When does the good of the group override the advantage of the individual?

In a system of N populations of n reproductive individuals apiece, in which each population has constant variance v² and lasts L generations, group selection on a quantitative character has a reasonable chance of overriding selection within populations if (and only if) the populations never exchange migrants, each population is founded by colonists from a single parent population, and the number of populations exceeds the effective number of reproductive individuals per population. If each population derives from a single parent population, then the exchange of a single successful migrant per population per L generations can triple the strength of group selection required to overcome a given selection within populations. If populations exchange no migrants, then the derivation of one in every N populations from two equally represented parents (while the others all derive from a single parent) doubles the strength of group selection required to prevail. Group selection is accordingly likely to be effective only in certain categories of parasites.     

Stochastic simulations of the exponential-beta function as an assessment of the validity of the choice of the Wagner-Nelson method for the analysis of ¹³C-octanoic acid breath tests

A compartmental model that generates the exponential-beta function μkβ(1 - e(-kt))(β - 1)?e(-kt) in order to run stochastic simulations has been constructed. The mathematical considerations that lead to the development of the model and the comparison of its performance with real data sets obtained from the studies of gastric emptying in healthy volunteers using 13C-octanoic acid breath tests are demonstrated. Stochastic simulations have been used to introduce randomness. These confirmed the choice of an exponential-beta function to model the physiological system, as agreement was obtained between experimental and theoretical data. The comparisons were made by visual inspection only, as the intention was to demonstrate that the stochastic exponential-β model would generate the full range of observed curve shapes.     

Anterior fissure of the right liver — the third door of the liver

Background/Purpose

Although the anterior segment of the liver has been divided into segments 8 and 5, we have, during surgical or interventional procedures, occasionally encountered patients in whom the right anterior portal vein does not bifurcate into the superior and inferior branches. Thus, the in vivo anatomy of the right liver was reevaluated to clarify the segmental anatomy.

Methods

We evaluated the hepatic venous and portal ramification patterns, using three-dimensional images reconstructed from computed tomography. In addition, liver volumetry was performed.

Results

All branches arising from the anterior trunk were divided into two groups: the right ventral portal branches (RVP) and the right dorsal portal branches (RDP), and the anterior fissure vein crossed between the RVP and RDP. The ventral and dorsal regions of the anterior segment were approximately equal from a volumetric point of view.

Conclusions

The anterior segment seems to be divided into the ventral and dorsal segments by the anterior fissure, and we propose a reclassification of the right liver that divides the right liver into three segments. Dissection of the parenchyma along the anterior fissure makes the third door of the liver open, resulting in the exposing of all Glissonian pedicles of the right liver. The introduction of our segmental anatomy and surgical procedure will allow more systematic and limited liver resections.     

Depressive Effect of the Antisense Oligonucleotides of C-myc and PCNA on the Proliferation of VSMC

Objectives To study the depressive effect of the antisense oligonuceotides (ASODN) of c-myc and proliferating cell nuclear antigen (PCNA) on the proliferation of VSMC. Methods Taking the VSMC obtained from rat aorta thoracalis cultured 4～8 generation as research object. The objects were divided into three groups to carry out control study: control group, PCNA ASODN group and c-myc ASODN group. The ASODNs' working concentration all were 1:50. The depressive effect of ASODN on VSMC proliferation was investigated by cell counting, MTT and 3H-TdR incorporation assay; PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA and c-myc ASODN into VSMC. Results PCNA and c-myc ASODN could inhibit the proliferation of VSMC significantly, compared with control group (P<0.05). ② Transferring PCNA and c-myc ASODN into VSMC obtained successfully; the corresponding gene was inhibited obviously; compared with control group (P<0.05). Conclusions PCNA and c-myc might play a considerable role in the VSMC proliferation process. The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC, and then the proliferation of VSMC was slowed down. This study presented a beneficial proposal and theoretical fundament for atherosclerotic treatment.     

Impairment of IFN-α production capacity in patients with hepatitis C virus and the risk of the development of hepatocellular carcinoma

AIM: To determine the utility of interferon (IFN) -αproduction capacity in patients with hepatitis C virus (HCV) infection for the measurement of immunosurveillance potential and for the early detection of hepatocellular carcinoma (HCC) by investigating the Sendai virus (HVJ) stimulated IFN-α production capacity of patients with HCV infection.METHODS: HVJ stimulated IFN-α production was determined in a large number of patients with HCV infection and the development of HCC was monitored for 3 years in patients with liver cirrhosis (LC).RESULTS: IFN-α production capacity decreases gradually with the progression of liver disease from chronic hepatitis (CH) to HCC. A significant correlation between the duration of HCV infection and impaired IFN-α production capacity was observed. IFN-α production in patients who developed HCC within 3 years was significantly lower than that of patients who remained in LC without developing HCC.CONCLUSION: Measurement of IFN-α production in LC patients may be useful for the early detection of HCC.     

Roles of Alcohol, Hepatitis Virus Infection, and Gender in the Development of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

To assess the interaction of alcohol, hepatitis C virus (HCV), and hepatitis B virus (HBV) infection in hepatocarcinogenesis, we prospectively observed 449 patients with liver cirrhosis (LC) who presented to our outpatient clinics in 1 month; 164 patients with habitual drinking [alcoholic liver-liver cirrhosis (AL-LC)] who had taken ≥72 g alcohol/day (HCV-positive 81 cases: HCV + AL; HCV-negative 83 cases: AL); 176 patients with HCV infection, but without alcohol intake; 34 patients with HBV infection; 6 patients with HCV and HBV coinfection; and 82 patients with liver diseases from other etiologies, such as primary biliary cirrhosis. In the HCV group, the cumulative occurrence rate of hepatocellular carcinoma (HCC) was 9%, 18%, and 23% in the first, second, and third years, respectively. In the HCV + AL group, that was 13%, 17%, and 28%, respectively. There was no difference in the HCC occurrence rate between the two groups. In the AL group, the cumulative HCC occurrence rate was only 1% during the observation period of 3 years. The occurrence rate was significantly lower in the AL group, compared with the HCV and the HCV + AL groups. In the HBV group, the cumulative occurrence rate of HCC during the observation period of 3 years was 17%, which was similar to that of the HBV + AL group, 14%. We also examined some other variables that might be related to the development of HCC. The cumulative occurrence rate of HCC in male patients was 31%, whereas that was 18% in female patients. In the HCV group, there was a significant increase of HCC occurrence rate in male patients. In contrast, no difference was observed in the HCC occurrence rate between male and female patients in the HBV group. The present study suggests that alcohol alone may not be an independent risk factor for HCC, nor does it accelerate HCC development in LC patients with HCV and HBV infection during the prospective observation of 3 years.     

National Survey of Hepatocellular Carcinoma in Heavy Drinkers in Japan

Background: The major cause of hepatocellular carcinoma (HCC) in the general Japanese population is an infection related to hepatotropic viruses, especially hepatitis virus C (HCV). Even in heavy drinkers, the major cause of HCC is HCV infection. However, HCC without viral infection has been reported in heavy drinkers. Alcohol has been also reported to be associated with an increased risk of cancer. In this study, we investigated aspects of HCC pathogenesis in heavy drinkers in Japan.
Methods: Questionnaires were sent to 1350 hospitals authorized by the Japanese Society of Gastroenterology. The questionnaires asked about the number of inpatients with the different types of alcoholic liver diseases, admitted to each hospital between 1998 and 2001.
Results: The percentage of heavy drinkers among all admitted patients with liver diseases or liver cirrhosis was approximately 15%. Of the patients with alcoholic liver cirrhosis, the cirrhosis was derived from alcohol alone in 61% and from alcohol plus a virus in 39% of patients. Furthermore, the percentage of patients with alcoholic liver cirrhosis caused by alcohol alone and who did not have HCC was 80%. However, the percentage of HCC patients who tested negative for viral hepatitis serum markers was 27% of the total number of heavy drinkers admitted for HCC. A study mainly on liver cirrhosis performed in the early 1990s demonstrated that the alcohol-alone group accounted for 44% of admitted patients with alcoholic liver cirrhosis and 18% of heavy drinkers admitted for HCC.
Conclusions: Because the consumption of alcohol is increasing in Japan, the frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral hepatitis infection, however, still plays an important role in hepatocarcinogenesis in heavy drinkers. Radiographical examination is recommended even in patients with alcoholic liver cirrhosis who test negative for serum markers of viral hepatitis.     

Clinical aspects and outcomes of volunteer blood donors testing positive for hepatitis‐C virus infection in Taiwan: a prospective study

Abstract: Background/Aim: The natural history of hepatitis‐C virus (HCV) infection has been explored in volunteer blood donors, but not yet in hepatitis‐B endemic areas. Whether previous or concurrent hepatitis‐B virus (HBV) infection influences the natural history of HCV infection remains unknown. Thus, we followed the anti‐HCV‐positive blood donors who had past or concurrent HBV infection in Taiwan. Methods: From 1992 to 1993, 1588 anti‐HCV reactive volunteer blood donors were referred to us from the Taipei Blood Center and 879 (55%) repeatedly reactive for anti‐HCV were enrolled. Two hundred and forty‐three donors (HCV RNA seropositive rate 49% by polymerase chain reaction (PCR)) received regular follow‐ups (mean period: 4.9 years) with their liver disease status determined mainly by clinical and biochemical parameters, serum alpha‐fetoprotein level and imaging studies. Hepatitis‐C virus genotype and occult HBV infection were determined by PCR‐based assays. Results: Of the initial 879 subjects, 250 (28%) had chronic hepatitis, nine (1%) had liver cirrhosis (LC) and two (0.2%) had hepatocellular carcinoma (HCC) already. In the 243 regularly followed donors, 30% had repeatedly normal serum alanine aminotransferase (ALT) and 70% had more than once elevated ALT. Cirrhosis developed in four (1.6%; follow‐up period range: 2–6 years) and HCC in two (0.8%; follow‐up period: 3 and 4 years, respectively). Distribution of HCV genotype and hepatitis‐B surface antigen (HBsAg) did not differ between those with and those without elevation of ALT. Of the 15 donors with LC and/or HCC, only 1(7%) was positive for both HBsAg and HBV DNA and the other 14 were negative for both HBsAg and serum HBV DNA. Conclusions: Incidentally detected hepatitis‐C was progressive in a small proportion of anti‐HCV‐positive volunteer blood donors in Taiwan. Occult HBV infection played a minimal role in the development of LC in this donor population.     

Development of hepatocellular carcinoma in a patient with chronic hepatitis C after 6 years of a sustained and complete response to IFN-alpha.

The authors report a rare case of hepatocellular carcinoma (HCC) that developed 6 years after a sustained and complete response to interferon (IFN) therapy for chronic hepatitis C. A 61-year-old Japanese man presented with a mass in the liver that was diagnosed as HCC. Six years earlier he was treated with IFN-alpha and responded successfully to therapy, with sustained normalization of serum aminotransferases and eradication of serum hepatitis C virus (HCV)-ribonucleic acid (RNA). HCV-RNA was also not detected in the resected tumorous and nontumorous liver tissues. The findings suggest that all patients with chronic HCV infection should be followed closely for as long as possible for the potential development of HCC even after a complete and sustained response to IFN treatment.     

Hepatitis C virus infection: 10 years after the discovery of the virus

The hepatitis C virus (HCV) causes an acute but very often chronic liver disease. An estimated 3% of the world population is chronically infected with HCV. Chronic hepatitis C is the major cause of cirrhosis and hepatocellular carcinoma (HCC), which most often lead to liver transplantation. HCV is a single-stranded enveloped RNA virus; it belongs to the flaviviridae family. The virus has been classified into six genotypes, some of which are distributed worldwide, others of which are confined to more restricted areas. The genotype is an independent predictor of response to antiviral treatment. Blood transfusion was a major risk factor for acquiring HCV infection before donor screening for surrogate marker testing for non-A, non-B (NANB) hepatitis began in the mid-1980s, followed by screening for antibody to HCV in 1990. Today, intravenous drug use and high-risk sexual activity are the most frequently identified risk factors associated with HCV infection. The prevalence of people with unknown HCV infection worldwide is high, so it is necessary to screen people with risk factors. The treatment of patients with chronic HCV infection who have not been treated previously should consist of interferon alpha (IFN-alpha) and ribavirin.     

Cryoglobulinemia due to chronic viral hepatitis infections is not a major problem in clinical practice

Background: Essential mixed cryoglobulinemia (EMC) is a systemic disease frequently associated with chronic viral hepatitis. This study was conducted in order to assess the prevalence of EMC in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. We also evaluated the possible associations of EMC with (1) the clinical, virological, and histological status of liver disease; (2) the presence of EMC-related symptoms; and (3) the response rate to interferon-alpha (IFN-alpha) treatment, in an attempt to address whether EMC is a major problem in hepatitis patients. Methodology: A total of 154 consecutive patients (104 with HBV and 50 with HCV infection) were investigated for the presence of rheumatoid factor (RF), cryoglobulins, and EMC-related manifestations. Sixty-two HBV patients were chronic carriers of hepatitis B surface antigen, 29 had chronic hepatitis B, and 13 HBV cirrhosis. Thirty-five HCV patients had chronic hepatitis C and 15 HCV cirrhosis. HCV genotyping was performed in 44 patients. Results: The prevalence of cryoglobulins was significantly higher (P<0.001) in HCV patients (46%) than in HBV patients (13.4%). EMC was associated with a high frequency of RF detection, older age, and longer duration of viral diseases. Weakness or malaise, arthralgias, and purpura were significantly more frequent in cryoglobulin-positive patients. These manifestations, however, were mild in most of the patients. The EMC-related symptoms were significantly associated with the presence of HCV infection, increased levels of cryoglobulins, and RF detection (P<0.01, P<0.05, and P<0.000005, respectively). Worse liver histology was unrelated to a higher prevalence or increased levels of cryoglobulins in both HBV and HCV infection. There was no relationship between EMC and a specific HCV genotype. IFN-alpha therapy led to the disappearance of cryoglobulins and EMC-related manifestations in most cases. The response rate to IFN-alpha was similar in both groups of patients (with and without EMC). Conclusions: A higher prevalence of EMC was observed in HCV patients than in HBV patients. However, this finding was unrelated to overt clinical manifestations of EMC, a specific HCV genotype, or worse liver histology. The latter suggests that EMC does not contribute to liver injury and vice versa, that EMC pathogenesis is rather unrelated to the degree of liver injury. From a clinical point of view, testing for cryoglobulins seems reasonable only for HCV patients with EMC-related manifestations, since this may have therapeutic consequences. RF detection could be used primarily as a surrogate marker for the existence of cryoglobulins.     

SEN virus: response to interferon alfa and influence on the severity and treatment response of coexistent hepatitis C

The SEN virus (SENV) is a recently identified single-stranded, circular DNA virus. A strong association between 2 SENV variants (SENV-D and SENV-H) and transfusion-associated non-A-to-E hepatitis has been reported. To clarify the effect of SENV infection on coexisting chronic hepatitis C and the effect of interferon alfa (IFN-alpha) therapy on SENV replication, SENV DNA was quantitated by polymerase chain reaction in serum samples from 186 patients with chronic hepatitis C. Thirty-nine of 186 (21%) patients with chronic hepatitis C were positive for SENV DNA. There were no differences in the clinical, virologic and histologic features between patients with and without SENV infection. Eighteen of 102 patients with chronic hepatitis C who received IFN-alpha were positive for SENV DNA. The sustained response rate for hepatitis C virus (HCV) clearance after IFN-alpha treatment did not differ significantly between patients with SENV (28%) and without SENV infection (39%). SENV DNA levels decreased during therapy in 15 of 16 patients, and 11 of the 16 patients (69%) had a sustained loss of SENV DNA in response to IFN-alpha. In coinfected patients, SENV responses to IFN-alpha were significantly better in those who failed to clear HCV RNA than in those who lost HCV RNA (P =.013). In conclusion, SENV infection was frequently found in patients with chronic hepatitis C. SENV infection had no apparent influence on the severity of HCV-related liver disease or the HCV response to IFN-alpha. SENV was sensitive to IFN-alpha therapy and the majority of patients had a sustained virologic response.     

Homeless patients with hepatocellular carcinoma in Osaka City, Japan.

BACKGROUND/AIMS: Although the number of homeless persons is increasing worldwide, studies delineating the health status of these persons according to various medical perspectives, including hepatology, are limited. However, such studies are important for understanding the pathogenesis of diseases and their prevention. METHODOLOGY: Thirty homeless patients with hepatocellular carcinoma (HCC) and 15 with liver cirrhosis (LC) who were admitted to the Osaka Socio Medical center Hospital during the past 6 years were analyzed clinicopathologically. All were from the Airin district of Osaka City. RESULTS: The patients with HCC had a history of long stay (mean: 25 years) in the district and many infectious opportunities and most of them were malnourished. The main causes of liver disease in the patients with HCC were hepatitis C virus (HCV) (77%), alcohol abuse (73%), and the combination of HCV and alcohol abuse (50%). Serum HCV RNA concentration was 10(5.8 +/- 0.9) copies/50 microliters in the 21 HCC patients and 10(6.5 +/- 0.7) copies/50 microliters in the 14 LC patients (p < 0.02). Six HCC patients (20%) were positive for the GB virus C/Hepatitis G virus (GBV-C/HGV) RNA in association with HCV or hepatitis B virus (HBV). Only 2 patients with HCC underwent the curative operations and most of the HCC cases were in progressed stages. CONCLUSIONS: A long stay in a hygiene-poor environment increases the opportunity for infection in homeless people. The causative agents in the HCC and LC patients were mostly HCV, alcohol abuse, and a combination of the two. Since the quantification of HCV-RNA in the HCC patients was lower, the high level of HCV-RNA may not be a risk factor for the development of HCC. GBV-C/HGV may not also. The reversion to former healthy living conditions and reduction in alcohol consumption as soon as possible may contribute to low incidence of HCC and save the tax dollar expenditures among homeless people.