Natural History of Cirrhosis: Changing Trends in Etiology Over the Years.

BACKGROUND AND GOALS: The aims of the present study were to investigate the natural history of cirrhosis and to determine trends in the etiology of cirrhosis. METHODS: Between January 2001 and January 2018, a total of 1,341 patients had been diagnosed with cirrhosis and were included. RESULTS: A total of 898 cirrhotic patients, who were followed up for at least 6 months were included into the analysis. The median age was 54 years. The median Child-Pugh and MELD scores were 7.5 and 11, respectively. Ascites (51%) was the most common causes of decompensation. Chronic viral hepatitis was the most frequent cause of cirrhosis (58%). Hepatitis B virus (HBV) infection was the main etiology (34%), followed by hepatitis C virus (HCV) infection (18%). Among 129 patients with cryptogenic cirrhosis (CC), 60 had metabolic abnormalities. If these 60 patients with CC were considered to have nonalcoholic fatty liver disease (NAFLD)-related cirrhosis, the proportion of NAFLD-related cirrhosis increased from 1.8 to 8.0%. At admission, 74 patients (8%) had been diagnosed with hepatocellular carcinoma (HCC). A new HCC developed in 80 patients during the follow-up period. The probability of developing HCC was 3.9% at 12 months. Logistic regression analysis showed that the development of HCC was significantly associated with older age (p < 0.001), male gender (p < 0.001), viral etiology (p = 0.026), and baseline high aspartate aminotransferase level (p = 0.01). Overall, 104 cirrhotic patients died. CONCLUSION: HBV and HCV remain the leading causes of etiology in cirrhosis and HCC. However, NAFLD-related cirrhosis is recognized as a growing burden.

Amantadine in non-responder patients with chronic hepatitis C: a randomized prospective study.

BACKGROUND/AIMS: The management of non-responders (NR) represents the most challenging of all aspects in the care of patients with chronic hepatitis C (CHC). The purpose of the study was to evaluate the efficacy of amantadine. METHODOLOGY: Fourty- three patients with CHC who did not respond to prior combination therapy [IFNα-2a plus ribavirin for 48 weeks] were enrolled into the study. The first group (n=21) was administered pegylated IFN-α2a (180 mcg/week) plus ribavirin (1000-1200 mg/day) and amantadine (200mg/day) for 48 weeks. After discontinuation of therapy, patients were followed-up for an additional 24 weeks. The second group (n=22) received only amantadine (200mg/day) daily for at least 24 weeks (mean 96 weeks) and starting from the 24th week, HCV-RNA was assessed every 12 weeks without discontinuation of therapy. RESULTS: Mean ALT levels before treatment were 115.30 units in the first and 107.73 units in the second group whereas they were 48.38 and 54.76 units, respectively, after the treatment (p<0.001 for both). Sustained viral response rate for the first group at the 72nd week was 52.3% (11/21) (p<0.025). Among patients receiving amantadine, 1 patient became HCV-RNA negative at the 24th and 3 patients at the 48th week (response rate at week 48 was 18.2%), 1 patient at the second year and 1 patient at the fourth year of the treatment (p=0.031). CONCLUSIONS: Amantadine has a potential anti-inflammatory activity that can be a safe alternative for NR-CHC subjects to combination therapy.

Pegylated interferon alfa-2B for chronic delta hepatitis: 12 versus 24 months.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of pegylated interferon (PEG-IFN) alfa-2b for short (one year) and long (two years) terms of treatment for chronic hepatitis D. METHODOLOGY: Eighteen patients with chronic hepatitis D were administered PEG-IFN alfa-2b 1.5µg/kg twice weekly for 1 month, after which they were randomly assigned (2:1) to receive PEG-IFN alfa-2b 1.5µg/kg/wk for an additional 23 months (n=11; group 1) or 11 months (n=7; group 2). All patients were followed-up for 6 months after completing therapy. RESULTS: In group 1, there was no significant difference between HDV-RNA and ALT levels at follow-up compared with baseline (p=0.219 and p=0.624, respectively). However, in group 2, HDVRNA levels, but not ALT levels, were significantly lower at the end of follow-up (EOF) than at baseline (p=0.016 and p=0.237, respectively). Three patients, all in group 2, had undetectable hepatitis B surface antigen (HBsAg) at the end of followup (EOF). However, there was no patient who had undetectable HBsAg in group I (p=0.043). There were statistical differences for all 18 patients in terms of baseline levels of HDV-RNA compared to end of treatment (EOT) (p=0.021) and EOF (p=0.003). CONCLUSIONS: Extending therapy from 12 to 24 months conferred no additional advantage in terms of HDV-RNA suppression and ALT normalisation.

The importance of iron and copper accumulation in the pathogenesis of non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The pathogenesis of non-alcoholic steatohepatitis (NASH) is poorly understood. Hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage. The aim of this study was to investigate the role of hepatic iron and copper accumulation in the development of NASH. METHODS: Fifty-three patients with NASH were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined. Serum iron, serum iron binding capacity (SIBC), transferrin saturation, ferritin, ceruloplasmin, and 24-hour urinary copper level were measured. The presence of stainable iron and copper on liver biopsy specimen was investigated. RESULTS: Serum iron level in 14 (26%) patients, SIBC in 2 (3.7%), ferritin level in 1 (1.9%) and transferrin saturation in 2 (3.7%) patients were elevated. One male patient had abnormality in serum iron metabolism showing the possibility of hemochromatosis. Slightly decreased serum ceruloplasmin level in 4 (7.5%) patients and slightly elevated 24-hour urinary copper amount in 6 (11%) patients were identified. No patients had the abnormality showing the possibility of Wilson disease. NASH was grade I in 25 (47%) patients, grade II in 20 (38%) and grade III in 8 (15%). Fourteen (26%) patients had no fibrosis, 31 (59%) patients had mild fibrosis. None of the patients had bridging or septal fibrosis or cirrhosis. No hepatic iron or copper staining was demonstrated in any patient. CONCLUSION: There was no correlation between hepatic iron and copper accumulation and the development of NASH.