OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.

METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 mg containing 94% pure EGCG, blood for EGCG levels and safety parameters was ascertained at 2, 4, and 10 hours.

RESULTS: C(max) and AUC to EGCG overlapped among the 3 groups, which suggests that the disposition of EGCG was not significantly altered in these patients with cirrhosis.

CONCLUSIONS: A single 400-mg oral dose of EGCG was safe and well tolerated by all of the patients in the study. These results provide guidance for the continued investigation of the long-term safety and antitumor potential of EGCG in cirrhotic patients with HCV.

Acrochorda (skin tags) are benign skin tumors that form primarily at skin creases, generally on the neck, armpit, and groin areas. There have been a small number of published studies in 1980s in patients who were found to have increased number of skin tags and colonic polyps, with a direct correlation described between the two. In addition, metabolic syndrome has been linked to adenomatous polyps, but a link between skin tags and metabolic syndrome has not been established.

The incidence of esophageal adenocarcinoma (EA) has increased more rapidly than any other cancer (with the exception of malignant melanoma) in the United States over the past 30 years. Gastroesophageal reflux disease (GERD) is the strongest risk factor for the development of Barrett’s esophagus, which in turn leads to the rise of most EA’s. In a large portion of persons with sleep disorders, perhaps as high as 30%, GERD is a major causal or contributing factor. It has been proposed that the use of hypnotics for the treatment of sleep disorders may exacerbate the damaging effects of refluxate on the esophageal epithelium by reducing the frequency and effectiveness of normal clearance mechanisms (figure 1).

METHODS: We studied the effects of IgGs purified from patients with SSc (SScIgGs) on cholinergic nerve stimulation in rat colon tissues. We also examined the effects of SScIgGs on M(3)-R activation by bethanechol (BeCh), M(3)-R occupancy, and receptor binding using immunofluorescence, immunoblot, and enzyme-linked immunosorbent analyses of human internal anal sphincter (IAS) smooth muscle cells, before and after administration of pooledhIgG. Functional displacement of M(3)-R occupancy by the SScIgGs was compared with that of other IgGs during the sustained phase of BeCh-induced contraction of intact smooth muscles from rats.

RESULTS: SScIgG significantly attenuated neurally mediated contraction and acetylcholine release in rat colon as well as BeCh-induced sustained contraction of the IAS smooth muscle. In immunofluorescence analysis, SScIgG co-localized with M(3)-R. In immunoblot and enzyme-linked immunosorbent analyses, M(3)-R loop-2 peptide and human IAS SMC membrane lysates bound significant amounts of SScIgG, compared with IgGs from healthy individuals and pooledhIgG. Binding was attenuated significantly by application of pooledhIgG, which by itself had no significant effect. Incubation of samples with pooledhIgG, or mixing pooledhIgG with SScIgG before administration to tissues, significantly reduced binding of SScIgG, indicating that pooledhIgG prevents SScIgG blockade of M(3)-R.

CONCLUSIONS: In studies of rat and human tissues, pooled human IgG prevent and reverses the cholinergic dysfunction associated with the progressive gastrointestinal manifestations of SSc by neutralizing functional M(3)-R antibodies present in the circulation of patients with SSc.

Purpose: The Accreditation Council for Graduate Medical Education (ACGME) next accreditation system (NAS) provides incentive for medical educators to understand and implement competency-based medical education (CBME) training and assessment in their programs. Noting decreasing enrollees for the American Board of Internal Medicine (ABIM) Transplant Hepatology (TH) exam, workforce concerns in TH, and questionnaire data from Gastroenterology (GI) fellows and Program Directors (PDs), we developed an ABIM-approved one-year competency-based TH pilot program.

METHODS: We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.

RESULTS: Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls (median, 0.20; range, 0.01-1.60) (P = 0.003). Consistently, longer RTLs conferred a significantly increased HCC risk compared to short RTLs in a univariate logistic regression analysis (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.02-2.33, P = 0.038). This association attenuated after multivariate adjustment (OR = 1.40, 95% CI = 0.90-2.19, P = 0.132). In a quartile analysis, a significant dose-response relationship was noted in univariate analysis (P(trend) = 0.017) which was again attenuated in multivariate analysis (P(trend) = 0.079). Further analyses revealed that the significant association between serum RTL and HCC risk was evident in non-cirrhotic (OR = 3.54, 95% CI 1.58-7.93 P = 0.002), but not cirrhotic (OR = 0.95, 95% CI 0.55-1.64, P = 0.860) HBV patients. Moreover, the significantly increased HCC risk conferred by cirrhosis was modulated by RTL with a significant interaction effect (P(interaction) = 0.013).

CONCLUSIONS: RTL in circulating cell-free serum DNA could potentially be used as a novel non-invasive biomarker for non-cirrhotic HCC. Prospective cohort studies are warranted to validate this finding and assess its clinical significance in HCC prevention.

Backgrounds and Aims:

The gastrointestinal (GI) tract is the most common internal organ system affected in SSc. We and others have shown before that the SSc immunoglobulins (IgGs) cause selective blockade of muscarinic type-3 cholinergic (M3-R) in the GI tract. Presently, there is no effective treatment for SSc although numerous cytotoxic and immunomodulatory agents have been employed with limited success and are marred with serious side effects. Present studies investigated the reversibility of SScIgGs-caused M3-R blockade by the pooled Intravenous immunoglobulins (IVIG).

Background and Aims:

Rectoanal incontinence is associated with defective Internal Anal Sphincter (IAS). Current therapies are not satisfactory, raising a potential for the replacement of the dysfunctional IAS with the reconstructs. Present studies were performed to develop human IAS smooth muscle reconstructs with functional and molecular attributes similar to the intact human IAS Smooth muscle (SM).

Background and Aims

Knowledge of molecular control mechanisms underlying the basal tone in the intact human IAS is critical for the pathophysiology and rational therapy for debilitating rectoanal motility disorders.

The patient presented below gives us the opportunity to discuss balloon-occluded retrograde transvenous obliteration (BRTO) for treatment of gastric varices. Although described since the mid-1990s and accepted as effective therapy, particularly in Japan, BRTO is used sporadically in the United States and Europe. In fact, it is not mentioned in the U.S. (AASLD) or European (EASL/Baveno V) guidelines. Hopefully, increased awareness of and expertise in this modality will generate the evidence-based data needed to establish the role and safety of BRTO in patients with gastric varices.

1. Self-reported adherence with published guidelines for HCC screening is poor among primary providers for HIV/HCV coinfected patients, including HIV specialists and University-based providers.

2. Unnecessary imaging is also frequently ordered on non-cirrhotics, particularly by University-based providers.

3. Improved adherence to guidelines is needed among primary providers as over 50% of HCC's may be missed, and many patients many not be referred for subspecialty GI or Liver care, where screening practices may differ.

1. The majority of primary providers were ambivalent toward or against LT for HIV/HCV coninfected patients.

2. Half of all respondents were unlikely to refer cirrhotic coinfected patients for LT evaluation.

3. HIV specialists were significantly more likely to believe transplant should be offered, but reported no difference in likelihood of LT referral.

4. These findings suggest that primary provider beliefs and self-reported practice patterns may partially explain the paucity of coinfected US liver transplant recipients.

Methods: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups.

Results: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (P = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different.

Conclusion: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL

Hepatorenal syndrome (HRS) is a relative contraindication to receiving gadolinium-based contrast media secondary to risk of nephrogenic systemic fibrosis (NSF)

Patients with cirrhosis frequently undergo magnetic resonance imaging (MRI) for hepatocellular cancer screening and liver transplant evaluation.

Most centers require documented serum creatinine levels within 10-14 days of performing MRIs on patients with cirrhosis.

Ascites can be readily detected on MRI without contrast enhancement.

Objective:

To determine whether the presence of ascites on MRI can be used to recommend against a diagnosis of HRS without knowledge of a serum creatinine level.