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Introduction: Little is known about hepatitis E virus (HEV) infection in patients with cirrhosis. The aim of the present study was to describe the frequency of HEV infection and associated risk factors in patients with cirrhosis from Argentina., Materials and Methods: We evaluated HEV seroprevalence (IgG anti-HEV) and acute infections (IgM and RNA) in patients with cirrhosis (n = 140) vs. healthy controls (n = 300). Additionally, we compared the same outcomes in individuals with alcohol-related cirrhosis (n = 43) vs. patients with alcohol use disorder (without cirrhosis, n = 72)., Results: The overall HEV seroprevalence in the cohort of subjects with cirrhosis was 25% (35/140), compared to 4% in the healthy control group [12/300; OR = 8; (95% CI = 4-15.99); p<0.05]. HEV seropositivity was significantly higher in alcohol-related cirrhosis compared to other causes of cirrhosis [39.5% vs. 12.4%; OR = 4.71; (95% CI = 1.9-11.6); p<0.05] and to healthy controls [OR = 15.7; (95% CI = 6.8-36.4); p = 0.0001]. The HEV seroprevalence in alcoholic-related cirrhosis vs. with alcohol use disorder was 39.5% vs. 12.5% [OR = 4.58; (95% CI = 1.81-11.58); p<0.001]., Conclusion: We found a high seroprevalence of HEV in patients with cirrhosis and in individuals with alcohol use disorder. The simultaneous presence of both factors (cirrhosis + alcohol) showed more association to HEV infection. Larger studies with prospective follow up are needed to further clarify this interaction., Competing Interests: The authors have declared that no competing interests exist.

As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 ± 3.6 and 17.8 ± 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 ± 2.6 and 17.3 ± 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 ± 6.9 and 12.7 ± 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 ± 1.9 and 26.2 ± 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23%, 26%, and 26% and 33%, 43%, and 49% in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE.

Although interferon (IFN)-α is known to exert immunomodulatory and antiproliferative effects on dendritic cells (DCs) through induction of protein-coding IFN-stimulated genes (ISGs), little is known about IFN-α-regulated miRNAs in DCs. Since several miRNAs are involved in regulating DC functions, it is important to investigate whether IFN-α's effects on DCs are mediated through miRNAs as well. In this study, we examined miRNA expression patterns in myeloid DCs (mDCs) and plasmacytoid DCs after exposing them to IFN-α. We report that IFN-α downregulates miR-221 in both DC subsets via inhibition of STAT3. We validated proapoptotic proteins BCL2L11 and CDKN1C as miR-221 targets suggesting that IFN-α can induce DC apoptosis via miR-221 downregulation. In addition, we validated another miR-221 target, SOCS1, which is known to be a negative regulator of JAK/STAT signaling. Consistent with this, miR-221 overexpression in mDCs enhanced the secretion of proinflammatory cytokines IL-6 and TNF-α. In peripheral blood mononuclear cells (PBMCs) of HIV-1/HCV co-infected individuals undergoing IFN-α-based treatment the baseline miR-221 expression was lower in non-responders compared with responders; and miR-221 expression directly correlated with DC frequency and IL-6/TNF-α secretion. In addition to PBMCs, we isolated total liver cells and kupffer cells from HCV-infected individuals and individuals with alcoholic cirrhosis. We found that both total liver cells and kupffer cells from HCV-infected individuals had significantly higher miR-221 levels compared with individuals with cirrhosis. Overall, we demonstrate that IFN-α exerts both antiproliferative and immunomodulatory effects on mDCs via miR-221 downregulation; and IFN-miR-221 axis can play important role in HCV pathogenesis and treatment.

Background & Aims: Occult hepatitis B virus infection (OBI) in patients undergoing liver transplantation (LT) is a suspected source of de novo hepatitis B virus (HBV) infection after LT. This study aimed to investigate the prevalence of OBI in liver transplant recipients with alcoholic cirrhosis and demonstrate the association between OBI and de novo HBV infection after LT in these patients., Methods: Forty-three patients with alcoholic cirrhosis who were negative for HBsAg before LT were recruited in this retrospective study. DNA was extracted from paraffin-embedded native liver tissues and quantified for HBV DNA by real-time PCR. Correlation between de novo HBV infection after LT (positive HBsAg and/or detectable HBV DNA in serum) and detection of intrahepatic HBV DNA before LT was analysed., Results: Detectable HBV DNA in the explanted liver was found in 41.9% (18/43) of the patients and was thus defined as OBI, which was correlated with the presence of serum hepatitis B core antibody (P = 0.008). De novo HBV infection occurred in 18.6% (8/43) of the recipients at a median of 10 months after LT. The rate of de novo HBV infection was 38.9% (7/18) in patients with OBI, compared with 4% (1/25) in patients without OBI (P = 0.004). Furthermore, de novo HBV infection was inversely correlated with the presence of hepatitis B surface antibody in recipients with OBI (P = 0.026)., Conclusion: With a prevalence of 41.9% in liver transplant recipients with alcoholic cirrhosis, OBI in the native liver can predict de novo HBV infection after LT., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Risk factors for hepatocellular carcinoma (HCC) have geographic variability but differences in care have not been described. We reviewed the presentation, management, and outcomes of HCC patients from two tertiary-referral centers in Central Saudi Arabia and Atlantic Canada during 1997-2002., Methods: Data were extracted from health records of 96 Saudi and 80 Canadian consecutive patients with HCC., Results: Mean age (± SEM) of the two groups were similar (64 + 1 and 65 + 1 years) with 93% versus 75% males amongst Canadian and Saudi patients, respectively. In Canada, underlying disease was alcohol-related cirrhosis (45%), cryptogenic cirrhosis (26%), or hepatitis C (13%). For Saudis, HCC cases were attributed to hepatitis C (47%), cryptogenic cirrhosis (27%), and hepatitis B (21%). At initial presentation, Saudi patients had more vascular invasion and distant metastases while Canadians had more advanced liver disease. The tumor-specific prognostic classifications were comparable. Due to center-specific expertise or preference, symptomatic treatment was more common amongst Saudi patients (83% versus 42%) while more Canadians underwent local palliative interventions (52% versus 12%). Frequency of potentially curative therapies including resection and transplantation were similar at both centers. There was no difference in overall median survival (14 versus 10 months) amongst Canadian and Saudi patients., Conclusions: This study validates divergence in HCC presentation between low and high endemic regions for viral hepatitis. In addition, for the first time, differences in cancer care of HCC are documented.

Background and Aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non-alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown., Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end-stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism-based assay., Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over-represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06-2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/(*) carriers), to 97/295 (32.9%; male C/(*) carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001)., Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis., (© 2011 John Wiley & Sons A/S.)

Background: High seroprevalence of human herpesvirus type 8 (HHV-8) in patients with cirrhosis has been reported to be associated with thrombocytopenia. Severe cirrhosis is always complicated with ascites. HHV-8 DNA levels in effusion from patients with primary effusion lymphoma has been reported to be significantly greater than in blood. The status of HHV-8 antibody and DNA in cirrhotic ascites is unclear., Aims: To assess the status of HHV-8 antibody and DNA in cirrhotic ascites compared to that in cirrhotic plasma., Methods: Plasma and ascites samples were collected from 85 patients with cirrhosis. HHV-8 antibody and DNA were detected by immunofluorescence assay and PCR, respectively., Results: Male patients seropositive for HHV-8 antibody were significantly younger than seropositive female patients (p=0.0039). The seropositive rate in patients with cirrhosis was not associated with thrombocytopenia (p=0.6860). Both positive rate and titres of antibody in plasma were much greater than in ascites (p<0.0001). More male or Child-Pugh class C than female or class B seropositive patients were positive for ascites. No hepatitis C virus-related ascites were positive for antibody. Neither plasma nor ascites samples from any subject were positive for HHV-8 DNA., Conclusions: In patients with cirrhosis, the seropositive rate for HHV-8 antibody is independent of thrombocytopenia. The positive rate for HHV-8 antibody in cirrhotic ascites seems to be associated with sex, disease severity and disease aetiology.

The aim of this prospective study was to analyze the incidence of serious infections and changes in immunological markers after liver transplantation (LT) in a cohort of patients with hepatitis C virus (HCV). This study included 34 patients who had LT, 20 patients with HCV etiology (HCV group), and 14 patients with alcoholic etiology (non-HCV group). Patients with HCV were more likely to have severe infections (80%) in comparison with patients in the non-HCV group (42%) (P=0.05). The HCV group had a 3-fold greater likelihood of early severe bacterial infections than the non-HCV group. At 1 week post LT, the HCV group showed higher values of CD19+ B cells/microL than the non-HCV group (P<0.05). At weeks 4 and 12 post LT, the HCV group had lower values of CD19+ B cells/microL (P<0.05). Our data suggest that HCV recurrence after LT was associated with a high incidence of early severe infections and immunological alterations, which may be related to this increased risk.

Background/aims: Alcohol may be a cocarcinogen in patients with chronic viral hepatitis. We investigated the effect of alcohol on the development of hepatocellular carcinoma (HCC) in liver cirrhosis (LC) caused by hepatitis B virus (HBV)., Methods: All patients with LC or HCC associated with HBV or alcohol, admitted between March 2001 and June 2005, were included. Patients were divided into three groups according to the etiology of LC: Alcohol (AL), HBV, or HBV alcohol (HBV AL). Age and laboratory data at the enrollment of study were analyzed. The logistic regression coefficiency for the prevalence of HCC was calculated by using variables such as age, gender, serologic markers, and etiology of LC., Results: In LC patients (n=342), the proportions of AL, HBV, and HBV AL groups were 44%, 39%, and 17%, respectively. The proportions of HCC in AL, HBV and HBV AL groups were 17%, 55%, and 76%, respectively. Age at the diagnosis of HCC was younger in HBV AL than in AL group (p=0.036). In logistic regression analysis for the risk factor of HCC, odds ratio of age was 1.056 (p0.001). Odds ratios of HBV and HBV AL group comparing AL were 8.449 (p0.001) and 17.609 (p0.001), respectively. Therefore, old age and chronic alcohol intake in patients with HBsAg were the risk factors of HCC., Conclusions: Chronic alcohol intake may be an additive factor for the development of HCC in patient with LC caused by HBV. However, a prospective cohort study is needed to confirm these findings.

Background/aims: The aim of this study is to clarify the clinical features of hepatocellular carcinoma that are negative for both hepatitis B surface antigen and anti-hepatitis C antibody., Methodology: Patients were classified according to viral markers: 45 patients (82%) had hepatitis B (B-HCC), 467 patients (82%) had hepatitis C (C-HCC), and 53 patients (9%) had neither hepatitis B nor hepatitis C (NBNC-HCC). Differences in clinical parameters among these three groups were analyzed., Results: Patients with NBNC-HCC were older than B-HCC and C-HCC patients. The incidence of alcoholism in NBNC-HCC patients was higher than in C-HCC patients. Patients with NBNC-HCC had similar rates of positive antibody to hepatitis B core antigen as did patients with C-HCC. NBNC-HCC patients were further classified according to median age. The younger group showed a greater tendency towards alcoholism than did the aged group. Liver functioning in the younger group was worse than in the older group. The older group had larger tumors than the younger group., Conclusions: The livers of younger NBNC-HCC patients were more cirrhotic, possibly because of alcoholism. Older NBNC-HCC patients presented with larger tumors, possibly because they did not receive regular medical check-ups due to their relatively preserved liver function.

Major etiologic factors associated with human hepatocellular carcinomas (HCCs) include infection with hepatitis C (HCV) and hepatitis B virus (HBV), excess alcohol intake and aflatoxin B(1) exposure. While the G-->T p53 mutation at codon 249 has been identified as a genetic hallmark of HCC caused by aflatoxin B(1), the genetic profile associated with other etiologic factors appears to be less distinctive. In our study, we screened HCCs resulting from HCV infection (51 cases), HBV infection (26 cases) or excess alcohol intake (23 cases) for alterations in genes involved in the RB1 pathway (p16(INK4a), p15(INK4b), RB1, CDK4 and cyclin D1), the p53 pathway (p53, p14(ARF) and MDM2) and the Wnt pathway (beta-catenin, APC). Alterations of the RB1 pathway, mainly p16(INK4a) methylation, loss of RB1 expression and cyclin D1 amplification, were most common (69-100% of cases). There was a significant correlation between loss of RB1 expression and RB1 methylation. All 24 HCCs with RB1 promoter methylation lacked RB1 expression, while none of the 67 cases with RB1 expression exhibited RB1 methylation (p < 0.0001), suggesting that promoter methylation is a major mechanism of loss of RB1 expression in HCCs. Alterations of the p53 pathway consisted mostly of p53 mutations or p14(ARF) promoter methylation (20-48%). Mutations of the p53 gene were found at a similar frequency (13-15%) in all etiologic groups, without any consistent base change or hot spot. Mutations of beta-catenin were found in 13-31% of cases, while no APC mutations were detected in any of the HCCs analyzed. With the exception of only 3 of 39 cases (8%), cyclin D1 amplification and beta-catenin mutations were mutually exclusive, supporting the view that cyclin D1 is a target of the Wnt signaling pathway. Overall, the RB1, p53 and Wnt pathways were commonly affected in HCCs of different etiology, probably reflecting common pathogenetic mechanisms, i.e., chronic liver injury and cirrhosis, but tumors associated with alcoholism had more frequent alterations in the RB1 and p53 pathways than those caused by HCV infection., (Copyright 2003 Wiley-Liss, Inc.)

Background: Detectable serum hepatitis C virus (HCV) RNA in HCV patients with persistently normal alanine transaminase (PNALT) has been found to be associated with significant liver damage., Aims: The primary outcome of this study was to compare the histological progression of fibrosis in patients with PNALT and elevated alanine transaminase (ALT)., Methods: Forty patients with PNALT (Group 1) and 41 patients with elevated ALT (Group 2) were recruited into this study. Only patients with fibrosis of F0 to F2 were recruited into this study., Results: The median time to second liver biopsies was 6.3 (range 2.0-11.1) years. Nine patients (22.5%) in Group 1 and 17 patients (41.5%) from Group 2 had progression of fibrosis. There was a trend towards a significantly higher cumulative probability of fibrosis progression in Group 2 (P=0.06). In patients with an initial F0 to F1 fibrosis, there was a significant difference in cumulative probability of fibrosis progression between Groups 1 and 2 (22.6% (7/31) vs. 43.3% (13/31), respectively, P=0.02)., Conclusions: Anti-HCV patients with PNALT with an initial fibrosis of F0 or F1 were less likely to develop progression of fibrosis than those with elevated ALT, although patients with PNALT may have histologically and clinically progressive disease.

Advanced donor age has been considered a risk factor for the use of organs for transplantation. We report the case of an orthotopic liver transplant performed using a 93-year-old donor. The donor had been admitted to the intensive care unit 3 days before due to cerebral hemorrhage. History, viral serology, liver function tests and hemodynamics were normal. At laparotomy, the liver appeared macroscopically normal; histology showed mild parenchymal congestion and focal signs of steatosis (less than 10%). The liver was therefore procured and transplanted into a 52-year-old recipient with alcoholic, post-hepatitis C. cirrhosis. Cold and warm ischemia times were 8 hours 20 min and 67 min, respectively. Production of bile was observed after reperfusion. Six months post-transplantation there is clinical and histological evidence of hepatitis C virus recurrence. Nevertheless, the patient enjoys an acceptable quality of life. Even very old donor livers can be used for transplantation, although it is still debatable whether hepatitis C virus-positive patients are good recipients of such livers.

Goals: We assessed the effect of HCV infection and abstinence from alcohol on survival in a cohort of patients with alcoholic cirrhosis., Background: Hepatitis C virus (HCV) infection may be an important cofactor for liver disease in chronic alcoholics., Study: The study population consisted of 213 patients with the diagnosis of alcoholic cirrhosis, 72 of these patients were infected by HCV. Complete alcohol abstinence after diagnosis of alcoholic cirrhosis was recorded in 86 patients. The reference group consisted of 89 patients with anti-HCV positivity who had never consumed alcohol. Survival was analyzed by the Kaplan and Meier method and predictors of survival by the Cox's multiple regression model., Results: HCV infection was not a determinant factor for survival in alcoholic cirrhosis. Age and Child-Pugh grade at the time of diagnosis of cirrhosis and persistence of alcohol consumption after diagnosis were independent predictors of poor outcome. The cumulative survival curve in abstinent alcoholics was significantly different from that of alcoholics who maintained the same pattern of alcohol consumption (log-rank = 4.30, p = 0.0381). Moreover, the cumulative survival in patients with anti-HCV-positive cirrhosis who stopped drinking after diagnosis was similar to that in patients with HCV-positive cirrhosis who had never consumed alcohol (log-rank 0.26, p = 0.61)., Conclusions: Cumulative survival in alcoholic cirrhosis does not seem to be influenced by the presence or absence of markers of HCV infection. Once liver cirrhosis has been diagnosed in the alcoholic patient, complete alcohol abstinence should be strongly recommended.

Objectives: Patients with alcoholic cirrhosis (AC) are frequently infected with hepatotropic viruses which could alter the clinical spectrum of the disease. We studied the seroprevalence of hepatitis B (HBV) and hepatitis C virus (HCV) and their impact on the clinical profile of patients with AC., Methods: Two hundred and ten hospitalized patients of AC were studied and screened for markers of HBV and HCV infection. Clinical, biochemical and virological correlation was done., Results: One hundred and forty (66.6%) patients had no viral infection Group I, 50 (23.8%) were positive for HBsAg Group II and 20 (9.5%) for anti-HCV Group III. All patients were males with comparable ages (43.9 years, 44 years and 45.9 years respectively). The amount of alcohol consumed by patients in Group III (130 +/- 115 g/d) was significantly less than Group II (204 +/- 130 g/d, P < 0.05) and Group I (281 +/- 188 g/d, p < 0.001). The duration of alcohol abuse was shorter in Group II and III, although not statistically significant. Presentation as jaundice was common in Group II and III (p < 0.05). The AST and ALT values (IU/L) were significantly higher in Group II (239 +/- 351, 197 +/- 266) and III (157 +/- 170, 86 +/- 52) than Group I (89 +/- 78, 66 +/- 54) (P < 0.05). The serum alkaline phosphatase (IU/L) was higher in Group III (349 +/- 223) as compared to Group II (263 +/- 186) and Group I (162 +/- 62) (P < 0.05). There was however, no difference in Child's grade or the discriminant function between the three groups of patients., Conclusions: (i) One-third of the hospitalized patients with AC are infected with HBV or HCV infection, (ii) these infections hasten clinical presentation of patients with alcoholic liver disease, with lesser amount of alcohol consumption and (iii) jaundice, raised ALT/AST and alkaline phosphatase are more common with superadded viral infection.

Background/aims: Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection., Methods: Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation., Results: The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV., Conclusion: Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.

Objectives: To describe the characteristics of anti-HCV positive patients who have died in France., Methods: Prospective study of deceased or transplanted anti-HCV positive patients between January 1994 and February 1996, followed in Gastroenterology and Liver Units in 18 French General Hospitals. Retrospective study of patients with cirrhosis unrelated to HCV infection who died during the same period in 8 of these hospitals., Results: Ninety-seven anti-HCV positive patients, 53 males and 44 females, deceased during the study period (except one transplanted patient), at a mean age of 67 (median: 71), from liver disease in 79% of cases (all had cirrhosis, and 49 hepatocellular carcinoma). The supposed sources of infection were: blood transfusion (44%), intravenous drug use (10%), unknown (46%). All 27 patients (22 men) with a daily alcohol intake of 80 g or more had cirrhosis, and died an average of 10 years earlier. The anti-HVC negative patients with alcoholic cirrhosis who died were three times as numerous, and had similar characteristics to anti-VHC positive alcoholic patients., Conclusion: HCV-infected patients who die of liver disease lose 5 to 10 years of life expectancy, and 10 years more if they drink 80 g or more of alcohol daily.

Background: Although multiple genes are involved in alcoholism and can contribute differently to the risk of dependence and liver damage, no studies have investigated susceptibility to addiction in combination with susceptibility to liver damage due to differences in ethanol metabolism., Methods: We evaluated the role of three polymorphic genes related to alcohol metabolism (CYP2E1) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in Florence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control series of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism methods., Results: No difference was found in the frequency of the CYP2E1 Rsal c2 allele (2.5% among alcoholics and 4.7% among controls) and the DraI C allele (6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1 genotype (B1/B1 or B1/B2) was significantly associated with smoking (p = 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant association, however, emerged in the group of alcoholics, with a five times higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus positive alcoholics., Conclusions: Overall, our results provided no evidence of an increased susceptibility to develop alcoholism that was associated with the three genotypes investigated, either alone or in combination. An increased risk of developing liver cirrhosis for S/S homozygous carriers among alcohol-dependent patients was observed for the first time.

Background/methods: To investigate the prevalence and clinical significance of hepatitis C virus (HCV) infection and its relationship with the development of hepatocellular carcinoma (HCC), 162 consecutive alcoholic patients with cirrhosis were studied. Alcohol intake and parenteral risk factors were investigated by interview using a questionnaire. All patients had consumed at least 80 g alcohol/day for at least the past 5 years. Sera were tested for anti-HCV using a third-generation enzyme immunoassay (EIA), hepatitis B s antigen (HBsAg), anti-HBs, anti-HBc and anti-HIV. Serum HCV-RNA was detected by a one-tube reverse transcription-polymerase chain reaction (RT-PCR) method. Patients were classified into three groups accroding to the presence or absence of viral markers: (i) cases without anti-HCV or HBsAg (group A); (ii) cases with HBsAg only (group B); and (iii) cases with anti-HCV only (group C). Demographic and clinical findings were compared among the three groups., Results: Anti-HCV was present in 17 cases (10.5%) and HBsAg was present in 47 cases (29%). No patient had both anti-HCV and HBsAg. Group C subjects were the oldest, but the duration of drinking in this group was similar to that of group A. There was no significant difference in the daily alcohol intake among the three groups. Previous surgical operations and tattooing were more frequent in group C. Only one patient in group C was an intravenous drug user. The combined rate of HCC was significantly higher in groups B and C than in groups A (34, 23.5 and 6.1%, respectively). Laboratory data showed a higher platelet count, higher albumin level, lower bilirubin level and lower aspartate aminotransferase/alanine aminotransferase ratio in group C patients than in the other two groups. Hepatitis C virus RNA was detected in 14 of 85 cases tested (16.5%), in 11 of 12 cases (91.7%) with anti-HCV and in three of 73 cases (4.1%) without anti-HCV., Conclusions: Hepatitis C virus infection is frequent in alcoholic patients with cirrhosis in Korea. Hepatitis C virus, as well as hepatitis B virus, infection may have a synergistic effect on the development of HCC in alcoholic patients.

In order to analyse the prevalence and significance of cryoglobulinaemia in patients with chronic hepatitis C virus (HCV) infection and the possible relationship of cryoglobulinaemia with the genotypes of HCV, we studied 89 patients with chronic HCV infection, 42 healthy controls and 22 patients with alcoholic cirrhosis. The patients with HCV were divided into three different groups according to the presence of cirrhosis and alanine aminotransferase levels. Moreover, in 20 patients with HCV and cryoglobulinaemia, HCV RNA sequences were quantified in serum and in cryoprecipitate. Cryoglobulins were detected more frequently in patients with chronic HCV infection than in healthy controls (42.6% vs. 4.7%; P<0.0001). Cryoglobulins were present in 68.4% of patients with HCV-related cirrhosis, which was nearly twice the figure in noncirrhotic HCV-infected patients and alcoholic cirrhotic patients. There were no differences in age, sex, aminotransferase levels or HCV genotype distribution in HCV-infected patients with or without cryoglobulinaemia. Only 13% of patients with chronic HCV infection and cryoglobulins showed symptoms of cryoglobulinaemia. There was a linear association between HCV RNA concentration in sera and in cryoprecipitates (P<0.0005). Patients with chronic HCV infection had a high prevalence of cryoglobulinaemia, especially in advanced forms of the disease, but clinical findings are few. There was no relationship with the genotype of HCV. The presence of HCV RNA in cryoprecipitates supported the hypothesis on the aetiological role of HCV in mixed cryoglobulinaemia.

Background: Epidemiological studies have detected up to a 9% incidence of hepatitis G (HGV)-RNA in patients with acute and chronic liver disease of unknown etiology. We sought to clarify the role of HGV as a causative agent in cryptogenic cirrhosis by analyzing archival liver tissue for HGV-RNA in patients undergoing orthotopic liver transplantation., Methods: Using a computer database, we identified 54 patients who underwent orthotopic liver transplantation for cryptogenic cirrhosis. After using rigorous serologic and histopathologic screening guidelines, 20 patients were studied, 7 of whom had concurrent hepatocellular carcinoma (HCC). RNA was extracted from archival paraffin-embedded liver tissue; HGV sequences were amplified by nested reverse transcription-polymerase chain reaction using primers designed from the 5' noncoding region., Results: HGV-RNA was absent from all 20 liver specimens, including those 7 with HCC. Beta-actin RNA, used as a positive control for cellular RNA, was isolated from all 20 liver specimens, including the 7 with HCC., Conclusions: Utilizing a highly sensitive reverse transcription-polymerase chain reaction assay for HGV-RNA, we were unable to detect HGV-RNA within the livers of patients with cryptogenic cirrhosis or in the HCC arising within them. This lends further evidence to HGV infection not being a cause of cryptogenic cirrhosis and not being associated with the development of HCC in cryptogenic cirrhosis.

Objectives: The possibility of "community-acquired" viral infection has been suggested in alcoholics. In order to assess this hypothesis, we evaluated the prevalence of antibodies against hepatitis A virus, a oro-fecally transmitted virus, in heavy drinkers., Patients and Methods: We retrospectively studied 258 heavy drinkers, 188 males and 70 females, divided into sub-groups of increasing age, and compared them to 277 similarly classified blood donors., Results: The prevalence of serum anti-hepatitis A antibodies was significantly higher in alcoholics than in controls (64.7 vs 52.3%, P < 0.01). The difference was particularly marked in patients younger than 45 years old (56.2 vs 39.1%, P < 0.01). In the alcoholics, there was no correlation between the prevalence of anti-hepatitis A antibodies and the socioeconomic level, the quantity of alcohol ingested, or the severity of the underlying liver disease., Conclusion: These results suggest that alcoholism is, per se, a risk factor for viral infections.

Serum HCV-RNA levels were determined by newly developed branched DNA probe (bDNA) assay in 87 patients with hepatocellular carcinoma (HCC), compared with 73 patients with chronic hepatitis active and 30 patients with liver cirrhosis. Patients with decompensated liver cirrhosis (LC-d) had a significant lower viremia (mean 3.2Meg.eq./ml, bDNA positive rate; 40%) than chronic hepatitis active (18.0; 64%) and compensated LC (LC-c, 17.9; 80%) (p < 0.05). Those data indicates that HCV replication may decrease as progression of LC. In contrast, there was no difference between the levels of HCC with LC-c (8.2; 85%) and LC-d (6.1; 89%), and their positive rate of bDNA assay were significantly higher than LC-d without HCC (p < 0.01). Therefore, patients undergoing LC in whom serum HCV-RNA sustained high level may correspond to the high risk group of HCC. In HCC of heavy drinker, serum HCV-RNA levels (11.3; 91%) were significantly higher than the levels (4.6; 79%) of HCC without heavy drink (p < 0.05). The result indicates that heavy drink may induced an increase in HCV replication.

A high prevalence of antibodies against hepatitis C virus (HCV) has been reported in patients with alcoholic cirrhosis. There are, however, doubts regarding the specificity of the first generation anti-HCV antibody assays used. We prospectively investigated HCV status in 47 Sri Lankan patients with alcoholic cirrhosis. A first generation assay (Ortho HCV enzyme-linked immunosorbent assay [ELISA]) and two second generation tests (Abbott HCV enzyme immunoassay and United Biomedical Incorporated HCV enzyme immunoassay) were used. Positive results were confirmed by the second generation recombinant immunoblot assay (RIBA 2). Of the 47 patients (46 males, mean age 41.7 years), 17 (36.2%) had previously had one or more blood or plasma transfusions. Seven (14.9%) of the samples were positive for anti-HCV antibodies using the Ortho-HCV ELISA, but only one (2.1%) sample was positive when tested with the second generation assays. The positive result was confirmed by RIBA 2. The prevalence of HCV in the patients was low despite many of them being exposed to blood or blood products. Hepatitis C virus, therefore, may not be an important pathogenic factor in alcoholic cirrhosis in Sri Lanka.