Systematic review with meta-analysis: effectiveness and tolerability of interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype 1 in routine clinical practice in Asia.

BACKGROUND: Direct-acting antiviral (DAA) regimens have shown high efficacy and tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials. However, robust real-world evidence of interferon (IFN)-free DAA treatment for HCV GT1-infected patients in Asia is still lacking. AIM: To systematically review and meta-analyse the effectiveness and tolerability of IFN-free DAA therapy for HCV GT1 infection in Asia. METHODS: We included studies that enrolled adult patients with HCV GT1 infection in routine clinical practice in Asia, using IFN-free DAA regimens, and reported sustained virological response (SVR) after 12/24 weeks end-of-treatment by 31 May 2017. The pooled SVR rates were computed with a random-effects model. Subgroup analysis and meta-regression as previously registered in PROSPERO were performed to determine how pre-planned variables might have affected the pooled estimates. RESULTS: We included 41 studies from eight countries and regions, comprising of 8574 individuals. The pooled SVR rates for GT1 were 89.9% (95% CI 88.6-91.1, I2  = 55.1%) with daclatasvir/asunaprevir (DCV/ASV) and 98.1% (95% CI 97.0-99.0, I2  = 41.0%) with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV). Baseline cirrhosis but not prior treatment history and age, attenuated the effectiveness of both regimens. Baseline resistance associated substitutions (RASs) severely attenuated SVR of DCV/ASV (65.4% vs 94.3%, P < 0.001) and only minimally with LDV/SOF ± RBV (94.5% vs 99.2%, P = 0.003). Patients with renal dysfunction treated with DCV/ASV showed a higher SVR rate (93.9% vs 89.8%, P = 0.046). Patients with hepatocellular carcinoma (HCC) LDV/SOF ± RBV achieved a lower SVR than those without HCC (94.1% vs 98.7%, P = 0.001). CONCLUSION: All oral DAA treatment of HCV GT1 resulted in high cure rates in Asian patients in routine clinical practice setting including elderly patients and those with end-stage renal disease.

Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment.

BACKGROUND: With the development of direct-acting anti-virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR). AIM: To evaluate the short-term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC. METHODS: This large-scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon-free sofosbuvir-based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan-Meier method and Cox proportional hazard analysis were used to calculate the cumulative HCC incidence and related factors of HCC. RESULTS: During the follow-up period (median: 17 months), 46 (2.7%) patients developed HCC. The 1-year cumulative rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P < 0.001). For cirrhotic patients, serum α-fetoprotein level at the end of treatment (EOT-AFP) was the strongest predictor of de novo HCC. The 1-year cumulative de novo HCC rates were 1.4% and 13.1% in the EOT-AFP < 9.0 ng/mL and ≥ 9.0 ng/mL groups (cut-off value) respectively (log-rank test: P < 0.001). The 1-year cumulative rates of HCC recurrence were 6.5% and 23.1% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P = 0.023). For cirrhotic patients, previous HCC characteristics were significantly associated with HCC recurrence. In contrast, sex, age and metabolic features did not influence de novo HCC or recurrence. CONCLUSIONS: For cirrhotic patients after elimination of HCV, serum EOT-AFP level and previous HCC characteristics would be useful markers for predicting de novo HCC or recurrence.

Serum WFA(+) -M2BP is a non-invasive liver fibrosis marker that can predict the efficacy of direct-acting anti-viral-based triple therapy for chronic hepatitis C.

BACKGROUND: The Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+) -M2BP) is a new liver fibrosis glycobiomarker with unique fibrosis-related glyco-alteration. WFA(+) -M2BP is also a useful surrogate marker for the risk of developing hepatocellular carcinoma and for the liver functional reserve. AIM: To evaluate the diagnostic ability of WFA(+) -M2BP for liver fibrosis in the clinical setting and the clinical utility of WFA(+) -M2BP for predicting the efficacy of direct-acting anti-viral (DAA) treatment for chronic hepatitis C patients. METHODS: The study included 159 genotype 1 hepatitis C patients who received DAA-based treatment (telaprevir or simeprevir) combined with pegylated-interferon alpha plus ribavirin (108 telaprevir- and 51 simeprevir-based triple treatment). The relation between baseline serum WFA(+) -M2BP and treatment efficacy was evaluated. RESULTS: The serum WFA(+) -M2BP level significantly increased with the progress of liver fibrosis. Area under the receiver operating characteristic curve analysis identified 2.17 as the cut-off index (COI) for WFA(+) -M2BP for diagnosing advanced fibrosis. The sustained virological response (SVR) rate was significantly, negatively correlated with the serum WFA(+) -M2BP level. Multiple logistic regression analysis found a low serum WFA(+) -M2BP level (<2.17 COI) to be independently associated with SVR (odds ratio, 4.35, P = 0.027). Even for prior nonresponders and patients with the interleukin-28B minor allele or histological advanced fibrosis, treatment outcome was favourable for patients with a low serum WFA(+) -M2BP level. CONCLUSION: Serum WFA(+) -M2BP is a non-invasive liver fibrosis marker useful for predicting the efficacy of DAA-based triple therapy for chronic hepatitis C patients.

Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure.

Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG-IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study was carried out to evaluate the effectiveness of simeprevir-based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir-based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG-IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve [3/4 (75.0%)] or with prior relapse [1/1 (100%)] or partial response [5/6 (83.3%)] to PEG-IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct-acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG-IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir-based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG-IFNα and ribavirin. For patients with prior null response to PEG-IFNα and ribavirin, retreatment with simeprevir-based triple therapy is not a useful option.

Valuable antiviral therapeutic options for the treatment of chronic hepatitis C patients with thrombocytopenia.

Thrombocytopenia in patients with chronic hepatitis C may represent an obstacle for the initiation of antiviral treatment. The aim of this study was to evaluate factors predictive of successful pegylated interferon (PEG-IFN) α2b and ribavirin (RBV) treatment for patients with thrombocytopenia with no history of splenectomy or partial splenic embolization. One hundred and fifty-one chronic hepatitis C patients (genotype 1: n = 110, genotype 2: n = 41) with TCP (<100 × 10(9) /L) at baseline were enrolled. Pretreatment variables included interleukin 28B (IL28B) genotype (rs8099917) and homoeostasis model assessment of insulin resistance score (HOMA-IR). The kinetics of haemoglobin and platelets according to the inosine triphosphatase (ITPA) genotype (rs1127354) were investigated. Sustained virological response (SVR) was significantly more frequent in hepatitis C virus (HCV) genotype 2 (65.9%) than in genotype 1 (34.5%) patients (P < 0.0001). Multiple logistic regression analysis of HCV genotype 1 extracted IL28B TT genotype [odds ratio (OR) 5.97, P = 0.006] and HOMA-IR <2.5 (OR 7.14, P = 0.0016) as significant independent pretreatment predictors of SVR. The analyses of HCV genotype 2 showed that HOMA-IR was significantly related to SVR, but IL28B genotype was not. Patients with ITPA CC genotype showed a significant haemoglobin reduction and lower degree of platelets decrease than those with ITPA CA/AA genotypes. The most common reason for premature discontinuation of treatment was the development of hepatocellular carcinoma (n = 8, 5.3%). In conclusion, HOMA-IR is a useful predictor of SVR for patients with thrombocytopenia infected with HCV genotype 1 or 2 treated with PEG-IFNα2b and RBV. The inclusion of IL28B, ITPA genotypes and HOMA-IR adds valuable therapeutic information.

Telaprevir-based triple therapy for chronic hepatitis C patients with advanced fibrosis: a prospective clinical study.

BACKGROUND: Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis-related complications. AIM: To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients with advanced fibrosis in a clinical practice setting. METHODS: This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3-4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin (RBV). RESULTS: The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment-naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG-IFNα2b (≥1.2 µg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight-adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection. CONCLUSIONS: The great gain in the SVR rate by telaprevir-based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment-naïve and prior relapse.

Serum pepsinogen and Helicobacter pylori infection--a Japanese population study.

The decreased ratio of serum pepsinogen (PG) I and II has good correlation with the presence of atrophic gastritis. A total of 1,540 residents aged 30-89 years were enrolled into this study to investigate which serum PG level of residents with Helicobacter pylori infection would represent an adjunct to the diagnosis and progression of atrophic gastritis. All participants received esophagogastroduodenoscopy. Serum antibody to H. pylori (anti-H. pylori) was measured by an enzyme-linked immunosorbent assay (ELISA). Serological atrophic gastritis was defined as serum PG I isozyme level ≤70 ng/ml and a PG I/II ratio of ≤3.0. Of the 1,540 participants, 923 (59.9%) were positive for anti-H. pylori. Serological atrophic gastritis was found significantly more often in anti-H. pylori-positive participants (40.8%) than in anti-H. pylori-negative participants (7.9%) (p ≤ 0.0001). The endoscopic findings of anti-H. pylori-positive participants with serological atrophic gastritis were significantly more frequent by 4.06 times for atrophic gastritis (p ≤ 0.0001) than anti-H. pylori-negative participants without serological atrophic gastritis. Eight anti-H. pylori-positive participants were diagnosed with gastric cancer, but no cancer was found in anti-H. pylori-negative participants without serological atrophic gastritis. Serum PG testing is clinically useful for the prediction of gastric lesions in H. pylori-infected persons.

Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese population study: results from the Kyushu and Okinawa Population Study (KOPS).

AIMS/HYPOTHESIS: Glycated albumin is a measure of the mean plasma glucose concentration over approximately 2-3 weeks. We determined reference values for glycated albumin, and assessed its utility for the diagnosis of type 2 diabetes mellitus in the general population. METHODS: We studied 1,575 men and women (mean age, 49.9 years; range, 26-78 years) who participated in a periodic health examination in a suburban Japanese town. HbA(1c) and fasting plasma concentrations of glucose (FPG) and glycated albumin were measured. Participants with FPG ≥ 7.0 mmol/l or HbA(1c) ≥ 6.5% (48 mmol/mol) were diagnosed as having diabetes. In our laboratory, the glycated albumin assay had intra-assay and inter-assay CVs of 1.1% and 1.6%, respectively. RESULTS: Glycated albumin levels were significantly correlated with HbA(1c) levels (r = 0.766, p < 0.001) and FPG (r = 0.706, p < 0.001). The presence of diabetes was significantly higher in participants with glycated albumin levels between 15.0% and 15.9% (five of 276, 1.81%) than in those with glycated albumin <14% (three of 672, 0.45%) (p = 0.037), and was markedly increased in those with a glycated albumin level >16% (58 of 207, 28.0%). Receiver operating characteristic curve analysis indicated that a glycated albumin level of ≥15.5% was optimal for predicting diabetes, with a sensitivity of 83.3% and a specificity of 83.3%. CONCLUSIONS/INTERPRETATION: There is merit to further investigating the potential for glycated albumin to be used as an alternative measure of dysglycaemia for future research and clinical practice.

Human T lymphotropic virus type 1 infection influences hepatitis C virus clearance.

To explore the effect of human T lymphotropic virus type 1 (HTLV-1) infection on hepatitis C virus (HCV) infection, a survey for these viral infections was conducted that involved 2280 residents in an area in which HTLV-1 and HCV are endemic. The response of patients with HCV and HTLV-1 to interferon (IFN)-alpha treatment was also assessed. Antibody to HCV was detected in 13.8% of the residents tested, and antibody to HTLV-1 was detected in 15.4%. The prevalence of HCV RNA was significantly higher among residents who had antibodies to both HCV and HTLV-1 than in those who had antibodies to HCV only (P<.05). Sustained elimination of HCV RNA by IFN was significantly more frequent among patients with HCV alone than among those with HCV and HTLV-1. By logistic regression analysis, HTLV-1 infection was associated with nonresponse to IFN treatment. Thus, HTLV-1 infection affects the clearance, both natural and in association with IFN treatment, of HCV.

Acute hepatitis C among Japanese hemodialysis patients: a prospective 9-year study.

OBJECTIVES: The aims of this prospective survey were to determine the incidence and clinical characteristics of newly acquired hepatitis C virus (HCV) infection in hemodialysis patients after the start of antibody to HCV (anti-HCV) screening for blood products in Japan in 1989. METHODS: In serial serum samples from 269 hemodialysis patients who were followed over a mean period of 6.6 yr (+/- 2.1 yr) from 1990 to 1998, HCV RNA and anti-HCV were detected by reverse transcription-polymerase chain reaction and second generation ELISA, respectively. RESULTS: During the observation period, newly acquired HCV infection was found in 26 (15.4%) of the 169 hemodialysis patients without anti-HCV or HCV RNA at entry, an annual incidence rate of 2.59%. Of these 26, only four had a history of blood transfusion, one of whom had received the blood transfusion after 1992, the year in which screening of blood products for anti-HCV by second-generation ELISA was introduced in Japan. Persistent HCV viremia was found in 17 (65.4%) of the 26 patients; the other nine (34.6%) had transient HCV infection. The mean period of continuous ALT abnormality was significantly longer in the former (12.4+/-13.6 months) than in the latter (1.9+/-3.5 months) (p = 0.0067). However, only three (17.6%) of 17 patients with chronic HCV viremia had continuous ALT abnormality for more than 24 months; in all of them, ALT eventually normalized. CONCLUSIONS: These findings indicate that newly acquired HCV infection has continued to occur in hemodialysis patients after the initiation of anti-HCV screening of blood products and that the abnormal ALT found in these patients is related to HCV chronicity.

Effectiveness of interferon treatment for patients with chronic hepatitis C virus infection and normal aminotransferase levels.

To determine the effects of interferon treatment, we studied 77 Japanese patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase (ALT). Of 77 patients, 37 were given natural interferon-alpha for 24 weeks, and 40 not given interferon acted as controls. Serum samples were tested for HCV RNA and genotypes by polymerase chain reaction (PCR). HCV RNA levels were measured by competitive PCR. Of 37 treated patients, 11 (29.7%) had sustained elimination throughout a six-month follow-up, while HCV RNA was not eliminated in any untreated patients. At 24 months, the number of patients with elevated ALT was not significantly different between treated (13.5%) and untreated patients (15%). Interferon eliminates HCV RNA in patients with normal ALT without severe side effects. The natural history of HCV infection should be clarified so that the interferon treatment regimen can be tailored to the needs of each patient.

A relationship between the evolution of hepatitis C virus variants, liver damage, and hepatocellular carcinoma in patients with hepatitis C viremia.

To clarify the mechanism of liver damage induced by hepatitis C virus (HCV) and to determine whether the damage is related to hepatocellular carcinoma (HCC), HCV RNA levels were measured serially, and HCV genome mutations were analyzed from serum of 274 Japanese patients with chronic HCV viremia during 1993-1998. All patients had alanine aminotransferase (ALT) levels measured during 1986-1998. Patients with consistently normal ALT levels had identical and highly conserved HCV core regions; however, those with consistently abnormal ALT levels had quasi species, and the population of the quasi species changed over time. HCV RNA levels did not change in the 274 patients. HCC developed in 31% of 80 patients with consistently abnormal ALT levels and in 4% of 92 patients with intermittently abnormal ALT levels but never in 102 patients with ALT levels consistently normal during 1993-1998. In patients with chronic HCV viremia, persistent liver damage plays an important role in the development of HCC.

Lower hepatitis G virus infection prevalence compared to hepatitis B and C virus infection prevalences.

To more accurately determine the seroprevalence of hepatitis G virus (HGV) infection, we surveyed antibody to HGV (anti-E2) by enzyme-linked immunosorbent assay (ELISA) and HGV RNA by nested polymerase chain reaction (PCR) in 298 residents of a hepatitis C virus (HCV)-endemic area of Japan and in 225 hemodialysis patients. We then compared these findings with known HCV and hepatitis B virus (HBV) infection prevalences. Anti-E2 and HGV RNA prevalences were 32 (10.7%) and 5 (1.7%) in the residents and 24 (10.7%) and 10 (4.4%) in the hemodialysis patients, respectively. Anti-E2 and HGV RNA concurrence was found in two of the hemodialysis patients. Total HGV marker (anti-E2 and/or HGV RNA) prevalences [37 (12.4%) in residents and 32 (14.2%) in hemodialysis patients], were significantly lower than the prevalences of antibody to HCV (anti-HCV) by ELISA [59 (19.8%) and 96 (42.7%)], and antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay (RIA) [87 (29.2%) and 101 (44.9%)] (P<0.05). The anti-HCV prevalence in subjects with total HGV marker was significantly higher than in those without total HGV marker. There was no significant difference in anti-HBc prevalence between those with and without total HGV marker. The viremic rate was highest in HCV infection (HCV RNA by PCR/anti-HCV) (83.2%), with HGV infection (HGV RNA/total HGV marker) (21.7%) intermediate, and HBV infection (hepatitis B surface antigen by RIA/anti-HBc) (5.3%) lowest (P<0.05). These findings indicate that HGV infection was less endemic than HCV and HBV. HGV was eliminated naturally more frequently than HCV infection and less frequently than HBV infection.

Hepatitis C virus infection in institutionalized psychiatric patients: possible role of transmission by razor sharing.

The objective of this study was to determine if HCV can be transmitted from patient to patient in psychiatric institutions and to determine possible routes of infection. We did a cross-sectional survey of 196 Japanese psychiatric patients tested for HCV and HBV markers and 400 age- and sex-matched controls. Anti-HCV was detected in 10.2% and antibody to hepatitis B core antigen was detected in 44.4% of the patients, a significantly higher prevalence than found among matched controls. A multiple regression logistic analysis was used to identify risk factors that could indicate the route of infection by HCV. Duration of hospitalization, age, razor sharing, and history of surgery proved to be statistically significant independent risk factors associated with positive anti-HCV results [odds ratio (OR), 4.00; 95% confidence interval (CI), CI, 1.74-9.19; OR, 2.19; 95% CI, 1.27-1.3.77; OR, 4.90; 95% CI, 1.29-18.86; OR, 3.35; 95% CI, 0.997-11.3, respectively]. These observations suggest that razor sharing played an important role in the spread of the HCV infection in the institutionalized psychiatric patients we studied.

Maintenance hemodialysis decreases serum hepatitis C virus (HCV) RNA levels in hemodialysis patients with chronic HCV infection.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major complication among hemodialysis patients the world over. To determine the natural course of HCV viremic levels in patients on maintenance hemodialysis, we prospectively quantified the HCV RNA levels in serial blood samples from hemodialysis patients and compared them with those in nonuremic subjects. METHODS: The population studied included 98 hemodialysis patients and 228 nonuremic subjects with chronic HCV infection. HCV RNA was detected by polymerase chain reaction (PCR) and the levels were determined by branched DNA probe assay. HCV RNA genotypes were determined by PCR using type-specific primers. RESULTS: HCV RNA levels were significantly lower in hemodialysis patients (median, 0.4x10(6) genome equivalent [Meq]/ml) than in nonuremic subjects (median, 3.0 Meq/ml) (p<0.05). HCV of genotype 1b was prevalent in the hemodialysis patients (81.6%) and nonuremic subjects (88.6%). HCV RNA levels in 20 hemodialysis patients with genotype 1b were significantly reduced after each hemodialysis procedure (p<0.05). The 3-yr prospective observation from 1995 to 1998 showed a significant decrease of HCV RNA levels in 47 hemodialysis patients with genotype 1b (median, 1.9-0.9 Meq/ml, p<0.05), whereas levels in 155 nonuremic subjects with genotype 1b did not decrease (median, 2.6-3.0 Meq/ml). There were no patients or nonuremic subjects with undetectable HCV RNA by a PCR assay during the observation period. CONCLUSIONS: These observations suggest that maintenance hemodialysis decreases the HCV RNA levels in hemodialysis patients with chronic HCV infection, but does not produce clearance of the viremia.

Increased frequency of interferon-gamma-producing peripheral blood CD4+ T cells in chronic hepatitis C virus infection.

OBJECTIVES: To determine the profile of cytokine secretion by CD4+ T helper (Th) cells in chronic hepatitis C virus (HCV) infection, we used flow cytometry to determine the percentage of interferon (IFN)-gamma and interleukin (IL)-4 producing cells from CD4+ T lymphocytes in peripheral blood obtained from patients chronically infected with HCV. METHODS: Peripheral blood mononuclear cells isolated from 89 HCV infected subjects (22 asymptomatic carriers, 56 patients with chronic hepatitis, and 11 patients with liver cirrhosis) and 24 healthy controls were stained with surface CD4 and intracellular IFN-gamma and IL-4. Serum soluble IL-2 receptor (sIL-2R) levels were analyzed by ELISA. RESULTS: The frequency of IFN-gamma producing CD4+ cells in asymptomatic HCV carriers, patients with chronic hepatitis, and patients with liver cirrhosis were significantly higher than those of healthy controls (p<0.01, respectively). In contrast, the percentages of IL-4-producing CD4+ cells were very low, and there were no significant correlations with disease progression. A significant elevation in serum sIL-2R levels was found in chronic HCV infection compared to healthy controls, and serum sIL-2R levels significantly correlated with the frequency of IFN-gamma-producing cells. CONCLUSIONS: In HCV infected subjects, both serum sIL-2R and IFN-gamma are increased in chronic HCV infection no matter the stage of disease, meaning they are no different in asymptomatic carriers, patients with chronic hepatitis, and patients with liver cirrhosis, and that Th1 cytokine or Th1 cells may participate in the pathogenesis of liver damage in chronic HCV infection.

Seroepidemiology of TT virus infection and relationship between genotype and liver damage.

TT virus (TTV) has been identified in patients with posttransfusion hepatitis of unknown etiology and is thought to be a new hepatitis virus. We determined the extent of TTV infection in the Japanese general population and the relationship between TTV DNA genotype and liver damage. In 1998, we tested 847 serum samples for TTV. TTV DNA was assayed by a nested polymerase chain reaction and classified into three different genotypes and eight subtypes. TTV DNA was detected in 25.3% and 32.4% of the inhabitants of the two areas studied, respectively. The genotype distribution was similar in both areas. G1, G2, and G3 were 60%, 20%, and 5%, respectively. Of the 20 subjects with TTV DNA alone and elevated serum ALT levels, 18 were G1, one was G2, and one was G3. TTV infection is endemic in the Japanese general population studied. The main TTV genotype, G1, may be related to the ensuing liver damage.

Liver damage in hemodialysis patients with hepatitis C virus viremia: a prospective 10-year study.

Hepatitis C virus (HCV) infection is a major problem associated with hemodialysis. The extent of liver damage in hemodialysis patients with chronic HCV infection has not been thoroughly documented. The aim of this study was to evaluate liver damage of hemodialysis patients infected with HCV. A total of 233 hemodialysis patients were categorized into two groups at entry: group X, 80 positive for serum HCV RNA, and group Y, 153 negative for serum HCV RNA. All were tested for serum alanine aminotransferase (ALT) serially from 1989 to 1998, and serum hyaluronic acid (HA), serum type-IV collagen (IV-C), platelet counts, and ultrasonographic examination of the liver was done in 1998. In group X, 61.3% had continuously abnormal ALT levels for over six months followed by normal ALT levels. Of the group X patients, 11.3% had abnormal ALT levels in 1998, and in three, hepatocellular carcinoma occurred. Mean HA and IV-C levels in group X (648.8 and 188.7 ng/ml, respectively) were significantly higher than in group Y (213.1 and 165.5 ng/ml, respectively) (P < 0.05). Ultrasonographic findings significantly correlated with serum HA level and platelet counts and showed significantly more abnormalities in group X than in group Y (P < 0.05). From these findings, a combined examination with ultrasonography and serum fibrogenesis markers is useful for detection of liver damage in hemodialysis patients with HCV viremia.

Rapidly growing primary gastric B-cell lymphoma after eradication of Helicobacter pylori.

Helicobacter pylori (H. pylori) infection plays a decisive role in primary gastric B-cell lymphoma especially of mucosa-associated lymphoid tissue (MALT)-type. We treated a 47-year-old male patient with primary gastric B-cell lymphoma associated with H. pylori infection. Although antibiotic therapy for eradication of H. pylori caused great improvement in the low-grade MALT lymphoma-like lesion, the small areas of high-grade lesion rapidly formed a new bulky mass in only 8 weeks. This suggests that eradication of H. pylori is not effective for high-grade lymphoma.