Anthony S. Tavill

Diagnosis and Management of Hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases

This guideline has been approved by the American Association for the Study of Liver Diseases (AASLD) and represents the position of the association.

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. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients’ baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. ≤33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. Results Seventy percent of patients were men and 80% were white. The mean age was 47.48 ± 5.70 years, mean BMI was 29.01 ± 5.01 kg/m2, and mean waist to hip ratio (W/H) was 0.90 ± 0.08. Patients with higher grade of steatosis had higher BMI (32.83 ± 6.26 vs. 28.49 ± 4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64 ± 5.23 vs. 29.90 ± 5.35 vs. 27.33 ± 4.07, P = 0.008; W/H: 0.97 ± 0.06 vs. 0.91 ± 0.08 vs. 0.87 ± 0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. Conclusion In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.

Connective tissue diseases and the liver.

Connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögrens 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. Although advanced liver disease with cirrhosis and liver failure is rare in patients with connective tissue diseases, clinical and biochemical evidence of associated liver abnormalities is common. Previous treatment with potentially hepatotoxic drugs or coincident viral hepatitis has usually been implicated as the main causes of liver disease in patients with connective tissue diseases. However, even after careful exclusion of these etiologies, the question remains whether to classify the patient as having a primary liver disease with associated autoimmune, clinical, and laboratory features or as having liver disease as a manifestation of generalized connective tissue disease. The main example of this pathogenetic dilemma is autoimmune hepatitis and SLE-associated hepatitis, which have been regarded as two different entities, although they have features in common of autoimmune syndromes. Several clinical and histopathologic features have been used to discriminate autoimmune hepatitis from SLE, a relevant diagnostic exercise because complications and therapy are quite different. Although hepatic steatosis and abnormal results on biochemical liver function tests are the most common hepatic abnormalities associated with connective tissue diseases, other less frequent abnormalities have been noted, such as nodular regenerative hyperplasia, portal vein obliteration and portal hypertension, features of primary biliary cirrhosis, and rarely portal fibrosis with abnormal lobular architecture. Vascular disorders of the liver also have been described, such as Budd-Chiari syndrome. Histologic assessment may reveal a variety of subclinical liver diseases. The aim of this contribution is to review the current published data regarding liver involvement in connective tissue diseases.

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. Clinically, hepatitis C is a more severe disease in HIV-infected individuals, characterized by rapid progression toward end-stage liver disease. Highly active antiretroviral therapy is the mainstay of current acquired immunodeficiency syndrome management. One of the limiting side effects of combination therapy for HIV is hepatotoxicity, which is more common and often more serious in patients with underlying liver disease. Management of coinfected patients has no strict guidelines, but it is generally accepted that HIV infection needs to be treated before HCV. Hepatitis C in coinfected individuals is probably best treated using combination therapy (interferon alpha and ribavirin). It appears that combination therapy can safely be administered to this population and that previous concerns about ribavirin/zidovudine antagonism are unsubstantiated in clinical practice. Although initial results using only interferon alpha showed poor results in HIV coinfected patients, combination therapy seems to be as effective as in the general population. All HIV–HCV coinfected patients should be vaccinated against hepatitis B and hepatitis A; vaccines are safe and effective.

Should all pregnant women be screened for hepatitis B

To assess the sensitivity of historical risk factors for identification for hepatitis B surface antigen (HBsAg)-positive parturients, 4399 pregnant women were consecutively screened for HBsAg. Information regarding risk for hepatitis B infection was obtained from each HBsAg-positive parturient. Twenty-three HBsAg-positive subjects were identified (5.2/1000 deliveries). The HBsAg carrier rate (18/2231, or 8.1/1000 deliveries) was significantly higher in women of black, Asian, or Hispanic origin than in the remaining ethnic groups (non-Hispanic whites plus all others, 5/2168, or 2.3/1000 deliveries) (chi square, 5.95; p = 0.016). Risk factors for identification of HBsAg-positive women were present in 10 of 22 asymptomatic subjects (sensitivity, 45%; 95% confidence interval, 24% to 68%). Much of the information required to assess one of these risk factors, previous infection, involved detailed questioning and is unlikely to be obtained in the context of conventional obstetrical care. Routine maternal HBsAg screening programs may be needed if transmission of hepatitis B from mother to infant is to be prevented.

In Vivo Differences Between the Turnover Rates of Leucine and Leucine's Ketoacid in Stable Cirrhosis

Based on urinary nitrogen excretion, previous studies have indicated increased protein breakdown rates in cirrhosis. However, studies using [1-13C]-leucine infusion methodology have found normal protein breakdown rates. Because abnormal partitioning between extracellular and intracellular leucine exists in cirrhosis, plasma enrichment of leucines keto acid (KIC), a marker of intracellular leucine, may more accurately reflect protein metabolism than plasma [1-13C]leucine enrichment. Therefore, protein breakdown and oxidation were calculated using both [1-13C]leucine and [1-13C]KIC and compared with urinary nitrogen excretion in seven cirrhotics and seven matched controls after an overnight fast. The ratio of KIC and leucine plasma enrichment was decreased (P less than 0.001) in cirrhosis because of lower KIC enrichment (P less than 0.006). Cirrhotics had increased rates of protein breakdown (P less than 0.006) and protein oxidation (P less than 0.05) based on KIC (P less than 0.006) but not leucine enrichment. In controls, protein oxidation calculated from urinary nitrogen excretion did not differ from KIC results (0.88 +/- 0.08 vs. 0.83 +/- 0.06) but was higher than the leucine method (0.88 +/- 0.08 vs. 0.73 +/- 0.05; P less than 0.01). However, in cirrhotics protein oxidation based on urinary nitrogen was lower than the KIC methodology (P less than 0.01). Therefore, cirrhotics have accelerated rates of protein breakdown and oxidation associated with increased extrarenal nitrogen loss. Furthermore, these results suggest abnormal leucine transport across cell membranes.

Screening for Hemochromatosis: Phenotyping or Genotyping or Both?

Recommendations for population screening for genetically determined human disorders are based on several important criteria (1, 2). First, the disorder should have a relatively high prevalence rate. Second, there should be a reasonable predictability of morbidity and mortality from the disease if undetected and untreated. Third, in the adult population there should be a latency of onset of disease that permits appropriate timing of population testing and the opportunity for preventive therapy to abort the onset of phenotype expression of life-threatening manifestations of the disorder. Fourth, it should be evident from long term follow-up studies that early diagnosis prevents morbidity and promotes survival, i.e., that there is a proven benefit for early diagnosis. Finally, there should be objective evidence for the cost-effectiveness of screening methods for early diagnosis. Hereditary hemochromatosis (HH) ideally satisfies the first four criteria for screening. To meet the fifth requirement there have been a number of cost-effectiveness analyses and early prospective studies of population screening in North America, Europe, and Australia (3, 4, 5, 6, 7, 8, 9). In this issue of the Journal, Dr. Adams and the late Dr. Valberg extend their earlier analysis of a screening strategy for blood donors to include an evaluation of the principal mutation of the newly discovered HFE gene (10, 11).

Corticosteroids in Severe Alcoholic Hepatitis

Excerpt Alcoholic hepatitis is the term for a clinicopathologic syndrome resulting from prolonged excessive alcohol consumption characterized by an acute or subacute clinical presentation and a dis...

CT-guided percutaneous catheter drainage of lymphocele complicating splenorenal anastomosis

We report the successful management by CT-guided percutaneous catheter drainage of a lymphocele complicating a Warren-Zeppa distal splenorenal venous anastomosis. The early postoperative course of this 31-year-old male with homozygous alpha 1-antitrypsin deficiency was complicated by chylous ascites and a large lymphocele demonstrable on CT scanning. The persistent 10.5 cm diameter lymphocele was drained percutaneously 5 weeks later by a CT-guided catheter. Drainage of lymph continued at decreasing rates for 13 days when the catheter was removed. Complete resolution of the lymphocele was confirmed at 2 1/2 months. The successful treatment of a lymphocele by percutaneous catheter drainage may obviate major surgery and has not been previously documented.

Metabolic liver diseases

In this review, we concentrate on those inherited metabolic disorders that manifest in hepatic disease as a predominant component of a generalized metabolic disturbance, often for the first time in adult or early adult life. They include hereditary hemochromatosis, Wilsons disease, α1-antitrypsin deficiency, and certain disorders of lipid storage such as Gauchers and Niemann-Pick diseases.