Gregorio Castellano

Effects of lumbar sympathetic block on kidney function in cirrhotic patients with hepatorenal syndrome

We studied the effects of unilateral lumbar sympathetic block on kidney function in eight patients with cirrhosis and hepatorenal syndrome. In five patients with basal glomerular filtration rate (GFR) below 25 ml/min, sympathetic block induced a significant increase in GFR, osmolal clearance, urinary sodium excretion, fractional excretion of filtered sodium (FENa) and effective renal plasma flow (ERPF) and a decrease in plasma renin activity. In the three patients with basal GFR greater than 25 ml/min, sympathetic block produced no significant change in renal function. We conclude that sympathetic block might improve renal function in cirrhotics with hepatorenal syndrome, particularly those with more impaired GFR.

Association of pretreatment serum interferon γ inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C

Background: Increased serum and intrahepatic interferon γ inducible protein 10 (IP-10) levels in patients with chronic hepatitis C (CHC) have been described. Aim: To analyse the possible association of serum IP-10 levels with different outcomes to antiviral therapy. Patients: A total of 137 CHC patients treated with peginterferon plus ribavirin. Methods: Serum IP-10 levels were determined by enzyme linked immunosorbent assay before therapy, after 12 weeks of treatment, and 24 weeks after cessation of therapy. Variables significantly associated with a sustained virological response (SVR) on univariate analysis were included in a multivariate logistic regression model. Results: Pretreatment serum IP-10 levels in patients with SVR were significantly lower than in non-responders (NR) (332.4 (222.1) v 476.8 (305.3) pg/ml, respectively; p = 0.004). Serum IP-10 concentrations significantly decreased in patients with SVR (pretreatment: 332.4 (222.1) pg/ml; post-treatment: 170.2 (140.1) pg/ml; p<0.001) but not in NR (pretreatment: 476.8 (305.3) pg/ml; post treatment: 387.3 (268.1) pg/ml; p = 0.06). By multivariate analysis, non-1 genotype (odds ratio (OR) 3.5 (95% confidence interval (CI) 1.1–10.4); p = 0.003) and low viral load at baseline (OR 0.34 (95% CI 0.14–0.79); p = 0.01) were independent predictors of SVR in all patients. When multivariate analysis was restricted to patients with genotype 1, only baseline viral load (OR 0.38 (95% CI 0.155–0.96); p = 0.04) and pretreatment serum IP-10 levels (OR 0.99 (95% CI 0.996–0.999); p = 0.03) were identified as predictive factors of SVR. Conclusion: Pretreatment serum IP-10 behaves as a predictive factor of SVR to peginterferon plus ribavirin therapy in genotype 1 infected patients.

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation

Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG‐IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)‐ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG‐IFN (1.5 μg/kg/week) and ribavirin (800‐1,000 mg/day) for 12 months. Follow‐up was based on biochemical (ALT), virological (RNA‐HCV), and histological (liver biopsy) examinations. Follow‐up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low γ‐glutamyltransferase GGT (P = 0.04) and HCV‐RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patients compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG‐IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy. Liver Transpl 12:1805‐1812, 2006.

Decreased bone mineral density after therapy with alpha interferon in combination with ribavirin for chronic hepatitis C

BACKGROUND/AIMS Several thousand patients with chronic hepatitis C have been treated with interferon plus ribavirin. After observing a male patient who developed severe bone loss during this treatment, we studied skeletal status and bone mineral metabolism in patients on therapy with interferon plus ribavirin. METHODS Bone mineral density and biochemical bone markers were studied in 32 male patients (31-58 years old) treated for 12 months with either interferon alone (group 1; n=13) or interferon plus ribavirin (group 2; n= 19). RESULTS Bone mineral density was significantly lower in group 2 (0.877-0.07 g/cm2) than in group 1 (1.108+/-0.08 g/cm2, p<0.001). Likewise, T- and Z-score values were also decreased in group 2 (T: -1.95+/-0.6. Z: -1.76+/-0.51) compared with group 1 (T: 0.19+/-0.6; p<0.001. Z: 0.26+/-0.6; p<0.001). Serum and urine biochemical bone markers were normal in both groups. However, urinary calcium excretion was decreased in patients on combined therapy. CONCLUSION Treatment of chronic hepatitis C with interferon plus ribavirin may induce bone loss. This secondary effect should be investigated during the follow-up of these patients, since they may require therapies aimed at prevention or amelioration of these defects.

Malignant lymphoma of Jejunum with common variable hypogammaglobulinemia and diffuse nodular hyperplasia of the small intestine : a case study and literature review

We report a patient with common variable hypogammaglobulinemia and diffuse nodular lymphoid hyperplasia of the small intestine complicated by a jejunal malignant lymphoma. Immunopathological and histological studies showed a polymorphous centroblastic lymphoma with intracytoplasmatic IgM immunoglobulin and lambda light chains. Some mucosal nodules separate from the tumor mass showed atypical lymphoid cell populations similar to lymphoma cells, suggesting a transition between hyperplastic nodules and lymphoma nodules. Four similar cases, and six other patients with malignant lymphoma of the small intestine, associated with diffuse nodular lymphoid hyperplasia, but without immunodeficiency, have already been described. All these cases suggest that nodular lymphoid hyperplasia increases the risk of small intestine lymphoma.

Antimitochondrial antibody-negative chronic nonsuppurative destructive cholangitis. Atypical primary biliary cirrhosis or autoimmune cholangitis?

We investigated whether autoimmune cholangitis (AC) has specific features that constitute an entity other than primary biliary cirrhosis (PBC). We compared clinical, laboratory, and liver biopsy features; response to treatment; and the follow-up of two groups of patients. The first group comprised seven patients with AC criteria-PBC with negative antimitochondrial antibodies (AMAs) and positive antinuclear antibodies (ANAs)-termed the PBC AMA-negative group; the second was made up of another seven PBC patients with positive AMA, labeled the PBC AMA-positive group. We found that the PBC AMA-negative group had, besides negative AMAs and positive ANAs, a significantly higher incidence of asthenia, a higher and earlier incidence of liver failure, and higher ANA titers and serum immunoglobulin G levels than the PBC AMA-positive group. There were no significant differences in the other laboratory tests, although the PBC AMA-negative group showed higher serum bilirubin and aminotransferase and lower serum alkaline phosphatase and immunoglobulin M levels. Liver histological data were similar in both groups. Patients in the PBC AMA-negative group, with more markedly abnormal liver tests, responded to immunosuppressive therapy. We concluded that patients with criteria for PBC but with negative AMAs and positive ANAs have a few specific features that fall between PBC and autoimmune chronic hepatitis. This finding suggests that these patients have a different disease, for which autoimmune cholangitis seems to be an appropriate name.

Effect of intrathoracic pressure on plasma arginine vasopressin levels

Abdominal distention during pneumoperitoneum results in a marked increase in plasma arginine vasopressin levels, which has been ascribed to an increase in intrathoracic pressure. Because of this relationship, tense ascites could contribute to nonosmotic release of antidiuretic hormone, to the development of hyponatremia, and eventually to further ascites formation. The effect of pneumoperitoneum, thoracocentesis, and paracentesis on plasma arginine vasopressin levels was studied in three groups of patients, and the mechanism by which these maneuvers may induce these changes was investigated. Patients with pleural effusion, pneumothorax, or ascites showed a significant increase in plasma arginine vasopressin levels, and thoracocentesis or paracentesis resulted in a decrease in these levels. Plasma vasopressin levels increased significantly during pneumoperitoneum, as did intrathoracic and atrial pressures; the atrial transmural pressure gradient declined. However, no changes in plasma levels of norepinephrine, aldosterone, and renin activity were observed during pneumoperitoneum. Changes in plasma arginine vasopressin levels correlated with the changes in intrathoracic and atrial pressures and transmural pressure gradient. The authors conclude that increased intrathoracic pressure is associated with an increase in plasma arginine vasopressin levels and propose that ascites could be a factor promoting vasopressin release by acting on intrathoracic volume receptors in decompensated cirrhotics.

Diffuse fatty liver in familial heterozygous hypobetalipoproteinemia.

A 34-year-old man had asymptomatic hepatomegaly, slightly increased serum alanine aminotransferase and gamma-glutamyl transpeptidase levels, and a sonographic pattern suggesting diffuse hepatic steatosis. Liver biopsy revealed fatty change in 25% to 50% of hepatocytes. The patient also had low serum levels of cholesterol and triglycerides and met clinical, biochemical, and familial diagnostic criteria of heterozygous hypobetalipoproteinemia. We could not relate his hepatic steatosis to any already known cause of fatty liver and could only attribute it to heterozygous hypobetalipoproteinemia. Familial heterozygous hypobetalipoproteinemia should be ruled out in patients with unexplained hepatic steatosis.

Factors Associated with the Presence of Nonalcoholic Steatohepatitis in Patients with Chronic Hepatitis C

OBJECTIVES:The aim of this study was to identify factors associated with the presence of nonalcoholic steatohepatitis (NASH) in patients with chronic hepatitis C (CHC).METHODS:We studied 98 patients with CHC [47 with NASH (group HCV/NASH), 51 without NASH (group HCV)] and 85 with NASH not infected with hepatitis C virus (HCV) (group NASH). We determined factors associated with the presence of NASH in patients with hepatitis C.RESULTS:Group HCV/NASH patients resembled those with NASH. Body mass index (BMI) was higher in group HCV/NASH than in group HCV, but was similar to group NASH. Most HCV/NASH patients had risk factors for NASH. In patients infected with HCV, NASH and NASH-related lesions were independently associated with BMI, while steatosis score was associated with HCV genotype 3 and BMI. Fibrosis stage was independently associated with steatosis, necroinflammatory activity index, and NASH lesions.CONCLUSION:While HCV genotype 3 infection and BMI are associated with the presence of steatosis in CHC, BMI is the only factor independently associated with the presence of NASH in these patients. We suggest that overweight-related factors might induce NASH in CHC patients.

Lipoprotein changes in patients with chronic hepatitis C treated with interferon-α

Objective:The aim of this study was to evaluate the effects of interferon-α therapy on the lipid profile of patients with chronic hepatitis C.Methods:In 36 consecutive patients with chronic hepatitis C, fasting lipoproteins were evaluated prospectively at baseline, 1, 3 and 6 months during interferon-α therapy and 3 months after the end of treatment.Results:During interferon-α therapy, there was a progressive increase in total and very low density lipoprotein (VLDL)-triglycerides, VLDL-cholesterol and a sustained raise in apolipoprotein (apo) B. In parallel, there was a reduction in high density lipoprotein (HDL)-cholesterol and apo A1 levels. In contrast, total and low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels remained essentially unchanged during interferon-α therapy. Three patients developed chylomicronemia, two of them with severe hypertriglyceridemia, although none of them presented with pancreatitis. Chylomicronemia and severe hypertriglyceridemia were more common in patients with basal triglycerides above 200 mg/dl. Nineteen patients responded to interferon-α therapy, but their lipid profile did nor differ from that of nonresponders. Three months after the end of interferon-α therapy lipid changes subsided, although VLDL and HDL-cholesterol and apo B did not reach basal levels.Conclusion:In patients with chronic hepatitis C, interferon-α therapy is associated with an increase of total and VLDL-triglycerides, VLDL-cholesterol and apo B, and a decline of HDL-cholesterol and apo A1. The development of chylomicronemia and severe hypertriglyceridemia in some cases makes mandatory a close monitoring of triglycerides during interferon-α therapy, particularly among patients with increased triglycerides at baseline.