Search

Summary: Background: Elbasvir‐grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4. Aim: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir‐grazoprevir in the United States. Methods: We conducted a retrospective cohort study of adults treated with elbasvir‐grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud‐based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post‐treatment (SVR12). Results: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non‐cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir‐grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent‐to‐treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4. Conclusion: Elbasvir‐grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12‐week therapy without ribavirin. [ABSTRACT FROM AUTHOR]

Portal hypertension is a predictor of liver-related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon-free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child-Pugh-Turcotte ( CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [ HVPG] >6 mm Hg) were randomized to receive 48 weeks of open-label sofosbuvir plus ribavirin at Day 1 or after a 24-week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy ( SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by -1.0 ( SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow-up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long-term follow-up. (Eudra CT 2012-002457-29). [ABSTRACT FROM AUTHOR]

Background Treatment of genotype 1 hepatitis C virus ( HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response ( SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. Aim To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. Methods We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. Results A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. Conclusions In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen. [ABSTRACT FROM AUTHOR]

Early data regarding the 'real-world' experience with novel therapies for hepatitis C ( HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response ( SVR) for ledipasvir-sofosbuvir ( LDV- SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV- SOF±ribavirin ( RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration ( FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV- SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV- SOF+ RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV- SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted. [ABSTRACT FROM AUTHOR]

Background Recent animal studies have shown that platelets directly activate hepatic stellate cells to promote liver fibrosis, whereas anti-platelet agents decrease liver fibrosis. It is unknown whether platelet inhibition by aspirin prevents liver fibrosis in humans. Aim To examine the association between aspirin use and liver fibrosis among adults with suspected chronic liver disease. Methods We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey III. We identified 1856 individuals with suspected chronic liver disease ( CLD). The degree of liver fibrosis was determined using four validated fibrosis indices and a composite index. Results The use of aspirin was associated with a significantly lower composite liver fibrosis index calculated from FIB4, APRI, Forns and NFS [0.24 standard deviation (s.d.) units lower; 95% CI −0.42 to −0.06, P = 0.009]. The association of aspirin with lower fibrosis scores was significantly larger among those with suspected CLD compared to those without (−0.23 vs. −0.03 s.d. units; P interaction = 0.05). The negative association between aspirin use and lower fibrosis index was consistent across all four fibrosis indices ( P = 0.002-0.08) in individuals with chronic viral hepatitis, suspected alcoholic liver disease and NASH. In comparison, no negative associations with liver fibrosis were seen with ibuprofen in parallel analyses. Conclusions The use of aspirin was associated with significantly lower indices of liver fibrosis among US adults with suspected chronic liver diseases. Aspirin and other anti-platelet drugs warrant further investigation for the prevention and treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Background Elevated fasting triglyceride is often associated with metabolic syndrome and non-alcoholic fatty liver disease ( NAFLD), the most common form of chronic liver disease. On the other hand, as liver disease progresses, patients may develop hepatocellular dysfunction that impairs triglyceride production. Aim To test the hypothesis that lower fasting triglyceride levels may paradoxically indicate more advanced liver disease. Methods A cross-sectional analysis of 11 947 adults aged 20 years or older without chronic viral hepatitis from the National Health and Nutrition Examination Survey 1999-2010 was performed to analyze the relationships between fasting triglyceride levels and five validated non-invasive indices of liver fibrosis, including Fibrosis 4 Score ( FIB4), NAFLD Fibrosis Score ( NFS), Ast-Platelet Ration Index, AST/ ALT ratio and BARD. Results Low-fasting triglyceride levels were consistently associated with elevated liver fibrosis indices. Individuals in the lowest quintile of triglycerides (TG) had an adjusted odds ratio ( OR) of 3.0 (95% CI, 1.7-5.2; P < 0.001) for advanced fibrosis estimated by FIB4 score and OR of 1.8 (95% Cl, 1.2-2.7; P = 0.009) estimated by NFS, compared to individuals in the highest quintile. This association remained highly significant when restricted to individuals with abnormal LFTs from suspected NAFLD. This inverse relationship was continuous, and more pronounced among men and whites ( P interaction <0.001 and 0.008 respectively), but not modified by age or body mass index. In addition, fasting TG had a stronger, more direct association with liver fibrosis indices than did albumin or total bilirubin. Conclusions Fasting triglyceride levels were inversely associated with liver fibrosis indicators in American adults, especially among white men. Our findings suggest that sequential lipid measurements may serve as a useful disease marker in the management of chronic liver disease patients. [ABSTRACT FROM AUTHOR]

Background and Aims: New therapies for HCV are rapidly emerging and providers are advising select patients to defer treatment and elect 'watchful waiting'. During the watchful waiting period, patients have been shown to have high rates of illness uncertainty and depression. We sought to answer the question of whether reassuring histological data (showing minimal fibrosis or no fibrosis progression over time) is associated with less illness uncertainty and depressive symptoms. Methods: This was a single-centre outpatient prospective cohort study to determine whether stage of fibrosis, fibrosis progression and reasons for treatment deferral were related to illness uncertainty and depressive symptoms in patients following watchful waiting. Results: Illness uncertainty was significantly related to depressive symptoms ( r = 0.49, P < 0.01). More than half of the participants (54%) had moderate levels of uncertainty. About 40% of the participants were at risk for clinical depression (21.7% at mild to moderate risk and 18.5% at high risk). Treatment naïve subjects had lower mean scores on both the CES-D (depressive symptoms measure) and the MUIS-A (illness uncertainty measure) total score, MUIS-A Ambiguity subscale and MUIS-A Inconsistency subscale than subjects who failed treatment or were interferon intolerant or ineligible. Surprisingly, liver fibrosis stage and progression were not significantly associated with overall illness uncertainty or depressive symptoms. Conclusion: Patients with chronic hepatitis C on watchful waiting are at high risk for significant illness uncertainty and depressive symptoms. Reassuring histological data does not seem to correlate with less uncertainty or depressive symptoms. [ABSTRACT FROM AUTHOR]

Background The treatment of HBeAg-negative chronic hepatitis B ( CHB) is considered to be open-ended, with no guidelines for treatment cessation. Aim To evaluate biochemical and virological relapse requiring retreatment in noncirrhotic HBeAg-negative CHB in patients who stopped treatment following a period of prolonged viral suppression with nucleotides/nucleosides. Methods We performed a single-centre retrospective chart review of patients with HBeAg-negative CHB who maintained viral suppression for 4-5 years on anti-viral treatment, and thus subsequently stopped treatment. The primary end point of composite relapse was defined by an increase in HBV DNA >2000 IU/mL, ALT elevation above 1.25 × normal or doubling of ALT from cessation, and re-initiation of anti-viral therapy. Results We identified 33 patients with HBeAg-negative CHB who stopped treatment following viral suppression. Mean treatment duration was 5.28 ± 2.73 years. Patients were treated with lamivudine (3), adefovir (14), entecavir (4), and tenofovir (12). Eleven (33%) patients met the primary end point of composite relapse. For individual end points, 21 (63%) patients had a viral relapse, 16 (48%) had a biochemical relapse, and 16 (48%) restarted treatment, leaving 17 (52%) patients who remained treatment-free over a median 36 months of follow-up. Lower pre-treatment ALT and detectable HBV DNA within the first month after treatment discontinuation were associated with increased rates of composite relapse ( HR 1.01; P = 0.022 for ALT and HR 1.01; P = 0.038 for HBV DNA). Conclusion Patients with noncirrhotic HBeAg-negative CHB can stop treatment after greater than 4-5 years of suppressive therapy with nucleosides/nucleotides with more than 50% remaining treatment-free. [ABSTRACT FROM AUTHOR]

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus ( HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention ( CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels. [ABSTRACT FROM AUTHOR]

Affecting 2-3% of the world's population, hepatitis C is a common viral infection which is a significant cause of morbidity and mortality. Hepatitis C genotype 1 is the dominant viral genotype among Western patients. For the last 20 years, in the era of interferon-based therapy, it was far more difficult to treat relative to genotypes 2 and 3. Accordingly, a significant focus of research was on new antiviral agents for the dominant genotype 1 patient. Now, as promising specific treatments are being introduced for genotype 1, the attention of clinicians and researchers has turned back to the 50-70 million patients infected with a nongenotype 1 hepatitis C. Furthermore, after recent, larger randomized trials, we have realized that genotype 2 is truly interferon sensitive while genotype 3 patients are far less successful with therapy. In this fundamentally altered landscape, genotype 3 is now potentially the most difficult to treat genotype and an area of intense research for new drug development. Herein we review the virology, natural history and the treatment of genotype 3 hepatitis C. [ABSTRACT FROM AUTHOR]

Background The extent to which potentially curative therapies are used in patients with hepatocellular cancer ( HCC) and their related outcomes are unknown in the US. Aim To determine the rate and outcomes of potentially curative treatment in patients with HCC. Methods Eleven US centers followed patients with HCC between 2001 and 2007. We determined rates of liver transplantation, surgical resection, or tumour ablation during follow-up, examined differences in adjusted survival of patients receiving these treatments, and determined the factors associated with receipt of potentially curative treatment. Results Of the 267 patients, 76 (28%) patients had early HCC, defined as Child A or B cirrhosis, with a solitary HCC or ≤3 nodules, each ≤3 cm. Of these, 53 (69.7%) received curative treatment. Thirty six percent of patients with non-early HCC received curative treatment. Compared to patients with non-early HCC who did not receive curative treatment, patients with early HCC and curative treatment had the best survival [hazard ratio, HR = 0.19 (95% CI, 0.08-0.42)] followed by patients with advanced HCC who received curative treatment [ HR = 0.37 (95% CI, 0.22-0.64)]. Baseline performance status was significantly associated with receipt of curative treatment as well as survival after adjusting for demographics, clinical characteristics, and HCC stage. Conclusions In this multicenter database, most of the patients with early HCC received potentially curative treatment. However, only 28% of patients had early HCC. One-third of patients with non-early HCC also underwent curative therapy. Potentially curative treatment improved survival and this effect was seen in patients with early as well as non-early HCC. [ABSTRACT FROM AUTHOR]

Summary. The aim of this study is to review clinical trial data on the newly approved protease inhibitors boceprevir and telaprevir to develop consensus recommendations on the optimal use of these agents for the treatment of patients with chronic hepatitis C virus (HCV) infection. An expert panel of seven leading authorities in viral hepatitis was convened to establish and disseminate a practical guide on best practices for incorporating boceprevir and telaprevir into therapy for HCV infection in both treatment-naive and treatment-experienced patients. The topics covered include selecting candidates for boceprevir- or telaprevir-based treatments, predictors of response and early viral kinetics, response-guided therapy approaches, on-treatment management strategies to optimize the likelihood of response and minimize the risk of drug resistance, management of adverse effects during therapy and key considerations for special populations. The expert panel incorporated the best available clinical evidence into recommendations on how boceprevir and telaprevir should be used in the clinical setting. They indicated how treatment regimens may differ according to the baseline factors, such as presence of cirrhosis and when therapy may need to be modified or stopped altogether because of adverse events or poor virologic response. This practical guide will serve as a valuable resource for clinicians embarking on the new treatment paradigm of boceprevir or telaprevir in combination with peginterferon/ribavirin for chronic genotype 1 HCV infection. [ABSTRACT FROM AUTHOR]

. Low-density lipoprotein cholesterol (LDL-C) levels and interleukin 28B ( IL28B) polymorphism are associated with sustained viral response (SVR) to peginterferon/ribavirin (pegIFN/RBV) for chronic hepatitis C (CHC) infection. IL28B has been linked with LDL-C levels using a candidate gene approach, but it is not known whether other genetic variants are associated with LDL-C, nor how these factors definitively affect SVR. We assessed genetic predictors of serum lipid and triglyceride levels in 1604 patients with genotype 1 (G1) chronic hepatitis C virus (HCV) infection by genome-wide association study and developed multivariable predictive models of SVR. IL28B polymorphisms were the only common genetic variants associated with pretreatment LDL-C level in Caucasians (rs12980275, P = 4.7 × 10−17, poor response IL28B variants associated with lower LDL-C). The association was dependent on HCV infection, IL28B genotype was no longer associated with LDL-C in SVR patients after treatment, while the association remained significant in non-SVR patients ( P < 0.001). LDL-C was significantly associated with SVR for heterozygous IL28B genotype patients ( P < 0.001) but not for homozygous genotypes. SVR modelling suggested that IL28B heterozygotes with LDL-C > 130 mg/dL and HCV RNA ≤600 000 IU/mL may anticipate cure rates >80%, while the absence of these two criteria was associated with an SVR rate of <35%. IL28B polymorphisms are the only common genetic variants associated with pretreatment LDL-C in G1-HCV. LDL-C remains significantly associated with SVR for heterozygous IL28B genotype patients, where LDL-C and HCV RNA burden may identify those patients with high or low likelihood of cure with pegIFN/RBV therapy. [ABSTRACT FROM AUTHOR]

Summary. There is increasing interest in developing noninvasive means to evaluate liver fibrosis in patients with chronic liver disease to determine disease severity, prognosis and optimal treatment. Transient elastography (TE) has previously been demonstrated to predict the presence or absence of advanced fibrosis. The current study was conducted to determine whether TE can identify patients with chronic liver disease at risk of clinical decompensation. A total of 667 patients underwent TE and were followed for a median of 861 days and 57 patients achieved the primary outcome, a composite of clinical endpoints including death, ascites, encephalopathy, increased Child Score ≥2, variceal bleed, hepatocellular carcinoma or listing for transplant. Overall, TE had an area under the receiver operating characteristic curve of 0.87 for predicting clinical outcome. Using a cut-off of 10.5 kPa, TE has a sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 94.7%, 63.0%, 19.3% and 99.2%, respectively. A predictive model for clinical events was developed using generalized cross-validation for clinical endpoints considering TE, liver biopsy results and multiple other predictors. Individually, TE performed better than biopsy, or any other variable, for predicting clinical outcome [Harrell's C Statistic 0.86 for TE, 0.78 for stage]. Patients with a TE score of >12.5 kPa were found to have a relative hazard for clinical event of 18.99 compared with patients with TE score <10.5. A combined variable model including TE, aspartate aminotransferase/alanine aminotransferase ratio and model for end-stage liver disease (MELD) yielded the highest predictive accuracy with Harrell's C value of 0.93. In the subset of patients with cirrhosis, TE was not found to be independently associated with clinical outcomes in univariate or multivariate analysis although it retained a high sensitivity and NPV of 97.5% and 92.3%, respectively, at a kPa cut-off of 10.5. TE can successfully identify patients with chronic liver disease who are at low risk of clinical decompensation over a time period of 2 years. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2012; 35: 255-265 Summary Background Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC. Aim To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC. Methods We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers. Results A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU ( P < 0.05) after 12 months of treatment. There were no changes in other liver function tests and fibrosis biomarkers. No adverse events were reported. Conclusions Oral DHA supplementation is associated with an increase in serum DHA levels and a significant decline in alkaline phosphatase levels in patients with PSC. These data support the need for a rigorous trial of DHA therapy in PSC. [ABSTRACT FROM AUTHOR]

The diagnosis of cirrhosis requires screening for oesophageal varices by upper gastrointestinal endoscopy. In many countries, serological tests and elastography are replacing liver biopsy for diagnosing cirrhosis. The aims of this study were to see whether there was an optimal cut-off of liver stiffness that could predict the presence of large (>F2) oesophageal varices and whether this was disease specific. A total of two hundred and twenty-two patients with all cause cirrhosis (Child class A) were screened, and 211 had successful elastography and are included in the analysis. Of the patients studied, one hundred and thirty-two patients had no or small F1 varices and 79 had large varices. Liver stiffness of 19.8 kPa had a negative predictive value of 91% and a positive predictive value of 55% with an area under the curve (AUC) on receiver operating characteristics (ROC) of 0.73 in differentiating between small and large varices. Seven patients with large varices would have been incorrectly classified. In the 157 patients with hepatitis C as the aetiology of cirrhosis, the negative predictive value was 98% and only one patient was misclassified. Liver stiffness was superior in diagnostic accuracy to platelet count in all patients. A liver stiffness of >19.8 kPa could be utilized as a cut-off for endoscopy and beta blocker utilization, particularly in patients with hepatitis C. [ABSTRACT FROM AUTHOR]

To evaluate the cost-effectiveness of Hepatitis C therapy, robust real-world data are needed to understand the costs and benefits of treatment alternatives. The objective of this study was to evaluate the true direct cost of treatment in an unselected sequential population of patients treated at a tertiary care centre for hepatitis C virus genotype 1. A total of 200 consecutive patients were treated with interferon, ribavirin and a first-generation direct-acting antiviral agent ( DAA) between 2011 and 2013. A total of 41% had cirrhosis, 31% were prior relapsers, and 41% were prior partial or null responders. Costs used were wholesale acquisition cost prices for medications, average hospital costs per day for each diagnosis code based on US inpatient hospital charges. All costs were adjusted to 2013 dollars. Sustained virologic response ( SVR) was achieved in 97 patients (48.5%). A total of 14% experienced relapse, 19% breakthrough or nonresponse, and 18.5% discontinued secondary to side effects. Twenty per cent of patients had at least one hospitalization attributable to a complication of therapy. Thirty-seven per cent of patients required erythropoietin-stimulating agents, 16% received filgastrim, and 15% needed a red blood cell transfusion. The mean overall cost of treatment was $83 851 per patient. The cost per SVR was $172 889; $266 670 for patients with cirrhosis. The costs per SVR after treatment with first-generation DAAs are dependent on the stage of disease and therapy side effects. These real-world costs significantly exceed those described in prior cost-effectiveness assessments and should be used instead for future studies. [ABSTRACT FROM AUTHOR]

Background Thrombocytopenia is a common hematologic toxicity among patients with chronic liver disease. Aim To give a brief overview of thrombocytopenia and its effects on patients with chronic liver disease. Results Thrombocytopenia is generally mild to moderate in severity and can thus be managed relatively easily. Severe thrombocytopenia (platelet count <50,000 /μL), however, may present significant challenges to patient management. Thrombocytopenia can increase the risk of bleeding associated with invasive or surgical procedures. Therefore, while perhaps less widely appreciated than the impact of anemia or neutropenia, effective prevention and management of thrombocytopenia is also critical for patients with liver disease. Conclusions This supplement to Alimentary Pharmacology & Therapeutics provides a comprehensive review of the significance of thrombocytopenia in patients with chronic liver disease, its pathophysiology and relationship to coagulation disorders, impact on clinical care and resource utilization, and novel therapies that may be able to supplant platelet transfusions. [ABSTRACT FROM AUTHOR]

Background Patients with chronic liver disease and hepatitis C virus (HCV) frequently experience thrombocytopenia that complicates the management of their disease. Traditional therapy for thrombocytopenia consists of platelet transfusion, which can be associated with significant safety and economic issues. Consequently, efforts have been directed toward developing novel approaches for the treatment of thrombocytopenia. Aim To summarize the available data on the limitations of traditional therapies and the effects of novel therapies currently in clinical development for the treatment of thrombocytopenia. Results Recent research has begun to reveal the complex mechanisms that regulate thrombopoiesis. Cytokines and growth factors, such as interleukin-11 and thrombopoietin (TPO), play a key role in the production of platelets. A number of recent clinical studies have provided evidence that pharmacologic agents that target megakaryocyte precursors and stimulate thrombopoiesis can effectively reverse thrombocytopenia. Here, we review the regulation of thrombopoiesis, the role of TPO, and a number of novel compounds that stimulate platelet production by acting through the TPO receptor. Agents that stimulate TPO include the orally available nonpeptidic agonists eltrombopag and AKR-501, peptidic agonists AMG-531 and Peg-TPOmp, and small engineered antibodies. Conclusion Results from clinical trials with these agents in healthy subjects confirm that activation of thrombopoiesis via the TPO pathway is an effective method of stimulating platelet production. This approach may provide safer, more effective treatment for thrombocytopenia in patients with chronic liver disease. Several of these agents are currently being tested in large scale trials. [ABSTRACT FROM AUTHOR]

Mucus is the viscoelastic secretion that lines, most epithelial surfaces forming a protective, lubricating barrier. The viscoelastic properties of mucus arise from mucin, a glycoprotein of molecular weight ranging from 2-10 million. In this paper we address two problems where the aggregation and interactions of mucin with colloidal particles is of physiological relevance. The first deals with gastric mucin and the question of the mechanisms that prevent the stomach from digesting itself. Using dynamic light scattering techniques we show that solutions of gastric mucin aggregate below pH 4. Very large aggregates with 100-fold slower diffusion constants than the mucin monomer are observed at pH 2. Viscosity measurements indicate that mucin will eventually gel at low pH, thus acting as a diffusional, barrier and protecting the stomach. The second problem is concerned with the role of mucin in the nucleation of cholesterol crystals which lead to gallstone formation. Using dynamic light scattering we have shown that mucin at relatively low concentrations (4 mg/ml) promotes the fusion of phospholipid + cholesterol vesicles. The time evolution of the fusion process was measured. No changes in the aggregation state of the gallbladder mucin were observed during the fusion process, suggesting that this phenomenon is related to physico-chemical interactions between the polymer (mucin) and the colloidal particle (vesicle). [ABSTRACT FROM AUTHOR]

Previous studies have shown that portal venous pressure increases in patients with cirrhosis after a protein meal. Since this increase may be mediated by an increase in hepatic blood flow or postsinusoidal hepatic vascular resistance, the present study was designed to examine the precise relation between the postprandial changes in these three variables in patients with cirrhosis and portal hypertension. Estimated hepatic blood flow (EHBF; indocyanine green clearance), portosystemic gradient (PSG; wedged free hepatic venous pressure), and postsinusoidal hepatic vascular resistance (PSR = PSG/EHBF) were measured simultaneously before and at 10 minute intervals after a high protein meal, containing 80 g protein, 40 g carbohydrate and 12 g fat (600 kcal) in nine patients (seven alcoholic, two non-alcoholic) with cirrhosis and portal hypertension. After the meal, the portosystemic gradient increased by 33% from mean (SEM) 15.6 (0.9) mm Hg to 20.7 (1.3) mm Hg, (p less than 0.01; Wilcoxon signed ranks test) within 30 minutes. Coincident with this increase in portosystemic gradient, estimated hepatic blood flow increased by 69.2% from 20.1 (1.7) ml/min/kg to 33.9 (2.5) ml/min/kg (p = 0.01), peak values occurring at 25 minutes, at which time the postsinusoidal hepatic vascular resistance had decreased by 31% from 1.10 (0.1) 10(-2) mm Hg/ml/min to 0.8 (0.5) 10(-2) mm Hg/ml/min (p = 0.01). These results suggest that the postprandial increase in portal venous pressure in patients with cirrhosis is mediated by an increase in hepatic blood flow and modified by a simultaneous decrease in postsinusoidal resistance. [ABSTRACT FROM PUBLISHER]

Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found to be heat labile and only present in an acid environment. Addition of tranexamic acid or sucralfate to gastric juice almost completely reversed this effect, whereas pepstatin was only partially effective. It is probable that acid dependent proteases other than pepsin are responsible for the marked fibrinolysis. The ulcer healing agent sucralfate might be useful in those patients at risk of bleeding or rebleeding from active peptic ulcer disease. [ABSTRACT FROM PUBLISHER]

Carbohydrate absorption from 100 gm of starch flour and 13.5 gm of lactulose was measured in 8 patients with irritable bowel syndrome and 4 normal controls. A wide range of hydrogen production was demonstrated but no significant inter-group variability was seen. Antibiotic therapy successfully altered colonic handling of carbohydrate in IBS patients but with no improvement in symptom score. Oro-caecal transit time was significantly faster in diarrhoea patients, suggesting abnormal intestinal motility in these patients. Colonic carbohydrate handling is unlikely to be of primary pathogenic significance in IBS. [ABSTRACT FROM AUTHOR]

Recent reports suggest that sleep apnoea syndromes, which have excited much interest since first described (Gastaut et al, 1966) may be underdiagnosed (Apps et al, 1983). The associated cardiac arrhythmias are potentially lethal and may lead to sudden death at night (Stradling, 1982; Guilleminault et al, 1980). This case illustrates the presentation of a patient with nocturnal cardiac bradyarrhythmias and the subsequent diagnosis and successful treatment of an underlying sleep apnoea syndrome. [ABSTRACT FROM AUTHOR]

A prospective study was undertaken to examine the immunohistochemical expression of tumor antigen Cal9-9 in 56 colorectal cancers and 95 colonic adenomas, divided into 65 primary polyps and 30 polyps synchronous with colorectal cancer. Seventy five per cent of tumours were positive for Cal9-9. Antigen was expressed more frequently in advanced Duke's C and D and poorly differentiated colorectal cancer. Overall 51% of adenomas were positive for Cal9-9. Antigen expression correlated significantly with increasing size (p less than 0.001), synchronicity with colorectal cancer (p less than 0.001), severe dysplasia (p less than 0.001) and villous typing (p less than 0.003). Discriminate analysis using the first three variables correctly classified 79% of positive and 89% of negative Cal9-9 results. The similar frequency of antigen expression seen in colorectal cancers and their synchronous adenoma suggests a field change in the tumour bearing colon. Adenomas positive for Cal9-9 may have a greater malignant potential for carcinomatous change. [ABSTRACT FROM PUBLISHER]

A response from the authors of the article "Aspirin use is associated with lower indices of liver fibrosis among adults in the United States" the 2016 issue is presented.

This article presents a question and its answer related to unusual cause of abdominal pain in a patient with hepatitis C cirrhosis. A 51-year man with a history of hepatitis C cirrhosis presented with a two-day history of lever, malaise, abdominal distension, and severe abdominal pain in his right upper quadrant. On examination he had significant tenderness and guarding in his right upper quadrant. He was taken to the operating room for an exploratory laparotomy that revealed a severely inflamed, enlarged, and indurated right hemicolon, without perforation.

WE compared the prevalence of serological markers of hepatitis B virus infection, hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb), in 98 alcoholics and 110 medical patients. HBsAg was not detected in either group. HBcAB was present in the serum of 7/98 alcoholics and in 5/110 medical patients (p=n.s.). This study suggests that when alcoholics are compared with a similar population receiving medical care for other reasons there is a similar prevalence of serological markers indicating previous exposure to hepatitis B virus. [ABSTRACT FROM AUTHOR]

Ca-19-9 and CEA were measured in serum from patients with a variety of malignancies. Ca-19-9 was elevated in 97% of 30 patients with pancreatic carcinoma and 53% of 15 patients with gastric carcinomas. The main advantage of Ca-19-9 over CEA as a marker for gastrointestinal malignancy is the low number of false positive elevations in patients with benign gastrointestinal disease. It is concluded that Ca-19-9 is the best presently available biochemical marker for cancer of the pancreas. [ABSTRACT FROM AUTHOR]