Shuhei Nishiguchi

Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis.

In a prospective randomised controlled study, 90 patients with chronic active hepatitis C and compensated cirrhosis were assigned symptomatic treatment or interferon alfa (IFN-alpha). We report data on decompensation, detection of hepatocellular carcinoma, and mortality rates. IFN-alpha gave a sustained response in only a small proportion of patients, but worsening of compensated cirrhosis was prevented and development of hepatocellular carcinoma was inhibited, increasing the survival rate. The risk ratio of IFN-alpha versus symptomatic treatment decreased by 0.250 for progression to Child-Pugh grade B, 0.256 for detection of hepatocellular carcinoma, and 0.135 for a fatal outcome.

Comparison of real-time quantitative polymerase chain reaction with three other assays for quantitation of hepatitis C virus.

Background and Aims: Evaluation of serum levels of hepatitis C virus (HCV) is important for predicting the response to interferon treatment and monitoring its therapeutic efficacy. The aim of this study was to evaluate real‐time quantitative polymerase chain reaction (PCR) as a method for the measurement of HCV‐RNA.

TT virus infection in patients with chronic liver disease of unknown etiology

The role of a novel virus, designated as TT virus (TTV), as a cause of chronic liver disease has not been well defined. We investigated the prevalence of TTV among 69 patients with chronic liver disease of unknown etiology and 50 volunteer blood donors with normal transaminase levels. TTV DNA was amplified by polymerase chain reaction (PCR) by using two different sets of primers: one based on the sequence of the original N22 clone within the open reading frame 1 (set A) and the other derived from the untranslated region (set B). The prevalence of TTV detected by PCR primers set A only, set B only, and in total (by either set A or B) was 11 (31%), 31 (86%), and 31 (86%) of 36 patients with chronic hepatitis; 2 (40%), 4 (80%), and 4 (80%) of 5 with cirrhosis; 11 (39%), 17 (61%), and 22 (79%) of 28 with hepatocellular carcinoma; and 9 (18%), 39 (78%), and 40 (80%) of 50 volunteer blood donors, respectively. Of the interpretable 25 PCR products amplified with primers set A, 9 were classified as genotype 1a, 10 as genotype 1b, 4 as genotype 2, 1 as genotype 3, and 1 as genotype 4. Molecular evolutionary analysis did not suggest any particular strains of TTV that might be associated with chronic liver disease. The nucleotide sequences of the untranslated region on which PCR primers set B were designed were highly conserved, and the interpretable 22 PCR products amplified with primers set B were not clearly divisible into distinct genotypes. Our findings provided no evidence that TTV is a causative agent of chronic liver disease. J. Med. Virol. 62:392–398, 2000.

Prevalence of TT virus in patients with fulminant hepatic failure in Japan

Abstract: A novel virus (TT virus) was isolated from patients with posttransfusion hepatitis of unknown etiology. We studied the prevalence of TT virus in 26 patients with fulminant hepatic failure without risk factors, including blood transfusion, and also examined 106 healthy blood donors as controls. We assayed serum TT virus DNA by seminested polymerase chain reactions and also examined the genotypes of this virus. Serum was obtained at admission from patients with fulminant hepatic failure. Serum samples at admission from seven (27%) of the 26 patients were positive for TT virus DNA. There were no differences in clinical findings, duration from onset to coma, or results of laboratory tests in patients with and without TT virus DNA. However, all 7 patients with TT virus died, whereas 9 of the 19 patients without TT virus died. The outcome for patients with fulminant hepatic failure and TT virus was significantly worse than for patients without the virus (P = 0.0227). TT virus was also detected in 29 (27%) of the 106 healthy blood donors. The genotype of the TT virus was mainly 1a in both groups. There were no differences in the rate of positivity and the genotypes of TT virus between patients with fulminant hepatic failure and healthy blood donors. TT virus infection may not cause severe hepatitis, such as fulminant hepatic failure, but it may indicate a poor outcome in such patients.

Randomized trial assessing gastric emptying in patients with chronic hepatitis C during interferon-α or -β therapy and effect of cisapride

We examined the effects of interferon-α or -β therapy on gastric emptying and digestive symptoms. The effects of cisapride on gastric emptying and digestive symptoms were also evaluated. The subjects were 48 patients with chronic hepatitis C. All patients were randomly assigned to one of four groups (A, interferon-α group; B, interferon-α and cisapride group; C, interferon-β group; D, interferon-β and cisapride group). Gastric emptying was measured before initiation of interferon therapy and two weeks after initiation of therapy. The half-time of gastric emptying (T1/2) was calculated. The T1/2 ratio was calculated by dividing the T1/2 after interferon therapy by the T1/2 before interferon therapy. Digestive symptom scores were determined at the time of the gastric emptying tests. The T1/2 after interferon therapy was higher than that before therapy in groups A and C (P = 0.002 and 0.059, respectively). The digestive symptom score after interferon therapy was higher than that before therapy in groups A and C (P = 0.012 and 0.093, respectively). The T1/2 ratio in group B was significantly lower than that in group A (P = 0.021), and the T1/2 ratio in group D was lower than that in group C, but the difference did not reach statistical significance (P = 0.057). Interferon-α is associated with a greater delay in gastric emptying and a higher symptom score than is interferon-β. Administration of cisapride corrects the delayed gastric emptying and relieves associated digestive symptoms.

Clinical need for both scintigraphy with technetium-99m GSA and per-rectal portal scintigraphy in some patients with chronic liver disease

Scintigraphy with99mTc-diethylenetriaminepentaacetate with galactosyl human serum albumin (99mTc-GSA) and per-rectal portal scintigraphy are useful for evaluating hepatic functional reserve and portal circulation, respectively. We did the procedures simultaneously in some patients to examine the relationship between hepatic functional reserve and portal circulation in chronic liver disease. Scintigraphy with99mTc-GSA was done in 10 healthy subjects, 45 patients with chronic hepatitis, and 165 patients with cirrhosis. Fifty-seven patients (13 with hepatitis and 44 with cirrhosis) also underwent per-rectal portal scintigraphy with99mTc-pertechnetate within two weeks. A receptor index was calculated by dividing the radioactivity of the liver region of interest (ROI) by that of the liver-plus-heart ROI at 15 min after the injection of99mTc-GSA. The index of blood clearance was calculated by dividing the radioactivity of the heart ROI at 15 min by that of the heart ROI at 3 min. A solution containing99mTc-pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. A per-rectal portal shunt index was determined by calculating the ratio of counts for the liver to counts for the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. The median receptor index was lower for more severe liver disorders, increasing in the order of chronic hepatitis, compensated cirrhosis and decompensated cirrhosis, and the median index of blood clearance was higher. The median receptor index was significantly lower when a complication (varices, ascites, or encephalopathy) was present, and the median index of blood clearance was higher. The shunt index was correlated significantly with the two other indices, but these values for some one-third of the patients disagreed in either indices. Scintigraphy with99mTc-GSA and per-rectal portal scintigraphy with99mTc-pertechnetate are both needed for accurate assessment of the severity of chronic liver disease before treatment-making decisions, because in some patients, results are not correlated.