Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy

BACKGROUND: The key end point for treatment efficacy in chronic hepatitis C is absence of detectable virus at six months after treatment. However, the incidence of clinical events during long term follow up of patients with sustained virological response is still poorly documented and may differ between the Eastern and Western world. AIMS: To assess clinical end points during long term follow up of European patients with a sustained virological response to interferon monotherapy. METHODS: Meta-analysis of individual patient data from eight European protocolled follow up studies of interferon treatment for chronic hepatitis C. RESULTS: A total of 286 sustained virological responders and 50 biochemical responders (detectable virus but normal alanine aminotransferase levels) were followed up for 59 months. Fifteen sustained virological responders (5.2%) had cirrhosis before treatment and 112 (39%) had genotype 1. The late virological relapse rate after five years of follow up was 4.7% (95% confidence interval (CI) 2.0-7.4) among sustained virological responders; all late relapses occurred within four years after treatment. Among sustained virological responders, the rate of decompensation after five years of follow up was 1.0% (95% CI 0.0-2.3) and none developed hepatocellular carcinoma (HCC). Survival was comparable with the general population, matched for age and sex, the standard mortality ratio being 1.4 (95% CI 0.3-2.5). Clinical outcome of patients with cirrhosis was similar to other sustained virological responders. For biochemical responders, the rates of development of decompensation and HCC during long term follow up were 9.1% (95% CI 0.5-17.7) and 7.1% (95% CI 0-15.0), respectively. CONCLUSIONS: Five year survival of European sustained virological responders was similar to the overall population, matched for age and sex. No HCCs were detected during long term follow up.     

Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease

Liver transplantation in patients with hepatitis B has been under discussion for 20 years because of inferior results without reinfection prophylaxis; therefore, we analyzed our overall experience with liver transplantation in hepatitis B patients with immunoprophylaxis, particularly the influence of the available antiviral treatment in different periods. From 1988 to 2000, 228 liver transplants in 206 hepatitis B patients were performed. Indications were acute liver failure (10%), hepatitis B virus (HBV) cirrhosis alone (67%) or with hepatitis D virus (HDV) (13%), or hepatitis C virus (HCV) coinfection (7%). All patients received long-term immunoprophylaxis (anti-HBs > 100 U/L). HBV DNA-positive patients were treated before and after surgery with famciclovir or lamivudine since 1993 and 1996, respectively. Since 1993, antivirals also were used for HBV reinfection. The 1-, 5-, and 10-year patient survival rates were 91%, 81%, and 73%. In patients with hepatocellular carcinoma (HCC) (60% 5-year survival, P <.01) or HBV reinfection (69% 5-year survival, P <.01) survival was significantly impaired. Those with HDV or HCV coinfection had a slightly better survival than with HBV monoinfection (P >.05, not significant). Preoperative positive HBV DNA (hybridization-assay) test results were associated with a slightly impaired patient survival (78% 5-year survival, P >.05, not significant versus DNA-negative). Preoperative positive hepatitis B e antigen (HBeAg) predicted significantly worse survival (P <.05 versus negative HBeAg). Graft loss caused by reinfection was most frequent before the availability of antiviral drugs. Two-year patient survival increased from 85% in era I (1988-1993) to 94% in era III (1997-2000, P <.05). The 2-year recurrence rates in these 2 periods were 42% and 8% (P <.05). In conclusion, excellent long-term results can be achieved in hepatitis B patients after liver transplantation with modern strategies, and survival rates are similar to other indications. Based on our experience, hepatitis B patients, including those with active viral replication, should not be excluded from liver transplantation.     

Sizing up Ethanol-Induced Plasticity: The Role of Small and Large Conductance Calcium-Activated Potassium Channels

Small (SK) and large conductance (BK) Ca²⁺-activated K⁺ channels contribute to action potential repolarization, shape dendritic Ca²⁺spikes and postsynaptic responses, modulate the release of hormones and neurotransmitters, and contribute to hippocampal-dependent synaptic plasticity. Over the last decade, SK and BK channels have emerged as important targets for the development of acute ethanol tolerance and for altering neuronal excitability following chronic ethanol consumption. In this mini-review, we discuss new evidence implicating SK and BK channels in ethanol tolerance and ethanol-associated homeostatic plasticity. Findings from recent reports demonstrate that chronic ethanol produces a reduction in the function of SK channels in VTA dopaminergic and CA1 pyramidal neurons. It is hypothesized that the reduction in SK channel function increases the propensity for burst firing in VTA neurons and increases the likelihood for aberrant hyperexcitability during ethanol withdrawal in hippocampus. There is also increasing evidence supporting the idea that ethanol sensitivity of native BK channel results from differences in BK subunit composition, the proteolipid microenvironment, and molecular determinants of the channel-forming subunit itself. Moreover, these molecular entities play a substantial role in controlling the temporal component of ethanol-associated neuroadaptations in BK channels. Taken together, these studies suggest that SK and BK channels contribute to ethanol tolerance and adaptive plasticity.     

Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes

Splenic lymphoma with villous lymphocytes (SLVL) is a recently defined subgroup of chronic B-cell lymphoproliferative diseases. The characteristic morphology of the tumor cells, together with phenotypic and cytogenetic findings, indicate that it is a distinct entity, but the nature of the cell or origin and its relationship to other low- grade lymphomas is unclear. For B-cell tumors, analysis of the variable region heavy chain (VH) genes used to encode the clonal Ig has shown marked differences between histologic categories, both in gene usage and extent of somatic mutation. An investigation of VH genes used in five typical cases of SLVL has shown somatic hypermutation from germline sequences in all cases, indicating that the cell of origin has been exposed to the hypermutation mechanism. However, no clonal heterogeneity was detectable, demonstrating that the tumor cell does not accumulate further mutations. These characteristics are similar to those found in mature postfollicular B cells, such as plasma cells. The distribution of mutations leading to replacement amino acids differed among the cases, with three of five cases showing clear evidence for antigen selection.     

Serological assessment of HBcAg and HBV DNA: its prognostic relevance in acute hepatitis B

Treatment of serum precipitates with sodium thiocyanate in patients with hepatitis B virus (HBV) replication results in liberation of circulating hepatitis core antigen (HBcAg) which can be demonstrated radioimmunologically. Follow-up investigations were performed in 80 patients with acute hepatitis B. Sera were examined for HBcAg. HBV DNA and conventional HBV markers. At the time of admission to hospital 34 of 80 (42%) patients were HBeAg positive. Twenty-six (76%) of the 34 HBcAg positive patients were HBV DNA positive, and circulating HBcAg was detectable in 25 of 34 (73%) HBcAg positive cases. In patients with uncomplicated courses of acute hepatitis B the serological HBcAg assay and HBV DNA became negative 1 to 8 weeks before elimination of HBeAg and up to 12 weeks earlier than the sera became negative for HBsAg. Five patients (6%) showed transition to chronic hepatitis B with persistence of HBsAg, HBeAg, HBV DNA and HBcAg in serum. One patient with acute hepatitis B and development of chronic hepatitis suffered from acquired immunodeficiency syndrome and showed delayed formation of anti-HBc. In this case uncomplexed HBcAg was demonstrable during the acute phase of hepatitis B. With the appearance of anti-HBc HBcAg circulated in a complexed form. The data indicate that serological determinations of HBcAg and HBV DNA can serve as prognostic markers in the early phase of acute hepatitis B. The demonstration of uncomplexed HBcAg in serum of a patient with inadequate formation of anti-HBc supports the hypothesis that circulating HBcAg is usually complexed by specific antibodies.     

Blood Donations Indeterminate in HIV4 Western Blot Analysed by IgM Immunoblot and Polymerase Chain Reaction

The presence of IgM antibodies to human immunodeficiency virus 1 (HIV-1) was investigated in blood donor sera which were indeterminate in anti-HIV-1 IgG Western blot testing. In 7 of 173 instances out of approximately 1,000,000 blood donation sera with an isolated anti-p24 IgG produced an anti-gp41-45 IgM immunoblot reaction. Applying polymerase chain reaction (PCR) to 29 indeterminate samples out of approximately 125,000 blood donations it was found that 2 of them were IgM-positive and also contained HIV-1-specific DNA sequences. Eleven months later 1 of these 2 donors was retested and found IgM and PCR negative.     

The "optimal" burr hole position for endoscopic third ventriculostomy: results from 31 stereotactically guided procedures.

ETV is a well established and successful method in contemporary neurosurgery. With growing experience there is a more efficient patient selection and further advances in technical know how. We evaluated retrospectively a consecutive group of 27 patients who were treated in our institution by stereotactic guided ETV between 1992 and 1996. When reviewing their postoperative imaging studies (MRI/CT) we could measure the position of the burr hole as port of entry for the rigid endoscope in 17 out of 23 finally selected patients. The median lateral position was 28 mm (mean 26.5 mm) from the midline and 8 mm (mean 6.5 mm) anterior of the coronal suture. We conclude that the optimal burr hole position should be 3 cm lateral to the midline and 1 cm anterior of the coronal suture, in the patients with normal anatomical findings.     

Direct myocardial anti-ischemic effect of diltiazem in the human

In a randomized double blind placebo-controlled study in 20 patients the influence of the calcium antagonist diltiazem (1.0 mg administered intracoronarily, distal from the stenosis) on the severity of myocardial ischemia during therapeutic coronary occlusion (transluminal coronary angioplasty) of the left anterior descending coronary artery was investigated. The severity and time of onset of ischemic ST and T wave changes as well as anginal pain were significantly reduced 3 and 8 minutes after diltiazem, whereas there was no definite change in the controls. Heart rate and blood pressure were not influenced by diltiazem or placebo. The results indicate a direct antiischemic effect of diltiazem on myocardial cells. The findings can neither be explained by an influence on cardiac afterload nor by coronary vessel reactions, nor a reduction of myocardial contractility. The findings do not permit conclusions in terms of the duration of this direct antiischemic mode of action.     

Niederenergetischer,gepulster Ultraschall zur Beeinflussung der Knochenregeneration

Trauma und Berufskrankheit - Durch die Anwendung von niederenergetischem, gepulstem Ultraschall kann die Knochenheilung beschleunigt werden. Die vorliegende Arbeit soll einen Überblick...     

Determination of the solute removal index for urea by using a partial spent dialysate collection method

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.