Search

In 18 of 547 patients who had received nucleoside analogue preparations for 1 year or more, multi-drug resistance was detected, after a median follow-up of 53 months. No patient showed liver failure related to multi-drug resistance acquisition. Multi-drug resistance was associated with entecavir (ETV) therapy in 7 lamivudine (LAM) -resistant patients, combination therapy with adefovir dipivoxil (ADV) in 8 LAM-resistant patients, LAM switching to ETV in 2 patients, and initial ETV administration in 1. For treatment, combination therapy with LAM and ADV was performed. In non-responders, combination therapy with ADV and ETV was employed. In all LAM- and ADV-resistant patients, and the HBV DNA level decreased to 3.0LC/ml or less. However, a similar decrease was noted in 7 (58.3%) of 12 LAM- and ETV-resistant patients. Of the 18 patients, 1 did not respond to combination therapy with ADV and ETV. Therapy with tenofovir disoproxil fumarate (TDF) was required.

In this symposium, we explained etiology, prevention and treatment for hepatocellular carcinoma (HCC). It has been revealed that the carcinogenesis in hepatocellular carcinoma is almost caused by the infection of hepatitis virus B and/or C. Therefore, the carcinogenesis in hepatocellular carcinoma is able to be prevented. Even if the carcinogenesis in hepatocellular carcinoma occurs, the diagnosis and treatment in the worldwide level; radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), hepatectomy, and liver transplantation will be offered to patients with HCC in Japan. We hope that this symposium would help the attendance to understand the prevention and treatment for HCC.

Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Since the HCV viral genome was molecularly cloned and antibody detection systems were established, a considerable amount of information on HCV has been accumulated. In the present study, I have examined the sera and liver tissues of the patients of type C chronic liver disease using molecular biological methods and tried to correlate the data obtained with the clinical, pathological and therapeutic outcomes. A reverse transcription-polymerase chain reaction (RT-PCR) method using radiolabeled nucleotides provided constant results in genome amplification, and could be shown to be a reliable method for quantifying the levels of HCV genome. The amount of HCV RNA in the serum tended to increase as a function of the duration of the disease and the progression of histopathologic changes of the liver. In addition, the serum HCV RNA titers correlated well with those of liver tissues, which showed that the amount of circulating HCV genome reflected the intrahepatic amount of HCV. HCV, a positive-stranded RNA virus, is likely to make a negative strand during viral replication. In studies to detect the positive and negative strands of HCV RNA separately using strand specific primers, the existence of both strands in the liver was demonstrated, confirming viral replication in the liver. The ratio of negative to positive strands ranged from 0.03% to 30%, being 3.7% in chronic persistent hepatitis, 4.8-6.0% in chronic aggressive hepatitis and 6.7% in liver cirrhosis. The viral factors influencing the interferon (IFN) response were also examined. Individuals who had low titers of HCV genome tended to respond well to IFN. Moreover, IFN was more effective for patients with HCV type III than for those with HCV type II. Thus, IFN response was shown to depend both on virus titers and genotypes. However, mean levels of HCV RNA were almost the same between the patients with HCV type II and those with HCV type III before the treatment, there were significant differences in the disappearance of HCV and the effects of IFN therapy. It is suggested that the susceptibility to IFN is different for each genotype. Hokkaido J Med Sci 69 (6), 1382-1398, 1994.

Genotypes of HCV have been reported to be one of the predictors of response to IFN therapy in patients with chronic hepatitis C. HCV genotypes were determined enzyme-linked immunoblot assay based on group I and II specific recombinant peptides of the NS-4 region (amino acid No. 1676-1670). We examined the correlation between HCV groups and response to IFN in patients with chronic hepatitis C. Among the 84 patients with chronic hepatitis C who underwent IFN treatment, 16 of 51 (31.4%) patients with group I and 12 of 23 (52.2%) patients with group II showed complete sustained response. These results suggest that HCV group assay may improve the ability to predict IFN treatment outcomes.

Interstitial pneumonia is known as one of the serious side effect of drugs. Recently, many investigators have reported that interstitial pneumonia (IP) which occurred during interferon (IFN) therapy for type C chronic hepatitis, and its appearance rate is considered to be more than 0.2% of patients who receive IFN. Though the mechanisms of IP during IFN therapy remains to be elucidated, one of the possible explanations is that excessive focal immune response in the lung derived from IFN might leads to the inflammation. For safe treatment, we must recognize that IFN induces IP during IFN therapy and give attention to its occurrence.

Hepatitis C virus (HCV) is a major cause of post transfusion non-A, non-B hepatitis. The virus contains a positive-strand RNA genome comprised of approximately 9,400 nucleotides. HCV E2/NS1 is probably an envelope glycoprotein (E2). The E2 hypervariable domain appears to contain isolate-specific antibody-binding linear epitopes. Recently, comparative sequence analysis of all the complete and partial HCV sequences published to date indicates that known genotypes of HCV can be classified into six basic groups. We report here that the prevalence of HCV-I, HCV-II, and a mixed form are 77.2%, 11.4%, and 11.4%, respectively. Patients with anti-HCV and HCV-RNA positive chronic active hepatitis received 6MU of interferon-alpha or beta everyday for two weeks followed by 6MU thrice a week for 14 weeks. Complete response to interferon treatment was defined as an ALT level normalized within six months after the end of treatment and maintained within the normal limit for an additional six months. Complete response was found in 42.9% of patients treated for 16 weeks. In a six month follow-up of the complete responders, clearance of viremia was observed in 90.3% at the end of interferon treatment and in 71.0% six months after the end of interferon treatment.

Plasmacytoma often forms an intramedullary mass in the vertebrae with absorption of trabecula and cortex of the bone. However, occasionally, it forms a mass in the extramedullary space of the vertebrae. The authors report such a rare case with plasmacytoma which formed a mass in the thoracic epidural space without evidence of involvement of the adjacent vertebra. On May 22, 1985, a 80-year-old man was admitted to our clinic with chief complaints of gait disturbance and hypesthesia below the umbilical level. Difficulty of walking developed approximately four months prior to admission with gradual aggravation and hypesthesia added thereafter. Neurological examinations at admission showed paraparesis with positive Babinski's and Chaddock's reflexes, hypesthesia and disturbances of vibration and position senses below the 9th thoracic nerve level. Myelography and CT scan using metrizamide indicated a presence of epidural mass at the 8th to 9th thoracic vertebrae. There was no abnormal bony change in the spine on plain X-ray and CT scan. On May 30, 1985, total removal of epidural tumor was performed by removing the laminae from the 7th to 10th vertebrae. Histological examinations including immunological stainings showed a plasmacytoma which produced monoclonal immunoglobulin of IgG-lambda type. Radiation therapy was not carried out. The serum protein fraction, immunoglobulin, immunoelectrophoresis, Bence-Jones protein and CSF immunoglobulin examined after operation, supported a histological diagnosis of plasmacytoma. Also, slight proliferation of plasma cells was noted in the bone marrow and peripheral blood.(ABSTRACT TRUNCATED AT 250 WORDS)

A 46-year-old woman was referred to our hospital because of liver dysfunction. She had been suffering from right hypochondralgia for two months. On admission, Laboratory data indicated extrahepatic cholestasis. Both X-ray and endoscopic examinations confirm a submucosal tumor of the papilla of Vater, and surgical diagnosis was performed. Histologically, the tumor was diagnosed as carcinoid, and a further immunohistochemical study by the PAP method using antisomatostatin serum indicated somatostatinoma. Electron microscopically, the tumor cells were found to contain numerous intracellular granules, which looked like D cells in the pancreatic islet. Somatostatinoma in the intestinal tract has been reported in only 13 cases, in only one of which was it located in the papilla of Vater. That means that, this is the second case so far.