Sachiko Hamamoto

SEROLOGICALLY SILENT HEPATITIS B VIRUS COINFECTION IN PATIENTS WITH HEPATITIS C VIRUS-ASSOCIATED CHRONIC LIVER DISEASE: CLINICAL AND VIROLOGICAL SIGNIFICANCE

Frequent coinfection of surface antigen‐negative hepatitis B virus (silent HBV) in hepatitis C virus (HCV)‐associated chronic liver disease (CLD) has been reported. The clinical and virological significance of silent HBV infection was investigated in 65 patients with HCV‐associated CLD who subsequently received interferon (IFN) therapy. HBV DNA was detected in 34 (52.3%) patients by a nested polymerase chain reaction (PCR). Virologically, all of the 34 patients were found to have HBV with an eight‐nucleotide deletion in the core promoter. Coinfection of silent HBV was more frequent with HCV genotype 1b than in 2a (64.3% vs 28.6%, P < .01). With HCV genotype 1b, the serum RNA level was significantly higher (≥106 copies per milliliter vs ≤105 copies per milliliter) in patients with silent HBV than those without coinfection (P < .01). Clinically, silent HBV was associated with a higher level of serum alanine aminotransferase (158.5 ± 104.8 vs 121.8 ± 78.6 IU/l; mean ± SD) and a greater histological activity of hepatitis as evaluated by histological activity index score (9.4 ± 3.8 vs 8.6 ± 4.5; mean ± SD), although it was not statistically significant. Silent HBV was also associated with poor efficacy of IFN therapy (P < .01). The results suggest that silent HBV has some promoting effect for HCV replication, at least for HCV genotype 1b, and may affect the histological activity of hepatitis and IFN response in HCV‐associated CLD. J. Med. Virol. 58:201–207, 1999.

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver

Intrahepatic mRNA levels of type‐I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co‐infection by serologically‐silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co‐infection of serologically‐silent HBV and type‐I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type‐I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surface antigen. Co‐infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co‐infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response, regardless of the HCV genotype. The findings suggest the possibility that co‐infection by serologically‐silent HBV is one of the factors that can lead to an unfavorable IFN response in chronic hepatitis C by down‐regulation of IFN receptor gene expression in the liver. J. Med. Virol. 63:220–227, 2001.

A new water instillation method for colonoscopy without sedation as performed by endoscopists-in-training

BACKGROUND Colonoscopy may be associated with discomfort when performed without sedation. A study was conducted to determine whether instillation of water into the colon at the beginning of the procedure reduces intubation time as well as patient discomfort and pain. METHODS Colonoscopy was performed in 259 patients by 3 endoscopists-in-training with limited experience. Patients were randomly allocated to 2 groups. In one, a technique was used in which 500 to 1000 mL of water is instilled into the colon by enema at the beginning of the procedure (instillation group, n = 130). In the other, patients underwent a conventional colonoscopy (control group, n = 129). Intubation time was measured and compared between the groups, and subjective discomfort experienced by the patients was measured upon completion of the examination. RESULTS Success rates for insertion to the cecum were similar, (95.4%, instillation group; 96.1%, control group). Detection rates for any colorectal diseases were not different between the groups (30.0% vs. 32.6%). Mean time to cecal intubation was 10.5 minutes in the instillation group and 16.2 minutes in the control group (p < 0.0001). The proportion of patients who complained of abdominal pain during the procedure was 17.1% in the instillation group and 33.3% in the control group (p < 0.001). CONCLUSIONS When used by endoscopists-in-training, the water-instillation colonoscopy technique was associated with less discomfort and faster cecal intubation with no decrease in the rate of detection of colorectal diseases.

Changes in serum lipid concentrations in patients with chronic hepatitis C virus positive hepatitis responsive or non-responsive to interferon therapy.

Background: Changes in serum lipid concentrations during the administration of interferon to patients with chronic hepatitis C virus (HCV) infection have not been fully investigated. The present study was designed to compare changes in serum lipid concentrations before, during and after interferon therapy in responders and non‐responders to treatment.

Clinical relevance of precore and basal core promoter variants of hepatitis B virus during natural hepatitis B e antigen seroconversion may be overstated.

Background Clinical relevance of nucleotide changes in precore and basal core promoters in the hepatitis B virus genome during hepatitis B e antigen seroconversion may be overstated. The authors investigated the existence and changes in the relative proportion of variants to wild virus that occur with seroconversion. Methods Sera from 30 school-aged long-term hepatitis B virus carriers, including 11 tested before and after seroconversion during 1 to 8 years of follow-up, were evaluated for variations in nucleotide sequences of the basal core promoter (T1762 and A1764), precore region (A1869), and carboxyl-terminus of the X region of the hepatitis B virus genome using an amplification refractory mutation detection system with mutant-specific primers. Results All variants were found to already exist before seroconversion at various wild-type/mutant ratios. The positive rates of these variants were not changed with loss of hepatitis B e antigen. Although there was a relative increase in the concentration of these mutants in wild-type/mutant mixed populations, most patients with only a wild-type population maintained the same pattern after loss of hepatitis B e antigen. Conclusions Our results indicate that hepatitis B virus exists as a quasi species, and correlations of nucleotide sequences with clinical and serologic findings must be done with caution.

Laparoscopic observations of hepatic capsular abnormalities: non-postoperative adhesions and hepatic capsular thickening.

BACKGROUND Hepatic capsular abnormalities (adhesions or thickening) are often striking at laparoscopy. However, their diagnosis is difficult because capsular abnormalities can also be caused by several pathologic conditions. The aim of this study was to systematically investigate the associated factors and prevalence of laparoscopically observed non-postoperative adhesions and hepatic capsular thickening. METHODS We reviewed all data and studied laparoscopically observed hepatic capsular abnormalities (non-postoperative adhesions and thickening) in 2500 consecutive patients who underwent laparoscopy from 1981 to 1997. RESULTS Non-postoperative adhesions were observed in 14.6% of cases and their frequency increased with age. Although several types of adhesions, from band-like to membrane-like, were seen, there were no correlations between type and underlying pathologic conditions, except tuberculous peritonitis with membrane-like adhesions and Fitz-Hugh-Curtis syndrome with violin string-like adhesions. Hepatic capsular thickening was observed in 9.7% of cases. The main associated factor was viral hepatitis followed by other liver diseases. CONCLUSIONS Hepatic capsular abnormalities are observed relatively frequently (21.5%) during laparoscopy. Initial laparoscopic diagnosis of non-postoperative adhesions may help in selecting patients with tuberculous peritonitis and Fitz-Hugh-Curtis syndrome for appropriate treatment.

Report of a case showing a recovery from liver cirrhosis to chronic hepatitis, type C, after glycyrrhizin injection for 2 years and a sustained response by the following interferon therapy.

TO THE EDITOR: We read with great interest the article recently published by Schepke et al. (1), which demonstrates that Doppler assessment of portal vein flow velocity allows an accurate distinction between responders and nonresponders to propranolol acute administration compared with hemodynamic assessment. This is an important step in the field of treatment of portal hypertension, because hemodynamic evaluation is a relatively safe but still invasive technique and not as available as Doppler. At the end of the article the authors advocate the need for studies correlating Doppler parameters with clinical endpoints such as variceal bleeding. We here remark on our experience in this field. On the basis of a previous study, demonstrating a peak effect on portal flow velocity between 2 and 4 h after administration of 40 mg p.o. of propranolol (2), we conducted a prospective study on cirrhotic patients with esophageal varices at high risk of bleeding. This study, presented in the 49th ASSLD meeting in 1998 and published in 1999 (3), demonstrated that the portal flow velocity test was a safe and feasible method to predict the efficacy of b blockers in the prevention of a first variceal bleeding. A

Intraperitoneal Rupture of Cholangiocarcinoma in a Patient With Liver Cirrhosis, Type C, With Hepatocellular Carcinoma

12% decrease in maximal portal flow velocity after propranolol acute administration was the best cutoff value with respect to efficacy of subsequent chronic treatment in preventing variceal bleeding, with a sensitivity of 69% and a specificity of 70%. Notwithstanding some methodological problems, our findings, also discussed by Garcia-Tsao (4), are clinically relevant and find further scientific support in Schepke et al.’s data. The slight difference between the cutoff point values reported in the two studies may be the consequence of the different endpoints and of operator and technical factors. It should be mentioned that the mean acute variation in portal flow velocity after the administration of b blocker reported in the literature ranges from 211.2% to 220.4% (5). We propose that the portal flow velocity test be used for response to propranolol administration before starting chronic therapy. If there is not a significant decrease in maximal portal flow velocity, the patient is a nonresponder and will not derive any clinical benefit, so the clinician should supplement or change the therapeutic approach.

Role of hepatitis B virus in non-B, non-C chronic liver disease: in vitro proliferation and interferon-γ production of peripheral blood mononuclear cells in response to hepatitis B core antigen and its relation to hepatitis activity

Intraperitoneal Rupture of Cholangiocarcinoma in a Patient With Liver Cirrhosis, Type C, With Hepatocellular Carcinoma

Partial obstruction of the colon caused by postoperative adhesions after cholecystectomy as a rare form of postcholecystectomy syndrome

OBJECTIVE:Although hepatitis B virus (HBV) DNA has been detected in the sera of patients with chronic liver disease with neither hepatitis B surface antigen nor anti–hepatitis C virus antibody (non-B, non-C [NBNC] CLD), whether HBV has some pathogenic role in NBNC CLD has not been made clear.METHODS:To investigate the significance of HBV DNA in NBNC CLD, we performed in vitro stimulation assays of peripheral blood mononuclear cells (PBMCs) in response to hepatitis B core antigen (HBcAg) in 17 NBNC CLD patients.RESULTS:HBV DNA with an 8-nucleotide deletion in the core promoter region was detected in 13 (76%) of the 17 patients by nested polymerase chain reaction. Interferon-γ (IFN-γ) production and proliferation of PBMCs of HBV DNA-positive patients showed a significant increase in response to HBcAg. The histological activity of hepatitis was also found to be significantly associated with the magnitude of IFN-γ production and proliferation of PBMCs in response to HBcAg. Although five (38%) of the 13 HBV DNA–positive NBNC CLD patients had anti-HBs and/or anti-HBc, there was no difference in response of PBMCs to HBcAg between the HBV DNA–positive and –negative groups.CONCLUSION:Our observation suggests that HBV may have a pathogenic role in HBV DNA–positive NBNC CLD, even in those patients without any serological markers of HBV.