Relation between plasma catecholamines, the severity of the liver disease and hemodynamics in patients with cirrhosis

Plasma noradrenaline and adrenaline concentrations were measured in 75 patients with cirrhosis in order to attempt to correlate these concentrations and liver failure and hemodynamic changes. The increased noradrenaline concentration was not correlated with the degree of liver failure estimated by Pugh's classification, with the cause of cirrhosis, with the presence of acute alcoholic hepatitis or with the presence of ascites. Adrenaline concentration was higher in cirrhotic patients with acute alcoholic hepatitis than in those without these lesions. Noradrenaline concentration was significantly correlated with heart rate, wedged hepatic venous pressure and renal blood flow. Noradrenaline concentration was also negatively correlated with stroke volume and adrenaline concentration was negatively correlated with cardiac output and stroke volume. These findings confirm the relationships between portal hypertension, sympathetic hyperactivity and renal function in patients with cirrhosis.     

The liver in heart failure

Severe congestive heart failure is associated with two distinct forms of liver dysfunction: jaundice that is related to passive congestion and acute hepatocellular necrosis that is caused by impaired perfusion. Cardiac cirrhosis (fibrosis) may result from prolonged recurrent congestive heart failure. Ischemic hepatitis (shock liver) usually manifests as asymptomatic elevation of the serum aminotransferase levels after an episode of hypotension, although the clinical presentation may mimic that of acute viral hepatitis. In most cases, ischemic hepatitis is of little clinical consequence and is self-limited. Acute liver failure may occur in patients with preexisting cirrhosis, severe chronic heart failure, or sustained hepatic ischemia.     

Metabolomics Discloses a New Non-invasive Method for the Diagnosis and Prognosis of Patients with Alcoholic Hepatitis

Introduction and aims. Alcoholic hepatitis is the most severe manifestation of alcoholic liver disease. Unfortunately, there are still some unresolved issues in the diagnosis and management of this disease, such as the need of histological diagnosis, an accurate prognostic stratification, and the development of novel targeted therapies. The present study aimed at addressing these issues by means of metabolomics, a novel high-throughput approach useful in other liver diseases.Material and methods. 64 patients with biopsy-proven alcoholic hepatitis were included and compared with 26 patients with decompensated alcoholic cirrhosis without superimposed alcoholic hepatitis, which was ruled out by liver biopsy.Results. The comparison of the metabolic profiles of patients with alcoholic hepatitis and decompensated cirrhosis showed marked differences between both groups. Importantly, metabolic differences were found among alcoholic hepatitis patients when subjects were stratified according to 90-day survival. Based on these findings, two non-invasive signatures were developed. The first one allowed an accurate non-invasive diagnosis of alcoholic hepatitis (AUROC 0.932; 95% CI 0.901-0.963). The second signature showed a good performance in the prognostic stratification of patients with alcoholic hepatitis (AUROC 0.963; 95% CI 0.895-1.000).Conclusions. Signatures based on metabolomics allowed an accurate non-invasive diagnosis and prognostic stratification of alcoholic hepatitis. The differences observed in the metabolic profile of the patients according to the presence and severity of alcoholic hepatitis are related with different mechanisms involved in the pathophysiology of alcoholic hepatitis such as peroxisomal activity, synthesis of inflammatory mediators or oxidation. This information could be useful for the development of novel targeted therapies.     

Long-term histologic follow-up study of alcoholic liver disease.

Forty Japanese patients with alcoholic liver disease (nonspecific change, 9; fatty liver, 5; hepatic fibrosis, 4; chronic hepatitis, 12; alcoholic hepatitis, 5; liver cirrhosis, 5) were followed for 3-17 yr (average 8 yr) with repeated liver biopsies (2-5 times; average 2.5 times) at intervals of more than 3 yr. All of the patients continued to consume alcohol during this observation period. Five out of 12 patients with chronic hepatitis and 2 of 5 patients with alcoholic hepatitis eventually progressed to cirrhosis, while none of the 4 patients with hepatic fibrosis became cirrhotic. Anti-hepatitis C virus antibody was positive in 2 patients with liver cirrhosis among 12 patients whose sera were available. Two patients with cirrhosis died of hepatic failure and one patient died of hepatocellular carcinoma. These data suggest that the long-term prognosis of alcoholic liver disease is not necessarily poor, but patients with chronic hepatitis or alcoholic hepatitis can be at risk of progression to cirrhosis.     

Alcohol-induced liver disease

Hepatic changes resulting from the regular ingestion of alcohol are many and include fat infiltration, alcoholic hepatitis, and cirrhosis. Only 10% to 15% of chronic alcoholics develop liver disease. Women are more susceptible. An area of considerable importance is the high prevalence of concomitant infection with hepatitis C virus in chronic alcoholics. Patients who have hepatitis C and alcohol-induced liver injury are much more likely to develop progressive liver disease and cirrhosis. Corticosteroid therapy has proven useful in the treatment of patients with severe acute alcoholic hepatitis.     

Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease

AIM: To analyze characteristics and outcome of patients with acute-on-chronic liver failure(ACLF) according to the severity of underlying liver disease. METHODS: One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis(type A), cirrhosis(type B) and cirrhosis with previous decompensation(type C).RESULTS: The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in typesB and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate(85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate(55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different(85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02).CONCLUSION: There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF.     

Relative Versus Absolute Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis

BACKGROUND: Carbohydrate-deficient transferrin has been described as a sensitive and specific marker for alcohol consumption. This study investigated the usefulness of carbohydrate-deficient transferrin as a marker of alcohol consumption in acute alcoholic hepatitis. METHODS: Absolute concentrations (U/I) and relative values (%) of carbohydrate-deficient transferrin determined in serum with commercial assays, as well as conventional markers for alcohol consumption, were compared with the alcohol consumption (as estimated by a questionnaire) in patients with acute alcoholic hepatitis (n = 19), alcoholic liver cirrhosis (n = 37), and nonalcoholic liver diseases (n = 16). RESULTS: The concentration of carbohydrate-deficient transferrin was increased (p < 0.001) in nonabstaining patients (median intake 80 g alcohol/day) with alcoholic liver cirrhosis (45.7 +/- 30 U/l), but not in patients with acute alcoholic hepatitis (20.0 +/- 7.8 U/l) despite higher alcohol consumption (median 130 g/d), nor in abstainers with alcoholic liver cirrhosis (19.4 +/- 6.0 U/l) or nonalcoholic liver disease (18.5 +/- 6.7 U/l). However, the relative values of carbohydrate-deficient transferrin were increased both in acute alcoholic hepatitis (7.9 +/- 2.1%) and nonabstainers with alcoholic liver cirrhosis (7.4 +/- 2.8%), but not in abstainers with alcoholic liver cirrhosis (4.6 +/- 3.5%) or nonalcoholic liver disease (3.8 +/- 0.9%) (p < 0.001). In acute alcoholic hepatitis, the sensitivity and specificity were only 32% and 87% for absolute concentrations, respectively, but 79% and 97% for relative values of carbohydrate-deficient transferrin. The concentrations of carbohydrate-deficient and total transferrin in serum were strongly correlated (r = 0.60; p = 0.008). CONCLUSIONS: The relative value (% of total), but not the absolute concentration, of carbohydrate-deficient transferrin in serum is a useful marker of alcohol consumption in acute alcoholic hepatitis.     

Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases

The centrilobular liver cell necrosis observed in hypoxic hepatitis is generally attributed to failure of hepatic blood perfusion. Accordingly, this injury of the liver is commonly recognized under the terms "shock liver" or "ischemic hepatitis." During a 10-year period, 142 episodes of hypoxic hepatitis were consecutively identified in the intensive care unit of a general hospital, and the clinical, biological, and hemodynamic parameters were prospectively collected on individual files. We conducted the current study to assess retrospectively the role of the hemodynamic mechanisms of tissue hypoxia: ischemia, passive venous congestion, and hypoxemia. Among the 142 episodes of hypoxic hepatitis, 138 were separated in 4 main groups based on clinical features: decompensated congestive heart failure (80 cases), acute cardiac failure (20 cases), exacerbated chronic respiratory failure (19 cases), and toxic/septic shock (19 cases). An elementary hemodynamic evaluation, including blood pressure, central venous pressure, and arterial blood gas analysis, was carried out in every episode and a more complete hemodynamic assessment through pulmonary artery catheterization was performed in 61 episodes.The hemodynamic mechanisms responsible for hypoxic hepatitis were different in the 4 groups. In congestive heart failure and acute heart failure, the hypoxia of the liver resulted from decreased hepatic blood flow (ischemia) due to left-sided heart failure and from venous congestion secondary to right-sided heart failure. In chronic respiratory failure, liver hypoxia was mainly due to profound hypoxemia. In toxic/septic shock, oxygen delivery to the liver was not decreased but oxygen needs were increased, while the liver was unable to use oxygen properly. In all conditions underlying hypoxic hepatitis, except toxic/septic shock, a shock state was observed in only about 50% of the cases. Therefore, the expressions "shock liver" or "ischemic hepatitis" are misleading and should be replaced by the more general term "hypoxic hepatitis."     

Prognostic Factors in Alcoholic Liver Disease

Two hundred eighty-one alcoholic patients were prospectively evaluated by clinical, biochemical, and histologic parameters during a 4-yr period to assess their prognosis. They were stratified into four categories of injury: 1) fatty liver (26 patients), 2) acute alcoholic hepatitis (106), 3) cirrhosis (39), and 4) cirrhosis with superimposed alcoholic hepatitis (111). The rate of survival and variables correlating with survival varied according to the group. At 48 months, 70% of the patients with fatty liver were alive, 58% in the alcoholic hepatitis group, 49% in cirrhosis, and 35% in alcoholic hepatitis superimposed upon cirrhosis. Within group one, deaths were due to causes unrelated to liver disease. In the alcoholic hepatitis group, factors significantly correlating with survival were ascites, alanine amino-transferase levels, grams of alcohol consumed, continuation of alcohol intake, and clinical severity of disease. Survival in patients of group three correlated significantly with prothrombin time and histologic severity score. Patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis, with the most significant predictors of survival being age, grams of alcohol consumed, the ratio of serum aminotransferases (AST:ALT) and the histologic and clinical severity of the disease. Although a different pattern of correlates was observed for each pathologic level of injury, knowledge of the various correlates aids in prognostic assessment.     

Contemporary Provider Management Practices and Attitudes Toward Referral for Advanced Heart Failure Therapies in Fontan Patients Across North America

Background: To date, no reports have described clinicians’ management practices for patients with Fontan circulatory failure or their understanding of risk factors for mortality and transplant outcomes in these patients.Methods and Results: A cross-sectional survey of caregivers across North America was conducted from February to September 2020. Responses were compared by primary specialty (heart failure/transplant vs non-heart failure/transplant), years of experience (early, mid, and late career), and Fontan center volume (low, medium, and high). Of 400 responses, the majority were from general cardiologists (111, 28%) followed by heart failure/transplant specialists (93, 23%). Although most agreed that patients with Fontan physiology will have signs/symptoms of heart failure (369 [93%]) and eventuate in heart transplant (286 [72%]), many disagreed (180 [45%]) that routine evaluation by a transplant cardiologist is needed without symptoms. Transplant providers were more likely than non-transplant providers to suggest referral for manifestations of Fontan circulatory failure such as protein-losing enteropathy, plastic bronchitis, liver fibrosis/cirrhosis, and worsening valve regurgitation. Non-transplant providers were more likely to suggest that protein-losing enteropathy, plastic bronchitis, and Fontan-associated liver disease lead to inferior outcomes after transplantation. Early career and transplant providers more favorably viewed ventricular assist device use for Fontan patients failing traditional heart failure therapy (P < .05 for all).Conclusions: There is significant variation in the management of Fontan patients, including heterogeneous timing of referral of such patients to the heart failure/transplant team, which may have implications for future outcomes.     

Anatomical cardiac alterations in liver cirrhosis: an autopsy study

Background. It has been suggested that liver cirrhosis (LC), regardless of etiology, may be associated with anatomical cardiac alterations.Objective. To describe the frequency and type of macroscopical anatomic cardiac abnormalities present in alcoholic and non-alcoholic cirrhotic patients in an autopsy series.Material and methods. The autopsy records performed at our institution during a 12-year period (1990-2002) were reviewed. All cases with final diagnosis of LC were included, their demographic characteristics as well as cirrhosis etiology and macroscopic anatomical cardiac abnormalities (MACA) analyzed. Patients with any known history of heart disease prior to diagnosis of cirrhosis were excluded.Results. A total of 1,176 autopsies were performed, of which 135 cases (11.5%) were patients with LC. Two patients with cardiac cirrhosis were excluded. Chronic alcohol abuse (29%) and chronic hepatitis due to hepatitis C virus (HCV) infection (20%) were the most common causes of cirrhosis. The etiology was not identified in 35% of the cases, even after exhaustive clinical, serological and/or radiological assessment. In the postmortem analysis, 43% of the cases were informed to have MACA (47% in the group of patients with alcoholic cirrhosis and 41% in other types of cirrhosis); this rate increased to 62% in patients with ascites. The most frequent alterations were cardiomegaly and left ventricular hypertrophy (LVH).Conclusion. The results confirm the high frequency of cardiac abnormalities in patients with cirrhosis, regardless of cirrhosis etiology.     

Hepatitis C: Basic and clinical studies

The HCV, a single stranded RNA virus belonging to the family of flavivirus, has been identified as the probable cause of the majority of cases of transfusion-associated NANB hepatitis and community-acquired NANB hepatitis in Japan. The hepatitis virus is present in a least 2% of the blood donor population and is extremely common in high risk groups, such as hemophiliacs and hemodialysis patients. The contribution of HCV infection to sporadic, acute and chronic hepatitis, liver cirrhosis and primary liver cancer has been established. Furthermore anti-HCV in 20% of alcoholic patients with liver injury suggest that HCV may be etiologically associated with liver disease previously attributed to other causes. Therapy of acute and chronic liver disease associated with HCV infection is likely to be undertaken with recombinant IFN alpha in the future to prevent the progression of the disease from acute hepatitis to chronic hepatitis, and from chronic hepatitis to liver cirrhosis or primary liver cancer. However the prevention of HCV infection will be the goal, in addition to screening of donor blood and exclusion to a large degree of positive units likely to decrease the incidence of post-transfusion hepatitis.     

Hepatitis C: basic and clinical studies.

The HCV, a single stranded RNA virus belonging to the family of flavivirus, has been identified as the probable cause of the majority of cases of transfusion-associated NANB hepatitis and community-acquired NANB hepatitis in Japan. The hepatitis virus is present in a least 2% of the blood donor population and is extremely common in high risk groups, such as hemophiliacs and hemodialysis patients. The contribution of HCV infection to sporadic, acute and chronic hepatitis, liver cirrhosis and primary liver cancer has been established. Furthermore anti-HCV in 20% of alcoholic patients with liver injury suggest that HCV may be etiologically associated with liver disease previously attributed to other causes. Therapy of acute and chronic liver disease associated with HCV infection is likely to be undertaken with recombinant IFN alpha in the future to prevent the progression of the disease from acute hepatitis to chronic hepatitis, and from chronic hepatitis to liver cirrhosis or primary liver cancer. However the prevention of HCV infection will be the goal, in addition to screening of donor blood and exclusion to a large degree of positive units likely to decrease the incidence of post-transfusion hepatitis.     

Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease

BACKGROUND/AIMS: Alcoholic cirrhosis is a common indication for liver transplantation. The present study was aimed to assess the influence of superimposed alcoholic hepatitis on the outcome of liver transplantation in patients with alcoholic cirrhosis.METHODS: Survival rates of 68 patients transplanted for alcoholic cirrhosis were compared with those of 101 patients transplanted for miscellaneous causes. Within the alcoholic group, explanted livers were searched for data of acute alcoholic hepatitis. The survival rate of patients with alcoholic hepatitis superimposed on liver cirrhosis was compared to that of patients with liver cirrhosis alone. Clinical severity of alcoholic hepatitis was assessed with Maddrey's score.RESULTS: Survival was similar in alcoholics and patients with other causes of liver disease. Among patients transplanted for alcoholic cirrhosis, survival was similar in patients with superimposed alcoholic hepatitis (n=36) and in cases with liver cirrhosis alone (n=32). There was no difference in survival between patients with mild (n=26) and severe (n=10) alcoholic hepatitis. Seven alcoholics (10%) returned to ethanol consumption. Recidivism was not associated with either alcoholic hepatitis in the explanted liver or graft loss.CONCLUSIONS: Survival after liver transplantation in patients with alcoholic cirrhosis plus alcoholic hepatitis detected in the explanted liver is similar to that of patients transplanted for other reasons. Even the presence of severe alcoholic hepatitis does not worsen the outcome of liver transplantation for end-stage alcoholic liver disease.     

Value of serum immunoglobulins in the diagnosis of liver disease

Serum immunoglobulins were determined in 145 consecutive patients with biopsy-proven steatosis, alcoholic hepatitis, alcoholic hepatitis with fibrosis, alcoholic hepatitis with cirrhosis, inactive cirrhosis, chronic active alcoholic hepatitis, chronic active hepatitis, primary biliary cirrhosis and nonspecific hepatitis. IgM was both a sensitive (90.5%) and specific (86.2%) marker for primary biliary cirrhosis, and mean IgM levels were higher in primary biliary cirrhosis than in other diagnostic categories (p less than 0.05). IgA levels were most commonly elevated in alcoholic liver disease (p less than 0.005). IgA detected 95% of alcoholic disease, but was poorly specific (41.1%). A trend of rising IgA with increasing severity of alcoholic injury was observed, but the differences were not significant. IgG was most commonly elevated in chronic active hepatitis and alcoholic hepatitis with cirrhosis, but the IgG values did not differ significantly from those found in other diagnostic categories. Our results substantiate assertions of a diagnostic sensitivity for elevated IgA in alcoholic liver disease and IgM in primary biliary cirrhosis. With the exception of IgM in primary biliary cirrhosis, however, serum immunoglobulins are not specific markers of liver histology.     

Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder

Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.     

Lipid-bound sialic acid (LSA) in liver diseases of different etiologies

Objective. There are evidences that the changes in glycosylation and sialylation of proteins and lipids play an important role in the pathogenesis and progression of various liver diseases. The aim of this study was to evaluate the changes in the sialylation of serum lipids measured by the level of lipid-bound sialic acid (LSA) in liver diseases of different etiologies.Materials and methods. Tested group consisted of 303 patients suffering from liver diseases: alcoholic and non-alcoholic cirrhosis, chronic non-viral hepatitis, toxic hepatitis, chronic viral C and B hepatitis, autoimmune hepatitis, primary liver cancer, liver cancer and cirrhosis (mixed group), acute hepatitis B, primary biliary cirrhosis and fatty liver. LSA was determined by the method of Katopodis and co-workers.Results. There were significant differences in the serum LSA concentrations between liver diseases of different etiologies. The level of LSA in liver tumors was higher than that in both types of cirrhosis: alcoholic and non-alcoholic. In turn, LSA level in non-alcoholic cirrhosis was lower than in toxic hepatitis and mixed group. There was no difference in LSA concentration between tumor and mixed group. Similarly to LSA, AFP level in tumor group was also higher than that in both cirrhotic groups, but there was no difference in AFP concentration between tumor and mixed group.Conclusions. The sialylation of serum lipids alters in liver diseases of different etiologies. Given the importance of glycans in biological systems we can speculate that the changes in lipids sialylation play an important role in liver pathology, especially in primary cancer, cirrhosis and toxic hepatitis.     

Hepato-cardiac disorders简

Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases     

A Case Report of Hepatocellular Carcinoma 5 Years After HBsAg Loss in Chronic Hepatitis Delta: How Long Surveillance is Required?

BackgroundHepatitis delta virus infection occurs as acute coinfection or as superinfection in patients with preexisting chronic hepatitis B. Chronic hepatitis delta leads to more severe disease than chronic hepatitis B, with more rapid progression of fibrosis and increased risk of hepatocelullar carcinoma.Case reportWe report a case of hepatocelullar carcinoma 5 years after spontaneous clearance of Hepatitis B surface antigen in a patient with previous chronic hepatitis delta. He had been diagnosed with acute hepatitis delta superinfection 30 years ago which evolved to chronic delta infection and subsequently development of liver cirrhosis. Despite no specific antiviral treatment, he lost HBsAg persistently with later regression of cirrhosis.ConclusionsIn patients with cirrhosis due to chronic hepatitis delta who cleared HBsAg with improvement of liver fibrosis by non invasive techniques, it remains unknown how long hepatocelullar carcinoma surveillance has to be maintained.     

Prevalence of anti-HCV among Chinese patients with acute and chronic liver disease

To assess whether the hepatitis C virus plays an important role in Chinese patients with acute and chronic liver disease, antibodies to HCV (anti-HCV) were measured by enzyme immunoassay in 67 patients with type A and B acute viral hepatitis, 165 patients with non-A, non-B (NANB) hepatitis, 438 patients with chronic hepatitis, 200 patients with postnecrotic liver cirrhosis, 72 patients with alcoholic liver disease, 55 patients with non-alcoholic fatty liver, 24 patients with toxic and drug-induced hepatitis, and 20 patients with other chronic liver diseases. Anti-HCV was not detected in sera from patients with type A and B acute viral hepatitis, toxic and drug-induced hepatitis, primary biliary cirrhosis, Wilson's disease, or lupoid hepatitis. The anti-HCV prevalence was found to be highest in patients with NANB hepatitis (59% in sporadic and 73.2% in transfusion-associated), 16.4% in non-alcoholic fatty liver, 5.6% in alcoholic liver disease, 6.8% in chronic hepatitis, and 16% in postnecrotic liver cirrhosis. In patients with chronic hepatitis, the anti-HCV prevalence was significantly higher in HBsAg-negative (15/34, 44.1%) than in HBsAg-positive cases (15/404, 3.7%; P less than 0.0001). The results indicate that HCV is a major agent of NANB hepatitis and plays an important role in HBsAg-negative chronic liver disease in Taiwan.