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.

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.

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.

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.

Mortality after percutaneous endoscopic gastrostomy in patients with cirrhosis: a case series.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tube placement can improve the nutritional status and the ability of a patient with cirrhosis to recover from surgery such as orthotopic liver transplantation. However, cirrhosis has been considered a significant contraindication to PEG tube placement. OBJECTIVE: Our aim in this study was to describe the mortality and complications in a series of cirrhotic patients who underwent PEG at our institution. DESIGN: Retrospective, single-institution case series. PATIENTS: This study involved 26 consecutive patients with cirrhosis who underwent PEG between 1995 and 2005. INTERVENTION: PEG tube placement. MAIN OUTCOME MEASUREMENTS AND RESULTS: The 30-day mortality of the series of patients was 10 of 26 (38.5%), whereas the 90-day mortality was 11 of 26 (42.3%). Nine of the 10 patients who died in the first 30 days had ascites at the time of PEG tube placement. Two patients died as a direct consequence of complications from the PEG procedure, whereas the other deaths were related to progression of liver disease or factors not directly related to the PEG. LIMITATIONS: The patients in this case series had varying levels of illness and reasons for PEG tube placement such that a generalization of outcomes may not be possible. CONCLUSIONS: The overall mortality of patients with cirrhosis who underwent PEG is high. Although there is an increased risk, PEG tube placement in cirrhotic patients without ascites may be less risky. The benefits of PEG tube placement in patients with cirrhosis should be weighed heavily against the risks.

Hepatocellular ballooning in NASH.

BACKGROUND & AIMS: Hepatocellular ballooning is a key finding in nonalcoholic steatohepatitis (NASH). It is conventionally defined by hemotoxylin and eosin (H&E) staining showing enlarged cells with rarefied cytoplasm and recently by changes in the cytoskeleton. Fat droplets are emerging as important organelles in cell metabolism. To address a possible relation between fat droplets and ballooning, we studied fat staining, H&E, and keratin 18 staining in human NASH. METHODS: Sequential staining and high resolution imaging were used to study freshly prepared cryo-sections from 10 patients with histologically confirmed steatohepatitis using oil red O for fat droplet identification, H&E to identify ballooning, and anti-K18 to confirm cytoskeletal changes. High resolution images were captured at each stage using the Aperio Scanscope. To provide ultrastructural correlation, glutaraldehyde-fixed specimens were studied using transmission electron microscopy (TEM) with serial sectioning for localization of ballooned cells by light microscopy and TEM in identical specimens. RESULTS: Serial staining consistently demonstrated that hepatocellular ballooning is associated with fat droplet accumulation evident by oil red O positivity and depletion of cytoplasmic keratin 18 with K-18 positive Mallory-Denk bodies (MDB). TEM confirmed the association between osmium stained fat droplets, MDB formation, and cellular enlargement and suggested droplet-associated dilation of the endoplasmic reticulum. CONCLUSIONS: These results indicate a relationship between cellular ballooning, fat droplet accumulation, and cytoskeletal injury in NASH. We speculate that injury to multiple, organelles including fat droplets and endoplasmic reticulum, contribute to this characteristic finding.

NASH and cryptogenic cirrhosis: a histological analysis.

INTRODUCTION: Epidemiological studies indicate that nonalcoholic steatohepatitis (NASH) is a common cause of cirrhosis described as 'cryptogenic'. To address this from a histological perspective and to examine the significance of residual histological findings as an indication of prior NASH, we looked back at biopsies in patients who presented with cirrhosis without sufficient histological features to diagnose NASH but who had prior histologically confirmed non-cirrhotic NASH. METHODS: Seven patients were identified with biopsy pairs showing non-specific (cryptogenic) cirrhosis in the latest specimen and a prior biopsy showing non-cirrhotic NASH. Using an expanded NASH-CRN system scored blindly by light microscopy, we compared the early and late biopsies to each other and to a cohort of 13 patients with cirrhosis due to hepatitis C without co-existing metabolic syndrome. RESULTS: Macrosteatosis, although uniformly present in the non-cirrhotic NASH specimens, declined in the late stage cirrhotic NASH specimens and was not useful in the distinction of late cirrhotic NASH from cirrhotic viral hepatitis. However, the presence of ballooned cells, Mallory-Denk bodies, and megamitochondria and the absence of apoptotic bodies were significantly different in late stage cirrhotic NASH compared to cirrhosis due to hepatitis C. CONCLUSIONS: Histologically advanced NASH presenting as non-specific or cryptogenic cirrhosis has residual changes which are consistent with prior steatohepatitis but which differ from cirrhosis due to hepatitis C. These results provide histological support for the more established epidemiological associations of NASH with cryptogenic cirrhosis and for criteria used in several proposed classifications of cryptogenic cirrhosis.

Endoscopic cyanoacrylate versus transjugular intrahepatic portosystemic shunt for gastric variceal bleeding: a single-center U.S. analysis.

BACKGROUND AND OBJECTIVES: Gastric variceal hemorrhage treatment remains a difficult issue for clinicians. There is controversy regarding whether first-line treatment should be endoscopic therapy with cyanoacrylate glue or placement of a transjugular intrahepatic portosystemic shunt (TIPS). We compared these methods on the basis of rebleeding, survival, and complications. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: This was a retrospective cohort analysis of cirrhotic patients with gastric variceal hemorrhage treated with endoscopic cyanoacrylate therapy or TIPS placement at a single U.S. center from 1997 to 2007. The groups were compared for rebleeding at 72 hours, 3 months, and 1 year; survival rates at 3 months and 1 year; and acute and extended complications and morbidity. MAIN OUTCOME MEASUREMENTS AND RESULTS: A total of 105 patients were included. There were no significant pretreatment differences between the 2 groups in age, sex, MELD (Model for End-Stage Liver Disease) score at the time of admission, or cause of liver disease. There were no significant differences in rebleeding at 72 hours, 3 months, and 1 year; survival at 3 months and 1 year; and aggregate long-term survival or acute complications. However, the TIPS group had a higher rate of long-term morbidity requiring hospitalization (41% with a TIPS and 1.6% in the cyanoacrylate arm, P < .0001). LIMITATIONS: Retrospective and uncontrolled samples. CONCLUSION: In patients with similar characteristics, cyanoacrylate therapy performed as well as a TIPS in controlling and preventing gastric variceal hemorrhage with no significant differences in survival. Patients receiving cyanoacrylate therapy experienced significantly less long-term morbidity related to therapy than patients who received a TIPS. Cyanoacrylate therapy appears to be safe and effective and compares favorably with TIPS therapy.

Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Non-alcoholic steatohepatitis (NASH) is a growing public health problem. Evaluation of risk factors for fibrosis in NASH will help to target resources to reduce development of cirrhosis. This study had two aims; the first to compile longitudinal histological data to characterize the natural history of fibrosis progression in NASH, and second, to identify predictive factors for progression to advanced fibrosis (stage 3 or greater) in NASH. METHODS: Subjects had to have a histological diagnosis compatible with NASH on their initial biopsy, received no intervention of proven histological benefit, and undergone two liver biopsies with at least an interval of one year between them. RESULTS: Ten studies were selected comprising 221 patients. 37.6% had progressive fibrosis over a mean follow-up interval of 5.3 years (SD, 4.2 years, median, 3.7 years, range 1.0-21.3 years). Proportional hazards regression analysis demonstrated that age (HR=0.98, p=0.009) and inflammation on initial biopsy (any inflammation, HR=2.5, p=0.001; grade 1, HR=2.5, p=0.001; grade 2, HR=2.4, p=0.003) are independent predictors of progression to advanced fibrosis. Other traditional parameters (e.g. obesity, diabetes, hypertension) were not statistically significant predictors. CONCLUSIONS: Presence of inflammation on the initial biopsy and age are independent predictors of progression to advanced fibrosis in patients with NASH.

Thiazolidinediones for the treatment in NASH: sustained benefit after drug discontinuation?

BACKGROUND: Although of unproven benefit for nonalcoholic steatohepatitis (NASH), thiazolidinediones (TZDs) have emerged as a promising therapy. Little evidence exists, however, regarding sustained effects of TZDs in NASH after drug discontinuation. A recent clinical study suggests that relapse of NASH pathophysiology is inevitable and that lifelong therapy may be needed to maintain histologic response. GOAL: We reviewed extended follow-up data of NASH patients previously treated with troglitazone to evaluate the influence of weight and physical activity on clinical and histologic parameters related to NASH recurrence. STUDY: After medical record review, 9 of 10 patients had complete data for follow-up and 5 had an extended follow-up biopsy 3 years or more after discontinuing troglitazone therapy. RESULTS: In contrast to recent work showing relapse of NASH to be nearly universal after discontinuation of TZD therapy, 2 of our patients had 1-stage improvement in fibrosis, normal aminotransferases, and absence of diabetes after median follow-up of 37 months after discontinuation of troglitazone. Both patients had sustained exercise programs and interval body mass index reduction. In contrast, active steatohepatitis, progression of fibrosis, and requirement of antidiabetic medications were seen in patients unable to achieve lifestyle modifications. CONCLUSIONS: We conclude that sustained histologic response after short-term TZD therapy for NASH is not invariably lost after medication discontinuation but rather is intimately related to sustained changes in lifestyle, particularly physical activity. Activity and diet in the setting of thiazolidinedione or other drug therapy of NASH is an essential consideration that warrants careful incorporation into future drug trials.

Therapy of NAFLD: antioxidants and cytoprotective agents.

Lipid peroxidation and secondary cellular injury are the dominant mechanism in the transition from relatively stable hepatic steatosis to potentially progressive steatohepatitis in nonalcoholic fatty liver disease (NAFLD). Oxidation of excessive fatty acids generates free radicals (reactive oxygen species) that damage organelles and stimulate signaling pathways leading to fibrosis and cellular injury. Both antioxidant agents (by breaking the chain reaction of lipid peroxidation) and cytoprotective agents (by stabilizing cellular and organelle phospholipid membranes) may be effective agents in treating an active steatohepatitis through amelioration of the driving force and attenuation of the secondary effects. Here we have reviewed the existing studies on such therapies, including vitamin E, S-adenosylmethionine (SAMe), betaine, and ursodeoxycholic acid. Small trials suggest possible improvement in liver enzymes with the use of these agents in NAFLD. However, controlled studies have not uniformly demonstrated benefit from these agents when compared with control groups treated with diet and weight loss alone, and measurement of reliable histologic endpoints is limited. These agents may show benefit in NAFLD through future larger controlled studies. Particular promise may exist in the use of these agents in combination therapy with ones that target other aspects in the pathogenesis of NAFLD, such as insulin-sensitizing agents.