Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease frequently leading to development of cirrhosis and its complications. Ursodeoxycholic acid (UDCA) is a beneficial medical therapy for patients with PBC. Improvement in some histological features, but not in histological stage, has been reported after 2 years of UDCA therapy. Thus, longer follow-up may be necessary to determine whether UDCA has a favorable effect on histological stage of disease and progression to cirrhosis. Our aim was to determine the long-term effects of UDCA therapy on histological stage and progression to cirrhosis in patients with PBC. Sixteen unselected patients with noncirrhotic PBC who had been on long-term UDCA therapy (13-15 mg/kg/d) for 6.6 +/- 0.4 years (range, 5-9 years) were identified and their histological finding during treatment compared with that of 51 noncirrhotic patients with PBC who had received ineffective therapy (D-penicillamine [DPCA] or placebo) for 5.6 +/- 0.07 years (range, 5-8 years). Histological stage was determined using the Ludwig classification. The rate of progression to cirrhosis (stage 4) was significantly less in the UDCA group than in the control group (13% vs. 49%; P =.009). Although the overall rate of progression of histological stage was less in the UDCA group than in the control group (50% vs. 71%), this difference was not significant (P =.1). A marked improvement in liver biochemistries and Mayo risk score was noted in all patients during UDCA therapy; however, this improvement was not significantly different between patients who progressed and those who did not. In conclusion, long-term UDCA therapy appeared to delay the development of cirrhosis in PBC.     

Dupuytren's contracture, alcohol consumption, and chronic liver disease

This prospective study was undertaken to assess the prevalence of Dupuytren's contracture (DC) and its relationship with possible causes, especially alcohol consumption and chronic liver disease. Four hundred thirty-two consecutively hospitalized patients were examined for evidence of DC. They were divided into five groups based on the following clinical, biologic, and histologic criteria: alcoholic cirrhosis (89 patients), noncirrhotic alcoholic liver disease (55 patients), chronic alcoholism without liver disease (46 patients), nonalcoholic chronic liver disease (68 patients), and a control group (174 patients). The prevalence of DC in these five groups of patients was 32.5%, 22%, 28%, 6%, and 12%, respectively; the prevalence of DC was higher in patients with cirrhotic or noncirrhotic alcoholic liver disease (25.5%) than it was in patients with nonalcoholic liver disease (6%), but it was not significantly different in alcoholic patients with or without liver disease. The relationship between DC and age, sex, manual labor, previous hand injuries, diabetes mellitus, alcohol consumption, and cigarette smoking was assessed by univariate and logistic regression methods. Nine variables were significantly different in patients with or without DC: age, sex, manual labor, previous hand injuries, diabetes mellitus, daily alcohol consumption, duration of alcohol consumption, total alcohol consumption, and duration of cigarette smoking. In our patients, variables that could explain DC were, in decreasing order, age, total alcohol consumption, sex (male), and previous hand injuries. In alcoholic patients, these variables were age and previous hand injuries; in nonalcoholic patients, these variables were age and cigarette smoking. These results emphasize the high prevalence of DC in alcoholic patients and the absence of a correlation between DC and chronic liver disease. Age and alcohol consumption are the best explanatory variables of DC in hospitalized patients.     

Carnitine metabolism in patients with chronic liver disease

Carnitine metabolism was studied in 79 patients with chronic liver disease, including 22 patients with noncirrhotic liver disease and 57 patients with different types of cirrhosis (22 patients with hepatitis B- or C-associated cirrhosis, 15 patients with alcohol-induced cirrhosis, 15 patients with primary biliary cirrhosis [PBC], and 5 patients with cryptogenic cirrhosis), and compared with 28 control subjects. In comparison with control subjects, patients with noncirrhotic liver disease showed no change in the plasma carnitine pool, whereas patients with cirrhosis had a 29% increase in the long-chain acylcarnitine concentration. Analysis of subgroups of patients with cirrhosis showed that patients with alcohol-induced cirrhosis had an increase in the total plasma carnitine concentration (67.8 +/- 29.5 vs. 55.2 +/- 9.9 micromol/L in control subjects), resulting from increases in both the short-chain and long-chain acylcarnitine concentration. In this group of patients, the acylcarnitine concentrations showed a close correlation with the total carnitine concentration, and the total carnitine concentration with the serum bilirubin concentration. Urinary excretion of carnitine was not different between patients with noncirrhotic or cirrhotic liver disease and control patients. However, patients with PBC showed an increased urinary excretion of total carnitine (52.5 +/- 40.0 vs. 28.0 +/- 16.7 micromol carnitine/mmol creatinine), resulting from an increase in the fractional excretion of both free carnitine and short-chain acylcarnitine. The current studies show that patients with cirrhosis are normally not carnitine deficient. Patients with alcohol-induced cirrhosis have increased plasma carnitine concentrations, which may result from increased carnitine biosynthesis because of increased skeletal muscle protein turnover. The increase in the fractional carnitine excretion in patients with primary biliary cirrhosis may result from competition of bile acids and/or bilirubin with tubular carnitine reabsorption and/or from a reduced activity of the carnitine transporter located in the proximal tubule.(Hepatology 1997 Jan;25(1):148-53)     

Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis

A prospective study was performed to evaluate the outcome of treatment withdrawal in 30 patients with "autoimmune" chronic active hepatitis in remission for periods of 1.5 to 9 years on maintenance corticosteroid and azathioprine therapy. Reactivation of disease, with marked rises in serum aminotransferase level (mean 668 +/- S.D. 458 IU per liter) and accompanied by severe symptoms, occurred in 25 (87%) patients within 52 weeks (median 9 weeks; range 5 to 52) and was associated with the histological features of piecemeal necrosis and lobular hepatitis in all 20 liver biopsies examined. Age, sex, duration of disease and remission, presence of cirrhosis, autoantibody status, or immunoglobulin levels did not differentiate patients who relapsed from those who remained in remission. The response to reinstitution of treatment with prednisolone was satisfactory in 25 patients and clinical and biochemical abnormalities resolved within 10 weeks (median 6; range 3 to 10), death occurred in one patient within 48 hr of readmission to hospital.     

Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease

OBJECTIVE: Thrombocytopenia or leukopenia in patients with chronic liver disease is often attributed to functional overactivity of the spleen (hypersplenism). Despite being a fairly common phenomenon, there is a paucity of reports on the prevalence of this syndrome in stable chronic liver disease patients with or without severe fibrosis/cirrhosis. The aim of this study was to establish the prevalence of peripheral blood cytopenia in patients with nonalcoholic cirrhosis/severe fibrosis versus patients with mild or no fibrosis on liver biopsy. METHODS: This is a retrospective chart review of 235 patients who underwent a liver biopsy. One hundred ninety-one patients met strict criteria for study entry; 28 different clinical and laboratory variables were collected from their charts review, and data were then analyzed using the SPSS statistical package. RESULTS: Of the cirrhotic patients, 64% were noted to have platelet counts consistently below 150,000 (lower limit of normal in our laboratory; mean, 144.6 +/- 89.4; median, 114), whereas only 5.5% of noncirrhotic patients had thrombocytopenia (mean, 252.2 +/- 103.4; median, 238). Leukopenia (WBC, <3,500) was relatively rare in the cirrhotic/fibrotic group, having a prevalence of 5% (7.59 +/- 4.3) versus 3.3% (10.62 +/- 14.2) of noncirrhotic patients. CONCLUSIONS: Of the patients with cirrhosis, 64% had thrombocytopenia (platelet count, <150,000). The likelihood ratio of finding a platelet count of <100,000 in patients with cirrhosis, as opposed to patients without cirrhosis, is almost 12.     

Urinary Level of L-Fucose as a Marker of Alcoholic Liver Disease

The urinary levels of L-fucose were measured in 93 alcoholics: 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L-fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease ( p < 0.001). The urinary L-fucose level was also significantly higher ( p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 ± 97 vs. 240 ± 95 μmol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 ± 29 vs. 155 ± 60 μmol/g of creatinine). The urinary level of L-fucose was significantly higher with alcoholic cirrhosis (384 ± 97 μmol/g of creatinine) than with viral cirrhosis (265 ± 42 μmol/g of creatinine) ( p < 0.001). The measurement of urinary L-fucose may be a useful marker of alcoholic liver disease.     

Hepatocellular carcinoma without cirrhosis in Japanese patients

Hepatocellular carcinoma is closely associated with cirrhosis, but it also develops, although much less frequently, in a noncirrhotic liver. It is suspected, without supporting evidence, that hepatocellular carcinoma has a different etiology when associated and not associated with chronic liver disease. In this study, 66 noncirrhotic cases found among 618 autopsies for hepatocellular carcinoma (10.7%) were analyzed retrospectively. The noncirrhotic liver was histologically unremarkable in 3 cases and in the histologically evaluable 56 cases it had fibrosis of varying degrees or mild cellular infiltrate, or both, in the portal tract. There was one liver that had portal venous changes compatible with those in idiopathic portal hypertension (Banti's syndrome). In these noncirrhotic livers, the parenchymal cells were generally unremarkable except for liver cell dysplasia that was seen in 26.8%. Serum hepatitis B surface antigen was positive in only 7.4% in contrast to 26.6% in cirrhotic cases. Three histologically unremarkable cases had no clinical or histologic evidence of chronic liver disease; two involved painter-plasterers and one a farmer. The liver weight in these cases ranged from 4400 to 6180 g. In contrast, the average liver weight in cirrhotic cases was 1998 g. Noncirrhotic patients when compared with cirrhotic patients had better liver function tests and much less frequent varices. It was concluded that approximately 11% of hepatocellular carcinoma cases in Japan are noncirrhotic, the majority having some histologic changes in the portal tracts suggestive of past or ongoing chronic liver disease, and that there are rare cases that have no histologic changes in the liver.     

Cirrhosis in children with celiac disease

BACKGROUND: Liver involvement represents an extra-intestinal feature of celiac disease (CD) and shows a clinical spectrum varying from nonspecific reactive hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5 children. PATIENTS AND METHODS: The mean age of the patients was 9.4 +/- 2.8 years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out. Intestinal and liver biopsies were performed to confirm the histologic diagnosis in all subjects. RESULTS: Three of the patients had chronic diarrhea and hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at presentation simultaneously. In the other 2 patients, CD was diagnosed following an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range, 64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum aminotransferase levels and clinical improvement were observed in 3 patients with strict GFD. The other 2 patients without improvement of the liver disease had poor dietary compliance. CONCLUSION: CD may be associated with severe hepatic damage in children and strict GFD may have beneficial effect on the course of liver disease. Serologic screening of CD should be included in differential diagnosis of chronic liver disease of unknown origin.     

AST/ALT Ratio Predicts Cirrhosis in Patients With Chronic Hepatitis C Virus Infection

Objective: A liver biopsy is necessary to grade and stage chronic hepatitis C virus (HCV) infection. In a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio > 1 suggested cirrhosis. We sought to examine the value of the AST/ALT ratio in distinguishing cirrhotic patients with chronic HCV infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices.
Methods: We retrospectively studied 139 patients with chronic HCV infection. Routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored.
Results: The mean AST/ALT ratio in the cirrhotic patients (  n = 47  ) was higher than in the noncirrhotic patients (  n = 92  ) (  1.06 ± 0.06 vs 0.60 ± 0.09  ;   p < 0.001  ). A ratio ≥1 had 100% specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2% sensitivity and 80.7% negative predictive value. The ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. Of the cirrhotic patients, 17% had no clinical or biochemical features suggestive of chronic liver disease except for an AST/ALT ratio ≥1.
Conclusion: The AST/ALT ratio is a dependable marker of fibrosis stage and cirrhosis in patients with chronic HCV infection.     

Prognosis and life expectancy in chronic liver disease

The aim of the present study was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population. After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population. Among patients with cirrhosis, prognosis was dependent upon the Child classification (P=0.001). Patients with alcoholic cirrhosis and fatty liver disease were younger (P=0.01) and had a lower life expectancy than patients with other causes of chronic liver disease (P=0.004). Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population. Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population. In patients with ₁-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P=0.01). For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population. In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and ₁-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population. Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment. In patients with hereditary liver disease, additional viral infection or alcohol abuse lead to a significant deterioration of life expectancy. Patients with alcoholic chronic liver disease have the poorest prognosis.     

Evaluation of risk factors for the development of cirrhosis in autoimmune hepatitis: Japanese NHO-AIH prospective study

Autoimmune hepatitis (AIH) is a chronic and progressive liver disease characterized by histological interface hepatitis and circulating autoantibodies. Our aims were to evaluate risk factors that contribute to the outcome and, particularly, the development of liver cirrhosis in a prospective multicenter cohort study of AIH. One hundred and seventy-four patients were enrolled. Histologically 21 (12.1%) had cirrhosis at the initial observation and the remaining 153 showed chronic or acute hepatitis at presentation. Among the latter 153 patients, 14 developed cirrhosis during the follow-up period (mean 8.0 years). Demographic, clinical, and laboratory indices associated with the development of cirrhosis were identified. Patients who developed cirrhosis differed in mean levels of alanine aminotransferase (ALT; 158 ± 182 vs. 441 ± 423 IU/ml) and platelet counts (14.7 ± 5.5 vs. 19.4 ± 6.9 × 10(4)/μl) at presentation and received lower doses of corticosteroid (13.9 ± 15.8 vs. 31.8 ± 85.5 mg/day). In a multivariate analysis, an independent predictor for progression to cirrhosis was an older age of onset (≥ 60 years). AIH patients with cirrhosis, or those who developed cirrhosis, had a worse survival. AIH patients with an older age of onset were likely to develop cirrhosis, and careful observation and aggressive treatments are necessary for such patients.     

Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center

BACKGROUND/AIMS: The natural history of chronic hepatitis C (HCV) is not completely understood. This study was aimed to evaluate the long-term outcome of the disease over a prolonged period of time and to identify factors associated with progression. METHODS: One hundred and sixteen patients with non-cirrhotic chronic non-A, non-B hepatitis consecutively diagnosed at a tertiary hospital between 1971 and 1977 were followed until December 1998 or until death. Patients with significant alcohol intake were excluded from the study. Variables obtained at the time of diagnosis, including epidemiological, clinical, laboratory, and histological data were recorded to determine risk factors associated with the development of liver cirrhosis and hepatic decompensation. RESULTS: Based on complete follow-up data, the development of liver cirrhosis and hepatic decompensation was evaluated in 94 and 114 of the 116 patients, respectively. Thirty-seven (39.3%) of 94 patients developed liver cirrhosis; an aspartate aminotransferase (AST) value higher than 70 IU/L was associated with development of cirrhosis (odds ratio (OR) 4.22, 95% CI 1.3-13.8). Hepatic decompensation occurred in 12 (10.5%) of 114 patients, its cumulative probability being 2.8% at 10 years, 5.2% at 15 years and 19.8% at 20 years. The only factor independently associated to the development of hepatic decompensation was the presence of fibrosis (stage 2 or 3) in the initial liver biopsy (OR 4.1, IC 95% 1.22-13.9). Liver-related death occurred only in seven (6%) of 114 patients. In comparison with the 116 patients diagnosed in the 1970's, patients with chronic hepatitis C diagnosed in 1999 were younger, more often asymptomatic, had lower AST and alanine aminotransferase (ALT) values and had significantly lower grade and stage histological scores. CONCLUSIONS: In summary, chronic hepatitis C had a high rate of progression to liver cirrhosis over a prolonged follow-up. However, this might be related to the fact that two decades ago the diagnosis was made at a significantly more advanced stage of the disease. Patients at high risk of progression can be identified by biochemical and histological variables at the time of diagnosis.     

Diagnostic Value of Serum γ-Glutamyl-Transferase Activity and Mean Corpuscular Volume in Alcoholic Patients with or without Cirrhosis

In an attempt to assess the diagnostic values of serum gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV) variations as markers of liver disease and of abstinence in alcoholic patients, we compared 174 patients with alcoholic cirrhosis, 175 with noncirrhotic alcoholic liver disease and 67 patients with nonalcoholic cirrhosis. GGT and MCV values were checked three times, the day of admission, 7 days later, and on the last sample available during follow-up (1 to 12 months), and were compared according to the liver disease and abstinence. A decrease of GGT activity during the 1st week of hospitalization was noted in alcoholics with (-9 IU/liter) or without (-13 IU/liter) cirrhosis and not in nonalcoholic cirrhosis (+8 IU/liter), without MCV variations. During follow-up, median GGT activity was strikingly different in abstinent patients with (27 IU/liter) or without (21 IU/liter) cirrhosis and in nonabstinent patients (99 IU/liter and 123 IU/liter, respectively) (p less than 0.001). MCV decrease was noted in alcoholics whatever their abstinence or not, contrasting with the absence of decrease in nonalcoholic patients. For the diagnosis of alcoholism in cirrhotic patients, the positive predictive value (PPV) of a GGT or a MCV decrease during the 1st week of hospitalization was 0.82 and 0.78, respectively, and the negative predictive value (NPV) was 0.33 and 0.70, respectively. For abstinence during follow-up, the PPV of a GGT activity less than 50 IU/liter was 0.92 and the NPV was 0.65.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum levels of cytokines in chronic liver diseases.

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and C-reactive protein (CRP) were investigated in patients with chronic liver diseases (CLD) and correlated with the type of underlying disease and various clinical and laboratory parameters. Two hundred sixty-four patients suffering from various CLD were studied; 136 cases presented with liver cirrhosis, and 128 patients were in the noncirrhotic stage of their underlying liver diseases. Serum levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and CRP were elevated in patients with CLD. Endogenous cytokine patterns in CLD were stage dependent and only marginally affected by the type of underlying disease. The cirrhotic group of CLD patients showed higher serum levels in IL-1 beta, IL-6, TNF-alpha, and CRP than did noncirrhotic cases, and these differences reached the level of statistical significance. IL-1 beta and TNF-alpha values were closely correlated but did not correlate with IL-6 levels. Elevated concentrations of cytokines represent a characteristic feature of CLD regardless of underlying disease. This and the apparent stage-dependency suggest that enhanced endogenous cytokine levels represent a consequence of liver dysfunction rather than of inflammatory disease.     

Bone disease in primary biliary cirrhosis: increased bone resorption and turnover in the absence of osteoporosis or osteomalacia

The role of vitamin D in hepatic osteodystrophy was examined. Eleven unselected patients with primary biliary cirrhosis (PBC) were assessed for disorders of mineral and vitamin D metabolism. Six were not receiving supplementary vitamin D, and five were being treated with oral vitamin D (50,000 IU daily). Serum levels of 25-hydroxyvitamin D were normal in all patients receiving oral therapy and in 4 of 6 untreated patients. Levels of serum 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D were normal or near normal in all patients. Studies were repeated after 6 months of therapy with parenteral vitamin D2 (100,000 IU i.m. monthly) in 7 patients. Initial bone histomorphometry revealed no evidence of osteomalacia or osteoporosis. However, the bone resorption surface of trabecular bone was increased. This abnormality was no longer present on repeat bone biopsies obtained after parenteral vitamin D therapy, and bone formation had decreased. In addition, trabecular bone volume remained normal in the face of the lower rate of bone formation. Increased bone resorption surface in the absence of osteoporosis or osteomalacia has not been previously described in PBC. Improvement in this bone parameter, associated with the finding of a decrease in the formation of bone and in hydroxyproline excretion in urine after parenteral vitamin D, suggests that increased turnover may be an early feature of the bone disease which complicates PBC and that parenteral vitamin D may retard the rate at which hepatic osteodystrophy develops in chronic cholestatic liver disease.     

Prognosis of alcoholic cirrhosis in the presence and absence of alcoholic hepatitis

Liver biopsy specimens (178 percutaneous and 39 transjugular) were assessed from 217 consecutive patients with alcoholic liver disease, 77 noncirrhotics and 140 cirrhotics, whose cases were followed for 5 yr. Cirrhotic patients were categorized into two groups, with and without "hepatitis" using a criteria to define "hepatitis" that included only degrees of inflammation, necrosis, and Mallory bodies that had a prognostic weight in terms of mortality in 1 yr. This classification resulted in a sharp separation between a group of 42 patients with cirrhosis without "hepatitis" and with low mortality, both at 1 yr (7.1% +/- 4.0%) and at 5 yr (31% +/- 7%), and another group of 98 patients with cirrhosis and "hepatitis" and a high mortality both at 1 yr (26.5% +/- 4.5%, p less than 0.01), and at 5 yr (47% +/- 5%, p less than 0.02). Importantly, the 1-yr mortality in patients with cirrhosis and no "hepatitis" was not statistically different from that of patients with no cirrhosis or "hepatitis" (most of whom had only fatty liver) both at 1 yr (6.9% +/- 3.3%) and at 5 yr (24% +/- 6%). There were marked differences in several variables between cirrhosis with and without "hepatitis" [combined clinical and laboratory index: no "hepatitis": 4.9 +/- 0.7, with "hepatitis": 7.8 +/- 0.5, p less than 0.01; score of collagen in space of Disse: no "hepatitis": 2.1 +/- 0.4, with "hepatitis": 3.7 +/- 0.3, p less than 0.01; hepatocyte cross-sectional surface area: no "hepatitis": 682 +/- 51 micron 2, with "hepatitis": 841 +/- 31 micron 2, p less than 0.01]. These findings were more severe in the transjugular group than in the percutaneous group. Collagen in the space of Disse and hepatocyte surface area were not statistically different when cirrhosis without "hepatitis" was compared with a similar no "hepatitis" group of patients having noncirrhotic alcoholic liver disease. In this patient sample the presence of parenchymal nodules and fibrous septa, per se, did not result in an increase in mortality with respect to alcoholic patients without cirrhosis and with no "hepatitis."     

Immunohistochemical detection of hepatitis C virus-infected hepatocytes in chronic liver disease with monoclonal antibodies to core, envelope and NS3 regions of the hepatitis C virus genome.

The localization of hepatitis C virus-infected hepatocytes in the human liver remains unclear despite the development of a serological assay for the antibody to hepatitis C virus. We studied their localization immunohistochemically with monoclonal antibodies to core, envelope and NS3 antigens of hepatitis C virus. We examined 48 liver biopsy samples from C100-3 antibody-positive patients with chronic liver disease (chronic persistent hepatitis, 5 cases; chronic active hepatitis, 41 cases; cirrhosis, 2 cases) and 12 liver biopsy samples from C100-3 antibody-negative patients with chronic liver disease (type B chronic hepatitis, 8 cases; alcoholic liver disease, 4 cases). In the C100-3 antibody-positive group, positive immunostaining for core antigen, envelope antigen and NS3 antigen was found in 23% (11 of 48), 24% (11 of 45) and 24% (11 of 46), respectively. Negative results were obtained in the C100-3 antibody-negative group. Hepatocytes with positive staining were scattered in the lobules, and they were found in the same regions irrespective of whether the antibody to core antigen, to envelope antigen or to NS3 antigen was used. Each positive cell was strongly stained in the cytoplasm; these decorations disappeared after absorption of the primary antibody with purified antigen. mean ALT levels in the patients with positive immunostaining for core, envelope or NS3 antigen (174.8 +/- 105.7 U/L) tended to be higher than in those with negative immunostaining (142.0 +/- 93.8 U/L). On histological evaluation of liver specimens with a scoring system of the histological activity index, intralobular inflammation and fibrosis had higher scores for samples with positive rather than negative immunostaining (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic (Noncirrhotic) Diffuse Liver Disease

Conclusions Chronic liver disease which is characterized histopathologically by portal fibrosis, portal round-cell infiltration, and/or fatty metamorphosis, in the absence of the perilobular fibrosis of cirrhosis, is usually a subclinical process, detected by the chance discovery of hepatomegaly. This hepatomegaly was a constant feature of the 67 patients reported upon, but it is highly probable that many other cases have been overlooked during the period of study because there was no liver enlargement. Mild splenomegaly and spider angiomas are not rare in chronic noncirrhotic liver disease.Esophageal varices are moderately common in patients with these forms of liver disease, but the precise incidence cannot be given because, as in cirrhosis, varices wax and wane and may disappear from time to time. In most instances they are only of mild or moderate size, and this makes radiologic detection impossible in most cases.Hemorrhage from esophageal varices is not nearly the threat that it is in cirrhosis, yet the risk exists and the ensuing hemorrhage may be severe.The esophageal varices which are encountered in cirrhosis may have their inception during the precirrhotic stages of chronic liver disease, before the beginning of lobular regeneration.     

Elevation of serum cystatin C concentrations in patients with chronic liver disease

OBJECTIVE: We examined serum cystatin C concentrations in patients to explore the possible clinical application of cystatin C as a marker of disease severity in cases of chronic liver diseases. METHODS: Serum cystatin C concentrations were determined by an enzyme-linked immunosorbent assay kit in 103 patients with various chronic liver diseases and compared with concentrations in healthy control volunteers. RESULTS: The mean cystatin C concentration was 0.68 +/- 0.03 mg/l in chronic hepatitis patients, 1.13 +/- 0.09 mg/l in liver cirrhosis patients and 1.16 +/- 0.10 mg/l in hepatocellular carcinoma patients, all significantly higher than concentrations in the control volunteers (P < 0.0001). Significant correlations were observed between cystatin C concentrations and total bilirubin levels, albumin levels, platelet levels, type IV collagen levels and hyaluronic acid levels. Serum cystatin C concentrations correlated well with histological stages despite the lack of correlation with histological grades. CONCLUSION: Our results show that serum cystatin C increases with the progression of chronic liver disease and that it is a potential marker for liver fibrosis.