Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older.

INTRODUCTION AND OBJECTIVES: Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies (OT-0401, REVERSE, CONFIRM). PATIENTS AND METHODS: The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal-defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 µmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death-and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events. RESULTS: Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data. CONCLUSIONS: Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome. CLINICAL TRIAL NUMBERS: OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT02770716.

Evaluation of INK4A promoter methylation using pyrosequencing and circulating cell-free DNA from patients with hepatocellular carcinoma.

BACKGROUND: Hyper-methylation of CpG dinucleotides in the promoter region of inhibitor of cyclin-dependent kinase 4A (INK4A) has been reported in 60%-80% of hepatocellular carcinoma (HCC). As INK4A promoter hypermethylation event occurs early in HCC progression, the quantification of INK4A promoter methylation in blood sample may represent a useful biomarker for non-invasive diagnosis and prediction of response to therapy. METHODS: We examined INK4A promoter methylation using circulating cell-free DNA (ccfDNA) in a total of 109 serum specimens, including 66 HCC and 43 benign chronic liver diseases. Methylation of the individual seven CpG sites was examined using pyrosequencing. RESULTS: Our results showed that there were significantly higher levels of methylated INK4A in HCC specimens than controls and that the seven CpG sites had different levels of methylation and might exist in different PCR amplicons. The area under receiver operating characteristic (ROC) curve was 0.82, with 65.3% sensitivity and 87.2% specificity at 5% (LOD), 39.0% sensitivity and 96.5% specificity at 7% LOD, and 20.3% sensitivity and 98.8% specificity at 10% LOD, respectively. CONCLUSIONS: Our results support additional studies incorporating INK4A methylation testing of ccfDNA to further validate the diagnostic, predictive, and prognostic characteristics of this biomarker in HCC patients. The knowledge of the existence of epi-alleles should help improve assay design to maximize detection.

Cholangitis Lenta: What Hepatologists Need to Know.

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Direct-Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis.

Patients with hepatitis C virus (HCV) often have elevated serum markers and histologic features of autoimmune hepatitis (AIH). We evaluated an HCV-positive (HCV+) study group that had elevated serum markers of AIH before starting direct-acting antiviral (DAA) therapy (n = 21) and compared them to an HCV+ control group that did not have laboratory studies suggesting AIH (n = 21). Several patients in the study (17/21) and control (11/21) groups had liver biopsies before DAA treatment, and many were biopsied due to elevated serum markers of AIH. Evaluation of pre-DAA treatment liver biopsies showed histologic features suggestive of AIH in 64.7% (11/17) of the study group and 45.5% (5/11) of the control group. Patients who were HCV+ with elevated serum markers of AIH had significantly increased hepatitis activity (P < 0.001) and slightly increased fibrosis stages (P = 0.039) in their pretreatment liver biopsies compared to controls. We hypothesized that the elevated serum markers and histologic features of AIH would resolve following DAA treatment. Serum markers of AIH in the study group began decreasing by 6 months posttreatment, and 52.4% (11/21) had complete resolution. Alanine aminotransferase levels significantly decreased into the normal range for all patients (21/21). Even patients that had persistence of serum markers of AIH after DAA treatment had normal transaminases. Six patients from the study patient group and 4 patients from the control group had follow-up liver biopsies after DAA treatment, and all biopsies showed resolution of the histologic features of AIH. Conclusion: The majority of HCV+ patients that have serum markers and/or histopathologic features of AIH should initially be treated with DAA.

Budd-Chiari syndrome: a rare and life-threatening complication of Crohn's disease.

Budd-Chiari syndrome (BCS) is characterised by obstruction of hepatic venous outflow and may be triggered by the prothrombotic state associated with inflammatory bowel disease (IBD). We reported a case of Crohn's disease (CD) that presented with anasarca, ascites, symptomatic hepatomegaly, elevated liver enzymes, increased prothrombin time and low albumin. Oesophagogastroduodenoscopy and colonoscopy confirmed active CD. Abdominal CT showed hepatic vein thrombosis. Liver biopsy revealed severe perivenular sinusoidal dilation with areas of hepatocyte dropout, bands of hepatocyte atrophy and centrizonal fibrosis, suggestive of BCS. The patient was treated with steroids for CD and systemic anticoagulants for BCS. His liver function and enzymes normalised, and he reported symptomatic improvement. The precise mechanism responsible for increased hypercoagulability in IBD remains unclear. Early recognition and treatment for possible thrombotic complications of CD is critical to prevent potentially fatal events like pulmonary embolism or liver failure.

HIV infection and the liver: the importance of HCV-HIV coinfection and drug-induced liver injury.

Hepatitis C virus-Human immunodeficiency virus (HCV-HIV) coinfections are identified in up to 30% of patients infected with HIV and in 8% of patients infected with HCV. Now that progression of HIV and deaths due to AIDS can be prevented by highly active antiretroviral therapy (HAART), it is clear that HCV coinfection is associated with accelerated progression to cirrhosis and increased liver-related morbidity and mortality. Antiviral therapy with pegylated interferon and ribavirin for HCV in HCV-HIV coinfected patients is less successful than in patients with HCV monoinfection, and HAART can cause drug-induced liver injury. Multiple barriers limit the number of HCV-HIV coinfected patients who receive antiviral therapy for HCV, and the role of orthotopic liver transplantation (OLT) in HIV monoinfected and HCV-HIV coinfected patients remains controversial. Clinical trials of HCV-specific protease or polymerase inhibitors combined with pegylated interferon and ribavirin are needed urgently in coinfected patients, both before and after OLT.

Endoscopic approaches for palliation of luminal gastrointestinal obstruction.

Much of the workload of a typical gastroenterologist is devoted to screening patients for gastrointestinal malignancies. Efforts such as colorectal cancer screening via colonoscopy and endoscopic surveillance of patients with Barrett's esophagus are widespread and widely endorsed. In recent years, the armamentarium of endoscopy has broadened considerably and now affords physicians a variety of nonsurgical means to palliate malignant obstruction of the gastrointestinal tract. This article reviews endoscopic techniques to treat malignant esophageal, biliary, small bowel, and colonic obstruction.