Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir.

Registration studies show entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg-positive and HBeAg-negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty-nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log10 IU/mL. Ninety-two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti-HBe positive; 14% became HBsAg negative and 13% anti-HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off-treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off-treatment, 3 of them showed HBeAg reversion and 4 lost anti-HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.

Breath-ammonia testing of healthy subjects and patients with cirrhosis.

BACKGROUND: Hepatic encephalopathy (HE) is a serious neuropsychiatric complication in both acute and chronic liver disease. AIMS: To establish the utility of a portable noninvasive method to measure ammonia in the breath of healthy subjects and patients with HE. METHODS: The study included 106 subjects: 44 women and 62 men, 51 healthy and 55 cirrhotic. The breath ammonia was measured with an electrochemical sensor and expressed in parts/billion (ppb). RESULTS: The breath ammonia in healthy subjects had an average value of 151.4 ppb (95% confidence interval [CI]: 149.4-153.4) and the average value in cirrhotic patients was 169.9 ppb (95% CI: 163.5-176.2) (P < 0.0001). In cirrhotic patients with and without HE, the corresponding values were 184.1 ppb (95% CI: 167.7-200.6) and 162.9 ppb (95% CI: 158.8-167.0), respectively (P = 0.0011). Ammonia levels ≥ 165 ppb permitted a differentiation between healthy and cirrhotic subjects; the area under the receiver operating characteristic (ROC) curve for the ammonia-level values in cirrhotic versus control patients was 0.86 (95% CI: 0.79-0.93). In cirrhotic patients, ammonia levels ≥ 175 ppb permitted the distinction between patients with and without HE; the area under the ROC curve in cirrhotic patients with versus without HE was 0.83 (95% CI: 0.73-0.94). CONCLUSION: A portable sensor for measuring breath ammonia can be developed. If the results of the present study are confirmed, breath-ammonia determinations could produce a significant impact on the care of patients with cirrhosis and could even include the possibility of self-monitoring.

Effectiveness of entecavir in chronic hepatitis B NUC-naive patients in routine clinical practice.

INTRODUCTION: Registration studies showed entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B virus (HBV), but its effectiveness in routine clinical practice is unknown. MATERIALS AND METHODS: Sixty-nine HBeAg positive and negative NUC naïve chronic HBV patients were treated with ETV for 110 weeks. 63% were HBeAg positive, 16% were cirrhotics, mean HBV-DNA was 7.09 log IU/ml and mean ALT was 157 IU/ml. RESULTS: Sixty-one (88%) patients achieved undetectable DNA, with 46%, 77% and 100% virological response rates at week 24, 48 and 96 of treatment, respectively. Thirty-seven (84%) patients in the HBeAg-positive population achieved undetectable DNA, with 67% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-four (96%) patients in the HBeAg-negative population achieved undetectable DNA, with 91% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-three (53%) patients cleared HBeAg and 19 (44%) patients seroconverted to antiHBe positive status; seven (10%) patients cleared hepatitis B surface antigen and five (7%) patients developed antiHBs. At the end of the study, 10 patients successfully stopped therapy: nine HBeAg positive (four developed antiHBs positive) and one HBeAg negative. None of the patients had primary non-response. ETV resistance was not tested. None of the patients developed hepatocellular carcinoma, underwent liver transplantation or died because of liver-related events. No serious adverse events were reported. CONCLUSION: The ETV monotherapy showed high virological response rates, a favourable safety profile for NUC-naive HBeAg-positive and negative patients treated in routine clinical practice.

Disfunción hepática en el trasplante de celulas progenitoras hematopoyéticas: Impacto sobre la mortalidad / Liver dysfunction in recipients of hematopoietic stem cells: Impact on mortality

El compromiso hepático en receptores de transplante alogénico de células progenitoras hemotopoyéticas (TCPH) es una complicación muy frecuente y es responsable de la morbimortalidad precoz. La toxicidad por fármacos la enfermedad injerto versus huésped ( EICH) , la enfermedad venooclusiva (EVO) y las infecciones fúngicas, bacterianas y virales constituyen las principales etiologias. El objetivo de este estúdio retrospectivo fue estabelecer la prevalencia y etiología de la afectación hepática, evaluar el impacto en la mortalidad y analizar el valor predictivo de las transaminasas pré TCPH en la ocurrencia de EICH agudo, crônico y mortalidad. De un total de 236 pacientes transplantados, se evaluaron 82 sometidos a TCPH alogénico. El 88% de los pacientes tuvo afectación hepática: EICH agudo 40.2%, EICH crônico 15.9%, de causa indeterminada 9.8% sepsis 7.3%, toxicidad por fármacos 6.1%, EVO 3.7%, hepatitis aguda y recidiva de enfermedad 2.4%. La mortalidad evaluada al año fue 36.6%. La insuficiência hepática aguda (IHA) represento el 10% de las muertes. Las causas de IHA fueron: progresón de EICH agudo, recidiva de la enfermedad hematológica en el hígado, hepatitis herpética y EVO. El valor predictivo positivo de las transaminasas pré TCPH para EICH agudo, crônico y mortalidad fue 0.27, 0.14 y 0.43 respectivamente. No se hallaron diferencias significativas entre pacientes con pruebas bioquímicas hepáticas pré TCPH alteradas o normales en la ocurrencia de EICH agudo, crónico o mortalidad.

[When is the best time to perform upper digestive endoscopy to detect the presence of esophageal varices in patients with cirrhosis?]. / 'Cuándo sería más rentable realizar una endoscopia digestiva alta para establecer la presencia de varices esofágicas en pacientes con cirrosis?

INTRODUCTION: Variceal hemorrhage occurs in 25 to 35% of cirrhotic patients and is associated with significant morbidity and mortality and elevated hospital costs. Endoscopic exploration of gastroesophageal varices (GEV) in cirrhotic patients increases costs and involves a certain degree of invasiveness and discomfort for patients. The association between the presence of GEV and spleen size, liver function and platelet count is controversial. The aim of this study was to determine the correlation between liver function, evaluated by Child-Pugh (Ch-P) classification, platelet count (PC) and spleen volume index (SVI) with the presence of GEV in patients with cirrhosis managed in the outpatient setting. PATIENTS AND METHOD: Sixty-eight patients were included. In all patients, a medical history was taken and biochemical tests, mode B and Doppler abdominal ultrasonography, and upper digestive video-endoscopy were performed. RESULTS: A total of 76.47% of the patients were men and 23.53% were women. The median age was 52.8 12.4 years. More than half (54.41%) of the patients were Ch-P grade A, 41.18% were grade B and 4.41% were grade C. The most frequent causes of cirrhosis were alcohol in 52.95% and hepatitis C virus in 17.65%. Esophageal varices (EV) were found in 85.29% of the patients. The median SVI was 50.5 9.2 and the median PC was 150 26 x 109/L. A correlation was found between the presence of EV, SVI >or= 45 and PC < or= 100 x 109/L (r = 0.327; p = 0.006). No correlation was found between the presence of EV and Ch-P grade A. In the multivariate analysis, only the presence of EV was associated with SVI >or= 45 (OR 7.4; 95% CI, 1.30-77.7; p = 0.02). CONCLUSION: The presence of EV in cirrhotic patients managed in the outpatient setting was correlated with SVI >or= 45 and PC

Transmisión sexual del virus de Hepatitis C / Sexual transmision of Hepatitis C virus

Fifty heterosexual partners out of 50 patients (index cases) without confirmed or probable risk factors of parenteral transmission by HCV were studied from 1/1997 to 1/2001. The index cases were HCV Ab (+) (EIA 3rd Abbott and PCR + by RT-nested PCR). The couples with probable or confirmed risk factors of parenteral transmission were strictly excluded. No case of HCV infection was found, suggesting that sexual via wouldn't be a direct transmission of HCV

[Sexual transmission of Hepatitis C virus]. / Transmisiòn sexual del virus de Hepatitis C.

Fifty heterosexual partners out of 50 patients (index cases) without confirmed or probable risk factors of parenteral transmission by HCV were studied from 1/1997 to 1/2001. The index cases were HCV Ab (+) (EIA 3rd Abbott and PCR + by RT-nested PCR). The couples with probable or confirmed risk factors of parenteral transmission were strictly excluded. No case of HCV infection was found, suggesting that sexual via wouldn't be a direct transmission of HCV.

[Acute liver failure: clinical-epidemiological characteristics]. / Insuficiencia hepática aguda: características clínico-epidemiológicas.

In order to ascertain the clinical and epidemiological features of acute liver failure (ALF), we analyzed the clinical histories of 22 patients from La Plata city, with the diagnosis of ALF (prothrombin level or factor V below 50%) seen between November 1996 and November 2000. Age, sex, hepatic encephalopathy, reason for consultation, etiology, hepatic biochemical tests, serum creatinine, glycemia, digestive hemorrhage, course and treatment variables were analyzed. What is remarkable is the high frequency of the toxic etiology and of infection by HDV, as well as the high prevalence of ascites and the low incidence of hepatic encephalopathy. We think that the high survival rate we found is due to the early diagnosis and early referral of the patients to the intensive care unit and to centers with programs for liver transplantation.

Insuficiencia hepática aguda: características clínico-epidemiológicas / Acute liver failure: clinical-epidemiological characteristics

Se analizaron las historias clínicas de 22 pacientes con IHA (Protrombina y/o factor V menor de 50 por ciento). La ictericia fue el motivo de consulta más frecuente (54.5 por ciento). Doce pacientes (54.5 por ciento) presentaron EH, sólo dos de los cuales la teníam en el momento del ingreso. Doce (54.5 por ciento) presentaron ascitis en algún momento de la evolución. Etiología desconocida en 6 (27.2 por ciento), fármacos 6 (27.2 por ciento), HBV 5 (22.7 por ciento) 2 de los cuales teníam además HDV y 3 (13.6 por ciento) autoimmune. Se halló una alta tasa de sobrevida.

Tratamiento antibiótico intratecal intraventricular en meningitis infecciosa postquirúrgica / Intrathecal-intraventricular antibiotic treatment in postoperative infectious meningitis

Realizamos una revisión de datos clínicos y microbiológicos de tres pacientes que desarrollaron infecciones postoperatorias, (dos cirugías craneales y una espinal). El tratamiento antibiótico intravenoso aislado falló, y debimos recurrir a la vía intraventricular-intratecal con buenos resultados. El tratamiento antibiótico intraventricular-intratecal aparece como una modalidad útil, en aquellas infecciones postoperatorias en que la terapia sistémica no da resultado.

[Acute liver failure by diphenylhydantoin]. / Insuficiencia hepática aguda por difenilhidantoina.

Diphenylhydantoin is a anticonvulsivant and antiarrhythmic drug. We reported a less frequent case of diphenylhydantoin associated acute hepatotoxicity in a 18-year old woman who immediately after child birth presented generalized tonic-clonic seizures secondary to arachnoid cyst in the left temporal-lobe. The patient developed a mononucleosis like coinciding with previous descriptions. Histological features observed in the liver biopsy specimen showed compatible changes with toxic acute liver failure (ALF). In the few cases published of ALF for Diphenylhydantoin is not specifically pointed out the absence of hepatic encephalopathy as it happened to our patient.

Insuficiencia hepática aguda por difenilhidantoina / Acute liver failure by diphenylhydantoin

Presentamos un caso poco frecuente de insuficiencia hepática aguda por difenilhidantoína en una joven de 18 años. La paciente fue tratada con dicho fármaco inmediatamente después de un parto normal por presentar convulsiones clónicas secundarias a un quiste aracnoideo del lóbulo temporal izquierdo. La paciente presentó un "tipo mononucleosis like" tal como ha sido descripto previamente. La enferma mejoró su función hepática estando en lista de espera para transplante ortotópico hepático y se recuperó totalmente hasta alcanzar el alta definitiva de dos meses después sin haber presentado manifestaciones de encefalopatía hepática en ningún momento de la evolución. La ausencia de encefalopatía hepática, tal como ocurrió en nuestra paciente, no fue señalada en ninguno de los pocos casos de insuficiencia hepática por difenilhidantoína comunicados previamente. Nos estimulan a poner en conocimiento de la comunidad médica un nuevo caso de insuficiencia hepática aguda por difenilhidantoína: 1) La ausencia de encefalopatía hepática (comunicada por primera vez en un caso de insuficiencia hepática aguda por difenilhidantoína. 2) La baja frecuencia de insuficiencia hepática aguda por difenilhidantoína. 3) La forma típica de presentación como "Síndrome Mononucleosis like" con la posibilidad que ella convella de confundir esta entidad con una infección por virus de Ebstein Bar.

[Anti HCV in hemodialyzed patients: reduction of the prevalence and association with epidemiological variables]. / Anti HCV en pacientes hemodializados: descenso de la prevalencia y asociación con variables epidemiológicas.

In order to establish the present prevalence of HCV in hemodialyzed patients (HD) from the city of La Plata, and to know the association between the prevalence and different variables, we have studied 217 hemodialyzed patients belonged to the Hemodialysis Unit of a Public Hospital and other 7 private Units. Serological reactivity to Anti HCV and Anti HBc IgG were investigated in all of them, as well as age, sex, number of transfusions, the time under dialysis treatment, the use of erythropoietin and hepatitis episodes were taken into account. We have found a prevalence of Anti HCV of 18.4% which was significantly superior to the blood donors' prevalence (P < 0.01) and significantly inferior to the one found in 1993 in HD patients of the same city (p = 0.002). We have found an association between the presence of Anti HCV and transfusions exposure, as well as more hemodialysis time. Our results may agree with the ones that suggest the aminotransferases are not good markers for hepatocellular injuries in Anti HCV (R) HD patients.

Anti HCV en pacientes hemodializados: descenso de la prevalencia y asociación con variables epidemiológicas / Anti HCV in hemodialyzed patients: reduction of the prevalence and association with epidemiological variables

Para estabelecer la prevalencia actual de infección por HCV en pacientes hemodializados (HD) de la ciudad de La Plata y determinar su asociación con diferentes variables se estudiaron 217 pacientes con Insuficiencia Renal Crónica de una Unidad de Hemodiálisis de un Htal público y de 7 Unidades del medio asistencial privado. En la totalidad de los pacientes se investigó la presencia sérica de anti-HCV y de anti-HBc y se valoró la edad, sexo, número de transfusiones, antigüedad del tratamiento hemodialítico, uso de eritropoyetina y episodios de hepatitis. Se halló una prevalencia de anti-HCV del 18,4 por ciento significativamente superior a la de los donantes de sangre (P<0,01) y significativamente enor a la hallada en pacientes HD de la misma ciudad en 1993 (P=0,002). También se encontró que la presencia de anti-HCV se asocia con el antecedente de haber recibido transfusiones y con mayor tiempo de ento hemodialítico. Nuestro resultados parecen coincidir con los que sugieren que las aminotransferasas en pacientes HD anti HCV © son un mal marcador de lesión hepatocelular.