Ivica Grgurević

Noninvasive Assessment of Liver Fibrosis with Acoustic Radiation Force Impulse Imaging: Increased Liver and Splenic Stiffness in Patients with Liver Fibrosis and Cirrhosis

PURPOSE To evaluate acoustic radiation force impulse imaging (ARFI) of the liver and spleen as a new method for the noninvasive assessment of liver fibrosis (LF). MATERIALS AND METHODS Three groups of 58 examinees were studied: (A) 20 healthy volunteers; (B) 18 patients with chronic viral hepatitis (CVH) B or C having liver fibrosis stages F 1 - 4 (assessed by liver biopsy; Ishak classification); and (C) 20 patients with liver cirrhosis (LC). All participants were examined using the Siemens ACUSON S 2000 Ultrasound Virtual Touch Tissue Quantification system. Ten measurements were performed on both liver lobes and three measurements on the spleen, and the obtained mean values (shear wave velocities [SWV] expressed in m/s) were compared between the groups. In 20 patients the splenic artery pulsatility index (SAPI) was also measured and correlated to the liver and splenic ARFI and histological stage of LF. RESULTS Hepatic ARFI measurements demonstrated a significant correlation to LB results (Spearmans ρ = 0.766; ρ < 0.001) and SWV cut-off values of 1.3 (AUC 0.96) and 1.86 (AUC 0.99) could reliably differentiate between healthy (A) and non-cirrhotic CVH (B), as well as between non-cirrhotic CVH (B) and LC (C). Splenic SWV cut-off value of 2.73 (AUC 0.82) could differentiate between the patients with LC and non-cirrhotic CVH. A significant correlation was also observed between the SAPI and liver ARFI results (ρ = 0.56; p = 0.013). CONCLUSION The hepatic and splenic SWV measured by ARFI increase with the LF stage, and the hepatic SWV correlate well with SAPI. This new technology enables simultaneous morphological, Doppler and elastometric examinations and might improve the accuracy of noninvasive liver fibrosis assessment.

Prevalence of HBV genotypes in Central and Eastern Europe

The importance of hepatitis B virus (HBV) genotypes for disease progression and response to interferon‐alpha‐based treatment is well established. While almost all patients in the Mediterranean area are infected with HBV genotype D, HBV genotype A is dominant in Northern Europe. However, the distribution of HBV genotypes is unknown for several Central and Eastern European countries. Data are described of 1313 HBsAg‐positive patients recruited at 14 referral centers in eight countries. There were only very few cases of HBV genotype B, C, E, F, and H infection while HBV genotypes A and D were found in 42% and 48% of patients, respectively. Eight percent of patients had positive bands for more than one genotype using the hybridization assay. The frequency of genotype A was higher in Poland (77%) and the Czech Republic (67%) as compared to Hungary (47%), Lithuania (41%), Croatia (8%), and Germany (32%). In contrast, HBV genotype D was most frequent in Croatian, Romanian, and Russian patients with 80%, 67%, and 93% of cases, respectively. In conclusion, HBV genotype A versus D showed significantly different distribution patterns in Central and Eastern Europe which deserves consideration for national guidelines and treatment decisions. J. Med. Virol. 80:1707–1711, 2008.

Acute interstitial nephritis due to mesalazine

SUMMARY:  A case of mesalazine‐induced acute interstitial nephritis (AIN) in a 41‐year‐old patient with ulcerative colitis (UC) is reported here. Clinical symptoms such as fever and arthralgia, and laboratory findings such as eosinophilia and renal failure suggested AIN, which was confirmed by biopsy. With withdrawal of mesalazine and intravenous methylprednisolone the patients renal function was recovered. It is observed that early discontinuation of mesalazine is associated with amelioration of interstitial nephritis in most patients, so the recommendation is that patients receiving mesalazine should undergo routine monitoring of renal function. Delayed diagnosis may lead to permanent renal function impairment.

Efficacy of Interferon-α in the Treatment of Chronic Hepatitis C in Dialysis Patients: Two Therapeutic Protocols Compared

Background: Data on the efficacy of particular therapeutic protocols of interferon-α (IFN-α) treatment for chronic hepatitis C in patients on hemodialysis (HD) vary. Aim: To compare the efficacy of two different therapeutic protocols for HD patients. Patients and Methods: 15 hepatitis C virus (HCV)-positive patients on chronic HD at two dialysis centers: 8 patients treated with IFN-α 3 × 3 MU/week s.c. for 6 months (group A), and 7 patients treated with IFN-α 3 × 5 MU/week for 3 months, then 1 × 5 MU/week for another 3 months (group B). End of treatment response (ETR) and sustained virologic response (SVR) were evaluated by HCV-RNA determination. There was no statistically significant difference between the two patient groups according to age, sex, duration of HD and HCV infection. Results: ETR was 87.5% (7/8) in group A and 28.5% (2/7) in group B, being statistically significant (p < 0.05). Although better SVR [50% (4/8) vs. 28.5% (2/7)] and lower drop-out rate [0% (0/8) vs. 28.5% (2/7)] were achieved in group A compared to group B, these differences did not reach statistical significance (p > 0.05). Conclusion: Therapy with IFN-α 3 × 3 MU/week s.c. for 6 months seems to be more appropriate for treatment of hepatitis C in HD patients, mostly due to better tolerability, i.e. lower drop-out rate. These differences could be attributed to different pharmacokinetic properties of the particular therapy protocol.

Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis

Aim Primary: to evaluate predictivity of liver stiffness (LS), spleen stiffness (SS), and their ratio assessed by real-time 2D shear wave elastography (RT-2D-SWE) for adverse outcomes (hepatic decompensation, hepatocellular carcinoma or death; “event”) in compensated liver cirrhosis (LC) patients. Secondary: to evaluate ability of these measures to discriminate between cirrhotic patients with/without esophageal varices (EV). Methods Predictivity of LS, SS, and LS/SS was assessed in a retrospectively analyzed cohort of compensated LC patients (follow-up cohort) and through comparison with incident patients with decompensated cirrhosis (DC) (cross-sectional cohort). Both cohorts were used to evaluate diagnostic properties regarding EV. Results In the follow-up cohort (n = 44) 18 patients (40.9%) experienced an “event” over a median period of 28 months. LS≥21.5 kPa at baseline was independently associated with 3.4-fold (95% confidence interval [CI] 1.16-10.4, P = 0.026) higher risk of event. Association between SS and outcomes was weaker (P = 0.056), while there was no association between LS/SS ratio and outcomes. Patients with DC (n = 43) had higher LS (35.3 vs 18.3 kPa, adjusted difference 65%, 95% CI 43%-90%; P < 0.001) than compensated patients at baseline. Adjusted odds of EV increased by 13% (95% CI 7.0%-20.0%; P < 0.001) with 1 kPa increase in LS. At cut-offs of 19.7 and 30.3 kPa, LS and SS had 90% and 86.6% negative predictive value, respectively, to exclude EV in compensated patients. Conclusion This is the first evaluation of RT-2D-SWE as a prognostic tool in LC. Although preliminary and gathered in a limited sample, our data emphasize the potential of LS to be a reliable predictor of clinical outcomes and the presence of EV in LC patients.

No adverse effect of ABVD chemotherapy in a patient with chronic hepatitis C and Hodgkin’s disease

SummaryThere is insufficient information on the effects of chemotherapy protocols for Hodgkin’s disease (HD) and the course of coexisting hepatitis C virus (HCV) infection. A single literature case reported a patient with HD who developed fulminant hepatitis and hepatic coma after receiving chemotherapy. The case described here is of a female patient previously exposed to prolonged war stress, complicated by intravenous drug abuse and chronic hepatitis C. One year after diagnosis of HCV infection she was diagnosed with HD (nodular sclerosis type II, clinical stage IIIB). The patient received six cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) resulting in complete remission of HD. There was no hepatitis flare either during or after chemotherapy. In conclusion, there were no adverse effects of the ABVD regimen on the course of HCV infection in this patient who was successfully treated for HD. Because concurrent HCV infection and HD is extremely rare, we discuss here the possibility of the synergistic contribution of chronic war stress and hepatitis C infection in the pathogenesis of HD.

Liver Elastography Malignancy Prediction (LEMP) score for noninvasive characterization of Focal Liver Lesions

To analyse elastographic characteristics of focal liver lesions (FLL)s and diagnostic performance of real‐time two‐dimensional shear‐wave elastography (RT‐2D‐SWE) in order to differentiate benign and malignant FLLs.

EUS-Guided Vascular Procedures: A Literature Review

Endoscopic ultrasound (EUS) is continuously stepping into the therapeutic arena, simultaneously evolving in different directions, such as the management of pancreatic and biliary diseases, celiac neurolysis, delivering local intratumoral therapy, and EUS-guided endosurgery. EUS-guided vascular procedures are also challenging, considering the variety of vascular pathology, proximity of the vascular structures to the GI tract wall, high resolution, and real-time guidance offering an attractive access route and precise delivery of the intervention. The literature on vascular therapeutic EUS demonstrates techniques for the management of upper GI variceal and nonvariceal bleeding, pseudoaneurysms, and coiling and embolization procedures, as well as the creation of intrahepatic portosystemic shunts. The paucity of studies, diversity of study designs, and the number of animal model studies hamper a systematic approach to the conclusion and decision making important to clinicians and healthcare policy makers. Nevertheless, theoretical benefits and findings up to date concerning technical feasibility, efficacy, and safety of the procedures drive further research and development in this rather young therapeutic arena.

Leptomeninges as the first and only dissemination site of colorectal cancer

Dear Editor, Colorectal cancer (CRC) is one of the most common cancer types in the world, ranked second in developed countries for both genders, with the incidence of around 70–80 per population of 100,000. CRC disseminates most frequently to liver, lung, and bones, whereas it is rather rare in other organs. The incidence of colorectal adenocarcinoma dissemination to the leptomeninges is not estimated and seems to be quite rare. We report a case of a woman with CRC and the disease dissemination to the leptomeninges as the first and only dissemination site. A 61-year-old woman presented to the infectious diseases emergency room with a one-month history of fatigue, fever, photophobia, and mild headache that progressed to severe headache and vertigo. All of these symptoms appeared shortly after a mild conjunctivitis on both eyes that was treated with tobramycin eye-drops. The patient also emphasized a 1-year history of strabismus of the right eye and substantial weight loss of about 12 kg in a period of several months. She had no history of malignancies or any other serious diseases. Fifteen years ago, she had cataract surgery with a plastic lens implemented in her left eye. Physical examination, except for nonparalytic convergent strabismus of the right eye, was unremarkable with no clinical signs of meningitis. Body temperature was 38.0°C. Upon admission to the infectious diseases ward, a lumbar puncture was performed. The cerebrospinal fluid (CSF) analysis showed hypercellular sterile CSF with predominantly adenocarcinoma cells of unknown origin with elevated total protein level (64.5 g/dL) and low glucose level (1.9 mmol/L—33% of the blood level). The contrast-enhanced computed tomography (CECT) of the brain, made in order to enlighten this finding, did not find any pathological substrate except mild maxillary sinusitis on the left. Computed tomography (CT) of the abdomen was performed thereafter, and a large tumor mass in the ascending colon was found, though the patient had no symptoms or clinical signs of gastrointestinal obstruction. No lesions elsewhere in the abdomen were detected. Chest X-ray examination was normal. Thereafter, the patient was referred to the gastroenterology ward. Physical examination on admission to the gastroenterology ward showed moderate pain on deep palpation in the right iliac region and nonparalytic convergent strabismus of the right eye with hypermature cataract of the same eye. Neurological examination revealed no evidence of motor dysfunction or sensory changes including pathologic reflexes, except the aforementioned convergent strabismus, photophobia, and vertigo. The complete blood count revealed mild anemia with hemoglobin concentration of 114 g/L. Laboratory serum examination results showed high cholesterol (7.56 mmol/L) and triglyceride (2.84 mmol/L) level, increased gamma glutamyl-transpeptidase (90 U/L) and low concentration of iron (2.5 μmol/L). Blood coagulation was also slightly impaired with prothrombin time of 0.93 INR, fibrinogen of 5.8 g/L, and prolonged fibrinolysis. Additionally, C-reactive protein of 31.1 mg/L was detected. Tumor marker carbohydrate antigen 19-9 was highly increased (>1,000 kIU/L) with carcinoembryonic Int J Colorectal Dis (2009) 24:355–356 DOI 10.1007/s00384-008-0560-7

Hepatitis C is now curable, but what happens with cirrhosis and portal hypertension afterwards?

Results from the interferon era have demonstrated reversibility of cirrhosis following viral eradication, but only for patients in the initial stage of cirrhosis. Although direct-acting antivirals (DAA) represent revolutionary treatment of hepatitis C, there are currently no studies showing histological effects of therapy on a large number of cirrhotic patients. However, studies involving transient elastography demonstrated a rapid decrease in liver stiffness after successful DAA therapy, probably due to resolution of inflammation, rather than fibrosis regression, as the latter requires a longer period of time. Reversal of fibrosis and cirrhosis upon viral eradication is a prerequisite for the reduction of portal pressure, but this effect has only been observed for the subclinical stage of portal hypertension (PH). On the other hand, the majority of patients with clinically significant PH remain at risk of decompensation and death, despite hepatitis C virus cure, as PH remains high in this setting. This calls for novel therapeutic approaches.