The effectiveness of interferon therapy on occurrence of hepatocellular carcinoma in chronic hepatitis C

To clarify the effect of interferon (IFN) therapy for chronic hepatitis C (CHC) on the occurrence of hepatocellular carcinoma (HCC), 149 patients who were observed over a period of five years (mean: 7.6 years) were studied. The C-1 group, 33 patients with complete response to IFN; the C-2 group, 55 patients with no response to IFN; and the C-3 group, 61 patients who did not receive IFN. The occurrence rate of HCC was 0.9%/year/person. In the C-1, C-2 and C-3 groups, the rates were 0%, 0.3%, and 1.6%, respectively. The rate in C-1 + C-2 groups was significantly lower than that of the C-3 group (P<0.05). These data suggest IFN may suppress the occurrence of HCC in CHC.     

The incidence of hepatocellular carcinoma in patients with chronic hepatitis C after interferon treatment

To determine whether serum hepatitis C virus (HCV) RNA disappearance after interferon (IFN) treatment prevents development of hepatocellular carcinoma (HCC), we evaluated retrospectively the incidence of HCC in patients with chronic hepatitis C. A total of 213 patients were monitored for more than 6 months after completion of IFN treatment. Sixty-three of the 213 patients (29.6%) achieved a complete response (CR) to treatment and 150 (70.4%) had no response (NR). HCC developed in 12 (5.6%), all of whom were NR. Logistic analysis showed age, alpha -fetoprotein, and staging of histological finding before IFN treatment were independent factors to development of HCC. The fact that there was no HCC development from CR provides a basis for IFN treatment in chronic HCV infection.     

Chronic liver diseases for the risk of hepatocellular carcinoma: a case-control study in Japan. Etiologic association of alcohol consumption, cigarette smoking and the development of chronic liver diseases

BACKGROUND/AIMS: A great number of hepatocellular carcinoma (HCC) develop from chronic liver disease. Among a total of 23,000 deaths of HCC in 1988 in Japan, 82% had positive antibodies against HBV and/or HCV. In the present study we investigated the etiological factors involved in this process, employing patients with chronic hepatitis as controls. METHODOLOGY: In this study, alcohol consumption and cigarette smoking were investigated in 104 male patients with HCC which developed from chronic liver disease and 104 male controls with chronic liver disease without HCC (one for each case) matched for age. RESULTS: When compared with non-drinkers and non-smokers, the relative risk (RR) for developing HCC rose to 17.9 among those with both drinking and smoking habits. The risk was greater than for those in whom either habit existed alone. The RR decreased among ex-smokers who were non-drinkers or ex-drinkers, but it was still as high as 9.4. For current smokers, even if they were non- or ex-drinkers, the RR was 15.4. CONCLUSIONS: Drinking and the cigarette smoking were both risk factors, but the existence of synergism between them was also suggested. Therefore, patients with chronic liver disease should be thoroughly counseled to refrain from both drinking and smoking.     

Lymphoblastoid alpha-interferon for chronic hepatitis C: a randomized controlled study

The orientation of the sella nasion (SN) line in lateral skull radiographs is important for accurate assessment of antero-posterior and vertical facial relationship. Lateral skull radiographs of a random sample were traced and digitized to produce a mean shape template of the sample, with the craniofacial centroid line (CFC) used as a base for superimposition of the sample. A geometrical triangle was formed using the sella nasion line, craniofacial centroid line and the mandibular plane as the sides of the triangle. Simple geometric calculations were done to re-orient both the mandibular plane and sella nasion line in cases with balanced clinical profiles, while the S-N-A and S-N-B measurements indicate otherwise.     

Differences of resected hepatocellular carcinoma with hepatitis B or C virus

BACKGROUND/AIMS: The purpose of this study was to clarify the clinicopathologic differences of hepatocellular carcinoma associated with the hepatitis B versus the hepatitis C virus. METHODOLOGY: One hundred and sixty-eight patients with resected hepatocellular carcinoma were tested for viral hepatitis. Ten (6%) had both the hepatitis B surface antigen and antibodies to the hepatitis C virus. Thirty-three (20%) had neither marker. Sixteen (9%) had only the hepatitis B surface antigen (group B), and 109 (65%) had only antibodies to the hepatitis C virus (group C). We compared groups B and C clinicopathologically. RESULTS: The mean tumor diameter was larger in group B than in group C (6.3 cm vs 3.4 cm), while group B patients were younger than group C (48 yrs vs 62 yrs, p<0.0001). Poor liver function, histologic cirrhosis and chronic active hepatitis were frequently found in group C. The 1- and 2-year tumor-free survival rates following surgery in group B were 67% and 33%, and those in group C were 73% and 49%. The 1-, 2-, and 3-year survival rates following surgery in group B were 78%, 68%, and 0%, while those in group C were 92%, 83%, and 76% (p=0.0189). CONCLUSIONS: Hepatocellular carcinoma with concomitant hepatitis B viral infection was found to present as larger tumors in younger patients with less severe liver dysfunction. Hepatocellular carcinoma with concomitant hepatitis C viral infection was often detected in follow-up studies when it was small.     

Outcome of hepatitis C patients with and without hepatocellular carcinoma undergoing liver transplant

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with development of hepatocellular carcinoma (HCC). The aim of this study was to examine clinical characteristics and outcome of patients with HCV with or without HCC undergoing liver transplant. METHODS: We reviewed the charts of all 55 patients transplanted between November 1990 and December 1996 for HCV cirrhosis with HCC and compared them with a control group of HCV patients without HCC. Patients with a history of alcohol abuse or HBsAg positivity were excluded. There were 37 men and 18 women, with a mean age of 57.6 yr (range, 19-70 yr) in the HCC group. RESULTS: There was no significant difference between the HCC and nonHCC groups regarding Child's class or United Network for Organ Sharing (UNOS) status at the time of transplant. Twenty-six (45%) patients were diagnosed or suspected of having HCC before transplant. Twenty-five patients (45.5%) had a single focus of HCC. Fourteen percent (seven of 50) of the patients with HCC had been treated with interferon, whereas 12% (six of 52) of patients in the nonHCC group had received interferon. Duration of interferon therapy ranged from 1 to 9 months. All interferon treatment occurred within 5 yr of transplant. A history of intravenous drug use or transfusion was identified in 37 (67%) of HCC patients. Thirty-two patients (58%) without HCC had a parenteral exposure. There was no significant difference in patient or graft survival rates between the patients with and without HCC. CONCLUSION: Approximately one-half of HCC was not detected before liver transplant. There was no significant difference in the mode of transmission, clinical status at the time of transplant, or outcome between the HCV patients with and without HCC.     

Prognosis of chronic hepatitis C: results of a large, prospective cohort study

The prognosis of chronic hepatitis C virus (HCV) infection is still ill-defined. The present study prospectively evaluated mortality and complications in a large cohort of patients with chronic hepatitis C. The study included 838 anti-HCV and HCV-RNA-positive patients who were followed for 50.2 +/- 26.9 months (mean +/- SD; range, 6-122 months) in a prospective protocol. During follow-up, 62 patients died (31 from liver disease and 31 from other causes), and 12 patients needed liver transplantation. When compared with a matched general population, hepatitis C increased mortality mainly when cirrhosis was present and in patients who were less than 50 years old at study entry. During follow-up, a further 30 patients developed nonlethal complications of cirrhosis. By multivariate regression, survival was decreased by cirrhosis, long disease duration, history of intravenous drug abuse, and excessive alcohol consumption, whereas interferon therapy improved survival. Alanine transaminase (ALT), bilirubin, sex, and genotype had no effect on survival. The risk of hepatocellular carcinoma (HCC) (n = 17) was increased by cirrhosis and to a lesser degree by long disease duration and high bilirubin, whereas interferon therapy, genotype, and other factors had no effect. Chronic hepatitis C is a disease with considerable mortality and morbidity when cirrhosis is present at diagnosis. Patients who acquire the infection early in life have a markedly increased mortality even when cirrhosis is absent at diagnosis. The age at diagnosis therefore should play a major role in therapeutic considerations. The present data also suggest that interferon therapy has a long-term clinical benefit, although it did not reduce the risk of liver cancer.     

The value of hepatitis B x antigen as a prognostic marker in the development of hepatocellular carcinoma

Chronic infection with hepatitis-B virus (HBV) is associated with high risk for the development of hepatocellular carcinoma (HCC). Several studies have implicated that the X gene product(s) of HBV are important to the pathogenesis of HCC. This study tests the hypothesis that immunohistochemical detection of hepatitis B x antigen (HBxAg) is closely associated with HCC. The patterns of HBxAg were determined by staining in tumor and non-tumor liver sections from 30 Chinese patients with HBV-associated HCC, and the results were compared with other markers of infection. HBxAg was the most prevalent marker of HBV infection both in tumor and in non-tumor tissues of HCC patients, as compared with the hepatitis-B surface and core antigens. This pattern was observed among carriers as well as several patients who were HBsAG- in serum. The HBxAg staining results were validated by Southern blotting with an X-region probe and by Western blotting with anti-HBx. These results suggest that the persistence of HBxAg is important to the pathogenesis of early HCC and that HBxAg expression in the liver during chronic HBV infection may be an important prognostic marker for the development of HCC.     

Preoperative chemoembolization of hepatocellular carcinoma: a comparative study

INTRODUCTION: Inappropriate discharges and/or improper inhibition of bradycardia pacing due to oversensing of extraneous signals in implantable cardioverter defibrillators (ICDs) have been described. With one exception, no previous report involving an intact lead system has cited myopotential oversensing as the cause. METHODS AND RESULTS: Two case reports of myopotential oversensing by a dual chamber ICD system are reported. In the first patient suffering from chronic pulmonary obstructive disease, intermittent myopotential sensing during labored respiration resulted in episodic inhibition of bradycardia pacing. In the second patient, oversensing of sustained myopotentials generated during strenuous isometric activity resulted in an inappropriate ICD discharge. For both, the ICD system consisted of a CPI model 1810 Ventak AV used in conjunction with a model 0125 Endotak lead, incorporating integrated bipolar sensing. CONCLUSION: Although modern ICDs have proven to be highly effective in detecting and terminating malignant tachyarrhythmias, the opportunity for improving their detection specificity remains.     

Development of hepatocellular carcinoma after clearance of hepatitis C virus with interferon therapy

Manifestations of fish allergy can include near-fatal anaphylactic reaction. In very sensitive patients, fish odors and cooking vapors may have some allergenic activity. We reported a case of life-threatening fish allergy in a girl of 39 months referred for three episodes of Quincke edema with wheezing, cyanosis and severe urticaria after fish consumption or inhalation. Reagins were found against codfish and direct skin prick test with fresh food (codfish) showed important local reaction. Strict avoidance of fish in the diet is usually the only recommended procedure. However, in this particular case, the life-threatening nature of the allergic reaction was the major consideration to perform a desensitization. The child was treated by RUSH immunotherapy using codfish extracts from BENCARD company, following the schedule for insect venom allergy described by Pharmacia. Immunotherapy was performed immediately after determination of the threshold of sensitivity by specific skin prick tests and intra-dermal injections. Desensitization was initiated with a 1/10 dilution of the cut-off solution and 5 subcutaneous injections were administered daily. When important local reactions were observed, additional doses were necessary to obtain tolerance. After the RUSH therapy, the child was submitted to uncooked codfish odors without any reaction. No reaction has been observed even when the child has accidentally eaten a little piece of codfish.     

Seroprevalence of hepatitis B and C viral markers in patients with primary hepatocellular carcinoma in Singapore

This paper reviews studies on the basic principles of biostimulation of wound healing by various low-energy lasers. It looks at the mechanism of action of biostimulation as well as the laser's effect on cell proliferation, collagen synthesis, and would healing.     

Treatment of chronic hepatitis C genotype 4 with alpha-interferon in Saudi Arabia: a multicenter study

BACKGROUND/AIM: Several studies have indicated that there are certain predictive factors (gender, duration of infection with HCV, cirrhosis and genotype of HCV) of a better response with alpha-interferon treatment in patients with chronic hepatitis C. The aim of this study was to evaluate these factors in Saudis and other Arab nationals with chronic hepatitis C-genotype 4-undergoing alpha-interferon treatment. METHODOLOGY: A multicenter study was conducted between 1992 and 1994 on 80 consecutive patients who were prospectively recruited and randomized in treatment and control groups. RESULTS: The results of this multicenter study indicated a low response rate to alpha-interferon with an overall response rate of 43%, of which 28% was complete. The sustained response was only 16%. Among the reasons for this low response in our study are the high percentage of patients with cirrhosis and the long infection interval, as about 80% of our HCV cases were community-acquired. CONCLUSION: Liver cirrhosis was found to be the main predetermining factor for response to interferon treatment. Genotype 4 was not a contributing factor to the difference in response rate.     

Prevention of hepatitis B and C virus infection for prevention of cirrhosis and hepatocellular carcinoma

In Taiwan, cirrhosis and hepatocellular carcinoma (HCC) have been common in medical practice since the 1960s. In 1969, Taiwan was shown to be a hyperendemic area of hepatitis B virus (HBV) infection with a high rate of hepatitis B surface antigen (HBsAg) positivity, 19% of the population being infected before the fourth decade of life. There is evidence indicating that more than 80% of chronic hepatitis, cirrhosis and HCC are the sequelae of chronic HBV infection. In 1984, after 3 years of preparation, a programme to control cirrhosis and HCC began. All neonates born to HBsAg+ mothers were given Pasteur plasma-derived vaccine 5 micrograms i.m. at 1, 5 and 9 weeks with a booster at 12 months. In 1986, all neonates were included in this programme. In addition, beginning in 1987, all non-vaccinated preschool children were also immunized and susceptible medical personnel and people from HBsAg+ households were recommended to receive the vaccine. Using data obtained from the 7-year evaluation study on the efficacy of this vaccine and some historical data, the HBsAg positivity rate in people born in the first few years after 1986 was estimated to be 2.6%. This rate is expected to decrease to 0.2% in those born after around 1990. In July 1992, an anti-hepatitis C virus (HCV) test was included in blood donor screening tests. This was followed by a decrease in the incidence of post-transfusion hepatitis (PTH) from 13 to 2.5% and there have been no anti-HCV+ PTH cases since. However, without immunization, the prevalence of HBsAg decreased among children in Taipei in 1989. This coincided with the widespread use of disposable syringes and needles and an improvement in the sterilization of medical instruments. Therefore, it is likely that HCV infection may also decrease as a result of these practices. Through the use of immunization and improved medical procedures, chronic hepatitis, cirrhosis and HCC may decrease in Taiwan by around 95%.     

Colchicine in chronic hepatitis B: a pilot study

INTRODUCTION: The authors report the case of an internal rotation of the lower limb, lately ascribed to a posterior placement of the acetabular component during total hip arthroplasty. MATERIAL AND METHOD: A 58 years old female had an irreducible internal rotation of the right hip 3 years after total hip arthroplasty for arthritis. When the hip was extended, the lower limb showed an irreducible internal rotation of 45 degrees. In flexion of the hip this rotation disappeared. AP radiograms showed femur and femoral stem in internal rotation, a healed fracture of the acetabulum, and the acetabular component seemed to be in correct position. On CT scan the acetabular component was 4 cm posterior to the anatomic location, although there was no abnormal anteversion of the stem and acetabular component. Revision, with relocation of the acetabular component, corrected lower limb rotation. DISCUSSION: Posterior position of the acetabular component has not been described as a cause of lower limb malrotation. Normally the strength of the external hip rotators muscles is three times as important as of the internal rotators. The transverse acetabular fracture led to backwards placement of the acetabular component and yelded in an automatic internal rotation of the femur, because the trochanter kept an anatomical position in the horizontal plane. The posteriorised rotation center of the hip had changed the balance of the different rotator muscles, some of them, originally external rotators, becoming internal rotators.     

Pathogenesis of hepatitis B and C-induced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is estimated to have an annual worldwide incidence of 0.25 to 1.2 million new cases per year. Both the prevalence and incidence of HCC vary markedly as a function of geography and the local prevalence of chronic viral hepatitis. Both chronic hepatitis B and chronic hepatitis C are recognized as risk factors for HCC. The prevalence of cirrhosis in individuals with HCC and chronic hepatitis B or C is reported to be 80.9% and 75.8%, respectively. HCC occurs at a lower rate in chronic viral hepatitis in the absence of cirrhosis. Moreover, hepatitis C virus (HCV) rather than hepatitis B virus (HBV) is associated with the majority of non-cirrhotic cases of HCC. It is probable that the ongoing process of hepatocyte necrosis and liver cell renewal coupled with inflammation, which is characteristic of chronic viral hepatitis, causes not only nodular regeneration and cirrhosis but also progressive genomic errors in hepatocytes as well as unregulated growth and repair mechanisms leading to hepatocyte dysplasia and, in some cases, hepatic carcinoma. Current concepts concerning virus-induced HCC are reported and discussed in the following review.