Biomedical subjects
Solko W Schalm
Publications and source records attributed to Solko W Schalm.
Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B.
Data on the long-term effects of interferon alfa (IFN) treatment on disease progression and mortality in patients with chronic hepatitis B (CHB) are limited. To evaluate factors that influence clinical outcome and survival, we performed a follow-up study on 165 hepatitis B e antigen (HBeAg) positive CHB patients treated with IFN between 1978 and 2002. The median IFN dose was 30 megaunits (MU)/week (range, 2-70 MU/week), and the median duration of therapy was 16 weeks (range, 1-92 weeks). Response to treatment was defined as HBeAg loss within 12 months after the end of IFN therapy. Median follow-up was 8.8 years (range, 0.3-24 years). Fifty-four patients (33%) responded to IFN treatment. Relapse (HBeAg reactivation) occurred in 7 of the 54 (13%) responders. Fifty-two percent of the responders lost hepatitis B surface antigen (HBsAg) as compared with 9% of the nonresponders (P <.001). Liver histology showed a decreased necroinflammatory activity and less progression of fibrosis in responders. Twenty-six patients died during follow-up. Hepatocellular carcinoma (HCC) was found in 8 patients, 6 of whom were nonresponders. Of the two responders who developed HCC, one patient had relapsed after discontinuation of therapy. Multivariate analysis showed significantly improved survival (relative risk (RR) of death 0.28, 95% CI 0.10-0.78) and reduced risk of developing HCC (RR 0.084, 95% CI 0.09-0.75) in responders. In conclusion, response to IFN therapy results in a prolonged clinical remission with an increased rate of HBsAg seroconversion and improved liver histology. Our results indicate that after correction for baseline factors, response to IFN therapy increases survival and reduces the risk of developing HCC.
Intrahepatic CD8 T-lymphocytes and HBV core expression in relation to response to antiviral therapy for chronic hepatitis B patients.
Recognition of HBV-infected hepatocytes by CD8 T-lymphocytes is important for viral clearance. Expression of hepatitis B core antigen (HBcAg) in HBV-infected hepatocytes can trigger this antiviral T-cell response. The intrahepatic CD8 T-lymphocytes and HBcAg expression were investigated in relation to response to antiviral therapy. Forty chronic HBeAg-positive patients treated with either lamivudine (n = 20) or interferon-alpha (n = 20) were investigated. Ten patients from each treatment group exhibited a response. Liver biopsies were carried out before and after therapy. CD8 T-lymphocytes and HBcAg expression were detected by immunohistochemistry. The number of pretreatment intrahepatic CD8 T-lymphocytes was significantly higher in responders (P = 0.008). In responders baseline nuclear HBcAg expression tended to be lower (P = 0.09). Cytoplasmic expression was not significantly different between responders and non-responders (P = 0.46). The number of CD8 T-lymphocytes correlated with cytoplasmic HBcAg (r(s) = 0.31; P = 0.04); CD8 T-lymphocytes were situated in clusters of hepatocytes with cytoplasmic HBcAg. Longitudinal analysis showed a significant reduction of CD8 T-lymphocytes after treatment in responders (P < 0.001). Multivariate analysis revealed pretreatment CD8 T-lymphocytes and age as independent prognostic factors for response (n = 40). The number of pretreatment CD8 T-lymphocytes was the only independent prognostic indicator for response to interferon-alpha (P = 0.03); it was of borderline significance for lamivudine therapy (P = 0.06). It is concluded that the number of pretreatment intrahepatic CD8 T-lymphocytes is an important predictor of response to HBV therapy with either interferon-alpha or lamivudine. Response to therapy led to a significant reduction of intrahepatic CD8 T-lymphocytes. Co-localisation of CD8 T-lymphocytes and HBcAg-positive hepatocytes suggests antiviral activity predominantly at the site of maximum HBV replication.
Reduction of relapse rates by 18-month treatment in chronic hepatitis C. A Benelux randomized trial in 300 patients.
BACKGROUND/AIMS: Treatment of chronic hepatitis C with interferon can be ineffective due to relapse. We aimed to reduce the 40% relapse rate of 6 months interferon-ribavirin combination therapy by prolonging treatment to 18 months. METHODS: Three hundred patients with treatment-naive hepatitis C, were randomized to 18 months combination therapy with interferon (3MU tiw) and ribavirin (1000-1200 mg/day), 18 months interferon combined with placebo, or 6 months combination therapy with interferon and ribavirin, in a double blinded manner. All 295 patients who received at least one dose of treatment were included in the intention to treat analysis. RESULTS: At the end of treatment, HCV RNA was undetectable in 55 and 49% of those on 6 and 18 months combination therapy, respectively, versus 26% of those on monotherapy (P<0.001). The relapse rate was 38% for 6 months combination therapy, 38% for 18 months monotherapy, and only 13% for 18 months combination treatment (P=0.002). The sustained response rates were 34% for 6 months combination therapy, 16% for 18 months monotherapy and 43% for 18 months combination therapy (P<0.05). CONCLUSIONS: Reduction of relapse rates to 15% or less is feasible by prolongation of interferon-ribavirin treatment to 18 months.
Paired measurements of quantitative hepatitis B virus DNA in saliva and serum of chronic hepatitis B patients: implications for saliva as infectious agent.
BACKGROUND: After intensive source and contact tracing 20 % of acute Hepatitis B virus (HBV) infections remain unexplained. Saliva may be an unexpected vehicle of HBV DNA transmission. OBJECTIVE: To further explore this hypothesis we evaluated the quantitative levels of HBV DNA in saliva and compared these with the HBV DNA levels measured in serum. STUDY DESIGN: Serum and saliva were collected from 27 chronic HBV patients attending our outpatient clinic. RESULTS: There were 16 men and 11 women; 15 patients were HBeAg positive, anti-HBe negative and 11 patients were HBeAg negative, anti-HBe positive. One patient was HBeAg and anti-HBe negative. Samples of serum and saliva were collected on the same day. All saliva specimens were clear on inspection. HBV DNA in serum was measured by the Digene Hybrid Capture II microplate assay (Digene Diagnostics), the HBV Monitor assay (Roche Diagnostics) as well as an in-house developed HBV DNA TaqMan assay. The HBV DNA TaqMan assay was used for the quantitative measurement of HBV DNA in saliva. Median HBV DNA levels in serum were 2.10 x 10(5) geq/ml and ranged from 373 genome equivalents per ml (geq/ml) to 4.13 x 10(9) geq/ml; median HBV DNA levels in saliva were 2.27 x 10(4) geq/ml and ranged from 373 geq/ml to 9.25 x 10(6) geq/ml. A clear correlation was shown between HBV DNA in serum and saliva; log HBV DNA in saliva=1.01 + 0.56 x (log HBV DNA in serum). CONCLUSIONS: this is the first report of precise quantitative measurements of HBV DNA levels in saliva and the relationship with HBV DNA levels in serum. Our findings show that saliva is a source of HBV DNA. This finding may have implications in selected patients for the infectivity of saliva and offer further insight in the routes of transmission of HBV infection.
The Liver Disease Symptom Index 2.0; validation of a disease-specific questionnaire.
The available liver disease-specific questionnaires do address severity of symptoms but hardly evaluate how patients experience these specific symptoms during daily activities. The Liver Disease Symptom Index 2.0 (LDSI) includes 18 items that measure symptom severity and symptom hindrance in the past week. In a large survey (n = 1175) conducted in collaboration with the Dutch liver patient association, convergent and divergent construct validity and the surplus value of including symptom severity and symptom hindrance items in the LDSI were examined. The LDSI items showed expected convergent and divergent correlations with Short Form-36 (SF-36) and Multidimensional Fatigue Index-20 (MFI-20) scales. Correlations revealed only a slight to moderate overlap between LDSI items and SF-36 and MFI-20 scales. The impact of symptom severity and symptom hindrance on generic health related quality of life (HRQoL) varied in a different way across liver patients, which indicated that symptom severity items and the symptom hindrance items measure different aspects of HRQoL. We conclude that the LDSI provides information complementary to the information given by the SF-36 and the MFI-20 and that it is psychometrically sound to include both symptom severity items and symptom hindrance items in the LDSI.
Polyarteritis nodosa associated with hepatitis B virus infection. The role of antiviral treatment and mutations in the hepatitis B virus genome.
Polyarteritis nodosa (PAN) is a systemic inflammatory disease causing vasculitis of medium sized and small arteries. Circulating immune complexes containing viral proteins have been implicated in the pathogenesis of hepatitis B virus (HBV) related PAN and several immunosuppressive and antiviral regimens have been used with varying success. In our hospital seven HBV positive patients with a confirmed diagnosis of PAN could be identified between 1984 and 2001. Most patients had an acute HBV infection and all patients were treated with prednisone. A combination of prednisone and antiviral therapy with alpha-interferon (IFN) was used only in the last four patients. HBV DNA was isolated from serum samples obtained before treatment from the four IFN treated patients and amplified by using the polymerase chain reaction technique. None of the patients without, but two of four with antiviral therapy exhibited HBsAg seroconversion. In three out of four patients HBV DNA decreased rapidly after starting IFN therapy. Clinical remission of PAN was observed in three of the four treated patients, but in none of the three patients who were not receiving antiviral medication. Analysis of the HBV genome revealed no mutations that could be associated with PAN. In one patient a stop codon in the pre-core region and a double mutation A1762T-G1764A were found during antiviral therapy. We did not find HBV heterogeneity predisposing to the development of PAN. In our group of patients it appeared that clinical remission of PAN was primarily related to spontaneous or therapy induced loss of HBV DNA replication. The combined administration of a priming steroid course and IFN appears to be an improvement over prednisone monotherapy and should be considered for every patient with HBV related PAN. The efficacy of new generation nucleoside analogues should be further elucidated in future studies.
Generic and disease-specific health related quality of life in non-cirrhotic, cirrhotic and transplanted liver patients: a cross-sectional study.
BACKGROUND: Studies on Health Related Quality of Life (HRQoL) of chronic liver patients were performed in clinical populations. These studies included various disease stages but small variations in aetiology and no transplanted patients. We performed a large HRQoL study in non-cirrhotic, cirrhotic and transplanted liver patients with sufficient variety in aetiology. We compared the generic HRQoL and fatigue between liver patients and healthy controls and compared the disease-specific and generic HRQoL and fatigue between non-cirrhotic, cirrhotic and transplanted liver patients, corrected for aetiology. METHODS: Members of the Dutch liver patient association received the Short Form-36, the Liver Disease Symptom Index and the Multidimensional Fatigue Index-20. Based on reported clinical characteristics we classified respondents (n = 1175) as non-cirrhotic, compensated cirrhotic, decompensated cirrhotic or transplants. We used linear, ordinal and logistic regression to compare the HRQoL between groups. RESULTS: All liver patients showed a significantly worse generic HRQoL and fatigue than healthy controls. Decompensated cirrhotic patients showed a significantly worse disease-specific and generic HRQoL and fatigue than non-cirrhotic patients, while HRQoL differences between non-cirrhotic and compensated cirrhotic patients were predominantly insignificant. Transplanted patients showed a better generic HRQoL, less fatigue and lower probabilities of severe symptoms than non-cirrhotic patients, but almost equal probabilities of symptom hindrance. CONCLUSIONS: HRQoL in chronic liver patients depends on disease stage and transplant history. Non-cirrhotic and compensated cirrhotic patients have a similar HRQoL. Decompensated patients show the worst HRQoL, while transplanted patients show a significantly better HRQoL than cirrhotic and non-cirrhotic patients.
The intrahepatic immune response during chronic hepatitis B infection can be monitored by the fine-needle aspiration biopsy technique.
Frequent analysis of the intrahepatic cellular immune response during chronic hepatitis B infection is not feasible with the liver tissue biopsy technique, due to its risk profile and patient discomfort. We investigated whether the relatively safe and patient-friendly cytological fine-needle aspiration biopsy (FNAB) technique is suited for this purpose. FNABs taken during hepatitis flares in three chronic hepatitis B patients treated with interferon-alpha, showed significant increments of CD8(+)-lymphocytes compared with the FNABs taken before and after the flares. No increments were observed in peripheral blood. The increments of intrahepatic CD8+ lymphocytes detected by the FNAB were related to anti-viral immune reactivity, since they coincided with significant serum hepatitis B virus DNA level reductions and in two of three patients with HBeAg seroconversion. In conclusion, the FNAB technique is suited to investigate the intrahepatic immune response during chronic hepatitis B infection on a frequent basis.
Pretreatment intrahepatic CD8+ cell count correlates with virological response to antiviral therapy in chronic hepatitis C virus infection.
We analyzed the relationship between virological response and baseline immune factors in 17 patients chronically infected with hepatitis C virus (HCV) who received interferon-alpha-ribavirin therapy for 26 weeks. The number of intrahepatic CD8(+) cells present in the portal tract before the start of treatment was found to be significantly higher in patients who responded to treatment than in nonresponders. The relationship between portal CD8(+) cell counts and the response to therapy could be described by a logistic curve. Neither peripheral cytokine levels nor HCV-specific T cell reactivity in peripheral blood mononuclear cells showed a relationship to response to therapy.
Retreatment of hepatitis C non-responsive to interferon. A placebo controlled randomized trial of ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378].
BACKGROUND: Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published until now. METHODS: One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%), HCV RNA above 2 x 10(6) copies/ml (55%) and cirrhosis (38%). Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw) and ribavirin (1000-1200 mg/day), 6 months ribavirin monotherapy (1000-1200 mg/day) or 6 months ribavirin placebo. The study was double blinded for the ribavirin/placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis. RESULTS: At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin monotherapy (p = 0.76). End of treatment WBC was significantly lower in patients treated with combination therapy, compared to ribavirin (p < 0.01) as well as for patients treated with ribavirin monotherapy compared to placebo (p < 0.01). DISCUSSION: This belated report on the only placebo controlled study of interferon ribavirin combination therapy in non responders to standard doses of interferon monotherapy documents the effectiveness, be it limited, of this approach as well as the dynamics of the effects on blood counts.
Endoscopic sclerotherapy compared with no specific treatment for the primary prevention of bleeding from esophageal varices. A randomized controlled multicentre trial [ISRCTN03215899].
BACKGROUND: Since esophageal variceal bleeding is associated with a high mortality rate, prevention of bleeding might be expected to result in improved survival. The first trials to evaluate prophylactic sclerotherapy found a marked beneficial effect of prophylactic treatment. These results, however, were not generally accepted because of methodological aspects and because the reported incidence of bleeding in control subjects was considered unusually high. The objective of this study was to compare endoscopic sclerotherapy (ES) with nonactive treatment for the primary prophylaxis of esophageal variceal bleeding in patients with cirrhosis. METHODS: 166 patients with esophageal varices grade II, III of IV according to Paquet's classification, with evidence of active or progressive liver disease and without prior variceal bleeding, were randomized to groups receiving ES (n = 84) or no specific treatment (n = 82). Primary end-points were incidence of bleeding and mortality; secondary end-points were complications and costs. RESULTS: During a mean follow-up of 32 months variceal bleeding occurred in 25% of the patients of the ES group and in 28% of the control group. The incidence of variceal bleeding for the ES and control group was 16% and 16% at 1 year and 33% and 29% at 3 years, respectively. The 1-year survival rate was 87% for the ES group and 84% for the control group; the 3-year survival rate was 62% for each group. In the ES group one death occurred as a direct consequence of variceal bleeding compared to 9 in the other group (p = 0.01, log-rank test). Complications were comparable for the two groups. Health care costs for patients assigned to ES were estimated to be higher. Meta-analysis of a large number of trials showed that the effect of prophylactic sclerotherapy is significantly related to the baseline bleeding risk. CONCLUSION: In the present trial, prophylactic sclerotherapy did not reduce the incidence of bleeding from varices in patients with liver cirrhosis and a low to moderate bleeding risk. Although sclerotherapy lowered mortality attributable to variceal bleeding, overall survival was not affected. The effect of prophylactic sclerotherapy seems dependent on the underlying bleeding risk. A beneficial effect can only be expected for patients with a high risk for bleeding.
A replicon-based bioassay for the measurement of interferons in patients with chronic hepatitis C.
Overall treatment results of chronic hepatitis C have improved markedly with the introduction of pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin combination therapy. However, cure rates in the most common genotype 1 infection are still unsatisfactory. IFN-alpha dose-response studies on viral kinetics suggest that inadequate dosing might be a key factor but drug levels have hardly been tested, which is in part due to difficulties in measuring this cytokine in patient samples. We have shown recently that hepatitis C virus (HCV) replicons are highly sensitive to IFN-alpha. In this report we tested whether the replicon system could be used as a sensitive bioassay to determine the amount of biologically active IFN-alpha in serum or heparinized plasma of patients under therapy. To facilitate the measurements, a stably replicating subgenomic HCV RNA was developed that carries the gene encoding the firefly luciferase. Dose response studies with IFN-alpha demonstrate that the amount of expressed luciferase directly correlates with the level of HCV replication. By using this cell-based assay, serum samples of HCV patients treated with different types and doses of IFN-alpha were analyzed in parallel to IFN-alpha standards made by serial dilutions of the same type of IFN-alpha the patient was treated with. Based on nonlinear logistic models serum concentrations corresponding to 1.3-19 U/ml were determined in patients under standard or high dose IFN-alpha therapy, and from 3.8 to 4.1 ng/ml in patients treated with PEG IFN-alpha. In conclusion, the HCV-replicon based bioassay allows determining the levels of biologically active IFN-alpha in serum and heparinized plasma of patients under treatment.
Combination therapy for chronic hepatitis B.
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The influence of baseline characteristics on viral dynamic parameters in chronic hepatitis B patients treated with lamivudine.
BACKGROUND/AIMS: Viral decline during lamivudine therapy in chronic hepatitis B patients is bi-phasic. We studied the influence of lamivudine dose and baseline characteristics on parameters obtained from a mathematical model. METHODS: Chronic hepatitis B patients were randomized to receive 150 mg (group 1; n=11) or 600 mg (group 2; n=10) lamivudine daily for 4 weeks. Hepatitis B virus DNA was measured frequently with the Digene Hybrid Capture II test and the Roche PCR assay. RESULTS: The description of viral decline in our closely monitored patients by means of the mixed-effects approach with both the bi-phasic model and a piecewise linear regression model resulted in a good fit. Baseline alanine aminotransferase (ALT) was significantly related to the slope of the second phase of viral decline. Previous lamivudine-treated patients showed a significant slower first phase than patients naive to lamivudine treatment. CONCLUSIONS: The initial observed difference in viral decline between 150 and 600 mg of lamivudine disappeared when baseline ALT was taken into account. This strengthens the hypothesis that the level of intrinsic activity is related to the turnover of infected hepatocytes. Moreover, reintroduction of lamivudine in previously lamivudine-treated patients should be considered carefully.
Viral dynamics in chronic hepatitis B patients during lamivudine therapy.
RATIONALE AND AIM: Recently, we described a first-order decay model for the description of a decrease in viral load during treatment with lamivudine for a chronic hepatitis B virus infection (HBV). However, more frequent sampling of viral load during the first month of treatment shows a bi-phasic viral decline. We therefore compared several mathematical models which are currently in use to describe the dynamics of various viruses and treatments. METHODS: HBV DNA positive chronic hepatitis B patients were treated with lamivudine 150-600 mg daily for four weeks. During the first two days, blood samples were drawn every 6 h, then daily during the first week and weekly during the following three weeks. HBV DNA was measured with the Digene Hybrid Capture II HBV DNA test and the sensitive Roche PCR assay, both calibrated on the Eurohep standard. RESULTS: Our HBV DNA data are most accurately described if we use the bi-phasic model previously described by Neumann et al. while introducing all consecutive data of all patients simultaneously (mixed effects model). This results in an effectiveness of blocking of viral replication of 93%, a half-life of free virus of 17 h and a half-life of infected hepatocytes of 7 day in patients treated with 150 mg of lamivudine. CONCLUSION: HBV dynamics during treatment with lamivudine can be explained by blocking of virion production with or without blocking of de novo infection. The bi-phasic model as described by Neumann et al. in combination with frequent blood sampling provides the most accurate fit and can be used to compare new nucleoside analogue profiles to lamivudine therapy.
Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B.
Elevated alanine transaminase (ALT) levels and low serum hepatitis B virus (HBV) DNA predict a higher likelihood of hepatitis B e antigen (HBeAg) loss in patients with chronic hepatitis B treated with interferon. Predictors of HBeAg loss in patients treated with lamivudine are not known. The objective of this analysis of 4 lamivudine-controlled Phase III trials was to determine patient-dependent or laboratory variables that predict HBeAg loss. Predictors of HBeAg loss in patients treated with interferon, lamivudine plus interferon, or placebo are also described. A total of 805 adults with chronic hepatitis B were treated either with lamivudine (n = 406), matching placebo (n = 196), interferon (n = 68), or the combination of lamivudine plus interferon (n = 135). Demographic and baseline disease characteristics were used in stepwise multivariate analyses to identify features that were predictive of lamivudine-induced HBeAg loss. HBeAg loss correlated with increased pretreatment ALT levels in all groups. The rate of HBeAg loss was highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal (ULN) and was most pronounced in the lamivudine group (56%). Multivariate modeling indicated that elevated baseline ALT levels (P <.001) and histologic activity index (HAI) score (P <.001) were important predictors of HBeAg loss in response to lamivudine. The effect of pretreatment ALT levels on HBeAg loss was similar for Asians and Caucasians. In conclusion, elevated pretreatment ALT levels and/or active histologic disease were the most important predictors of lamivudine-induced HBeAg loss. Asians and Caucasians had similar rates of response to lamivudine at comparable ALT levels.
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.