Based on variation in nucleotide sequence within restricted regions in the putative C (core) gene of hepatitis C virus (HCV), four groups of HCV have been postulated in a panel of 44 HCV isolates. They were provisionally designated types I, II, III and IV. A method for typing HCV was developed, depending on the amplification of a C gene sequence by polymerase chain reaction using a universal primer (sense) and a mixture of four type-specific primers (antisense). HCV types were determined by the size of the products specific to each of them. Type II was found in HCV samples from 131 (82%) of 159 blood donors, more often than in those from 48 (60%) of 80 patients with non-A, non-B (NANB) liver disease in Japan (P< 0-01). In 11 haemophiliacs who had received imported coagulation factor concentrates, type I was found in five, as against type II in four. Double infection with two different HCV types was found in two patients with chronic NANB liver disease (types I and II; II and III) and two haemophiliacs (types I and II; I and III). HCV types were identical in mother and baby in each of two examples of perinatal transmission, and were also identical in donor and recipient in a case of accidental needle exposure.

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The complete nucleotide sequence of a hepatitis C virus derived from plasma of a human carrier in Japan was determined. The cDNA of the isolate (HC-J6) contained 9481 nucleotides and an additional T stretch of 30 to 108 nucleotides at the 3' end, and had one large open reading frame coding for a polyprotein of 3033 amino acids. It differed by 31.8 to 32.1% in the nucleotide sequence and by 27-4 to 27-7 % in the amino acid sequence from an American isolate and two Japanese isolates previously reported. Among these four isolates, the 5' non-coding region of 329 to 341 nucleotides was well conserved (>93% identity), whereas the 3' non-coding region of 39 to 45 nucleotides (T stretches not included) was more variable (>30% identity). An excellent degree of conservation of the 5' non-coding region would reflect its pivotal role in replication, and primers deduced from this region could be applied for the sensitive and specific detection of viral RNA by polymerase chain reaction. Due to a high degree of similarity in the amino acid sequence of the putative core protein (>90%), antigen probes deduced from it would be suitable for the serological diagnosis of HCV infection. Low sequence similarity in the putative envelope protein (> 53 % identity), however, would have to be taken into account in considering the immunoprophylaxis of HCV infection.

<b><i>Background and Aims:</i></b> It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy. <b><i>Methods:</i></b> In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively. <b><i>Results:</i></b> Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m²) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51–4.25) and 2.56 (95% CI: 1.14–5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61–2.33). <b><i>Conclusions:</i></b> Obesity and heavy alcohol consumption increased the risk of HCC development after SVR.

IgM anti-HBc was measured by radioimmunoassay in serially collected serum samples during 20 acute exacerbations which developed in 14 patients with anti-HBe positive chronic type B hepatitis. IgM anti-HBc became positive in 12 of the 14 (86%) patients and in 18 of the 20 (90%) exacerbations, and elevation of IgM anti-HBc which was believed to be significant was also observed in the remaining two patients. In most of the patients who also had determinations of serum hepatitis B virus DNA, the hepatitis B virus DNA became positive. These results suggest that ALT elevation in anti-HBe positive chronic type B hepatitis is associated with active replication of hepatitis B virus. It is considered to be useful to measure IgM anti-HBc for the purpose of identifying the causes of ALT elevation in anti-HBe positive chronic type B hepatitis.

The peptide which is encoded by the pre-S(2) region of hepatitis B virus DNA, the pre-S(2) antigen, was determined quantitatively by an enzyme immunoassay system employing monoclonal antibodies. The prevalence and titer of pre-S(2)Ag were 91.9% (91/99) and 10,356 +/- 19,053 units (mean +/- S.D., arbitrary units) for hepatitis B e antigen (HBeAg)-positive patients with acute and chronic HBV infection and 86.0% (74/86) and 952 +/- 1,565 units for HBeAg-negative subjects. In four patients with acute hepatitis B, pre-S(2)Ag titers changed in parallel with HBV DNA levels, and the disappearance of pre-S(2)Ag from serum was associated with a rapid fall of ALT levels into the normal range, whereas the fluctuation of pre-S(2)Ag titer correlated with persistence of ALT elevations. In all of the 19 episodes of acute exacerbation of hepatitis which occurred in nine patients with chronic active hepatitis B, a significant elevation of pre-S(2)Ag titer was observed, closely overlapping an increase or appearance of HBV DNA, and its peak preceded peaks of ALT by 1 to 11 weeks (mean +/- S.D. = 4.26 +/- 2.57 weeks). These observations suggest that quantitative measurement of pre-S(2)Ag would be useful for estimation of the magnitude of HBV replication and would help predict the prognosis of acute hepatitis B and of acute exacerbation in chronic hepatitis B.

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We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% +/- 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% +/- 27.8% in 32 patients with chronic persistent hepatitis and 65.6% +/- 23.3% in 21 patients with chronic active hepatitis (p less than 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B.