Development of hepatocellular carcinoma in elderly patients with chronic hepatitis C with or without elevated aspartate and alanine aminotransferase levels

Objective. Hepatocellular carcinoma (HCC) in the elderly infected with hepatitis C virus (HCV) is expected to increase globally within the next two decades. The purpose of the study was to define the natural history of elderly patients with chronic hepatitis C needs in order to prevent HCC from arising in these patients. Material and methods. Treatment-naive patients aged ≥65 years with platelet counts >120×10³/mm³ were classified as 120 with aspartate and alanine aminotransferase (ASAT and ALAT) levels ≦40 IU/l (group A) and 212 with either or both levels ≥41 (group B) and followed-up for 3 years or longer without antiviral treatment. Results. Cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 for both). In particular, of the patients aged 65–69 years at entry, cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 and p=0.001, respectively). Liver-related causes of death were more common in group B than in group A (20/34 (59%) versus 1/9 (11%), p=0.021). HCC developed more frequently in men than in women (p=0.033). Conclusions. In elderly patients with chronic hepatitis C, cirrhosis and HCC develop more frequently in those with elevated transaminase levels than in those without elevated transaminase levels. Therefore, transaminase levels need to be suppressed below ≦40 IU/l, using antiviral treatments or other agents, in order to prevent cirrhosis and HCC arising in these patients. In view of rare liver-related deaths, aggressive antiviral treatment would not be necessary in the elderly with chronic hepatitis C who have normal transaminase levels.     

Prevalence of hepatitis C virus antibodies in chronic liver disease and hepatocellular carcinoma patients in India

The prevalence of antibodies to hepatitis C virus (HCV) was investigated in 129 patients with chronic liver disease (85 with chronic active hepatitis and 44 with cirrhosis) and 53 patients with hepatocellular carcinoma. The commercially available second generation anti-HCV enzyme immunoassay kit was used. Antibodies to hepatitis C virus were detected in 16.2% of the patients with chronic liver disease and in 15.1% with hepatocellular carcinoma. Of the HCV positive patients in all groups 51.7% were positive for hepatitis B virus (HBV) markers indicating present or past infection. Prevalence of HBV markers in all the three groups (CAH, cirrhosis and HCC) was higher as compared with anti-HCV prevalence. These results suggest that HCV infection may not be a major cause of chronic liver disease and hepatocellular carcinoma in India and indicate the presence of other aetiological agents.     

Hepatitis B virus markers and antibodies to hepatitis C virus in Japanese patients with hepatocellular carcinoma

Sera from Japanese patients with chronic liver disease were tested for hepatitis B virus (HBV) markers and antibodies to hepatitis C virus (anti-HCV), and the results were correlated to the presence of hepatocellular carcinoma. In chronic non-A, non-B liver disease, anti-HCV prevalence was high both in patients with hepatocellular carcinoma (78/89, 88%) and without it (66/84, 79%), while previous HBV infection was more common in patients with hepatocellular carcinoma (65/89, 73%) than in those without it (46/84, 55%) (P<0.05). Coexistence of anti-HCV and antibodies to HBV was observed frequently in patients with hepatocellular carcinoma (56/89, 63%) compared with patients without it (39/84, 46%) (P<0.05). In chronic HBV carriers, anti-HCV was more common in patients with hepatocellular carcinoma (12/38, 32%) than in those without it (3/62, 5%) (P<0.01). These results suggest that infection with the two viruses may be a risk factor for more serious liver disease.This work was supported by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan.     

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma

This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen (HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg-negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and four (18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface (S), core (C), polymerase (P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%) patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or only in the nontumorous liver (one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg-negative, anti-HCV-positive HCCs, including three (10%) who were also negative for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV-associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs.     

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: A nationwide cohort study

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC ), and surveillance with ultrasound (US ) and alpha‐fetoprotein (AFP ) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR ) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona‐Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0‐3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY ), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI 95% 0.4‐1.5] in 2002‐2003 to 2.9/100 PY [2.4‐3.4] in 2012‐2013. One‐year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP  ≥ 20 ng mL^?1 was 17%. Twenty‐three (21%) patients were diagnosed with early‐stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early‐stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.     

Hepatic steatosis and the risk of hepatocellular carcinoma in chronic hepatitis C

BACKGROUND AND AIM: Obesity associated hepatic steatosis has been suggested to have a premalignant potential. We determined whether hepatic steatosis predisposes to liver cancer in persons with chronic hepatitis C virus (HCV) infection. METHODS: We compared the histological severity of steatosis in the index liver biopsies of 25 patients with chronic hepatitis C who subsequently developed hepatocellular carcinoma (HCC) with matched controls who did not. Cases were aged (mean) 54.7 years, 84% males, 76% genotype 1, and 64% fibrosis stage 4; and controls were matched for these characteristics. Those with a sustained virologic response to antiviral therapy were excluded. RESULTS: Duration of HCV infection, concomitant alcohol intake, body mass index and indices of past hepatitis B virus (HBV) infection were comparable between the groups. Controls were followed for a longer period after the index liver biopsy than were cases (113 months vs 55 months, P < 0.001). As determined by percentage area of biopsy core occupied by steatosis on computer assisted morphometric evaluation, and graded by semiquantitative histological assessment, steatosis was comparable among cases and controls. The odds of developing HCC among those with steatosis grades 1 and 2 did not differ significantly from those without steatosis. There was no association between increasing morphometric percentage area occupied by steatosis and the subsequent development of HCC. Neither steatosis grade or percent area of steatosis on biopsy were selected in multivariate regression analysis as independent predictors for the development of HCC. CONCLUSIONS: Hepatic steatosis does not augment the risk of hepatocarcinogenesis in patients with chronic HCV infection.     

Hepatocellular carcinoma in patients with autoimmune hepatitis

AIM： To evaluate and confirm the low incidence of hepatocellular carcinoma （HCC） in patients with autoimmune hepatitis （AIH）. At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare. METHODS： In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS： Eighty-nine patients （32%） were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION： We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.     

Hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma

Hepatitis C virus (HCV) is the major etiologic agent of parenterally transmitted non-A,non-B hepatitis. To determine whether there is a relationship between this virus agent and hepatocellular carcinoma (HCC), the sera of patients with HCC and chronic hepatitis were assessed using a sensitive immunoassay for HCV antibody. Anti-HCV was detected in 65% of 132 patients with HCC, without any relationship with the presence of the hepatitis B surface antigen (HB_sAg). The prevalence (74%) of anti-HCV was high, as expected in patients with putative non-A,non-B cirrhosis also. The prevalence of anti-HCV was less in patients with HB_sAg-positive cirrhosis (28%) and in patients with disease not related to viral hepatitis and healthy controls (8%). These data suggest, but do not prove, that HCV is an important factor associated with HCC.Presented at the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.     

Helicobacter infection in patients with HCV-related chronic hepatitis,cirrhosis, and hepatocellular carcinoma

Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). HCC represents one of the most common human cancers. Incidence rates for this tumor vary widely on a worldwide, suggesting that environmental factors such as infectious microorganisms, carcinogens, or nutrition play a role in its pathogenesis. Several Helicobacter spp. colonize the liver of animals and induce hepatitis. The aim of this study was to determine whether Helicobacter infection was associated with HCV-related liver diseases in humans. Liver tissue samples, including biopsy and surgically excised tissues, were collected from patients positive for hepatitis C viruses (HCV) RNA in the serum. Genomic DNA was extracted from sections of formalin-fixed paraffin-embedded tissues by using the QIAamp Tissue Kit and subjected to polymerase chain reaction (PCR) analysis using two sets of Helicobacter-specific 16S ribosomal RNA primers. To identify positive samples for H. pylori, a set of primers specific for a conserved region in the H. pylori vacA gene were also used. The patients' H. pylori status was determined by ELISA. Forty-one patients (mean age 54.9, range 19–78 years; 24 men) were studied. Thirty patients had chronic viral hepatitis (CH) without (N = 18) or with (N = 12) cirrhosis (CIR), and 11 patients had HCC. Anti-H. pylori IgG was detected in 54%. The expected 422- and 210-bp fragments of Helicobacter 16S rRNA were amplified from 27% of liver samples, including 17% of CH-CIR and 55% of HCC (P = 0.004). The vacA sequence was amplified in 10 of 41(24%) samples (27% of those with HCC).: These data confirm the presence of H. pylori DNA sequences in human liver and suggest an association of Helicobacter spp. with HCV-related chronic liver diseases. Further studies are needed to ascertain whether Helicobacter spp. infection plays a role in the development of HCC.     

Prevention of hepatocellular carcinoma complicating chronic hepatitis C

Chronic hepatitis C virus (HCV) infection accounts for most cases of hepatocellular carcinoma (HCC) in Japan and is the second major cause in many other countries. Development of HCC takes a considerable time after onset of HCV infection, between 20–40 years in most cases, and usually develops after cirrhosis is established. Although only a minority of HCV infections reach this stage, the high prevalence of chronic HCV infection in many countries (1–3%) is such that HCC related to HCV infection poses a significant public health issue 20–50 years after the onset of HCV epidemics. Due to advances in testing, and accessibility of clean, disposable medical apparatus including syringes and needles, and particularly screening of donor blood for anti-HCV and by nucleic acid testing, new cases of HCV infection have decreased in most countries, except for continued transmission by injection drug users (IDU). A key difference between HBV and HCV infection is that HCV can be eradicated by effective antiviral treatment. Sustained eradication of HCV reverses hepatic fibrosis, thereby preventing progression to cirrhosis and risk of HCC. Further, it has been well demonstrated that interferon-based antiviral therapy suppresses development of HCC in high-risk patients, particularly when sustained viral response (SVR) is obtained. In summary, the two key approaches to prevent development of HCV-related HCC are primary prevention of HCV infection (adequate programs to screen donor blood, universal precautions to stop medical transmission of blood-borne viruses, curbing transmission by IDU) and potent antiviral therapy of chronic HCV infection.     

Overexpressed cyclo-oxygenase-2 in the background liver is associated with the clinical course of hepatitis C virus-related cirrhosis patients after curative surgery for hepatocellular carcinoma

BACKGROUND: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC. METHODS: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53-73 years; follow-up period; range 22-159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin-biotin-peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery. RESULTS: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann-Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann-Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival. CONCLUSIONS: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.     

Development rate of chronic kidney disease in hepatitis C virus patients with advanced fibrosis after interferon therapy

Aim: The aim of this retrospective cohort study is to assess the development incidence and predictive factors for chronic kidney disease (CKD) after the termination of interferon therapy in hepatitis C virus (HCV) positive Japanese patients with liver cirrhosis. Methods: A total of 650 HCV positive, liver cirrhotic patients who were treated with interferon and showed an estimated glomerular filtration rate (eGFR) of ≥60 mL/min per 1.73 m² after the termination of interferon therapy were enrolled. CKD was defined as an eGFR of <60 mL/min per 1.73 m². End‐stage‐CKD was defined as an eGFR of <15 mL/min/1.73 m². The primary goal is the new development of CKD and end‐stage‐CKD. Results: Eighty‐five patients developed CKD, and six patients progressed to end‐stage‐CKD. The development rate of CKD was 5.2% at the 5th year, 14.5% at the 10th year and 30.6% at the 15th year. Multivariate Cox proportional hazards analysis showed that CKD occurred when patients had age increments of 10 years (hazard ratio: 2.32; 95% confidence interval [CI] 1.61–3.35; P < 0.001), eGFR decrements of 10 mL/min per 1.73 m² (hazard ratio: 1.66; 95% CI 1.27–2.16; P < 0.001), hypertension (hazard ratio: 2.00; 95% CI 1.13–3.53; P = 0.017), diabetes (hazard ratio: 1.79; 95% CI 1.02–3.14; P = 0.042), and non‐clearance of HCV (hazard ratio: 2.67; 95% CI 1.34–5.32; P = 0.005). The development rate of end‐stage‐CKD was 0.4% at the 5th year, 1.6% at the 10th year and 2.8% at the 15th year. Conclusions: The annual incidence for CKD among cirrhotic patients with HCV was determined to be about 1.0–1.5%. In addition, the annual incidence for end‐stage‐CKD is one order of magnitude lower than that of CKD.     

Hepatocellular carcinoma in long-term sustained virological responders following antiviral combination therapy for chronic hepatitis C

Summary.  Antiviral treatment results in a sustained virologic response (SVR) in 50–75% of patients with chronic hepatitis C. Long-term follow up studies have observed ongoing SVR in the overwhelming majority of them. Thus chronic hepatitis C is considered 'cured' if an SVR is achieved. Consequently, it is expected that in sustained virologic responders long-term complications of hepatatic C virus (HCV) related chronic liver disease including hepatocellular carcinoma are eliminated or have a decreased incidence. We report on five patients (three from Austria, two from USA) who developed hepatocellular carcinoma during follow up (3–6 years) after achieving SVR. During follow up and at diagnosis all were HCV-RNA neg. None of the patients had other liver diseases. One patient presented with bilateral adrenal metastasis, the remaining four with large hepatic tumours. Three patients were noncirrhotic at the start of treatment at the time of tumour diagnosis. Successful antiviral treatment in HCV patients does not prevent development of hepatocellular carcinoma even in non-cirrhotic livers. Long-term follow up of patients with SVR is mandatory and should include surveillance for hepatocellular carcinoma.     

Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus-associated hepatocellular carcinoma

BACKGROUND: The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects. METHODS: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese. RESULTS AND CONCLUSION: There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required.     

Hepatocellular carcinoma surveillance rates in commercially insured patients with noncirrhotic chronic hepatitis B

American association for the study of liver diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines recommend biannual hepatocellular carcinoma (HCC) screening for noncirrhotic patients with chronic hepatitis B infection (HBV), yet there are no data estimating surveillance rates or factors associated with surveillance. We performed a retrospective cohort study of US patients using the Truven Health Analytics databases from 2006 to 2010 and identified patients with noncirrhotic chronic HBV. Surveillance patterns were characterized using categorical and continuous outcomes, with the continuous measure of the proportion of time ‘up to date’ with surveillance (PUTDS), with the 6‐month interval following each ultrasound categorized as ‘up to date’. During a median follow‐up of 26.0 (IQR: 16.2–40.0) months among 4576 noncirrhotic patients with chronic HBV (median age: 44 years, IQR: 36–52), only 306 (6.7%) had complete surveillance (one ultrasound every 6‐month interval), 2727 (59.6%) incomplete (≥1 ultrasound) and 1543 (33.7%) none. The mean PUTDS was 0.34 ± 0.29, and the median was 0.32 (IQR: 0.03–0.52). In multinomial logistic regression models, patients diagnosed by a nongastroenterologist were significantly less likely to have complete surveillance (P < 0.001), as were those coinfected with HBV/HIV (P < 0.001). In linear regression models, nongastroenterologist provider, health insurance subtype, HBV/HIV coinfection, rural status and metabolic syndrome were independently associated with decreased surveillance. Patients with HIV had an absolute decrease in the PUTDS of 0.24, while patients in less populated rural areas had an absolute decrease of 0.10. HCC surveillance rates in noncirrhotic patients with chronic HBV in the United States are poor and lower than reported rates of HCC surveillance in cirrhotic patients.     

Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real‐world chronic hepatitis C patients cohort

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow‐up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child‐Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow‐up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.     

Type C chronic hepatitis with the discovery of a small hepatocellular carcinoma 7 years after successful interferon therapy

The patient, a 61-year-old man, had sustained injuries in a traffic accident at the age of 26, for which he received a blood transfusion. Since 1988 (age, 49 years), abnormal hepatic function had been detected, and, because of the presence of hepatitis C virus antibodies, he was diagnosed as having type C chronic hepatitis. Based on a liver biopsy that was conducted in July 1992 (age, 53), a histological diagnosis of chronic active hepatitis (F₁/A₂) was made. Over a period of 6 months, starting in 1992, the patient was treated with interferon (IFNα-2a; total dosage, 720 MU). At the end of this regimen, the alanine aminotransferase level was normalized and serum hepatitis C virus—ribonucleic acid was negative. This condition was maintained until August 1996 (age, 57), after which the patient stopped reporting to our hospital. In June 2000 (age, 61) when he was hospitalized for an adhesive ileus, a small hepatocellular carcinoma (a solitary lesion measuring 18 mm in diameter) at S₈ was found, and it was extirpated by a segmental excision in July. The case is introduced to call attention to the need for longterm follow-up observation, even after effective IFN therapy. Received: October 18, 2001 / Accepted: February 8, 2002 Reprint requests to: M. Tomimatsu Editorial on page 417     

Treatment of chronic hepatitis C virus infection in patients with cirrhosis

Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20–30% of patients and to hepatocellular carcinoma (HCC) in 1–5% of patients. Rates of sustained virological response with standard interferon-α (IFN-α) are low in patients without cirrhosis (generally < 20%) and are even lower in those with cirrhosis. Combination therapy with IFN and ribavirin improves response rates in patients with chronic hepatitis C without cirrhosis, and the results from subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are encouraging. Importantly, treatment with IFN slows progression of liver fibrosis, regardless of HCV genotype or early response to therapy, and reduces the risk of HCC by two- to fivefold. The risk of development of HCC is also lower in patients who show at least a partial response to IFN therapy compared with those who show no response. There is a clear need for more definitive studies of treatment in patients with chronic hepatitis C and cirrhosis, ideally using therapies with greater efficacy. Nonetheless, based on the potential to slow the progression of liver fibrosis (regardless of treatment response) and to reduce the risk of HCC, a greater number of HCV-infected patients with cirrhosis should be considered as candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have improved virological response rates and may have additional clinical benefits in the prevention or reduction of fibrosis and retardation of progression of cirrhosis and HCC in these patients.