Journal of Gastroenterology and Hepatology (1992) 7 , 30-35
LIVER AND BILIARY High prevalence of antibody to hepatitis C virus in heavy drinkers with chronic liver diseases in Japan SATOSHI SHIMIZU,“: KENDO KIYOSAWA,” TAKESHI SODEYAMA,” EIJI TANAKA AND MASAYUKI NAKANOt :!’Departmentof Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan and tDepartment of Chemicobiological Interaction, Research Center for Pathologic Fungi and Microbial Toxicoses, Chiba University, Chiba, Japan Abstract To investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80g of ethanol daily for 5 years or more. Findings for anti-HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.30/0)of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti-HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/12 I , 4.2%). Considering histologic findings in the anti-HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti-HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti-HCV, histologic findings indicated the possibility of viral infection. Key words: alcoholic liver disease, antibody to HCV, heavy drinking, hepatitis C virus, hepatitis virus marker.
INTRODUCTION Although the histological findings in alcohol-induced liver disease are usually classified as fatty liver (FL), alcoholic fibrosis (AF) alcoholic hepatitis (AH) and liver cirrhosis (LC), findings compatible with chronic hepatitis (CH) are not unusual. Hepatocellular carcinoma (HCC) is associated with the chronic intake of alcohol.2 It has been reported that infection with hepatitis B virus (HBV) in heavy drinkers may predispose to the development of chronic liver disease. It has been also observed by many investigators that serological markers of past or present infection with HBV are found more often in patients with alcoholic cirrhosis than in alcoholics without liver disease, or in healthy non-alcoholic Because the incidence of chronic liver disease due to the blood-borne non-A, non-B hepatitis virus is increasing in Japan, the diagnosis of HCV infection should be considered in heavy drinkers with chronic liver disease.’ As there had been no diagnostic markers available for detecting infection by the agents for non-A, non-B hepatitis,
’
there are cases in which alcohol-induced liver injury was difficult to differentiate from the chronic liver disease caused by these viruses. Recently, however, the cloning of the genome of a blood-borne non-A, non-B hepatitis virus designated hepatitis C virus (HCV), has allowed detection of the antibody (anti-HCV) in human serum.’*’ Accordingly, in this study we assayed anti-HCV in the sera of Japanese heavy drinkers with chronic liver disease confirmed by liver biopsy and in those of heavy drinkers without apparent liver injury. The histological features of the biopsy specimens were correlated with serological findings.
METHODS Patients We studied a total of 113 heavy drinkers with biopsy-proven liver disease who had been admitted to the Second Department of Internal Medicine of the Shinshu University Hospital between January 1985 and December 1989. There were
Correspondence: Kendo Kivosawa MD, Second Department of Internal Medicine, Shinshu University School of Medicine, 3-1-I , Asahi, Matsumoto, Nagano-ken 390, Japan. Accepted for publication 8 March 1991.
31
Anti-HCV in alcoholic liver disease
105 males and 8 females, aged 24 to 71 years, mean age 46.5 years. All had consumed more than 80 g ethanol per day for 5 years or longer. Patients with liver cirrhosis or hepatocellular carcinoma in particular had consumed more than 130g ethanol per day for ten years or longer. In addition, we evaluated 121 patients with chronic alcoholism who visited a psychiatric clinic. This group included 114 males and 7 females, aged 28 to 83 years (mean: 53.0 years), with normal liver function tests, who had consumed more than lOOg ethanol per day for 9 years or longer. Patients with liver injury attributable to auto-immune mechanisms, drug administration, parasitic infections, metabolic disorders, or to congestive heart failure, were excluded from this study. Also, patients who were HBsAg positive or had abused drugs, and those who had a history of blood transfusion, were excluded.
Blood biochemical examination Thirty-one patients of 39 cirrhotics were evaluated for liver function tests between admission and 1 month later. Liver function tests were: serum total bilirubin (T.Bil), serum total protein (TP), serum albumin, serum glutamic oxaloacetic transaminase (GOT), serum glutamic pyruvic transaminase (GPT),and gamma-glutamyl transpeptidase (y-GTP). Eight cases did not comply with evaluation because of lack of laboratory data. All patients continued drinking until admission but stopped during hospitalization. The changes in liver function tests were compared between anti-HCV positive and negative patients with cirrhosis.
Assessment of alcohol intake Each participant was interviewed by the authors to obtain detailed information about their drinking habits. They were asked to answer questions on the duration of drinking and mean daily alcohol intake. Using this information we calculated the cumulative total consumption of alcohol.
Serological tests for viral hepatitis markers Serum samples were collected on the day of admission or on the day that liver biopsy was performed. Sera were then tested for HBsAg and anti-HCV. The assay for HBsAg was done by a standard enzyme immunoassay method (Enzygnost HBs, Behringwerke, AG). Anti-HCV was tested by an enzyme immunoassay using a HCV antibody enzyme-linked immunosorbent assay (ELISA) test system (Ortho Diagnostics Co., Raritan, NJ) according to the manufacturer’s directions. Yellow end-products were read by a micro-well reader at 490 k 2 nm and the cut-off value was set at an optical density derived from the negative control mean + 0.400.Samples with values exceeding the cut-off values for controls were tested in duplicate. Samples that exceeded the cut-off value were tested by Chiron recombinant immunoblot assay (RIBA) to evaluate the presence of antiHCV antibody. This test uses recombinant antigen c-100 expressed in yeast (used in the ELISA test) plus a subsequence of c-100 (5-1-1) expressed in Escherichia coli. Both antigens are coated in distinct band on nitrocellulose strips. Results (reactive, indeterminate or negative) are obtained by comparing the antigen band colour with that of positive controls.
Morphological examination All histological analyses were made by the same pathologist (N.M.) without knowledge of the clinical and laboratory findings. Liver sections were stained with haematoxylin and eosin, and Azan Mallory. In suspected cases of liver cirrhosis, peritoneoscopy was performed and the surface of the liver was observed macroscopically. Nodules on the liver surface were classified into two groups according to diameter: micro (< 3 mm) and macro (> 3 mm). Histological diagnosis was made according to the conventional classification, as fatty liver (10 cases), alcoholic hepatic fibrosis (22 cases), alcoholic hepatitis (3 cases) and cirrhosis (39 cases). Fifteen patients were diagnosed as having chronic hepatitis. In 24 patients, the diagnosis was hepatocellular carcinoma, based on high serum level of a-fetoprotein, ultrasonographic and computerized tomography findings, and also by selective angiographic examination. In patients with hepatocelMar carcinoma, liver specimens including the tumorous portion were not always available for every patient. In patients with liver cirrhosis, the histological features were analysed systematically. They included lymph follicle formation in the portal area, mesenchymal inflammatory cellular infiltration, piecemeal necrosis, focal necrosis in the lobule, fatty changes in hepatocytes, hydropic swelling of hepatocytes, megamitochondria, cholestasis, hemosiderin pigment deposition, fibrosis and pericellular fibrosis.
Statistical analyis Data were analysed by the Chi-squared test, Student’s t-test and Fisher’s exact test. The probability level was P < 0.05.
RESULTS Prevalence of anti-HCV in heavy drinkers Fifty-six of 234 alcoholics (50 with liver disease and 6 without documented liver disease) tested positive for antiHCV by ELISA. Fifteen of these were non-reactive or indeterminate in the RIBA assay, resulting in a ‘confirmed’ anti-HCV prevalence of 18% (41 of 234). As shown in Table 1, positive findings for anti-HCV by RIBA testing were found in none of 10 patients with FL, none of 22 patients with AF, none of 3 patients with AH, 5 (4.2%) of the 121 alcoholics with no liver injury, 14 (35.9%) of 39 patients with LC, 8 (53.3%) of 15 patients with CH and 14 (58.3%) of 24 patients with HCC. There was a significant difference in the prevalence of anti-HCV between the broad two categories of disease evaluated - that is between FL, AF, AH and alcoholism versus LC, CH and HCC.
S . Shirnim et al.
32
Comparison of liver fqnction tests between antiHCV positive and negative patients with liver cirrhosis In anti-HCV positive patients, serum values of T.Bi1, TP, albumin, GOT, GPT and y-GTP did not change significantly during the clinical course after admission. On the other hand, in anti-HCV negative patients, GOT, GPT and y G T P levels decreased significantly (GOT: P < 0.01, GPT: P < 0.01, y-GTP: P < 0.05). In anti-HCV negative patients, y-GTP and IgA levels in sera were significantly higher than in anti-HCV positive patients on admission (1'-GTP: P < 0.01, IgA: P < 0.02; Table 2).
Size of nodules in anti-HCV positive vs anti-HCV negative patients with liver cirrhosis In the 39 patients with liver cirrhosis, 29 (74%) had a micronodular liver and 10 (26%) a macronodular liver. Of the latter, 7 (70%) were positive for anti-HCV, a significantly higher prevalence than in patients with a micronodular liver (7 of 29, 24.1Oh; Table 3). Results of histologic evaluation of cirrhotic patients are presented in Table 4. There was a significant difference between 14 anti-HCV positive cirrhotics and 25 anti-HCV negative ones in findings of lymph follicle formation in the portal area (71% vs O%, P < 0.001), mesenchymal inflammatory cellular infiltration (79% vs 36%, P < 0.05) and piecemeal necrosis (79% vs 12%, P < 0.001). The dense fibrosis composed of fibres and dark matrix characteristicof chronic alcoholism (Fig. 1)'' was found in 80% (20 of 25) of anti-HCV negative cases compared with 35.7% (5 of 14) of anti-HCV positive cases, and loose fibrosis composed of distinct collagen fibres and clear space (Fig. Ib) was observed in 64.3% (9 of 14) of antiHCV positive cases, compared with 20% (5 of 25) of antiHCV negative cases (P < 0.02).
Table 1 Prevalence of anti-HCV in heavy drinkers with or without liver disease Anti-HCV (%)
Histologic diagnosis No. M : F Age (years)
Fatty liver Alcoholic fibrosis Alcoholic hepatitis Chronic hepatitis Liver cirrhosis Hepatocellular carcinoma Alcoholism
10 22 3 15 39
10 : 0 35.5 rt 8.5 21 : 1 49.6 rt 9.5 3 : 0 32.3 rt 1.5 14: 149.8 f 11.8 34: 5 49.1 rt 8.9
ELISA
RIBA
0 (0.0) 1 (4.5) 0 (0.0) 11 (73.3) 18 (46.2)
0 (0.0) 0 (0.0) 0 (0.0) 8 (53.3Y 14 (35.9)' li
24 23: 1 60.2 f 7.3 20 (83.3) 14 (58.3)+ 121 114: 7 53.0 ? 10.4 6 (5.0) 5 (4.2)*
P < 0.02 (vs FL, AF). P < 0.01 (ns AF). tP < 0 01 (vs FL, AF). ' P < 0.01 (vs FL + AF + AH
+ CH + LC + HCC).
Table 3 Correlation of anti-HCV and sue of liver surface nodule in liver cirrhosis (n = 39) Anti-HCV Size of nodule
No.
Micronodule (< 3 mm) Macronodule (> 3 mm)
29 10
Positive (Yu) Negative (YO) 7 (24.1) 7 (70.0).!:
22 (75.9) 3 (30.0)
:::P= 0.0139 (Fisher's exact test).
Correlation of prevalence of anti-HCV and history of ethanol consumption in patients with CH, LC and HCC The number of patients with alcoholic fibrosis (AF) who were positive for anti-HCV was too small to permit statistical analysis. Thus, a comparison was made only in the 78
Table 2 Comparison of serial changes in liver function tests after hospitalization between anti-HCV positive and negative patients with cirrhosis Anti-HCV positive n
At admission
1 month
Anti-HCV negative Significance
n
At admission
1 month
Significance
1.5 f 1.3 7.4 f 0.7 3.5 t 0.6 51 f 2 5 32 f 13 149 +_ 149
NS NS NS P
LIVER AND BILIARY High prevalence of antibody to hepatitis C virus in heavy drinkers with chronic liver diseases in Japan SATOSHI SHIMIZU,“: KENDO KIYOSAWA,” TAKESHI SODEYAMA,” EIJI TANAKA AND MASAYUKI NAKANOt :!’Departmentof Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan and tDepartment of Chemicobiological Interaction, Research Center for Pathologic Fungi and Microbial Toxicoses, Chiba University, Chiba, Japan Abstract To investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80g of ethanol daily for 5 years or more. Findings for anti-HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.30/0)of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti-HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/12 I , 4.2%). Considering histologic findings in the anti-HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti-HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti-HCV, histologic findings indicated the possibility of viral infection. Key words: alcoholic liver disease, antibody to HCV, heavy drinking, hepatitis C virus, hepatitis virus marker.
INTRODUCTION Although the histological findings in alcohol-induced liver disease are usually classified as fatty liver (FL), alcoholic fibrosis (AF) alcoholic hepatitis (AH) and liver cirrhosis (LC), findings compatible with chronic hepatitis (CH) are not unusual. Hepatocellular carcinoma (HCC) is associated with the chronic intake of alcohol.2 It has been reported that infection with hepatitis B virus (HBV) in heavy drinkers may predispose to the development of chronic liver disease. It has been also observed by many investigators that serological markers of past or present infection with HBV are found more often in patients with alcoholic cirrhosis than in alcoholics without liver disease, or in healthy non-alcoholic Because the incidence of chronic liver disease due to the blood-borne non-A, non-B hepatitis virus is increasing in Japan, the diagnosis of HCV infection should be considered in heavy drinkers with chronic liver disease.’ As there had been no diagnostic markers available for detecting infection by the agents for non-A, non-B hepatitis,
’
there are cases in which alcohol-induced liver injury was difficult to differentiate from the chronic liver disease caused by these viruses. Recently, however, the cloning of the genome of a blood-borne non-A, non-B hepatitis virus designated hepatitis C virus (HCV), has allowed detection of the antibody (anti-HCV) in human serum.’*’ Accordingly, in this study we assayed anti-HCV in the sera of Japanese heavy drinkers with chronic liver disease confirmed by liver biopsy and in those of heavy drinkers without apparent liver injury. The histological features of the biopsy specimens were correlated with serological findings.
METHODS Patients We studied a total of 113 heavy drinkers with biopsy-proven liver disease who had been admitted to the Second Department of Internal Medicine of the Shinshu University Hospital between January 1985 and December 1989. There were
Correspondence: Kendo Kivosawa MD, Second Department of Internal Medicine, Shinshu University School of Medicine, 3-1-I , Asahi, Matsumoto, Nagano-ken 390, Japan. Accepted for publication 8 March 1991.
31
Anti-HCV in alcoholic liver disease
105 males and 8 females, aged 24 to 71 years, mean age 46.5 years. All had consumed more than 80 g ethanol per day for 5 years or longer. Patients with liver cirrhosis or hepatocellular carcinoma in particular had consumed more than 130g ethanol per day for ten years or longer. In addition, we evaluated 121 patients with chronic alcoholism who visited a psychiatric clinic. This group included 114 males and 7 females, aged 28 to 83 years (mean: 53.0 years), with normal liver function tests, who had consumed more than lOOg ethanol per day for 9 years or longer. Patients with liver injury attributable to auto-immune mechanisms, drug administration, parasitic infections, metabolic disorders, or to congestive heart failure, were excluded from this study. Also, patients who were HBsAg positive or had abused drugs, and those who had a history of blood transfusion, were excluded.
Blood biochemical examination Thirty-one patients of 39 cirrhotics were evaluated for liver function tests between admission and 1 month later. Liver function tests were: serum total bilirubin (T.Bil), serum total protein (TP), serum albumin, serum glutamic oxaloacetic transaminase (GOT), serum glutamic pyruvic transaminase (GPT),and gamma-glutamyl transpeptidase (y-GTP). Eight cases did not comply with evaluation because of lack of laboratory data. All patients continued drinking until admission but stopped during hospitalization. The changes in liver function tests were compared between anti-HCV positive and negative patients with cirrhosis.
Assessment of alcohol intake Each participant was interviewed by the authors to obtain detailed information about their drinking habits. They were asked to answer questions on the duration of drinking and mean daily alcohol intake. Using this information we calculated the cumulative total consumption of alcohol.
Serological tests for viral hepatitis markers Serum samples were collected on the day of admission or on the day that liver biopsy was performed. Sera were then tested for HBsAg and anti-HCV. The assay for HBsAg was done by a standard enzyme immunoassay method (Enzygnost HBs, Behringwerke, AG). Anti-HCV was tested by an enzyme immunoassay using a HCV antibody enzyme-linked immunosorbent assay (ELISA) test system (Ortho Diagnostics Co., Raritan, NJ) according to the manufacturer’s directions. Yellow end-products were read by a micro-well reader at 490 k 2 nm and the cut-off value was set at an optical density derived from the negative control mean + 0.400.Samples with values exceeding the cut-off values for controls were tested in duplicate. Samples that exceeded the cut-off value were tested by Chiron recombinant immunoblot assay (RIBA) to evaluate the presence of antiHCV antibody. This test uses recombinant antigen c-100 expressed in yeast (used in the ELISA test) plus a subsequence of c-100 (5-1-1) expressed in Escherichia coli. Both antigens are coated in distinct band on nitrocellulose strips. Results (reactive, indeterminate or negative) are obtained by comparing the antigen band colour with that of positive controls.
Morphological examination All histological analyses were made by the same pathologist (N.M.) without knowledge of the clinical and laboratory findings. Liver sections were stained with haematoxylin and eosin, and Azan Mallory. In suspected cases of liver cirrhosis, peritoneoscopy was performed and the surface of the liver was observed macroscopically. Nodules on the liver surface were classified into two groups according to diameter: micro (< 3 mm) and macro (> 3 mm). Histological diagnosis was made according to the conventional classification, as fatty liver (10 cases), alcoholic hepatic fibrosis (22 cases), alcoholic hepatitis (3 cases) and cirrhosis (39 cases). Fifteen patients were diagnosed as having chronic hepatitis. In 24 patients, the diagnosis was hepatocellular carcinoma, based on high serum level of a-fetoprotein, ultrasonographic and computerized tomography findings, and also by selective angiographic examination. In patients with hepatocelMar carcinoma, liver specimens including the tumorous portion were not always available for every patient. In patients with liver cirrhosis, the histological features were analysed systematically. They included lymph follicle formation in the portal area, mesenchymal inflammatory cellular infiltration, piecemeal necrosis, focal necrosis in the lobule, fatty changes in hepatocytes, hydropic swelling of hepatocytes, megamitochondria, cholestasis, hemosiderin pigment deposition, fibrosis and pericellular fibrosis.
Statistical analyis Data were analysed by the Chi-squared test, Student’s t-test and Fisher’s exact test. The probability level was P < 0.05.
RESULTS Prevalence of anti-HCV in heavy drinkers Fifty-six of 234 alcoholics (50 with liver disease and 6 without documented liver disease) tested positive for antiHCV by ELISA. Fifteen of these were non-reactive or indeterminate in the RIBA assay, resulting in a ‘confirmed’ anti-HCV prevalence of 18% (41 of 234). As shown in Table 1, positive findings for anti-HCV by RIBA testing were found in none of 10 patients with FL, none of 22 patients with AF, none of 3 patients with AH, 5 (4.2%) of the 121 alcoholics with no liver injury, 14 (35.9%) of 39 patients with LC, 8 (53.3%) of 15 patients with CH and 14 (58.3%) of 24 patients with HCC. There was a significant difference in the prevalence of anti-HCV between the broad two categories of disease evaluated - that is between FL, AF, AH and alcoholism versus LC, CH and HCC.
S . Shirnim et al.
32
Comparison of liver fqnction tests between antiHCV positive and negative patients with liver cirrhosis In anti-HCV positive patients, serum values of T.Bi1, TP, albumin, GOT, GPT and y-GTP did not change significantly during the clinical course after admission. On the other hand, in anti-HCV negative patients, GOT, GPT and y G T P levels decreased significantly (GOT: P < 0.01, GPT: P < 0.01, y-GTP: P < 0.05). In anti-HCV negative patients, y-GTP and IgA levels in sera were significantly higher than in anti-HCV positive patients on admission (1'-GTP: P < 0.01, IgA: P < 0.02; Table 2).
Size of nodules in anti-HCV positive vs anti-HCV negative patients with liver cirrhosis In the 39 patients with liver cirrhosis, 29 (74%) had a micronodular liver and 10 (26%) a macronodular liver. Of the latter, 7 (70%) were positive for anti-HCV, a significantly higher prevalence than in patients with a micronodular liver (7 of 29, 24.1Oh; Table 3). Results of histologic evaluation of cirrhotic patients are presented in Table 4. There was a significant difference between 14 anti-HCV positive cirrhotics and 25 anti-HCV negative ones in findings of lymph follicle formation in the portal area (71% vs O%, P < 0.001), mesenchymal inflammatory cellular infiltration (79% vs 36%, P < 0.05) and piecemeal necrosis (79% vs 12%, P < 0.001). The dense fibrosis composed of fibres and dark matrix characteristicof chronic alcoholism (Fig. 1)'' was found in 80% (20 of 25) of anti-HCV negative cases compared with 35.7% (5 of 14) of anti-HCV positive cases, and loose fibrosis composed of distinct collagen fibres and clear space (Fig. Ib) was observed in 64.3% (9 of 14) of antiHCV positive cases, compared with 20% (5 of 25) of antiHCV negative cases (P < 0.02).
Table 1 Prevalence of anti-HCV in heavy drinkers with or without liver disease Anti-HCV (%)
Histologic diagnosis No. M : F Age (years)
Fatty liver Alcoholic fibrosis Alcoholic hepatitis Chronic hepatitis Liver cirrhosis Hepatocellular carcinoma Alcoholism
10 22 3 15 39
10 : 0 35.5 rt 8.5 21 : 1 49.6 rt 9.5 3 : 0 32.3 rt 1.5 14: 149.8 f 11.8 34: 5 49.1 rt 8.9
ELISA
RIBA
0 (0.0) 1 (4.5) 0 (0.0) 11 (73.3) 18 (46.2)
0 (0.0) 0 (0.0) 0 (0.0) 8 (53.3Y 14 (35.9)' li
24 23: 1 60.2 f 7.3 20 (83.3) 14 (58.3)+ 121 114: 7 53.0 ? 10.4 6 (5.0) 5 (4.2)*
P < 0.02 (vs FL, AF). P < 0.01 (ns AF). tP < 0 01 (vs FL, AF). ' P < 0.01 (vs FL + AF + AH
+ CH + LC + HCC).
Table 3 Correlation of anti-HCV and sue of liver surface nodule in liver cirrhosis (n = 39) Anti-HCV Size of nodule
No.
Micronodule (< 3 mm) Macronodule (> 3 mm)
29 10
Positive (Yu) Negative (YO) 7 (24.1) 7 (70.0).!:
22 (75.9) 3 (30.0)
:::P= 0.0139 (Fisher's exact test).
Correlation of prevalence of anti-HCV and history of ethanol consumption in patients with CH, LC and HCC The number of patients with alcoholic fibrosis (AF) who were positive for anti-HCV was too small to permit statistical analysis. Thus, a comparison was made only in the 78
Table 2 Comparison of serial changes in liver function tests after hospitalization between anti-HCV positive and negative patients with cirrhosis Anti-HCV positive n
At admission
1 month
Anti-HCV negative Significance
n
At admission
1 month
Significance
1.5 f 1.3 7.4 f 0.7 3.5 t 0.6 51 f 2 5 32 f 13 149 +_ 149
NS NS NS P
