Hepatitis C is a common cause of end-stage liver disease, and the main indication for liver transplantation in Latin America. Treatment of hepatitis C infected patients improves important long-term outcomes as mortality. Sustained viral response is reached in near 50% of patients with the previous management based in pegylated interferon and ribavirin. Recently new drugs were available increasing sustained viral response significantly, changing the standard of care to triple therapy. This guidelines provides a framework for practitioner in Latin America, to the management of patients with hepatitis C chronic infection. 

Background.

Liver involvement in celiac disease (CD) varies from asymptomatic mild non-specific hepatitis to liver failure. Here we report the first child with liver failure due to a sclerosing cholangitis associated with CD. Case report. An 11 year old girl presented with fatigability for 1 year and jaundice and abdominal distension for 3 weeks. On examination, the growth parameters were below 3rd percentile; she had splenomegaly and severe ascites. Liver function tests revealed elevated liver enzymes (ALT 84 U/L, total bilirubin 98.7 μmol/L, and direct 58.3 μmol/L, gamma-glutamyltransferase 111 U/L, INR 2.7, and albumin 16 g/L). Extensive investigations excluded infectious, metabolic, structural, and endocrine causes of chronic liver disease. Because of the short stature and anemia, CD was suspected, and serological evaluation revealed increased IgA antibodies to tissue transglutaminase (385 units; normal, 0-20 units). Histopathological examination of small intestinal biopsies showed total villous atrophy consistent with celiac disease. Liver biopsy showed bridging fibrosis, portal tract expansion by lymphocytes, plasma cells, and neutrophils, bile ductular proliferation, and periductular fibrosis. Magnetic resonance cholangiography revealed beading and narrowing appearance of intra- and extrahepatic bile ducts. The histopathological and imaging findings are diagnostic of sclerosing cholangitis. The child was initiated on ursodeoxycholic acid, gluten free diet for life, and steroid that was tapered over 3 months. At 3 month follow up, liver function tests completely normalized.

Conclusion.

CD is a potentially treatable cause of liver failure. All patients with severe unexplained liver disease should undergo serological screening for CD.

Hepatic carcinosarcoma (HCS) is defined as a malignant tumor containing an intimate mixture of carcinomatous and sarcomatous elements. Here, we report the case of a 72-year-old man who developed HCS from an otherwise normal liver. The patient had no history of alcohol abuse or hepatitis B or C infection. An enhanced abdominal CT scan revealed a 9-cm heterogeneous tumor, with enhancement during the arterial phase and delayed wash-out in the latter phases. Also, a marked elevation in alpha-fetoprotein level (15,164 ng/mL; normal range, < 10 ng/mL) was noted. He underwent resection of liver segments V and VI under a pre-operative diagnosis of atypical hepatocellular carcinoma (HCC). The diagnosis of HCS was made based on thorough pathologic examination with a panel of immunohistochemical staining. Following surgery, the patient made an uneventful recovery, and at present, 16 months post-surgery, he remains well with no evidence of tumor recurrence. In conclusion, pre-operative diagnosis of HCS is difficult and radical resection in the early stage is encouraged to improve the prognosis of these patients.

A 40-year old woman presented with symptomatic intrahepatic gallstones in one liver segment only four years after cholecystectomy for cholelithiasis. Multiple small, yellow and round calculi were completely removed from the intrahepatic bile ducts via ERCP. The young age of the patient, recurrence of gallstones after cholecystectomy and intrahepatic gallstones suggested a subtype of the low-phospholipid associated cholelithiasis syndrome, a monogenic form of cholesterol cholelithiasis due to variations of the ABCB4 gene that encodes the canalicular phospholipid transporter MDR3.

Background.

MUC2 and MUC5AC overproduction is considered to be associated with hepatolithiasis and related to inflammation. However, mechanisms underlying MUC upregulation under inflammatory stimulation in human intrahepatic biliary epithelial cells (HIBECs) are not completely understood. Material and Methods. Expression of MUC2 and MUC5AC mRNA in HIBECs was detected by real-time PCR. Expression of COX-2, EP4, and phosphorylated ERK, JNK and p38MAPK protein was detected by Western blot. Concentrations of PGE2, IL-1β and TNF-α in cell culture supernatants were measured using the Quantikine Elisa kit.

Results.

COX-2 expression as well as PGE2 production in HIBECs was upregulated significantly by LPS, which was completely blocked by either TLR4 antagonist or NFκB inhibitor. Selective COX-2 inhibitor suppressed LPS-induced MUC2 and MUC5AC mRNA expression remarkably. Exogenous PGE2 increased MUC2 and MUC5AC mRNA expression in a dosage-dependent manner independent of IL-1β and TNF-α. PGE2 receptor EP4 agonist elevated MUC2 and MUC5AC expression, whereas EP4 antagonist had the opposite effect. Expression of phosphorylated p38MAPK was upregulated by exogenous PGE2, and p38MAPK inhibitor reduced MUC2 and MUC5AC expression in HIBECs. In addition, it was found that levels of PGE2, MUC2 and MUC5AC in bile samples from the hepatic ducts affected by intrahepatic stones were significantly higher than those from the unaffected hepatic ducts of patients with hepatolithiasis.

Conclusions.

Our findings indicate that PGE2 induces MUC2 and MUC5AC expression in HIBECs via EP4-p38MAPK signaling.

Background.

The relationships between the metabolic parameters and the endoscopic findings of esophageal varices have been poorly investigated. We investigated the association of the branched-chain amino acids to tyrosine ratio (BTR) with the severity of liver fibrosis and esophageal varices. Material and methods. We studied hepatitis C virus (HCV)-positive chronic liver disease patients who had undergone liver biopsy (n = 149). The relationship between the BTR values and the liver fibrotic stage was investigated. We also studied whether the BTR value was associated with the presence and bleeding risk of varices in patients with HCV-related compensated cirrhosis.

Results.

The mean values of the BTR decreased with the progression of the fibrosis (METAVIR score: F0-1: 6.40 ± 1.19; F2: 5.85 ± 1.33; F3: 5.24 ± 0.97, F4: 4.78 ± 1.14). In the 58 patients with HCVrelated compensated cirrhosis, the mean values of the BTR decreased with the severity of varices (patients without varices: 5.01 ± 1.15, patients with a low-risk varices: 4.42 ± 1.06, patients with a high-risk varices: 3.86 ± 1.02). The BTR value was significantly lower in the patients with varices than in those without varices (4.17 ± 1.07 vs. 5.01 ± 1.15, P < 0.01). The BTR value was also significantly lower in the patients with a high risk of hemorrhage than in those with a low risk (3.86 ± 1.02 vs. 4.78 ± 1.14, P < 0.01). Furthermore, the BTR value was the most significantly different parameter, with the smallest P-value among all the factors examined, including the platelet count and albumin level.

Conclusion.

A decreased BTR value was found to be associated with the progression of liver fibrosis and severity of varices.

Introduction.

Liver cirrhosis is associated with hyperdynamic circulation which can result in heart failure. Transjugular intrahepatic portosystemic shunt (TIPS) due to increase of cardiac output is a stressful stimulus for cardiovascular system. Therefore, new methods for early detection of heart failure are needed. Transmitral flow is a marker of diastolic dysfunction.

Aim.

To analyze short- and long-term effect of TIPS procedure on transmitral flow. Material and methods. 55 patients (38 men and 17 women, 55.6 ± 8.9 years) with liver cirrhosis treated with TIPS were enrolled in the study. Echocardiography was performed before, 24 h, 7, 30 and 180 days after the procedure. During 6 month follow up 22 patients died.

Results.

Left ventricle end-diastolic diameter was increasing during the follow-up [baseline: 47 (44.7-51.2) mm, day 7: 50 (46.5-51.3) mm, p < 0.05; day 30: 49.5 (46.7-55.2) mm, p < 0.01; 6 months: 52.5 (48.3-55.2) mm, p < 0.01)]. The peak early filling velocity (E) was significantly increasing [before: 75.5 (60.5-87.3) cm/s, 24 h: 88 (74.3-109.7), p < 0.01; day 7: 89 (81.5-105) p < 0.01; 1 month: 94 (82.7-108.5) p < 0.01; 6 month: 91 (80.1-120.2) p < 0.01]. Peak late atrial filling velocity (A) significantly increased within 24 h after the procedure: 85.1 (76.2-99.5) vs. 91.2 (81.5-104.5) cm/s, p < 0.05. The E/A ratio was increasing during the follow up (baseline: 0.88, 24 h after: 0.89, 1 week: 1.0, 30 days: 1.13, 6 month: 1.06 p < 0.01).

Conclusion.

Hemodynamic changes following TIPS procedure can be monitored using echocardiography. Transmitral flow analysis can serve as a useful tool for evaluating of diastolic function in these patients.