The number needed to treat to prevent mortality and cirrhosis-related complications among patients with cirrhosis and HCV genotype 1 infection

Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis-related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical disease progression (any cirrhosis-related event or death) in one patient was determined with the adjusted (event-free) survival among patients without SVR and adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of 8.3 (IQR 6.2-11.1) years. Fifty-nine (24%) patients attained SVR. Among patients without SVR, the adjusted 5-year survival and event-free survival were 94.4% and 80.0%, respectively. SVR was associated with reduced all-cause mortality (HR 0.15, 95% CI 0.05-0.48, P = 0.002) and clinical disease progression (HR 0.16, 95% CI 0.07-0.36, P < 0.001). The NNT to prevent one death in 5 years declined from 1052 (95% CI 937-1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54-101) at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected with triple therapy, the estimated NNT was 43 (95% CI 38-71). The NNT to prevent clinical disease progression in one patient in 5 years was 302 (95% CI 271-407), 18 (95% CI 16-24) and 13 (95% CI 11-17) at 2%, 35% and 50% SVR, respectively. In conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with HCV genotype 1 has declined enormously with the improvement of antiviral therapy.

Effect of thrombocytopenia on treatment tolerability and outcome in patients with chronic HCV infection and advanced hepatic fibrosis.

BACKGROUND & AIMS Pegylated interferon is still the backbone of hepatitis C treatment and may cause thrombocytopenia, leading to dose reductions, early discontinuation, and eventually worse clinical outcome. We assessed associations between interferon-induced thrombocytopenia and bleeding complications, interferon dose reductions, early treatment discontinuation, as well as SVR and long-term clinical outcome. METHODS All consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis (Ishak 4-6) who initiated interferon-based therapy between 1990 and 2003 in 5 large hepatology units in Europe and Canada were included. RESULTS Overall, 859 treatments were administered to 546 patients. Baseline platelets (in 10(9)/L) were normal (⩾150) in 394 (46%) treatments; thrombocytopenia was moderate (75-149) in 324 (38%) and severe (<75) in 53 (6%) treatments. Thrombocytopenia-induced interferon dose reductions occurred in 3 (1%); 46 (16%), and 15 (30%) treatments respectively (p<0.001); interferon was discontinued due to thrombocytopenia in 1 (<1%), 8 (3%), and in 8 (16%) treatments respectively (p<0.001). In total, 104 bleeding events were reported during 53 treatments. Only two severe bleeding complications occurred. Multivariate analysis showed that cirrhosis and a platelet count below 50 were associated with on-treatment bleeding. Within thrombocytopenic patients, patients attaining SVR had a lower occurrence of liver failure (p<0.001), hepatocellular carcinoma (p<0.001), liver related death or liver transplantation (p<0.001), and all-cause mortality (p=0.001) compared to patients without SVR. CONCLUSIONS Even in thrombocytopenic patients with chronic HCV infection and advanced hepatic fibrosis, on-treatment bleedings are generally mild. SVR was associated with a marked reduction in cirrhosis-related morbidity and mortality, especially in patients with baseline thrombocytopenia.

Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters.

OBJECTIVE Reliable tools to predict long-term outcome among patients with well compensated advanced liver disease due to chronic HCV infection are lacking. DESIGN Risk scores for mortality and for cirrhosis-related complications were constructed with Cox regression analysis in a derivation cohort and evaluated in a validation cohort, both including patients with chronic HCV infection and advanced fibrosis. RESULTS In the derivation cohort, 100/405 patients died during a median 8.1 (IQR 5.7-11.1) years of follow-up. Multivariate Cox analyses showed age (HR=1.06, 95% CI 1.04 to 1.09, p<0.001), male sex (HR=1.91, 95% CI 1.10 to 3.29, p=0.021), platelet count (HR=0.91, 95% CI 0.87 to 0.95, p<0.001) and log10 aspartate aminotransferase/alanine aminotransferase ratio (HR=1.30, 95% CI 1.12 to 1.51, p=0.001) were independently associated with mortality (C statistic=0.78, 95% CI 0.72 to 0.83). In the validation cohort, 58/296 patients with cirrhosis died during a median of 6.6 (IQR 4.4-9.0) years. Among patients with estimated 5-year mortality risks <5%, 5-10% and >10%, the observed 5-year mortality rates in the derivation cohort and validation cohort were 0.9% (95% CI 0.0 to 2.7) and 2.6% (95% CI 0.0 to 6.1), 8.1% (95% CI 1.8 to 14.4) and 8.0% (95% CI 1.3 to 14.7), 21.8% (95% CI 13.2 to 30.4) and 20.9% (95% CI 13.6 to 28.1), respectively (C statistic in validation cohort = 0.76, 95% CI 0.69 to 0.83). The risk score for cirrhosis-related complications also incorporated HCV genotype (C statistic = 0.80, 95% CI 0.76 to 0.83 in the derivation cohort; and 0.74, 95% CI 0.68 to 0.79 in the validation cohort). CONCLUSIONS Prognosis of patients with chronic HCV infection and compensated advanced liver disease can be accurately assessed with risk scores including readily available objective clinical parameters.

Long-term results of therapeutic local anesthesia (neural therapy) in 280 referred refractory chronic pain patients

BACKGROUND: Can the application of local anesthetics (Neural Therapy, NT) alone durably improve pain symptoms in referred patients with chronic and refractory pain? If the application of local anesthetics does lead to an improvement that far exceeds the duration of action of local anesthetics, we will postulate that a vicious circle of pain in the reflex arcs has been disrupted (hypothesis). METHODS: Case series design. We exclusively used procaine or lidocaine. The inclusion criteria were severe pain and chronic duration of more than three months, pain unresponsive to conventional medical measures, written referral from physicians or doctors of chiropractic explicitly to NT. Patients with improvement of pain who started on additional therapy during the study period for a reason other than pain were excluded in order to avoid a potential bias. Treatment success was measured after one year follow-up using the outcome measures of pain and analgesics intake. RESULTS: 280 chronic pain patients were included; the most common reason for referral was back pain. The average number of consultations per patient was 9.2 in the first year (median 8.0). After one year, in 60 patients pain was unchanged, 52 patients reported a slight improvement, 126 were considerably better, and 41 pain-free. At the same time, 74.1 % of the patients who took analgesics before starting NT needed less or no more analgesics at all. No adverse effects or complications were observed. CONCLUSIONS: The good long-term results of the targeted therapeutic local anesthesia (NT) in the most problematic group of chronic pain patients (unresponsive to all evidence based conventional treatment options) indicate that a vicious circle has been broken. The specific contribution of the intervention to these results cannot be determined. The low costs of local anesthetics, the small number of consultations needed, the reduced intake of analgesics, and the lack of adverse effects also suggest the practicality and cost-effectiveness of this kind of treatment. Controlled trials to evaluate the true effect of NT are needed.

The Nelaton Catheter Guard for Safe and Effective Placement of Subdural Drain for Two-Burr-Hole Trephination in Chronic Subdural Hematoma: A Technical Note

BACKGROUND For chronic subdural hematoma, placement of a Blake drain with a two-burr-hole craniotomy is often preferred. However, the placement of such drains carries the risk of penetrating the brain surface or damaging superficial venous structures. OBJECTIVE To describe the use of a Nelaton catheter for the placement of a subdural drain in two-burr-hole trephination for chronic subdural hematoma. METHOD A Nelaton catheter was used to guide placement of a Blake drain into the subdural hematoma cavity and provide irrigation of the hematoma cavity. With the two-burr-hole method, the Nelaton catheter could be removed easily via the frontal burr hole after the Blake drain was in place. RESULTS We used the Nelaton catheters in many surgical procedures and found it a safe and easy technique. This method allows the surgeon to safely direct the catheter into the correct position in the subdural space. CONCLUSIONS This tool has two advantages. First, the use of a small and flexible Nelaton catheter is a safe method for irrigation of a chronic subdural hematoma cavity. Second, in comparison with insertion of subdural drainage alone through a burr hole, the placement of the Nelaton catheter in subdural space is easier and the risk of damaging relevant structures such as cortical tissue or bridging veins is lower. Thus this technique may help to avoid complications when placing a subdural drain.