Libuše Husová

Immunoglobulin G4-Related Cholangitis: A Variant of IgG4-Related Systemic Disease

IgG4-related sclerosing cholangitis as part of IgG4 systemic-related diseases is commonly associated with autoimmune pancreatitis. Major clinical manifestations of IgG4-related sclerosing diseases are apparent in the organs in which tissue fibrosis with obstructive phlebitis is pathologically induced. IgG4-related sclerosing cholangitis is included within the heterogeneous group of ‘sclerosing cholangitis’. Sclerosing cholangitis may be associated with choledocholithiasis, infection or biliary malignancies. Sclerosing cholangitis of unknown etiology is called primary sclerosing cholangitis (PSC). Conservative therapy of PSC is usually unsuccessful, the disease involves extra- and/or intrahepatic biliary tree, and the end point of this disease is liver cirrhosis. Typically, PSC is identified at the age of 30 to 40 years, and the disease is frequently associated with inflammatory bowel diseases. On the other hand, IgG4-related sclerosing cholangitis is not associated with inflammatory bowel diseases. In patients with IgG4-related sclerosing cholangitis, a first symptom can be obstructive jaundice, whereas obstructive jaundice is rarely present in PSC. Clinically, patients with IgG4-related sclerosing cholangitis are older at diagnosis compared to patients with PSC. A typical diagnostic feature of IgG4-related sclerosing cholangitis is elevation of serum immunoglobulin G4. In patients with IgG4-related sclerosing cholangitis, response to steroid therapy is high; in patients with PSC corticosteroid therapy is unsuccessful. Histochemically abundant infiltration of IgG4-positive plasma cells is detected in the biliary duct wall. Histologically, we can identify dense lymphoplasmacytic infiltration of the bile duct wall, transmural fibrosis, lymphoplasmacytic infiltration and fibrosis in the periportal area of the liver – a typically obliterative phlebitis. The biliary epithelium is usually intact in contrast to PSC, where mucosal erosion is often present. Steroids are the first-choice therapy of IgG4-related sclerosing cholangitis. In the literature, cholangiocarcinoma in patients with IgG4- related sclerosing cholangitis was not described, whereas cholangiocarcinoma develops in up to 10–30% of patients with PSC.

Variceal bleeding in portal hypertension: bacterial infection and comparison of efficacy of intravenous and per-oral application of antibiotics--a randomized trial.

Objective To determine the prevalence of bacterial infection in patients admitted to hospital with variceal bleeding in comparison with patients with liver cirrhosis admitted because of another reason. To compare the effect of orally administered antibiotics vs. intravenous antibiotics. Methods Bacteriological investigation of blood culture, urine, throat smear, perianal smear and ascites (polymorphonuclear count as well in ascites) was made in 46 cirrhotic patients admitted to hospital with variceal bleeding and 48 cirrhotic patients admitted because of another reason. Bleeders were treated endoscopically (sclerotization) and pharmacologically (terlipressin 1 mg every 4 h for 5 days), and were randomly allocated to the treatment with oral norfloxacin (25 patients) or intravenous ampicillin/sulbactam (21 patients). Early and late mortalities were evaluated. Results The incidence of infection was high in both groups (63.0% bleeders vs. 54.2% controls), but bleeding patients more often had positive blood culture (17.3% vs. 8.6%) and statistically significantly more positive findings in the throat smears (36.9% vs. 17.3%, P=0.04), which gives the evidence of increased pathological colonization in these patients. No difference in survival was seen in patients with per-oral or intravenous administration of antibiotics. Conclusion Bacterial infection was demonstrated in high percentage in patients with liver cirrhosis admitted to hospital. The administration of antibiotics is indicated in these patients. Intravenous application is probably of the same efficacy as per-oral one.

Spontaneous bacterial peritonitis in the Czech Republic: prevalence and aetiology.

&NA; The aim of the study was to determine the prevalence and detailed data concerning the incidence of spontaneous bacterial peritonitis in the Czech Republic. Ninety‐nine patients with liver cirrhosis and ascites were examined. Spontaneous bacterial peritonitis was diagnosed in 35 patients (35.4%). It was revealed more often in patients with alcoholic aetiology of cirrhosis whose anamnesis involved sub‐febrile or febrile states and the deterioration of ascites. Elevated serum leucocyte counts and increased levels of C‐reactive protein can contribute to the diagnosis. A low level of total protein and albumin in ascites predisposes to the increase of this infection. The reduction of the platelet count in a set of patients with spontaneous bacterial peritonitis indicates the influence of portal hypertension in the aetiology of the disease.

Sarcoidosis associated with interferon-alpha therapy for chronic hepatitis B

Sarcoidosis is one of the possible rare complications of interferon-alpha (IFN-alpha) therapy. Only a few reports have been published on this disease, and these have been associated with the treatment of malignant diseases, essential thrombocytosis, and chronic hepatitis C. We report on a 64-year-old man with chronic hepatitis B (HBsAg, HBeAg, HBV DNA-positive) who was treated with recombinant IFN-alpha-2b (5 MU three times weekly) for 28 weeks. Tolerance to treatment was very good; only a mild flu-like syndrome appeared. Twelve months after completing the therapy, a chest X-ray was performed that revealed bilateral hilar masses, and high-resolution computed tomography (HRCT) of the chest indicated the presence of lymphadenopathy of the anterior and middle mediastinum. Therefore, a right-sided thoracoscopy was performed with excision of a 27-mm lymph node and a histological diagnosis of sarcoidosis was made. No medication for sarcoidosis was indicated. Complete normalization of mediastinal lymphadenopathy (verified on HRCT and chest X-ray) was confirmed 1 year following the thoracoscopy. To our knowledge, this is the first case wherein occurrence of sarcoidosis in a chronic hepatitis B patient treated with IFN-alpha is described. We suppose that IFN-alpha, as a potent stimulator of T-helper 1 (Th1) immune responses, may trigger the compartmentalized Th1 reaction that has been shown to take place in sarcoidosis.

Paracentesis vs. intraperitoneal reinfusion of concentrated ascites — effect on opsonic activity of ascites

Abstract Background. Spontaneous bacterial peritonitis is a frequent and serious complication of cirrhotic ascites. An important defense mechanism of ascites against infection is opsonic activity, where the most important part is played by specific antibodies and C3 and C4 components of complement. The authors wanted to find out whether reinfusion of concentrated ascites or paracentesis can influence this activity. Methods. Twenty-six patients with cirrhosis of the liver and refractory ascites not corresponding to salt restriction and diuretics were divided into two groups. In 14 patients, a total of 25 therapeutic paracenteses were made; in 12 patients, a total of 19 reinfusions of concentrated ascites were performed intraperitoneally. In all patients, levels of IgG, IgA, IgM, C3 and C4 components of complement were assessed in ascites before and 24 h after the intervention. Results. After paracentesis no change of the investigated parameters was found. Reinfusion of concentrated ascites, on the other hand, led to a significant rise of IgG, IgA, IgM, C3 and C4 at the 0.5% level of significance. Conclusion. Treatment of refractory ascites by ultrafiltration and reinfusion intraperitoneally seems to increase opsonic activity of ascites and could be useful in the prevention of the development of spontaneous bacterial peritonitis.

Efficacy of Pegylated Interferon Alpha-2a and Ribavirin Treatment in Chronic Hepatitis C Patients Depends on Various Baseline Parameters and Early Viral Kinetics

OBJECTIVE The aim of the study was to compare efficacy and viral kinetics during antiviral treatment in different chronic hepatitis C patients--naïve, relapsers and non-responders to previous pegylated interferon alpha (PEG-IFN) and ribavirin treatment, with different genotypes, baseline viremia, body weight, age and gender--and to find some baseline parameters which can predict Sustained Virological Response (SVR; negative serum HCV RNA 24 weeks after treatment). MATERIAL AND METHODS 216 chronic hepatitis C patients were treated with PEG-IFN alpha-2a 180 mg/wk and ribavirin 1 000 or 1 200 mg/day. There were 140 men and 76 women, mean age 40, range 19-70 years; 142 (66 %) naïve, 37 (17 %) relapsers after previous PEG-IFN and ribavirin treatment, and 37 (17 %) non-responders to this treatment. 172 (79,6%) has genotype 1 infection, 4 (1,9 %) genotype 2, 34 (15,6 %) genotype 3, 1 (0,5 %) genotype 4 or 6 infection, and 4 (1,9 %) were infected by unknown viral genotype. Quantitative detection of HCV RNA was done at baseline (216 pts.), 24 hours (83 pts.), 14 days (85 pts.), 28 days (88 pts.), and 84 days (211 pts.) after the first dose of PEG-IFN. RESULTS 195 patients have completed the treatment period and 179 patients the 24-week follow-up period. The probability of SVR was significantly higher (P < 0,001) in naïve patients (74/114, 64,9 %) and relapsers (22/30, 73,3 %) than in non-responders (9/35, 25,7 %) and in genotype 3 patients (23/28, 82,1%) than genotype 1 patient (77/143, 53,8 %) (P = 0,002). The patients with SVR comparing those without SVR have significantly lower weight (mean 72,8 kg vs. 79,1, P = 0,008(, were younger (mean 36,2, vs. 45,5, P > 0,001), and had lower baseline viremia (mean 1,014 3 106 IU/mL vs. 2,415 3 106 IU/mL, P > 0,001). SVR was more frequent in women than in men (43/63, 62,8 % vs. 62/116, 53,4 %) but difference was not significant (P = 0,059). Undetectable serum HCV RNA at week 12 was more predictive of SVR than early viral response (minimum 2 log decrease of serum HCV RNA during the first 12 weeks of treatment)--98/122 (80,3 %) versus 104/141 (73,1 %) of SVR. CONCLUSIONS 1) The monitoring of viral kinetics during first 12 weeks of antiviral therapy in hepatitis C patients was an important predictive value for SVR. 2) Negative serum HCV RNA at week 12 was more predictive of SVR than early viral response. 3) The probability of SVR was significantly higher in patients with lower baseline viremia, body weight and younger adults. 4) Gender was not significant for the efficacy of treatment.

Results of interferon-free hepatitis C therapy in the Czech Republic in real-life

Souhrn: Práce prezentuje první reálná data o úspěšnosti bezinterferonové léčby chronické hepatitidy C v ČR. Pacienti byli léčeni kombinovanou terapií paritaprevir/ ritonavir + ombitasvir + dasabuvir s ribavirinem nebo bez něj. Soubor tvořilo 109 pacientů, převážně mužů (62; 57 %). Převládajícím genotypem byl subtyp 1b (101 ze 109 pacientů; 93 %), infekce subtypem 1a byla přítomna u šesti (5 %) a genotypem 4 u dvou (2 %) nemocných. Byli léčeni jak pacienti dříve neléčení – naivní (43 ze 109; 39 %), tak již v minulosti neúspěšně léčení kombinací pegylovaného interferonu a ribavirinu (66 ze 109; 61 %). Setrvalé virologické odpovědi 12 týdnů po ukončení terapie (SVR12) bylo dosaženo u 107 pacientů (98,2 %). Pokud z analýzy vyloučíme dva pacienty, kteří nedosáhli SVR12 z jiného důvodu než virologického selhání léčby, byla úspěšnost léčby 100%. Klíčová slova: chronická hepatitida C – paritaprevir/ ritonavir – ombitasvir – dasabuvir – ribavirin

Mass ascites in Mulibrey nanism

Mulibrey nanism is a rare inherited disease characterized by growth failure and multi-organ manifestations. Mulibrey nanism is extremely rare in the Czech Republic,only this one patient has been reported yet. Mass ascites was the main clinical finding in this 22-year-old male patient. Combined treatment with spironolactone and furosemide improved significantly the patients quality of life and allowed conservative treatment of ascites with no need of repeated punctures. Current clinical status of the patient was satisfactory but various complications in the future are very probable because this patient has multiple organs, especially cardial, impairment.