Microbiota, NASH, HCC and the potential role of probiotics.

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Clearly identifiable risk factors are lacking in up to 30% of HCC patients and most of these cases are attributed to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Beyond the known risk factors for NAFLD, the intestinal microbiota, in particular dysbiosis (defined as any change in the composition of the microbiota commonly found in healthy conditions) is emerging as a new factor promoting the development of chronic liver diseases and HCC. Intestinal microbes produce a large array of bioactive molecules from mainly dietary compounds, establishing an intense microbiota-host transgenomic metabolism with a major impact on physiological and pathological conditions. A better knowledge of these 'new' pathways could help unravel the pathogenesis of HCC in NAFLD to devise new prevention strategies. Currently unsettled issues include the relative role of a 'negative microbiota' (in addition to the other known risk factors for NASH) and the putative prevention of NAFLD through modulation of the gut microbiota.

Sustained complete response of advanced hepatocellular carcinoma with metronomic capecitabine: a report of three cases.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related death. Sorafenib, a multitarget angiogenesis inhibitor, is an approved frontline treatment for advanced HCC in Western countries, although a complete response (CR) to treatment is infrequently reported. Capecitabine, an oral fluoropyrimidine, has been shown to be effect in both treatment-naïve patients and those previously treated with sorafenib. To date, however, only one case of sustained CR to metronomic capecitabine has been reported. CASE PRESENTATION: We describe three cases of advanced HCC treated with metronomic capecitabine where a CR was obtained. In the first case, capecitabine was administered as first line therapy; in the second case, capecitabine was used after intolerance to sorafenib; while in the third case, capecitabine was administered after sorafenib failure. CONCLUSION: Capecitabine is a potentially important treatment option for patients with advanced HCC and may even represent a cure in certain cases.

Fulminant hepatitis in a patient with hepatocellular carcinoma related to nonalcoholic steatohepatitis treated with sorafenib.

We describe a case of acute liver failure in a patient with advanced hepatocellular carcinoma related to nonalcoholic steatohepatitis during sorafenib treatment. A 74-year-old man with diabetes mellitus and hypertension was diagnosed with hepatocellular carcinoma associated with fatty liver. Three weeks after sorafenib therapy, at Eastern Cooperative Oncology Group performance status 3, he developed jaundice, general weakness, flapping tremor, nausea, and anorexia. Sorafenib was stopped: laboratory tests showed a relevant elevation of transaminases suggesting diagnosis of acute hepatitis. During hospital admission, the patient died of liver failure. Sorafenib is the first successful target therapy effective for advanced hepatocellular carcinoma. The most common adverse events are fatigue, hand-foot skin reaction, skin rash/desquamation, diarrhea, and hypertension, whereas liver dysfunction is uncommon. To our knowledge, this is the first patient reported in the literature with hepatocellular carcinoma related to nonalcoholic steatohepatitis who died of rapid worsening of liver function during sorafenib treatment.

Urease-positive bacteria other than Helicobacter pylori in human gastric juice and mucosa.

BACKGROUND AND AIM: Many bacteria carry the urease enzyme in different human ecosystems, but Helicobacter pylori is the only known bacterium showing urease activity in gastric ecosystems. For this reason, the rapid urease test (RUT) on gastric biopsies and urea breath test (C-UBT) are used to detect H. pylori infection. The aim of this study was to evaluate the presence of urease-positive bacteria other than H. pylori in gastric juice and mucosa in hypochlorhydric subjects. METHODS: Twenty-five hypochlorhydric and 10 normochlorhydric patients were analyzed for the presence of H. pylori and bacterial overgrowth both in gastric juice and on the mucosa. During upper gastrointestinal endoscopy at 8.00 a.m. gastric juice samples and biopsy specimens were taken from the antrum and corpus. All samples were analyzed using standard microbiological procedures like aerobic/anaerobic growth, gram-staining, gas chromatography, API test, 96-clone method, and selective medium to search for specific bacteria. In addition, all strains isolated were screened for urease activity using the CP-test. Urease positive strains were tested for the capacity to survive in an acid environment with or without urea (10 mM/L), at pH 7, 4, 3, and 2, respectively, at different times (0, 20, 30, and 60 min). RESULTS: Six hypochlorhydric patients had 10 strains of urease-positive non-H. pylori bacteria among which Staphylococcus capitis urealiticum showed the strongest urease activity. CONCLUSIONS: Hypochlorhydric patients present many urease-positive bacteria other than H. pylori. The strong urease activity may be responsible for false positive results at RUT or UBT test in patients with suspected H. pylori infection.