Two cases of malignant lymphoma with reactivation of resolved hepatitis B virus infection after bendamustine hydrochloride monotherapy.

A 63-year-old female and a 63-year-old male with resolved HBV infection suffered a relapse of malignant lymphoma. After bendamustine hydrochloride monotherapy, HBV reactivation occurred. Entecavir treatment was commenced immediately, with tests for HBV DNA negative without development of hepatitis. Regular monitoring of HBV DNA based on the guidelines from the Japan Society of Hepatology was useful.

The incidence and risk factors for the development of hepatocellular carcinoma after peginterferon plus ribavirin therapy for chronic hepatitis C.

BACKGROUND/AIMS: Although the incidence of hepatocellular carcinoma (HCC) has been shown to be reduced after pegylated glycol-interferon plus ribavirin (Peg-IFN/RBV) therapy in patients with chronic hepatitis C, the risk factors for the development of HCC are not fully understood. The aim of this study was to clarify the incidence and the risk factors for the development of HCC after Peg-IFN/RBV therapy in patients with chronic hepatitis C. METHODOLOGY: A total of 474 patients with chronic hepatitis C who received Peg-IFN/RBV therapy between December 2004 and August 2010 were enrolled and followed in a multicenter trial. The patients were assessed for HCC by either ultrasound or computed tomography every 6 months. The incidence and risk factors for the development of HCC were identified. RESULTS: Of the 474 patients, 23 developed HCC during a median follow-up of 4 years and 8 months (range 1-6 years and 3 months) after completion of Peg-IFN/RBV therapy. According to a univariate analysis, higher age, low platelet counts, a low level of serum albumin, a high level of alpha-fetoprotein (AFP) and a sustained viral response (SVR) to Peg-IFN/RBV therapy were independent factors associated with the occurrence of HCC. The multivariate analysis using the Cox proportional hazard model revealed the risk factors for HCC were the platelet count, AFP level and the outcome of Peg-IFN/RBV therapy. CONCLUSIONS: To reduce the incidence of HCC in chronic hepatitis C, attainment of a sustained response rate is an essential issue. For patients with low platelet counts and/or a high AFP level, strict surveillance should be continued even after eradication of HCV because the risk of HCC was found to be higher for these patients.

Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population.

Limited epidemiological evidence suggests that genetic polymorphisms of drug-metabolizing enzymes such as cytochrome P450 (CYP), glutathione S-transferase (GST) and N-acetyltransferase (NAT) may be involved in tobacco-related hepatocarcinogenesis. We conducted a case-control study, including 209 incident cases with hepatocellular carcinoma (HCC) and two different control groups [275 hospital controls and 381 patients with chronic liver disease (CLD) without HCC], to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking. Overall, no significant associations with HCC were observed for any genotypes against either control group. However, we found a significant interaction (P = 0.0045) between CYP1A2 -3860G>A polymorphism and current smoking on HCC risk when we compared HCC cases with CLD patients; adjusted odds ratios [ORs; and 95% confidence intervals (CIs)] for G/A and A/A genotypes relative to G/G genotype were 0.28 (0.12-0.66) and 0.18 (0.04-0.94), respectively, among current smokers (P trend = 0.002), as compared with 1.28 (0.80-2.06) and 0.76 (0.34-1.71), respectively, among never/former smokers (P trend = 0.96). Similarly, in CYP1A2 G/G genotype, significant risk increase was observed for current smoking (OR = 4.08, 95% CI = 2.02-8.25) or more recent cigarette use (e.g. pack-years during last 5 years, P trend = 0.0003) but not in G/A and A/A genotypes combined (OR for current smoking = 1.39, 95% CI = 0.63-3.03; P trend for pack-years during last 5 years = 0.40). These results suggest that the CYP1A2 -3860G>A polymorphism modifies the smoking-related HCC risk among CLD patients.

[A case of diffuse hepatic arteriovenous fistulae with hepatic encephalopathy, postprandial abdominal pain and biliary injury].

A 60-year-old woman with hepatic encephalopathy was admitted to our hospital. Ultrasonography, computed tomography and hepatic arteriography revealed diffuse hepatic arteriovenous fistulae (HAVF). Overt portosystemic shunt could not be identified. Right heart catheterization showed increased cardiac output. However the patient had never shown any signs of heart failure. Other than that, marked hepatopetal arterial flow from some branches of the superior mesenteric artery was detected and mesenteric arterial flow remarkably decreased. Extensive HAVF can lead to significant complications, including high output heart failure, pulmonary hypertension, portal hypertension, hepatic encephalopathy, biliary ischemia, cirrhosis, postprandial abdominal pain, and reduced liver function. Embolization or ligation of the hepatic artery provides temporal improvement of clinical symptoms, but long-term results are unsatisfactory because of the development of collateral circulation and the risk of refractory intrahepatic cholangitis, subsequently leading to liver failure. Liver transplantation offers another therapeutic option and can be a successful curative treatment.

Case-control study on cigarette smoking and the risk of hepatocellular carcinoma among Japanese.

Emerging epidemiologic data suggest that cigarette smoking may increase the risk of hepatocellular carcinoma (HCC), yet considerable controversies (e.g. inconsistent dose-response relationships) still exist with this association. We examined whether smoking was associated with HCC risk in a case-control study including 209 incident HCC cases and two different control groups (256 hospital controls and 381 patients with chronic liver disease [CLD] without HCC). Comparison of HCC cases with CLD patients, but not with hospital controls, demonstrated a significantly increased risk of HCC for current smokers. After adjustment for sex, age, heavy drinking history and hepatitis virus markers, odds ratios (and 95% confidence intervals) for former and current smokers relative to never smokers were 1.0 (0.6-1.7) and 2.5 (1.4-4.6), respectively, against CLD patients, as compared with 0.8 (0.3-2.3) and 1.8 (0.6-5.1), respectively, against hospital controls. In terms of pack-years during lifetime, dose-response relationship was not evident against either control group (P trend = 0.43), but it became clearer for more recent cigarette use among CLD patients. For example, regarding cumulative cigarette consumption during the last 5 years, adjusted odds ratios (and 95% confidence intervals) for 1-4 and 5+ pack-years relative to no use were 1.9 (1.1-3.6) and 2.8 (1.5-5.2) (P trend = 0.003), respectively. These results suggest that cigarette smoking may play a crucial role in the late stage of HCC development and that CLD patients may benefit from their earliest smoking cessation.

Diabetes Mellitus Prevents an Improvement in the Serum Albumin Level During Interferon-free Sofosbuvir-based Therapy for Chronic Hepatitis C Patients: A Multi-institutional Joint Study.

Objective Interferon-free regimens of direct-acting antiviral agents have improved the treatment response for chronic hepatitis C virus (HCV) infection, and improvement in the serum albumin level during interferon-free therapy has been reported. The aim of this study was to identify the factors that influence the improvement in the serum albumin level in patients receiving interferon-free antiviral therapy. Methods This retrospective, multicenter study consisted of 471 Japanese patients with chronic hepatitis and compensated liver cirrhosis infected with HCV who completed 12-week interferon-free sofosbuvir (SOF)-based therapy [SOF plus ledipasvir for genotype 1 (n=276) and SOF with ribavirin for genotype 2 (n=195)]. We evaluated the changes in the serum albumin level from baseline to the end of treatment (ΔAlb). Results When compared with the normal-albumin group (baseline serum albumin >35 g/L, n=406), the low-albumin group (baseline serum albumin ≤35 g/L, n=65) showed a significant increase in the mean ΔAlb (5.5 g/L vs. 1.0 g/L, p<0.001). In the low-albumin group, a multivariate logistic regression analysis extracted diabetes mellitus as a negative predictive factor of median ΔAlb >5.0 g/L (odds ratio: 0.19, 95% confidence interval: 0.048-0.79, p=0.020). In the low-albumin group, the mean ΔAlb was significantly lower in the diabetic patients (n=14) than in the non-diabetic patients (n=51) (3.9 g/L and 5.7 g/L, p=0.049). Conclusion Interferon-free SOF-based therapy significantly improved the serum albumin in the low-albumin group patients with chronic HCV infection. However, the improvement in the serum albumin level was significantly lower in the diabetic patients than in the non-diabetic patients.

Trends in clinical characteristics, treatment and prognosis of hepatocellular carcinoma.

BACKGROUND/AIMS: This study was undertaken to evaluate the serial changes of various factors in patients with hepatocellular carcinoma, including hepatitis viruses, age distribution, female-to-male ratio, size and the number of hepatocellular carcinoma tumors at initial detection, the types of treatment and survival during a 12-year period. METHODOLOGY: Seven hundred and four consecutive patients with hepatocellular carcinoma lesions observed from Jan 1989 to Dec 2000 (12 years) at the Internal Medicine Department, Saga Prefectural Hospital Koseikan were retrospectively enrolled in the study. The follow-up period was divided into four terms as follows: 1989-91, 1992-94, 1995-97 and 1998-2000. The serial changes of causal hepatitis viruses, age distribution, gender ratio, tumor size, the number of hepatocellular carcinoma tumors at initial detection, the types of treatment and survival were analyzed and compared among the four different terms. RESULTS: Regarding viral markers, the association of an HCV infection has become more predominant in hepatocellular carcinoma cases, while the ratio of hepatocellular carcinoma patients infected with HBV has decreased during this 12-year period. In addition, the rate of hepatocellular carcinoma measuring 3 cm or less in diameter or solitary hepatocellular carcinoma at initial detection has increased during the 12-year period. The female-to-male ratio has increased from 33.6% in 1989-1991, 34.8% in 1992-1994, 48.7% in 1995-1997 to 60.6% in 1998-2000, respectively. Due to increased early detection, the types of treatment for hepatocellular carcinoma have shifted from arterial interventional therapy to local ablation therapy combined with or without interventional therapy. Therefore, although the age distribution of all 704 hepatocellular carcinoma patients has shifted to slightly older ages as shown by the ages of 64.1 years old, 63.4 years old, 66.6 years old and 67.3 years old in the four terms, respectively, the survival of the patients with hepatocellular carcinoma proved to had become significantly longer than before during the 12-year period. CONCLUSIONS: Hepatocellular carcinoma patients tended to show an increased prevalence of HCV, a higher age distribution, an increasing female prevalence, an earlier detection, advanced multidisciplinary therapies and prolonged survival in the last 12 years.

Comparison of the clinical characteristics among hepatocellular carcinoma of hepatitis B, hepatitis C and non-B non-C patients.

BACKGROUND/AIMS: The present study was undertaken to compare the clinical characteristics, availability of initial treatment options and prognostic features of patients with hepatocellular carcinoma in relation to hepatitis B or C viral infection. METHODOLOGY: Six hundred and ninety-two patients with hepatocellular carcinoma treated during the 12-year-period from Jan 1989 to Dec 2000 were categorized into three groups as follows: 1) 59 were classified as the HBV group: positive for hepatitis B surface antigen (HBsAg) and negative for antibody to hepatitis C (HCVAb), 2) 594 were placed in the HCV group: negative for HBsAg and positive for HCVAb, and 3) 39 were put into the Non-B, Non-C (NBNC) group: negative for both HBsAg and HCVAb. The age distribution, gender ratio, serum alpha-fetoprotein level, the presence of underlying cirrhosis, tumor size, the number of hepatocellular carcinoma tumors at the initial detection, the types of follow-up until the initial detection of hepatocellular carcinoma, the initial treatments chosen, and the survival were analyzed and compared among the three groups. RESULTS: Regarding age, the HBV group showed a younger age (56.3 +/- 12.2 years old) than the other two groups (the HCV group: 66.3 +/- 8.3, the NBNC group: 67.9 +/- 8.5 years old), however, no difference was observed in the male-to-female ratio of the three groups. The serum alpha-fetoprotein level, the prevalence of hepatocellular carcinoma measuring more than 3 cm in diameter, non-solitary hepatocellular carcinoma and portal thrombosis were strongly demonstrated at the initial detection in the HBV group, which was most likely due to the poor follow-up until detection. Consequently, the 1-, 3-, 5- and 7-year survivals of the patients in the HBV group were 40.4, 25.1, 18.8 and 5.2%, and were significantly shorter than both the HCV group which were 72.6, 44.9, 25.0 and 10.0%, and the NBNC group which were 71.2, 41.4, 31.1 and 31.1%, respectively. As for the NBNC group, in spite of the lack of a careful follow-up a longer survival was observed probably because they had a better preserved liver condition. CONCLUSIONS: Regarding the hepatocellular carcinoma patients, those infected with HBV presented at the advanced stage due to the lack of a careful follow-up, thus resulting in a shorter survival. As a result, hepatocellular carcinoma patients infected with HBV need to be strictly followed up.

Clinical characteristics among patients with hepatocellular carcinoma according to the serum levels of alpha-fetoprotein and des-y-carboxy prothrombin.

BACKGROUND/AIMS: Only limited amounts of data are available at present regarding the clinical differences in cases of hepatocellular carcinoma who have seropositivity or seronegativity for AFP (alpha-fetoprotein) and DCP (des-y-carboxy prothrombin). In the current study we investigated the different clinical variables in patients with hepatocellular carcinoma according to the serum levels of AFP and DCP. METHODOLOGY: Analyses were performed based on 168 consecutive patients with hepatocellular carcinoma observed for 4 years between July 1997 and December 2000 at the Internal Medicine Department, Saga Prefectural Hospital Koseikan. They were retrospectively evaluated for the analysis in the study. They were classified into four groups according to their serum levels of positivity for AFP and DCP as follows: a Negative group; seronegative for both AFP below 20 ng/mL and DCP below 40mAU/mL, an AFP group; seropositive for AFP above 100 ng/mL and seronegative for DCP, a DCP group; seronegative for AFP and seropositive for DCP above 100mAU/mL and an AFP/DCP group; seropositive for both AFP and DCP. Different clinical variables were compared among the four groups. RESULTS: There were no significant differences among the groups regarding age, viral markers or the presence of underlying cirrhosis. The DCP group and the AFP/DCP group occurred more often in male patients and they also tended to have a higher incidence of large hepatocellular carcinoma measuring 3 cm or more in greatest dimension compared to the Negative group and the AFP group. The AFP/DCP group showed higher incidences of non-solitary hepatocellular carcinoma and larger hepatocellular carcinoma measuring 3 cm or more in greatest dimension, and the presence of portal thrombosis in comparison to the other three groups and also showed a shorter survival. CONCLUSIONS: Hepatocellular carcinomas seropositive for DCP were predominantly found in male patients, and hepatocellular carcinoma seropositive for both DCP and AFP tended to be initially diagnosed at an advanced stage which resulted in a shorter survival.

Impact of hepatologists to extend survival of hepatocellular carcinoma patients with cirrhosis: a comparison with non-hepatologists.

BACKGROUND/AIMS: Whether or not generalists and specialist physicians can make an appropriate adaptation of their practice patterns when caring for their patients currently remains a matter of debate. The present study was undertaken to explore whether the clinical characteristics of hepatocellular carcinoma at its time of detection, the initial treatment options and the survival vary between patients with hepatocellular carcinoma associated with cirrhosis who were treated by hepatologists and those who were treated by non-hepatologists. METHODOLOGY: A retrospective study with 626 patients with hepatocellular carcinoma associated with cirrhosis was performed. The patients were stratified into three groups as follows; 1) a hepatologist group: 280 patients followed up and treated consistently by hepatologists, 2) a non-hepatologist group: 126 patients followed up and treated consistently by non-hepatologists, and 3) the other group: 220 patients either followed up by hepatologists and treated by non-hepatologists, or vice versa, or those identified to have tumors incidentally without any follow-up. To confirm the clear difference between generalists and specialists, the gender ratio, age, hepatitis B and C virus markers, serum alpha-fetoprotein level, tumor size, the number of tumors, Child's grade, portal thrombosis at the initial detection, the types of follow-up until the initial detection of hepatocellular carcinoma, the initial treatments chosen, and survival were compared between the hepatologist group and the non-hepatologist group. RESULTS: There were no statistically significant differences between the two groups with respect to gender ratio, age, hepatitis virus markers and the alpha-fetoprotein level. However, the tumor size, the number of tumors, Child's grade and portal thrombosis at the initial detection were more advanced in the non-hepatologist group, which was most likely due to the poorer follow-up until the detection of hepatocellular carcinoma compared with that in the hepatologist group (p value: 0.0237). Regarding therapy for hepatocellular carcinoma, intensive therapies were more often performed in the hepatologist group and, in addition, non-treated cases were less frequently found in the hepatologist group. Consequently, the 1-, 3- and 5-year survivals of the patients in the hepatologist group were 84.7, 61.1 and 35.1%, respectively, which were significantly longer than those in the non-hepatologist group, which were 80.7, 45.8 and 31.8%, respectively (p value: 0.0434). CONCLUSIONS: Hepatocellular carcinoma patients with cirrhosis who were treated by hepatologists can expect to obtain a longer survival because hepatocellular carcinoma tends to be detected at a smaller size, while such patients also usually receive more appropriate treatment modalities.

Interaction between interleukin-1beta -31T/C gene polymorphism and drinking and smoking habits on the risk of hepatocellular carcinoma among Japanese.

The risk of hepatocellular carcinoma (HCC) increases with the severity of hepatic inflammation. Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are proinflammatory cytokines with multiple biological effects and may play essential roles in inflammation-linked tumor development. We conducted a case-control study including 209 incident HCC cases and two control groups (275 hospital controls and 381 patients with chronic liver disease [CLD] without HCC) to investigate whether IL-1B and TNF-A gene polymorphisms influence HCC susceptibility with any interaction with alcohol and tobacco. By comparing HCC cases with CLD patients, we found that IL-1B -31T/C polymorphism was associated with HCC risk among never drinkers and current smokers; adjusted odds ratios (and 95% confidence intervals) for C/T and T/T genotypes compared with C/C genotype were 1.70 (0.76-3.77) and 2.46 (1.05-5.76) (P trend=0.03), respectively, among never drinkers, and 1.53 (0.60-3.99) and 2.54 (0.81-7.95) (P trend=0.11), respectively, among current smokers. Similarly, HCC risk associated with heavy alcohol intake and current smoking differed by this polymorphism among CLD patients. IL-1B -31T/C polymorphism may modify HCC risk in relation to alcohol intake or smoking.

Inverse association between coffee drinking and the risk of hepatocellular carcinoma: a case-control study in Japan.

Coffee use has consistently been associated with lower serum liver enzyme levels and a reduced risk of liver cirrhosis. A limited number of cohort and case-control studies also suggest a decreased risk of hepatocellular carcinoma (HCC) among coffee drinkers, but mostly without consideration of hepatitis virus infection. In the present case-control study, we recruited 209 incident HCC cases and three different controls (1308 community controls, 275 hospital controls, and 381 patients with chronic liver disease [CLD] without HCC), all of whom were aged 40-79 years and residents of Saga Prefecture, Japan. A questionnaire survey elicited information on coffee use during the last 1-2 years and 10 years before, and plasma hepatitis B surface antigen and antibodies to hepatitis C virus were tested for all but community controls. After adjustment for sex, age, heavy alcohol use, smoking status and hepatitis virus markers (except for community controls), coffee use during the last 1-2 years was associated with a decreased risk against any control group. For coffee use 10 years before, comparison between HCC cases and either community controls or CLD patients revealed a decreased risk; adjusted odds ratios for occasional use, 1-2 cups/day and > or =3 cups/day compared with no use were 0.33, 0.27 and 0.22 (P trend < 0.001), respectively, against community controls, and 0.86, 0.62 and 0.53 (P trend = 0.05), respectively, against CLD patients. These results suggest that coffee may protect against the development of HCC, yet further elaborate studies (hopefully, intervention studies) are warranted to corroborate these findings.

Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population.

Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene-alcohol interactions on HCC risk remain to be elucidated. We conducted a case-control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two-pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)]. Multiple logistic regression analyses revealed that heavy drinkers consuming >or=3 "go"s/day of sake (69 g of ethanol/day) showed an increased risk of HCC based on comparison of HCC cases with hospital controls [adjusted odds ratio (OR) = 13.5; 95% confidence interval (CI) 3.3-54.3] or CLD patients (adjusted OR = 7.0; 95% CI 2.5-19.2), whereas the overall risk was not elevated among light to moderate drinkers consuming <3 "go"s/day. Interestingly, light to moderate drinking was associated with an increased risk among those with ALDH2*1/*2 (adjusted OR = 4.5 or 2.0), but not among those with ALDH2*1/*1 (adjusted OR = 0.8 or 1.0; p interaction = 0.03 or 0.13). However, this gene-alcohol interaction was not observed for heavy drinking. Among light to moderate drinkers, people with the combination of ALDH2*1/*2 and ADH2*2/*2 revealed the highest risk of HCC. These findings indicate that the ALDH2 polymorphism may modify HCC risk among light to moderate drinkers.

hOGG1 Ser326Cys polymorphism and risk of hepatocellular carcinoma among Japanese.

BACKGROUND: The Ser326Cys polymorphism in human oxoguanine glycosylase 1 (hOGG1), which is involved in the repair of 8-hydroxy-2-deoxyguanine in oxidatively damaged DNA, has been associated with susceptibility to certain cancers, but has not been examined in causation of hepatocellular carcinoma (HCC). METHODS: We conducted a case-control study to investigate whether this polymorphism was related to HCC risk with any interaction with alcohol consumption and cigarette smoking. Genotyping was performed by a polymerase chain reaction with confronting two-pair primers among 209 newly diagnosed HCC cases, 275 hospital controls, and 381 patients with chronic liver disease (CLD) without HCC. RESULTS: Overall, the hOGG1 genotype was not significantly associated with HCC; adjusted odds ratios (and 95% confidence intervals) for the Ser/Cys and Cys/Cys genotypes compared with the Ser/Ser genotype were 0.79 (0.35-1.79) and 0.48 (0.18-1.27) against hospital controls, and 1.51 (0.96-3.37) and 0.86 (0.50-1.47) against CLD patients. We could not detect any significant gene-alcohol interaction (p = 0.95 or 0.16) or gene-smoking interaction (p = 0.70 or 0.69). CONCLUSIONS: These results suggest that the hOGG1 Ser326Cys polymorphism may not play a major role as an independent factor in hepatocarcinogenesis.

Longer survival in female than male with hepatocellular carcinoma.

AIM: There is a limited amount of data regarding the gender difference in the survival in cases of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the difference in the survival between males and females with HCC and the possible factors affecting the gender difference of survival in HCC. METHODS: Analyses were performed based on 704 consecutive patients with HCC observed for 12 years between January 1989 and December 2000 at the Internal Medicine Department, Saga Prefectural Hospital Koseikan, who were retrospectively enrolled in the study. The 1-, 3-, 5- and 7-year survivals and various factors at the detection of HCC were compared between 487 male and 217 female patients with HCC using the Kaplan-Meier method, Mantel-Cox test, chi squared test and Fisher's exact analysis. RESULTS: There was a significant difference in survival between male and female patients with a 1-, 3-, 5- and 7-year survival estimate of 67.7, 40.6, 23.8 and 8.7%versus 73.5, 50.3, 26.3 and 15.4%, respectively (P-value: 0.0167). Of the clinical variables examined, the significant factors related to gender difference were found to be age, tumor size, the number of tumors, the presence of portal thrombosis and the type of follow-up. Of the patients with HCC lesions measuring 3 cm or less in the greatest dimension or those with solitary HCCs, however, there was no significant difference in survival between both sexes. The patients were divided into three categories: closely followed-up group (regular periodic follow-up with monthly alpha-fetoprotein measurements plus ultrasonography at least every 4 months); a non-closely followed-up group; and an incidental group (incidentally discovered due to related symptoms). The detection rates of HCC through the closely followed-up, non-closely followed-up and incidental groups were 19.3%, 46.2% and 34.5% in men and 28.1%, 46.5% and 25.4% in women, respectively, which reached a significant difference between both sexes (P-value: 0.0097). CONCLUSION: The survival of female cases of HCC was longer than that of male cases. Disparities in the type of follow-up for women in comparison to men exist and may contribute to gender disparities in survival. Women with a high risk for HCC tended to be better cared for during the follow-up. To reduce gender disparities in survival, efforts should be directed at the earlier identification of HCC.

Atrophic corpus gastritis and Helicobacter pylori infection in primary biliary cirrhosis.

Chronic atrophic corpus gastritis, termed as autoimmune corpus gastritis or type A gastritis, and primary biliary cirrhosis (PBC) are characterized by a common immunological process against the exocrine glandular structures of both the stomach and bile duct. However, there has been controversy over whether atrophic corpus gastritis is associated with PBC. Recently, it has been suggested that Helicobacter pylori plays an important role in the early stage of atrophic corpus gastritis due to the induction of autoantibodies that are reactive with a protein in the gastric parietal cells. One hypothesis is that molecular mimicry, possibly resulting from H. pylori infection, might be responsible for initiating an autoimmune response in a predisposed host due to cross-reactivity among gastric mucosal, bile ductular, and bacterial antigens. The aim of this study is to assess whether atrophic changes of the gastric corpus could affect patients with PBC, and to determine the correlation with H. pylori infection. Sixteen patients with PBC were enrolled in this study. All patients were examined by serological studies of anti-pyruvate dehydrogenase (PDH) antibody, anti-H. pylori antibody, gastrin and vitamin B12. Gastroscopy was performed on all patients in order to verify the histological findings and to microscopically identify H. pylori. Atrophic corpus gastritis was found in 2 of 16 patients with PBC (12.5%), one of whom was confirmed to have pernicious anemia, a developed stage of atrophic corpus gastritis. H. pylori infection in the gastric corpus and the anti-H. pylori antibody were found in 7 (43.8%) and 11 (68.8%) of 16 patients, respectively. Anti-H. pylori antibody was confirmed to be positive in both of the patients with atrophic corpus gastritis, although H. pylori was absent in the gastric biopsy specimen. There was a positive correlation between anti-PDH antibodies and anti-H. pylori antibodies in sera from patients with PBC. Atrophic corpus gastritis is not frequently involved in PBC. However, H. pylori is a possible pathogenic factor in atrophic corpus gastritis in PBC patients because of the presence of anti-H. pylori antibody. A positive correlation between the titer of anti-PDH antibodies and the titer of anti-H. pylori antibodies was confirmed. Consequently, H. pylori infection could induce autoimmune responses in the development of both PBC and atrophic corpus gastritis. H. pylori infection associated with PBC requires further study.

Optimal treatment strategy for elderly patients with hepatocellular carcinoma.

BACKGROUND AND AIMS: The age distribution of patients with hepatocellular carcinoma (HCC) now peaks at nearly 70 years in Japan and this is continually increasing. Whether such elderly patients with HCC aged 80 years or older should be treated, and if so, how they should be selected for treatment remains uncertain. The present study was undertaken to determine any differences in the clinical characteristics and prognostic features between patients with HCC aged 80 years or older and those younger than 80 years of age. We also aimed to identify any significant variables in the prognosis of elderly patients with HCC aged 80 years or older. METHODS: Seven hundred and four patients with HCC, diagnosed during a 12-year period from January 1989 to December 2000, were categorized into two groups as follows: (i) 36 patients aged 80 years or older at the detection of HCC were defined as the elderly group and; (ii) 668 patients younger than 80 years of age were placed in the non-elderly group. Clinical variables were analyzed and compared between the two groups, and any significant variables in the prognosis were simultaneously determined. RESULTS: Regarding sex, viral markers, concentration of serum alpha-fetoprotein, diameter and number of tumors, Child's grade, presence of portal thrombosis, histology grade of HCC and any types of treatment, no significant difference was found between the two groups. The 1-year and 3-year survival rates in the elderly group (54.1 and 28.1%, respectively) were not significantly different from those in the non-elderly group (69.9 and 43.2%, respectively; P = 0.1053). The only significant factor in the prognosis in the elderly group was the presence of portal thrombosis, although a Child's grade of B or C was almost a significant factor with a P-value of 0.063. Tumor size measuring more than 3 cm in the greatest dimension, non-solitary tumor, Child's grade of B or C, and the presence of portal thrombosis were all found to be prognostic factors in the non-elderly group using a multivariate analysis. CONCLUSIONS: An advanced stage of HCC, not advanced age, influenced the survival rate in these elderly patients. Therefore, an optimal treatment strategy should be applied for elderly patients with HCC who demonstrate less prognostic factors in the same manner as that for non-elderly patients.