Concomitant presentation of collagenous sprue and HFE hemochromatosis.

Collagenous sprue (CS) is a progressive malabsorptive disorder characterized by collagen deposition beneath the basement membrane of small bowel epithelium in refractory celiac sprue. CS is a pathologically distinct entity from celiac disease, despite a similar clinical presentation. The etiology of CS is unclear, although there are speculations that CS and celiac disease may share similar pathogenetic pathways.

Liver disease in alpha 1-antitrypsin deficiency: a review.

Alpha 1-antitrypsin deficiency is an inherited metabolic disorder that predisposes the affected individual to chronic pulmonary disease, in addition to chronic liver disease, cirrhosis, and hepatocellular carcinoma. Just over one-third of genetically susceptible adult patients with the most severe phenotype, PiZZ, develop clinically significant liver injury. The clinical presentation of liver disease is variable, and the genetic and environmental factors that predispose some individuals to liver disease while sparing others are unknown.

A diagnostic approach to hemochromatosis.

In the present clinical review, a diagnostic approach to hemochromatosis is discussed from the perspective of two clinicians with extensive experience in this area. The introduction of genetic testing and large-scale population screening studies have broadened our understanding of the clinical expression of disease and the utility of biochemical iron tests for the detection of disease and for the assessment of disease severity. Liver biopsy has become more of a prognostic test than a diagnostic test.

Pegylated interferon alpha-2b, ribavirin and amantadine for chronic hepatitis C.

In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon alpha-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed.

Alcohol and iron.

Iron in its free ferrous and ferric states may serve as a physiological regulator of normal intracellular functions but can be a double-edged sword when linked to several pathways of cellular toxicity. In particular, oxidative stress-induced cytotoxicity leading to both necrosis and apoptosis (so-called necrapoptosis) may be promoted by increased intracellular free iron. When hepatocyte iron accumulates to excess in clinical alcohol abuse or in an experimental, combined model of iron and alcohol hepatotoxicity, there is evidence for synergy among the putative pathways of oxidative stress.

Obesity and non-alcoholic fatty liver disease in chronic hepatitis C.

Background: Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C.

Methods: One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included.

Connective tissue diseases and the liver.

Connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, and scleroderma are systemic disorders that may have an autoimmune basis. The system manifestations vary, and there is frequent overlap among the syndromes. Liver involvement in patients with connective tissue diseases has been well documented but is generally considered rare.

Hepatitis C and human immunodeficiency virus coinfections.

Hepatitis C virus (HCV) has become a major contributor to morbidity and mortality in patients with human immunodeficiency virus (HIV). It is estimated that 30% to 50% of patients with HIV are coinfected with HCV. Advances in antiretroviral therapy and improved life expectancy of HIV patients have resulted in an emergence of HCV-induced liver disease as a leading cause of significant morbidity and death in this population.

Wilson's Disease.

Early diagnosis permits preventive therapy to preempt development of organ damage. In all diagnosed patients, both symptomatic and asymptomatic, pharmacologic therapy is lifelong, and maintenance treatment to prevent copper toxicity is mandatory. Patients with either fulminant hepatic failure or hepatic insufficiency unresponsive to medical therapy should be considered for orthotopic liver transplantation, which effectively cures Wilson's disease.

Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial.

Hepatic iron concentration has consistently been observed as being directly correlated with the response to interferon therapy in chronic hepatitis C virus (HCV). We therefore conducted a randomized, controlled trial comparing iron reduction by phlebotomy with iron reduction followed by retreatment with interferon in 96 patients with chronic hepatitis C who had previously not responded to a course of interferon. During the initial phase when all patients were undergoing phlebotomy, we found that serum alanine transaminase (ALT) activities decreased but by less than 50% from baseline in 67 patients (89%), decreased by more than 50% in 12 patients (13%) and became normal in 9 patients (9%) with no overall change in HCV-RNA levels.

Iron reduction before and during interferon therapy of chronic hepatitis C: results of a multicenter, randomized, controlled trial.

Patients with chronic hepatitis C and low serum and hepatic iron stores may have an improved response to interferon (IFN). We tested whether iron reduction before and during IFN therapy would lead to an improved sustained biochemical and virological response compared with IFN alone. Eighty-two previously untreated patients with chronic hepatitis C were randomized to either: group A IFN-alpha2b 3 MU 3 times per week for 6 months, or group B iron reduction before and during IFN-alpha2b 3 MU 3 times per week for 6 months.

Nonalcoholic fatty liver (NASH syndrome).

Nonalcoholic steatohepatitis (NASH) is the term used for a common form of fatty liver presenting in adults with varied clinical manifestations. The most common presentation is asymptomatic elevation of liver enzymes (AST or SGOT and ALT or SGPT), which can be discovered incidentally in the course of an annual checkup, life insurance examination, or as part of surrogate screening before blood donation. At the other end of the clinical spectrum is the patient with complications from cryptogenic cirrhosis, who also shows a lack of evidence of alcohol as an etiological factor in pathogenesis.

Primary prophylaxis of variceal bleeding in cirrhosis: a cost-effectiveness analysis.

Background & Aims: Prophylaxis against the first variceal bleeding has been proposed to reduce morbidity and mortality in cirrhotic patients. No previous information is available regarding the cost-effectiveness of prophylaxis. The aim of this study was to compare the cost-effectiveness of variceal bleeding prophylaxis with propranolol, sclerotherapy, and shunt surgery in cirrhotic patients stratified by bleeding risk.

An update on iron metabolism: summary of the Fifth International Conference on Disorders of Iron Metabolism.

HHC is the most common inherited metabolic disease among the white population worldwide, with a gene frequency of about 10% and a frequency of homozygosity of about 1 of 250. Many patients harbor a common haplotype of informative markers on chromosome 6p2l.23, suggesting a strong founder effect exerted by a common Celtic ancestor.

Primary liver cancer and survival in patients undergoing liver transplantation for hemochromatosis.

Cirrhotic patients with hereditary hemochromatosis (HHC) have an increased risk of primary liver cancer (PLC). The purpose of this study was to determine the prevalence of primary liver cancer in patients with HHC undergoing orthotopic liver transplantation (OLT). Five liver transplant centers were surveyed; clinical and pathological data on 37 patients with HHC undergoing OLT were retrospectively collected and analyzed.