Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals / Evaluación de la rigidez hepática y esplénica mediante Fibroscan® para la predicción de varices esofágicas en pacientes con cirrosis hepática por VHC tratados con antivirales orales

Introduction: The aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents. Patients and methods: This cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness–spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed. Results: Ninety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p=0.02), spleen stiffness measurement (39.4 vs 46.05; p=0.04), liver stiffness–spleen diameter to platelet ratio score (1.21 vs 2.02; p=0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p=0.04) and variceal risk index (−3.4 vs −1.02; p=0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3kPa for liver stiffness measurement and 27kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance. Discussion: Liver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.(AU)

Introducción: El objetivo de este estudio fue evaluar la rigidez hepática y esplénica medidas con Fibroscan® para la predicción de várices esofágicas (VE), en pacientes con cirrosis hepática por VHC tratados con antivirales orales. Pacientes y métodos: Estudio observacional y transversal que incluyó pacientes con cirrosis hepática por VHC compensada y respuesta virológica sostenida tras tratamiento. Se recogieron datos clínico-analíticos, ecográficos y endoscópicos y marcadores no invasivos como el Fibroscan® hepático y esplénico, el modelo predictivo «Liver stiffness-spleen diameter to platelet ratio score» (LSPS), el «Varices Risk Index» (VRI) y el índice n° plaquetas/diámetro mayor del bazo. Resultados: Se incluyeron 97 pacientes consecutivos. Los valores del Fibroscan® hepático (12,2 vs. 16; p = 0,02), esplénico (39,4 vs. 46,05; p = 0,04), LSPS (1,21 vs. 2,02; p = 0,008), índice n.° plaquetas/diámetro mayor del bazo (1.102,19 vs. 829,7; p = 0,04) y VRI (-3,4 vs. -1,02; p = 0,01) mostraron diferencias significativas entre pacientes sin/con VE. El mejor punto de corte del fibroscán hepático y esplénico para descartar la presencia de várices fue 12,3 y 27 kPas, respectivamente, con precisión diagnóstica moderada (AUROC: 0,671 y 0,624, respectivamente). La combinación de los parámetros no invasivos no mejoró el rendimiento global de estas pruebas. Discusión: Los valores del Fibroscan® hepático y esplénico mostraron resultados subóptimos para la evaluación no invasiva de VE en pacientes cirróticos por VHC tratados con antivirales orales. Nuestros resultados sugieren que estas pruebas no pueden sustituir a los procedimientos estándar para predecir la presencia de várices en esta subpoblación.(AU)

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals.

INTRODUCTION: The aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents. PATIENTS AND METHODS: This cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness-spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed. RESULTS: Ninety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p=0.02), spleen stiffness measurement (39.4 vs 46.05; p=0.04), liver stiffness-spleen diameter to platelet ratio score (1.21 vs 2.02; p=0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p=0.04) and variceal risk index (-3.4 vs -1.02; p=0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3kPa for liver stiffness measurement and 27kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance. DISCUSSION: Liver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.

Entecavir has high efficacy and safety in white patients with chronic hepatitis B and comorbidities.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t)ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. METHODS: We retrospectively analysed data from 237 nucleos(t)ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. RESULTS: The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. CONCLUSION: Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence.

[The value of FibroScan® in the follow-up of patients with chronic hepatitis B virus infection without indication for treatment]. / Valor del FibroScan® en el seguimiento de los pacientes con infección crónica por virus B sin indicación de tratamiento.

Transient elastography (TE) is a noninvasive method of assessing hepatic fibrosis in a quick, simple and reproducible manner. FibroScan is the best-known elastography apparatus and can assess a tissue volume 100 times greater than hepatic biopsy. Given that it lacks complications, TE can be repeated in the follow-up visit, thereby providing evolutionary information. One of its limitations, however, is its failure rate (4.5% of examinations), mainly in obese patients. TE has certain characteristics in chronic hepatitis B (HBV) infection. Transaminase levels and necroinflammation increase in reactivations, with hepatic stiffness increasing by 1.2 to 4.4 times. The second characteristic is related to macronodular cirrhosis caused by HBV, with less fibrous tissue compared with that produced by hepatitis C. Therefore, the cutoff values are smaller for hepatitis B than for hepatitis C. FibroScan helps categorize patients with chronic HBV infection into 4 fibrosis groups (approximate mean values and adding 1-2 more points with high transaminase levels): not significant (<6 kPa), grey area (6-9 kPa), significant (>9 kPa) and cirrhosis (>12 kPa). Thus, Fibroscan contributes to the treatment decision, and its repeated use during treatment enables us to verify that fibrosis has not progressed. In cases with no indication for treatment (chronic hepatitis with no criteria, inactive carrier state, immune-tolerant), the periodic reapplication of TE helps determine whether the inactivity continues or not. If the results are compatible with cirrhosis, hepatocarcinoma surveillance should be started.

Valor del FibroScan en el seguimiento de los pacientes con infección crónica por virus B sin indicación de tratamiento / The value of FibroScan in the follow-up of patients with chronic hepatitis B virus infection without indication for treatment

La elastografía de transición (ET) es un método no invasivo para valorar la fibrosis hepática de manera rápida, sencilla y reproducible. El fibroScan (FS) es el aparato más conocido de elastografía y valora un volumen de tejido 100 veces superior al de la biopsia hepática. Como carece de complicaciones, el FS puede repetirse en el seguimiento de las enfermedades hepáticas, aportando información evolutiva. Una limitación es la tasa de fracasos (4,5% de las exploraciones), fundamentalmente en pacientes obesos. La ET presenta particularidades en la infección crónica por virus de la hepatitis B (VHB): en las reactivaciones aumentan las transaminasas y la necroinflamación, incrementándose la rigidez hepática entre 1,2 a 4,4 veces; la segunda particularidad se relaciona con la cirrosis macronodular que provoca el VHB, con menos tejido fibroso comparado con la que produce la hepatitis C. Por ello, los valores de corte son menores que en la hepatitis C. El FS permite clasificar a los pacientes con infección crónica por VHB en 4 grupos de fibrosis (valores medios aproximados y sumando 1-2 puntos más con transaminasas elevadas): no significativa (< 6 kPa), zona gris (6-9 kPa), significativa (> 9 kPa) y cirrosis (> 12 kPa). Así, el FS contribuye a la decisión de tratamiento y su repetición durante este permite constatar la no progresión de la fibrosis; en casos sin indicación de tratamiento (hepatitis crónica sin criterios, estado portador inactivo, inmunotolerancia), su repetición periódica ayuda a saber si continúa la inactividad o no; si es compatible con cirrosis, se iniciará la vigilancia del hepatocarcinoma

Transient elastography (TE) is a noninvasive method of assessing hepatic fibrosis in a quick, simple and reproducible manner. FibroScan is the best-known elastography apparatus and can assess a tissue volume 100 times greater than hepatic biopsy. Given that it lacks complications, TE can be repeated in the follow-up visit, thereby providing evolutionary information. One of its limitations, however, is its failure rate (4.5% of examinations), mainly in obese patients. TE has certain characteristics in chronic hepatitis B (HBV) infection. Transaminase levels and necroinflammation increase in reactivations, with hepatic stiffness increasing by 1.2 to 4.4 times. The second characteristic is related to macronodular cirrhosis caused by HBV, with less fibrous tissue compared with that produced by hepatitis C. Therefore, the cutoff values are smaller for hepatitis B than for hepatitis C. FibroScan helps categorize patients with chronic HBV infection into 4 fibrosis groups (approximate mean values and adding 1-2 more points with high transaminase levels): not significant (<6 kPa), grey area (6-9 kPa), significant (>9 kPa) and cirrhosis (>12 kPa). Thus, Fibroscan contributes to the treatment decision, and its repeated use during treatment enables us to verify that fibrosis has not progressed. In cases with no indication for treatment (chronic hepatitis with no criteria, inactive carrier state, immunetolerant), the periodic reapplication of TE helps determine whether the inactivity continues or not. If the results are compatible with cirrhosis, hepatocarcinoma surveillance should be started

Tratamiento de la hepatitis C en grupos de pacientes especiales / Hepatitis C treatment in special patient groups

El plan de tratamiento de la hepatitis crónica C en las poblaciones especiales varía en función de la comorbilidad y las evidencias de tratamiento existentes. En los pacientes con coinfección por virus de la hepatitis C y virus de la inmunodeficiencia humana, los resultados del tratamiento con biterapia (interferón pegilado más ribavirina) son pobres. En los pacientes infectados por virus de genotipo 1, la terapia triple (biterapia más boceprevir o telaprevir) ha duplicado la tasa de respuesta, pero los inhibidores de la proteasa pueden interactuar con algunos fármacos antirretrovirales y provocan más efectos adversos. Estos inconvenientes no los presentan los nuevos antivirales directos de segunda generación. En los pacientes candidatos a trasplante hepático o portadores ya de un trasplante hepático, la mejor opción terapéutica actual es combinar los nuevos antivirales, con o sin ribavirina y sin interferón. El tratamiento de los enfermos en hemodiálisis por enfermedad renal crónica continúa siendo la biterapia (en muchos casos, con dosis reducidas de interferón pegilado y ribavirina), pues no se dispone todavía de suficiente información sobre la triple terapia ni los nuevos antivirales. En la crioglobulinemia mixta, aunque existe poca experiencia, la triple terapia parece ser superior a la biterapia y puede rescatar pacientes que no responden a la biterapia; pero siempre debe decidirse si el tratamiento antiviral debe asociarse o posponerse al tratamiento inmunosupresor

The treatment plan for chronic hepatitis C in special populations varies according to comorbidity and the current evidence on treatment. In patients with hepatitis C virus and HIV coinfection, the results of dual therapy (pegylated interferon plus ribavirin) are poor. In patients with genotype 1 infection, triple therapy (dual therapy plus boceprevir or telaprevir) has doubled the response rate, but protease inhibitors can interact with some antiretroviral drugs and provoke more adverse effects. These disadvantages are avoided by the new, second-generation, direct-acting antiviral agents. In patients who are candidates for liver transplantation or are already liver transplant recipients, the optimal therapeutic option at present is to combine the new antiviral agents, with or without ribavirin and without interferon. The treatment of patients under hemodialysis due to chronic renal disease continues to be dual therapy (often with reduced doses of pegylated interferon and ribavirin), since there is still insufficient information on triple therapy and the new antiviral agents. In mixed cryoglobulinemia, despite the scarcity of experience, triple therapy seems to be superior to dual therapy and may be used as rescue therapy in non-responders to dual therapy. However, a decision must always be made on whether antiviral treatment should be used concomitantly or after immunosuppressive therapy

[Hepatitis C treatment in special patient groups]. / Tratamiento de la hepatitis C en grupos de pacientes especiales.

The treatment plan for chronic hepatitis C in special populations varies according to comorbidity and the current evidence on treatment. In patients with hepatitis C virus and HIV coinfection, the results of dual therapy (pegylated interferon plus ribavirin) are poor. In patients with genotype 1 infection, triple therapy (dual therapy plus boceprevir or telaprevir) has doubled the response rate, but protease inhibitors can interact with some antiretroviral drugs and provoke more adverse effects. These disadvantages are avoided by the new, second-generation, direct-acting antiviral agents. In patients who are candidates for liver transplantation or are already liver transplant recipients, the optimal therapeutic option at present is to combine the new antiviral agents, with or without ribavirin and without interferon. The treatment of patients under hemodialysis due to chronic renal disease continues to be dual therapy (often with reduced doses of pegylated interferon and ribavirin), since there is still insufficient information on triple therapy and the new antiviral agents. In mixed cryoglobulinemia, despite the scarcity of experience, triple therapy seems to be superior to dual therapy and may be used as rescue therapy in non-responders to dual therapy. However, a decision must always be made on whether antiviral treatment should be used concomitantly or after immunosuppressive therapy.

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C.

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to peginterferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400,000 vs ≥ 400,000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d). RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventy-eight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 µg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.

Pathogenesis of occult chronic hepatitis B virus infection.

Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this "occult" HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

Asociación entre hiperhomocisteinemia y esteatosis hepática en pacientes con hepatitis crónica C / Association of hyperhomocysteinemia with liver steatosis in patients with chronic hepatitis C

Fundamento y objetivo: La esteatosis hepática en la hepatitis crónica C (HCC) se relaciona con factores virales, metabólicos y posiblemente genéticos. El objetivo de este estudio es conocer si la hiperhomocisteinemia y el polimorfismo de la metilentetrahidrofolato reductasa (MTHFR)-C677T se asocian a esteatosis hepática en pacientes no alcohólicos con HCC. Pacientes y método: Se estudiaron 54 pacientes consecutivos diagnosticados de HCC mediante biopsia, con consumo de alcohol menor de 40g/semana, y sin otras causas de enfermedad hepática. Todas las variables se obtuvieron al tiempo de la biopsia. En 128 sujetos sanos, con edad y sexo similares a los pacientes, también se determinó el polimorfismo de la MTHFR-C677T. Resultados: Se encontró esteatosis hepática en 33 pacientes (61%), siendo en 30 de grado leve. En los pacientes con esteatosis existía una prevalencia más elevada de hiperhomocisteinemia (61% frente al 24%, p=0,008) y el sobrepeso tendía a ser más prevalente (61% frente al 33%, p=0,05). Todos los pacientes con genotipo 3 del virus C tenían esteatosis. La carga viral, actividad inflamatoria y fibrosis hepática no fueron diferentes en los pacientes con y sin esteatosis. El polimorfismo de la MTHFR-C677T fue similar en controles y casos, y en los casos con y sin esteatosis. La regresión logística múltiple mostró que la hiperhomocisteinemia se asociaba a esteatosis hepática tras ajustar por edad y sexo (odds ratio [OR] 3,94, intervalo de confianza del 95% [IC 95%] 1,09-14,29) y por sobrepeso (OR 4,43, IC 95% 1,27-15,51). Conclusiones: En pacientes no alcohólicos con HCC, la esteatosis hepática de grado leve es frecuente y se asocia a hiperhomocisteinemia. No se comprueba asociación de la esteatosis con el polimorfismo de la MTHFR-C677T (AU)

Background and objectives: Liver steatosis in chronic hepatitis C (CHC) is related to viral and metabolic factors and likely to genetic factors. The aim of this study was to know if hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR)-C677T polymorphisms are associated with liver steatosis in nonalcoholic patients with CHC.Patients and method: In 54 consecutive patients with CHC, alcohol consumption less than 40g/week, and no other causes of liver disease, a liver biopsy was performed. All variables were obtained at the time of biopsy. MTHFR-C677T was also performed in 128 healthy subjects, with age and gender similar to the patients. Results: Liver steatosis was found in 33 patients (61%), 30 of them having a mild degree. Hyperhomocysteinemia was more prevalent in patients with steatosis (61% vs 24%; p=0.008) and overweight tended to be more prevalent in the same patients (61% vs 33%; p=0.05). All patients with virus C genotype 3 had steatosis. Viral load, liver inflammatory and fibrosis score were not different in patients with and without steatosis. MTHFR-C677T polymorphism was similar in controls and cases and in cases with and without steatosis. A multiple logistic regression showed that hyperhomocysteinemia was associated with liver steatosis after adjustment for age and sex (OR: 3.94; 95% CI: 1.09-14.29), and adjustment for overweight (OR: 4.43; 95% CI: 1.27-15.51). Conclusions: In nonalcoholic patients with CHC mild liver steatosis is frequent, and is associated with hyperhomocysteinemia. An association between steatosis and MTHFR-C677T polymorphism was not found (AU)

[Association of hyperhomocysteinemia with liver steatosis in patients with chronic hepatitis C]. / Asociación entre hiperhomocisteinemia y esteatosis hepática en pacientes con hepatitis crónica C.

BACKGROUND AND OBJECTIVES: Liver steatosis in chronic hepatitis C (CHC) is related to viral and metabolic factors and likely to genetic factors. The aim of this study was to know if hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR)-C677T polymorphisms are associated with liver steatosis in nonalcoholic patients with CHC. PATIENTS AND METHOD: In 54 consecutive patients with CHC, alcohol consumption less than 40g/week, and no other causes of liver disease, a liver biopsy was performed. All variables were obtained at the time of biopsy. MTHFR-C677T was also performed in 128 healthy subjects, with age and gender similar to the patients. RESULTS: Liver steatosis was found in 33 patients (61%), 30 of them having a mild degree. Hyperhomocysteinemia was more prevalent in patients with steatosis (61% vs 24%; p=0.008) and overweight tended to be more prevalent in the same patients (61% vs 33%; p=0.05). All patients with virus C genotype 3 had steatosis. Viral load, liver inflammatory and fibrosis score were not different in patients with and without steatosis. MTHFR-C677T polymorphism was similar in controls and cases and in cases with and without steatosis. A multiple logistic regression showed that hyperhomocysteinemia was associated with liver steatosis after adjustment for age and sex (OR: 3.94; 95% CI: 1.09-14.29), and adjustment for overweight (OR: 4.43; 95% CI: 1.27-15.51). CONCLUSIONS: In nonalcoholic patients with CHC mild liver steatosis is frequent, and is associated with hyperhomocysteinemia. An association between steatosis and MTHFR-C677T polymorphism was not found.

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation.

Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG-IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)-ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG-IFN (1.5 microg/kg/week) and ribavirin (800-1,000 mg/day) for 12 months. Follow-up was based on biochemical (ALT), virological (RNA-HCV), and histological (liver biopsy) examinations. Follow-up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low gamma-glutamyltransferase GGT (P = 0.04) and HCV-RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patient's compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG-IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy.

Factors associated with the presence of nonalcoholic steatohepatitis in patients with chronic hepatitis C.

OBJECTIVES: The aim of this study was to identify factors associated with the presence of nonalcoholic steatohepatitis (NASH) in patients with chronic hepatitis C (CHC). METHODS: We studied 98 patients with CHC [47 with NASH (group HCV/NASH), 51 without NASH (group HCV)] and 85 with NASH not infected with hepatitis C virus (HCV) (group NASH). We determined factors associated with the presence of NASH in patients with hepatitis C. RESULTS: Group HCV/NASH patients resembled those with NASH. Body mass index (BMI) was higher in group HCV/NASH than in group HCV, but was similar to group NASH. Most HCV/NASH patients had risk factors for NASH. In patients infected with HCV, NASH and NASH-related lesions were independently associated with BMI, while steatosis score was associated with HCV genotype 3 and BMI. Fibrosis stage was independently associated with steatosis, necroinflammatory activity index, and NASH lesions. CONCLUSION: While HCV genotype 3 infection and BMI are associated with the presence of steatosis in CHC, BMI is the only factor independently associated with the presence of NASH in these patients. We suggest that overweight-related factors might induce NASH in CHC patients.

Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis.

Mitochondrial dysfunction might play a central role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The aims of this study were to evaluate whether free fatty acid (FFA) transport into the mitochondria or the activity of mitochondria respiratory chain (MRC) complexes are impaired in NASH. In patients with NASH and control subjects, we measured free carnitine, short-chain acylcarnitine (SCAC) and long-chain acylcarnitine (LCAC) esters, carnitine palmitoyltransferase (CPT) activity, and MRC enzyme activity in liver tissue as well as serum concentration of tumor necrosis factor alpha (TNF-alpha), homeostatic metabolic assessment of insulin resistance (HOMA(IR)), and body mass index (BMI). In patients with NASH, the LCAC/free carnitine ratio was significantly increased and the SCAC/free carnitine ratio was decreased. In patients with NASH, the activity of the MRC complexes was decreased to 63% +/- 20% (complex I), 58.5% +/- 16.7% (complex II), 70.6% +/- 10.3% (complex III), 62.5% +/- 13% (complex IV), and 42.4% +/- 9.1% (adenosine triphosphate synthase) of the corresponding control values. Activity of these complexes correlated significantly with serum TNF-alpha and HOMA(IR). Serum TNF-alpha (36.3 +/- 23.1 pg/mL), HOMA(IR) (4.5 +/- 2.38), and BMI (29.9 +/- 3.5 kg/m(2)) values were significantly increased in patients with NASH. In conclusion, activities of MRC complexes were decreased in liver tissue of patients with NASH. This dysfunction correlated with serum TNF-alpha, insulin resistance, and BMI values.

A pilot study of beta-interferon for treatment of patients with chronic hepatitis B who failed to respond to alpha-interferon.

BACKGROUND/AIMS: Alpha-interferon achieves persistent loss of hepatitis B virus (HBV) in about 30-40% of patients with chronic hepatitis B. In non-responder patients, the disease may progress leading to complications such as cirrhosis and hepatocellular carcinoma. The aim of the current study was to evaluate the efficacy of beta-interferon in patients with chronic hepatitis B who did not respond to one course of alpha-interferon. METHODS: Twenty nine alpha-interferon-non-responder patients with chronic hepatitis B (11 hepatitis B e antigen, HBeAg-positive; 18 HBeAg-negative) were treated with 6 million units beta-interferon five times a week for 24 weeks. The post-treatment follow-up lasted for 48 weeks. RESULTS: At the end of treatment, 38% of patients (18% HBeAg-positive; 50% HBeAg-negative) had normal serum aminotransferase levels and negative serum HBV DNA. At the end of follow-up, HBV DNA was no longer detectable in serum in 21% of patients (18% HBeAg-positive; 22% HBeAg-negative). Beta-interferon was well tolerated and safe. CONCLUSIONS: This pilot study suggests that beta-interferon therapy is effective and safe in the retreatment of patients with chronic hepatitis B who had not responded to a previous alpha-interferon cycle.

Chronic hepatitis C and autoimmune cholangitis: a case study and literature review.

We present a case of a chronic hepatitis C with damage of bile ducts resembling primary biliary cirrhosis. The immunological profile (negative antimitochondrial antibodies and positive anti-nuclear antibody) was characteristic of the autoimmune cholangitis. One year of treatment with ursodeoxycholic acid returned the liver tests to the normal range but the liver lesions remained unchanged.