endoscopy and can be distinguished based on their appearance or location in the stomach. In some situations, especially in patients with liver cirrhosis and portal hypertension, a diffuse pattern and involvement of gastric mucosa are seen with both GAVE and severe PHG. The diagnosis in such cases is hard to determine on visual inspection, and thus, biopsy and histologic evaluation can be used to help differentiate GAVE from PHG.

Ascites and spontaneous bacterial peritonitis: recommendations from two United States centers.

Cirrhosis affects millions of people throughout the world. Two of the most serious complications of liver cirrhosis are ascites and spontaneous bacterial peritonitis (SBP). The development of ascites is related to the severity of portal hypertension and is an indicator of increased mortality. Although sodium restriction and diuretic therapy have proven effective, some patients may not respond appropriately or develop adverse reactions to diuretic therapy. In such cases, interventions such as transjugular intrahepatic portosystemic shunt (TIPS) placement are warranted. SBP is a complication of ascites that confers a very high mortality rate. Recognition and prompt treatment of this condition is essential to prevent serious morbidity and mortality. Initiation of prophylaxis in SBP remains controversial. Given the burden of liver cirrhosis on the health care system, ascites and SBP will continue to provide challenges for the primary care provider, hospitalist, internist, and gastroenterologist alike.

The treatment of cholangiocarcinoma: a hepatologist's perspective.

Cholangiocarcinoma (CCA) is a rare but lethal adenocarcinoma with cholangiocyte differentiation that arises within the biliary tree at variable locations. Curative options are available in the form of surgical resection and/or liver transplantation (LT) in early stage CCA; however, these are offered to a small fraction of patients as they are usually asymptomatic and remain undiagnosed. Primary sclerosing cholangitis (PSC) is a well-known risk factor of CCA, and cirrhosis, viral hepatitis, and metabolic syndrome are recently identified as risk factors of CCA. This emerging evidence places hepatologists in a vital position to diagnose, prognosticate, and manage CCA by planning treatment of each individual patient based on the stage and extent of malignancy. With appropriate selection of patients and the involvement of a multidisciplinary team, surgical resection of localized CCA, LT coupled with neoadjuvant chemoradiation for perihilar CCA, or locoregional or systemic chemotherapy and/or endoscopic interventions for advanced CCA can be offered.

Management of stomal varices with transvenous obliteration utilizing sodium tetradecyl sulfate foam sclerosis.

The management of parastomal varices is not established. Transjugular intrahepatic portosystemic shunt (TIPS) creation is the most commonly described treatment; however, the rebleed rate after TIPS is 21-37%. The purpose of the study is to determine the effectiveness of transvenous obliteration using sodium tetradecyl sulfate (STS) and to describe a new simplified technique in obliterating these varices. Four patients are presented who underwent transvenous obliteration using STS. One was obliterated using balloon occlusion from the systemic veins, the second was obliterated without balloon from a transhepatic antegrade approach, and the last two patients were obliterated using the direct antegrade technique. This simplified technique requires only a micropuncture kit (not requiring balloons or coils) and ultrasound transducer compression of the systemic draining veins, relying on high portal pressure to keep the sclerosant confined to the varices. The sclerosant is essentially trapped between the portal pressure and the ultrasound-transducer compression (10-15 min). Technical success was achieved in all four patients without procedural or postprocedural complications and no rebleeding for a mean follow-up of 17 (range 2-33) months. Transvenous obliteration of parastomal varices utilizing STS as a sclerosant is safe and effective. The newly described technique is simple, feasible, and requires minimal equipment (no balloons or coils or catheters).

Management of Bleeding Duodenal Varices with Combined TIPS Decompression and Trans-TIPS Transvenous Obliteration Utilizing 3% Sodium Tetradecyl Sulfate Foam Sclerosis.

OBJECTIVES: Endoscopic experience in the management of duodenal varices (DVs) is limited and challenging given the anatomic constraints and limited experience. The endovascular management of DVs is not yet established and the controversy of whether to manage them by decompression with a transjugular intrahepatic portosystemic shunt (TIPS) or by transvenous obliteration is unresolved. In the literature, the 6-12 month rebleeding rate of DVs after TIPS is 21-37% and after transvenous obliteration is 13%. The purpose of the study is to evaluate the clinical outcome of combined TIPS decompression and transvenous obliteration/sclerosis. MATERIALS AND METHODS: This is a retrospective study (case series) of two institutions, evaluating patients who underwent TIPS and/or transvenous obliteration/sclerosis for bleeding DVs (from January 2009 to June 2013). TIPS was performed according to a standard procedure using covered stents. Transvenous obliteration (variceal sclerosis) from the systemic and/or portal venous circulation was performed utilizing 3% sodium tetradecyl sulfate foam. Transvenous obliteration was commonly augmented with coils and/or vascular plugs. Technical (technical success of establishing TIPS and completely obliterating the DVs) and clinical outcomes (rebleeding rate and survival) were evaluated. RESULTS: Five patients with liver cirrhosis presenting with bleeding DVs were included in the study with all eventually (and coincidentally) receiving TIPS and transvenous obliteration. Two of the five patients underwent concomitant TIPS and transvenous obliteration in the same procedural setting. However, three patients underwent transvenous obliteration due to bleeding despite a patent TIPS that had been previously placed. The average time from TIPS placement to transvenous obliteration was 125 days (range: 3-324 days). After having both procedures, there was no rebleeding in the patients during a mean follow-up period of 22 months (6-50 months). Coils and/or metallic vascular plugs were used to augment the sclerosant obliteration in four of five patients. CONCLUSION: The combination of TIPS decompression and foam sclerosant transvenous obliteration appears to be effective in preventing rebleeding in this limited case series and compares favorably with the existing evidence for either approach [TIPS or balloon-occluded retrograde transvenous obliteration (BRTO)] alone.

Protective value of TIPS against the development of hydrothorax/ascites and upper gastrointestinal bleeding after balloon-occluded retrograde transvenous obliteration (BRTO).

OBJECTIVES: The objective of this study was to evaluate the incidence of post-balloon-occluded retrograde transvenous obliteration (BRTO) ascites/hepatic hydrothorax and rebleeding rate (variceal and non-variceal) in the presence and absence of a transjugular intrahepatic portosystemic shunt (TIPS). METHODS: A retrospective audit of consecutive patients undergoing BRTO was performed (August 2007-October 2010). The population was divided into two groups: patients who underwent BRTO only (BRTO-only group) and those who underwent BRTO in the presence of TIPS (BRTO+TIPS group). Post-BRTO rebleeding was categorized for the source of bleeding. Ascites and/or hepatic hydrothorax were categorized according to clinical severity. Comparisons, utilizing the Kaplan-Meier method, between both groups were made for patient survival, incidence of ascites/hydrothorax, and rebleeding. RESULTS: Thirty-nine patients underwent BRTO (three technical failures of BRTO-only group). Of the 36 technically successful BRTO procedures, 27 patients (75%) underwent BRTO-only and 9 patients (25%) underwent BRTO in the presence of a TIPS. Pre-BRTO ascites/hydrothorax resolved in BRTO-only vs. BRTO+TIPS in 7% (N=2/27) and 56% (N=5/9), respectively (P=0.006). The ascites/hydrothorax free rate at 6, 12, and 24 months after BRTO for BRTO-only vs. BRTO+TIPS was 58%, 43%, 29%, and 100%, 100%, 100%, respectively (P=0.01). Recurrent hemorrhage for BRTO-only vs. BRTO+TIPS groups, and for the same time periods was 9%, 9%, 21% vs. 0%, 0%, 0%, respectively (P=0.03). The 1-year patient survival of both groups (80-88%) was similar (P>0.05). CONCLUSIONS: This study concludes that the presence of TIPS has a protective value against the development of post-BRTO ascites/hydrothorax as well as recurrent hemorrhage but this does not translate to improved patient survival.

A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation.

UNLABELLED: Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-α2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n = 44/2/1) were randomized 2:1 to treatment (n = 31) or untreated control (n = 16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-α2b, starting at 0.75 µg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (P = 0.29); per-protocol values were 13 (22%) and 0 (0%) (P = 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for <8, 8-16, and >16 weeks, respectively (P = 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%; P = 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3; P = 0.003). CONCLUSION: Pretransplant treatment with Peg-IFN-α2b/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.

Pre- and post-balloon-occluded retrograde transvenous obliteration clinical evaluation, management, and imaging: indications, management protocols, and follow-up.

Patients with gastric variceal bleeding require a multidisciplinary team approach, which includes hepatologists, endoscopists, diagnostic radiologists, and interventional radiologists. Upper gastrointestinal endoscopy is the first-line diagnosis and management tool for bleeding gastric varices (GVs) as it is with all upper gastrointestinal bleeding scenarios. Traditionally, in the United States, when endoscopy fails to control gastric variceal bleeding, a transjugular intrahepatic portosystemic shunt (TIPS) is performed along the classic teachings of decompressing the portal circulation. However, TIPS has shown inconsistent effectiveness in controlling gastric variceal bleeding. Conversely, the balloon-occluded retrograde transvenous obliteration (BRTO) procedure has become common practice in Asia for the management of GVs. The BRTO procedure is gaining popularity in the United States. BRTO has shown to be effective in controlling gastric variceal bleeding with low gastric variceal rebleed rates. Regardless of the endovascular management (TIPS vs BRTO vs both), a multidisciplinary team with adequate preprocedural clinical assessment and management and endoscopic and imaging evaluation is required before and after the endovascular procedure. The article discusses the pre- and post-BRTO clinical evaluation and management, as well as endoscopic and imaging evaluation. Moreover, the article proposes indications, contraindications, and management protocols for the management of GVs.

Hepatic encephalopathy.

Chronic liver disease and cirrhosis affect hundreds of millions of patients all over the world. The majority of patients with cirrhosis will eventually develop complications related to portal hypertension. One of these recurrent and difficult to treat complications is hepatic encephalopathy. Studies have indicated that overt hepatic encephalopathy affects 30 to 45% of patients with cirrhosis and a higher percentage may be affected by minimal degree of encephalopathy. All of these factors add to the impact of hepatic encephalopathy on the healthcare system and presents a major challenge to the gastroenterologist, hospitalist and primary care physician.

Does external beam radiation therapy improve survival following transarterial chemoembolization for unresectable hepatocellular carcinoma?

BACKGROUND: Transcatheter arterial chemoembolization (TACE) improves survival in patients with unresectable hepatocellular carcinoma (HCC). Partial liver radiotherapy with modern techniques has been shown to be safe. The purpose of this study was to evaluate the survival value of external beam radiation therapy (EBRT) with concurrent chemotherapy combined with TACE. METHODS: A University of Virginia Interventional Radiology patient log was used to identify patients treated with TACE ± another modality from 1999 through 2005. During this time, 44 patients received TACE for unresectable HCC, and 7 of these received adjuvant EBRT. Univariate analysis and multivariable proportional hazards survival modeling were used to identify factors impacting survival. RESULTS: We compared 37 patients receiving TACE alone to 7 receiving TACE and EBRT (5 with concurrent capecitabine). Unadjusted mean transplant-free survival times were TACE only = 376 days (standard error [SE] = 63 days), TACE + EBRT = 879 days (SE = 100 days). EBRT, TNM stage, and MELD score were important predictors for survival on univariate analysis (p < .10). The adjusted hazard ratio for transplant or death in the TACE + EBRT group was 0.15 (0.02-0.95, p = .026). CONCLUSION: EBRT with concurrent chemotherapy following TACE is feasible and well tolerated with modern treatment techniques. Further research should be directed toward determining the potential overall survival benefit of adjuvant EBRT with chemotherapy following TACE for hepatocellular carcinoma.

Sorafenib therapy for hepatocellular carcinoma prior to liver transplant is associated with increased complications after transplant.

This study compared post-transplant outcomes of patients with hepatocellular carcinoma (HCC) who took sorafenib prior to orthotopic liver transplantation (OLT) with those patients who were not treated with sorafenib. Thirty-three patients with HCC who were listed for liver transplantation were studied: 10 patients were treated with sorafenib prior to transplantation in an attempt to prevent progression of HCC while awaiting transplant. The remaining 23 patients were considered controls. The mean duration of sorafenib use was 19.2 (SD 25.2) weeks. Overall death rates were similar between the sorafenib group and control group (20% vs. 8.7%, respectively, P = 0.56). However, the patients in the sorafenib group had a higher incidence of acute cellular rejection following transplantation (67% vs. 22%, OR = 7.2, 95% CI 1.3-39.6, P = 0.04). The sorafenib group also had a higher rate of early biliary complications (67% vs. 17%, OR = 9.5, 1.6-55.0, P = 0.01). The use of sorafenib was found to be an independent predictor of post-transplant biliary complications (OR 12.6, 1.4-116.2, P = 0.03). Sorafenib administration prior to OLT appears to be associated with an increase in biliary complications and possibly in acute rejection following liver transplantation. Caution should be taken in this setting until larger studies are completed.

Bleeding gastric varices obliteration with balloon-occluded retrograde transvenous obliteration using sodium tetradecyl sulfate foam.

PURPOSE: Balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding gastric varices (GV) is well described in the literature. Using ethanolamine oleate as the sclerosing agent in BRTO, but it is not readily available in the United States in the desired concentrations. The authors' aim is to describe their initial experience with BRTO using sodium tetradecyl sulfate (STS) foam as an alternative sclerosing agent. MATERIALS AND METHODS: The authors performed a retrospective review of their initial series in which STS foam was used to treat bleeding GV using BRTO. All study subjects had endoscopic evidence of gastric variceal bleeding. STS foam was made using a combination of agents with a 3:2:1 ratio of gas: 3% STS: Lipiodol (Ethiodol; Savage Laboratories, Melville, New York). Mean values and ranges were calculated for each variable, and clinical and imaging outcomes were assessed. RESULTS: The authors performed BRTO in 22 cirrhotic patients (11 men and 11 women) with a mean age of 52 years (range, 23-83 years). Technical success was achieved in 20 of 22 (91%) patients. Complications occurred in three of 22 (14%) patients. The overall mean dose of STS used was 300 mg (range, 30-600 mg) with mean total volume of sclerosant mixture of 34.1 mL (range, 10-65 mL). Follow-up imaging was available for 18 of 20 (90%) technically successful procedures with a mean period of 89 days (range, 1-359 days). Complete obliteration of GV was achieved in 16 of 18 (89%) patients. There were no cases of recurrent variceal bleeding with a mean clinical follow-up period of 130 days (range, 1-510). CONCLUSIONS: BRTO utilizing STS foam appears effective in obliterating bleeding GVs with good short-term outcomes.

Medical and endoscopic management of gastric varices.

In the past 20 years, our understanding of the pathophysiology and management options among patients with gastric varices (GV) has changed significantly. GV are the most common cause of upper gastrointestinal bleeding in patients with portal hypertension after esophageal varices (EV) and generally have more severe bleeding than EV. In the United States, the majority of GV patients have underlying portal hypertension rather than splenic vein thrombosis. The widely used classifications are the Sarin Endoscopic Classification and the Japanese Vascular Classifications. The former is based on the endoscopic appearance and location of the varices, while the Japanese classification is based on the underlying vascular anatomy. In this article, the authors address the current concepts of classification, epidemiology, pathophysiology, and emerging management options of gastric varices. They describe the stepwise approach to patients with gastric varices, including the different available modalities, and the pearls, pitfalls, and stop-gap measures useful in managing patients with gastric variceal bleed.

Balloon-occluded Retrograde Transvenous Obliteration (BRTO): Preprocedural Evaluation and Imaging.

Patients undergoing balloon retrograde transvenous obliteration (BRTO) are mostly decompensated cirrhotic with either bleeding gastric varices (GV) or hepatic encephalopathy. It is crucial that clinicians are up-to-date with the assessments needed prior to BRTO to anticipate and prevent complications, and to deliver critical quality care. These patients will require preprocedural assessments and management, including endoscopic, clinical, laboratory, and imaging evaluation. Endoscopic evaluation is mandatory prior to BRTO, and it is highly recommended that it be performed at the same institution where BRTO will be performed. It is essential that clinicians are aware of the potential benefits and complications that may result from BRTO. These complications should be anticipated and prevented when possible. For GV bleeders, there should be consideration of a transvenous intrahepatic portosystemic shunt (TIPS) during or before BRTO in patients with refractory ascites or pleural effusion, as well as endoscopic banding or a TIPS in patients with high-risk esophageal varices. Patients undergoing BRTO are usually complicated and require a team approach. In this article, the authors address these assessment and preparatory management and planning procedures prior to the BRTO procedure as well as expected outcomes and potential complications.

Balloon-occluded Retrograde Transvenous Obliteration (BRTO): Follow-Up and Postprocedural Imaging.

The majority of patients undergoing balloon retrograde transvenous obliteration (BRTO) are decompensated cirrhotic for either bleeding gastric varices (GV) or hepatic encephalopathy. These patients will require close follow-up and assessments pre- and post-BRTO including clinical, laboratory, endoscopic, and imaging evaluations. It is essential that clinicians are aware of the potential benefits and complications that may result from BRTO. These complications may include fever, chest or epigastric pain, hemoglobinuria, transient hypertension, nausea or vomiting, and many more. These complications usually resolve within the first 10 days. Laboratory abnormalities are transient and uncommon. Radiologic and endoscopic follow-up are required including computed tomography (CT), magnetic resonance imaging (MRI), routine upper endoscopy and endoscopic ultrasound (EUS), which are detailed in this review. Patients undergoing BRTO are usually complicated and will require a team approach. This team should include the hepatologist, endoscopist, and interventional radiologist. Understanding and open dialogue are essential in the management of post-BRTO patients. The authors review the possible benefits, potential complications, and the evaluation tools needed to improve outcomes.