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Abstract
Alcohol abuse remains a significant problem world-wide. The most commonly affected organ remains the liver with a risk of alcoholic liver disease (ALD) which can range from asymptomatic to alcoholic hepatitis to alcoholic cirrhosis. In 2010, alcohol-attributable cirrhosis was responsible for 0.9% of all global deaths. Given the sheer magnitude of alcohol abuse and alcoholic liver disease, an update on this topic is pertinent and relevant. This issue will focus on a variety of topics including alcoholism, the pathogenesis of ALD, the spectrum of ALD, the pathology of ALD, and the long-term management of patients with ALD. Alcoholic hepatitis is a particular type of ALD with a high mortality. This issue will explore the syndrome of alcoholic hepatitis, its prognostic markers, and the available therapies. Because alcohol intake can influence so many other conditions of the liver (especially hepatitis C), articles in this issue will also explore the impact of alcohol abuse on other liver conditions. In addition, several other topics such as nutritional therapy for ALD, ALD and liver cancer, and ALD and infection risk will be explored. Also, even though it is quite controversial, we will also explore liver transplant as a therapy for alcoholic liver disease including alcoholic hepatitis.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Alcoholic Liver Disease | i | ||
| Copyright | ii | ||
| Contributors | iii | ||
| CONSULTING EDITOR | iii | ||
| EDITOR | iii | ||
| AUTHORS | iii | ||
| Contents | vii | ||
| Preface: Alcoholic Liver Disease | vii | ||
| Spectrum of Alcoholic Liver Disease | vii | ||
| Unhealthy Alcohol Use | vii | ||
| Pathogenesis of Alcoholic Liver Disease | vii | ||
| Diagnosis of Alcoholic Liver Disease: Key Foundations and New Developments | viii | ||
| The Pathology of Alcoholic Liver Disease | viii | ||
| Prognosis and Prognostic Scoring Models for Alcoholic Liver Disease and Acute Alcoholic Hepatitis | viii | ||
| Acute Alcoholic Hepatitis, the Clinical Aspects | viii | ||
| Acute Alcoholic Hepatitis: Therapy | ix | ||
| Alcoholic Liver Disease and Liver Transplantation | ix | ||
| Nutrition and Alcoholic Liver Disease: Effects of Alcoholism on Nutrition, Effects of Nutrition on Alcoholic Liver Disease, ... | ix | ||
| Long-Term Management of Alcoholic Liver Disease | ix | ||
| Alcoholic Liver Disease: High Risk or Low Risk for Developing Hepatocellular Carcinoma? | x | ||
| The Effects of Alcohol on Other Chronic Liver Diseases | x | ||
| Infection and Alcoholic Liver Disease | x | ||
| CLINICS IN LIVER DISEASE | xi | ||
| FORTHCOMING ISSUES | xi | ||
| November 2016 | xi | ||
| February 2017 | xi | ||
| May 2017 | xi | ||
| RECENT ISSUES | xi | ||
| May 2016 | xi | ||
| February 2016 | xi | ||
| November 2015 | xi | ||
| Preface:\rAlcoholic Liver Disease | xiii | ||
| Spectrum of Alcoholic Liver Disease | 419 | ||
| Key points | 419 | ||
| INTRODUCTION | 419 | ||
| EPIDEMIOLOGY OF ALCOHOLIC LIVER DISEASE | 419 | ||
| Age and Alcoholic Liver Injury | 420 | ||
| Gender and Alcoholic Liver Injury | 420 | ||
| Ethnicity, Genetics, and Alcoholic Liver Disease | 420 | ||
| Drinking Patterns, Alcohol Intake, and Alcoholic Liver Injury | 422 | ||
| NATURAL HISTORY OF ALCOHOLIC LIVER DISEASE | 422 | ||
| Simple Steatosis | 422 | ||
| Alcoholic Foamy Degeneration | 424 | ||
| Alcoholic Hepatitis | 424 | ||
| Alcoholic Cirrhosis | 424 | ||
| SUMMARY | 425 | ||
| REFERENCES | 425 | ||
| Unhealthy Alcohol Use | 429 | ||
| Key points | 429 | ||
| INTRODUCTION | 429 | ||
| DEFINITIONS AND CLASSIFICATION | 430 | ||
| Moderate Drinking | 430 | ||
| At-Risk Drinking | 430 | ||
| Alcohol Use Disorder | 430 | ||
| Binge Drinking | 430 | ||
| EPIDEMIOLOGY | 431 | ||
| GENETICS AND ENVIRONMENT | 431 | ||
| COMMON PROBLEMS ASSOCIATED WITH ALCOHOL USE DISORDER | 431 | ||
| Medical Problems | 431 | ||
| Psychiatric Problems | 432 | ||
| Other Behavior-Related Problems | 432 | ||
| SCREENING AND ASSESSMENT | 432 | ||
| TREATMENT APPROACHES FOR PATIENTS WITH UNHEALTHY ALCOHOL USE | 433 | ||
| MANAGEMENT OF AT-RISK DRINKERS WITH BRIEF INTERVENTION THERAPY | 434 | ||
| MANAGEMENT OF ALCOHOL USE DISORDERS | 435 | ||
| Alcohol Withdrawal Syndrome | 435 | ||
| PSYCHOTHERAPEUTIC APPROACHES TO THE TREATMENT OF ALCOHOL DEPENDENCE | 437 | ||
| Self-Help Groups | 437 | ||
| PHARMACOLOGIC TREATMENTS TO PREVENT RELAPSE | 437 | ||
| SUMMARY | 439 | ||
| REFERENCES | 439 | ||
| FURTHER READING | 444 | ||
| Pathogenesis of Alcoholic Liver Disease | 445 | ||
| Key points | 445 | ||
| SPECTRUM, RISK FACTORS, AND COMORBIDITIES | 445 | ||
| Risk Factors | 446 | ||
| Diagnosis | 446 | ||
| PATHOGENESIS | 446 | ||
| Ethanol-Mediated Liver Injury | 446 | ||
| Binge drinking and the National Institute on Alcohol Abuse and Alcoholism model | 446 | ||
| Acetaldehyde | 446 | ||
| Damage-associated molecular patterns | 448 | ||
| Metabolism | 448 | ||
| Inflammatory Immune Response to Injury | 448 | ||
| Innate immune system | 448 | ||
| Adaptive immunity | 449 | ||
| Immune paralysis | 449 | ||
| Intestinal Permeability Changes and Microbiome | 449 | ||
| Zinc | 449 | ||
| Impaired Regeneration | 449 | ||
| Epigenetics and MicroRNAs | 450 | ||
| Protective Mechanisms | 450 | ||
| Autophagy | 450 | ||
| Forkhead box O3 | 450 | ||
| Hepatocellular Carcinoma Development in Alcoholic Liver Disease | 451 | ||
| CURRENT THERAPIES AND FUTURE APPROACHES | 451 | ||
| S-Adenosylmethionine | 451 | ||
| Microbiome, Lipopolysaccharide, and the Gut Barrier | 451 | ||
| Interleukin-1 Antagonist | 451 | ||
| Inhibition of Apoptosis | 451 | ||
| Farnesoid X Receptor | 452 | ||
| Interleukin-22 | 452 | ||
| Osteopontin | 452 | ||
| Cannabinoid | 452 | ||
| REFERENCES | 452 | ||
| Diagnosis of Alcoholic Liver Disease | 457 | ||
| Key points | 457 | ||
| INTRODUCTION | 457 | ||
| RISK FACTORS | 458 | ||
| HISTORY | 458 | ||
| SYMPTOMS AND PHYSICAL EXAMINATION | 460 | ||
| LABORATORY FINDINGS | 461 | ||
| NOVEL BIOMARKERS | 463 | ||
| IMAGING STUDIES | 464 | ||
| LIVER BIOPSY | 465 | ||
| SUMMARY | 466 | ||
| REFERENCES | 467 | ||
| The Pathology of Alcoholic Liver Disease | 473 | ||
| Key points | 473 | ||
| INTRODUCTION | 473 | ||
| STEATOSIS (FATTY LIVER) | 474 | ||
| ALCOHOLIC STEATOHEPATITIS (ALCOHOLIC HEPATITIS) | 475 | ||
| Distinction Between Steatosis and Steatohepatitis | 477 | ||
| Grading Alcoholic Steatohepatitis | 478 | ||
| MACROVESICULAR STEATOSIS AND STEATOHEPATITIS IN OTHER CONDITIONS | 479 | ||
| DISTINCTION BETWEEN ALCOHOLIC AND NONALCOHOLIC FATTY LIVER DISEASE | 479 | ||
| Cholestatic Alcoholic Liver Disease Mimicking Extrahepatic Biliary Obstruction | 479 | ||
| Alcoholic Foamy Degeneration | 480 | ||
| Sclerosing Hyaline Necrosis | 481 | ||
| FIBROSIS IN ALCOHOLIC LIVER DISEASE | 481 | ||
| Staging Fibrosis | 483 | ||
| Alcoholic Cirrhosis and Hepatocellular Carcinoma | 484 | ||
| ALCOHOLIC HEPATITIS HISTOLOGIC SCORE | 484 | ||
| COMORBID CONDITIONS IN ALCOHOLIC LIVER DISEASE | 485 | ||
| SUMMARY | 487 | ||
| REFERENCES | 487 | ||
| Prognosis and Prognostic Scoring Models for Alcoholic Liver Disease and Acute Alcoholic Hepatitis | 491 | ||
| Key points | 491 | ||
| INTRODUCTION | 491 | ||
| MODIFIED DISCRIMINANT FUNCTION OR MADDREY SCORE | 492 | ||
| GLASGOW ALCOHOLIC HEPATITIS SCORE | 493 | ||
| AGE, SERUM BILIRUBIN, INTERNATIONAL NORMALIZED RATIO AND CREATININE SCORE | 494 | ||
| LILLE SCORE | 494 | ||
| MODEL FOR END-STAGE LIVER DISEASE | 495 | ||
| COMBINING PROGNOSTIC MODELS | 496 | ||
| SUMMARY | 496 | ||
| REFERENCES | 496 | ||
| Acute Alcoholic Hepatitis, the Clinical Aspects | 499 | ||
| Key points | 499 | ||
| INTRODUCTION | 499 | ||
| Prevalence of Alcoholic Hepatitis | 500 | ||
| Patterns of Alcohol Intake Leading to Alcoholic Hepatitis | 500 | ||
| Risk Factors for Alcoholic Hepatitis | 500 | ||
| Age | 500 | ||
| Sex | 500 | ||
| Ethnicity | 501 | ||
| Obesity | 501 | ||
| Malnutrition | 501 | ||
| Coexistent hepatitis C virus infection | 501 | ||
| Hereditary factors | 501 | ||
| CLINICAL PRESENTATION | 501 | ||
| Symptoms and Signs | 501 | ||
| Laboratory Findings | 502 | ||
| Ruling out Infection | 502 | ||
| Ruling out Other Liver Diseases | 503 | ||
| DIAGNOSIS | 503 | ||
| Clinical Prognostic Scoring Models of Alcoholic Hepatitis | 503 | ||
| Role of Liver Biopsy | 503 | ||
| Histologic Prognostic Scoring of Alcoholic Hepatitis | 504 | ||
| Noninvasive Diagnostic Modalities | 505 | ||
| OUTCOMES | 505 | ||
| Short-Term and Long-Term Survival | 505 | ||
| Progression to Cirrhosis | 505 | ||
| Recidivism | 505 | ||
| Recurrent Alcoholic Hepatitis | 506 | ||
| REFERENCES | 506 | ||
| Acute Alcoholic Hepatitis: Therapy | 509 | ||
| Key points | 509 | ||
| INTRODUCTION | 509 | ||
| PATIENT EVALUATION OVERVIEW | 510 | ||
| TREATMENT OF ALCOHOLIC HEPATITIS: OVERVIEW | 512 | ||
| PHARMACOLOGIC TREATMENT OPTIONS | 513 | ||
| Corticosteroids | 513 | ||
| Pentoxifylline | 514 | ||
| Anti–Tumor Necrosis Factor α Agents | 515 | ||
| Antioxidants | 515 | ||
| Miscellaneous Agents | 515 | ||
| SURGICAL TREATMENT OPTIONS | 516 | ||
| Liver Transplantation | 516 | ||
| SUMMARY | 517 | ||
| REFERENCES | 517 | ||
| Alcoholic Liver Disease and Liver Transplantation | 521 | ||
| Key points | 521 | ||
| INTRODUCTION | 521 | ||
| EPIDEMIOLOGY OF ALCOHOL USE AND ALCOHOLIC LIVER DISEASE | 522 | ||
| LIVER TRANSPLANTATION AND ALCOHOLIC LIVER DISEASE | 523 | ||
| ALCOHOLIC LIVER DISEASE IN THE PRETRANSPLANT PERIOD | 524 | ||
| POSTTRANSPLANT OUTCOMES IN ALCOHOLIC LIVER DISEASE | 527 | ||
| LIVER TRANSPLANTATION IN ALCOHOLIC HEPATITIS | 528 | ||
| SUMMARY | 530 | ||
| REFERENCES | 530 | ||
| Nutrition and Alcoholic Liver Disease | 535 | ||
| Key points | 535 | ||
| INTRODUCTION | 535 | ||
| PREVALENCE AND METHODS TO QUANTIFY MALNUTRITION IN ALCOHOLIC LIVER DISEASE | 536 | ||
| CLINICAL CONSEQUENCES OF MALNUTRITION IN ALCOHOLIC LIVER DISEASE | 537 | ||
| MOLECULAR AND METABOLIC PERTURBATIONS CONTRIBUTING TO MALNUTRITION IN ALCOHOLIC LIVER DISEASE | 540 | ||
| ROLE OF THE GUT IN MALNUTRITION IN ALCOHOLIC LIVER DISEASE | 542 | ||
| MANAGEMENT OF MALNUTRITION IN ALCOHOLIC LIVER DISEASE | 542 | ||
| Abstinence | 543 | ||
| Nutrition | 543 | ||
| Exercise in Alcoholic Liver Disease | 544 | ||
| NOVEL THERAPEUTIC TARGETS | 545 | ||
| Myostatin | 545 | ||
| Muscle-Targeted Antioxidants | 545 | ||
| Autophagy Regulators | 545 | ||
| Mitoprotective Agents | 545 | ||
| SUMMARY | 545 | ||
| REFERENCES | 546 | ||
| Long-Term Management of Alcoholic Liver Disease | 551 | ||
| Key points | 551 | ||
| INTRODUCTION | 551 | ||
| MANAGEMENT OF ALCOHOLISM | 552 | ||
| Screening for Problem Drinking | 552 | ||
| Abstinence Therapies | 553 | ||
| Recidivism | 554 | ||
| Natural History of Alcoholic Liver Disease | 554 | ||
| DIAGNOSIS OF ALCOHOLIC LIVER DISEASE | 555 | ||
| Clinical and Laboratory Findings | 555 | ||
| Imaging | 556 | ||
| Role of Liver Biopsy in Alcoholic Liver Disease | 556 | ||
| Management of Alcoholic Liver Disease | 556 | ||
| Alcoholic Liver Disease Without Cirrhosis | 557 | ||
| Alcoholic Liver Disease with Cirrhosis | 557 | ||
| Gastroesophageal varices | 557 | ||
| Hepatocellular carcinoma | 558 | ||
| Alcohol and Cancer, in General | 559 | ||
| Alcohol and Other Effects in the Body | 559 | ||
| SUMMARY | 559 | ||
| REFERENCES | 559 | ||
| Alcoholic Liver Disease | 563 | ||
| Key points | 563 | ||
| INTRODUCTION | 563 | ||
| AS A PRIMARY CAUSE: THE RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH ALCOHOLIC LIVER DISEASE–ASSOCIATED CIRRHOSIS | 564 | ||
| Evidence Suggesting Patients with Alcoholic Cirrhosis are at Low Risk for Hepatocellular Carcinoma | 565 | ||
| Evidence Suggesting Patients with Alcoholic Cirrhosis are at Medium–High Risk for Hepatocellular Carcinoma | 565 | ||
| ALCOHOL CONSUMPTION PATTERNS AND HOST FACTORS | 571 | ||
| Alcohol Consumption and Alcoholic Liver Disease Risk: Dose Dependent or Threshold Effect? | 572 | ||
| Drinking Patterns: With or Without a Meal | 572 | ||
| The Effect of Abstinence on the Risk of Cirrhosis and Hepatocellular Carcinoma | 573 | ||
| Gender and Hormones | 573 | ||
| Race and Ethnicity | 573 | ||
| ALCOHOL AS A COFACTOR WITH OTHER CAUSES OF LIVER DISEASE FOR HEPATOCELLULAR CARCINOMA DEVELOPMENT | 573 | ||
| Hepatitis B: Chronic or Occult | 573 | ||
| Chronic Hepatitis C | 574 | ||
| Hereditary Hemochromatosis | 574 | ||
| Genetics and Polymorphisms | 575 | ||
| Diabetes and Obesity | 575 | ||
| SUMMARY | 576 | ||
| REFERENCES | 576 | ||
| The Effects of Alcohol on Other Chronic Liver Diseases | 581 | ||
| Key points | 581 | ||
| EFFECT OF ALCOHOL ON NONALCOHOLIC FATTY LIVER DISEASE | 581 | ||
| ALCOHOL AND HEPATITIS C | 583 | ||
| ALCOHOL AND HEPATITIS B | 587 | ||
| ALCOHOL AND HEMOCHROMATOSIS | 587 | ||
| ALCOHOL AND AUTOIMMUNE LIVER DISEASES | 588 | ||
| SUMMARY | 588 | ||
| REFERENCES | 589 | ||
| Infection and Alcoholic Liver Disease | 595 | ||
| Key points | 595 | ||
| THE EFFECT OF ALCOHOL ON IMMUNE RESPONSES | 595 | ||
| The Effect of Alcohol on the Innate Immune System | 596 | ||
| Effect on gut permeability | 596 | ||
| Effect on phagocytic responses | 596 | ||
| Effect on innate humoral response | 598 | ||
| The Effect of Alcohol on the Adaptive Immune System | 598 | ||
| Effect on dendritic cells and T-cell response | 598 | ||
| Effect on B-cell response | 599 | ||
| EFFECT OF ALCOHOL ON VIRAL INFECTIONS | 599 | ||
| Effect on Human Immunodeficiency Virus Infection | 599 | ||
| Effect on Hepatitis C Virus Infection | 599 | ||
| Effect on Hepatitis B Virus Infection | 600 | ||
| ALCOHOL USE AND PREDISPOSITION TO BACTERIAL INFECTIONS | 600 | ||
| Mechanisms of Pulmonary Injury and Increased Susceptibility to Pneumonia | 600 | ||
| Immune Dysregulation and Bacterial Infection in Alcoholic Hepatitis | 601 | ||
| Alcohol Use and Predisposition to Mycobacterial Infection | 601 | ||
| CONTINUED RISK OF INFECTION IN PATIENTS TRANSPLANTED FOR ALCOHOLIC CIRRHOSIS | 602 | ||
| SUMMARY | 603 | ||
| REFERENCES | 603 |