Mechanisms of autoimmune liver disease.

Several lines of evidence suggest that autoimmune hepatitis and primary biliary cirrhosis are autoimmune diseases. This article discusses both the immunologic mechanisms of liver injury and the mechanisms of cell injury mediated by lymphocytes. This article also reviews the proposed immunopathogenesis of autoimmune hepatitis and primary biliary cirrhosis.

Review article: interferon and hepatitis C--factors predicting therapeutic outcome.

Hepatitis C chronically infects approximately 1.5% of Americans and is the most common clinical problem facing hepatologists. Since the virus was initially described in 1989, development of an effective therapy has been challenging. Although several different therapeutic agents have been used, no therapy has been shown to reliably eradicate the virus. Interferon-alpha, a cytokine with immunostimulatory and anti-viral properties, has become the therapy of choice for patients with chronic hepatitis C infection. Trials assessing the efficacy of interferon-alpha have characterized host and viral factors predictive of responses to treatment. A thorough understanding of these predictive factors is requisite to providing cost-effective therapeutic decisions for the patient with chronic hepatitis C infection.

Dipeptidyl peptidase I and granzyme A are coordinately expressed during CD8+ T cell development and differentiation.

Dipeptidyl peptidase I (DPPI) is a granule protease that plays a requisite role in processing the proenzyme form of the CTL granule serine proteases (granzymes). This study assesses DPPI mRNA and enzyme expression during T lymphocyte ontogeny and CTL differentiation. The most immature CD3- CD4- CD8- thymocytes were found to express >40-fold higher levels of DPPI mRNA, although levels of DPPI enzymatic activity in CD3- CD4- CD8- thymocytes were only modestly higher than those seen for CD4+ CD8+ or CD4+ CD8- thymocytes. More mature CD8+ CD4- thymocytes and CD8+ splenocytes expressed significantly higher levels of DPPI mRNA and enzymatic activity than CD4+ CD8+ or CD4+ CD8- thymocytes. Granzyme A mRNA expression was observed in DPPI expressing CD3- CD4- CD8- and CD8+ CD4- thymocytes and was also observed in CD8+ CD4- splenocytes; however, expression was not observed in CD4+ CD8+ or CD4+ CD8- thymocytes. Both DPPI mRNA and granzyme A mRNA expression in CD8+ T cells decreased to very low or undetectable levels during the first 48 h after allostimulation in MLCs. However, peak levels of both DPPI and granzyme A expression were observed later in the course of CD8+ T cell responses to alloantigen, with DPPI mRNA expression peaking on either day 3 or day 4 and granzyme A expression peaking at the end of a 5-day MLR. These data indicate that DPPI is expressed at all stages of T cell ontogeny and differentiation in which granzyme A mRNA is detected; consequently, DPPI appears to be available for the processing and activation of granzyme A during both CD8+ T cell development and differentiation.

Pulmonary infections in hospitalized patients with cirrhosis.

We have further characterized pulmonary infections by bronchoalveolar lavage in hospitalized patients with cirrhosis. Sixty-seven consecutive patients admitted to the Ohio State University Medical Center from 1992 to 1995 with liver disease who underwent bronchoscopy with bronchoalveolar lavage were identified. Twenty-one patients with cirrhosis and pneumonia were further analyzed. During the same period, we consecutively identified 23 patients without liver disease or immunosuppression, 19 patients with HIV infections, and 30 patients with cancer or pharmacologic immunosuppression who had bronchoscopy with bronchoalveolar lavage for pneumonia. These groups were included in these analyses as a control and immunosuppressed controls, respectively. Bronchoscopy isolated respiratory pathogens in 16 patients (76.2%) with cirrhosis and 6 patients (26.1%) in the control group (p = 0.002). Fungal organisms were most commonly found in patients with cirrhosis although several patients had more than one organism identified. The control group had mostly bacterial pathogens; the immunosuppressed controls were commonly infected with opportunistic organisms. Six (85.7%) of 7 patients with cirrhosis and fungal pneumonia died of their respiratory illness. Hospitalized patients with cirrhosis commonly have opportunistic pulmonary infections; diagnostic bronchoscopy and empiric antifungal therapy should be considered in those who do not respond to antibiotics.

Exposure to domestic cats: risk factor for Pasteurella multocida peritonitis in liver cirrhosis?

Pasteurella multocida is most commonly associated with acute skin and soft tissue infections following an animal bite or scratch. Peritonitis caused by P. multocida in patients with cirrhosis is rarely reported. We present a case of spontaneous bacterial peritonitis with P. multocida in a patient with cirrhosis, squamous cell cancer of the head and neck, and nontraumatic domestic cat exposure. Nasopharyngeal colonization with P. multocida, with subsequent transient bacteremia and seeding of the peritoneum in immunocompromised (particularly cirrhotic) cat-owners, could play an important pathogenetic role in the development of spontaneous bacterial peritonitis. A review of the literature showed that in nine of 13 patients with cirrhosis and P. multocida peritonitis, exposure to domestic animals was reported. The mortality rate is high in this setting, even with prompt antibiotic treatment. Preventive strategies for immuno-compromised patients should include minimization of animal contact, especially cats, which have a high carriage rate (70-90%) of P. multocida.

Upper-gastrointestinal bleeding from angiodysplasia of the minor papilla.

Angiodysplasia is an often unrecognized cause of upper-gastrointestinal bleeding, most commonly found in the antrum of the stomach but also in the duodenum and rarely in the esophagus. Small-intestinal angiodysplasia is the source of gastrointestinal bleeding of obscure origin in 30-40% of cases. The diagnosis is usually made by esophagogastroduodenoscopy, push enteroscopy, or selective angiography. We report the first case of angiodysplasia of the minor papilla diagnosed by side-viewing duodenoscopy.

Cirrhosis: a risk factor for cryptococcal peritonitis.

Cryptococcal peritonitis is usually associated with end-stage renal disease and peritoneal dialysis. Significant liver disease has not been well recognized as a risk factor for its development. We report two patients with cirrhosis who developed peritoneal infections with Cryptococcus neoformans. We also retrospectively review all cases of cryptococcal illness at the Ohio State University Medical Center from October 1990 to January 1994 and present a review of the literature regarding cryptococcal peritonitis associated with hepatic dysfunction. Cirrhotic patients with this entity present with subtle, nonspecific complaints resulting in delayed diagnoses, dissemination, and death. We suggest that clinicians maintain an increased awareness of this unusual but lethal entity in patients with liver impairment. Early and frequent abdominal paracenteses with bedside inoculations of fungal culture medium, India ink preparations, and serum cryptococcal antigen testing may hasten the diagnosis and institution of appropriate therapy.

Normal arterial blood gas in a patient with saddle pulmonary artery embolus: diagnosis by transesophageal echocardiography.

This article describes a patient with a large, main pulmonary artery thromboembolus with normal arterial blood gas results, including normal alveolar-arterial oxygen gradient. The diagnosis was established using transesophageal echocardiography and confirmed with pulmonary angiography. The patient subsequently underwent anticoagulation and eventually was discharged without complications.

Fulminant hepatic failure associated with etodolac use.

Etodolac is a new pyranocarboxylic acid nonsteroidal anti-inflammatory agent with a unique chemical structure indicated for use in patients with painful musculoskeletal disorders and rheumatoid disease. Hepatotoxicity, in the form of reversible elevations in transaminases or bilirubin, occurs rarely. We present the first reported case of fulminant hepatic failure related to etodolac.