Doppler parameters of hepatic and renal hemodynamics in patients with liver cirrhosis.

Introduction. There are limited studies on simultaneous evaluation of liver and renal blood flow using Doppler methods. We evaluated and compared the changes of liver and renal Doppler US parameters in patients with liver cirrhosis according to the degree of liver disease. Material and Methods. We assessed a large spectrum of liver and renal Doppler US parameters in 67 patients with liver cirrhosis. Results. Significant differences between Child's classes or score, as well as MELD score, were observed in all investigated intrarenal blood flow Doppler US parameters, except renal artery peak systolic velocity, but only in some of the hepatic ones. The deviations of renal Doppler US parameters were also related with the complications of liver cirrhosis, as well as serum urea and creatinine levels. There was relationship between Doppler US parameters of hepatic artery and the corresponding renal artery Doppler US parameters. The changes of Doppler US parameters were age independent. Conclusion. Our results show, renal Doppler US parameters correlate with the severity and complications of liver cirrhosis. Because of dynamic deviations of renal Doppler US parameters with advance of liver cirrhosis, we recommend Doppler US of renal artery as a part of follow up of these patients.

Low-dose IL-2 therapy reduces HCV RNA and HBV DNA: case report.

BACKGROUND: Patients with concomitant hepatitis C (HCV) and B (HBV) infection are difficult to treat due to lack of medicines that control these viral infections and the high risk of hepatocellular carcinoma. Currently, there are insufficient data regarding the therapeutic effect of interleukin-2 (IL-2) during chronic viral infection, but this cytokine has shown antineoplastic activity and may have also an antiviral effect. CASE REPORT: We present the case of a 44-year-old patient with hemophilia A, HBV and HCV related compensated liver cirrhosis (Child-Pugh A) with several zones in the liver, highly suspicious for hepatocellular carcinoma. The patient was treated with low-dose intermittent subcutaneous IL-2 immunotherapy, followed by standard therapy with pegasys and copegus. During 23 months' follow-up, no tumour progression occurred, and the patient remained in Child-Pugh A stage. The initial HCV and HBV loads were significant (538,207 IU/ml) and minimal (825 copies/ml), respectively. The patient was treated with intermittent subcutaneously applied low-dose IL-2 cycles for ten months. HBV DNA and HCV RNA were undetectable 3 months after the last IL-2 cycle. After cessation of IL-2 therapy, the patient received standard antiviral treatment with pegasys and copegus. Nine months later, a slight reactivation of viruses was observed: HBV DNA was 18,600 copies/ml and HCV RNA was 58 IU/ml. Twenty-three months after the last IL-2 treatment (at the time of writing), the patient is alive and in a good clinical condition. CONCLUSION: The decrease of HBV and HCV nucleic acids during immunotherapy with IL-2 predicts a possible new therapeutic option for these chronic viral infections.

A case of hepatocellular carcinoma (HCC): treatment with local application of alcohol and interleukin 2 (IL-2).

A case of an inoperable hepatocellular carcinoma due to liver cirrhosis is presented. Surgical treatment was not clinically warranted. So we decided to induce tumor necrosis by intratumoral injections of 10 mL of ethanol followed by two treatments with 9 x 10(6) U Chiron interleukin-2 with an interval of 1 month. This ethanol-interleukin-2 cycle was repeated three times with intervals of 6 months. Interleukin-2 injections were given by a fine needle, under ultrasound control in the periphery and in the center of the tumor. The initial size of the tumor was 55-60 mm. During the follow-up period of 2 years the tumor size remained relatively unchanged. The patient died due to gastric hemorrhage. The treatment elicited no adverse clinical effects. The clinical status improved greatly after this treatment. Local interleukin-2 application after alcohol-induced tumor ablation might be an alternative if surgical treatment is not warranted.

Non-melanoma and non-renal cell carcinoma malignancies treated with interleukin-2.

Some positive results have been observed after interleukin-2 treatment, especially in melanoma, and pulmonary metastasis of renal carcinoma. The aim of the following article is to analyze the response to interleukin-2 in patients with non-melanoma and non-renal cells malignancies. The response was studied with reference to the interleukin-2 dose, the way of application, the kind of tumor and the other treatments. A database search was performed to trace studies describing interleukin-2 tumor treatment in non-melanoma and non-renal cells malignancies, published between 1.1.1999 and 30.01.2001. We found 38 communications for the use of interleukin-2 in a total of 1030 patients. The literature review suggests that the optimal way of application of interleukin-2 in metastatic colorectal carcinoma is the local use in a low dose, with intervals between applications, for 4-6 months, after some pretreatment. In unresectable pancreatic head carcinoma a total response was 85% with twice prolonged survival. In malignant mesothelioma--stable disease was achieved in 56% with potential advantages of local application. In hematological malignancies interleukin-2 treatment was followed by remission or increase in immune defense depending on the histological type. In breast cancer interleukin-2 induced immunologically functional graft. Metastatic pulmonary carcinoma has a favorable prognosis concerning response and survival. The maintenance treatment with low doses of interleukin-2 in responders to previous chemotherapy is promising. Better results are observed with lower dose, cyclic application and combining chemotherapy. Cycles with longer duration (4-6 months) have a better effect also for patients with response to former treatment.

Lamivudine induced stable reversal in HBV liver cirrhosis Child C: a case report.

A 40-year-old viremic woman with HBV related liver cirrhosis (Child-Plugh - C) received 100 mg lamivudine daily for 24 months. Initially the patient was with hepato-splenomegaly, marked ascites and mild jaundice. There were no signs of portal encephalopaty and gastrointestinal haemorrhage. The baseline ALT was about 6 times above the upper limit of normal. Hypoalbuminemia of 29 g/l as well as hyperbilirubinemia of 40 mmol/L and decreased protrombin index of 47% was found. Serological tests showed positive serum HBsAg and anti-HBe antibodies. The patient was HBeAg negative, but with detectable serum HBV DNA (500 pg/mL) by dot-blot hybridization HDV, HCV and HIV co-infections were excluded. A marked improvement in liver function had been found at the end of the third month of therapy, with normalization of bilirubin and ALT activity. Serum albumin and protrombine index increased from 29 g/l to 36 g/l and from 47% to 92%, respectively. The patient was without ascites and Child-Plough score decreased from 10 to 5 points. Serum HBV DNA rapidly decreased at the end of first treatment month and was undetectable three months after the initiation of lamivudine therapy. We found two viremic episodes during the lamivudine treatment. However, Child-Pugh score did not increased and the patient remained with compensated liver disease and with lower ALT than baseline value. The main question is haw long such patients have to receive the lamivudine treatment.

Characteristics and trends in macrolide resistance among Helicobacter pylori strains isolated in Bulgaria over four years.

Macrolide resistance trends were examined among Helicobacter pylori strains from 154 patients between 1994 and 1998. Applicabilities of screening agar method (SAM) and modified disk diffusion method (MDDM) were evaluated. Overall primary resistance rates to erythromycin and clarithromycin were 14.8% and 8.7%, respectively. No association was found with age, sex, and diseases. Clarithromycin-resistance rate reached 12.5% in the last 2 years. Secondary resistance to erythromycin occurred more often (in 62.5%) than to clarithromycin (in 42.9%). Therapy with spiramycin or erythromycin in four cases induced no clarithromycin resistance. These data show a considerable prevalence of H. pylori resistance to macrolides, which exhibited a tendency to increase and was often associated with metronidazole resistance. By comparing the MDDM with SAM, an overall agreement was obtained in 81 (94.2%) of 86 results. MDDM and SAM are reliable techniques for testing H. pylori susceptibility to macrolides.

Chronic HBV infection. Immunomodulation with levamisole in viremic HBeAg positive or anti-HBe positive patients--a pilot study.

BACKGROUND/AIMS: We evaluated the effect of immunomodulatory treatment with levamisole in HBeAg positive or anti-HBe positive patients with chronic HBV infection and ongoing viral replication. The majority of patients had an expected poor response to IFN-alpha. METHODOLOGY: Twenty-five viremic patients (15 males and 10 females) with chronic HBV infection were treated with Levamisole for 12 months or until negative serum HBV DNA occurred for at least 3 months. Viral replication and aminotransferase activity were controlled at the end of 3, 6, 9 and 12 months during the treatment. RESULTS: A decrease of serum HBV DNA was noted when serum HBV DNA levels before and after treatment with levamisole were compared, by t-test for dependent samples (p < 0.05). There was a significant reduction of ALT activity, too. HBV DNA fell below the detection limit of our assay at the end of 3, 6, 9 and 12 months in 7, 7, 8 and 10 of the patients, respectively. In 3 of 16 initially HBeAg positive patients, seroconversion to anti-HBe antibody occurred. At the end of 12 months 10 patients were with negative serum HBV DNA and normal ALT activity. Two of them lost HBsAg during the treatment. Ten patients were without any effect from the therapy. The potential responder initially is anti-HBe positive, with low serum HBV DNA < 500 pg/ml and low ALT activity (< 3 times the upper limit of normal). CONCLUSIONS: Immunomodulation with levamisole may benefit some patients with chronic ongoing viral replication including patients with expected poor response to IFN-alpha. This treatment could be used as an alternative therapeutic schedule in patients contraindicated for IFN-alpha, and also because it lowers treatment costs.

Liver damage score--a new index for evaluation of the severity of chronic liver diseases.

BACKGROUND/AIMS: Many hepatologists believe that the Child's classification is not the ultimate prognostic tool for liver disease. Our aim was to develop an index for the estimation of the severity of liver damage, to evaluate its predictive power for the short-term and long-term prognosis of patients with chronic liver disease, and for the estimation of the effect of different therapeutic regimens. METHODOLOGY: The Liver Damage Score (LDS) was developed based on the analysis of the laboratory data of 151 randomly selected patients with liver diseases. Variables for reduced protein synthesis, increased production of antibodies, cytolysis, cholestasis, functional renal failure were combined into LDS according to the results of cluster analysis. The evaluation of the liver injury was analyzed in 696 patients with different liver diseases. RESULTS: There are three groups of liver diseases: mild-with LDS of 1-2 U, moderate with LDS 3-4.5 U and severe with LDS > 5.0 U. There was a good correlation between the LDS and the scores for liver cirrhosis. Values above 4-6 U carry bad prognosis. The LDS truthfully reflects the evolution of liver diseases over time and the effect of therapy. CONCLUSION: The LDS is a new, simple, low-cost, biomathematically and pathophysiologically based index, useful for monitoring practically all patients with liver diseases, no matter what the etiology and stage of the liver injury is. It allows a quantitative expression of the disease severity and the improvement or deterioration in its course.

Ebrotidine versus ranitidine in the treatment of acute duodenal ulcer. A multicentre, randomized, double-blind, controlled clinical trial.

A total of 478 patients with endoscopically confirmed duodenal ulcer entered this randomized, parallel, double-blind trial. Patients were randomly assigned to receive ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfona mid e, CAS 100981-43-9, FI-3542) 400 mg or ranitidine 300 mg tablets (4:1) respectively, administered in single evening doses. Endoscopy, clinical examination and symptom assessment were performed at baseline and at weeks 4 and 8. Safety evaluations including laboratory tests, treatment compliance and antacid consumption checks were conducted at the beginning and/or at the 4 and 8 week visits. Patients whose ulcer showed endoscopic healing at the 4-week control left the study. Both groups were matched in all parameters studied. The healing rates at 4 weeks were 76.4% and 75.3% for ebrotidine and ranitidine respectively, while at 8 weeks the final rates were 95% and 91.8% respectively. Accompanying symptoms disappeared rapidly and the patients returned to normal. Smoking proved to be a highly significant negative risk factor, since healing rates were 83.4% and 71.2% at 4 weeks and 97.4% and 92.3% at 8 weeks in non-smokers and smokers respectively (p = 0.0046). Smokers treated with ranitidine showed significantly lower final healing rates than non-smokers (86% vs 100%; p = 0.0358), while the healing rates among patients treated with ebrotidine were similar regardless of whether they were smokers or not (93.9% and 96.7% N.S.). Ebrotidine (94%) proved to be more effective than ranitidine (86%) in smokers with higher healing rates (p < 0.05). Alcohol intake showed no significant relationship with the healing rates. Both drugs demonstrated an excellent safety. There were no changes in blood parameters, and no significant adverse events were reported.

Hepatitis C virus infection: a possible promoting agent in porphyria cutanea tarda.

The study aimed to differentiate the factors triggering porphyria cutanea tarda, paying special attention to the presumed role of hepatitis C virus infection. In a representative Bulgarian contingent, HCV-antibodies were identified using ELISA II and immunoblot. Seropositivity was significantly higher (p < 0.01) in the sporadic form (36 out of 57 patients; 63.2%) compared with the familiar form (4 out of 20 subjects; 20%). Alcohol abuse was the most common factor preceding the expression of open porphyria both in the sporadic and the familiar forms. In 10 sporadic cases, no precipitating factors were observed, except for the fact that they were anti-HCV positive. In another 2 anti-HCV positive patients, porphyria cutanea tarda was preceded by blood transfusions. Renewed consumption of alcohol after successful treatment was a common reason for relapse, but relapses were most frequent in anti-HCV positive patients (35 relapses in 12 patients), in whom other promoting factors were absent. Analysis of triggering factors shows that most probably hepatitis C virus infection could contribute to the expression of porphyria cutanea tarda and the association of both diseases is not coincidental.

Quantitative assessment of severity of biliary tract infection.

BACKGROUND/AIMS: It is very important for physicians to evaluate the severity of the biliary infection. At the moment, there is no useful quantitative system. In this study, we propose a scoring system for assessing the severity of biliary infections and evaluation of the efficacy of antibacterial and endoscopic treatments. MATERIALS AND METHODS: We created a biliary tract infection score (BTIS) including local physical and ultrasound findings, signs of inflammation and hepatobiliary involvement. The BTIS was calculated in 317 patients: group I-155 pts with cholecystitis and cholangitis, treated only by antibiotics and group II-162 pts with acute cholangitis treated by endoscopic procedures. RESULTS: The BTIS allowed the differentiation of the severity of biliary infections: 15.50 +/- 0.52 in acute cholangitis group and 5.77 +/- 2.79 in group I (p < 0.001). The BTIS significantly decreased after antibacterial therapy (excluding only the cefotiam subgroup) and in endoscopicaly treated patients. CONCLUSIONS: The BTIS is a combination of simple, reliable, acceptable and low cost parameters, reflecting the principal pathological processes and degree of abnormalities. A BTIS facilitated the assessment of severity of biliary infection and comparison of the results of various methods of treatment.

Effects of low molecular weight glycoproteins in chronic hepatitis B.

BACKGROUND/AIMS: We evaluated the effect of low molecular weight glycoproteins isolated from animal spleen (Polyerga) in ten patients with biopsy proven chronic HBV infection with ongoing replication. MATERIAL AND METHODS: Polyerga was given intramuscularly trice weekly and orally 3 tablets daily for 24 weeks. The effect on viral replication was evaluated by measuring HBV-DNA and HBeAg in serum. RESULTS: In three out of ten, HDV-DNA became undetectable and ALT decreased (mean pre-treatment ALT 87.2 +/- 55.38SD, mean post-treatment ALT 62.6 +/- 41.86SD p = 0.026 t-test and Wilcoxon test p = 0.014). During the first month of Polyerga application transient increase of serum ALT was observed in 50%. In HBeAg negative patients and in patients with low pre-treatment level of HBV-DNA (below 250pg/ml) there was significant decrease of ALT by t-test (p = 0.022), Wilcoxon (p = 0.028) and Sign test (p = 0.041) in contrast to those with HBV-DNA above 250pg/ml. CONCLUSION: The effect of increasing the cytolysis shows that these drugs are active, probably by increasing the lymphokine secretion and the generation of cytotoxic T-cells. The absence of side effects, its ability to reduce viral replication and lower ALT activity even in patients with liver cirrhosis warrants further studies as a "second drug" or as a drug of choice when IFN is contraindicated.

GI amyloidosis treated with megadoses of i.v. gammaglobulin.

A 50-year-old-man with peripheral edema and muscle cramps without proteinuria as presenting symptoms was found to have hypoproteinemia due to amyloidosis of the stomach. After failure to control the symptoms with diuretics, oral calcium supplement and colchicine, large doses of intact gamma-globulin (250 mg/kg bodyweight, total, 3 separate infusions every other day) infused i.v., helped to control the symptoms for more than 8 months.

Clinical meaning of GGT activity in follow-up of patients with alcohol-related liver injury and cholestasis.

The dynamics of GGT was investigated in three groups of patients after removing some primary causes of GGT increase. Group A included 34 patients with alcohol-related liver disease, group B included 16 patients with alcoholic liver injury and cholestasis, caused by concomitant alcoholic pancreatitis and group C included 17 patients with extrahepatic cholestasis, caused by choledocholithiasis. Follow-up assays of GGT were performed on the 7th, 14th and 30th days. Our results showed that the dynamics of GGT was more rapid after removing the cause for cholestasis than in stopping alcohol consumption in patients with chronic liver diseases. On the 14th day more than a 50% decrease in GGT activity was noted in 20% of the patients from groups A and B and in almost all cases from group C. On the 30th day, the reference range of GGT was not attained by any of the patients with liver disease nor in five patients from group C. No significant correlation was found between the severity of liver damage and the extent of GGT increase at the beginning and at the end of the follow-up period.