Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosis.

BACKGROUND: Although fragmentation of a liver biopsy specimen has been considered to be suggestive of cirrhosis, the evidence for this is difficult to find in the published literature. AIM: To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis. METHODS: One hundred and eighty-six patients underwent percutaneous liver biopsy prospectively. The specimens were measured for the length and number of fragments. The extent of fibrosis was scored by a pathologist blind to the clinical data. Length and fragmentation data were compared between the different stages. RESULTS: The overall median fragment length was 1.85 cm and the median fragment number was four. Specimens with advanced fibrosis (stages III-IV) had more fragments than those with no or mild fibrosis (stages 0-II) (P < 0.0001). The aggregate fragment length decreased with increasing stage of fibrosis (P < 0.0001). Specimens with greater than 12 fragments were seen only with advanced fibrosis. CONCLUSIONS: Fragmentation of percutaneous liver biopsy specimens is common and increases with progression from early to advanced fibrosis. Fibrotic specimens fragment more often and more extensively.

A randomized trial of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon.

BACKGROUND: Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C-infected patients. The use of high-dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved. AIM: To compare the efficacy and safety of re-treatment with an induction regimen of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy. METHODS: Previous virological non-responders to standard dose interferon (3-5 MU three times weekly for > or = 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha-2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000-1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy. RESULTS: End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow-up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06). CONCLUSIONS: In this small pilot study, a 36-week high-dose induction interferon monotherapy protocol did not yield sustained responses in previous non-responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High-dose interferon with ribavirin appears to be a therapeutic option for non-responders to conventional interferon monotherapy.

Fas-mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption, and may be associated with hepatic fibrosis: mechanisms of liver cell injury in chronic hepatitis C virus infection.

Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C virus (HCV) infection is associated with advanced liver disease, including cirrhosis. The aims of this study were to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in HCV-infected patients and to determine the role of Fas in HCV-mediated apoptosis. Liver tissue from 44 HCV-infected patients with variable alcohol consumption, and 10 normal control subjects who did not consume alcohol was examined for hepatocyte apoptosis, proliferation and Fas expression. Alcohol consumption was assessed using the 'Lifetime Drinking History' alcohol questionnaire. HCV RNA, alanine aminotransferase (ALT) and ferritin were also assessed in addition to demographic data. Hepatocyte apoptosis was significantly greater in HCV-infected patients compared to controls. Expression of Fas (CD95) was found in HCV patients but not in controls. The degree of Fas expression correlated with hepatocyte apoptosis as detected by terminal UTP nick end labelling (TUNEL). Active ethanol consumption led to a significant increase in hepatocyte apoptosis. Fas expression correlated with fibrosis in HCV-infected patients who were not actively drinking ethanol. In summary, HCV leads to increased apoptotic cell death in hepatocytes. Programmed cell death can be further up-regulated by active ethanol consumption. The correlation between Fas expression and TUNEL supports the hypothesis that the Fas-Fas ligand interaction is the major mechanism for HCV-induced hepatocyte apoptosis.

Changes in hepatitis C-related liver disease in a large clinic population.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant problem in the Australian community. Over the past few years, the number of patients with diagnosed hepatitis C has increased greatly. The aims of the present study were to define the clinical features of a large group of patients with chronic HCV infection and to examine changes occurring in the referral base and epidemiological characteristics of this group since analysis of the first 342 patients in 1994. METHODS: The study included 1,546 consecutive anti-HCV-positive patients who had been referred to St Vincent's Hospital from January 1990 to June 1998. Clinical and laboratory data were collected on all patients. RESULTS: Referrals from general practitioners increased from 31% to 70% of all patients between 1990-1993 and 1994-1998. A history of injecting drug use (IDU) was present in 64% of the patients. While 89% of the IDU group was Australasian born, 49% of those in the sporadic group were born overseas. Cirrhosis was found in 18% of biopsied patients. Age, infection duration, age at infection, Mediterranean or Asian origin and a history of transfusion or lack of HCV risk factors were associated with cirrhosis on univariate analysis. Patient age was the only independent predictor of cirrhosis. CONCLUSION: The majority of patients with HCV are diagnosed in general practice. A risk factor for infection is identified in 82% of patients. While our reported prevalence of cirrhosis may be an overestimate of that in the overall HCV community, the ultimate disease burden is likely to be significant.

Hepatitis B infection in patients with acute liver failure in the United States.

Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B.

Acute hepatic failure: a Western perspective.

Acute hepatic failure (AHF) is an uncommon, devastating syndrome, which results in death or the need for liver transplantation in more than 50% of cases. While AHF has numerous causes, most cases are due to viral hepatitis and drug toxicity or idiosyncratic reactions. A significant group with indeterminate causation remains, despite careful investigation. In many of these cases a viral aetiology is suspected, although yet not proven. Major differences exist in the aetiology of AHF between the West and Eastern countries. A wider range of aetiologies exists in the West. Common causes include acetaminophen toxicity and idiosyncratic drug reactions, while viral hepatitis is less frequent. Hepatitis E infection is rarely seen in Western countries in contrast to its high prevalence in the East. The mainstay of AHF management is supportive care in an intensive care unit. Liver transplantation is now the standard of care in many Western liver units for individuals who have a less than 20% probability of survival. Lack of availability of donor livers at short notice remains a significant problem. Methods of liver support used while waiting for a donor liver or for the native liver to regenerate include bioartificial livers, extracorporeal liver-assist devices, extracorporeal whole organ perfusion (human and transgenic pig) and hepatocyte transplantation. The effectiveness of these methods remains unproven and awaits controlled clinical trials. Both transplantation and liver-support methods require specialized units and expensive and complicated equipment. Further research is necessary to identify modalities of therapy that would be effective as well as widely accessible.

Severity of liver disease in hepatitis C infection contracted through injecting drug use.

BACKGROUND: Injecting drug use (IDU) is currently the most common route of hepatitis C virus (HCV) transmission in Australia and many other Western countries. Most reports on the natural history of HCV have examined populations that included patients from all risk groups, but it is possible that this increasingly important subgroup is different. AIMS: To assess the severity of liver disease in individuals who acquired HCV through IDU. METHODS: Three hundred and forty-six patients with confirmed HCV infection and a history of IDU, who had had a liver biopsy performed were recruited from a liver clinic. Demographic data, liver function tests and hepatitis B serology were obtained on all patients. A detailed drug use history and HCV viral studies were also available in a subgroup of 142 patients. RESULTS: Mean age of the group was 34 years and 73% were male. Mean duration of HCV infection was 14.6 years. Forty one per cent were infected with genotype 3a, 19% - 1a, 17% - 1 (nonsubtypable), 14% - 1b and 4% - 2b. Cirrhosis was present in 12% of patients. Patients with cirrhosis (38 years) were older than those with chronic hepatitis (34 years; p=0.0003) and had a longer duration of infection (17.2 vs 14.3 years; p=0.003). On multivariate analysis, however, patient age was the only factor independently associated with cirrhosis (odds ratio 4.2; 95% confidence interval 1.4-12.6). CONCLUSION: While cirrhosis is less common in this group than in other HCV infected populations, its prevalence may increase as these patients are followed over a longer period of time.

Role of alcohol in the progression of liver disease caused by hepatitis C virus infection.

In patients with chronic hepatitis C, alcohol consumption has been proposed as a risk factor for the progression of liver disease; however, evidence for this remains conflicting. Two hundred thirty-four anti-hepatitis C virus (HCV)-positive patients who had a liver biopsy performed within the past 24 months were studied. Demographic data and information on risk factors were recorded. A detailed lifetime alcohol consumption history was obtained. Viral studies included HCV viral titer and HCV genotype. Mean age (+/- SEM) of the group was 40.8 +/- 0.7 years. One hundred sixty-six (71%) were male. A risk factor for HCV infection was found in 195 patients (86%). Genotype distribution was: 1b: 22%; 1a: 15%; 1(nonsubtypable): 15%; 3a: 34%; and 2: 7%. Fifty (21%) patients had cirrhosis. Patients with cirrhosis were older (51.6 +/- 1.8 years) than those with chronic hepatitis (37.6 +/- 0.6 years; P = .0001), were infected at an older age (25.9 +/- 2.0 vs. 20.9 +/- 0.6 years; P = .001), and had a longer duration of infection (20.5 +/- 1.3 vs. 16.2 +/- 0.5 years; P = .0008). Patients with cirrhosis had a greater total lifetime alcohol consumption (288,765 +/- 58,115 g) than those with chronic hepatitis (189,941 +/- 15,453 g; P = .018). Cirrhotic patients also had greater total alcohol consumption during the period of infection with HCV (240,962 +/- 63,756 g vs. 146,510 +/- 12,862 g; P = .02). On multivariate analysis, subject age and total alcohol consumption were independently associated with the presence of cirrhosis. Total lifetime alcohol consumption is a risk factor for the progression of liver disease caused by HCV.

[Treatment of abdominal liposarcoma in children (author's transl)]. / Therapeutischer Beitrag zum Liposarkom im Kindesalter.

A patient with abdominal liposarcoma is described, and the treatment of this in children extremely uncommon tumor is discussed. After complete surgical excision, local irradion with 5000-6000 rad should be considered only if no vital organs are irradiated. Because of the high tendency for local recurrence and for distant metastases of this tumor a primary polychemotherapy beginning immediately after surgical excision is proposed as in cases of other solid tumors in children for instance rhabdomyosarcoma or fibrosarcoma. 18 months after the surgical excision and after the beginning of polychemotherapy our patient is clinically well without demonstrable tumor growth.

[Results after fracture of the os calcis (author's transl)]. / Ergebnisse der Calcaneusfrakturen.

A double study over a period of 40 years was undertaken--from 1935 to 1954 in Berlin and from 1955 to 1976 in Salzgitter--including a total of 393 fractures of the os calcis. The results of different types of treatment are presented. It is the type and severity of the fractures, not the way of treatment which determines the outcome. 161 patients have been followed clinically and radiologically at least 5 years after fracture of the os calcis. Third degree fractures were objectively and subjectively less favourable regardless of therapy. Active surgical treatment should be post-poned and consist in fusion of the subtalar joint.

[Primary double pinning of the neck of the femur (author's transl)]. / Primäre Doppelbolzung der medialen Schenkelhalsfraktur

From a total of 351 fractures of the neck of the femur, 125 were of mid-cervical form, and from these 107 were dominated by type III after Pauwels. We have used double pinning as an optimal method of treatment for this fracture during the past 10 years. In 12% of the cases this method leads to pseudarthrosis, and in 10% to necrosis of the head of the femur. The double pinning technique is an especially optimal and less onerous method for patients at an advanced age, allowing a complete stabilisation of the fracture while concurrently correcting errors of rotation. We recommend the alloplastic restitution of the hip joint in the form of a total endoprothesis (TEP) as a secondary measure, only in rare cases as a primary operative method.