Hepatitis C is an infectious disease caused by the hepatitis C virus. If such an infection persists for more than six months, it is deemed chronic hepatitis C, and this condition bears high risks of liver cirrhosis or malignant degeneration.
An acute stage of hepatitis C infection has been described, but most patients remain asymptomatic until years later. If symptoms manifest, they are consistent with a mild case of liver inflammation: malaise, nausea, jaundice and upper abdominal pain may be observed and may last for several weeks.
About 75% of patients who contract hepatitis C develop chronic hepatitis C, but disease progress is very slow. During years, fatigue and recurrent nausea may be the only signs of a persistent infection. Symptoms exacerbate over time and correspond to increasing replacement of hepatocytes by fibrous connective tissue. A patient presenting with liver cirrhosis may claim lethargy, nausea, vomiting, anorexia, weight loss and loss of libido. Jaundice and dermatological symptoms are frequently observed. Patients may feel pressure pain in the upper right abdomen. Neurological symptoms have been described and may comprise difficulties in concentration and memory impairment. Symptoms associated with hepatocellular carcinoma are similar and in fact, most patients who are diagnosed with hepatitis C-induced cancer also suffer from cirrhosis .
Ideally, patients who present with symptoms of acute hepatitis are submitted to a thorough workup to identify its etiologic agent. In fact, molecular biological techniques allow for the confirmation of hepatitis C as early as a few days after infection. Identification of a particular genotype is possible. Reverse transcription polymerase chain reaction has to be applied to detect viral RNA. Distinct test systems are available . Enzyme-linked immunoassay provide reliable results, too, but positive results are not to be expected until about two months after exposure. Of note, the here described tests confirm an infection with hepatitis C virus but they don't reveal any information regarding the duration of infection. In order to diagnose chronic hepatitis C, tests need to be repeated months after initial diagnosis of hepatitis C.
Serological testing may also be conducted, but specific antibodies may be detected in patients with an active hepatitis C infection as well as in those individuals that have overcome the disease. Therefore, serological methods cannot be applied to evaluate response to treatment. For an initial diagnosis of hepatitis C infection, they are very valuable, though.
Laboratory analyses of blood samples should be conducted. Parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin need to be evaluated to assess liver function.
Detailed information about the condition of hepatic parenchyma may be obtained by histopathological analysis of a liver biopsy. While such a procedure is not required to confirm hepatitis C infection, it is very helpful to assess current inflammation, fibrous remodeling and possible malignant degeneration.
Because liver cirrhosis is a major risk factor for hepatocellular carcinoma, patients diagnosed with the former should be regularly screened for the latter . Sonography and measurement of serum α-fetoprotein are applied to this end.
Direct-acting antivirals and possibly pegylated interferon are the mainstays of therapy. Treatment aims at complete elimination of hepatitis C virus, a condition that may be revised by means of molecular biological testing.
Until a few years ago, ribavirin and interferon have been administered for up to ten months in a combined approach to treat hepatitis C infections. This prolonged therapy has not only been associated with high incidences of side effects, but its efficacy was often not satisfactory. Direct-acting antivirals fill both gaps: If applied during twelve weeks, high cure rates can be achieved, and the incidence of side effects is much lower. Thus, nowadays, genotyping and administration of specific direct-acting antivirals is the treatment of choice. The following compounds are available:
Direct-acting antivirals may be combined or supplemented with ribavirin or pegylated interferon if this becomes necessary to treat intractable cases.
Unfortunately, direct-acting antivirals are very expensive drugs.
A liver transplant may be the only chance to treat hepatitis C-induced cirrhosis. However, recurrence in the graft is very likely. Common therapeutic approaches to hepatocellular carcinoma are surgical excision, arterial embolization and radiofrequency ablation.
About 75% of hepatitis C infections become chronic and approximately 25% of patients suffering from chronic hepatitis C will eventually develop liver cirrhosis, an irreversible end-stage hepatopathy characterized by extensive replacement of hepatocytes with connective tissue. Direct-acting antivirals show good efficacy in hepatitis C treatment, but the risk of hepatocellular carcinoma remains increased in cirrhosis patients even after complete elimination of the causative pathogen . Additional risk factors for malignant degeneration are diabetes mellitus and alcohol intake  .
Hepatitis C is caused by a single-stranded, positive RNA virus pertaining to the family of Flaviviridae and the genus Hepacivirus. Other human pathogen viruses belonging to the family of Flaviviridae are those viruses causing Dengue fever, yellow fever and West Nile fever. To date, no other viruses have been classified as Hepacivirus. Of note, the etiologic agents of hepatitis A and B pertain to the families of Picornaviridae and Hepadnaviridae, respectively.
According to genomic differences, at least seven genotypes of hepatitis C virus have been described. In many countries, genotypes 1 and 3 are the most common triggers of hepatitis C. There seems to be no relation between social status and the likelihood to contract these virus strains. In contrast, genotypes 4 and 5 account for major shares of cases only in low-income countries . Infections with multiple genotypes of hepatitis C virus have repeatedly been described.
It has been proposed that hepatitis C virus genotypes evolved in a process that conferred increasing resistance to the human immune system . This is of major importance for treatment of hepatitis C infections, since individual genotypes may be more or less sensitive to current therapeutic options.
Additionally, genotypic differences have to be considered in vaccine development. Current research mainly focuses on genotype 1, because no other genotype causes that many cases of hepatitis C. However, more than half of all cases are non-genotype 1 hepatitis C .
The hepatitis C virus is distributed throughout the whole world and it has been estimated that worldwide prevalence ranges between 2 and 3% . This would correspond to up to 220 million people - an alarming number that also results from the high share of chronic hepatitis C cases. Indeed, most infections with hepatitis C virus become chronic. During early stages of the disease, patients are asymptomatic, and this fact often delays diagnosis and initiation of treatment. Long-term consequences of chronic hepatitis C are hepatic failure due to cirrhosis and hepatocellular carcinoma. These sequelae cause more than 350,000 deaths every year; about one out of four patients presenting with liver cirrhosis or hepatocellular carcinoma suffers from chronic hepatitis C.
The hepatitis C virus is one of several human pathogen hepatotropic viruses. It replicates within hepatocytes and may cause direct cytopathic effects, but according to current knowledge, liver damage in hepatitis C patients does not primarily result from virus-mediated cell lysis. Instead, host immune mechanisms seem to account for hepatic inflammation and induction of remodeling processes if the virus cannot be eliminated in a timely manner. Cytotoxic T lymphocytes have been proposed as effective inhibitors of viral replication, but these same cells may cause progressive liver damage .
If the above described pathomechanisms persist for more than half a year, for several years or decades even, replacement of functional liver parenchyma with fibrous connective tissue leads to cirrhosis. The inability to clear the virus may result from evasion of host defense mechanisms by the pathogen, e.g., by modulation of lymphocyte function or generation of mutated quasispecies.
Sexual transmission of hepatitis C virus continues to be a matter of debate. However, men who have sex with men seem to have a high risk for contracting the disease, possibly because anal intercourse predisposes for lesions that lead to direct contact to blood . Consequently, practice of safer sex is highly recommended to prevent acute and chronic hepatitis C.
Health care givers are considered at risk for hepatitis C infections. If an accident such as a needle-stick injury is registered, the affected person should be tested for hepatitis C virus repeatedly until six months later. This way, a possible infection may be recognized early and treatment can be initialized in a timely manner.
Hepatitis C is an infectious disease that frequently follows a chronic course, thus leading to chronic hepatitis C. Its causative agent is an RNA virus designated hepatitis C virus. Transmission mainly occurs through blood of infected individuals. Thus, transfusion of untested blood and blood products, organ transplantation, intravenous drug abuse and utilization of non-sterile needles are associated with significant risks of infection. However, routine screens of blood and organ donations as well as the implementation of measures to prevent graft infection have contributed to decrease the rate of hepatitis C infections acquired in medical procedures . This may not necessarily apply to developing countries.
While the infection is initially asymptomatic, the majority of patients develops chronic hepatitis C and in about 25% of these people, viral infection of the liver will eventually lead to liver cirrhosis or hepatocellular carcinoma. More than 20 years may pass between infection and irreversible fibrosis or malignant degeneration and in some patients, only very mild symptoms manifest before they reach this final stage of the disease.
Treatment consists in long-term administration of direct-acting antivirals like sofosbuvir and ledipasvir as well as pegylated interferon; the specific regime should be adapted to the hepatitis C virus genotype that is causing the disease in an individual patient. Current research is focusing on the development of new antiviral drugs that induce less side effects. To date, chronic hepatitis C treatment often requires application of more than one drug and many patients claim flu-like complaints during therapy. While elimination of the pathogen is achievable, hepatic remodeling processes and degeneration may not be reversible.
Hepatitis C is mainly transmitted through blood of infected individuals. Thus, intravenous drug abuse and utilization of non-sterile needles to pierce or tattoo are associated with significant risks of infection. Before routine screens of blood and organ donations were implemented, transfusion and transplantation were common sources of infection, too.
Within the first weeks after infection, hepatitis C may manifest in form of malaise, nausea, jaundice and upper abdominal pain, but some patients don't experience any symptoms. After remission of these complaints, patients are usually asymptomatic for years or even decades. However, chronic hepatitis C is associated with progressive liver damage and significant shares of patients develop liver cirrhosis or liver cancer many years later. The above mentioned symptoms aggravate, patients may lose appetite, weight and libido.
The presence of hepatitis C virus can be confirmed by means of molecular biological techniques. Diagnosis of chronic hepatitis C requires several positive tests over the course of more than six months.
Additionally, blood samples may be analyzed to assess liver function. In some cases, a liver biopsy needs to be obtained.
In advanced cases of chronic hepatitis C, particularly in patients suffering from cirrhosis, regular screens are recommended to detect possible malignant degeneration of hepatocytes.
A variety of antiviral drugs are available to eliminate the pathogen. Modern therapeutic approaches require medication over the course of three months, while significantly longer treatment was necessary until a few years ago. The overall prognosis is good.
Unfortunately, cirrhosis is an irreversible condition that does predispose for liver cancer. Thus, even though the virus is eliminated, hepatic function may remain impaired in cases of advanced chronic hepatitis C.