Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

Ultrasound screening for hepatocellular carcinoma (HCC) in cirrhosis: the evidence for an established clinical practice.

Improvement in our current knowledge of epidemiology, natural history and treatment modalities form the background to generalize the use of ultrasound screening in cirrhosis. The cumulative probability of developing cancer is extremely high in cirrhotics and allows to focus screening programs on a well defined risk group thus maximizing cost-effectiveness. This review article highlights scientific evidences in favour of a generalized practice of US screening.

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Association between HLA class II alleles and protection from or susceptibility to chronic hepatitis C.

BACKGROUND/AIMS: Recent studies have suggested that the course of chronic hepatitis C may be influenced by the immunogenetic background of the host. Specifically, HLA-DR11 (5) has been associated with less advanced hepatitis C virus (HCV)-related liver disease. The aim of the present study was to investigate whether HLA-DRB1*11 subtypes or HLA-DQA1 and DQB1 genes might be associated with protection from or susceptibility to chronic HCV infection, histological severity of HCV-induced liver disease and infecting HCV genotype. METHODS: Ninety-nine unrelated outpatients with histologically documented chronic hepatitis C were studied and their allele frequencies were compared with those of 179 ethnically matched controls and with those of 41 HCV RNA-positive patients with persistently normal aminotransferase levels (HCV carriers). HLA-DQ types and HLA-DRB1*11 subtypes were determined by polymerase chain reaction gene amplification with sequence specific primers. RESULTS: None of 10 DQA1 or 12 DQB1 alleles was significantly associated with susceptibility to or protection from chronic HCV infection or with histological staging or with HCV genotype. However, analysis of DQA1-DQB1 combinations showed that DQA1*0201-DQB1*0201 combination was significantly more frequent in patients compared to controls, both in cis (26.3% vs 16.2%, p = 0.04, odds ratio = 1.8, 95% confidence interval, 0.96-3.5) and in trans (12.1% vs. 1.1%, p = 0.0001, OR = 12.2, 95% CI, 2.6-113.7). HCV carriers did not differ from controls or from patients in the frequency of DQA1-DQB1 combinations. The extended haplotype DRB1*1104, DQA1*0501, DQB1*0301 was seen significantly less frequently in patients than in controls (8% vs 22.3%, p = 0.0025, OR = 0.31, 95% CI, 0.12-0.7) or HCV-RNA carriers (8% vs 26.8%, p = 0.003, OR = 0.24, 95% CI, 0.08-0.73). CONCLUSIONS: Immunogenetic factors may play a role in determining both protection from and susceptibility to chronic hepatitis C, the trans-dimer DQA1*0201-DQB1*0201 predisposing to and the DRB1*1104, DQA1*0501, DQB1*0301 haplotype protecting from chronic hepatitis C.

Are alanine aminotransferase, hepatitis B virus DNA or IgM antibody to hepatitis B core antigen serum levels predictors of histological grading in chronic hepatitis B?

Paired sera and liver biopsies from 105 patients with chronic hepatitis B virus infection (34 HBeAg positive and 71 anti-HBe positive) were studied to investigate the relation between the degree of histological activity and alanine aminotransferase (ALT), hepatitis B virus DNA (HBV-DNA) or IgM antibody to hepatitis B core antigen (IgM anti-HBc) levels. ALT levels were significantly higher in patients with piecemeal necrosis (155 +/- 124 vs 75 +/- 42, p = 0.0017), but there were no differences in the ALT values of patients with or without intralobular necrosis. ALT values were within normal range in 29% of 31 patients without versus 15% of 65 with piecemeal necrosis (p = 0.19). Serum HBV-DNA levels were not related to the grade of lobular or portal/periportal activity in HBeAg-positive patients. Anti-HBe-positive subjects with piecemeal necrosis had higher HBV-DNA levels (34 +/- 93 vs 4 +/- 6, p = 0.01). IgM anti-HBc indexes were significantly higher in patients with intralobular necrosis (0.635 +/- 0.600 vs 0.356 +/- 0.367, p = 0.0005) or piecemeal necrosis (0.671 +/- 0.633 vs 0.321 +/- 0.219, p = 0.0002). In summary, since serum IgM anti-HBc-IMx indexes can reflect the grade of histological activity, the quantitative assessment of this antibody could be useful for non-invasive monitoring of hepatocellular damage in chronic hepatitis B.

[The interstitial photocoagulation with laser light of liver tumors]. / Fotocoagulazione interstiziale con luce laser dei tumori del fegato.

INTRODUCTION: Interstitial laser photocoagulation (ILP) is a recent interventional procedure performed under US or CT guidance which is capable of inducing thermal necrosis in solid tumors. We have used this technique for about 2 years to treat primary and secondary liver cancers. MATERIALS AND METHODS: Thirty-five patients, 20 of them with liver metastases and 15 with HCC, have been examined: 59 lesions in all, ranging in diameter 10 to 65 mm. Forty-nine lesions have been followed-up for at least 2 months and 25 for at least 6 months. The treatment was performed positioning one to six (18-21 G) modified Chiba needles in the lesions to be treated, according to their sizes, under US or CT guidance. The optical fibers (400-800 mu) were then inserted and the Laser was fired to administer 1,000 Joule/session, with 5-10 W power range. The US and CT patterns of the ILP-treated lesions are reported. RESULTS: Dynamic CT examinations 2 months after treatment showed complete tumor destruction in 77.5% of the lesions. The best results were obtained in the lesions < 3 cm phi; in particular, 32/38 lesions (84.2%) < 3 cm and with at least 2 months' follow-up exhibited complete necrosis, as did 6 of 11 lesions (54.6%) over 3 cm phi. When residual tumor tissue was demonstrated, further ILP sessions were useless. We observed only few complications which resolved spontaneously in all cases. CONCLUSIONS: At present, ILP remains an experimental procedure: further studies on larger series of patients and comparison with the results of other interventional procedures are needed to confirm its efficacy in treating primary and secondary liver cancers.

Serum cholesterol and chronic hepatitis C.

Total serum cholesterol levels have been studied in 100 patients with histological diagnoses of chronic hepatitis B and 100 wit chronic Hepatitis C, all without cirrhosis, and two age- and sex-matched control groups (B and C). Mean serum cholesterol levels of the groups were compared also in relation to sex, liver function, duration of the disease, alcohol intake, mass index, liver enzymes, presence of liver steatosis and severity of the liver disease on the basis of the histological activity index. The percentages of patients with serum cholesterol level < 150 mg/dl and > 240 mg/dl were also calculated. The mean serum cholesterol level was significantly lower in hepatitis C: 176 md/dl vs 194 mg/dl of hepatitis B (p = 0.004) and 198 of control C (p = 0.000). Twenty eight hepatitis C patients had serum cholesterol < 150 mg/dl vs 10 with hepatitis B (p = 0.001). In multivariate regression analysis, only the type of virus infection was independent related to serum cholesterol level (p = 0.0063).

Treatment of chronic hepatitis B (HBeAg-HBV DNA-positive) with lymphoblastoid alpha interferon with or without corticosteroids: short- and long-term follow-up.

Efficacy and safety of therapy with lymphoblastoid interferon-alpha alone or combined with deflazacort has been investigated in 38 HBsAg-HBeAg+ patients with biopsy-proven chronic hepatitis. Group I received 5 MU/m2 interferon thrice a week for 26 weeks; group II took interferon for 26 weeks simultaneously with a 6-week course of deflazacort. Follow-up was 18-72 months (median 42). After 12 months, responses were achieved in 3 (18%) out of 17 patients on interferon alone vs 5 (26%, p > 0.05) out of 19 on combined therapy. Blind histological assessment revealed no improvement in either group or in patients who responded to therapy within the first year of follow-up ("early responders"). "Delayed" responses were observed in 4 (29%) patients who took interferon alone vs 5 (36%, p > 0.05) who took the combined therapy. Serum HBV DNA levels decreased significantly during treatment and remained low up to 24 and 36 months of follow-up in both groups. One early responder developed hepatocellular carcinoma, another had exacerbation of liver disease in long-term follow-up. No non-responders developed liver failure or hepatocellular carcinoma. These results indicate that lymphoblastoid interferon-alpha inhibits HBV replication and corticosteroids have no synergistic effect in treatment of HBsAg-HBeAg+ chronic hepatitis.

Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study.

BACKGROUND & AIMS: Viral genotypes have been associated with different severity and outcome of hepatitis C virus (HCV)-related liver disease. The aim of this study was to determine whether HCV genotypes may influence the cirrhosis-related risk of the development of hepatocellular carcinoma (HCC). METHODS: Three groups of patients were studied: 593 patients with chronic hepatitis, 166 patients with HCC and cirrhosis, and 219 patients with cirrhosis but without HCC. A cross-sectional study of frequency distribution and a case-control analysis were performed. HCV genotypes were detected according to Okamoto. RESULTS: HCV type 1b infection was more prevalent among patients with HCC compared with patients with cirrhosis but without HCC (P < 0.01) and chronic hepatitis (P < 0.001). Age, male sex, and HCV type 1b significantly influenced the risk of cancer in cirrhosis by univariate analysis. A pairwise comparison performed on 162 patients with HCC and an equal number of patients with cirrhosis matched by age, sex, and Child's class showed that HCV type 1b was independently associated with HCC (odds ratio, 1.7; P = 0.026). CONCLUSIONS: HCV type 1b is overrepresented in patients with cirrhosis and HCC and significantly influences the risk of HCC in cirrhosis, independent of sex, age, and Child's class.

HLA typing in chronic type B, D and C hepatitis.

AIMS: We aimed to test the hypothesis that susceptibility to chronic HBV, HDV and HCV infections or their pathology is influenced by host genetic factors. METHODS: The Human Leukocyte Antigens (HLA) (A, B, DR and DQ) were determined by microlymphocytotoxicity assay in patients with chronic C (n = 117), B (n = 97) or D (n = 27) hepatitis and their frequencies were compared with those of 489 healthy controls. RESULTS: No statistically significant association was found between any HLA antigen and chronic B or D hepatitis. A significantly higher frequency of HLA-B14 was observed in patients with chronic persistent or active C hepatitis (16.7% of 90 versus 5.9% of 489, chi(2) = 10.9, pc < 0.05, Relative Risk = 3.17, Etiological Fraction = 0.11). The frequency of HLA-DR5 was lower in HCV positive patients (24.8%) than in controls (45%, chi(2) = 15.1, pc < 0.005, RR = 0.4, EF = -0.37). CONCLUSIONS: No correlation could be observed between clearance of HBV or HDV and HLA phenotype. Immunogenetic factors may have a role in determining susceptibility to chronic HCV hepatitis, and in Italian patients HLA-DR5 is a protective factor.

Inflammatory pseudotumour of the liver with malignant transformation. Report of two cases.

Inflammatory pseudotumour is a rare pathologic lesion, of unknown aetiology, rarely involving the liver. Resection seems to be the treatment of choice and it is generally associated with a good prognosis. Histologically, these processes appear to be benign, nevertheless, aggressive courses or recurrences of inflammatory pseudotumour with tumor-like deaths have been reported. The cases of two patients are described who underwent hepatic lobectomy for a liver mass that was diagnosed as liver inflammatory pseudotumour at the initial histopathological assessment: albeit a malignant course followed and both the patients died cachectic. One patient, a 39-year-old man, had an unusually aggressive clinical course and recurrence of the disease with multiple hepatic masses and extension into the thorax six years later. In the other case, in a 28-year-old woman, the hepatic lesion was identified as a low-grade hepatic sarcoma only seven years after surgery.

Liver transplantation for hepatocellular carcinoma: prognostic factors associated long-term survival.

Between December 1985 and February 1995, 260 orthotopic liver transplantations (OLTX) were performed on 238 patients at Niguarda Hospital. Sixty-three patients had hepatocellular carcinoma (HCC); in 13 of the patients HCC was incidental. All patients had negative lymph nodes. According to the Child classification, 13 patients were Child A, 30 Child B, and 18 Child C. According to the TNM classification, 11 patients were stage I, 22 stage II, 15 stage III, and 15 stage IVa. Pre-OLTX chemoembolization was performed on 25 patients. The perioperative mortality rate was 27% (17 patients). Overall survival and disease-free actuarial survival rates at 1, 3, and 5 years were 94%, 76%, 76%, and 83%, 75%, 75%, respectively. Survival curves were compared for 16 different variables. No difference was observed for all parameters analyzed except tumor site, TNM stage, pre-OLTX AFP levels and vascular infiltration. These results seem to demonstrate that the OLTX for unresectable HCC can be considered in specifically selected cases as the treatment of choice. An adequate tumor staging is also necessary for a better patient selection in order to increase survival.

Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma: a multivariate analysis of prognostic factors.

A total of 84 patients with hepatocellular carcinoma and cirrhosis were analyzed retrospectively to investigate prognostic factors. All patients received transarterial oily chemoembolization as the only anticancer therapy. The follow-up range was 1 to 39 mo (median, 9.5 mo). The overall actuarial survival rates at 12, 24 and 30 mo were 62%, 31% and 24%, respectively. According to univariate analysis, variables significantly associated with survival were age, Child-Pugh grade, total serum bilirubin, Okuda stage, tumor size, degree of labeling of the tumor with Lipiodol, gelatin foam use, changes with treatment in tumor size and changes with treatment in alpha-fetoprotein concentration. Two multivariate analyses were performed. When pretreatment and treatment variables were considered, parameters with independent prognostic value were age, Child-Pugh grade, total serum bilirubin, tumor size and degree of Lipiodol labeling of the tumor. When follow-up variables were also considered, we (a) confirmed the prognostic significance of all these parameters (age, Child-Pugh grade, total serum bilirubin, tumor size) and (b) found the independent prognostic value of the change in tumor size (or change in alpha-fetoprotein concentration). Both models yielded different risk coefficients for each class of each variable. Two simple prognostic indexes, based on these coefficients, are proposed: an "initial" index (including pretreatment and treatment variables) and a "follow-up" index (also including follow-up variables). According to the two indexes, the patients were classified into three groups with different prognoses: good (93% and 100% actuarial survival at 1 yr for the initial and follow-up indexes, respectively), intermediate (65% and 53%, respectively) and poor (27% for both indexes).

Diabetic nephropathy: clinical and histological study in 22 patients.

Twenty-two patients with insulin-dependent diabetes mellitus and renal involvement were submitted to renal biopsy. Mean age was 42 years; 10 were males, 12 females. The mean interval between clinical manifestation of nephropathy and biopsy was about 2 years. At the time of biopsy, 4 groups were distinguished according to clinical conditions, depending on the presence or absence of nephrotic syndrome and renal failure. Renal lesions were semiquantitatively evaluated, a separate score being considered for glomerular and vascular lesions. Immunofluorescence most frequently showed a pattern of faint linear IgG deposits along glomerular basement membranes. Severity of histological lesions and pattern of urinary abnormalities were not correlated with the duration of diabetes or the patients' age. Both glomerular and vascular lesions were correlated with the presence of renal failure, while no relationship with the pattern of urinary abnormalities was found. Fourteen patients were followed for more than one year after biopsy: 5 had normal renal function, 4 were in chronic renal insufficiency and 5 in end-stage renal failure (3 were in dialysis, 2 died). There was no correlation between the 3 above-mentioned types of evolution and glomerular histological findings. Nevertheless a higher score of vascular impairment at biopsy was observed among patients who subsequently were found to have a more unfavorable prognosis. Therefore renal biopsy, by providing information on the degree of renal vascular damage, may have some value in predicting the clinical course of diabetic nephropathy.