Reviews on Recent Clinical Trials - Volume 11, Issue 3, 2016

Alcohol represents the oldest substance of abuse known and Alcoholic Liver Disease (ALD) is the most common cause of chronic liver disease worldwide. The ALD includes a wide spectrum of injury and may lead progressively from simple steatosis to frank cirrhosis. The ALD diagnosis may be hard and it is mainly defined by the history of chronic alcohol intake, physical and laboratory abnormalities suggestive of liver disease. Abstinence is the cornerstone of ALD therapy. Although the burden on health of ALD is not negligible, in the last decades few therapeutic advances have been made. Because of the complex pathogenetic mechanisms, the therapy of ALD and especially of severe Alcoholic Hepatitis (AH), represents a thorny problem in the clinical practice. In severe forms of acute AH, some specific drug treatments, including glucorticoids or pentoxifylline, have been defined and are, at the moment, recommended by international guidelines. On the contrary, specific long-term treatments of ALD, aimed at stopping the progression of fibrosis, are not yet approved.

Alcohol represents the oldest substance of abuse known, existed at least as early as the Neolithic period. In the present era, almost half of the world’s population consumes alcohol and it represents the third largest risk factor for disease and disability and the most prevalent cause of advanced liver disease worldwide. In fact, when alcohol consumption reaches “unsafe quantities” an Alcoholic Liver Disease (ALD) is very likely. ALD comprises a large spectrum of diseases, ranging from simple steatosis to steatohepatitis with fibrosis and cirrhosis. Alcohol related cirrhosis is responsible of almost 50% of all cirrhosis-related and 1% of all-cause deaths worldwide. Even if ALD and alcoholic cirrhosis represent a large part of liver diseases, to know exactly the global burden of these phenomena is very difficult. This is mostly due to diagnostic and nosological issues, being ALD represented by several types of diseases and the diagnosis very often based on voluntary questionnaires. Also the natural history of ALD is somewhat difficult to predict, since there is not a definite evolution between the various stages of the disease and, indeed, they may coexist in a single subject. In this brief review we will report on the global burden of ALD, the principal factors influencing its prevalence among populations and the different presentations of its natural history.

Liver biopsy due to the limitations is not recommended for all patients with suspected Alcoholic Liver Disease (ALD) but useful for establishing the stage and severity of ALD, in case of aggressive forms or severe steatohepatitis requiring specific therapies, for distinguishing comorbid liver pathology. Procedure is invasive and that’s why associated with some potential adverse effects and complications which may be minor (pain or vagal reactions, transient hypotension) or major such as visceral perforation, bile peritonitis or significant bleeding. The typical histological features in patients with ALD include steatosis, hepatocellular damage (ballooning and/or Mallory-Denk bodies), lobular inflammation with basically polymorphonuclear cells infiltration, with a variable degree of fibrosis and lobular distortion that may progress to cirrhosis which confers a high risk of complications (ascites, variceal bleeding, hepatic encephalopathy, renal failure and bacterial infections).

Alcohol is considered one of the most common hepatotoxin, and chronic alcoholic liver disease is affecting millions of subjects worldwide. The three most frequently manifestations of alcoholic liver disease are steatosis, acute alcoholic hepatitis and liver cirrhosis. The diagnosis of Alcoholic Liver Diseases (ALD) is made by clinical and laboratory analysis. Actually do not exist a single laboratory test able to confirm the diagnosis of ALD, but in the last years several serum markers and laboratory abnormalities have been discovered in these patients. In particular the combination of tests and markers can increase the diagnostic accuracy, for this reason the last studies are focusing on the development of serum biomarkers panel able to diagnose alcohol-related liver damage.

The prevalence of Alcohol related Liver Disease (ALD) continues to rise all over the world due to changing drinking behaviour of the population. Liver disease due to excessive alcohol consumption causes significant morbidity and mortality, and poses a substantial economic burden to the health care resources. Early diagnosis and treatment of ALD may help prevent progression to cirrhosis and hepatocellular carcinoma. The last decade has seen a rising interest in potential use of non-invasive tests in clinical practice, including diagnosis and monitoring of chronic liver diseases. Over the past few decades, breath testing has been investigated extensively in the diagnosis of ALD, and has shown promising results in predicting the early stages of ALD. A variety of breath tests have been utilised in this regard including the13Clabelled breath tests, aminopyrine breath test , galactose breath test , methacetin breath test, and keto-isocaproic acid breath test. These tests have demonstrated good results in identification of both significant and severe liver disease among patients with ALD. Volatile Organic Compounds (VOC) are chemicals, which can be quantified in breath and other biological fluids, and represent physio-pathological activities within an individual. Alteration in the pattern of breath VOCs can be correlated with a number of diseases including ALD. Early stages of ALD can be detected using these breath tests, which can lead to adoption of preventive measures to reduce the progression of liver disease. This review focuses on the clinical utility of current and future breath tests, including breath VOC, as a non-invasive means of predicting early stages of ALD.

The Gastrointestinal (GI) tract is one of the most affected systems by alcohol consumption. Alcohol can affect the esophagus in several ways: induces mucosal inflammation, increases the risk for Barrett esophagus and esophageal cancer, and also impairs the esophageal motility. Numerous studies have reported an increased prevalence of Gastroesophageal Reflux Disease (GERD) or erosive esophagitis in alcoholics. Some alcoholics exhibit an abnormality of esophageal motility known as a “nutcracker esophagus”. Alcohol effect on gastric motility depends on the alcohol concentration. In general, beverages with high alcohol concentrations (i.e., above 15 percent) appear to inhibit gastric motility and low alcohol doses (wine and beer) accelerate gastric emptying. Also, acute administration of ethanol inhibits the gastric emptying, while chronic administration of a large dose of alcohol accelerates gastric motility. The effect of alcohol on small bowel motility differs according to the type of consumption (acute or chronic). Acute administration of alcohol has been found to inhibit small bowel transit and chronic administration of a large dose of alcohol accelerates small bowel transit. This article reviews some of the below findings.

Alcohol, in addition to well-known damages on the liver and pancreas, produces direct and indirect injuries in the mucosa of the oesophagus, stomach, small intestine and large bowel. Different damages can be produced both when a large amount of alcohol is acutely drunk and when this is taken chronically. Almost all these lesions can be detected and treated by endoscopy as shown in the present article. When, over time, cirrhosis ensues the role of endoscopy is not different from that played with cirrhosis of different etiology. Beside hemorrhagic episodes, esophagitis, gastritis and cancer are the main alcohol related diseases that can be managed by endoscopy.

Alcoholic and virus C hepatitis currently represent the main causes of chronic liver disease worldwide. Every year many people die and are subjected to complex hospitalization and medical assistance due to these pathologies. Alcoholic liver disease and hepatitis C virus chronic infection are often present in the same patient. These two pathologies sinergically act in determining the onset and progression of liver damage that, from the chronic hepatitis staging, may rapidly progress to fibrosis, cirrhosis and hepatocellular carcinoma. In this review we analysed physiopathological aspects and biomolecular interactions that relate ethanol and hepatitis C virus in determining liver damage; moreover we took into account the effect on the natural history of liver disease deriving from the co-presence of these pathologies. Therefore we paid particular attention to the ability of ethanol and hepatitis C virus to in inducing oxidative stress or lipid accumulation, and analyzed the basic mechanisms of fibrogenesis that both diseases have got, amplified by their co-presence in the same patient. Finally we paid attention to the oncogenetic mechanisms inducing hepatocellular carcinoma and variability of response to antiviral therapy that derives from alcohol abuse in a subject affected by C hepatitis.

Background: Chronic ethyl alcohol consuming is well known independent negative predictor of unfavorable natural course and therapy outcome of Chronic Hepatitis C (CHC) infection. Objective: The aim of the present study was to clarify the impact of alcohol consumption on fibrosis rate progression in patients with CHC and Sustained Virologic Response (SVR) rates in patients undergoing treatment with pegylated interferon and ribavirin. Method: This cross sectional retrospective study included 807 CHC patients underwent liver biopsy and hospitalized at Clinical center of Vojvodina, Novi Sad, Serbia. According to the alcohol consumption equal or greater than 50 g/day prior to liver biopsy, patients were divided into two groups. We compared demographic, clinical, virologic and histopathological markers of CHC, as well as response to antiviral therapy. Results: We find statistically significant difference (p=0.001) in gender, but not in age (p=0.081), estimated duration of the CHC (p=0.470) and hepatitis C genotype (p=0.545) between two groups. Among patients with CHC who consume alcohol ≥50 g/day there were significantly higher incidence of intravenous drug users (p=0.000). Binary logistic regression showed that the only independent predictors of moderate to severe fibrosis (fibrosis ≥2) were age (p=0.000) and alcohol use (p=0.027). There was not statistically significant difference in SVR rate between two groups (p=0.810). Conclusion: We believe that this good result in treatment outcome was the consequence of proper selection of patients based primarily on regulations of Republic of Serbia on the necessity of abstinence from the use of alcohol and psychoactive substances at least one year before starting antiviral therapy.

The gut–liver axis model has often explained liver disease physiopathology. Among the latter we can mention Non-Alcoholic Liver Steatosis (NAFLD), Liver Steatohepatitis (NASH), liver cirrhosis. In this frame an altered Intestinal Permeability (IP) is the gate for antigenic/toxic substances from gut lumen until target organs such as liver in NAFLD. Altered intestinal permeability was discovered almost forty years ago as consequence of acute and chronic alcohol ingestion. Alcohol Liver Disease (ALD) is a systemic pathology whose beginning and end belong to the intestine. Several recent evidences from the literature show how gut microbiota composition can be altered by alcohol, affects IP and can be modulated by several nonpharmacological and pharmacological agents, becoming the target for ALD treatment. In this review we describe the definition of ALD, gut microbiota composition in healthy and ALD, definition and role of IP in ALD physiopathology and emerging evidences on gut microbiota modulation in ALD treatment from preliminary clinical and non-clinical studies.

Background: Alcoholic Liver Disease (ALD) can be defined as the hepatic manifestations caused by excessive alcohol intake. ALD comprises a spectrum from simple steatosis to cirrhosis. Objective: To review diverse clinical and metabolic characteristics and their impact in ALD. Conclusion: The concurrence of metabolic alterations, including obesity and diabetes, and alcohol consumption increase the risk of liver injury and also the morbidity and mortality associated with chronic liver disease.

Alcoholism is currently listed as the third leading cause of death. Chronic alcohol consumption brings serious medical complications like gastrointestinal, cardiovascular, musculoskeletal, respiratory system disorders. Liver can be seriously damage by alcohol misuse. Alcoholic Liver Disease (ALD) is the first important warning sign of alcohol abuse. Since effective therapies for ALD are still limited, natural products in the treatment of ALD become very important. In this regard, there have been done very few clinical trials with poor results. Silymarin, glycyrrhizin, garlic show some promising results in ALD patients while the in vivo and in vitro studies with green tee, quercetin and curcumin indicate positive effect on patients with ALD.

Hepatocellular Carcinoma (HCC) is a major healthcare problem. Almost ninety percent of HCCs develops on cirrhosis due to chronic viral hepatitis, Non-Alcoholic Steatohepatitis (NASH) and alcohol abuse. Alcohol itself is defined a strong human carcinogenic agent. Some genetic polymorphisms in alcohol-metabolizing systems and more recently, some sequence variations within the genes coding for patatin-like phospholipase encoding 3 (PNPLA3) and Transmembrane 6 superfamily 2 (TM6SF2), have been found to promote liver fibrosis in alcohol abuse, until HCC development. The current management of HCC is related to tumor burden and liver function and it does not differ in alcoholics, although in alcoholics the surveillance for HCC could be less effective because socioeconomic context, such as the recall policy, the stage at the diagnosis and the prognosis are not different compared to viral HCCs. On regards of loco-regional treatment options, there have not been significant advances in the last few years, though an increasing role will be probably reserved to radio embolization and irreversible electroporation in the next future. Sorafenib (SOR) is still the only drug approved as systemic therapy in patients with HCC, whereas immunotherapy represents a promising approach for the treatment of HCC.

Alcoholic Liver Disease (ALD) represents the second most common indication for Liver Transplantation (LT) worldwide. Outcomes of LT for ALD are comparable with those of liver transplantation for other aetiologies of liver disease; however, it's still considered a controversial indication to LT, mainly because ALD is considered a self inflicted disease, and for the risk of relapse after LT. Most transplant programs require 6 months of abstinence in order to consider a patient suitable for LT, however the role of the length of pre transplant abstinence as predictor of alcohol relapse after LT is still controversial. A psycho-social assessment to establish the likelihood of long-term abstinence after LT should be performed in patients with ALD potential candidates for LT. Acute alcoholic hepatitis is considered a contraindication to transplantation in most transplant centers. However, early LT, in selected patients, with a first episode of severe alcoholic hepatitis not responding to medical therapy, has been shown to improve survival. Further studies are needed to better assess the risk of alcohol relapse after LT in patients with acute alcoholic hepatitis.

Currently, many novel therapies are available for physicians treating cancer; some of them are associated with adverse cardiac events. One of the most worrisome cardiac event is QT prolongation, which is a risk factor for developing the potentially fatal torsade de pointe. Many classes of drugs, both anticancer and concomitant agents, are involved in this issue. We report a review of old and new commonly used agents with torsadogenic potential.

Introduction: Adverse Drug Reactions (ADRs) are common in hospitalized oncology patients. The kinds of ADRs experienced by cancer patients are varied. Therefore, the identification of appropriate manner in order to prevent ADRs may improve patient outcome. Aims: The present study evaluated the incidence, frequency and common types of adverse drug reactions among hospitalized oncology patients. Methods: Patients hospitalized at a university oncology center (children and adult) during the calendar year 2012 were randomly selected. Data were collected by reviewing of medical records. The outcome measures included the incidence of observed ADRs and ADR-related admissions and achieving strategies to prevent the emergence of chemotherapy side effects. Results: ADRs frequently occurred in the age group less than 20 years (22%). Prevalence of leukemia (27%), colon cancer (16.5%) and breast cancer (14%) was higher in our region. Most ADRs were recorded in patients receiving cisplatin (44%), doxorubicin (24%) and 5-fluouracil (20%) as chemotherapy. The most frequently observed ADRs were nauseavomiting, neutropenia and constipation in both pediatric and adult population. Conclusion: This study shows that ADRs occur more frequently in the pediatric group compared to adults. Therefore, optimum use of preventative strategy program may contribute to reducing the incidence and severity of ADRs especially in this group.

Introduction: We propose in this study to analyze the results obtained in the experience of Dar El Amal by comparing the two age groups 45-49 years versus over 50 years. This experience of Dar Al Amal was started in Sfax (Tunisia) in 2004. The project had included women over a period of six and a half years. The target population was all women over the age of 45 years. Results: In the period of the study, 10 000 women had at least one mammography within the first round in Dar El Amal. The average age was 51.56 years. The recall rate was more important in women aged 45-49 years compared with those over 50 years with a statistically significant relationship (p=0.013). Tests classified ACR0 and ACR3 predominated in women aged between 45 and 49 years with a statistically significant relationship. The positive predictive value (PPV) of mammography was better in those over 50 years (p=0.012). Conclusion: The majority of countries in the world opt for screening from the age of 50 years. Women under 50 years are not routinely concerned, but they have more right to a targeted and appropriate screening.