Role of antiviral treatment for HCC prevention

Chemoprevention of hepatocellular carcinoma (HCC) is listed as a yet highly debated long-term benefit of a successful treatment of patients with chronic viral hepatitis. In the hepatitis B virus (HBV) arena, the retrospective scrutiny of both interferon and nucleos(t)ide analogues (NUC) studies failed to provide robust evidence for HCC chemoprevention, due to a number of confoundings in the studies that were originally designed to assess the antiviral activity of interferon therapy. However, the reanalysis of outcomes following patients stratification for risk factors of HCC, provided a clue to find an association between NUC therapy and a reduced risk of liver cancer in non cirrhotic patients, only. In the hepatitis C scenario, a meta analysis of 30 observational studies of patients treated with interferon demonstrated a more than 70% reduction of HCC risk occurring independently of severity of underlying liver fibrosis which was less pronounced in aged patients and those with more advanced liver fibrosis. While the reasons for the residual risk of HCC in virological responders remain largely unexplained, international societies recommend surveillance for HCC of both HBV and HCV responders to antiviral therapy.     

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.     

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.     

Strategies for the prevention of hepatocellular carcinoma in the context of chronic viral hepatitis

Liver cirrhosis induced by HBV and HCV infections is the main risk factor for the development of hepatocellular carcinoma (HCC). Therefore, prevention of chronic infection with hepatitis viruses and prevention of the development of cirrhosis are essential for the primary prevention of HCC. A consequent vaccination program for HBV is suitable to reduce the rate of infections and the HCC-associated mortality. Since no vaccine is available for HCV, the reduction of risky behaviour and the improvement of hygiene standards are the mainstays for prevention of HCV. An efficient antiviral therapy aimed at the durable suppression of the viral load reduces the risk of progression to cirrhosis and development of HCC in precirrhotic stages of chronic HBV or HCV infections. In cirrhotic patients, the risk of developing HCC remains elevated even if a sustained virological response is achieved, thus requiring further screening with the intention of the early detection of HCC. It is too early to judge whether virological nonresponders profit from continued antiviral therapy. Therefore, the early diagnosis of chronic HBV or HCV infection is the single most important factor for the prevention of HCC. Secondary prevention after surgical resection or local ablative therapy may reduce the frequency of late recurrence. Liver transplantation is today the most effective measure of secondary prevention for selected patients with HCC. Due to its antiproliferative effects, the immunosuppressive drug sirolimus may play a role for secondary prevention of HCC following transplantation.     

Relative Risk for the Development of Hepatocellular Carcinoma in Alcoholic Patients with Cirrhosis: A Multiple Logistic-Regression Coefficient Analysis

The hepatitis B virus (HBV) or hepatitis C virus (HVC) markers are frequently positive in alcoholic patients with hepatocellular carcinoma (HCC). However, the role of the relationship between HBV or HCV infection and alcohol drinking in the development of HCC has not been clearly documented. In the present study, the relative risk in 1200 cirrhotic patients with different etiologies who were admitted to five different hospitals in Japan was calculated using the multiple logistic-regression coefficient analysis. In the HCV+ alcohol group, HCC patients tended to be younger, and the odds ratio for the development of HCC was significantly higher compared with the HCV-alone group. Furthermore, the interaction coefficient of alcohol and HCV for the development of HCC was significant statistically. However, the interaction between HBV and alcohol was not significant. Because the proportion of male patients with HCC was significantly higher in the alcohol-alone and HBV-related groups than in the HCV-related group, the multiple logistic-regression analysis was also performed in male patients only. The results were nearly the same as those in male and female patients combined. These results suggest strongly that alcohol and HCV together accelerate the development of HCC. However, a similar relationship was not found between alcohol and HBV.     

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

AIM： To investigate the correlation between hepatitis B virus surface antigen （HBsAg）, hepatitis C virus （HCV） expression in hepatocellular carcinoma （HCC）, the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein （AFP） level.
METHODS： The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immunohistochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index （HAIl score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups： patients positive for HBsAg （HBsAg group）, patients positive for HCV （HCV group）, patients negative for both HCV and HBsAg （NBNC group） and patients positive for both HBsAg and HCV （BC group）.
RESULTS： The BC group had significantly higher HAI scores than the other three groups. （BC 〉 HCV 〉 HBsAg 〉 NBNC）. HBV and HCV virus infection was positively correlated with HAI （rs = 0.39, P = 0.00011. The positive rate of AFP （85.7%） and the value of AFP （541.2 ng/mL） in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate （53.3%） of AFP and the value of AFP （ 53.3 ng/mL） in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP（rs = 0.38, P = 0.0001）.
CONCLUSION： The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The-serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman＇s rank correlation analysis, we can conclude that the severity of virally induced     

Chemoprevention against hepatocellular carcinoma

Since the majority of hepatocellular carcinoma (HCC) arises from a background of chronic liver diseases caused by infection with hepatitis?C virus (HCV) and hepatitis?B virus (HBV), chemoprevention targeting patients at high risk of HCC is feasible. In this review article, we summarize current knowledge of chemoprevention against HCC mostly using phytochemicals which have less toxicity than pharmaceutical agents. We describe in?vivo and in?vitro evidence and proposed mechanisms of beneficial effects of several compounds on the liver, including acyclic retinoid (ACR), angiotensin-converting enzyme inhibitors (ACEIs), caffeine, capsaicin, cepharanthine (CEP), cinnamaldehyde, curcumin, diallyl sulfide (DAS), eicosapentaenoic acid (EPA), epigallocatechin-3-gallate (EGCG), genistein, lycopene, resveratrol, silymarin, sulforaphane (SFN), and xanthohumol (XN). Because antihepatocarcinogenic effects by these compounds are mostly based on experimental studies, clinical evidence is urgently necessary.     

SEN virus infection in patients with hepatocellular carcinoma

Although most cases of hepatocellular carcinoma (HCC) are associated with either the hepatitis B or C viruses (HBV, HCV), about 10-20% of HCCs occur in patients with chronic hepatitis that is aetiologically undefined. The aim of the present study was to determine the prevalence of the transfusion-transmitted SEN virus (SEN-V) in patients with HCC, including those patients who do not otherwise appear to be infected with HBV or HCV. Fragments of SEN-V subtypes D and H were amplified separately by PCR from the sera of 50 patients with HCC (31 from Canada and 19 from Japan) as well as from HCC and adjacent nontumourous liver tissues from eight of the Canadian patients. SEN-V DNA was found in the serum of 10 of 31 (32%) Canadian patients and eight of 19 (42%) Japanese patients [overall, 18 of 50 (36%) HCC patients]. SEN-V DNA was detected in the serum of 10 of 23 (43%) HCC patients with antibody to HCV (anti-HCV), six of 11 (55%) with hepatitis B surface antigen (HBsAg), and two of 16 (12%) without detectable anti-HCV or HBsAg. Twenty-three HCC patients in this study had 'silent HBV,' characterized by the detection of HBV DNA in the absence of HBsAg; eight of these (35%) also had SEN-V infections. SEN-V DNA was detected in HCC patients most typically in those with coexistent HBV or HCV infection. SEN-V was found in only one of seven HCC patients without HBV (without HBsAg or HBV DNA) or HCV and thus does not appear to be an important cause of 'cryptogenic' HCC.     

AETIOPATHOGENESIS OF HEPATOCELLULAR CARCINOMA

Abstract Most patients with hepatocellular carcinoma (HCC) in Japan have hepatitis B virus (HBV)-or hepatitis C virus (HCV)-associated cirrhosis. In the present study, the risk of HCC in patients with cirrhosis was analysed by the levels of serum alanine aminotransferase (ALT). One hundred and one (78%) of 129 patients with cirrhosis registered from April 1979 were followed at monthly intervals with the measurement of serum ALT. Of 101 patients, 38 tested positive for hepatitis B surface antigen (HBsAg) but negative for antibody to HCV (anti-HCV; HBV group), 47 tested negative for HBsAg but positive for anti-HCV (HCV group) and nine tested positive and seven tested negative for both. Mean serum ALT during follow-up was calculated on the basis of monthly values during the observation period that started at enrolment and ended with the detection of HCC or at the end of March 1994. By the end of March 1994, 37 (37%) patients developed HCC; 12 were in the HBV group, 21 in the HCV group and four were in the group positive for both. Mean serum ALT during the observation period was similar in patients who developed HCC and those who did not develop HCC in the HBV group. In contrast, the value was significantly higher in patients who developed HCC than in patients who did not develop HCC in the HCV group (P < 0.05).     

Hepatocellular carcinoma in the U.S.A., etiologic considerations. Localization of hepatitis B antigens.

The serologic and tissue markers of hepatitis B virus (HBV) were studied in 50 patients in whom hepatocellular carcinoma (HCC) was confirmed at autopsy. Serologic and tissue markers included serum hepatitis B surface antigen (HBsAg), tissue HBsAg, tissue hepatitis core antigen (HBcAg), and serum antibody to HBcAg (anti-HBc). Twenty-two patients had HCC arising in alcoholic cirrhosis; 2 of the 22 (9.1%) had one or more of the HBV tissue and serologic markers. This infection rate is similar to the rate of 7.9% observed in 63 control alcoholic cirrhotic patients without HCC. In contrast, 15 of 20 (75.0%) patients with HCC in nonalcoholic chronic active liver disease showed evidence of active HBV infection. One of 8 patients with HCC in normal liver had serum HBV markers. This result indicates that there is an extremely high prevalence of HBV infection among HCC patients with nonalcoholic chronic liver disease in the U.S.A. The prevalence of HBV infection in these patients is as high as that observed in Asia and Africa. Thus, it can be concluded that the lower prevalence rate of active HBV infection in HCC patients in the U.S.A. is the result of statistical dilution of HCC-B-viral disease by the large numbers of the alcoholic cirrhotic patients with HCC, and that if chronic active hepatitis type B were as common in the United States as it is in Africa and Asia, the frequency of occurrence of HCC might also be as high.     

Hepatocellular carcinoma in long-term oral contraceptive use

Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies in certain parts of the world, particularly in Africa and Asia, but it is less commonly encountered in the United States. It is closely associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and almost always develops in a cirrhotic liver. In non-cirrhotic livers, HCC is found in about 20% of asymptomatic carriers of HBV and rarely in patients taking androgenic-anabolic or oral contraceptive (OC) steroids. We report four patients, who developed HCC after prolonged use of OC steroids. Whether OC steroids act as mutagen or co-carcinogen in hepatocarcinogenesis is not clear. To exclude latent HCV and HBV infections which may occur in the absence of their serological markers, we employed polymerase chain reaction for the detection of HBV and HCV sequences in the tumor and non-tumorous liver tissue. Viral sequences of HBV and HCV were undetectable in all four cases. These findings suggest OC use as the only known risk factor in these cases and, therefore, strengthen its possible role in hepatocar-cinogenesis.     

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.     

Comparison of recurrence after hepatic resection in patients with hepatitis B vs. hepatitis C-related small hepatocellular carcinoma in hepatitis B virus endemic area.

PURPOSE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are two important factors in the development of hepatocellular carcinoma (HCC). The carcinogenic mechanism of HBV and HCV is considered to be different. It is interesting to compare the recurrence after hepatic resection in patients with small HCC who were infected with HBV or HCV. METHODS: From 1991 to 1995, 145 patients who were positive for hepatitis B surface antigen (HBsAg) or antibody to HCV (anti-HCV) and diagnosed as small HCC (< or =3 cm) in three medical centers in Taiwan were evaluated in this study. All patients underwent hepatic resection. Among them, 83 (57.2%) were infected by HBV, 51 (35.2%) were infected by HCV, and 11 (7.6%) had dual HBV and HCV infection. RESULTS: Anti-HCV+ HCCs were associated with older age, lower serum albumin, higher alanine transaminase (ALT) level and multi-nodular tumors during diagnosis. During the follow-up, 92 (63.4%) patients developed tumor recurrence. Anti-HCV + HCC had a higher cumulated recurrence rate than HBsAg+ HCC (72.4% vs 53.6 % at 5 year, P = 0.032). In multivariate analysis, the presence of vascular invasion and lower serum albumin levels (<3.9 g/dl) were the determinants for tumor recurrence. CONCLUSIONS: HCV infection, as compared with HBV infection, had a higher cumulated recurrence after hepatic resection in patients with small HCC. Low serum albumin level was significantly associated with recurrence among these patients.     

Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach

BACKGROUND/AIMS: To evaluate by meta-analysis of available literature whether interferon (IFN) reduces the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV)-related Child A cirrhosis. METHODS: Three randomized controlled trials and 15 nonrandomized controlled trials, including 4614 patients and comparing IFN to no treatment, were selected. Data on the incidence of HCC in IFN treated and untreated patients were extracted from each study. Meta-analysis by the DerSimonian and Laird risk difference (RD) method was used to pool observations. RESULTS: A different incidence of HCC between treated and untreated cirrhotic patients was observed for HCV (overall RD -12.8%; 95% CI -8.3 to -17.2%, P < 0.0001) and HBV (overall RD -6.4%; 95% CI -2.8 to -10%, P < 0.001). In HCV-related cirrhosis, the rate of HCC development was lower in sustained responders to IFN than in untreated patients (overall RD -19.1%; 95% CI -13.1 to -25.2%, P < 0.00001), with low heterogeneity among trials (P=0.053), and also in nonresponders vs. untreated patients (overall RD -11.8%; 95% CI -6.4 to -19.1%, P < 0.0001), although with significant heterogeneity. Inconsistency among the studies was a major problem, both for HCV (chi2 = 58.16 with 13 DF; P < 0.0001) and HBV (chi2 = 26.4 with 6 DF; P = 0.0001) related cirrhosis, and also when follow-up was shorter than 60 months. Consistent results were only observed when assessing data from European reports: in this subgroup no preventive effect of HCC was shown for HBV (overall RD -4.8%; 95% CI -11.1-1.5%, P, not significant), and only a weak effect for HCV (overall RD -10%; 95% CI -5.9 to -14.2%; P < 0.0001). CONCLUSIONS: Literature data pooling suggests a slight preventive effect of IFN on HCC development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit might be due to spurious associations. The preventive effect is more evident among sustained responders to IFN. IFN does not seem to affect the rate of HCC in HBV-related cirrhosis.     

Comparison of surgical outcomes for small hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a Chinese experience

BACKGROUND: Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are well recognized risk factors for hepatocellular carcinoma (HCC), little is known with respect to how HBV and HCV infection affect HCC recurrence in postoperative HCC Chinese patients. The objective of this study was to determine if differences exist in preoperative characteristics and postoperative HCC recurrence in patients with different HBV and HCV infection status. METHODS: The study population consisted of 413 patients undergoing a curative resection at Tianjin Cancer Hospital for small HCC (< or =3 cm) from January 1997 to December 2003. The patients were divided into four groups: HCV only (n = 75), HBV only (n = 251), HBV and HCV (n = 33), and neither HBV nor HCV (NBNC, n = 54). The preoperative status and postoperative HCC recurrence were recorded. Survival analyses were used to assess the impact of HBV/HCV status on HCC recurrence. RESULTS: Patients with HCV had a significant association with older age, lower mean preoperative platelet counts and albumin levels, higher mean prothrombin time, alanine aminotransferase and total bilirubin levels and multinodular tumors during diagnosis. Patients with HCV also had significantly less differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to the other groups. During the follow-up, the HCV group showed a higher incidence of intrahepatic recurrence and multiple recurrent lesions than the other patients. CONCLUSIONS: Patients with HCV infection tended to be older, and were characterized by more severe cirrhosis and higher incidence of tumor multicentricity. The statistically significant determinants for reoccurrence in patients with small HCC were HCV infection, presence of vascular invasion and multiple tumors.     

乙型与丙型肝炎病毒感染对小肝癌患者预后的影响

目的 探讨HBV、HCV感染对小肝癌的外科治疗策略及其预后的影响.方法 回顾性分析1997年1月-2003年12月天津医科大学附属肿瘤医院413例手术根治切除治疗的小肝痛(≤3 cm)患者的临床资料,将其分为4组:HCV感染组75例、HBV感染组251例、HCV、HBV混合感染组33例和尢HCV、HBV感染组54例,对可能影响预后的因素采用Kaplan-Meier生存分析、log-rank时序检验.结果 413例患者术后1、3、5年尢瘤生存率分别为83%、66%和58%,术后共有168(40.8%)例患者出现肝内复发,5年复发率HCV感染组最高(64.2%),其次为HBV/HCV感染组(48.4%),HBV感染组(37.8%)及无感染组(32.3%).肝内复发肿瘤为多发者在HCV感染组发生率最高(占肝内复发肿瘤的66.0%),其次为HBV/HCV感染组(28.6%),HBV感染组(23.3%)及无感染组(17.6%).413例小肝癌患者术后1、3、5年总生存率分别为89%、70%和61%,HCV感染组预后最差.和其他组相比,HCV感染组肝硬化程度严重,肿瘤细胞分化低,更易发生血管侵犯.在随访过程中,HCV感染组肝内复发率高,且复发类型常为多结节型.结论 HCV感染相关肝癌的临床肝硬化症状更重,而且术后复发率较高,预后更差.     

Impact of occult hepatitis B virus infection on efficacy and prognosis of interferon-alpha therapy for patients with chronic hepatitis C.

BACKGROUND/AIMS: It is reported that some patients with undetectable hepatitis B surface antigen (HBsAg) have serum hepatitis B virus (HBV) DNA in patients with chronic hepatitis C (HCV). The aim of this study was to elucidate the impact of occult HBV infection on the efficacy and prognosis of interferon-alpha (IFN) therapy in HCV patients. METHODS: One hundred and forty HCV patients without HBsAg who received IFN therapy were studied. Serum HBV DNA was quantified by real-time detection polymerase chain reaction. RESULTS: Of 140 patients, 11 (7.9%) were HBV DNA-positive before IFN therapy. The serum HBV DNA levels ranged from 106 to 884 copies/ml. Four of these 11 patients showed a sustained virologic response by IFN, compared with 39 of 129 without HBV DNA (P = NS). Interestingly, two of the 11 patients developed hepatocellular carcinoma (HCC) after therapy, compared with 16 of 129 without HBV DNA (P = NS). In the serial study, serum HBV DNA was transiently undetectable during and after IFN; however, most became positive during follow-up. CONCLUSIONS: Occult HBV infection may not have a significant impact on response to IFN therapy for chronic HCV and development of HCC after therapy. Occult HBV may be sensitive to IFN although HBV is not completely eradicated.     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

Long-term survival and recurrence after curative resection for hepatocellular carcinoma in patients with chronic hepatitis C virus infection: a multicenter observational study from China

BackgroundHepatocellular carcinoma (HCC) is a recognized sequalae of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. This study aimed to identify long-term survival and prognostic factors after curative resection for HCC among patients with chronic HCV infection.MethodsFrom a Chinese multicenter database, the data of consecutive patients with HCV infection undergoing curative liver resection for initial HCC between 2006 and 2015 were retrospectively reviewed. Postoperative 30-day mortality and morbidity, long-term overall survival (OS) and recurrence-free survival (RFS) were evaluated.ResultsAmong 382 HCC patients with HCV infection, 68 (18%) had concurrent HBV infection and 110 (29%) had portal hypertension. Postoperative 30-day morbidity and mortality rates were 45% and 2.9%, respectively. The 5-year OS and RFS rates were 45% and 34%, respectively. Multivariable Cox-regression analyses identified that concurrent HBV infection, presence of portal hypertension, largest tumor size > 5 cm, and macrovascular and microvascular invasion were independently associated with worse OS and RFS, while postoperative regular anti-HCV therapy was independently associated with better OS.ConclusionLong-term prognosis after HCC resection among patients with HCV infection was worse in those with concurrent HBV infection and concomitant portal hypertension. Postoperative regular anti-HCV therapy was associated with better OS.     

Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients

OBJECTIVES: The aim of this study was to compare the prognosis of patients with hepatitis B surface antigen (HBsAg) positive and those with antibody to hepatitis C (anti-HCV) positive cirrhosis. METHODS: This was a retrospective cohort study of 297 untreated Western European patients with compensated viral cirrhosis (Child class A; 161 patients with hepatitis type B and 136 with type C) who were followed for a median period of 6.6 yr. RESULTS: At diagnosis, median age was lower (48 vs 58 yr, respectively) in HBsAg-positive cirrhotic patients. The Kaplan-Meier 5-yr probability of hepatocellular carcinoma (HCC) was 9% and 10% in HBsAg and anti-HCV-positive cirrhotic patients, respectively; the corresponding figures for decompensation unrelated to HCC were 16% and 28% and for survival were 86% and 84%, respectively. After adjustment for clinical and serological differences at baseline, the relative risk (95% CI) for HCC, decompensation and mortality was 1.53 (CI = 0.81-2.89), 0.59 (CI = 0.37-0.94), and 1.44 (CI = 0.85-2.46) respectively, in HBsAg-positive patients compared with anti-HCV-positive cirrhotic patients. Among HBsAg-positive cirrhotic patients, the relative risk for HCC, decompensation, and mortality was 0.89 (CI = 0.30-2.63), 4.05 (CI = 1.09-15.1), and 5.9 (CI = 1.64-21.3), respectively, in HBV-DNA positive (HBeAg positive or negative) compared with HBV-DNA negative (HBeAg negative) patients at entry. CONCLUSIONS: Patients with HBV infection may present with cirrhosis about 10 yr earlier than those with HCV infection. HCV infection tends to be associated with a higher risk of decompensation, but these data should take into consideration the heterogeneity of HBV-related cirrhosis in terms of viremia levels and risk of hepatic failure. Survival shows no significant differences according to HBV or HCV etiology in Western European cirrhotic patients.