Health education interventions are successful in modifying lifestyle. Functional health literacy (FHL) can determine patient adherence to clinic visits and procedures and may adversely impact the success of these interventions. We sought to evaluate the hypothesis that a health education intervention would improve compliance with hepatocellular cancer (HCC) screening and that poor FHL would reduce such compliance. We assessed FHL using a short version test of functional health literacy in adults (STOFHLA). Cirrhotic patients free of HCC were prospectively enrolled from clinics and provided an educational intervention consisting of focused physician-led discussion regarding cirrhosis and HCC, along with written material on these topics for the subject to review at home. Patients were subsequently followed for 6 months (prospective time period), and the same cohort’s clinic/HCC screening behavior between 6 and 12 months prior to the educational intervention (retrospective time period) was compared. In total, 104 cirrhotic patients (age 60.01 ± 8.58 years, 80% men, MELD 12.70 ± 5.76) were included. Of these, 89 (85.57%) of patients had educational level 12th grade and higher. There were 76% (n = 79) with adequate, while 24% (n = 25) had inadequate/marginal FHL on S-TOHFLA. The number of HCC-related imaging increased from 59 (56.7%) to 86 (82.6%, p < 0.0001) post-education in the prospective compared to prior time period which was similar regardless of FHL. While the educational intervention was successful in improving compliance with HCC screenings, FHL status did not impact the power of this intervention. Hence, the combination of specific verbal information, along with targeted written material, improved compliance with clinic visits and liver imaging for HCC.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly common in the United States and the Western World. In the United States, NAFLD and NASH are estimated to affect 1/3 and 1/10 Americans, respectively putting large proportion of the U.S. population at risk of advanced liver disease, cirrhosis and liver cancer. Transient Elastography or Fibroscan was approved in the United States in 2013 by the FDA as a non-invasive diagnostic test for the detection of steatosis and fibrosis in a variety of liver diseases including NAFLD. Until recently, access to Fibroscan has been limited primarily to academic research centers and tertiary care hospitals with the true status of NAFLD in the community and general U.S. population largely unknown. In this study, we report the status of NAFLD in a suburban community practice as identified by Fibroscan. METHODS: In this retrospective study, steatosis and fibrosis scores were analyzed in 489 NAFLD patients that had a Fibroscan (Fibroscan Compact 530) in a community hospital from February to November 2018. All the patients were referred for Fibroscan by gastroenterologists due to a fatty liver found on prior imaging studies by abdominal ultrasounds and / or CT scans. Patients with significant alcohol use (more than 2 drinks a day) and chronic liver disease (hepatitis B, Hepatitis C, autoimmune liver diseases and etc) were excluded from the analysis. RESULTS: Number of patient (percentage %). 1. *Steatosis score : S0 = 46 (9.40%), S1 = 15 (3.06%), S2 = 37 (7.56%) and S3 = 391 (79.95%). 2.** Fibrosis score : F0-F1 = 205 (41.92%), F2 = 148 (30.26%), F3 = 68 (13.90%) and F4 = 68 (13.90%). *Steatosis scoring: S0 = no fat, S1 = mild fat, S2 = moderate fat, S3 = severe fat. **Fibrosis scoring: F0-F1 = none to minimal scarring, F2 = moderate scarring, F3 = severe scarring, F4 = advanced fibrosis / cirrhosis. CONCLUSION: In this general population with incidental fatty liver, an alarming number of patients of nearly 80% have severe fatty liver disease (S3) and nearly a third (27.80%) have severe to advanced fibrosis / cirrhosis. With the higher than expected significant abnormal findings from this observational study, we recommend Transient Elastography (Fibroscan) as a screening tool to all clinicians managing patients with fatty liver disease. To confirm the validity of advanced liver disease found on Fibroscan, a liver biopsy should be considered in patients with severe or advanced (S3/4) liver fibrosis.

Background and Aims: Functional health literacy can determine patient adherence to clinic visits and procedures and is often ignored by clinicians.Screening for hepatocellular cancer (HCC) is an important goal in standard cirrhosis management but there is variability in pts getting imaging.We hypothesized that poor health literacy could be a factor defining HCC screening.Aim: To assess health literacy using short version test of functional health literacy in adults (S-TOFHLA) and determine the impact on knowledge of cirrhosis and HCC risk in cirrhotic pts.Methods: Cirrhotic pts who had been seen in clinics for at least 1 year and were free of HCC were enrolled.Pts underwent S-TOFHLA (has a total score and divides pts into low/marginal & good health literacy), a questionnaire inquiring about their knowledge of cirrhosis, HCC and Screening options.This was followed by focused education regarding future screening.Results: 69 cirrhotic pts (age 59.0±8.41,81%men, MELD 12.75±5.80,33% prior HE, 46% HCV, 20% alcohol) were included.In the preceding one year, the majority of patients (85%) had either one or more visits in the clinic with almost all (95%) saying that they had liver imaging done during this time period.On inquiry, the majority (n=61) knew they had cirrhosis but only 21 (31%) knew that their liver imaging was for HCC screening.22% thought it was to check liver function, 13% to check for scarring, 5% to check liver size, 11% since the doctor ordered it, 5% were not aware and13% had multiple answers.Health literacy: The mean TOFHLA Score was 27.32±8.75;70% had adequate, while 30% had marginal/inadequate functional health literacy.This was similar between pts with/without HE (28.1±7.9VS 25.5±10.3,p=0.34).Pts with low/marginal health literacy were more likely be older (62.9±7 vs 57.4±8.5, p=0.008) but had similar MELD (12.8±5.2 vs 12.7±6.1,p=0.97) &% alcoholic etiology (33% vs28%, p=0.42) compared to adequate health literacy.Awareness of the role of Liver imaging: The pts who were not aware that liver imaging was for HCC screening had a lower TOHFLA Score (25.5±9.6 vs 30.8±5.7, p=0.007) and higher percent of those with marginal/low health literacy (59% vs 13%, p= 0.03).The MELD score and other variables were similar between the groups.Conclusions: Functional health literacy is affected in almost a third of cirrhotic outpatients, which could impact their perception of the need for liver imaging.Simpler communication and better education could improve their understanding of the importance of liver imaging for HCC Screening.

Gastroesophageal variceal hemorrhage is a medical emergency with high morbidity and mortality. Endoscopic therapy is the mainstay of management of bleeding varices. It requires attention to technique and the appropriate choice of therapy for a given patient at a given point in time. Subjects must be monitored continuously after initiation of therapy for control of bleeding, and second-line definitive therapies must be introduced quickly if endoscopic and pharmacologic treatment fails.

There are an estimated 40 million HIV infected individuals worldwide, with chronic liver disease being the 2nd leading cause of mortality in this population. Elevated liver functions are commonly noted in HIV patients and the etiologies are varied. Viral hepatitis B and C, fatty liver and drug induced liver injury are more common. Treatment options for viral hepatitis C are rapidly evolving and are promising, but treatments are limited for the other conditions and is primarily supportive. Opportunistic infections of the liver are now uncommon. Irrespective of etiology, management requires referral to specialized centers and with due diligence mortality can be reduced.

Hepatic encephalopathy (HE) can manifest with a broad range of neuropsychiatric abnormalities of varying severity, acuity and time course with significant clinical implications. Lack of precise nomenclature and classification had hampered research in this complex clinical problem. A multiaxial classification system based on underlying etiology, clinical severity, time course and presence or absence of precipitating factors has been developed over the recent years and has been fully incorporated in the newly published AASLD-EASL guidelines on HE management. This multiaxial classification is expected to bring uniformity in describing and categorizing of HE across centers and nations, foster clinical research and improve patient care and outcome.

Multi-organ failure and infections are a major source of mortality in acute liver failure (ALF). Evidence-based guidance is limited because of the rarity, acuity, severity, and heterogeneity of the illness. ALF patients are believed to have an increased susceptibility for infections as a result of impaired functions of leukocytes/macrophages and complement systems (also referred as immunoparesis) owing to widespread hepatocyte destruction.1Antoniades C.G. Berry P.A. Wendon J.A. et al.The importance of immune dysfunction in determining outcome in acute liver failure.J Hepatol. 2008; 49: 845-861Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar The risks of infection are amplified owing to the presence of indwelling lines, catheters, and tubes in these critically ill patients. Microbial infections have been documented in up to 80% of cases.2Rolando N. Philpott-Howard J. Williams R. Bacterial and fungal infection in acute liver failure.Semin Liver Dis. 1996; 16: 389-402Crossref PubMed Scopus (170) Google Scholar The classic signs of infection such as fever and leukocytosis, however, can be absent in up to 30% of patients with ALF.3Rolando N. Harvey F. Brahm J. et al.Prospective study of bacterial infection in acute liver failure: an analysis of fifty patients.Hepatology. 1990; 11: 49-53Crossref PubMed Scopus (280) Google Scholar Sepsis leads to negative outcomes among patients with ALF. Bacteremia and systemic inflammatory response syndrome are associated with an increased severity of hepatic encephalopathy, coagulopathy, and renal failure.4Vaquero J. Polson J. Chung C. et al.Infection and the progression of hepatic encephalopathy in acute liver failure.Gastroenterology. 2003; 125: 755-764Abstract Full Text Full Text PDF PubMed Scopus (298) Google Scholar, 5Kumar R. Shalimar Sharma H. et al.Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure.Clin Gastroenterol Hepatol. 2012; 10: 925-931Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 6Hadem J. Tacke F. Bruns T. et al.Acute Liver Failure Study Group Germany. Etiologies and outcomes of acute liver failure in Germany.Clin Gastroenterol Hepatol. 2012; 10: 664-669Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar Sepsis can affect the success of liver transplantation adversely, and increases mortality in patients with ALF, with the reported attributable mortality ranging from 10% to 52%.2Rolando N. Philpott-Howard J. Williams R. Bacterial and fungal infection in acute liver failure.Semin Liver Dis. 1996; 16: 389-402Crossref PubMed Scopus (170) Google Scholar Therefore, in the absence of clinical prognostic indicators to predict infections, antibiotic prophylaxis has emerged in clinical practice at most centers managing ALF patients.7Bernal W. Wendon J. Acute liver failure.N Engl J Med. 2013; 369: 2525-2534Crossref PubMed Scopus (666) Google Scholar The Acute Liver Failure Study Group (ALFSG) previously had recommended use of antimicrobial prophylaxis in ALF patients with advanced hepatic encephalopathy, refractory hypotension, presence of systemic inflammatory response syndrome components, and for patients listed for liver transplantation.8Stravitz R.T. Kramer A.H. Davern T. et al.Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group.Crit Care Med. 2007; 35: 2498-2508Crossref PubMed Scopus (300) Google Scholar The utility and impact of such practice, however, remain questionable. In this issue of Clinical Gastroenterology and Hepatology, Karvellas et al,9Karvellas C.J. Cavazos J. Battenhouse H. et al.Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study.Clin Gastroenterol Hepatol. 2014; 12: 1942-1949Scopus (44) Google Scholar on behalf of the ALFSG, present their results of a large retrospective observational study aimed to answer the following question: what is the impact of antibiotic prophylaxis in ALF? Karvellas et al9Karvellas C.J. Cavazos J. Battenhouse H. et al.Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study.Clin Gastroenterol Hepatol. 2014; 12: 1942-1949Scopus (44) Google Scholar analyzed 1551 patients with ALF; 34% of whom had infections, of whom 14% had blood stream infections (BSIs) or bacteremia. BSI was associated significantly with reduced short term (21-day) survival, especially in the nonacetaminophen group. The survival rates of those who received liver transplantation, however, were comparable (86% vs 91%) irrespective of BSI. Antimicrobial prophylaxis neither prevented BSI nor improved the 21-day survival rate. Patients who received antimicrobial prophylaxis were noted to have worse disease severity and organ failure rates. This is consistent with the initial ALFSG recommendations8Stravitz R.T. Kramer A.H. Davern T. et al.Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group.Crit Care Med. 2007; 35: 2498-2508Crossref PubMed Scopus (300) Google Scholar advocating for antimicrobial prophylaxis among ALF patient subgroups, and in patients with this critical illness severity the tendency is to maximize treatments given to the patient. On the other hand, although antimicrobial prophylaxis did not appear to offer any benefit, there was no specific mention of nosocomial-resistant or fungal infections in patients who did receive this prophylaxis. Karvellas et al9Karvellas C.J. Cavazos J. Battenhouse H. et al.Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study.Clin Gastroenterol Hepatol. 2014; 12: 1942-1949Scopus (44) Google Scholar need to be commended for this work that, despite being a retrospective observational study, adds to our understanding of ALF and could provide strong guidance in the clinical management of this critical illness. This is because prospective randomized studies examining the impact of infections or of antimicrobial prophylaxis are lacking. The leading finding was that although BSI worsened mortality, antimicrobial prophylaxis did not improve it. A reason for this potentially could be the choice of the prophylactic drugs used. In other words, would antifungal or broader-spectrum coverage in every patient have helped? There has been a growing trend of gram-negative and fungal sepsis among critically ill patients.10Karvellas C.J. Pink F. McPhail M. et al.Predictors of bacteraemia and mortality in patients with acute liver failure.Intensive Care Med. 2009; 35: 1390-1396Crossref PubMed Scopus (59) Google Scholar, 11Vincent J.L. Rello J. Marshall J. et al.EPIC II Group of InvestigatorsInternational study of the prevalence and outcomes of infection in intensive care units.JAMA. 2009; 302: 2323-2329Crossref PubMed Scopus (2224) Google Scholar, 12Fagan R.P. Edwards J.R. Park B.J. et al.Incidence trends in pathogen-specific central line–associated bloodstream infections in US intensive care units, 1990–2010.Infect Control Hosp Epidemiol. 2013; 34: 893-899Crossref PubMed Scopus (62) Google Scholar, 13Rosenthal V.D. Central line-associated bloodstream infections in limited-resource countries: a review of the literature.Clin Infect Dis. 2009; 49: 1899-1907Crossref PubMed Scopus (70) Google Scholar Also of note, 38% of the positive cultures in this study had not been speciated and were classified as others. Additional potential reasons why antimicrobial prophylaxis did not improve mortality rates were as follows: was prophylaxis started too late, or was it because simple nonantibiotic interventions aimed at aseptic line insertion and maintenance to prevent central line–associated blood stream infections (CLABSI) would have a bigger impact than antibiotics alone? Although each center has their own central line guidelines in such a large cohort, the systematic recording of these BSI prevention measures is important. According to this study, sepsis leads to increased mortality, but prophylaxis is not the solution. Are there other options to prevent BSI? The reported incidence of BSI among intensive care unit (ICU) patients ranges from 3% to 12% of admissions and 1.6 to 44.6 cases per 1000 central line days, with increased age, number of central lines, mechanical ventilation, and length of ICU stay being among the major risk factors.11Vincent J.L. Rello J. Marshall J. et al.EPIC II Group of InvestigatorsInternational study of the prevalence and outcomes of infection in intensive care units.JAMA. 2009; 302: 2323-2329Crossref PubMed Scopus (2224) Google Scholar, 13Rosenthal V.D. Central line-associated bloodstream infections in limited-resource countries: a review of the literature.Clin Infect Dis. 2009; 49: 1899-1907Crossref PubMed Scopus (70) Google Scholar, 14Thompson D.S. Estimates of the rate of acquisition of bacteremia and associated excess mortality in a general intensive care unit: a 10 year study.J Hosp Infect. 2008; 69: 56-61Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 15Laupland K.B. Zygun D.A. Davies H.D. et al.Population-based assessment of intensive care unit-acquired bloodstream infections in adults: incidence, risk factors, and associated mortality rate.Crit Care Med. 2002; 30: 2462-2467Crossref PubMed Scopus (101) Google Scholar The BSI rate of 14% as reported in this study11Vincent J.L. Rello J. Marshall J. et al.EPIC II Group of InvestigatorsInternational study of the prevalence and outcomes of infection in intensive care units.JAMA. 2009; 302: 2323-2329Crossref PubMed Scopus (2224) Google Scholar and others2Rolando N. Philpott-Howard J. Williams R. Bacterial and fungal infection in acute liver failure.Semin Liver Dis. 1996; 16: 389-402Crossref PubMed Scopus (170) Google Scholar, 10Karvellas C.J. Pink F. McPhail M. et al.Predictors of bacteraemia and mortality in patients with acute liver failure.Intensive Care Med. 2009; 35: 1390-1396Crossref PubMed Scopus (59) Google Scholar is indicative that ALF patients are particularly vulnerable to this infection. CLABSIs are major but preventable problems among ICU patients with a reported mortality rate of 12% to 25%.16Centers for Disease Control and Prevention (CDC)Vital signs: central line-associated blood stream infections-United States, 2001, 2008, and 2009.MMWR Morb Mortal Wkly Rep. 2011; 60: 243-248PubMed Google Scholar In recent years, several health care initiatives have shown up to a 70% reduction in CLABSI rates by increasing adherence to recommended best practices for insertion of central lines.17Pronovost P. Needham D. Berenholtz S. et al.An intervention to decrease catheter-related bloodstream infections in the ICU.N Engl J Med. 2006; 355: 2725-2732Crossref PubMed Scopus (3077) Google Scholar The Centers for Disease Control and Prevention recently put out their updated evidence-based guidelines for the prevention of intravascular catheter-related infections.18O’Grady N.P. Alexander M. Burns L.A. et al.Guidelines for the prevention of intravascular catheter-related infections.Am J Infect Control. 2011; 39: S1-S34Abstract Full Text Full Text PDF PubMed Scopus (793) Google Scholar The key components, also called the central line bundle, is a group of evidence-based interventions for patients with central venous catheters that individually improve care and, when implemented together, result in substantially better outcomes (Table 1).18O’Grady N.P. Alexander M. Burns L.A. et al.Guidelines for the prevention of intravascular catheter-related infections.Am J Infect Control. 2011; 39: S1-S34Abstract Full Text Full Text PDF PubMed Scopus (793) Google Scholar, 19Centers for Disease Control and Prevention. Checklist for prevention of central line associated blood stream infection. Available: http://www.cdc.gov/HAI/pdfs/bsi/checklist-for-CLABSI.pdf. Accessed April 25, 2014.Google Scholar The education and training of health care personnel who insert and maintain catheters, bundling up of kits and supplies, implementing checklists, and empowering nursing staff to stop the procedure if checklists are violated are instrumental parts of these strategies. These bundled strategies are used as benchmarks for quality assurance and performance improvement because they have been effective in preventing BSIs both in ICU and non-ICU settings.16Centers for Disease Control and Prevention (CDC)Vital signs: central line-associated blood stream infections-United States, 2001, 2008, and 2009.MMWR Morb Mortal Wkly Rep. 2011; 60: 243-248PubMed Google Scholar There has been a concerted push from the Centers for Disease Control and Prevention and other stakeholders to enhance and improve these practices with a goal of zero CLABSIs. Aggressive use and systematic tracking of these nonantibiotic infection control measures such as the central line bundle could prevent CLABSI in ALF patients and improve survival.Table 1Key Components of the Central Line BundleAdapted using data from O’Grady et al18O’Grady N.P. Alexander M. Burns L.A. et al.Guidelines for the prevention of intravascular catheter-related infections.Am J Infect Control. 2011; 39: S1-S34Abstract Full Text Full Text PDF PubMed Scopus (793) Google Scholar and the Centers for Disease Control and Prevention.19Centers for Disease Control and Prevention. Checklist for prevention of central line associated blood stream infection. Available: http://www.cdc.gov/HAI/pdfs/bsi/checklist-for-CLABSI.pdf. Accessed April 25, 2014.Google ScholarHand washingMaximal sterile barrier precautions during central venous catheter insertionUsing 0.5% chlorhexidine for skin preparationAvoidance of femoral vein for central venous catheters in adult patientsDaily assessment of the need and prompt removal of unnecessary central venous cathetersAseptic techniques at line access and dressing change Open table in a new tab Based on the evidence, antimicrobial prophylaxis cannot be advocated for ALF patients. However, as is the case with many other rare diseases, the wait for evidence to answer this question is going to be a long one. Therefore, the clinical practice of initiating antibiotic prophylaxis likely will continue but should remain within the antibiotic susceptibility profile of the isolate and infection control policies of the hospital using the clinicians’ best judgment. To this end, it may be of interest to re-examine the impact in the nonacetaminophen ALF in future trials because this subgroup appears to do worse in the presence of BSI. The rather protracted clinical course and the ensuing compensatory inflammatory response syndrome in these patients with subacute liver failure likely render them more vulnerable to sepsis than the acetaminophen ALF group presenting with hyperacute liver failure. To conclude, this large multicenter study once again makes it clear that sepsis, particularly BSIs, are important predictors of mortality in ALF patients2Rolando N. Philpott-Howard J. Williams R. Bacterial and fungal infection in acute liver failure.Semin Liver Dis. 1996; 16: 389-402Crossref PubMed Scopus (170) Google Scholar, 4Vaquero J. Polson J. Chung C. et al.Infection and the progression of hepatic encephalopathy in acute liver failure.Gastroenterology. 2003; 125: 755-764Abstract Full Text Full Text PDF PubMed Scopus (298) Google Scholar, 10Karvellas C.J. Pink F. McPhail M. et al.Predictors of bacteraemia and mortality in patients with acute liver failure.Intensive Care Med. 2009; 35: 1390-1396Crossref PubMed Scopus (59) Google Scholar; this is in line with data from cirrhotic patients and those with acute on chronic liver failure.20Bajaj J.S. O'Leary J.G. Reddy K.R. et al.Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American Consortium for the Study of End-stage Liver Disease (NACSELD) experience.Hepatology. 2012; 56: 2328-2335Crossref PubMed Scopus (282) Google Scholar, 21Moreau R. Jalan R. Gines P. et al.CANONIC Study Investigators of the EASL–CLIF ConsortiumAcute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology. 2013; 144: 1426-1437Abstract Full Text Full Text PDF PubMed Scopus (1625) Google Scholar Preventing infection through evidence-based guidelines using drug and non–drug-based approaches should continue to be a goal of future clinical trials. Effects of Antimicrobial Prophylaxis and Blood Stream Infections in Patients With Acute Liver Failure: A Retrospective Cohort StudyClinical Gastroenterology and HepatologyVol. 12Issue 11PreviewWe investigated whether antimicrobial prophylaxis alters the incidence of bloodstream infection in patients with acute liver failure (ALF), and whether bloodstream infections affect overall mortality within 21 days after development of ALF. Full-Text PDF

Refractory ascites accounts for 5-10 % of all ascites and portends a very poor prognosis. Refractory ascites can be diuretic-resistant (unresponsive to maximal dose of diuretics) or diuretic-intractable (inability to use an effective dose of diuretics due to development of complications). Management is challenging as therapeutic options are limited. Available options include serial large volume paracentesis or placement of transjugular intrahepatic portosystemic shunt. A novel device involving an automated low flow ascites pump and a peritoneo-vesical shunt has been recently developed but long term safety and efficacy data are awaited. Liver transplantation is the only modality proven to improve long-term survival.

Owing to shared routes of transmission and common risk factors, coinfection with hepatitis B virus (HBV) and HIV is common. As AIDS-related opportunistic infections have declined with successful antiretroviral therapy (ART), liver-related mortality has emerged as the second leading cause of death among patients infected with HIV HIV infection negatively impacts the natural history of HBV, increasing the risks for cirrhosis, hepatocellular carcinoma, and liver-related mortality. With the availability of effective antiviral therapy active against both HIV and HBV and simplified treatment algorithms, it has become easier than ever to treat coinfected patients. However, the issues of suboptimal response, incomplete viral suppression, adverse effects of long-term antiviral treatment, and potential hepatotoxicity of ART remain major challenges.

Commentary on : Kohli A, Shaffer A, Kottilil S. Treatment of hepatitis C: a systematic review. JAMA 2014;312:631–40.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Hepatitis C virus (HCV) infects over 185 million people worldwide and can lead to progressive liver fibrosis, cirrhosis, hepatocellular carcinoma and death. Antiviral treatment can prevent these complications and improve survival. Interferon has been the backbone of anti-HCV therapy, but has been plagued by side effects, treatment failure and relapse. HCV treatment has seen significant changes with the advent of directly acting antiviral agents with nearly 100% cure rate with all oral, interferon and ribavirin-free regimens. This systematic review of randomised controlled trials (RCTs) and cohort studies aimed to examine the safety, tolerability and efficacy of all Food and Drug Administration (FDA)-approved regimens against HCV genotypes 1, 2 and 3. All studies between January 2009 and May 2014 were included if they were published in English, used FDA-approved antiviral therapies, included sustained virological response (SVR) as the study outcome, and defined treatment … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.volume%253D312%26rft.spage%253D631%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.2014.7085%26rft_id%253Dinfo%253Apmid%252F25117132%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.2014.7085&link_type=DOI [3]: /lookup/external-ref?access_num=25117132&link_type=MED&atom=%2Febmed%2F20%2F1%2F23.atom [4]: /lookup/external-ref?access_num=000340136400022&link_type=ISI

The following baseline variables were asked in the first survey.Demographic factors included nationality, educational, marital and socioeconomic status.Lifestyle factors assessed included smoking, alcohol intake, body mass index, number of live births and a history of a prolapse repair.The number of stressful life events in the past year was assessed as was depression using the Centre for Epidemiological Studies-Depression scale (CES-D).Domains of quality of life were assessed using the valid SF-36.RESULTS: Of the 3716 women who responded to the first and follow-up survey, we found 1501 (40.3%) developed constipation over the 9 year period.Univariately, we found an increased number of live births, increased number of stressful life events, lower socioeconomic status and reduced functioning in the following SF 36 domains: general health, bodily pain, mental health, physical and social functioning, role emotional and physical and vitality to be significantly associated with new onset constipation.However in a multiple regression model that included these significant variables we found the rate of constipation in those women who have given birth versus those who had not (43% vs 34%; OR= 1.1; 95%CI 1.0-1.1,P=0.003) and reduced functioning on the SF-36 subscales for vitality (M=6.4 vs M=6.8; OR=0.9; 95%CI 0.9-1.0,P=0.000) and bodily pain (M=6.8 vs M=7.4; OR=0.9; 95%CI0.9-1.0,P=0.001) were independent risk factors for developing constipation among women who did not report constipation on the first survey.CONCLUSIONS: Constipation is an extremely common problem among older community dwelling women and causes decrement in health related quality of life.Our prospective data suggests factors related to childbirth and generally being unwell as reflected by poor quality of life are risk factors for developing new onset constipation among older women.

BACKGROUND:Double-stranded RNA-activated protein kinase (PKR), an interferon (IFN)-stimulated gene, is activated by binding with double-stranded RNA, a putative replicative intermediate of the hepatitis C virus (HCV). Activated PKR phosphorylates the alpha subunit of eukaryotic initiation factor-2 to inhibit the translation of viral protein.AIMS/METHODS:We established stable PKR knockdown Huh7 cells using RNA interference and investigated the effect of PKR against HCV replication using a subgenomic replicon that expressed luciferase reporter protein and the JFH1 full-length HCV genome.RESULTS:In stable PKR knockdown cells that harboured a subgenomic replicon, luciferase activity was approximately three times higher than that of control cells, indicating that the subgenomic replicon replicated with a higher efficiency in stable PKR knockdown cells than that in control cells. Furthermore, stable PKR knockdown cells secreted significantly more HCV particles than did control cells after transfection with the full-length HCV genome. The replication of the subgenomic replicon was suppressed by the addition of IFN-alpha in both cells. Although the extent of suppression was significantly lower in stable PKR knockdown than control cells using a low concentration (2.5-5 U/ml) of IFN-alpha, even 10 U/ml IFN-alpha suppressed the replication of subgenomic replicon by >98% in both cells.CONCLUSIONS:Double-stranded RNA-activated protein kinase plays an important role in suppressing HCV replication in an innate state, but may not be essential in IFN therapy.

Background: Progression of disease after hepatitis C virus (HCV) infection differs among individuals, indicating a possibility of participation of host genetic factors. 20-50-oligoadenylate synthetase 1 (OAS-1), an important component of the innate immune system, has an antiviral function, and may therefore have a certain relationship with progression of disease. Aim: To evaluate single nucleotide polymorphisms (SNPs) of OAS-1 and its relationship with the disease status of HCV infection. Methods: Six SNPs of OAS-1 were selected and examined in 409 Japanese patients with chronic HCV infection using the TaqMan PCR genotyping method. The relationship of SNP genotypes and clinical manifestations of patients was analysed. Then, a pair of OAS-1-expression plasmids mimicking the clinical-related SNPs were created and transfected into liver cells carrying the HCV subgenomic replicon or the full-length genome, JFH1, and HCV replication after transfection was compared. Results: Patients with genotypes A/A, A/G and G/G of an SNP of OAS-1 at the exon 3 of its coding sequence were at gradient increased risks of suffering from higher serum alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P = 0.001), higher degree of liver fibrosis (P = 0.010) and higher presence of liver cirrhosis (P = 0.001). By multivariate logistic regression analysis, genotype G/G was an independent factor associated with cirrhosis (P = 0.013, odds ratio 3.11, 95% confidence interval 1.27-7.63). In liver cells, OAS-1 with the G allele showed lower ability to inhibit virus replication than OAS-1 with the A allele (P = 0.004). Conclusions: The SNP of OAS-1 at the exon 3 of its coding sequence was associated with progression of disease in Japanese patients with HCV infection.

UNLABELLED:Infection by hepatitis C virus (HCV) usually results into chronic hepatitis that can ultimately lead to cirrhosis and hepatocellular carcinoma. Type 1 interferons (IFN-alpha/beta) constitute the primary cellular defense against viral infection including HCV. IFN binding to their receptors activates associated Jak1 and Tyk2 kinases, which ultimately leads to phosphorylation and assembly of a signal transducer and activator of transcription protein (STAT)1-STAT2-interferon regulatory factor (IRF)9 trimetric complex called interferon-stimulated gene factor 3 that translocates into the nucleus and binds to the interferon- stimulated response elements (ISRE), leading to transcriptional induction of several antiviral genes, including double-stranded RNA-activated protein kinase (PKR), 2',5'- oligoadenylate synthetase (OAS), and myxovirus resistance protein A (MxA). Understanding the mechanisms of how the virus evades this cellular innate defense and establishes a chronic infection is the key for the development of better therapeutics against HCV infection. Here, we demonstrate that p53 could have a crucial role in the cellular innate defense against HCV. We observed significantly higher levels of HCV RNA replication and viral protein expression in the Huh7 cells when their p53 expressions were knocked down. Moreover, IFN treatment was less effective in inhibiting the HCV RNA replication in the p53-knocked-down (p53kd) Huh7 cells. In fact, the activation of the ISRE and the induction of ISGs were significantly attenuated in the p53kd Huh7 cells and p53 was found to directly interact with IRF9. CONCLUSION:These observations underscore the potential contributions of the tumor suppressor p53 in cellular antiviral immunity against HCV with possible therapeutic implications.

BACKGROUND AND AIMS:Interferon (IFN) regulatory factor 7 (IRF-7) has been shown to play an essential role in the transcriptional activation of virus-inducible cellular genes, especially IFN genes. Polymorphisms of the IRF-7 gene may probably affect both the quality and the quantity of IRF-7. We investigated the role of IRF-7 polymorphisms in Japanese patients with chronic hepatitis C virus (HCV) infection.METHODS:We studied a total of nine polymorphisms of the IRF-7 gene including SNP1047A/G (Lys/Glu) and SNP2157A/G (Gln/Arg) using the Taqman allelic discrimination and sequencing techniques in 406 Japanese patients with chronic HCV infection. We further performed functional analysis of SNP1047 and SNP2157 by transcriptional activation of the IFNA promoter.RESULTS:We found that SNP1047AG and SNP2157AG genotypes were in complete linkage disequilibrium and were present in a significantly higher proportion in HCV-infected patients with cirrhosis (5.6%) than in those without cirrhosis (1.7%) (P=0.03). Multivariate analysis also revealed that SNP1047 and SNP2157 were independently associated with cirrhosis at an odds ratio of 2.5. Functional analysis revealed that SNP1047G and SNP2157G alleles increased IFNA expression.CONCLUSION:SNP1047AG and SNP2157AG genotypes were strongly associated with cirrhosis. SNP1047G and SNP2157G alleles might be used as markers of host factors associated with a higher risk of cirrhosis in Japanese patients with chronic HCV infection.

Purpose: The typical case of papillary stenosis is described as middle aged female who presents with recurrent episodes of right upper abdominal pain occurring several years after cholecystectomy with mild elevations of LFTs. Here we report an unusual case of papillary stenosis who presented with acute pancreatitis like symptoms with very high levels of LFTs and amylase and lipase followed by rapid improvement. Methods: A 53-year-old white female s/p cholecystectomy came to the emergency department because of epigastric pain, nausea and vomiting for 2 days. On physical exam, she had epigastric tenderness but no jaundice or dehydration. The liver enzymes were grossly elevated, with an aspartate aminotransferase (AST) level of 2006 IU/L, an alanine aminotransferase (AST) level of 1359 IU/L, and an alkaline phosphatase (ALP) value of 180 IU/L. Total and direct bilirubin levels were 2.2 mg/dL and 1.3 mg/dL respectively. Serum amylase and lipase were 1536 U/L and 1915 U/L respectively. A CT scan of abdomen and pelvis and abdominal sonogram were negative for pancreatitis or stones in the pancreato-biliary tree. ERCP revealed a normal papilla. Cholangiogram showed a dilated common hepatic duct of 8 mm with benign tapering to the ampulla. The cystic duct joined the common hepatic duct only few millimeters away from the ampulla. Hence the patient had a very small common bile duct. No stones were noted in the biliary tree. With the elevated LFTs, biliary pain and dilated duct, this was a case of type 1 papillary stenosis. Sphincterotomy was performed. Post ERCP follow up labs showed a marked decline in LFTs and amylase and lipase and there was marked improvement in abdominal pain. At follow up visit one week after sphincterotomy, the patient remained completely asympomatic and the LFTs and amylase and lipase were almost completely normalized (AST = 33, ALT = 154, ALP = 195, amylase = 101, lipase = 46 and total bilirubiN = 0.3). Conclusion: Papillary stenosis is not a common condition and often presents diagnostic dilemma to the clinicians. An ERCP with sphincterotomy is instrumental in diagnosing and treating papillary stenosis, and should be considered in postcholecystectomy cases with abdominal pain and elevated LFTs. Endoscopic sphinceteotomy is a recommended treatment for papillary stenosis (type 1 SOD) and is very effective and safe in experienced hands.