Norio Ogata

Risk factors and the effect of interferon therapy in the development of hepatocellular carcinoma: A multivariate analysis in 343 patients

The aims of the present study were to clarify the risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection and to investigate the effectiveness of interferon (IFN) therapy. We retrospectively studied 343 patients who had been admitted to our hospital; 161 with chronic hepatitis, 49 with liver cirrhosis, 42 with chronic hepatitis bearing HCC and 91 with liver cirrhosis bearing HCC. The mean (±SD) observation period was 41.6 ± 31.1 months. The mean age of HCC and non‐HCC patients was 63.5 ± 7.6 and 56.9 ±12.5 years, respectively (P< 0.001). The HCV genotype II (1b) was the most prevalent genotype (92.5%) in HCC patients and the mean age was highest among patients with this genotype (63.6 ± 7.7 years). Multivariate analysis identified age (P< 0.001), the male gender (P<0.01), HCV genotype II (1b) (P<0.05) and excessive alcohol intake (P<0.05) as independent factors associated with the development of HCC. There was no relationship between the development of HCC and serum HCV levels as quantified by branched DNA assay or competitive reverse transcription polymerase chain reaction. The incidence of HCC in patients who had not received IFN therapy was 10.4/100 person‐year, while that of patients who had received IFN therapy was 1.2/100 person‐year (P<0.01) by the person‐year method. The low incidence of HCC in patients treated with IFN suggests that IFN may prevent the development of HCC.

A case of exacerbation of ulcerative colitis induced by combination therapy with PEG-interferon α-2b and ribavirin

A 55 year old man with chronic hepatitis C presented with diarrhoea and bloody stools in July 2003. Colonoscopic examination showed redness and oedematous mucosa in the rectum and ulcerative colitis was suspected. Biopsy of the lesion confirmed the diagnosis and treatment was initiated with mesalazine (5-ASA 2250 mg/day). However, he showed short term improvement and mesalazine was discontinued. He was treated with percutaneous radiofrequency ablation therapy (RFA)(Cool-tip) for adenomatous hyperplasia in S5 of the liver in December 2004. After providing consent to treatment with interferon (IFN), the patient underwent combination therapy with PEG-IFNα-2b (100 mg/week) and ribavirin (800 mg/day) for chronic hepatitis C. Liver biopsy and blood biochemistry revealed chronic active hepatitis C virus (HCV) F3/A2, genotype 1b, liver injury associated with HCV, aspartate aminotransferase (AST) 109 IU/l, alanine aminotransferase (ALT) 126 IU/l, and HCV RNA 3400.0 KIU/ml (by reverse transcription nested polymerase chain reaction, high range method). One …

Genetic and Biological Characterization of Two Hepatitis B Virus Variants: A Precore Mutant Implicated in Fulminant Hepatitis and a Surface Mutant Resistant to Immunoprophylaxis

Two hepatitis B virus (HBV) variants were studied in chimpanzees to determine their genetic and biological characteristics. The first variant, mutant HBV strain HT, had an in-frame stop codon at the 28th position of the precore gene and caused fulminant hepatitis in two individuals. Strain HT had an infectivity of ≥107 chimpanzee infectious doses per ml and caused moderately severe hepatitis in all three infected animals. Analysis of the complete nucleotide and deduced amino acid sequence of strain HT showed significant heterogeneity when compared to 33 published HBV sequences. The most notable differences were found within a region that spans the 3′ half of the X gene, through the precore/ core gene, to the 5′ end of the polymerase gene. Thus, strain HT is highly infectious and pathogenic, and possesses a unique genome sequence. The second variant, mutant HBV strain AS, emerged in a vaccinated infant and had an Arg-substitution at the 145th codon of the surface gene. Strain AS had an infectivity titer of 106 chimpanzee infectious doses per ml and caused hepatitis in seronegative chimpanzees. Analysis indicated that wild-type virus was also present. A polymerase chain reaction-based nucleotide assay showed that an inoculum at the end point of infectivity consisted exclusively of the mutant virus. This was confirmed by detection of only the mutant in the serum of a chimpanzee infected with the end point (10−6) dilution of the reference serum. Thus, strain AS is infectious and pathogenic. To test whether licensed recombinant HB vaccines could protect against challenge with strain AS, we infected 4 chimpanzees that had received one of two commercially available vaccines. All chimpanzees were protected during the 6-month duration of the study. Therefore, strain AS may not pose a threat to properly immunized individuals.

The long-term clinical outcome of 1-year treatment of chronic hepatitis B with lamivudine-5 years observation

The biochemical and virological outcomes of 19 patients with chronic hepatitis B who had been treated with 100 mg per day of lamivudine (LMV) for 1 year from 1995 to 1996 were evaluated. Fourteen patients were followed for 4.5-5 years since the end of the treatment without any further active antiviral treatment. During the treatment, DNA levels of hepatitis B virus (HBV) were under the detection limit of a hybridization assay in all the 19 patients. However, YMDD mutants appeared in 5 (26%) patients during the course of treatment and were accompanied in all five by the elevation of serum alanine aminotransferase (ALT). Mutated HBV DNA was not detected at 1 year after the end of treatment in any of the 5 patients. Of the patients who were followed for 4.5-5 years, the rate of seroconversion to anti-HBe and negativity for HBV DNA fluctuated during the course. Four of 11 patients who initially had been positive for hepatitis B virus e antigen (HBeAg) became positive for anti-HBe and all of them remained positive for HBV DNA by a transcription-mediated amplification test at the end of the follow-up. Thus, a 1-year treatment with LMV for chronic hepatitis B resulted in the relapse of HBV viraemia in most of the patients who had been positive for HBeAg, although the clinical course ameliorated in some patients. In addition, HBV DNA remained positive and ALT values were elevated at the end of the follow-up in the three patients who had been treated with interferon, with or without LMV, during the follow-up.

Remote development of hepatocellular carcinoma in patients with liver cirrhosis type B serologically cured for HBs antigenemia with long-standing normalization of ALT values.

In this report, we examine two patients with chronic hepatitis B virus (HBV) infection that had been diagnosed as precirrhosis or liver cirrhosis more than a decade previously. These patients had been cleared of HBsAg and had developed anti-HBs at a later time, yet hepatocellular carcinoma (HCC) eventually occurred. Both patients had been found negative for HBV DNA, using sensitive methods. Interestingly, a nontumor specimen of the liver obtained at surgical resection showed a marked reduction of fibrosis when compared to the histology observed when the patient was diagnosed as precirrhosis. Our findings suggest that the fibrosis from liver cirrhosis had been absorbed to a large extent during the long-term absence of active viremia and the normalization of alanine aminotransferase (ALT) levels. However, the cancer-prone biological characteristics of liver cirrhosis remained. Thus, patients with liver cirrhosis due to past chronic hepatitis B should be monitored carefully for the development of HCC even if HBV infection has been serologically resolved.

Complete response in a patient with colonic mantle cell lymphoma with multiple lymphomatous polyposis treated with combination chemotherapy using anti-CD20 antibody and cladribine

A 59-year-old woman suspected of having colonic malignant lymphoma was transferred to our hospital (Japan Labour Health and Welfare Organization Tsubame Rosai Hospital, Tsubame, Niigata, Japan) in October 2003. Systemic CT scan showed no swollen lymph nodes. Gallium scintiscan useful in localising lymphoma, showed no abnormal accumulation. Endoscopic findings of the oesophagogastroduodenal tract showed no tumour lesions. Colonoscopic examination was performed in November 2003, and clearly revealed multiple small elevations (fig 1A). Endoscopic mucosal resections were performed on lesions and the resected specimens suggested mantle cell lymphoma (MCL). A second colonoscopic examination performed in July 2004 revealed increased numbers of polyps, indicating a case of multiple lymphomatous polyposis (MLP). Biopsy was performed again to confirm the diagnosis of colonic MCL. Figure 1B–D shows the histopathological findings of both resected and biopsy specimens. Immunohistochemical examination of these specimens revealed positive immunoreactivity for CD20 and CD5 (fig 1E), and negative …

Localized Hepatic Tuberculosis with Imaging Changes Caused by the Progression of Tuberculosis

Localized hepatic tuberculosis (LHTB) is difficult to diagnose preoperatively, and most cases of LHTB are diagnosed based on pathological findings. A relationship between imaging features and the pathological stage of hepatic tuberculosis (TB) has recently been reported, which could aid in the diagnosis of hepatic TB. We herein present a case study of a patient with LHTB diagnosed postoperatively who demonstrated imaging changes due to the progression of TB. An awareness of the presence of LHTB might have permitted a preoperative diagnosis. This is the first report of an LHTB patient who exhibited imaging changes during the course of the disease.