Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis

Introduction and objectivesHepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis.Patients and methodsA retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed.ResultsAfter a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40–4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87–17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM.ConclusionsElder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.     

Risk factors and prevention of hepatocellular carcinoma in HCV infection

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Several risk factors for HCC development have been identified, including cirrhosis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection. With regard to cirrhosis, multivariate analysis indicates that alcohol abuse, HBsAg positivity, and anti-HCV seropositivity are independent variables associated with an increased risk for HCC in the cirrhotic patient. A close relationship between chronic HBV infection and HCC has been established by epidemiological studies and laboratory investigations. Evidence indicates that HCV also plays a leading role in development of HCC. Most patients with HCV-related HCC develop the tumor as a consequence of long-standing infection accompanied by chronic and progressive liver damage. In our study of 290 consecutive patients with cirrhosis, patients with persistently elevated or fluctuating ALT levels had a significantly greater rate of HCC development. The mechanism of HCC development in HCV infection remains to be elucidated. The annual cumulative risk of developing HCC is approximately 1% in patients without cirrhosis at inclusion and 3–10% in those with cirrhosis, depending on the stage of cirrhosis and presence of etiological cofactors. Although some evidence suggests that patients infected with the HCV genotype 1b are at increased risk for development of more severe liver disease, including HCC, results of our prospective study do not support a difference between cirrhotic and noncirrhotic patients in terms of the natural course of cirrhosis and the rate of developing HCC based on genotype. Strategies to prevent HCV-related HCC include blood screening and treatment of chronic HCV infection with interferon-α. Recent studies suggest that interferon-α treatment may prevent the development of HCC in HCV infection. Further research is warranted.     

Prognostic Significance of Serum Galectin-3 Levels in Patients with Hepatocellular Cancer and Chronic Viral Hepatitis

Background/Aim:

Galectins affect diverse physiological and pathophysiological processes such as development, inflammation, and tumor growth. We aimed to compare serum galectin-3 levels in three patient groups with chronic hepatitis B and C virus (HBV, HCV), cirrhosis secondary to HBV or HCV, and hepatocellular carcinoma (HCC) secondary to HBV or HCV and evaluate the role of galectin-3 during HCC progression.

Patients and Methods:

Nineteen patients with hepatocellular cancer, 22 patients with cirrhosis, and 24 patients with chronic hepatitis B and C were included in this study. Serum galectin-3 levels in different liver diseases were assessed by enzyme-linked immunosorbent assay.

Results:

The mean galectin-3 levels were 4.61 ng/mL (±2.32) in HCC patients, 5.68 ng/mL (±2,2) in cirrhotic patients, 1.98 ng/mL (±1.50) in chronic viral hepatitis group. There were no statistical differences between HCC and cirrhotic patients (P = 0.5), but lower in chronic hepatitis group statistically compared with cirrhosis and HCC (P < 0.001, P = 0.002, respectively). In case of cirrhotic patients, galectin-3 levels were significantly higher in patients with cirrhosis secondary to HCV compared with HBV (P = 0.03). When we evaluated galectin-3 levels in HCC patients, it was found to be 3.92 ng/mL in HCC secondary to hepatitis B and 5.37 ng/mL in HCC secondary to hepatitis C.

Conclusion:

Serum galectin-3 levels in patients with chronic HBV or HCV may guide us about progression to cirrhosis or HCC and prognosis of the disease. Especially, galectin-3 levels may be more pronounced in case of HCV.     

Dermatomyositis associated with hepatocellular carcinoma in an elderly female patient with hepatitis C virus-related liver cirrhosis

A 79-year-old female patient with hepatitis C virus-related liver cirrhosis was diagnosed as having hepatocellular carcinoma (HCC) with a diameter of 2.0 cm. She refused therapy for HCC. Nine months after the diagnosis, she developed dermatomyositis when the HCC enlarged to a diameter of 6.0 cm. She underwent therapy for dermatomyositis, and then transcatheter arterial chemoembolization for HCC. Although the manifestations of dermatomyositis improved and entire tumor necrosis was achieved, she died of pneumonia 2 mo after the treatment of HCC. HCC and/or chronic hepatitis C virus infection might be involved in the pathogenesis of dermatomyositis.     

Previous hepatitis E virus infection,cirrhosis and insulin resistance in patients with chronic hepatitis C

Background

Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance.

Hepatitis B and C virus infection as risk factors for liver cirrhosis and cirrhotic hepatocellular carcinoma: a case-control study

To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC), a case-control study of 102 cirrhotic HCC patients, 102 sex-matched and age-matched patients with liver cirrhosis, and 102 matched patients with non-hepatic disease controls was performed. The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) in HCC (70.5%, 39.2%) and liver cirrhosis (74.5%, 27.4%) were higher than controls (16.6%, 10.5%) (P = 0.0001). In HBsAg-negative patients, the prevalence of anti-HCV in cirrhotic HCC (66.6%) and liver cirrhosis (46.1%) was higher than in controls (10.5%; P = 0.0001). There was no such difference in HBsAg-positive patients. Multivariate analysis revealed that both HBsAg and anti-HCV were important risk factors for HCC (odds ratio, 6.52 and 4.59, respectively) and liver cirrhosis (odds ratio, 4.22 and 2.29, respectively). There was no difference in odds ratio when HCC and liver cirrhosis were compared. Our result implies that both HBV and HCV are independent risk factors for cirrhotic HCC and liver cirrhosis in Taiwan.     

A Case Report of Hepatocellular Carcinoma 5 Years After HBsAg Loss in Chronic Hepatitis Delta: How Long Surveillance is Required?

BackgroundHepatitis delta virus infection occurs as acute coinfection or as superinfection in patients with preexisting chronic hepatitis B. Chronic hepatitis delta leads to more severe disease than chronic hepatitis B, with more rapid progression of fibrosis and increased risk of hepatocelullar carcinoma.Case reportWe report a case of hepatocelullar carcinoma 5 years after spontaneous clearance of Hepatitis B surface antigen in a patient with previous chronic hepatitis delta. He had been diagnosed with acute hepatitis delta superinfection 30 years ago which evolved to chronic delta infection and subsequently development of liver cirrhosis. Despite no specific antiviral treatment, he lost HBsAg persistently with later regression of cirrhosis.ConclusionsIn patients with cirrhosis due to chronic hepatitis delta who cleared HBsAg with improvement of liver fibrosis by non invasive techniques, it remains unknown how long hepatocelullar carcinoma surveillance has to be maintained.     

Clinical prognostic variables in young patients (under 40 years) with hepatitis B virus-associated hepatocellular carcinoma

OBJECTIVE: The aim of this study was to determine the impact of hepatocelluar carcinoma (HCC) screening in chronic hepatitis B patients who did not meet the current screening recommendations. METHODS: Patients who were admitted to Bellevue Hospital Center with HCC were assessed for risk factors, cirrhosis and tumor‐specific factors. Eligibility for liver transplantation or resection with favorable outcome was determined by applying Milan criteria. RESULTS: In all 93 patients were diagnosed with hepatitis B virus (HBV)‐associated HCC, 18 of whom were under 40 years. Cirrhosis was infrequently associated with HCC in this group, with most cancers occurring in non‐cirrhotic patients (12/18, 66.7%). No patient developed HCC outside the American Association for the Study of Liver Diseases (AASLD) cancer screening recommendations (young age, non‐cirrhotic) were eligible for liver transplantation or resection with favorable outcomes (within Milan criteria). However, HCC patients who were diagnosed within AASLD screening recommendations did meet Milan criteria in 17.3% (14/81) patients. CONCLUSIONS: Current guidelines for HCC screening in patients with HBV may lead to a delay in diagnosis in non‐cirrhotic patients under 40 years. Consideration should be given to modifying current recommendations to advocate entering HBV patients into a cancer‐screening program at young age.     

Effects of antiviral therapy in patients with chronic hepatitis B and cirrhosis

Introduction: Hepatitis B virus (HBV) infection is the major cause of cirrhosis worldwide. The ultimate goal of current antiviral treatments for chronic hepatitis B (nucleos(t)ide analogs and interferon-α) is to prevent the development of end-stage liver diseases.

Areas covered: We present a review of the current literature on antiviral therapy in patients with chronic hepatitis B and cirrhosis. Medline search was performed to identify relevant literature from 1993 through January of 2017.

Expert commentary: One randomized controlled trial and a number of observational studies have shown that nucleos(t)ide analogs can decrease the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis. Data from clinical trials of entecavir and tenofovir have shown that histological improvement and regression of fibrosis can be achieved in the majority of patients with chronic hepatitis B by successful viral suppression. Entecavir and tenofovir are the preferred antiviral agents for treatment of chronic hepatitis B in patients with cirrhosis due to their high antiviral potency and high genetic barrier to resistance. Pegylated interferon-α is another therapeutic option for chronic hepatitis B patients with well-compensated cirrhosis. However, interferon therapy is contraindicated in patients with decompensated cirrhosis, and evidence for reduced HCC is currently insufficient.     

Expression of oncogenes in human liver disease

To elucidate the role of oncogene expression in hepatocarcinogenesis, we examined the expression of 8 cellular oncogenes by dot blot and/or northern blot analysis in neoplastic, cirrhotic and non-cirrhotic human liver tissues obtained at surgery. Significantly higher levels of c-myc gene expression were observed in tissues of hepatocellular carcinoma (HCC) and adjacent cirrhotic tissues than in apparently normal liver tissues or those of chronic hepatitis (normal-chronic hepatitis). There was a tendency to higher c-myc mRNA levels in HCC than in liver cirrhosis. However, when tumorous and adjacent cirrhotic tissues from the same patient were compared, c-myc mRNA levels were not consistently higher in HCC. No significant differences in mRNA levels of c-fos, N-myc, N-ras, Ha-ras, c-erbA, c-erbB and c-abl were observed among the HCC, cirrhosis and normal-chronic hepatitis groups. Although the significance of increased c-myc gene expression in liver cirrhosis and HCC is still not known, it is conceivable that the persistent elevation of c-myc gene expression in cirrhosis contributes to the development of HCC.     

Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues

SUMMARY. We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.     

Evaluation of the diagnostic value of serum and tissue apoptotic cytokeratin-18 in patients with chronic hepatitis C

Background and study aimsHepatitis C virus (HCV) is considered the most common aetiology of chronic liver disease (CLD) in Egypt. The disease severity ranges from mild illness to cirrhosis and hepatocellular carcinoma. A role for apoptosis in liver damage caused by HCV chronic infection has been suggested. Cytokeratin 18 (CK-18) is the major intermediate filament protein in the liver and is a known caspase substrate in hepatocyte apoptosis. Therefore, we analysed the serum and tissue levels of CK-18 in patients with chronic HCV infection to evaluate its role in hepatocyte apoptosis. We also correlated CK-18 expression with the severity of hepatic pathology.Patients and methodsThis study examined 80 Egyptian patients with liver disease. There were 69 patients with chronic hepatitis C and 11 patients with hepatitis C-induced cirrhotic changes. Fifteen healthy controls were also included in the study. The levels of CK-18 fragment were quantified in paired serum and liver biopsy samples.ResultsThe serum and tissue CK-18 levels were reduced in chronic HCV patients compared to early cirrhosis patients. This result indicates that serum levels of CK-18 and the hepatic expression of CK-18 might play an important role in disease progression. The serum and tissue levels of CK-18 were significantly increased and directly correlated with inflammation severity, stage of fibrosis, and ALT levels in the chronic HCV group and the cirrhotic liver group. There was no significant difference in viral load between patient cohorts.ConclusionThe serum level and the hepatic expression of CK-18 are related to disease activity and are directly correlated with METAVIR scoring. This result suggests that serum CK-18 levels may be useful for monitoring disease activity in chronic HCV and liver cirrhosis patients.     

DNA measurements in chronic hepatitis, cirrhosis and hepatocellular carcinoma

It has been documented that chronic hepatitis may progress to cirrhosis and then develop hepatocellular carcinoma (HCC). To test whether abnormal cellular DNA increases along this line of development, liver tissues from 48 patients with chronic hepatitis, 17 with cirrhosis, and 8 with HCC were investigated for cellular DNA content with a scanning microdensitometer. Seven of 8 HCCs and 2 cirrhotic livers adjacent to HCC had abnormally increased cellular DNA content. Only 4 livers from patients with chronic liver diseases other than HCC had abnormal cellular DNA content. The cellular DNA content in livers not accompanying HCC was not related to the patient's age, histological diagnosis, and hepatitis inflammatory activity. The results confirmed the increase of cellular DNA content in HCC, but did not provide evidence of a progressively increasing DNA content from chronic hepatitis to liver cirrhosis. However, cirrhotic livers with abnormal hepatocytic DNA content deserve careful follow-up for the early detection of HCC.     

Risk and outcome of hepatocellular carcinoma in liver cirrhosis in Southern Sweden: a population-based study

Background and aims: Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC). While the HCC risk is thought to be highest in hepatitis B and hepatitis C, the risk in other cirrhosis etiologies is not fully established. Therefore, we aimed to study the risk and outcome of HCC in alcoholic cirrhosis compared to cirrhosis of other etiologies, in Sweden.

Material and methods: We used population-based medical registries to identify patients diagnosed with cirrhosis in the Scania region in southern Sweden between 2001 and 2010. Medical records were reviewed to identify all HCC cases and to register clinical parameters. All patients were followed until death, emigration or December 2017.

Results: The cohort comprised 1317 patients with cirrhosis. A total of 200 patient developed HCC, including 75 with prevalent HCC. The annual incidence of HCC after six months was 1.5% in alcoholic cirrhosis and 4.7% in hepatitis C cirrhosis. In alcoholic cirrhosis, 40 patients were diagnosed with HCC during follow-up, of which 15 patients fulfilled the Milan criteria and 10 received treatment, curative or palliative. The overall median survival after HCC diagnosis was 7.7 months, with 4.5, 11 and 9.3 months, in cirrhosis due to alcohol, hepatitis C or remaining causes, respectively.

Conclusion: We find an annual incidence of HCC in alcoholic cirrhosis of 1.5% indicating need for surveillance in these patients. Survival after HCC diagnosis was worst in alcoholic cirrhosis due to more advanced stage at diagnosis with few patients eligible for treatment.     

Hepatocellular carcinoma with sarcomatous change arising in primary biliary cirrhosis

We report an autopsy case of hepatocellular carcinoma (HCC) with sarcomatous change arising in the context of primary biliary cirrhosis (PBC) in a 79-year-old man. Primary biliary cirrhosis was diagnosed (stage I according to Scheuer's classification) by findings on blood biochemical analysis, laparoscopy, and liver biopsy at age 69 years. Five years later, (at age 74 years), a mass lesion was detected in the S₆ region of the liver by abdominal ultrasonography, and target biopsy revealed well differentiated HCC. Blood biochemistry, ultrasonography, and computed tomography findings showed that the PBC had progressed to stage IV (cirrhotic stage). Percutaneous ethanol injection therapy (PEIT) was administered to the HCC several times over a 5-year period; however, the patient died of liver failure in February, 1994 (at age 79 years). Viral markers for hepatitis B and C were negative during the course, and hepatitis C virus RNA was not detected by polymerase chain reaction. Autopsy findings showed liver cirrhosis and diffuse involvement of spindle-shaped sarcomatoid cells in the liver, particularly in the S₆ region, associated with several nodules of trabecular HCC cells. A zone of transition between the sarcomatoid cells and the trabecular hepatocellular carcinoma cells was observed. The sarcomatoid cells were diffusely disseminated in the peritoneal cavity and had metastasized to multiple organs. Immunohistochemically, the cells were positive for fibrinogen, as were the coexisting trabecular hepatocellular carcinoma cells. The HCC had been treated several times with PEIT. Of interest, PEIT may be an important factor in this type of tumor progression.     

Presence of Active Hepatitis Associated with Liver Cirrhosis Is a Risk Factor for Mortality Caused by Posthepatectomy Liver Failure

The histologic activity of associated hepatitis was examined in 285 patients who underwent hepatectomy for hepatocellular carcinoma (HCC), to determine if the histologic activity is an independent risk factor for postoperative mortality due to liver failure. The proportion of patients with liver cirrhosis who died due to liver failure (6/180, 3.3%) was not different from that of patients with chronic hepatitis (2/68, 2.9%). However, mortality was higher in patients with liver cirrhosis and active hepatitis (4/46, 8.7%) than in those with cirrhosis and inactive hepatitis (2/134, 1.5%, P < 0.05). Such difference was not observed in the chronic hepatitis group. Multivariate analysis showed that clearance of indocyanine green at 15 min (ICGR15) and activity of hepatitis were two independent risk factors for postoperative mortality due to liver failure. In conclusion, histologic activity of associated hepatitis should be taken into account in hepatic resection of HCC in cirrhotic liver, in addition to the functional reserve of the liver.     

Meshwork pattern is an important risk factor for development of hepatocellular carcinoma in patients with HBV-related chronic hepatitis and cirrhosis

We analyzed the importance of ‘meshwork pattern’, a sign representing severe irregularity on the intra-hepatic echogram, in hepatitis B virus (HBV)-related chronic hepatitis and cirrhosis, as a risk factor for development of hepatocellular carcinoma (HCC). Two hundred and thirty-one patients (143 men and 88 women) with HBV-related chronic hepatitis and cirrhosis who visited our hospital from January 1993 to December 1994 were enrolled in this study. Since enrollment, abdominal ultrasonography had in principle been performed every 3 months for cirrhotic patients and every 4–6 months for patients with chronic hepatitis for HCC screening. Cumulative HCC incidences in patient groups positive or negative for meshwork pattern were calculated by the Kaplan–Meier method. The incidence of HCC was significantly higher in the group positive for meshwork pattern (average incidence per year: 4.4%) than in the group negative for it (average incidence per year: 0.5%) (P<0.0001, Mantel–Cox test). On regression analysis with Cox's proportional hazards model, sex, α-fetoprotein and meshwork pattern were selected as independent risk factors for HCC. In conclusion, meshwork pattern appears to be an ultrasonographic sign useful for detecting a latent risk factor for HCC in patients with HBV-related chronic hepatitis and cirrhosis.     

SEN virus infection in patients with chronic liver disease and hepatocellular carcinoma in Thailand

Background: SEN virus (SENV) has been recently identified as a candidate agent of non-A-E hepatitis virus. However, the exact role of this novel virus in the pathogenesis of chronic liver disease, including chronic hepatitis and cirrhosis, and the development of hepatocellular carcinoma (HCC) remains to be established. Methods: Using seminested polymerase chain reaction (PCR) amplification to detect SENV-D and SENV-H strains in serum, we investigated SENV infection in voluntary blood donors and in patients with chronic liver disease and HCC. Results: SENV was detected in 5 of 100 blood donors (5%), in 15 of 60 patients with chronic liver disease (25%), and in 25 of 60 patients with HCC (42%). The prevalence of SENV in patients with HCC was higher than that in patients with chronic liver disease (P = 0.05) and in blood donors (P < 0.001). An age-specific prevalence of SENV was found at high levels among individuals aged 21–40 years, but was not detected among individuals in the lower age group. No differences between SENV-infected and non-infected patients were demonstrated with respect to demographic data, assumed source of infection, biochemical abnormalities, and severity of chronic liver disease and HCC. Moreover, SENV infection had no apparent effect on the survival of patients with HCC. Conclusions: Our data suggest that SENV infection is frequent among patients with chronic liver disease and HCC. However, pathogenic effects associated with SENV infection in chronic liver disease and HCC need further investigation. Received: April 4, 2002 / Accepted: July 26, 2002 Acknowledgments. We would like to express our gratitude to the entire staff of the Viral Hepatitis Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, for their tireless effort in this research project. We also would like to thank the Center of Excellence Fund, Rachadaphisek Somphot Endowment, Chulalongkorn University, and the Thailand Research Fund, Senior Research Scholar, for supporting this research. Reprint requests to: Y. Poovorawan     

Incidence of hepatocellular carcinoma in chronic Hepatitis B and C: A prospective study of 251 patients

The incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included). Of the cases of chronic hepatitis B, 5 cases of HCC (3.9%) were detected; among the chronic hepatitis C cases, 13 cases (10.4%) were detected. Thus, although the mean follow-up periods were in the same range, the incidence of hepatocellular carcinoma was 2.7 times higher in hepatitis C than in hepatitis B (x² = 3.116, P < .05). Using the Kaplan-Meier method, the incidence of HCC was significantly higher in chronic hepatitis C (P = .0194, generalized Wilcoxon test). In hepatitis C, the incubation period until HCC was detected was shorter when the liver disease was more advanced. Such a tendency was not observed in hepatitis B. In the 13 cases of HCC occurring in chronic hepatitis C, noncirrhotic liver was seen in only 1 case (7.7%), whereas 2 of the 5 cases of HCC (40%) in chronic hepatitis B were noncirrhotic. The prevalence of hepatitis C virus (HCV) genotypes II and III was the same in the total followed cases and HCC cases.