Serum immunoglobulins in patients with chronic hepatitis C: a surrogate marker of disease severity and treatment outcome.

BACKGROUND/AIMS: Moderate polyclonal hypergammaglobulinemia is a common finding in chronic viral liver disease; however, its clinical significance has not been completely elucidated. We attempted to determine whether serum immunoglobulin levels were correlated with the disease severity and the treatment outcome in patients with chronic hepatitis C. METHODOLOGY: In a total of 102 patients with chronic hepatitis C, we performed serum tests on immunoglobulins and determined the histology activity index (HAI) score by liver biopsy. In 97 patients, immunoglobulin levels were followed prior to and 6 months after interferon (IFN) therapy. RESULTS: Serum gamma (y)-globulin and immunoglobulin (IgG) were well correlated with HAI score (both; p < 0.0001), grading score (both; p < 0.01), and staging score (both; p < 0.0001). Among the 97 patients who received 6 months of IFN monotherapy, 31, 29, and 37 patients were complete, transient and non-responders, respectively. In the three subgroups, a significant difference was found in histological HAI, grading, and staging scores (p < 0.01, p < 0.05 and p < 0.0001, respectively), and in serum levels of gamma-globulin and IgG (both; p < 0.0001). Following IFN treatment, serum gamma-globulin and IgG were significantly decreased in the complete responders (both; p < 0.0001). Furthermore, serum levels of gamma-globulin and IgG of 1.5 g/dL were useful for predicting the treatment outcome of IFN monotherapy. CONCLUSIONS: The measurement of serum gamma-globulin and IgG is a valuable non-invasive tool for assessing the disease severity and treatment outcome in patients with chronic hepatitis C.

Hepatobiliary cystadenoma with mesenchymal stroma in a patient with chronic hepatitis C.

Hepatobiliary cystadenoma was suggested to be uncommon and it is often difficult to make a differential diagnosis. We report a case of a 65-year-old woman who presented with changes in the structure of a cyst that had been observed for the previous 10 years. Diagnostic imaging revealed a 7-cm-diameter cystic lesion with internal septations and papillary projections in her liver. All laboratory test results were normal; however, cystic fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were raised, at 160 ng/ml andover 200,000 U/ml, respectively. Owing to changes in the structure of the cyst and the difficulty of differential diagnosis from cystadenocarcinoma, a complete surgical excision was performed. The histological findings indicated that the tumor consisted of a multilocular cyst lined by glandular cells (with cuboidal or tall columnar cystoplasm), which were immunohistochemically positive for cytokeratin, CEA, epithelial membrane antigen, and CA 19-9. The underlying stroma was composed of proliferating primitive spindle cells which were immunoreactive for vimentin, alpha-smooth muscle actin, muscle-specific actin, and desmin, and resembled ovarian stroma. From these findings, this tumor was diagnosed as hepatobiliary cystadenoma with mesenchymal stroma. Even though the tumor was previously diagnosed as a simple liver cyst, it was necessary to pay special attention to the changes in the structure of the cyst, using ultra sonography and/or computed tomography, bearing in mind hepatobiliary cystadenoma with mesenchymal stroma. The malignant potential of this tumor is stressed, and complete surgical resection is the recommended therapy.

Development of hypoxemia in alcoholic liver disease.

The aim of this study was to investigate the arterial hypoxemia in Japanese patients with alcoholic liver disease (ALD) with regard to alcohol consumption and/or disease severity. Hypoxemia was observed in 78% patients with ALD and in all 46 patients with alcoholic liver cirrhosis (ALC) and 33 (56%) of 59 patients with noncirrhotic alcoholic liver disease (NCALD) (P < 0.0001). The partial pressure of oxygen (PaO2) was 71.1 +/- 5.2 mm Hg in ALC and 78.7 +/- 6.3 mm Hg in NCALD (P < 0.0001). The oxygen consumption in ALD was significantly higher than that in control subjects (P < 0.0001), and a high oxygen consumption was seen in 88% of the patients with ALD, in all 46 ALC patients, and in 46 (78%) of 59 NCALD patients (P < 0.01). Following abstinence from alcohol, the PaO2 and oxygen consumption significantly recovered after day 2 (P < 0.0001), whereas the prothrombin index did not change in either NCALD or ALC patients. Multivariate analysis showed that alcohol consumption and oxygen consumption were significant independent predictors of PaO2. In conclusion, the present findings suggest that increased oxygen consumption due to alcohol ingestion is principally responsible for the hypoxemia in ALD patients.

Hyperendothelinemia and ICG clearance in alcoholic and nonalcoholic cirrhosis.

Plasma endothelin (ET) levels are generally increased in cirrhosis patients in line with the severity of disease; however, the pathophysiological significance remains to be clarified. We evaluated the plasma ET levels in 49 patients with alcoholic cirrhosis and in 53 patients with nonalcoholic cirrhosis of the same disease severity. The plasma ET level was significantly elevated in alcoholic patients (P < 0.0001) and slightly so in nonalcoholic patients (P < 0.01); the difference was significant between the groups (P < 0.0001). The plasma ET level was positively correlated with the Child-Pugh score (P < 0.0001) and negatively correlated with prothrombin index (P < 0.001) and indocyanine green (ICG) clearance (P < 0.0001). The plasma ET level decreased 32% in alcoholic patients after abstinence (P < 0.001), but remained correlated with ICG clearance (P < 0.001) and the Child-Pugh score (P < 0.01), but not with prothrombin index. Regression analysis revealed that the plasma ET level was correlated with estimated hepatic blood flow and alcohol abuse. These findings suggest that hyperendothelinemia in cirrhosis patients is related to alcohol abuse and disease severity, especially to impaired hepatic hemodynamics.