Anemia as a predictor of response to antiviral therapy in chronic hepatitis C.

BACKGROUND: The standard therapy for chronic HCV infection is the administration of pegylated interferons in combination with ribavirin. Anemia is a dose-dependent side-effect of ribavirin administration. The degree of anemia could be indicative of the individual exposure to ribavirin. AIMS: 1) To evaluate the correlation of HGB level decreases at specified time-points with a sustained virological response during the antiviral treatment. 2) To compare these parameters with the virological predictors for responses. METHODS: A retrospective analysis of cohort, which comprised 164 patients treated with standard therapy at a tertiary center in Prague, Czech Republic. RESULTS: We identified several predictive factors for a sustained virological response in females: baseline HGB level ≤140 g/l (p=0.025), maximum drop from baseline >40 g (p=0.039), and a HGB drop in week 4 >30 g (p=0.044). There was only one predictor identified for males: reaching the lowest HGB level after week 19 (p=0.021). The strongest positive predictor of response was a rapid virological response. A low viral load (<600 000 IU/ml) at baseline was not associated with a sustained response in either gender. CONCLUSIONS: The parameters of HGB decrease during antiviral treatment are better correlated with a sustained response in females. None of these response predicting parameters was as significant as that of rapid virological response as that of rapid virological response (Tab. 4, Fig. 1, Ref. 15).

[Wilsons disease]. / Wilsonova choroba.

Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilsons disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilsons disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The dia-gnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, KayserFleischer ring). The dia-gnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilsons disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc is used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects.

[Liver disorders in diabetic patients]. / Onemocnení jater u diabetiku

There is a mutual relationship between diabetes and liver disorders. Diabetic patients suffer from liver disorders more frequently and, vice versa, patients with liver disorders are at a higher risk of developing diabetes. Diabetes is probably the most common cause of chronic liver disorders in developed countries. Liver disorders related to diabetes include a wide spectrum of conditions, from a simple steatosis related to a slight elevation of liver tests through nonalcoholic steatohepatitis with various degrees of fibrosis up to cirrhosis, hepatocellular carcinoma and acute liver failure. Non alcoholic liver steatosis is the most common pathological condition that is, at present, considered to be a component of or to actually be the liver manifestation of metabolic syndrome, accompanied with an insulin resistance and other clinical components, such as central obesity, dyslipidemia, arterial hypertension and the already mentioned type 2 diabetes mellitus. The steatosis itself is a benign condition and the unfavourable development of the liver disorder is related to an inflammatory reaction (steatohepatitis) and subsequent fibrosis. There is no specific treatment for nonalcoholic steatohepatitis. The basic measures include weight reduction, lifestyle changes and treatment of the concurrent conditions, such as diabetes and dyslipidemia. Formerly popular "hepatoprotective" substances do not play an important role in the treatment of steatohepatitis.

[Hepatic cein catheterisation -  selected assessment aspects]. / Katetrizace jaterních zil -  vybrané aspekty hodnocení

INTRODUCTION: Hepatic vein catheterisation and portal hypertension assessment using the value of portal hepatic gradient (HVPG) is currently a method of choice. METHODOLOGY: In our paper we shall compare HVPG with the so called direct gradient -  using the difference in pressure in the portal vein and free hepatic vein in 5 groups of patients with liver cirrhosis. RESULTS: Hepatic vein catheterisation is reliable for assessing the portal hypertension in the group of patients with liver cirrhosis of ethylic etiology. In patients with liver cirrhosis resulting from hepatitis B, Wilsons disease or primary biliary cirrhosis, a statistically significant difference between HVPG and the direct gradient has been found. In patients with liver cirrhosis resulting from hepatitis C the obtained values differed but without statistical significance. CONCLUSION: In catheterisation of hepatic veins the HVPG value in liver cirrhosis with a presinusoidal component may be reduced, which has to be primarily taken into account when assessing the relationship to some critical values of the portal hepatic gradient.

Sleep disorders in Wilson's disease.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive inherited disease with copper accumulation; neurodegeneration is associated with dopaminergic deficit. The aim of the study is to verify sleep co-morbidity by questionnaire and objective sleep examinations (polysomnography, multiple sleep latency test). METHODS: fifty-five patients with WD (22 hepatic, 28 neurological, five asymptomatic form) and 55 age- and sex-matched control subjects completed a questionnaire concerning their sleep habits, sleep co-morbidity, Epworth sleepiness scale (ESS), and answered screening questions for rapid eye movement (REM) behaviour disorder (RBD-SQ). Twenty-four patients with WD and control subjects underwent polysomnographic examination. RESULTS: unlike the controls, patients with WD were more prone to daytime napping accompanied by tiredness and excessive daytime sleepiness, cataplexy-like episodes and poor nocturnal sleep. Their mean ESS as well as RBD-SQ was higher than that of the controls. Total sleep time was lower, accompanied by decreased sleep efficiency and increased wakefulness. Patients with WD had lower latency of stage 1 and stage 2 of non-rapid eye movement (NREM) sleep and less amount of NREM sleep stage 2. One-third of the patients with WD were found to have short or borderline multiple sleep latency test (MSLT) values independent of nocturnal pathology (sleep apnoea, periodic leg movements and/or restless leg syndrome). CONCLUSIONS: patients with WD often suffer from sleep disturbances (regardless of the clinical form). The spectrum of sleep/wake symptoms raises the suspicion that altered REM sleep function may also be involved.

Acute responses of hepatic fat content to consuming fat, glucose and fructose alone and in combination in non-obese non-diabetic individuals with non-alcoholic fatty liver disease.

We have recently demonstrated that a high-fat load can induce immediate increase in hepatic fat content (HFC) and that such an effect can be modified differently by co-administration of fructose or glucose in healthy subjects. Therefore, we addressed the question how consumption of these nutrients affects changes in HFC in subjects with non-alcoholic fatty liver disease (NAFLD). Eight male non-obese non-diabetic patients with NAFLD underwent 6 experiments each lasting 8 hours: 1. fasting, 2. high-fat load (150 g of fat (dairy cream) at time 0), 3. glucose (three doses of 50 g at 0, 2, and 4 hours), 4. high-fat load with three doses of 50 g of glucose, 5. fructose (three doses of 50 g at 0, 2, and 4 hours), 6. high-fat load with three doses of 50 g of fructose. HFC was measured using magnetic resonance spectroscopy prior to meal administration and 3 and 6 hours later. Plasma triglycerides, non-esterified fatty acids, glucose and insulin were monitored throughout each experiment. HFC increased by 10.4 ± 6.9% six hours after a high-fat load and by 15.2 ± 12.5% after high-fat load with fructose. When co-administering glucose with fat, HFC rose only transiently to return to baseline at 6 hours. Importantly, NAFLD subjects accumulated almost five times more fat in their livers than healthy subjects with normal HFC. Consumption of a high-fat load results in fat accumulation in the liver of NAFLD patients. Fat accumulation after a fat load is diminished by glucose but not fructose co-administration.

Alcoholic liver disease.

Chronic intake of large quantities of alcohol causes damage to many organs, the liver being the most often affected one. In advanced countries, mortality due to liver diseases is directly proportional to alcohol consumption. 30 g of pure alcohol per day is regarded as a "safe" dose. Alcoholic liver disease may take the form of chronic illness (steatosis, steato-hepatitis, fibrosis and cirrhosis) or acute involvement (alcoholic hepatitis). Whereas steatosis is a relatively benign illness, the presence of cirrhosis of the liver means major life expectancy shortening. The actual stage of cirrhosis depends on the presence of complications--portal hypertension with bleeding oesophageal varices, ascites or hepatic encephalopathy. The median survival time of patients with advanced cirrhosis is 1-2 years. Serious alcoholic hepatitis has a mortality record of up to 50%. Absolute abstinence is a sine qua non condition for any treatment of alcoholic liver disease, the other therapeutic procedure are of a supportive nature and questionable significance. Corticoids can be used in the management of serious alcoholic hepatitis. Treatment in the stage of liver cirrhosis is similar to that in cirrhosis of any other aetiology. Cirrhotic patients who demonstrably abstain can be considered for transplantation leading to a markedly prolonged life expectancy.

[Wilson's disease]. / Wilsonova choroba.

Wilson's disease is an inherited disorder leading to accumulation of copper in tissues, mainly in the liver and brain. Genetic defect is in the gene coding ATPase type P (ATP7B). The inheritance is autosomal recessive. Up to now, more then 500 mutations causing Wilson's disease were described. The most frequent mutation in Central Europe is mutation H1069Q. The manifestation of Wilson's disease is usually hepatic or neurologic. Hepatic form is manifested by acute or chronic hepatitis, steatosis or cirrhosis. Neurologic involvement is manifested usually after 20 year of age by motor disturbances (tremor, disturbed speech, problems with writing), which could progress into severe extrapyramidal syndrome with tremor, rigidity, dysartria, dysfagia and muscle contracture. Diagnosis is based on clinical and laboratory examinations (neurologic symptoms, liver disease, low serum ceruloplasmin levels, elevated free copper concentration in serum, high urine copper excretion, and presence of Kayser-Fleischer rings). Confirmation of diagnosis is done by hepatic copper concentration in liver biopsy or by genetic examination. Untreated disease leads to the death of a patient. Treatment is based on chelating agents decreasing the copper content by excretion into urine (D-penicillamine, trientine) or on agents preventing absorption of copper from food (zinc, ammonium-tetrahiomolybdene). Patients with asymptomatic Wilson's disease have to be treated as well. In Czech Republic either penicillamine or zinc are used. Liver transplantation is indicated in patients with fulminant liver failure or decompensated cirrhosis. Screening in families of affected patients (all siblings) is obvious.

[Efficacy of combination treatment with pegylated interferon plus ribavirin in patients chronically infected with HCV]. / Ucinnost terapie pegylovaným interferonem a ribavirinem u pacientu s chronickou HCV infekcí.

THE AIM OF THE STUDY: To evaluate the efficacy of combined antiviral treatment with pegylated interferon alpha plus ribavirin in patients with chronic HCV infection who have not yet been treated with antivirals (treatment-naive patients). To compare the treatment effect in patients with low (< 600,000 IU/ml) and high (> or = 600,000 IU/ml) initial viremia. METHODS AND TREATMENT REGIME: Treatment-naive patients with chronic HCV infection treated with the combination therapy of pegylated interferon-alpha2a plus ribavirin. Treatment response was evaluated at weeks 12, 24 and 48 when treatment was ongoing and at weeks 12, 24 and 48 after the treatment was finished. Commercially available sets from various manufacturers were used for serum and molecular genetic diagnostics of HCV infection. PATIENT SAMPLE: Antiviral treatment was initiated in 175 patients between 2001 and 2007. The complete data sets suitable for statistical analysis were available for 143 patients. End of treatment response and sustained viral response analyses were conducted separately for HCV genotype 1 (n = 124) and genotype 2 + 3 (n = 7). RESULTS: In the genotype 1 group, 76% of patients achieved end of treatment response and 59% of patients achieved sustained viral response. Both types of response were observed in 100% of the genotype 2 and 3 infected patients. When a correlation between initial viremia and sustained viral response was analysed, no statistically significant difference was observed between patients with low (< 600,000 IU/ml) and high (> or = 600,000 IU/ml) initial viremia. CONCLUSION: The results observed in the present study are generally slightly better than comparable results from large registration studies. In contrary to the published literature, the threshold of 600,000 IU/ml for initial viremia did not correlate statistically significantly with SVR.

[Incidence of hiatal hernias in the current endoscopic praxis]. / Výskyt hiátové hernie v bezné endoskopické praxi.

BACKGROUND: Hiatal hernia represents penetration of the oral part of stomach together with the distal part of oesophagus via oesophageal hiatus into the thoracic cavity. On the basis of endoscopic examination hiatal hernia is defined as circular pull out of the gastric mucosa longer then 2 cm from the diaphragm to Z line, measured at the end of examination during removing the endoscope. Hiatal hernia is usually an acquired state which can worsen oesophagitis by holding refluxate and thus by prolonging the duration of purgation. METHODS AND RESULTS: Endoscopic and radiological studies show that 50 to 94 % of patients with gastroesophageal reflux disease have an axial hiatal hernia while in control persons the incidence fluctuates between 13 % and 59 %. Hiatal hernia is a frequent finding during upper gastrointestinal endoscopy. Hernia can contribute to the development of reflux into the proximal oesophagus. A cohort of one thousand patients (18 to 94 years) who underwent upper gastrointestinal endoscopy was analysed retrospectively. Endoscopy was performed between January and June 2005 at the Endoscopic center of the 4th Medical Department of the University Hospital in Prague. CONCLUSIONS: Presented study has shown that in patients who underwent endoscopy, hiatal hernia occurs in 16.6%, more frequently in men (53.6%). The most common type is an axial hiatal hernia with incidence of 94.58%. In 50% of patients with hiatal hernia the reflux oesophagitis of various degrees was diagnosed.

[Diagnostics and therapy of hepatorenal syndrome. Recommendations of of the working group on portal hypertension of the Czech Hepatology Society and the J. E. Purkinje Czech Medical Society]. / Doporuceny postup pro diagnostiku a lécbu hepatorenálního syndromu. Doporucený postup vypracovaný skupinou pro portální hypertenzi pri Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne a schválený výborem Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne.

Hepatorenal syndrome is a functional renal failure in patients with advanced cirrhosis and portal hypertension or acute liver failure. It is caused by extreme vasoconstriction in renal arterial bed. Type I HRS presents as an acute renal failure, while type II HRS is chronic alteration of renal function in patients with refractory ascites. Prognosis of HRS is very poor with survival reaching several weeks in patients with HRS type I. Causal treatment is liver transplantation, other treatment options include use of splanchnic vasoconstrictors (terlipressin) together with plasmaexpansion (albumin) and TIPS. It is important to exclude nephrotoxic medication (non-steroid anti inflammatory drugs, aminoglycosides) and properly treat all infective complications in prevention of HRS.

[The diagnostics and therapy of hepatic encephalopathy. Recommendations of of the working group on portal hypertension in the Czech Hepatology Society and the J. E. Purkinje Czech Medical Society]. / Diagnostika a lécba jaterní encefalopatie. Doporucený postup vypracovaný skupinou pro portální hypertenzi pri Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne a schválený výborem Ceské hepatologické spolecnosti Ceské lékarské spolecnosti J. E. Purkyne.

UNLABELLED: Hepatic encephalopathy (HE) is a set of reversible neuropsychic features which occur in connection with hepatic cirrhosis or acute hepatic failure. We distinguish manifest HE (with clinical symptoms) and minimal FE (normal clinical finding, abnormal psychometric or neurophysiologic exam). The diagnosis is clinical or laboratory one. From the auxiliary examinations in common practice the number connection test is sufficient. THERAPY: Presence of hepatic encephalopathy should lead to the consideration of the possibility to solve basic disease by hepatic transplantation. Conservative therapy lies in 1. Basic disease elimination, 2. Measures lowering the ammonia level in blood--optimalization of protein intake, administration of indigestible disaccharides (lactulose, lactitol) and fill sterilisation by antibiotics (Rifaxin, Metronidazol), ornitine-aspartate administration, 3. Influencing the changes in amino acid metabolism (administration of branched chain amino acids--BCAA). Prognosis depends on the advancement of the disease, after hepatic transplantation the clinical symptoms of HE are mostly fully reversible.

[Protective mechanism of the gastric mucosa]. / Ochranné mechanizmy zaludecní sliznice.

The gastric mucosa represents a masterpiece in the functional design. As the tissue lining the stomach, it secretes aggressive combination of digestive fluids, powerful enough to digest any tissue. Nonetheless, the gastric mucosa remains undamaged by the effect of its inherent protective mechanisms. The possibility of development of gastric erosions and ulcers remains vivid evidence that the gastric mucosa is not always resistant to injury.

[Hepatitis C viral infection at the beginning of twenty-first century]. / Infekce virem hepatitidy C na pocátku 21. století.

The article reviews basic information on the epidemiology, origin, diagnostics and therapy of hepatitis C viral infection. Virus of the hepatitis C was identified in 1989. The most frequent transmission pathway till 1992 was the reception of blood derivatives, after that year, when transfusion centres started to use detection sets to prove anti-HCV antibodies, the incidence of post-transfusion hepatitis C dropped almost to zero. The most common route of transmission at present is the intravenous toxicomany, and significant participation represents the medical care. The basic serological marker of HCV infection is the presence of anti-HCV antibodies. Those antibodies signify markers of the human contact with the virus; they need not automatically mean the encounter of infection. More often it is contrariwise--because the C viral hepatitis develops the chronic stadium up in 85%, the anti-HVC positivity signifies usually the active form of infection. To prove the active form of infection it is necessary to identify viral nucleic acids in the serum of the examined patient. The standard therapy of the chronic form of the C viral hepatitis is at present a combination of pegylated interpherons alpha and ribavirin. Such form of therapy can result the permanent elimination of the virus in about 60% of cases. In the C viral hepatitis neither the specific pre-exposition nor post-exposition prophylaxis is available. The only prevention of the transmission of infection is the avoidance of any risk factor of transmission, namely in the medical care.

[Long-term pharmacological treatment of portal hypertension]. / Dlouhodobá farmakologická lécba portální hypertenze.

Portal hypertension is an unavoidable complication of liver cirrhosis, which usually limits the survival (bleeding from esophageal varices, ascites). Increase in portal pressure is not only due to mechanical obstruction of portal circulation, but there is also a dynamic component (endothelial dysfunction of hepatic microcirculation) and increased blood flow through the splanchnic circulation. For the long-term treatment of portal hypertension two groups of medicaments are available at present: non-selective betablockers (vasoconstriction in splanchnic bed) and nitrates (lowering of intrahepatic resistance). Long-term treatment is necessary in these situations: Primary prophylaxis of bleeding from esophageal varices (in patients, who never bled, but with "risk" varices)--non-selective betablockers; secondary prophylaxis (in patients after variceal bleeding)--non-selective betablockers (possibly with nitrates) or endoscopic treatment. It is clearly documented, that this treatment lowers the risk of the first or repeated bleeding from varices and hence lowers the mortality and morbidity due to this complication in patients with liver cirrhosis. Another serious complication of liver cirrhosis is the spontaneous bacterial peritonitis. All patients after that infection have to receive prophylactic treatment with antibiotics. This treatment should be long life, till the disappearance of ascites or till the liver transplantation.

[Diagnostics and treatment of hepatocellular carcinoma. Recommendations of the Portal Hypertension Working Group of the Czech Hepatology Society and the J.E. Purkinje Czech Medical Society ]. / Diagnostika a lécba hepatocelulárního karcinomu.

Hepatocellular carcionma (HCC) is almost exclusively associated with liver cirrhosis as a significant HCC risk marker in advanced countries. Applicable therapy depends on early diagnosis, and risk patients should be screened for the presence of HCC on a regular basis. Liver ultrasound and determination of alpha-fetoprotein serum levels (AFP) are the screening methods used. Spiral CT is the most often used method for HCC staging. Non-invasive methods may under certain circumstances replace aimed biopsy. There are 3 basic curative therapies for the early stage of HCC: liver transplantation, surgical resection and different methods of local destruction of tumour (i.e., ethanolisation, thermoablation, etc.). Patients at medium stage of HCC may profit from chemoembolisation. Current available systemic chemotherapy is ineffective. Patients with advanced HCC are treated symptomatically. Patient survival prognosis after the application of one of the above treatment methods may be similar with that for HCC free cirrhosis patients, however, prognosis for advanced HCC patients is bad, with survival period from one to nine months.

Intraluminal brachytherapy and selfexpandable stents in nonresectable biliary malignancies--the question of long-term palliation.

BACKGROUND/AIMS: To evaluate the effect of a combination of intraluminal brachytherapy and metallic stent implantation in the treatment of patients with nonresectable biliary tumors. METHODOLOGY: Thirty-two patients aged 41-80 years with nonresectable biliary malignancies--Klatskin's tumor (n = 17), gallbladder carcinoma (n = 11) and carcinoma of papilla Vateri (n = 4)--were treated with a combination of intraluminal brachytherapy (source Ir192, high-dose radiation regimen, total dose 30 Gy) and metallic stent implantation. Intraluminal brachytherapy and stent insertion (metallic, spiral-Z stent) were performed percutaneously in all patients. RESULTS: The mean survival in patients with Klatskin's tumor was 457 days (range: 64-1186; median: 358 days), in patients with gallbladder carcinoma 237 days (range: 92-609; median: 210 days) and in patients with carcinoma of papilla Vateri 850 days (range: 48-1518; median: 1277 days). The rate of 2-year survival in these groups as 27, 0 and 50%, respectively. The survival time differed significantly at the 5% level. The mean time of stent patency was 418, 220 and 850 days, respectively. No complications related directly to intraluminal brachytherapy were observed. CONCLUSIONS: Intraluminal brachytherapy combined with stent implantation is a safe method and appears to prolong survival in inoperable patients with Klatskin's tumor and carcinoma of papilla Vateri compared with nontreated patients in previous studies. In contrast no similar effect should be expected in patients with gallbladder carcinoma.

Double-blind randomized, comparative multicenter study of the effect of terlipressin in the treatment of acute esophageal variceal and/or hypertensive gastropathy bleeding.

BACKGROUND/AIMS: 1) To compare the effect of 2-day application of 0.2 mg terlipressin i.v. every 4 hours (group I) with that of 5-day application of 1 mg i.v. every 4 hours (group II) in the treatment of bleeding esophageal varices and portal gastropathy. 2) To assess the incidence of adverse events. METHODOLOGY: Eighty-six patients with liver cirrhosis (54 men and 32 women, average age 51 years) were randomized over a period of 2 years into 2 groups. Acute bleeding was diagnosed endoscopically within 24 hours of its onset. The two groups fully comparable; treatment failure rated according to "Baveno II". RESULTS: Success rate in group I was 78% at day 2 and 75% at day 5; in group II 89% and 79%, respectively (no statistical significance). Rebleeding had occurred by day 5 in 15% in group I, and in 16.3% in group II. Transfusion needs by day 2 were significantly lower in group II (2.4 units compare to 3.4 units in I). The 30-day mortality was 17.1% in group I and 20% in group II. No statistical difference between I and II in the occurrence of adverse events. CONCLUSIONS: At a dosage of 1 mg i.v. every 4 hours, the success rate at day 2 was as much as 90% while blood consumption was significantly lower compared with the lower dosage. Rebleeding during first 48 hours occurred almost exclusively at lower dosage. There was no increase in the rate of adverse events relative to the higher dosage.

[Transhepatic cholangioscopy in the treatment of choledocholithiasis]. / Transhepatální cholangioskopie v lécbe choledocholitiázy.

Endoscopic methods gained the leading position in the treatment of choledocholithiasis. Transhepatic cholangioscopy and contact lithotripsy is used, if standards methods (ERC) are not successful. The transhepatic approach is predominantly used for the therapy of complicated choledocholithiasis. Cholangioscopy and lithotripsy can be performed after PTC, external drainage of bile ducts and dilatation of intrahepatic channel. The success rate for transhepatic methods is 90 to 100%, the major complication rate is 5 to 7.5%.