Mohannad Dugum

Hepatitis C virus: Here comes all-oral treatment

Treatment for chronic hepatitis C virus (HCV) infection is evolving rapidly. The approval in 2013 of two new directacting antivirals—sofosbuvir (a polymerase inhibitor) and simeprevir (a second-generation protease inhibitor)— opens the door for an all-oral regimen, potentially avoiding interferon and its harsh side effects. Other direct-acting antivirals are under development. Direct-acting antiviral drugs open the door for an all-oral regimen, potentially eliminating the need for interferon and thus avoiding its harsh side effects.

Sonic hedgehog signaling in hepatocellular carcinoma: A pilot study

Hedgehog signaling is involved in the pathogenesis of several tumor types; however, its role in hepatocellular carcinoma (HCC) has not been fully elucidated. Biomarkers that reflect tumor aggressiveness are of potential value in selecting HCC patients for liver transplantation (LT). The aim of the present study was to assess the tissue expression of sonic hedgehog (Shh) biomarkers in HCC and surrounding non-tumorous liver tissue, and to correlate this expression with HCC recurrence following LT. Patients who underwent LT for HCC at the Cleveland Clinic (Cleveland, OH, USA) between 2002 and 2006 were randomly selected for analysis. Tissue samples were retrieved from the explanted tumorous livers. Routine immunohistochemistry was used to detect three specific Shh pathway biomarkers: The ligand Shh, the receptor patched-1 (Ptch) and the transcription factor glioma-associated oncogene homolog 1 (Gli1). Computerized quantitative analysis was used to evaluate the expression levels of these markers in HCC and surrounding non-tumorous liver tissue. Analysis of variance was used to compare the differential tissue expression between patients with and those without HCC recurrence. A time-to-event analysis was performed to assess the association of hedgehog biomarker expression with the risk of HCC recurrence following LT. A total of 53 tissue specimens from 21 patients were analyzed. The mean patient age was 57±8 years and 86% of the patients were male. A total of 62% patients had hepatitis C virus infection, 14% had hepatitis B virus infection, 43% had alcoholic cirrhosis and 91% fulfilled the Milan criteria at the time of LT. The average follow-up time after LT was 36±15 months, during which 19% of the patients developed HCC recurrence and 29% died. Shh, Ptch and Gli1 were detected in the HCC tissues of all the patients. Ptch was overexpressed in HCC compared with the surrounding non-tumorous tissue. The statistical power of this study was unable to associate Shh pathway markers with HCC recurrence following LT. In a proof-of-concept study, we demonstrated tissue expression of three Shh biomarkers within HCC tumors, and also identified differences in Ptch expression between tumor and surrounding non-tumorous tissue. Further larger studies are required to assess the utility of these biomarkers in HCC.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Chronic constipation: Update on management

Managing chronic constipation involves identifying and treating secondary causes, instituting lifestyle changes, prescribing pharmacologic and nonpharmacologic therapies, and, occasionally, referring for surgery. Several new drugs have been approved, and others are in the pipeline. If conservative treatments fail, clinicians can choose from a growing list of new ones.

Hepatocellular Carcinoma in the Setting of Chronic Hepatitis B Virus Infection: Tumor Recurrence and Survival Rates After Liver Transplantation

BACKGROUND Higher rates of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection have been reported. This can influence their selection for LT and post-LT monitoring. OBJECTIVE The aim of this work was to compare the rates of post-LT HCC recurrence and survival in HBV and non-HBV patients with the use of the United Network for Organ Sharing (UNOS) database. METHODS After accessing the UNOS database, we analyzed patients with HCC stage T2 who underwent LT from cadaveric donors on or after August 24, 1998. Propensity score matching based on age, Model for End-Stage Liver Disease (MELD), and donor risk index was used to match HBV-HCC patients to HCC patients with other underlying liver diseases: hepatitis C virus (HCV), alcoholic liver disease (ALD), both HCV + ALD, and nonalcoholic steatohepatitis (NASH). Kaplan-Meier plots and multivariable analysis (with the use of propensity score, age, sex, and race) were used to assess post-LT HCC recurrence and overall survival. RESULTS A total of 4,480 HCC patients were matched. Their average age was 57 ± 7.8 years and average calculated MELD score was 13. Within 5 years of LT, 5.5% of patients had HCC recurrence and 20% died. HBV-HCC patients had 1.9 and 1.8 times higher hazard of tumor recurrence compared with ALD and NASH patients, respectively, and a 32% lower hazard of death than patients with HCV + ALD. There was no evidence of any other significant difference in HCC recurrence or survival among the etiology groups. CONCLUSIONS HCC recurrence and survival rates following LT for HCC patients with chronic HBV infection are similar to those of HCC patients with other underlying liver diseases. These findings support LT as a viable option for HCC-HBV patients.

Alcoholic hepatitis: Challenges in diagnosis and management.

Alcoholic hepatitis, in its severe form, is a devastating acute condition that requires early recognition and specialized tertiary medical care. This paper summarizes its epidemiology, pathophysiology, assessment, and treatment. Severe alcoholic hepatitis is a devastating acute condition that requires early recognition and specialized tertiary medical care.

Clinical outcomes of isolated renal failure compared to other forms of organ failure in patients with severe acute pancreatitis

AIM To assess differences in clinical outcomes of isolated renal failure (RF) compared to other forms of organ failure (OF) in patients with severe acute pancreatitis (SAP). METHODS Using a prospectively maintained database of patients with acute pancreatitis admitted to a tertiary medical center between 2003 and 2016, those with evidence of persistent OF were classified to renal, respiratory, cardiovascular, or multi-organ (2 or more organs). Data regarding demographics, comorbidities, etiology of acute pancreatitis, and clinical outcomes were prospectively recorded. Differences in clinical outcomes after development of isolated RF in comparison to other forms of OF were determined using independent t and Mann-Whitney U tests for continues variables, and χ2 test for discrete variables. RESULTS Among 500 patients with acute pancreatitis, 111 patients developed persistent OF: mean age was 54 years, and 75 (67.6%) were male. Forty-three patients had isolated OF: 17 (15.3%) renal, 25 (21.6%) respiratory, and 1 (0.9%) patient with cardiovascular failure. No differences in demographics, etiology of acute pancreatitis, systemic inflammatory response syndrome scores, or development of pancreatic necrosis were seen between patients with isolated RF vs isolated respiratory failure. Patients with isolated RF were less likely to require nutritional support (76.5% vs 96%, P = 0.001), ICU admission (58.8% vs 100%, P = 0.001), and had shorter mean ICU stay (2.4 d vs 15.7 d, P < 0.001), compared to isolated respiratory failure. None of the patients with isolated RF or isolated respiratory failure died. CONCLUSION Among patients with SAP per the Revised Atlanta Classification, approximately 15% develop isolated RF. This subgroup seems to have a less protracted clinical course compared to other forms of OF. Isolated RF might be weighed less than isolated respiratory failure in risk predictive modeling of acute pancreatitis.

Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy: a comparative study

Background and Aim: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. Methods: Search of the Cleveland Clinic’s CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. Results: Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn’s disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35–1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54–1.4; P = 0.58) between IBD and non-IBD patients. Conclusion: Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions.

Acute Alcoholic Hepatitis, the Clinical Aspects.

Alcoholic hepatitis is an acute form of alcoholic liver disease with variable severity that develops in patients who usually have a history of prolonged and recent alcohol abuse. The diagnosis is clinical and depends on history, physical examination, and laboratory derangements. Liver biopsy is diagnostic but not universally performed, and noninvasive diagnostic modalities are under development. Scoring systems are used to assess severity of disease, predict mortality, and guide decisions for initiation of specific therapies. The natural history and long-term outcomes of alcoholic hepatitis, including recurrence, progression to cirrhosis, and mortality, vary and depend partly on abstinence from alcohol use.

The Assessment and Management of Pain in Cirrhosis

Purpose of ReviewThe treatment of pain in patients with cirrhosis is complicated by unpredictable hepatic drug metabolism and a higher risk of adverse drug reactions. We aimed to conduct a scoping review regarding pain management in cirrhosis.Recent FindingsDespite the high prevalence of pain in patients with cirrhosis, there is little literature to guide the management of pain in this population. Complex pain syndromes and disease-specific pain etiologies are common in patients with cirrhosis. There are numerous contraindications and limitations when considering pharmacotherapy for analgesia in cirrhosis, specifically with nonsteroidal anti-inflammatory drugs and opioid medications. Non-pharmacologic therapies for pain have not been specifically assessed in this population.SummaryAs with other populations, a multi-dimensional treatment approach to pain with a focus on physical, behavioral, procedural, and pharmacologic treatment is recommended when caring for patients with cirrhosis and pain. However, more research is needed to evaluate opioid-sparing and non-pharmacologic analgesia in this population.