Raymundo Paraná

Nonalcoholic steatohepatitis and hepatocellular carcinoma: natural history?

onstrated that the gastric mucous cells gain entry into the blood stream after gastric biopsy by using the glycosyltransferase,a4GnT as a cell-specific marker for gastric gland mucous cells. This fact, in turn, strongly suggests that gastric cancer cells could also enter the bloodstream after biopsy of the gastric cancer. Although the presence of circulating gastric cancer cells in peripheral blood do not necessarily lead to the (micro)metastasis of cancer cells, the results of our present study warn that the biopsy of gastric cancer tissues should be kept enough to a minimum for pathological examinations of the gastric mucosa.

Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy

Background and aims: The rates of fibrosis progression in chronic hepatitis C are significantly different between males and females. The antifibrogenic effect of oestrogen has been proposed, possibly via inhibition of stellate cells. The aim of this study was to evaluate the severity of chronic hepatitis C in women, in relation to the menopause, steatosis and hormone replacement therapy (HRT). Methods: From November 2003 to October 2004, women with chronic hepatitis C were enrolled prospectively. A questionnaire was completed prospectively and a blood sample was obtained on the day of biopsy. We identified characteristics associated with moderate/severe fibrosis using univariate and multivariate analysis. Results: 251 women were included in the study. 122 women (52%) were menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe fibrosis (F2–F4, Metavir score) had a longer known duration of infection (>15 years), a higher body mass index and presented with steatosis more frequently than 190 (76%) women with mild fibrosis (F0–F1). Women with F2–F4 were more often menopausal (67% v 47%). The probability of fibrosis F2–F4 was lower for menopausal women receiving HRT (p = 0.012). Steatosis was more frequent and more severe in menopausal women. Conclusions: Severity of fibrosis was associated with a longer duration of infection (>15 years), a higher body mass index, advanced steatosis and the menopause. Menopausal women receiving HRT presented with a lower stage fibrosis. These results reinforce the hypothesis of a protective role of oestrogens in the progression of fibrosis. Steatosis may be implicated in the progression of fibrosis after the menopause.

Association between hepatitis C and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer, the third most common cause for cancer death in the world, a major cause of death in patients with chronic hepatitis C virus infection, and responsible for approximately one million deaths each year. Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of HCC. The incidence of HCC is expected to increase in the next two decades, largely due to hepatitis C infection and secondary cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. Potential preventive strategies in the development of HCC are being recognized. The natural history of HCC is highly variable and the clinical management choices for HCC can be complex, hence patient assessment and treatment planning have to take the severity of the nonmalignant liver disease into account. This review summarizes the inter-relationship between HCV and liver carcinogenesis.

HBV epidemiology in Latin America.

In Latin America, despite the paucity of population studies, hepatitis B is considered endemic. The western Amazonia is a highly endemic area where hepatitis D is also prevalent. In this area, outbreaks of fulminant hepatitis due to H13V and HDV are frequently reported. Non-safe sexual activity seems to be the most important transmission route, but intrafamilial transmission, during early childhood, is extremely significant in Amazonia. The H13V genotype distribution is heterogeneous with a high prevalence of genotype F in the Amazonian region and genotype A in all other areas. In the region where Asian and Italian immigration occurred, genotypes B, C and D are also described.

Intrafamilial prevalence of hepatitis B virus in Western Brazilian Amazon region: Epidemiologic and biomolecular study

Background:  Hepatitis B is endemic in the Amazon region.

Intravenous Vitamin Complexes Used in Sporting Activities and Transmission of HCV in Brazil

Intravenous Vitamin Complexes Used in Sporting Activities and Transmission of HCV in Brazil

Telaprevir twice daily is noninferior to telaprevir every 8 hours for patients with chronic hepatitis C.

BACKGROUND & AIMS We performed an open-label, multicenter, phase 3 study of the safety and efficacy of twice-daily telaprevir in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with cirrhosis. METHODS Patients were randomly assigned to groups treated with telaprevir 1125 mg twice daily or 750 mg every 8 hours plus peginterferon alfa-2a and ribavirin for 12 weeks; patients were then treated with peginterferon alfa-2a and ribavirin alone for 12 weeks if their level of HCV RNA at week 4 was <25 IU/mL or for 36 weeks if their level was higher. The primary objective was to demonstrate noninferiority of telaprevir twice daily versus every 8 hours in producing a sustained virological response 12 weeks after the end of therapy (SVR12) (based on a -11% lower limit of the 95% lower confidence interval for the difference between groups). RESULTS At baseline, of 740 patients, 85% had levels of HCV RNA ≥800,000 IU/mL, 28% had fibrosis (F3-F4), 14% had cirrhosis (F4), 57% were infected with HCV genotype 1a, and 71% had the non-CC IL28B genotype. Of patients who were treated with telaprevir twice daily, 74.3% achieved SVR12 compared with 72.8% of patients who were treated with telaprevir every 8 hours (difference in response, 1.5%; 95% confidence interval, -4.9% to 12.0%), so telaprevir twice daily is noninferior to telaprevir every 8 hours. All subgroups of patients who were treated with telaprevir twice daily versus those who were treated every 8 hours had similar rates of SVR12. The most frequent adverse events (AEs) in the telaprevir phase were fatigue (47%), pruritus (43%), anemia (42%), nausea (37%), rash (35%), and headache (26%); serious AEs were reported in 9% of patients. Rates of AEs and serious AEs were similar or slightly higher among patients treated with telaprevir every 8 hours. CONCLUSIONS Based on a phase 3 trial, telaprevir twice daily is noninferior to every 8 hours in producing SVR12, with similar levels of safety and tolerability. These results support use of telaprevir twice daily in patients with chronic HCV genotype 1 infection, including those with cirrhosis. ClinicalTrials.gov, Number: NCT01241760.

Clinical and histopathological features of NASH in workers exposed to chemicals with or without associated metabolic conditions

Background/Aims: Non‐alcoholic steatohepatitis (NASH) has been associated with exposure to chemicals among workers from an industrial complex in Brazil. We investigated the NASH profile of these individuals associated or not with metabolic conditions.

IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections

Interleukin (IL)‐22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL‐22 may also cause inflammation and abnormal cell proliferation. The binding of IL‐22 to its receptor is competed by IL‐22 binding protein (IL‐22BP), which may limit the deleterious effects of IL‐22. The role of IL‐22 and IL‐22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL‐22 transcripts and inhibit accumulation of IL22‐BP transcripts in schistosome‐infected mice, and that schistosome eggs selectively stimulate production of IL‐22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL‐22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL‐22/IL‐22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL‐22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV‐induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4]). Conclusions: These results provide strong evidence that IL‐22 protects against and IL‐22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL‐22 BP may be an effective strategy to limit cirrhosis. (Hepatology 2015;61:1321–1331)

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800 mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.