Effect of hepatitis C virus treatment in fibrosis progression rate (FPR) and time to cirrhosis (TTC) in patients co-infected with human immunodeficiency virus: a paired liver biopsy study.

BACKGROUND/AIMS: Patients with hepatitis C and human immunodeficiency virus coinfection have rapid fibrosis progression. The effect on fibrosis progression rate and time to cirrhosis of HCV treatment has not been extensively studied. First aim of the study was to assess changes in FPR and TTC and staging after HCV therapy vs. no treatment. Secondary aim was to study changes in FPR/staging of sustained viral responders and non-responders to Peg-IFN alfa-2a and RBV. METHODS: Seventy-four (74) co-infected patients were grouped in three according to HCV treatment, Group 1 - None (n=9), Group 2 - IFN (n=30), Group 3-Peg-IFN alfa-2a (n=35). Paired liver biopsies were analyzed and FPR/TTC calculated for each biopsy. RESULTS: Baseline characteristics, duration of treatment and time between biopsies were similar among groups. HCV therapy, improved grading, but only Peg-IFN alfa-2a therapy resulted in staging decrease. Group 2 had significant staging increase and Group 1 had doubling of FPR and (TTC) reduction from 22.7 to 9.09 years. Peg-IFN alfa-2a treated patients had negative change in FPR and stabilization in TTC. SVR and NR with Peg-IFN alfa-2a/RBV had same FPR and staging. CONCLUSIONS: In patients with HIV/HCV co-infection Peg-IFN alfa 2a based treatment produced regression or stable fibrosis in contrast to accelerated progression in those without treatment.

Efficacy and safety of peg-IFN alfa-2a with ribavirin for the treatment of HCV/HIV coinfected patients who failed previous IFN based therapy.

BACKGROUND: Interferon (IFN) regimens for HCV treatment are less effective in HCV/HIV-coinfected patients. There are no effective treatments for patients who fail IFN therapies. We examined the safety and efficacy of peginterferon alfa-2a (peg-IFNalpha-2a) plus ribavirin (RBV) in 41HCV/HIV-coinfected patients non-responsive to prior IFN treatment. METHODS: Patients received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks (n=41). At week 24, patients with non-detectable HCV RNA or > or =2-log decrease from baseline, received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks further. Patients not responding to treatment at week 24 were discontinued. RESULTS: Intent to treat (ITT) sustained viral response (SVR) was 21.9%. Patients who received at least 24 weeks of peg-IFNalpha-2a plus RBV treatment (n=35), SVR rates were 25.7%. SVR was associated with significant improvements in liver histology grade (p=0.02), stage (p=0.02), and fibrosis progression rate (FPR) (p=0.03). Patients that failed to achieve SVR had statistically significant decreases in grade (p=0.09) and FPR (p=0.01). CONCLUSION: peg-IFNalpha-2a plus RBV is effective and safe to achieve SVR in HCV/HIV coinfected patients non-responsive to prior IFN treatment. Patients that achieve SVR have significant improvements in liver histology parameters. In patients that do not achieve SVR there are histological benefits beyond virological response that suggest that peg-IFNalpha-2a+RBV therapy may decrease risk of progression to end stage liver disease.

Progression to cirrhosis in Latinos with chronic hepatitis C: differences in Puerto Ricans with and without human immunodeficiency virus coinfection and along gender.

BACKGROUND: Hepatitis C virus (HCV) infection is prevalent in Latinos. There is some evidence that progression to cirrhosis is more rapid. END POINTS: To calculate time of cirrhosis from time of HCV infection in a large Latino population. Other end points were to assess variables that predict cirrhosis and the effect of gender, alcohol, and human immunodeficiency virus (HIV) infection status on time to cirrhosis. METHODS: Four hundred sixty-nine Latino patients evaluated at a referral center in Puerto Rico were included. Several demographic parameters, such as risk factors, estimated duration of HCV infection, alcohol use, HIV status, and findings from the usual HCV and HIV laboratory tests were noted. All patients had liver biopsy specimens assessed by Ishak score. RESULTS: Monoinfected and coinfected latinos have a median cumulative risk/hazard for cirrhosis of 42.0 vs. 32.0 years after infection (P = 0.0016). The median age of cirrhotic patients is 53.0 years in monoinfections and 42.0 years in coinfection. Among coinfected patients there is no gender-associated difference in time to onset of cirrhosis (P = 0.785). Among monoinfected patients, males have a shorter median risk/hazard to cirrhosis than females (11.0-year difference; P = 0.05) and have a shorter time until onset of cirrhosis by fibrosis progression rate (FPR) (33.33 vs. 41.66 years; P = 0.021). There is no difference between male patients with regard to HIV status (P = 0.199). Alcohol use is significant in monoinfected males (59.2 g/day) vs. females (11.4 g/day; P = 0.001). Variables that predict cirrhosis are male sex, age, and Ishak grade in monoinfected patients and alanine aminotransferase value in coinfected patients. CONCLUSIONS: Puerto Ricans with HCV have a median risk/hazard time to cirrhosis at younger age than other populations. Males who are HIV/HCV-coinfected have the same median risk/hazard and time to cirrhosis than those monoinfected with HCV. Special attention for early diagnosis and treatment is mandatory.

Double-blind pilot study of mesalamine vs. placebo for treatment of chronic diarrhea and nonspecific colitis in immunocompetent HIV patients.

Chronic diarrhea and colitis are common in patients positive for human immunodeficiency virus (HIV) under highly active antiretroviral treatment (HAART). This prospective double-blind study explores the effect of mesalamine vs. placebo in HIV-positive patients. Thirteen HIV-infected patients with noninfectious chronic diarrhea and > 250 CD4+ cells/mm(3) were randomized to mesalamine (2.4 g/day; n = 9) or placebo (n = 4) for 6 weeks. Colonoscopy was performed at baseline and week 6, and biopsies were obtained to calculate the Biopsy Activity Index (BAI). Diarrhea was assessed at baseline and end of treatment using the Disease Activity Index (DAI). Patients and clinicians completed Patient Global Improvement index (PGI) and Clinical Global Improvement index (CGI) at weeks 2 and 6. Comparisons at week 6 were statistically significant between mesalamine and placebo groups for BAI (P = 0.03), DAI (P = 0.007), PGI (P = 0.008), and CGI (P = 0.008). Furthermore, major improvements were documented in the mesalamine group at week 6 compared to baseline for all variables, whereas the placebo group did not have any. Mesalamine was effective for treatment of chronic diarrhea and moderate nonspecific colitis in HIV patients.

Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy.

BACKGROUND/AIMS: HIV/HCV-coinfected patients reportedly have a faster fibrosis progression rate (FPR) than HCV-monoinfected patients. This study examined whether HIV suppression through highly active antiretroviral therapy (HAART) attenuates this accelerated fibrosis progression. METHODS: In two hepatitis C centers, a retrospective analysis identified 656 consecutive treatment-naïve HCV-infected patients who had undergone a liver biopsy, had a presumed date of HCV infection, and had been tested for HIV, 274 of them HIV-positive (95.2% on HAART) and 382 HIV-negative. The primary outcome measure was the FPR, defined as Ishak fibrosis score [0-6] over estimated duration of HCV infection. RESULTS: Among HIV/HCV-coinfected patients, 51.2% had undetectable HIV RNA (< 400 copies/mL). There was no difference in FPR between HIV/HCV-coinfected and HCV-monoinfected patients (0.136 vs. 0.128 Ishak fibrosis units/year, P=0.29). However, HIV/HCV-coinfected patients with any detectable HIV viral load >400 copies/mL had a faster FPR (0.151) than HCV-monoinfected patients (0.128, P=0.015) and than HIV/HCV-coinfected patients with undetectable plasma HIV RNA (0.122, P=0.013) who in turn had the same FPR as HCV-monoinfected subjects (0.128, P=0.52). An accelerated FPR in HIV viremic patients was seen with CD4+ cells <500/mm(3) (0.162 vs. 0.123, undetectable HIV RNA, P=0.005) but not with CD4+ cells >500/mm(3) (0.118 vs. 0.121, P=0.89). In multivariable linear regression analysis of HIV/HCV-coinfected patients, log(10) HIV RNA level, necroinflammation, and age at HCV infection were independently correlated to FPR, but not alcohol use or CD4+ cell count (r(2)=0.45 for model). CONCLUSIONS: HIV/HCV-coinfected patients with undetectable HIV RNA through HAART have a slower FPR than those with any HIV RNA level and an FPR similar to HCV-monoinfected individuals.

High eradication rates of Helicobacter pylori infection with first- and second-line combination of esomeprazole, tetracycline, and metronidazole in patients allergic to penicillin.

H. pylori eradication is a challenge in patients allergic to penicillin, both first-line and failures of prior therapy. We aimed to assess the eradication rate of H. pylori in patients allergic to penicillin, first-line and failures of prior therapy, the efficacy of healing of active duodenal ulcer disease (DUD) and erosive gastritis, and the safety and tolerability of the combination. Twenty patients with documented allergy to penicillin, DUD, and H. pylori infection, 17 (85%) for first-line treatment and 3 (15%) prior therapy failures, were given a 10-day regimen of esomeprazole, 40 mg qid, tetracycline, 500 mg qid, and metronidazole, 500 mg qid. Baseline and follow-up panendoscopy > or =30 days after end of treatment was performed for rapid urease test (Clotest), and four site biopsies for H. pylori, and to document endoscopic peptic ulcer disease. All adverse events during treatment were documented. Eradication rates by intention to treat (ITT) were 85% for first-line treatment and 100% for failures. Seventy percent of all cases had a normal endoscopy at follow-up, and 85 and 100% of patients had healed erosive gastritis and DUD, respectively, from baseline. There were histological improvements in most patients. A high eradication rate was obtained even in patients who had a shorter duration of treatment. The combination was well tolerated. A combination of esomeprazole, tetracycline, and metronidazole is effective for eradication of H. pylori in patients allergic to penicillin, for both first-line treatment and failures of prior treatment.

Steatosis as a predictive factor for treatment response in patients with chronic hepatitis C.

BACKGROUND: Hepatic steatosis has been described in 31-72% of chronic hepatitis C virus (HCV) liver biopsies. Steatosis has been related to disease progression and suggested as a predictor of treatment response in chronic HCV. This study aims to evaluate the presence and degree of steatosis in liver histology of patients with chronic HCV prior to combination therapy with interferon (INF) and ribavirin (RBV), and how it influences treatment response. METHODS: The medical charts of patients with chronic HCV who received treatment at the San Juan Veterans Affairs (VA) Medical Center from 1998 to 2002 were reviewed. Selected patients completed therapy, had a pre-treatment liver biopsy, genotype determination, and pre and post treatment HCV-RNA levels. Patient's age, sex and body mass index (BMI) were determined. Pre-treatment liver biopsy slides were reviewed and graded for steatosis by a hepatopathologist blinded to the treatment outcome. Steatosis was graded by the presence of fat in total biopsy area as: mild (<33%), moderate (33-66%), severe (>66%) or absent. Treatment response was defined as virological clearance measured by HCV RNA at the end of treatment and 24 weeks after completion of treatment. The presence of steatosis was compared to BMI, HCV genotype and treatment response. RESULTS: 46 patients met the inclusion criteria. All patients were male of Hispanic origin. Mean age: 52.7 years (range: 40-68). Mean BMI: 27.5 kg/m2 (range: 21.1-35.9). HCV genotype 1 was present in 67% of patients. 82.6% (38/46) of the patients had hepatic steatosis: 29 (63%) mild, 7 (15%) moderate and 2(4%) severe. 16.6% (8/46) of the biopsies did not show steatosis. Overall, the response rate for those with steatosis was 31.6% (12/38): 10/29 (34.5%) mild, 1/7 (14.3%) moderate and 1/2 (50%) of severe. 75% (6/8) of those without steatosis responded to treatment. This difference (31.6% vs. 75%) was statistically significant (p=.042). The mean BMI of both groups was similar (27.7 kg/m2 for those with steatosis and 26.6 kg/m2 for those without steatosis). This difference was not statistically significant (p=.308). CONCLUSIONS: The results of our study show a high prevalence of steatosis in the liver histology of patients with chronic HCV. The presence and degree ofsteatosis in our HCV patients appears to be unrelated to either genotype or BMI. Furthermore, the response to therapy is negatively influenced by the presence of steatosis regardless of genotype. Hepatic steatosis, mild, moderate or severe, appears to be an independent predictor of poor response to therapy.

Elevated alt activity in volunteer blood donors

Actualmente, la causa más común de hepatitis post-transfusional es infección con el virus de la hepatitis C (anteriormente llamado el virus de la hepatitis no-A, no-B). Durante la década del 1980, se encontró una incidencia aumentada de casos de hepatitis post-transfusional en paciente que habían recibido sangre de donantes con valores de ALT anormalmente altos y/o con la presencia del anticuerpo al "core" del virus de la hepatitis B. Se asumió que esos casos habían sido causados por el virus de la hepatitis C (llamado entonces "no-A, no-B") en la sangre del donante. Hasta hace poco, no existía una prueba específica de laboratorio para detectar este virus en sangre donada. Basándo-se en esta asociación estadística, la Asociación Americana de Bancos de Sangre recomendó en el 1986 que se le hicieran pruebas de ALT y de la presencia de HBcb a toda unidad de sangre donada para detectar indirectamente la presencia del virus de la hepatitis C. Esto ocasionó que se acumulara una gran cantidad de datos sobre niveles poblacionales de ALT y de HBcAb. En este estudio, los niveles de actividad de ALT en 3108 donantes de sangre del Banco de Sangre del Hospital Universitario Ramón Ruiz Arnau fueron analizados retrospectivamente usando sus expedientes. El ALT promedio entre estos donantes fue 35.91 unidades/litro. Este promedio es significativamente más alto que los promedios reportados previamente en otras poblaciones. Se discute tambien las posibles causas de la elevación local de ALT

Increased alanine aminotransferase (ALT-SGPT) activity in Puerto Rican blood donors

Se obtuvieron datos de 4,189 expedientes de donaciones de sangre procedentes de dos bancos de sangre en Puerto Rico para determinar si los puertorriqueños tienden a tener niveles en sangre de ALT-SGPT más altos en comparación con donantes de sangre de otros grupos étnicos. El promedio general de ALT-SGPT fue de 36.84 u/l (alcance 1-910, desviación estandard 37.8). El logarítmo de ALT FUE DE 1.47 (alcance 1-2.96, desviación estandard). Analisis de cada banco de sangre en dos períodos de tiempo demostraba promedios de ALT-SGPT consistentemente altos aún cuando excluían donaciones positivas para hepatitis B, H. I. V. y sífilis. Aunque las causas de estos hallazgos no estan claras, factores ambientales como el consumo de alcohol deben considerar-se como posibles explicaciones