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A case of symptomatic polycystic liver disease treated by fenestration and segmental liver resection is reported. The intraoperative use of ultrasound to define the plane of liver resection is emphasised. No significant post-operative complication was encountered. The clinical presentation, management and treatment are discussed.
Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.
BACKGROUND: Development of de novo autoimmune liver disease has not been well documented in patients with malignant diseases. METHODS/RESULTS: In this paper we report on a series of six patients with neoplastic disorders who acquired liver disease with autoimmune features. Five patients had suffered from haematological neoplasms and one from colonic cancer. In two patients, liver disease was detected at the time of presentation with malignancy. In the remaining four, all of whom were successfully treated for malignancies, features of liver disease presented at intervals 24-72 months after the cancer diagnosis. Twelve liver specimens (11 biopsies and one hepatectomy specimen) were obtained at time intervals of 1-76 months after initial presentation of neoplastic disease. Biopsies from three patients showed features of hepatitis (one acute, one sub-acute, one chronic). Two patients had histological features suggestive of an overlap syndrome (one autoimmune hepatitis/primary biliary cirrhosis, one autoimmune hepatitis/primary sclerosing cholangitis). The sixth patient had features of autoimmune cholangiopathy. All but one responded well to steroid therapy with complete clinical and biochemical remission obtained 4 weeks to 8 months after steroid introduction. We discuss briefly possible aetiologies of autoimmune liver disease in these patients. CONCLUSIONS: Autoimmune liver disease may be precipitated by therapy for neoplastic disease or malignant disease itself. The unusually heterogeneous clinicopathological findings in this group as well as the response to treatment support the concept of a wide spectrum of manifestations of autoimmune liver disease. The results may also suggest that autoimmune liver disease may be possibly added to the list of paraneoplastic syndromes. Further prospective studies are required to confirm a causal association and to determine whether the mechanisms involved are disease- or treatment-related.
Thiamine state was investigated in patients with alcoholic liver disease, patients with various non-alcoholic liver diseases, and controls using a direct technique (thiochrome assay) to measure thiamine, thiamine monophospate, and the active coenzyme thiamine pyrophosphate in whole blood after isolating the fractions by ion exchange chromatography. Overall nutrition was similar in all groups as assessed by anthropometry, and no patient had clinical evidence of thiamine deficiency. There was no significant difference among the groups in mean concentration of any form of thiamine. The scatter was much greater in patients with alcoholic liver disease but only 8.7% had biochemical thiamine deficiency (defined as a blood concentration of the active coenzyme greater than 2 SD below the mean control value). An unexpected finding was of abnormally high total thiamine concentrations (greater than 2 SD above the mean control value) in 17.4% of patients with alcoholic liver disease, the highest concentrations being found in two patients with severe alcoholic hepatitis and cirrhosis. The ratio of phosphorylated to unphosphorylated thiamine was calculated as an index of phosphorylation and, although the mean did not differ significantly among the groups, the range was greatest in alcoholic liver disease. The lowest ratios occurred in the two patients with severe alcoholic hepatitis, but neither had evidence of thiamine pyrophosphate deficiency. Contrary to studies using indirect assay techniques, these results suggest that thiamine deficiency is unusual in well nourished patients with alcoholic liver disease. The new finding of unexpectedly high thiamine concentrations in some patients may be due to abnormalities of hepatic storage or release in liver disease, particularly in severe alcoholic hepatitis. There was no convincing evidence of impaired thiamine phosphorylation in any patients with liver disease. Conclusions from studies using indirect assays on the prevalence and mechanisms of thiamine deficiency in liver diseases may not be valid.
BACKGROUND & AIMS: The liver plays a central role in vitamin D metabolism. Our aim was to determine the prevalence and type of vitamin D-parathyroid hormone (PTH) disturbance in ambulatory patients with noncholestatic chronic liver disease (CLD) and its relationship with disease severity and liver function. METHODS: We studied 100 consecutive outpatients (63 men, 37 women; mean age, 49.0 +/- 12.1 [SD] y) with noncholestatic CLD caused by alcohol (n = 40), hepatitis C (n = 38), hepatitis B (n = 12), autoimmune hepatitis (n = 4), hemochromatosis (n = 4), and nonalcoholic steatohepatitis (n = 2); 51 patients had cirrhosis. Serum concentrations of 25-hydroxyvitamin D (25[OH]D), PTH, calcium, phosphate, magnesium, creatinine, and liver function tests were determined. RESULTS: Serum 25(OH)D levels were inadequate in 91 patients: vitamin D deficiency (<50 nmol/L) was found in 68 patients and vitamin D insufficiency (50-80 nmol/L) was found in 23 patients. Secondary hyperparathyroidism (serum PTH, >6.8 pmol/L) was present in 16 patients. The prevalence of vitamin D deficiency was significantly higher in cirrhotic vs noncirrhotic patients (86.3% vs 49.0%; P = .0001). In Child-Pugh class C patients, 25(OH)D levels were significantly lower than in class A patients (22.7 +/- 10.0 nmol/L vs 45.8 +/- 16.8 nmol/L; P < .001). Serum 25(OH)D independently correlated with international normalized ratio (negatively; P = .018) and serum albumin (positively; P = .007). Serum 25(OH)D levels of less than 25 nmol/L predicted coagulopathy, hyperbilirubinemia, hypoalbuminemia, increased alkaline phosphatase, and anemia and thrombocytopenia. CONCLUSIONS: Vitamin D inadequacy is common in noncholestatic CLD and correlates with disease severity, but secondary hyperparathyroidism is relatively infrequent. Management of CLD should include assessment of vitamin D status in all patients and replacement when necessary.
Drug-induced liver disease (DILD) causes significant morbidity and mortality and impairs new drug development. Currently, no known criteria can predict whether a drug will cause DILD or what risk factors make an individual susceptible. Although it has been shown in mouse studies that the disruption of key regulatory factors, such as cyclooxygenase-2 (COX-2), interleukin (IL)-6, and IL-10, increased susceptibility to DILD caused by acetaminophen (APAP), no single factor seems to be absolute. As an approach to better understand the multifactorial basis of DILD, we compared the hepatic proteome of mice that are resistant (SJL) and susceptible (C57Bl/6) to APAP-induced liver disease (AILD), using solution-based isotope-coded affinity tag (ICAT) liquid chromatography mass spectrometry. Several novel factors were identified that were more highly expressed in the livers of SJL mice, including those involved in stress response, cell proliferation and tissue regeneration, and protein modification, implicating these proteins as potential hepatoprotective factors. There was also a selective loss of several mitochondrial proteins from the livers of the susceptible C57Bl/6 mice, suggesting that the loss of functional mitochondria may indeed play a role in AILD. These findings indicate that comparative hepatic proteomic analyses of susceptible and resistant mouse strains may provide a global approach for identifying potential risk factors and mechanistic pathways responsible for DILD.
BACKGROUND/AIMS: The effect of heterozygosity for the C282Y mutation in the HFE hemochromatosis gene on iron accumulation and disease progression in liver disease patients is unclear. METHODS: We investigated the prevalence of this mutation in 531 patients and 205 healthy controls. In addition, we assessed the influence of the mutation on liver histology in 34 C282Y heterozygous and 124 age-, sex- and disease-matched controls without the mutation using the modified HAI and Chevallier score. RESULTS: The highest prevalence of the C282Y mutation was observed in patients with autoimmune hepatitis (17.2%, p<0.01) compared to 6.4% in healthy controls. Heterozygotes with hepatitis C and B virus infection showed higher ferritin and hepatic iron concentrations than patients without the mutation. However, we did not detect significant differences in necroinflammatory or fibrosis scores between carriers of the mutation and controls. CONCLUSIONS: There are marked differences in the prevalence of the C282Y mutation in patients with different liver diseases, with the highest prevalence rates in autoimmune hepatitis and PBC. However, the C282Y mutation alone only leads to a mild increase in iron accumulation in the majority of the patients, with the exception of H63D/C282Y compound heterozygotes. We found no evidence for more pronounced fibrosis in C282Y heterozygotes.
In the liver biopsy of 100 patients with chronic liver diseases, the activity of 7-ethoxycoumarin O-deethylase (ECOD) was determined as a parameter of hepatic monooxygenase system and was compared with some markers of fibrosis e.g. collagen peptidase and hydroxyproline. ECOD was significantly different in healthy liver, fatty liver, chronic active hepatitis (CAH) and cirrhosis. The importance of the fibrotic process was shown by the significant correlations between ECOD and the signs of fibrosis in the liver biopsy. A connection between ECOD and the markers of fibrosis was not found. Further research is necessary to clarify this difference.
Observations in 136 liver biopsies from patients with alcoholic and nonalcoholic liver diseases reveal that IgA deposition in liver tissues appears to have a high degree of morphologic specificity for alcohol injury. Using a direct immunofluorescence technic with fluorescein-conjugated anti-IgG, anti-IgA, anti-IgM, and anti-C1q, four different staining patterns are recognized. These are labelled as "continuous," "discontinuous," "granular," and "pericellular" types depending on their morphologic characteristics and distribution patterns. Fifty of 64 biopsies from alcoholics showed a "continuous" pattern of anti-IgA activity while only three of 72 biopsies from nonalcoholics showed a similar pattern (P less than 0.001). A "pericellular" pattern of anti-IgA activity appears to indicate a more aggressive behavior of alcoholic liver disease. "Continuous" and "pericellular" patterns are seen in "chronic active hepatitis of alcoholics" but not in chronic active hepatitis in nonalcoholics. Anti-IgM activity appears to indicate chronicity of the disease process but does not have any specificity.
BACKGROUND: Cystic fibrosis-related liver disease peaks in adolescence with up to 20% of patients developing chronic liver disease. Early changes in the liver may ultimately result in end stage liver disease with patients needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. OBJECTIVES: To assess the effectiveness of ursodeoxycholic acid in cystic fibrosis liver disease. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register, and contacted drug companies. Date of the most recent search of the Group's specialised register: June 1999. SELECTION CRITERIA: Randomised and quasi-randomised trials of use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. MAIN RESULTS: Three trials involving 118 patients were included. The complex study design used in two trials meant that data could only be analysed for subsets of patients. There was no difference in weight change (weighted mean difference -0.496, 95% confidence interval -1.545 to +0.553) based on 30 patients from two trials. Improvement in biliary excretion was reported in only one study and no significant change after treatment was shown. Long term outcomes such as death or need for liver transplantation were not reported. REVIEWER'S CONCLUSIONS: There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify is its routine use in cystic fibrosis.
A method of quantitative liver tomoscintigraphy (SPECT) was compared for accuracy with planar scintigraphy (PS) in a group of patients with diffuse alcoholic liver disease. SPECT sensitivity was also compared with that of transmission computed tomography (CT), US, aminopyrine breath test (ABT) and liver chemistries (LC). One hundred and fourteen alcoholic patients with proven liver disease and 17 patients free of liver disease were included. Seven quantitative scintigraphic features and a score, including all criteria were considered. With a specificity of 95%, the sensitivity was 79% in steatosis and 97% in cirrhosis. SPECT showed a better sensitivity than PS (SPECT 89%, PS 66%), especially in patients with steatosis. In the same subsets of patients, SPECT sensitivity also compared favorably with that of transmission CT (SPECT 92%, CT 65%), ultrasonography (SPECT 88%, US 53%) and ABT (SPECT 90%, ABT 63%).
We prospectively screened for liver disease patients with cystic fibrosis who were more than 3 years of age and who were followed at the cystic fibrosis center of the University of Milan. From January 1991 to December 1992, we screened 189 patients; clinical, biochemical, and echographic abnormalities suggestive of overt liver disease were present in 34 (18%). To define risk factors for the development of liver disease associated with cystic fibrosis, we evaluated the possible role of specific mutations of the CFTR (cystic fibrosis transmembrane regulator) gene and of different clinical and demographic characteristics (sex, pancreatic status, meconium ileus or its equivalent) through a comparison of patients with cystic fibrosis and overt liver disease (n = 34) and those without liver disease (n = 155). Genetic analysis failed to reveal any significant difference in the allele frequencies of defined (delta F508, 1717-1G-A, G542X, N1303K, W1282X, R553X) and undefined mutations of the CFTR gene in the two groups of patients; genotype frequencies were also not significantly different. Pancreatic insufficiency was present in all patients with liver disease and in 87.3% of those without liver disease. A male predominance was found in the group with liver disease. The frequency of meconium ileus or its equivalent was significantly higher in patients with cystic fibrosis and liver disease (35.3%) than in patients without liver disease (12.3%) (p = 0.0025). In the 31 patients with a history of meconium ileus or its equivalent, the following hepatic abnormalities occurred more frequently than in the 155 patients with cystic fibrosis who did not have meconium ileus: hepatomegaly, biochemical abnormalities, heterogeneous echographic pattern of the liver, and microgallbladder. Twenty-four patients with a history of meconium ileus or its equivalent underwent hepatobiliary scintigraphy (with technetium-labeled iminodiacetic acid derivatives), which showed morphologic abnormalities suggestive of impaired biliary drainage in 21 patients and abnormalities in function in 11. The risk of acquiring liver disease was increased almost fourfold in patients with a history of meconium ileus or its equivalent, in comparison with patients who had cystic fibrosis but were unaffected by these complications (odds ratio, 3.9043; 95% confidence interval, 1.666 to 9.149). We conclude that patients with cystic fibrosis and meconium ileus or its equivalent may benefit from prophylactic treatment with ursodeoxycholic acid; genetic analysis of the major mutations present in this population failed to provide evidence of the existence of a specific genetic marker for the development of liver disease in patients with cystic fibrosis.
BACKGROUND/PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease ranging in severity from steatosis to cirrhosis. Type 2 diabetes mellitus is a cause of primary NAFLD. Thiazolidinediones have been shown to enhance insulin sensitivity, improve glycemic control in type 2 diabetes patients and to improve the histologic markers of nonalcoholic steatohepatitis. This study aims to determine the safety and effectiveness of rosiglitazone in inadequately controlled type 2 diabetes patients with NAFLD. METHODS: Taiwanese type 2 diabetes patients with inadequate control on insulin secretagogues and metformin, with no history of significant alcohol ingestion, with mildly elevated serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and a diagnosis of fatty liver determined by ultrasonography were enrolled. Patients were treated for 24 weeks with rosiglitazone, 4-8 mg daily. Primary endpoints were change in AST and ALT levels from baseline and reduction in A1C < 6.5%. RESULTS: Out of a total of 68 patients, 60 (88.2%) completed the study treatment without serious adverse events. Treatment in two (2.9%) patients was discontinued due to elevated AST or ALT levels to more than three times the upper limit of normal, and noncompliance or loss of follow-up in six (8.8%) patients. Of the 60 patients who completed the study treatment, mean fasting plasma glucose, A1C, fasting plasma insulin, mean ALT and homeostasis model assessment for insulin resistance were all significantly reduced. Normal AST and ALT levels were achieved and maintained for at least three consecutive measurements and through to the end of the study period in 20 (33.3%) patients. Weight increased by a mean of 2.6 +/- 2.4 kg (p < 0.001). CONCLUSION: Rosiglitazone was reasonably well tolerated in patients with inadequately controlled type 2 diabetes and NAFLD. One-third of patients showed improved liver function after treatment.
The association between chronic liver disease and plasmatic lipids and glucidic metabolism was studied. The liver was evaluated with biochemical variables, ultrasound and upper gastrointestinal endoscopy. 12 chronic liver diseases patients and 10 normal were studied. 83.3% of patients showed lipidic abnormalities, 66.6% on the cholesterol levels and 41.7%, reduced HDL. When patients received 100 gr of glucose the response was abnormal in 83.3%. These results were compared with other "liver function test". 75% had abnormal bilirubin, 58.3% abnormal albumin, prothrombin time 58.3%, aminotransferases 75%. Esophageal verices were found in 75% of cases and ultrasound abnormalities in 91.6% (27.3% cirrhosis, 54.4% diffuse abnormal patter and 18.2% splenomegaly). These findings show that lipidic and glucidic metabolism, and ultrasound, in chronic liver diseases are the more frequent abnormalities.
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The effects of liver disease on pharmacokinetics and pharmacodynamics are highly variable, and difficult to predict as the mechanisms of these effects are not well understood. Since the majority of the published literature is concerned with cirrhotic liver disease, this review also focuses mainly on this area. Four different theories have been proposed to account for the effects of chronic liver disease with cirrhosis on hepatic drug elimination: the sick cell theory; the intact hepatocyte theory; the impaired drug uptake theory; and the oxygen limitation theory. While some data in support of each of the first 2 theories have been published recently, a large amount of clinical data would appear to refute both of these theories. These clinical data are substantially consistent with the latter 2 theories, which regard the decreased permeability of the capillarised sinusoid as the critical feature in cirrhosis. Further work is required to determine the applicability of each of these theories. In cirrhosis, drug glucuronidation is spared relative to oxidative drug metabolism; however, in advanced cirrhosis this pathway may also be impaired substantially. There is evidence that in cirrhosis other conjugation pathways may also be impaired to variable degrees. Growing evidence suggests that biliary drug excretion is impaired in cirrhosis. Recent studies with several racemic drugs indicate that the disease can have different effects on the hepatic elimination of individual enantiomers, which may lead to a change in the concentration-response relationships of racemic drugs in cirrhosis. A major finding which has emerged in recent years is that, even with moderate degrees of hepatic impairment, there is a decrease in clearance of drugs or active metabolites normally cleared by the kidney. The effect on renal clearance of unbound drug may be masked if there is a concomitant decrease in plasma protein binding of the drug. Neither serum creatinine levels nor creatinine clearance are useful markers of the renal dysfunction associated with cirrhosis. Both may greatly overestimate renal function in patients with cirrhosis due to increased fractional renal tubular secretion of creatinine. Altered receptor sensitivity has been observed with some drugs in cirrhosis, while for other drugs there is no change in pharmacodynamics. Precise determination of drug dosage in cirrhosis requires information on changes in pharmacodynamics and plasma protein binding in addition to changes in drug elimination. Pharmacokinetic investigations in a variety of chronic liver diseases without cirrhosis (e.g. carcinoma, schistosomiasis and viral hepatitis) suggest that in the absence of cirrhosis, impairment of drug elimination is not sufficient to warrant reduction of drug dosage. However, if cirrhosis is present, 'safe' drug use requires an awareness of the possibility of multiple interactions between changes in hepatic and renal disposition and pharmacodynamics. In chronic liver disease with cirrhosis, dosage reduction is the general rule regardless of the route of elimination of drug or metabolite.
Donor organ shortage calls for widening of criteria for organ transplantation. In exceptional cases, even livers with macroscopic alterations may be accepted for transplantation. The case of a patient who received a liver graft from a donor with previously unknown adult polycystic degeneration is reported. The liver showed only small bilobar cysts with less than 10% of hepatic replacement and was successfully used for orthotopic liver transplantation. Two years after transplantation the patient is in good clinical condition and has returned to work.
BACKGROUND: The association of diabetes with liver disease is well known. AIM: To study the spectrum of liver disease in patients of chronic liver disease (CLD) with diabetics and compare it with age and sex matched patients of CLD without diabetes. METHODS: We studied the patients of chronic liver disease presenting over a period of one year and their diagnosis were established by biochemical studies, imaging, endoscopic examination and liver biopsy when required. They were evaluated for the aetiological causes of liver diseases. RESULTS: A total of 53 patients of CLD with diabetes, M:F 43:8, with an age range of 35-70 years, median age of 51 years were taken as study group. Demographic picture of control group was n = 115, with M:F = 100: 15, age range of 37-68 years, with a median age of 52 years. Spectrum of liver disease in diabetic group were as follows: 56.6% cirrhosis, 15.1% chronic hepatitis, 22.6% fatty liver, 5.7% cirrhosis + hepatocellular carcinoma (HCC). The spectrum in control group was as follows, cirrhosis 46.1%, chronic hepatitis 36.5%, fatty liver 14.8%, cirrhosis and HCC 2.6%. Aetiology of chronic liver disease in diabetic group was as follows: Non-alcoholic steatohepatitis (NASH) with cirrhosis 11.3%, NASH 18.9%, cryptogenic cirrhosis 22.6%, hepatitis B virus (HBV) 17%, hepatitis C virus (HCV) 13.2%, alcohol 17%. Aetiology of chronic liver disease in nondiabetic group was as follows: NASH with cirrhosis 1.7%, NASH 13.0%, cryptogenic cirrhosis 7.8%, HBV 30.43%, HCV 13%, alcohol 29.6% and autoimmune in 4.3%. Incidence of NASH with cirrhosis and cryptogenic cirrhosis were found to be statistically significantly high in diabetic group. Incidence of diabetes in cryptogenic cirrhosis was found to be 57% versus 30% in noncryptogenic cirrhosis. CONCLUSION: NASH, NASH with cirrhosis and cryptogenic cirrhosis are the major causes of chronic liver disease in patients with diabetes mellitus. Alcohol and viral causes are found to be important aetiologies in nondiabetic control group. Diabetes mellitus is an important risk factor for chronic liver disease and progression of NASH to cirrhosis, which may present as cryptogenic cirrhosis.